ID ABL1_HUMAN Reviewed; 1130 AA. AC P00519; A3KFJ3; Q13869; Q13870; Q16133; Q17R61; Q45F09; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 24-JAN-2006, sequence version 4. DT 28-JAN-2026, entry version 292. DE RecName: Full=Tyrosine-protein kinase ABL1; DE EC=2.7.10.2 {ECO:0000269|PubMed:20357770, ECO:0000269|PubMed:28428613}; DE AltName: Full=Abelson murine leukemia viral oncogene homolog 1; DE AltName: Full=Abelson tyrosine-protein kinase 1; DE AltName: Full=Proto-oncogene c-Abl; DE AltName: Full=p150; GN Name=ABL1; Synonyms=ABL, JTK7; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM IA), ALTERNATIVE SPLICING, CHROMOSOMAL RP TRANSLOCATION WITH BRC, AND VARIANT PRO-140. RX PubMed=3021337; DOI=10.1016/0092-8674(86)90450-2; RA Shtivelman E., Lifshitz B., Gale R.P., Roe B.A., Canaani E.; RT "Alternative splicing of RNAs transcribed from the human abl gene and from RT the bcr-abl fused gene."; RL Cell 47:277-284(1986). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM IA). RC TISSUE=Fibroblast; RX PubMed=2687768; RA Fainstein E., Einat M., Gokkel E., Marcelle C., Croce C.M., Gale R.P., RA Canaani E.; RT "Nucleotide sequence analysis of human abl and bcr-abl cDNAs."; RL Oncogene 4:1477-1481(1989). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS IA AND IB). RC TISSUE=Lung; RX PubMed=7665185; DOI=10.1006/geno.1995.1008; RA Chissoe S.L., Bodenteich A., Wang Y.-F., Wang Y.-P., Burian D., RA Clifton S.W., Crabtree J., Freeman A., Iyer K., Jian L., Ma Y., RA McLaury H.-J., Pan H.-Q., Sarhan O.H., Toth S., Wang Z., Zhang G., RA Heisterkamp N., Groffen J., Roe B.A.; RT "Sequence and analysis of the human ABL gene, the BCR gene, and regions RT involved in the Philadelphia chromosomal translocation."; RL Genomics 27:67-82(1995). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS VAL-706; PRO-852; SER-900 RP AND LEU-972. RG NIEHS SNPs program; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15164053; DOI=10.1038/nature02465; RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., RA Dunham I.; RT "DNA sequence and analysis of human chromosome 9."; RL Nature 429:369-374(2004). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM IB). RC TISSUE=Cerebellum; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP NUCLEOTIDE SEQUENCE [MRNA] OF 27-40, AND SUBCELLULAR COMPONENT. RX PubMed=2825022; DOI=10.1038/330386a0; RA Fainstein E., Marcelle C., Rosner A., Canaani E., Gale R.P., Dreazen O., RA Smith S.D., Croce C.M.; RT "A new fused transcript in Philadelphia chromosome positive acute RT lymphocytic leukaemia."; RL Nature 330:386-388(1987). RN [9] RP NUCLEOTIDE SEQUENCE OF 360-426. RX PubMed=6191223; DOI=10.1038/304167a0; RA Groffen J., Heisterkamp N., Reynolds F.H. Jr., Stephenson J.R.; RT "Homology between phosphotyrosine acceptor site of human c-abl and viral RT oncogene products."; RL Nature 304:167-169(1983). RN [10] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 825-845. RX PubMed=7545908; RA Inokuchi K., Futaki M., Dan K., Nomura T.; RT "Sequence analysis of the mutation at codon 834 and the sequence variation RT of codon 837 of c-abl gene."; RL Leukemia 8:343-344(1994). RN [11] RP MYRISTOYLATION AT GLY-2 (ISOFORM IB). RX PubMed=2542016; DOI=10.1002/j.1460-2075.1989.tb03397.x; RA Jackson P., Baltimore D.; RT "N-terminal mutations activate the leukemogenic potential of the RT myristoylated form of c-abl."; RL EMBO J. 8:449-456(1989). RN [12] RP DOMAIN, AND DNA-BINDING. RX PubMed=2183353; DOI=10.1126/science.2183353; RA Kipreos E.T., Wang J.Y.; RT "Differential phosphorylation of c-Abl in cell cycle determined by cdc2 RT kinase and phosphatase activity."; RL Science 248:217-220(1990). RN [13] RP FUNCTION. RX PubMed=9037071; DOI=10.1073/pnas.94.4.1437; RA Yuan Z.M., Huang Y., Ishiko T., Kharbanda S., Weichselbaum R., Kufe D.; RT "Regulation of DNA damage-induced apoptosis by the c-Abl tyrosine kinase."; RL Proc. Natl. Acad. Sci. U.S.A. 94:1437-1440(1997). RN [14] RP INTERACTION WITH RIN1, AND FUNCTION. RX PubMed=9144171; DOI=10.1073/pnas.94.10.4954; RA Han L., Wong D., Dhaka A., Afar D.E.H., White M., Xie W., Herschman H., RA Witte O., Colicelli J.; RT "Protein binding and signaling properties of RIN1 suggest a unique effector RT function."; RL Proc. Natl. Acad. Sci. U.S.A. 94:4954-4959(1997). RN [15] RP FUNCTION, AND INTERACTION WITH RAD51. RX PubMed=9461559; DOI=10.1074/jbc.273.7.3799; RA Yuan Z.M., Huang Y., Ishiko T., Nakada S., Utsugisawa T., Kharbanda S., RA Wang R., Sung P., Shinohara A., Weichselbaum R., Kufe D.; RT "Regulation of Rad51 function by c-Abl in response to DNA damage."; RL J. Biol. Chem. 273:3799-3802(1998). RN [16] RP INTERACTION WITH INPPL1. RX PubMed=10194451; RA Wisniewski D., Strife A., Swendeman S., Erdjument-Bromage H., Geromanos S., RA Kavanaugh W.M., Tempst P., Clarkson B.; RT "A novel SH2-containing phosphatidylinositol 3,4,5-trisphosphate 5- RT phosphatase (SHIP2) is constitutively tyrosine phosphorylated and RT associated with src homologous and collagen gene (SHC) in chronic RT myelogenous leukemia progenitor cells."; RL Blood 93:2707-2720(1999). RN [17] RP FUNCTION, ACTIVITY REGULATION, AND INTERACTION WITH TP73. RX PubMed=10391250; DOI=10.1038/21697; RA Agami R., Blandino G., Oren M., Shaul Y.; RT "Interaction of c-Abl and p73alpha and their collaboration to induce RT apoptosis."; RL Nature 399:809-813(1999). RN [18] RP DNA-BINDING. RX PubMed=10325413; DOI=10.1093/nar/27.11.2265; RA David-Cordonnier M.H., Payet D., D'Halluin J.C., Waring M.J., Travers A.A., RA Bailly C.; RT "The DNA-binding domain of human c-Abl tyrosine kinase promotes the RT interaction of a HMG chromosomal protein with DNA."; RL Nucleic Acids Res. 27:2265-2270(1999). RN [19] RP REVIEW ON FUNCTION. RX PubMed=11114745; DOI=10.1038/sj.onc.1203878; RA Wang J.Y.; RT "Regulation of cell death by the Abl tyrosine kinase."; RL Oncogene 19:5643-5650(2000). RN [20] RP INTERACTION WITH SORBS1. RX PubMed=11374898; DOI=10.1006/geno.2001.6541; RA Lin W.-H., Huang C.-J., Liu M.-W., Chang H.-M., Chen Y.-J., Tai T.-Y., RA Chuang L.-M.; RT "Cloning, mapping, and characterization of the human sorbin and SH3 domain RT containing 1 (SORBS1) gene: a protein associated with c-Abl during insulin RT signaling in the hepatoma cell line Hep3B."; RL Genomics 74:12-20(2001). RN [21] RP FUNCTION, AND INTERACTION WITH RAD52. RX PubMed=12379650; DOI=10.1074/jbc.m208151200; RA Kitao H., Yuan Z.M.; RT "Regulation of ionizing radiation-induced Rad52 nuclear foci formation by RT c-Abl-mediated phosphorylation."; RL J. Biol. Chem. 277:48944-48948(2002). RN [22] RP FUNCTION, AND INTERACTION WITH RAD9A. RX PubMed=11971963; DOI=10.1128/mcb.22.10.3292-3300.2002; RA Yoshida K., Komatsu K., Wang H.-G., Kufe D.; RT "c-Abl tyrosine kinase regulates the human Rad9 checkpoint protein in RT response to DNA damage."; RL Mol. Cell. Biol. 22:3292-3300(2002). RN [23] RP UBIQUITINATION. RX PubMed=12475393; DOI=10.1042/bj20021539; RA Soubeyran P., Barac A., Szymkiewicz I., Dikic I.; RT "Cbl-ArgBP2 complex mediates ubiquitination and degradation of c-Abl."; RL Biochem. J. 370:29-34(2003). RN [24] RP FUNCTION. RX PubMed=12531427; DOI=10.1016/s0898-6568(02)00090-6; RA Sanguinetti A.R., Mastick C.C.; RT "c-Abl is required for oxidative stress-induced phosphorylation of RT caveolin-1 on tyrosine 14."; RL Cell. Signal. 15:289-298(2003). RN [25] RP FUNCTION. RX PubMed=12672821; DOI=10.1074/jbc.m301447200; RA Tani K., Sato S., Sukezane T., Kojima H., Hirose H., Hanafusa H., RA Shishido T.; RT "Abl interactor 1 promotes tyrosine 296 phosphorylation of mammalian RT enabled (Mena) by c-Abl kinase."; RL J. Biol. Chem. 278:21685-21692(2003). RN [26] RP REVIEW ON FUNCTION. RX PubMed=12775773; DOI=10.1242/jcs.00622; RA Woodring P.J., Hunter T., Wang J.Y.; RT "Regulation of F-actin-dependent processes by the Abl family of tyrosine RT kinases."; RL J. Cell Sci. 116:2613-2626(2003). RN [27] RP INTERACTION WITH BCR. RX PubMed=15302586; DOI=10.1016/j.yexcr.2004.05.010; RA Laurent C.E., Smithgall T.E.; RT "The c-Fes tyrosine kinase cooperates with the breakpoint cluster region RT protein (Bcr) to induce neurite extension in a Rac- and Cdc42-dependent RT manner."; RL Exp. Cell Res. 299:188-198(2004). RN [28] RP FUNCTION. RX PubMed=15556646; DOI=10.1016/j.febslet.2004.10.054; RA Grossmann A.H., Kolibaba K.S., Willis S.G., Corbin A.S., Langdon W.S., RA Deininger M.W., Druker B.J.; RT "Catalytic domains of tyrosine kinases determine the phosphorylation sites RT within c-Cbl."; RL FEBS Lett. 577:555-562(2004). RN [29] RP FUNCTION. RX PubMed=15031292; DOI=10.1074/jbc.m311479200; RA Perkinton M.S., Standen C.L., Lau K.F., Kesavapany S., Byers H.L., Ward M., RA McLoughlin D.M., Miller C.C.; RT "The c-Abl tyrosine kinase phosphorylates the Fe65 adaptor protein to RT stimulate Fe65/amyloid precursor protein nuclear signaling."; RL J. Biol. Chem. 279:22084-22091(2004). RN [30] RP REVIEW ON FUNCTION. RX PubMed=15686624; DOI=10.1038/sj.cr.7290261; RA Shaul Y., Ben-Yehoyada M.; RT "Role of c-Abl in the DNA damage stress response."; RL Cell Res. 15:33-35(2005). RN [31] RP FUNCTION. RX PubMed=15886098; DOI=10.1016/j.cub.2005.03.049; RA Hu H., Bliss J.M., Wang Y., Colicelli J.; RT "RIN1 is an ABL tyrosine kinase activator and a regulator of epithelial- RT cell adhesion and migration."; RL Curr. Biol. 15:815-823(2005). RN [32] RP FUNCTION, AND INTERACTION WITH CASP9. RX PubMed=15657060; DOI=10.1074/jbc.m413787200; RA Raina D., Pandey P., Ahmad R., Bharti A., Ren J., Kharbanda S., RA Weichselbaum R., Kufe D.; RT "c-Abl tyrosine kinase regulates caspase-9 autocleavage in the apoptotic RT response to DNA damage."; RL J. Biol. Chem. 280:11147-11151(2005). RN [33] RP INTERACTION WITH YWHAB; YWHAE; YWHAG; YWHAH; SFN AND YWHAZ, PHOSPHORYLATION RP AT THR-735, IDENTIFICATION BY MASS SPECTROMETRY, SUBCELLULAR LOCATION, AND RP MUTAGENESIS OF THR-735. RX PubMed=15696159; DOI=10.1038/ncb1228; RA Yoshida K., Yamaguchi T., Natsume T., Kufe D., Miki Y.; RT "JNK phosphorylation of 14-3-3 proteins regulates nuclear targeting of c- RT Abl in the apoptotic response to DNA damage."; RL Nat. Cell Biol. 7:278-285(2005). RN [34] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-569, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling RT networks."; RL Cell 127:635-648(2006). RN [35] RP ACETYLATION AT LYS-711, AND SUBCELLULAR LOCATION. RX PubMed=16648821; DOI=10.1038/sj.embor.7400700; RA di Bari M.G., Ciuffini L., Mingardi M., Testi R., Soddu S., Barila D.; RT "c-Abl acetylation by histone acetyltransferases regulates its nuclear- RT cytoplasmic localization."; RL EMBO Rep. 7:727-733(2006). RN [36] RP PHOSPHORYLATION AT TYR-70; TYR-115; TYR-128; TYR-139; TYR-172; TYR-185 RP TYR-215; TYR-226 AND TYR-393, INTERACTION WITH HCK; LYN AND FYN, AND RP IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=16912036; DOI=10.1074/jbc.m605902200; RA Meyn M.A. III, Wilson M.B., Abdi F.A., Fahey N., Schiavone A.P., Wu J., RA Hochrein J.M., Engen J.R., Smithgall T.E.; RT "Src family kinases phosphorylate the Bcr-Abl SH3-SH2 region and modulate RT Bcr-Abl transforming activity."; RL J. Biol. Chem. 281:30907-30916(2006). RN [37] RP FUNCTION. RX PubMed=16943190; DOI=10.1074/jbc.m603126200; RA Tanos B., Pendergast A.M.; RT "Abl tyrosine kinase regulates endocytosis of the epidermal growth factor RT receptor."; RL J. Biol. Chem. 281:32714-32723(2006). RN [38] RP FUNCTION, AND INTERACTION WITH PSMA7. RX PubMed=16678104; DOI=10.1016/j.molcel.2006.04.007; RA Liu X., Huang W., Li C., Li P., Yuan J., Li X., Qiu X.B., Ma Q., Cao C.; RT "Interaction between c-Abl and Arg tyrosine kinases and proteasome subunit RT PSMA7 regulates proteasome degradation."; RL Mol. Cell 22:317-327(2006). RN [39] RP FUNCTION. RX PubMed=17306540; DOI=10.1016/j.cub.2007.01.057; RA Boyle S.N., Michaud G.A., Schweitzer B., Predki P.F., Koleske A.J.; RT "A critical role for cortactin phosphorylation by Abl-family kinases in RT PDGF-induced dorsal-wave formation."; RL Curr. Biol. 17:445-451(2007). RN [40] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH WASF3. RX PubMed=17623672; DOI=10.1074/jbc.m701484200; RA Sossey-Alaoui K., Li X., Cowell J.K.; RT "c-Abl-mediated phosphorylation of WAVE3 is required for lamellipodia RT formation and cell migration."; RL J. Biol. Chem. 282:26257-26265(2007). RN [41] RP PHOSPHORYLATION AT SER-618 AND SER-619, AND INTERACTION WITH ABI2 AND CRK. RX PubMed=18161990; DOI=10.1021/bi701533j; RA Jung J.H., Pendergast A.M., Zipfel P.A., Traugh J.A.; RT "Phosphorylation of c-Abl by protein kinase Pak2 regulates differential RT binding of ABI2 and CRK."; RL Biochemistry 47:1094-1104(2008). RN [42] RP FUNCTION, AND ACTIVITY REGULATION. RX PubMed=18328268; DOI=10.1016/j.bbamcr.2008.01.028; RA Xiong X., Cui P., Hossain S., Xu R., Warner B., Guo X., An X., RA Debnath A.K., Cowburn D., Kotula L.; RT "Allosteric inhibition of the nonMyristoylated c-Abl tyrosine kinase by RT phosphopeptides derived from Abi1/Hssh3bp1."; RL Biochim. Biophys. Acta 1783:737-747(2008). RN [43] RP FUNCTION. RX PubMed=18945674; DOI=10.1074/jbc.m804543200; RA Yogalingam G., Pendergast A.M.; RT "Abl kinases regulate autophagy by promoting the trafficking and function RT of lysosomal components."; RL J. Biol. Chem. 283:35941-35953(2008). RN [44] RP PHOSPHORYLATION AT TYR-70, AND INTERACTION WITH ABI1. RX PubMed=18775435; DOI=10.1016/j.jmb.2008.08.040; RA Chen S., O'Reilly L.P., Smithgall T.E., Engen J.R.; RT "Tyrosine phosphorylation in the SH3 domain disrupts negative regulatory RT interactions within the c-Abl kinase core."; RL J. Mol. Biol. 383:414-423(2008). RN [45] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-50; SER-569; SER-659; RP THR-814; THR-844 AND SER-977, AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the RT kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [46] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-569; THR-852 AND SER-917, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [47] RP REVIEW ON FUNCTION. RX PubMed=18182299; DOI=10.1016/j.tibs.2007.10.006; RA Backert S., Feller S.M., Wessler S.; RT "Emerging roles of Abl family tyrosine kinases in microbial pathogenesis."; RL Trends Biochem. Sci. 33:80-90(2008). RN [48] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [49] RP FUNCTION. RX PubMed=19891780; DOI=10.1186/1471-2121-10-80; RA Fernow I., Tomasovic A., Siehoff-Icking A., Tikkanen R.; RT "Cbl-associated protein is tyrosine phosphorylated by c-Abl and c-Src RT kinases."; RL BMC Cell Biol. 10:80-80(2009). RN [50] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-569, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200; RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., RA Mann M., Daub H.; RT "Large-scale proteomics analysis of the human kinome."; RL Mol. Cell. Proteomics 8:1751-1764(2009). RN [51] RP IDENTIFICATION IN A COMPLEX WITH UNC119; ABL2 AND CRK. RX PubMed=19381274; DOI=10.1371/journal.pone.0005211; RA Vepachedu R., Karim Z., Patel O., Goplen N., Alam R.; RT "Unc119 protects from Shigella infection by inhibiting the Abl family RT kinases."; RL PLoS ONE 4:E5211-E5211(2009). RN [52] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-50 AND SER-569, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [53] RP FUNCTION. RX PubMed=20417104; DOI=10.1016/j.cub.2010.03.048; RA Michael M., Vehlow A., Navarro C., Krause M.; RT "c-Abl, Lamellipodin, and Ena/VASP proteins cooperate in dorsal ruffling of RT fibroblasts and axonal morphogenesis."; RL Curr. Biol. 20:783-791(2010). RN [54] RP INTERACTION WITH MYLK AND CTTN. RX PubMed=20861316; DOI=10.1091/mbc.e09-10-0876; RA Dudek S.M., Chiang E.T., Camp S.M., Guo Y., Zhao J., Brown M.E., RA Singleton P.A., Wang L., Desai A., Arce F.T., Lal R., Van Eyk J.E., RA Imam S.Z., Garcia J.G.N.; RT "Abl tyrosine kinase phosphorylates nonmuscle Myosin light chain kinase to RT regulate endothelial barrier function."; RL Mol. Biol. Cell 21:4042-4056(2010). RN [55] RP REVIEW ON FUNCTION, AND DOMAIN. RX PubMed=20841568; DOI=10.1126/scisignal.3139re6; RA Colicelli J.; RT "ABL tyrosine kinases: evolution of function, regulation, and RT specificity."; RL Sci. Signal. 3:RE6-RE6(2010). RN [56] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [57] RP INTERACTION WITH STX17. RX PubMed=23006999; DOI=10.1016/j.bbamcr.2012.09.003; RA Muppirala M., Gupta V., Swarup G.; RT "Tyrosine phosphorylation of a SNARE protein, Syntaxin 17: Implications for RT membrane trafficking in the early secretory pathway."; RL Biochim. Biophys. Acta 1823:2109-2119(2012). RN [58] RP FUNCTION, AND INTERACTION WITH NEDD9. RX PubMed=22810897; DOI=10.1126/scisignal.2002632; RA Gu J.J., Lavau C.P., Pugacheva E., Soderblom E.J., Moseley M.A., RA Pendergast A.M.; RT "Abl family kinases modulate T cell-mediated inflammation and chemokine- RT induced migration through the adaptor HEF1 and the GTPase Rap1."; RL Sci. Signal. 5:ra51-ra51(2012). RN [59] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-253; TYR-257; TYR-413; RP SER-559; SER-569; SER-620; SER-683; SER-718; THR-751; THR-781; THR-823; RP THR-844; THR-852; SER-855 AND SER-917, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [60] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-569, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [61] RP FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION. RX PubMed=28428613; DOI=10.1038/s41598-017-00800-w; RA Cobbaut M., Derua R., Doeppler H., Lou H.J., Vandoninck S., Storz P., RA Turk B.E., Seufferlein T., Waelkens E., Janssens V., Van Lint J.; RT "Differential regulation of PKD isoforms in oxidative stress conditions RT through phosphorylation of a conserved Tyr in the P+1 loop."; RL Sci. Rep. 7:887-887(2017). RN [62] RP STRUCTURE BY NMR OF SH2 DOMAIN. RX PubMed=1505033; DOI=10.1016/0092-8674(92)90437-h; RA Overduin M., Rios C.B., Mayer B.J., Baltimore D., Cowburn D.; RT "Three-dimensional solution structure of the src homology 2 domain of c- RT abl."; RL Cell 70:697-704(1992). RN [63] RP STRUCTURE BY NMR OF SH2 DOMAIN. RX PubMed=1281542; DOI=10.1073/pnas.89.24.11673; RA Overduin M., Mayer B.J., Rios C.B., Baltimore D., Cowburn D.; RT "Secondary structure of Src homology 2 domain of c-Abl by heteronuclear NMR RT spectroscopy in solution."; RL Proc. Natl. Acad. Sci. U.S.A. 89:11673-11677(1992). RN [64] RP 3D-STRUCTURE MODELING OF SH3 DOMAIN. RX PubMed=7892170; DOI=10.1002/prot.340200302; RA Pisabarro M.T., Ortiz A.R., Serrano L., Wade R.C.; RT "Homology modeling of the Abl-SH3 domain."; RL Proteins 20:203-215(1994). RN [65] RP STRUCTURE BY NMR OF SH3 DOMAIN. RX PubMed=8590002; DOI=10.1016/s0969-2126(01)00243-x; RA Gosser Y.Q., Zheng J., Overduin M., Mayer B.J., Cowburn D.; RT "The solution structure of Abl SH3, and its relationship to SH2 in the RT SH(32) construct."; RL Structure 3:1075-1086(1995). RN [66] RP X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 64-121. RX PubMed=9698566; DOI=10.1006/jmbi.1998.1932; RA Pisabarro M.T., Serrano L., Wilmanns M.; RT "Crystal structure of the abl-SH3 domain complexed with a designed high- RT affinity peptide ligand: implications for SH3-ligand interactions."; RL J. Mol. Biol. 281:513-521(1998). RN [67] RP STRUCTURE BY NMR OF 62-122 IN COMPLEX WITH CRK. RX PubMed=12384576; DOI=10.1073/pnas.212518799; RA Donaldson L.W., Gish G., Pawson T., Kay L.E., Forman-Kay J.D.; RT "Structure of a regulatory complex involving the Abl SH3 domain, the Crk RT SH2 domain, and a Crk-derived phosphopeptide."; RL Proc. Natl. Acad. Sci. U.S.A. 99:14053-14058(2002). RN [68] RP X-RAY CRYSTALLOGRAPHY (3.42 ANGSTROMS) OF 27-512, MYRISTOYLATION AT GLY-2 RP (ISOFORM IB), ACTIVITY REGULATION, AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=12654251; DOI=10.1016/s0092-8674(03)00194-6; RA Nagar B., Hantschel O., Young M.A., Scheffzek K., Veach D., Bornmann W., RA Clarkson B., Superti-Furga G., Kuriyan J.; RT "Structural basis for the autoinhibition of c-Abl tyrosine kinase."; RL Cell 112:859-871(2003). RN [69] RP X-RAY CRYSTALLOGRAPHY (1.91 ANGSTROMS) OF 229-513 OF MUTANT PRO-396 IN RP COMPLEX WITH INHIBITOR VX-680, FUNCTION, AND ACTIVITY REGULATION. RX PubMed=16424036; DOI=10.1158/0008-5472.can-05-2788; RA Young M.A., Shah N.P., Chao L.H., Seeliger M., Milanov Z.V., RA Biggs W.H. III, Treiber D.K., Patel H.K., Zarrinkar P.P., Lockhart D.J., RA Sawyers C.L., Kuriyan J.; RT "Structure of the kinase domain of an imatinib-resistant Abl mutant in RT complex with the Aurora kinase inhibitor VX-680."; RL Cancer Res. 66:1007-1014(2006). RN [70] RP X-RAY CRYSTALLOGRAPHY (2.27 ANGSTROMS) OF 38-512, IDENTIFICATION BY MASS RP SPECTROMETRY, MYRISTOYLATION AT GLY-2 (ISOFORM IB), PHOSPHORYLATION AT RP SER-50, AUTOINHIBITORY MECHANISM, AND ACTIVITY REGULATION. RX PubMed=16543148; DOI=10.1016/j.molcel.2006.01.035; RA Nagar B., Hantschel O., Seeliger M., Davies J.M., Weis W.I., RA Superti-Furga G., Kuriyan J.; RT "Organization of the SH3-SH2 unit in active and inactive forms of the c-Abl RT tyrosine kinase."; RL Mol. Cell 21:787-798(2006). RN [71] RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 229-512 IN COMPLEXES WITH RP ATP-PEPTIDE CONJUGATE, AND CONFORMATION CHANGES DURING ACTIVATION. RX PubMed=16640460; DOI=10.1371/journal.pbio.0040144; RA Levinson N.M., Kuchment O., Shen K., Young M.A., Koldobskiy M., Karplus M., RA Cole P.A., Kuriyan J.; RT "A Src-like inactive conformation in the abl tyrosine kinase domain."; RL PLoS Biol. 4:E144-E144(2006). RN [72] RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 229-500 IN COMPLEXES WITH IMATINIB RP AND WITH THE INHIBITORS NVP-AEG082; NVP-AFN941; NVP-AFG210 AND PD180970. RX PubMed=17164530; DOI=10.1107/s0907444906047287; RA Cowan-Jacob S.W., Fendrich G., Floersheimer A., Furet P., Liebetanz J., RA Rummel G., Rheinberger P., Centeleghe M., Fabbro D., Manley P.W.; RT "Structural biology contributions to the discovery of drugs to treat RT chronic myelogenous leukaemia."; RL Acta Crystallogr. D 63:80-93(2007). RN [73] RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 64-121 OF MUTANT ALA-114 IN RP COMPLEX WITH PROLINE-RICH PEPTIDE. RX PubMed=17452790; DOI=10.1107/s0907444907011109; RA Camara-Artigas A., Palencia A., Martinez J.C., Luque I., Gavira J.A., RA Garcia-Ruiz J.M.; RT "Crystallization by capillary counter-diffusion and structure determination RT of the N114A mutant of the SH3 domain of Abl tyrosine kinase complexed with RT a high-affinity peptide ligand."; RL Acta Crystallogr. D 63:646-652(2007). RN [74] RP X-RAY CRYSTALLOGRAPHY (1.4 ANGSTROMS) OF 60-121 IN COMPLEX WITH RP PROLINE-RICH PEPTIDE P41. RX PubMed=19906645; DOI=10.1074/jbc.m109.048033; RA Palencia A., Camara-Artigas A., Pisabarro M.T., Martinez J.C., Luque I.; RT "Role of interfacial water molecules in proline-rich ligand recognition by RT the Src homology 3 domain of Abl."; RL J. Biol. Chem. 285:2823-2833(2010). RN [75] RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 121-232 IN COMPLEX WITH ANTIBODY RP MIMIC HA4, FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=20357770; DOI=10.1038/nsmb.1793; RA Wojcik J., Hantschel O., Grebien F., Kaupe I., Bennett K.L., Barkinge J., RA Jones R.B., Koide A., Superti-Furga G., Koide S.; RT "A potent and highly specific FN3 monobody inhibitor of the Abl SH2 RT domain."; RL Nat. Struct. Mol. Biol. 17:519-527(2010). RN [76] RP DISEASE, AND CHROMOSOMAL TRANSLOCATION WITH NUP214. RX PubMed=15361874; DOI=10.1038/ng1425; RA Graux C., Cools J., Melotte C., Quentmeier H., Ferrando A., Levine R., RA Vermeesch J.R., Stul M., Dutta B., Boeckx N., Bosly A., Heimann P., RA Uyttebroeck A., Mentens N., Somers R., MacLeod R.A., Drexler H.G., RA Look A.T., Gilliland D.G., Michaux L., Vandenberghe P., Wlodarska I., RA Marynen P., Hagemeijer A.; RT "Fusion of NUP214 to ABL1 on amplified episomes in T-cell acute RT lymphoblastic leukemia."; RL Nat. Genet. 36:1084-1089(2004). RN [77] RP VARIANTS GLY-47; LYS-166; VAL-706; LEU-810 AND LEU-972. RX PubMed=17344846; DOI=10.1038/nature05610; RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G., RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., RA Futreal P.A., Stratton M.R.; RT "Patterns of somatic mutation in human cancer genomes."; RL Nature 446:153-158(2007). RN [78] RP INVOLVEMENT IN CHDSKM, VARIANTS CHDSKM CYS-226 AND THR-337, AND RP CHARACTERIZATION OF VARIANTS CHDSKM CYS-226 AND THR-337. RX PubMed=28288113; DOI=10.1038/ng.3815; RA Wang X., Charng W.L., Chen C.A., Rosenfeld J.A., Al Shamsi A., RA Al-Gazali L., McGuire M., Mew N.A., Arnold G.L., Qu C., Ding Y., RA Muzny D.M., Gibbs R.A., Eng C.M., Walkiewicz M., Xia F., Plon S.E., RA Lupski J.R., Schaaf C.P., Yang Y.; RT "Germline mutations in ABL1 cause an autosomal dominant syndrome RT characterized by congenital heart defects and skeletal malformations."; RL Nat. Genet. 49:613-617(2017). CC -!- FUNCTION: Non-receptor tyrosine-protein kinase that plays a role in CC many key processes linked to cell growth and survival such as CC cytoskeleton remodeling in response to extracellular stimuli, cell CC motility and adhesion, receptor endocytosis, autophagy, DNA damage CC response and apoptosis. Coordinates actin remodeling through tyrosine CC phosphorylation of proteins controlling cytoskeleton dynamics like CC WASF3 (involved in branch formation); ANXA1 (involved in membrane CC anchoring); DBN1, DBNL, CTTN, RAPH1 and ENAH (involved in signaling); CC or MAPT and PXN (microtubule-binding proteins). Phosphorylation of CC WASF3 is critical for the stimulation of lamellipodia formation and CC cell migration. Involved in the regulation of cell adhesion and CC motility through phosphorylation of key regulators of these processes CC such as BCAR1, CRK, CRKL, DOK1, EFS or NEDD9 (PubMed:22810897). CC Phosphorylates multiple receptor tyrosine kinases and more particularly CC promotes endocytosis of EGFR, facilitates the formation of CC neuromuscular synapses through MUSK, inhibits PDGFRB-mediated CC chemotaxis and modulates the endocytosis of activated B-cell receptor CC complexes. Other substrates which are involved in endocytosis CC regulation are the caveolin (CAV1) and RIN1. Moreover, ABL1 regulates CC the CBL family of ubiquitin ligases that drive receptor down-regulation CC and actin remodeling. Phosphorylation of CBL leads to increased EGFR CC stability. Involved in late-stage autophagy by regulating positively CC the trafficking and function of lysosomal components. ABL1 targets to CC mitochondria in response to oxidative stress and thereby mediates CC mitochondrial dysfunction and cell death. In response to oxidative CC stress, phosphorylates serine/threonine kinase PRKD2 at 'Tyr-717' CC (PubMed:28428613). ABL1 is also translocated in the nucleus where it CC has DNA-binding activity and is involved in DNA-damage response and CC apoptosis. Many substrates are known mediators of DNA repair: DDB1, CC DDB2, ERCC3, ERCC6, RAD9A, RAD51, RAD52 or WRN. Activates the CC proapoptotic pathway when the DNA damage is too severe to be repaired. CC Phosphorylates TP73, a primary regulator for this type of damage- CC induced apoptosis. Phosphorylates the caspase CASP9 on 'Tyr-153' and CC regulates its processing in the apoptotic response to DNA damage. CC Phosphorylates PSMA7 that leads to an inhibition of proteasomal CC activity and cell cycle transition blocks. ABL1 also acts as a CC regulator of multiple pathological signaling cascades during infection. CC Several known tyrosine-phosphorylated microbial proteins have been CC identified as ABL1 substrates. This is the case of A36R of Vaccinia CC virus, Tir (translocated intimin receptor) of pathogenic E.coli and CC possibly Citrobacter, CagA (cytotoxin-associated gene A) of H.pylori, CC or AnkA (ankyrin repeat-containing protein A) of A.phagocytophilum. CC Pathogens can highjack ABL1 kinase signaling to reorganize the host CC actin cytoskeleton for multiple purposes, like facilitating CC intracellular movement and host cell exit. Finally, functions as its CC own regulator through autocatalytic activity as well as through CC phosphorylation of its inhibitor, ABI1. Regulates T-cell CC differentiation in a TBX21-dependent manner (By similarity). Positively CC regulates chemokine-mediated T-cell migration, polarization, and homing CC to lymph nodes and immune-challenged tissues, potentially via CC activation of NEDD9/HEF1 and RAP1 (By similarity). Phosphorylates TBX21 CC on tyrosine residues leading to an enhancement of its transcriptional CC activator activity (By similarity). {ECO:0000250|UniProtKB:P00520, CC ECO:0000269|PubMed:10391250, ECO:0000269|PubMed:11971963, CC ECO:0000269|PubMed:12379650, ECO:0000269|PubMed:12531427, CC ECO:0000269|PubMed:12672821, ECO:0000269|PubMed:15031292, CC ECO:0000269|PubMed:15556646, ECO:0000269|PubMed:15657060, CC ECO:0000269|PubMed:15886098, ECO:0000269|PubMed:16424036, CC ECO:0000269|PubMed:16678104, ECO:0000269|PubMed:16943190, CC ECO:0000269|PubMed:17306540, ECO:0000269|PubMed:17623672, CC ECO:0000269|PubMed:18328268, ECO:0000269|PubMed:18945674, CC ECO:0000269|PubMed:19891780, ECO:0000269|PubMed:20357770, CC ECO:0000269|PubMed:20417104, ECO:0000269|PubMed:22810897, CC ECO:0000269|PubMed:28428613, ECO:0000269|PubMed:9037071, CC ECO:0000269|PubMed:9144171, ECO:0000269|PubMed:9461559}. CC -!- CATALYTIC ACTIVITY: CC Reaction=L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + CC ADP + H(+); Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA- CC COMP:20101, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858, CC ChEBI:CHEBI:61978, ChEBI:CHEBI:456216; EC=2.7.10.2; CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10028, CC ECO:0000269|PubMed:20357770, ECO:0000269|PubMed:28428613}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000250|UniProtKB:P00520}; CC -!- ACTIVITY REGULATION: Stabilized in the inactive form by an association CC between the SH3 domain and the SH2-TK linker region, interactions of CC the N-terminal cap, and contributions from an N-terminal myristoyl CC group and phospholipids. Activated by autophosphorylation as well as by CC SRC-family kinase-mediated phosphorylation. Activated by RIN1 binding CC to the SH2 and SH3 domains. Also stimulated by cell death inducers and CC DNA-damage. Phosphatidylinositol 4,5-bisphosphate (PIP2), a highly CC abundant phosphoinositide known to regulate cytoskeletal and membrane CC proteins, also inhibits the tyrosine kinase activity (By similarity). CC Activated by 5-(1,3-diaryl-1H-pyrazol-4-yl)hydantoin, 5-[3-(4- CC fluorophenyl)-1-phenyl-1H-pyrazol-4-yl]-2,4-imidazolidinedione (DPH) CC (PubMed:28428613). Inhibited by ABI1, whose activity is controlled by CC ABL1 itself through tyrosine phosphorylation. Also inhibited by CC imatinib mesylate (Gleevec) which is used for the treatment of chronic CC myeloid leukemia (CML), and by VX-680, an inhibitor that also acts on CC imatinib-resistant mutants (PubMed:28428613). {ECO:0000250, CC ECO:0000269|PubMed:10391250, ECO:0000269|PubMed:12654251, CC ECO:0000269|PubMed:16424036, ECO:0000269|PubMed:16543148, CC ECO:0000269|PubMed:18328268, ECO:0000269|PubMed:28428613}. CC -!- SUBUNIT: Interacts with SORBS1 following insulin stimulation. Found in CC a trimolecular complex containing CDK5 and CABLES1. Interacts with CC CABLES1 and PSTPIP1. Interacts with ZDHHC16, ITGB1 and HCK (By CC similarity). Interacts with STX17; probably phosphorylates STX17. CC Interacts with INPPL1/SHIP2. Interacts with the 14-3-3 proteins, YWHAB, CC YWHAE, YWHAG, YWHAH, SFN and YWHAZ; the interaction with 14-3-3 CC proteins requires phosphorylation on Thr-735 and, sequesters ABL1 into CC the cytoplasm. Interacts with ABI1, ABI2, BCR, CRK, FGR, FYN, HCK, LYN, CC PSMA7 RAD9A, RAD51, RAD52, TP73 and WASF3. A complex made of ABL1, CTTN CC and MYLK regulates cortical actin-based cytoskeletal rearrangement CC critical to sphingosine 1-phosphate (S1P)-mediated endothelial cell CC (EC) barrier enhancement. Interacts (via SH3 domain) with CASP9; the CC interaction is direct and increases in the response of cells to CC genotoxic stress and ABL1/c-Abl activation. Found in a complex with CC ABL1, ABL2, CRK and UNC119; leading to the inhibition of CRK CC phosphorylation by ABL kinases. Interacts with TBX21 (By similarity). CC Interacts with NEDD9/HEF1; interaction is induced by CXCL12 promotion CC of ABL-mediated phosphorylation of NEDD9/HEF1 (PubMed:22810897). CC {ECO:0000250|UniProtKB:P00520, ECO:0000269|PubMed:10194451, CC ECO:0000269|PubMed:10391250, ECO:0000269|PubMed:11374898, CC ECO:0000269|PubMed:11971963, ECO:0000269|PubMed:12379650, CC ECO:0000269|PubMed:12384576, ECO:0000269|PubMed:15302586, CC ECO:0000269|PubMed:15657060, ECO:0000269|PubMed:15696159, CC ECO:0000269|PubMed:16424036, ECO:0000269|PubMed:16678104, CC ECO:0000269|PubMed:16912036, ECO:0000269|PubMed:17452790, CC ECO:0000269|PubMed:17623672, ECO:0000269|PubMed:18161990, CC ECO:0000269|PubMed:18775435, ECO:0000269|PubMed:19381274, CC ECO:0000269|PubMed:19906645, ECO:0000269|PubMed:20357770, CC ECO:0000269|PubMed:20861316, ECO:0000269|PubMed:22810897, CC ECO:0000269|PubMed:23006999, ECO:0000269|PubMed:9144171, CC ECO:0000269|PubMed:9461559}. CC -!- INTERACTION: CC P00519; Q8IZP0: ABI1; NbExp=11; IntAct=EBI-375543, EBI-375446; CC P00519; Q9NYB9: ABI2; NbExp=3; IntAct=EBI-375543, EBI-743598; CC P00519; O14672: ADAM10; NbExp=2; IntAct=EBI-375543, EBI-1536151; CC P00519; P10275: AR; NbExp=2; IntAct=EBI-375543, EBI-608057; CC P00519; Q13315: ATM; NbExp=4; IntAct=EBI-375543, EBI-495465; CC P00519; Q4KMG0: CDON; NbExp=2; IntAct=EBI-375543, EBI-7016840; CC P00519; P46108: CRK; NbExp=5; IntAct=EBI-375543, EBI-886; CC P00519; P46109: CRKL; NbExp=4; IntAct=EBI-375543, EBI-910; CC P00519; P35222: CTNNB1; NbExp=2; IntAct=EBI-375543, EBI-491549; CC P00519; P00533: EGFR; NbExp=3; IntAct=EBI-375543, EBI-297353; CC P00519; P04626: ERBB2; NbExp=2; IntAct=EBI-375543, EBI-641062; CC P00519; Q03468: ERCC6; NbExp=8; IntAct=EBI-375543, EBI-295284; CC P00519; Q14315: FLNC; NbExp=2; IntAct=EBI-375543, EBI-489954; CC P00519; P36888: FLT3; NbExp=2; IntAct=EBI-375543, EBI-3946257; CC P00519; P08631: HCK; NbExp=5; IntAct=EBI-375543, EBI-346340; CC P00519; P05107: ITGB2; NbExp=4; IntAct=EBI-375543, EBI-300173; CC P00519; P10721: KIT; NbExp=2; IntAct=EBI-375543, EBI-1379503; CC P00519; Q38SD2: LRRK1; NbExp=3; IntAct=EBI-375543, EBI-1050422; CC P00519; Q92918: MAP4K1; NbExp=3; IntAct=EBI-375543, EBI-881; CC P00519; Q7Z434: MAVS; NbExp=6; IntAct=EBI-375543, EBI-995373; CC P00519; O43196: MSH5; NbExp=10; IntAct=EBI-375543, EBI-6092730; CC P00519; P15941: MUC1; NbExp=4; IntAct=EBI-375543, EBI-2804728; CC P00519; P15941-12: MUC1; NbExp=4; IntAct=EBI-375543, EBI-34603716; CC P00519; P16333: NCK1; NbExp=2; IntAct=EBI-375543, EBI-389883; CC P00519; O43900: PRICKLE3; NbExp=2; IntAct=EBI-375543, EBI-1751761; CC P00519; Q13905: RAPGEF1; NbExp=4; IntAct=EBI-375543, EBI-976876; CC P00519; Q86UR5: RIMS1; NbExp=2; IntAct=EBI-375543, EBI-1043236; CC P00519; Q13671: RIN1; NbExp=6; IntAct=EBI-375543, EBI-366017; CC P00519; P31947: SFN; NbExp=5; IntAct=EBI-375543, EBI-476295; CC P00519; Q15464: SHB; NbExp=5; IntAct=EBI-375543, EBI-4402156; CC P00519; O75751: SLC22A3; NbExp=2; IntAct=EBI-375543, EBI-1752674; CC P00519; P37840: SNCA; NbExp=3; IntAct=EBI-375543, EBI-985879; CC P00519; Q9BX66: SORBS1; NbExp=2; IntAct=EBI-375543, EBI-433642; CC P00519; O60504-2: SORBS3; NbExp=5; IntAct=EBI-375543, EBI-1222956; CC P00519; Q07890: SOS2; NbExp=2; IntAct=EBI-375543, EBI-298181; CC P00519; P12931: SRC; NbExp=2; IntAct=EBI-375543, EBI-621482; CC P00519; P51692: STAT5B; NbExp=2; IntAct=EBI-375543, EBI-1186119; CC P00519; Q9Y4G6: TLN2; NbExp=3; IntAct=EBI-375543, EBI-1220811; CC P00519; P11387: TOP1; NbExp=7; IntAct=EBI-375543, EBI-876302; CC P00519; P04637: TP53; NbExp=2; IntAct=EBI-375543, EBI-366083; CC P00519; P15498: VAV1; NbExp=5; IntAct=EBI-375543, EBI-625518; CC P00519; Q92558: WASF1; NbExp=3; IntAct=EBI-375543, EBI-1548747; CC P00519; Q9Y6W5: WASF2; NbExp=2; IntAct=EBI-375543, EBI-4290615; CC P00519; P62258: YWHAE; NbExp=6; IntAct=EBI-375543, EBI-356498; CC P00519; P61981: YWHAG; NbExp=8; IntAct=EBI-375543, EBI-359832; CC P00519; P63104: YWHAZ; NbExp=4; IntAct=EBI-375543, EBI-347088; CC P00519; O35158: Cdon; Xeno; NbExp=4; IntAct=EBI-375543, EBI-7016767; CC P00519-1; P37840: SNCA; NbExp=6; IntAct=EBI-5278159, EBI-985879; CC P00519-2; P48165: GJA8; NbExp=3; IntAct=EBI-9254597, EBI-17458373; CC P00519-2; Q15323: KRT31; NbExp=3; IntAct=EBI-9254597, EBI-948001; CC P00519-2; P37840: SNCA; NbExp=5; IntAct=EBI-9254597, EBI-985879; CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton. Nucleus. Mitochondrion CC {ECO:0000250}. Note=Shuttles between the nucleus and cytoplasm CC depending on environmental signals. Sequestered into the cytoplasm CC through interaction with 14-3-3 proteins. Localizes to mitochondria in CC response to oxidative stress (By similarity). {ECO:0000250}. CC -!- SUBCELLULAR LOCATION: [Isoform IB]: Nucleus membrane; Lipid-anchor. CC Note=The myristoylated c-ABL protein is reported to be nuclear. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=IA; CC IsoId=P00519-1; Sequence=Displayed; CC Name=IB; CC IsoId=P00519-2; Sequence=VSP_004957; CC -!- TISSUE SPECIFICITY: Widely expressed. CC -!- PTM: Acetylated at Lys-711 by EP300 which promotes the cytoplasmic CC translocation. {ECO:0000269|PubMed:16648821}. CC -!- PTM: Phosphorylation at Tyr-70 by members of the SRC family of kinases CC disrupts SH3 domain-based autoinhibitory interactions and CC intermolecular associations, such as that with ABI1, and also enhances CC kinase activity. Phosphorylation at Tyr-226 and Tyr-393 correlate with CC increased activity. DNA damage-induced activation of ABL1 requires the CC function of ATM and Ser-446 phosphorylation (By similarity). CC Phosphorylation at Ser-569 has been attributed to a CDC2-associated CC kinase and is coupled to cell division (By similarity). Phosphorylation CC at Ser-618 and Ser-619 by PAK2 increases binding to CRK and reduces CC binding to ABI1. Phosphorylation on Thr-735 is required for binding 14- CC 3-3 proteins for cytoplasmic translocation. Phosphorylated by PRKDC (By CC similarity). {ECO:0000250}. CC -!- PTM: Polyubiquitinated. Polyubiquitination of ABL1 leads to CC degradation. {ECO:0000269|PubMed:12475393}. CC -!- DISEASE: Leukemia, chronic myeloid (CML) [MIM:608232]: A clonal CC myeloproliferative disorder of a pluripotent stem cell with a specific CC cytogenetic abnormality, the Philadelphia chromosome (Ph), involving CC myeloid, erythroid, megakaryocytic, B-lymphoid, and sometimes T- CC lymphoid cells, but not marrow fibroblasts. Note=The gene represented CC in this entry is involved in disease pathogenesis. CC -!- DISEASE: Note=A chromosomal aberration involving ABL1 has been found in CC patients with chronic myeloid leukemia. Translocation t(9;22)(q34;q11) CC with BCR. The translocation produces a BCR-ABL found also in acute CC myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). CC {ECO:0000269|PubMed:3021337}. CC -!- DISEASE: Note=A chromosomal aberration involving ABL1 is found in a CC form of acute lymphoblastic leukemia (PubMed:15361874). Translocation CC t(9;9)(q34;q34) with NUP214 (PubMed:15361874). CC {ECO:0000269|PubMed:15361874}. CC -!- DISEASE: Congenital heart defects and skeletal malformations syndrome CC (CHDSKM) [MIM:617602]: An autosomal dominant disorder characterized by CC congenital heart disease with atrial and ventricular septal defects, CC variable skeletal abnormalities, and failure to thrive. Skeletal CC defects include pectus excavatum, scoliosis, and finger contractures. CC Some patient exhibit joint laxity. {ECO:0000269|PubMed:28288113}. CC Note=The disease is caused by variants affecting the gene represented CC in this entry. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein CC kinase family. ABL subfamily. {ECO:0000255|PROSITE-ProRule:PRU00159}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/1/ABL"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M14752; AAA51561.1; -; mRNA. DR EMBL; X16416; CAA34438.1; -; mRNA. DR EMBL; U07563; AAB60394.1; -; Genomic_DNA. DR EMBL; U07563; AAB60393.1; -; Genomic_DNA. DR EMBL; U07561; AAB60393.1; JOINED; Genomic_DNA. DR EMBL; DQ145721; AAZ38718.1; -; Genomic_DNA. DR EMBL; AL359092; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL161733; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471090; EAW87948.1; -; Genomic_DNA. DR EMBL; BC117451; AAI17452.1; -; mRNA. DR EMBL; S69223; AAD14034.1; -; Genomic_DNA. DR CCDS; CCDS35165.1; -. [P00519-2] DR CCDS; CCDS35166.1; -. [P00519-1] DR PIR; S08519; TVHUA. DR RefSeq; NP_005148.2; NM_005157.6. [P00519-1] DR RefSeq; NP_009297.2; NM_007313.3. [P00519-2] DR PDB; 1AB2; NMR; -; A=120-220. DR PDB; 1AWO; NMR; -; A=65-119. DR PDB; 1BBZ; X-ray; 1.65 A; A/C/E/G=64-121. DR PDB; 1JU5; NMR; -; C=62-122. DR PDB; 1OPL; X-ray; 3.42 A; A/B=27-512. DR PDB; 1ZZP; NMR; -; A=1007-1130. DR PDB; 2ABL; X-ray; 2.50 A; A=57-218. DR PDB; 2E2B; X-ray; 2.20 A; A/B=229-515. DR PDB; 2F4J; X-ray; 1.91 A; A=229-513. DR PDB; 2FO0; X-ray; 2.27 A; A=38-512. DR PDB; 2G1T; X-ray; 1.80 A; A/B/C/D=229-512. DR PDB; 2G2F; X-ray; 2.70 A; A/B=229-512. DR PDB; 2G2H; X-ray; 2.00 A; A/B=229-512. DR PDB; 2G2I; X-ray; 3.12 A; A/B=229-512. DR PDB; 2GQG; X-ray; 2.40 A; A/B=229-500. DR PDB; 2HIW; X-ray; 2.20 A; A/B=230-512. DR PDB; 2HYY; X-ray; 2.40 A; A/B/C/D=228-500. DR PDB; 2HZ0; X-ray; 2.10 A; A/B=228-497. DR PDB; 2HZ4; X-ray; 2.80 A; A/B/C=228-500. DR PDB; 2HZI; X-ray; 1.70 A; A/B=229-500. DR PDB; 2O88; X-ray; 1.75 A; A/B=64-121. DR PDB; 2V7A; X-ray; 2.50 A; A/B=229-512. DR PDB; 3CS9; X-ray; 2.21 A; A/B/C/D=229-500. DR PDB; 3EG0; X-ray; 2.30 A; A=60-121. DR PDB; 3EG1; X-ray; 1.85 A; A/B=60-121. DR PDB; 3EG2; X-ray; 1.80 A; A=60-121. DR PDB; 3EG3; X-ray; 1.40 A; A=60-121. DR PDB; 3EGU; X-ray; 2.25 A; A=60-121. DR PDB; 3K2M; X-ray; 1.75 A; A/B=121-232. DR PDB; 3PYY; X-ray; 1.85 A; A/B=229-512. DR PDB; 3QRI; X-ray; 2.10 A; A/B=229-499. DR PDB; 3QRJ; X-ray; 1.82 A; A/B=229-499. DR PDB; 3QRK; X-ray; 2.30 A; A=229-499. DR PDB; 3T04; X-ray; 2.10 A; A=112-232. DR PDB; 3UE4; X-ray; 2.42 A; A/B=229-512. DR PDB; 3UYO; X-ray; 1.83 A; A=112-232. DR PDB; 4J9B; X-ray; 1.70 A; A=60-121. DR PDB; 4J9C; X-ray; 1.05 A; A=60-121. DR PDB; 4J9D; X-ray; 1.50 A; A/C/E=60-121. DR PDB; 4J9E; X-ray; 1.40 A; A/C/E=60-121. DR PDB; 4J9F; X-ray; 1.09 A; A/C/E=60-121. DR PDB; 4J9G; X-ray; 1.80 A; A/C/E=60-121. DR PDB; 4J9H; X-ray; 1.70 A; A/B/C/D/E/F=60-121. DR PDB; 4J9I; X-ray; 2.20 A; A/C/E=60-121. DR PDB; 4JJB; X-ray; 1.65 A; A=60-121. DR PDB; 4JJC; X-ray; 1.60 A; A=60-121. DR PDB; 4JJD; X-ray; 1.60 A; A=60-121. DR PDB; 4TWP; X-ray; 2.40 A; A/B=233-503. DR PDB; 4WA9; X-ray; 2.20 A; A/B=246-512. DR PDB; 4XEY; X-ray; 2.89 A; A/B=119-515. DR PDB; 4YC8; X-ray; 2.90 A; A/B=229-512. DR PDB; 4ZOG; X-ray; 2.30 A; A/B=229-511. DR PDB; 5DC0; X-ray; 2.23 A; B=112-232. DR PDB; 5DC4; X-ray; 1.48 A; A=112-232. DR PDB; 5DC9; X-ray; 1.56 A; A=112-232. DR PDB; 5HU9; X-ray; 1.53 A; A=229-500. DR PDB; 5MO4; X-ray; 2.17 A; A=27-515. DR PDB; 5NP2; X-ray; 1.60 A; A/B=64-120. DR PDB; 5OAZ; X-ray; 1.03 A; A/B=60-121. DR PDB; 6AMV; NMR; -; A=26-236. DR PDB; 6AMW; NMR; -; A=26-236. DR PDB; 6BL8; X-ray; 2.50 A; A/B=233-504. DR PDB; 6NPE; X-ray; 2.15 A; A/B=229-512. DR PDB; 6NPU; X-ray; 2.33 A; A/B=229-512. DR PDB; 6NPV; X-ray; 1.86 A; A/B=229-512. DR PDB; 6XR6; NMR; -; A=229-515. DR PDB; 6XR7; NMR; -; A=229-515. DR PDB; 6XRG; NMR; -; A=229-515. DR PDB; 7CC2; X-ray; 2.72 A; A/B=229-510. DR PDB; 7DT2; X-ray; 2.30 A; A/B=229-510. DR PDB; 7N9G; X-ray; 2.20 A; A/B/C=229-499. DR PDB; 7PVQ; X-ray; 1.55 A; A/B=63-120. DR PDB; 7PVR; X-ray; 1.65 A; A=63-120. DR PDB; 7PVS; X-ray; 1.05 A; A/B=63-120. DR PDB; 7PVV; X-ray; 1.82 A; A=63-120. DR PDB; 7PW2; X-ray; 1.10 A; A=63-120. DR PDB; 7W7X; X-ray; 2.00 A; A/B=229-500. DR PDB; 7W7Y; X-ray; 2.20 A; A/B=229-504. DR PDB; 8H7F; X-ray; 2.45 A; A/B=229-500. DR PDB; 8H7H; X-ray; 2.28 A; A/B=229-500. DR PDB; 8I7S; X-ray; 1.95 A; A/B=229-500. DR PDB; 8I7T; X-ray; 2.80 A; A/B=229-500. DR PDB; 8I7Z; X-ray; 2.25 A; A/B=229-500. DR PDB; 8SSN; X-ray; 2.86 A; A/B=64-510. DR PDBsum; 1AB2; -. DR PDBsum; 1AWO; -. DR PDBsum; 1BBZ; -. DR PDBsum; 1JU5; -. DR PDBsum; 1OPL; -. DR PDBsum; 1ZZP; -. DR PDBsum; 2ABL; -. DR PDBsum; 2E2B; -. DR PDBsum; 2F4J; -. DR PDBsum; 2FO0; -. DR PDBsum; 2G1T; -. DR PDBsum; 2G2F; -. DR PDBsum; 2G2H; -. DR PDBsum; 2G2I; -. DR PDBsum; 2GQG; -. DR PDBsum; 2HIW; -. DR PDBsum; 2HYY; -. DR PDBsum; 2HZ0; -. DR PDBsum; 2HZ4; -. DR PDBsum; 2HZI; -. DR PDBsum; 2O88; -. DR PDBsum; 2V7A; -. DR PDBsum; 3CS9; -. DR PDBsum; 3EG0; -. DR PDBsum; 3EG1; -. DR PDBsum; 3EG2; -. DR PDBsum; 3EG3; -. DR PDBsum; 3EGU; -. DR PDBsum; 3K2M; -. DR PDBsum; 3PYY; -. DR PDBsum; 3QRI; -. DR PDBsum; 3QRJ; -. DR PDBsum; 3QRK; -. DR PDBsum; 3T04; -. DR PDBsum; 3UE4; -. DR PDBsum; 3UYO; -. DR PDBsum; 4J9B; -. DR PDBsum; 4J9C; -. DR PDBsum; 4J9D; -. DR PDBsum; 4J9E; -. DR PDBsum; 4J9F; -. DR PDBsum; 4J9G; -. DR PDBsum; 4J9H; -. DR PDBsum; 4J9I; -. DR PDBsum; 4JJB; -. DR PDBsum; 4JJC; -. DR PDBsum; 4JJD; -. DR PDBsum; 4TWP; -. DR PDBsum; 4WA9; -. DR PDBsum; 4XEY; -. DR PDBsum; 4YC8; -. DR PDBsum; 4ZOG; -. DR PDBsum; 5DC0; -. DR PDBsum; 5DC4; -. DR PDBsum; 5DC9; -. DR PDBsum; 5HU9; -. DR PDBsum; 5MO4; -. DR PDBsum; 5NP2; -. DR PDBsum; 5OAZ; -. DR PDBsum; 6AMV; -. DR PDBsum; 6AMW; -. DR PDBsum; 6BL8; -. DR PDBsum; 6NPE; -. DR PDBsum; 6NPU; -. DR PDBsum; 6NPV; -. DR PDBsum; 6XR6; -. DR PDBsum; 6XR7; -. DR PDBsum; 6XRG; -. DR PDBsum; 7CC2; -. DR PDBsum; 7DT2; -. DR PDBsum; 7N9G; -. DR PDBsum; 7PVQ; -. DR PDBsum; 7PVR; -. DR PDBsum; 7PVS; -. DR PDBsum; 7PVV; -. DR PDBsum; 7PW2; -. DR PDBsum; 7W7X; -. DR PDBsum; 7W7Y; -. DR PDBsum; 8H7F; -. DR PDBsum; 8H7H; -. DR PDBsum; 8I7S; -. DR PDBsum; 8I7T; -. DR PDBsum; 8I7Z; -. DR PDBsum; 8SSN; -. DR AlphaFoldDB; P00519; -. DR BMRB; P00519; -. DR SMR; P00519; -. DR BioGRID; 106543; 234. DR CORUM; P00519; -. DR DIP; DIP-1042N; -. DR FunCoup; P00519; 2642. DR IntAct; P00519; 284. DR MINT; P00519; -. DR STRING; 9606.ENSP00000361423; -. DR BindingDB; P00519; -. DR ChEMBL; CHEMBL1862; -. DR DrugBank; DB08043; 1-[4-(PYRIDIN-4-YLOXY)PHENYL]-3-[3-(TRIFLUOROMETHYL)PHENYL]UREA. DR DrugBank; DB08583; 2-amino-5-[3-(1-ethyl-1H-pyrazol-5-yl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-N,N-dimethylbenzamide. DR DrugBank; DB07831; 2-{[(6-OXO-1,6-DIHYDROPYRIDIN-3-YL)METHYL]AMINO}-N-[4-PROPYL-3-(TRIFLUOROMETHYL)PHENYL]BENZAMIDE. DR DrugBank; DB08350; 5-[3-(2-METHOXYPHENYL)-1H-PYRROLO[2,3-B]PYRIDIN-5-YL]-N,N-DIMETHYLPYRIDINE-3-CARBOXAMIDE. DR DrugBank; DB12597; Asciminib. DR DrugBank; DB00171; ATP. DR DrugBank; DB06626; Axitinib. DR DrugBank; DB06616; Bosutinib. DR DrugBank; DB12267; Brigatinib. DR DrugBank; DB01254; Dasatinib. DR DrugBank; DB11904; Flumatinib. DR DrugBank; DB12010; Fostamatinib. DR DrugBank; DB00619; Imatinib. DR DrugBank; DB13749; Magnesium gluconate. DR DrugBank; DB08231; Myristic acid. DR DrugBank; DB03878; N-[4-Methyl-3-[[4-(3-Pyridinyl)-2-Pyrimidinyl]Amino]Phenyl]-3-Pyridinecarboxamide. DR DrugBank; DB04868; Nilotinib. DR DrugBank; DB08339; PD-166326. DR DrugBank; DB08901; Ponatinib. DR DrugBank; DB08052; PP-121. DR DrugBank; DB12323; Radotinib. DR DrugBank; DB13005; Rebastinib. DR DrugBank; DB08896; Regorafenib. DR DrugBank; DB11805; Saracatinib. DR DrugBank; DB14989; Umbralisib. DR DrugBank; DB05184; XL228. DR DrugCentral; P00519; -. DR GuidetoPHARMACOLOGY; 1923; -. DR MoonDB; P00519; Predicted. DR GlyCosmos; P00519; 1 site, 1 glycan. DR GlyGen; P00519; 5 sites, 1 O-linked glycan (3 sites). DR iPTMnet; P00519; -. DR PhosphoSitePlus; P00519; -. DR BioMuta; ABL1; -. DR DMDM; 85681908; -. DR CPTAC; CPTAC-1776; -. DR CPTAC; CPTAC-1788; -. DR CPTAC; CPTAC-3041; -. DR CPTAC; CPTAC-3042; -. DR jPOST; P00519; -. DR MassIVE; P00519; -. DR PaxDb; 9606-ENSP00000361423; -. DR PeptideAtlas; P00519; -. DR ProteomicsDB; 51259; -. [P00519-1] DR ProteomicsDB; 51260; -. [P00519-2] DR Pumba; P00519; -. DR ABCD; P00519; 12 sequenced antibodies. DR Antibodypedia; 3637; 2143 antibodies from 44 providers. DR DNASU; 25; -. DR Ensembl; ENST00000318560.6; ENSP00000323315.5; ENSG00000097007.21. [P00519-1] DR Ensembl; ENST00000372348.9; ENSP00000361423.2; ENSG00000097007.21. [P00519-2] DR GeneID; 25; -. DR KEGG; hsa:25; -. DR MANE-Select; ENST00000318560.6; ENSP00000323315.5; NM_005157.6; NP_005148.2. DR UCSC; uc004bzv.4; human. [P00519-1] DR AGR; HGNC:76; -. DR CIViC; 25; 507 evidence items across 205 molecular profiles. DR ClinPGx; PA24413; -. DR CTD; 25; -. DR DisGeNET; 25; -. DR GeneCards; ABL1; -. DR HGNC; HGNC:76; ABL1. DR HPA; ENSG00000097007; Low tissue specificity. DR MalaCards; ABL1; -. DR MIM; 189980; gene. DR MIM; 608232; phenotype. DR MIM; 617602; phenotype. DR OpenTargets; ENSG00000097007; -. DR Orphanet; 585909; B-lymphoblastic leukemia/lymphoma with t(9;22)(q34.1;q11.2). DR Orphanet; 521; Chronic myeloid leukemia. DR Orphanet; 643503; Marfanoid habitus-facial dysmorphism-skeletal abnormality-heart defect syndrome. DR Orphanet; 99861; Precursor T-cell acute lymphoblastic leukemia. DR VEuPathDB; HostDB:ENSG00000097007; -. DR eggNOG; KOG4278; Eukaryota. DR GeneTree; ENSGT00940000153838; -. DR HOGENOM; CLU_002795_0_0_1; -. DR InParanoid; P00519; -. DR OMA; TRNSEQM; -. DR OrthoDB; 98077at2759; -. DR PAN-GO; P00519; 2 GO annotations based on evolutionary models. DR PhylomeDB; P00519; -. DR BRENDA; 2.7.10.2; 2681. DR PathwayCommons; P00519; -. DR Reactome; R-HSA-2029482; Regulation of actin dynamics for phagocytic cup formation. DR Reactome; R-HSA-428890; Role of ABL in ROBO-SLIT signaling. DR Reactome; R-HSA-525793; Myogenesis. DR Reactome; R-HSA-5663213; RHO GTPases Activate WASPs and WAVEs. DR Reactome; R-HSA-5685938; HDR through Single Strand Annealing (SSA). DR Reactome; R-HSA-5693565; Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks. DR Reactome; R-HSA-69231; Cyclin D associated events in G1. DR Reactome; R-HSA-8939236; RUNX1 regulates transcription of genes involved in differentiation of HSCs. DR Reactome; R-HSA-8940973; RUNX2 regulates osteoblast differentiation. DR Reactome; R-HSA-9664422; FCGR3A-mediated phagocytosis. DR Reactome; R-HSA-983231; Factors involved in megakaryocyte development and platelet production. DR Reactome; R-HSA-9841922; MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis. DR Reactome; R-HSA-9860927; Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZO1 and integrins in endothelial cells. DR SignaLink; P00519; -. DR SIGNOR; P00519; -. DR Agora; ENSG00000097007; -. DR BioGRID-ORCS; 25; 30 hits in 1205 CRISPR screens. DR CD-CODE; 041D4500; Synthetic Condensate 000036. DR CD-CODE; 1CD3856C; Synthetic Condensate 000003. DR CD-CODE; 7ADEF05E; Synthetic Condensate 000039. DR CD-CODE; A13F0EB5; Synthetic Condensate 000320. DR CD-CODE; B5B9A610; PML body. DR ChiTaRS; ABL1; human. DR EvolutionaryTrace; P00519; -. DR GeneWiki; ABL_(gene); -. DR GenomeRNAi; 25; -. DR Pharos; P00519; Tclin. DR PRO; PR:P00519; -. DR Proteomes; UP000005640; Chromosome 9. DR RNAct; P00519; protein. DR Bgee; ENSG00000097007; Expressed in frontal pole and 196 other cell types or tissues. DR ExpressionAtlas; P00519; baseline and differential. DR GO; GO:0015629; C:actin cytoskeleton; TAS:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IDA:CAFA. DR GO; GO:0005829; C:cytosol; IDA:MGI. DR GO; GO:0030425; C:dendrite; ISS:ARUK-UCL. DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl. DR GO; GO:0030426; C:growth cone; IEA:Ensembl. DR GO; GO:0005739; C:mitochondrion; NAS:ParkinsonsUK-UCL. DR GO; GO:0043025; C:neuronal cell body; ISS:ARUK-UCL. DR GO; GO:0016604; C:nuclear body; IDA:HPA. DR GO; GO:0031965; C:nuclear membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005730; C:nucleolus; IDA:MGI. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central. DR GO; GO:0098794; C:postsynapse; TAS:ARUK-UCL. DR GO; GO:0014069; C:postsynaptic density; IEA:Ensembl. DR GO; GO:0032991; C:protein-containing complex; IPI:CAFA. DR GO; GO:0001726; C:ruffle; IEA:Ensembl. DR GO; GO:0051015; F:actin filament binding; IEA:Ensembl. DR GO; GO:0003785; F:actin monomer binding; TAS:UniProtKB. DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB. DR GO; GO:0000405; F:bubble DNA binding; IDA:ARUK-UCL. DR GO; GO:0070097; F:delta-catenin binding; IEA:Ensembl. DR GO; GO:0003677; F:DNA binding; NAS:UniProtKB. DR GO; GO:0008047; F:enzyme activator activity; IDA:BHF-UCL. DR GO; GO:0019899; F:enzyme binding; IPI:BHF-UCL. DR GO; GO:0046875; F:ephrin receptor binding; ISS:ARUK-UCL. DR GO; GO:0000400; F:four-way junction DNA binding; IDA:ARUK-UCL. DR GO; GO:0016301; F:kinase activity; IMP:UniProtKB. DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB. DR GO; GO:0030145; F:manganese ion binding; IDA:UniProtKB. DR GO; GO:0051019; F:mitogen-activated protein kinase binding; IPI:BHF-UCL. DR GO; GO:0038191; F:neuropilin binding; IPI:BHF-UCL. DR GO; GO:0004515; F:nicotinate-nucleotide adenylyltransferase activity; TAS:UniProtKB. DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IDA:UniProtKB. DR GO; GO:0001784; F:phosphotyrosine residue binding; IPI:CAFA. DR GO; GO:0070064; F:proline-rich region binding; IDA:UniProtKB. DR GO; GO:0004672; F:protein kinase activity; IDA:MGI. DR GO; GO:0005080; F:protein kinase C binding; IPI:ParkinsonsUK-UCL. DR GO; GO:0043539; F:protein serine/threonine kinase activator activity; IDA:ParkinsonsUK-UCL. DR GO; GO:0004674; F:protein serine/threonine kinase activity; IMP:UniProtKB. DR GO; GO:0004713; F:protein tyrosine kinase activity; IDA:UniProtKB. DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL. DR GO; GO:0042169; F:SH2 domain binding; IPI:CAFA. DR GO; GO:0019905; F:syntaxin binding; IPI:UniProtKB. DR GO; GO:0003713; F:transcription coactivator activity; TAS:ARUK-UCL. DR GO; GO:0030036; P:actin cytoskeleton organization; ISS:UniProtKB. DR GO; GO:0030041; P:actin filament polymerization; IEA:Ensembl. DR GO; GO:0050798; P:activated T cell proliferation; IEA:Ensembl. DR GO; GO:0046632; P:alpha-beta T cell differentiation; IEA:Ensembl. DR GO; GO:0008306; P:associative learning; IEA:Ensembl. DR GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW. DR GO; GO:0002322; P:B cell proliferation involved in immune response; IEA:Ensembl. DR GO; GO:0050853; P:B cell receptor signaling pathway; IEA:Ensembl. DR GO; GO:0001922; P:B-1 B cell homeostasis; IEA:Ensembl. DR GO; GO:0060020; P:Bergmann glial cell differentiation; IEA:Ensembl. DR GO; GO:0030509; P:BMP signaling pathway; IEA:Ensembl. DR GO; GO:0007249; P:canonical NF-kappaB signal transduction; IEA:Ensembl. DR GO; GO:0060038; P:cardiac muscle cell proliferation; IEA:Ensembl. DR GO; GO:0098609; P:cell-cell adhesion; IEA:Ensembl. DR GO; GO:1903351; P:cellular response to dopamine; TAS:ParkinsonsUK-UCL. DR GO; GO:0070301; P:cellular response to hydrogen peroxide; IDA:ParkinsonsUK-UCL. DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IEA:Ensembl. DR GO; GO:0034599; P:cellular response to oxidative stress; IDA:BHF-UCL. DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; IEA:Ensembl. DR GO; GO:0090398; P:cellular senescence; IEA:Ensembl. DR GO; GO:0021587; P:cerebellum morphogenesis; IEA:Ensembl. DR GO; GO:1904157; P:DN4 thymocyte differentiation; IEA:Ensembl. DR GO; GO:0071103; P:DNA conformation change; IDA:ARUK-UCL. DR GO; GO:0006974; P:DNA damage response; IDA:UniProtKB. DR GO; GO:0043542; P:endothelial cell migration; IMP:BHF-UCL. DR GO; GO:0048013; P:ephrin receptor signaling pathway; IEA:Ensembl. DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; IBA:GO_Central. DR GO; GO:0070371; P:ERK1 and ERK2 cascade; IEA:Ensembl. DR GO; GO:0051649; P:establishment of localization in cell; IEA:Ensembl. DR GO; GO:0038096; P:Fc-gamma receptor signaling pathway involved in phagocytosis; TAS:Reactome. DR GO; GO:0007229; P:integrin-mediated signaling pathway; IMP:BHF-UCL. DR GO; GO:0035556; P:intracellular signal transduction; IDA:UniProtKB. DR GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; TAS:UniProtKB. DR GO; GO:0030035; P:microspike assembly; IEA:Ensembl. DR GO; GO:0006298; P:mismatch repair; TAS:ProtInc. DR GO; GO:0051882; P:mitochondrial depolarization; TAS:ParkinsonsUK-UCL. DR GO; GO:0000278; P:mitotic cell cycle; TAS:ParkinsonsUK-UCL. DR GO; GO:0051450; P:myoblast proliferation; IEA:Ensembl. DR GO; GO:0030514; P:negative regulation of BMP signaling pathway; IEA:Ensembl. DR GO; GO:0022408; P:negative regulation of cell-cell adhesion; IEA:Ensembl. DR GO; GO:2000773; P:negative regulation of cellular senescence; IEA:Ensembl. DR GO; GO:2000042; P:negative regulation of double-strand break repair via homologous recombination; IDA:UniProtKB. DR GO; GO:2000352; P:negative regulation of endothelial cell apoptotic process; IEA:Ensembl. DR GO; GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; IEA:Ensembl. DR GO; GO:1900272; P:negative regulation of long-term synaptic potentiation; ISS:ARUK-UCL. DR GO; GO:0045930; P:negative regulation of mitotic cell cycle; IEA:Ensembl. DR GO; GO:0051444; P:negative regulation of ubiquitin-protein transferase activity; IDA:MGI. DR GO; GO:0001843; P:neural tube closure; IEA:Ensembl. DR GO; GO:0060563; P:neuroepithelial cell differentiation; IEA:Ensembl. DR GO; GO:0050885; P:neuromuscular process controlling balance; IEA:Ensembl. DR GO; GO:0051402; P:neuron apoptotic process; IEA:Ensembl. DR GO; GO:0030182; P:neuron differentiation; IEA:Ensembl. DR GO; GO:0038189; P:neuropilin signaling pathway; IMP:BHF-UCL. DR GO; GO:0030845; P:phospholipase C-inhibiting G protein-coupled receptor signaling pathway; IMP:MGI. DR GO; GO:0035791; P:platelet-derived growth factor receptor-beta signaling pathway; IMP:UniProtKB. DR GO; GO:1903210; P:podocyte apoptotic process; IEA:Ensembl. DR GO; GO:0043065; P:positive regulation of apoptotic process; IDA:UniProtKB. DR GO; GO:1905555; P:positive regulation of blood vessel branching; IEA:Ensembl. DR GO; GO:0043123; P:positive regulation of canonical NF-kappaB signal transduction; IEA:Ensembl. DR GO; GO:0090050; P:positive regulation of cell migration involved in sprouting angiogenesis; IEA:Ensembl. DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IMP:MGI. DR GO; GO:1900006; P:positive regulation of dendrite development; IEA:Ensembl. DR GO; GO:0010595; P:positive regulation of endothelial cell migration; IMP:BHF-UCL. DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IEA:Ensembl. DR GO; GO:1903905; P:positive regulation of establishment of T cell polarity; ISS:UniProtKB. DR GO; GO:1903055; P:positive regulation of extracellular matrix organization; IEA:Ensembl. DR GO; GO:0048146; P:positive regulation of fibroblast proliferation; IEA:Ensembl. DR GO; GO:0051894; P:positive regulation of focal adhesion assembly; IMP:BHF-UCL. DR GO; GO:0032743; P:positive regulation of interleukin-2 production; IEA:Ensembl. DR GO; GO:0045931; P:positive regulation of mitotic cell cycle; IEA:Ensembl. DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; IEA:Ensembl. DR GO; GO:0033690; P:positive regulation of osteoblast proliferation; IEA:Ensembl. DR GO; GO:0141214; P:positive regulation of phospholipase C/protein kinase C signal transduction; IDA:ParkinsonsUK-UCL. DR GO; GO:0051281; P:positive regulation of release of sequestered calcium ion into cytosol; IEA:Ensembl. DR GO; GO:0051496; P:positive regulation of stress fiber assembly; IMP:BHF-UCL. DR GO; GO:1900026; P:positive regulation of substrate adhesion-dependent cell spreading; IMP:BHF-UCL. DR GO; GO:2000406; P:positive regulation of T cell migration; ISS:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; TAS:ARUK-UCL. DR GO; GO:0032729; P:positive regulation of type II interferon production; IEA:Ensembl. DR GO; GO:0045907; P:positive regulation of vasoconstriction; IEA:Ensembl. DR GO; GO:2000096; P:positive regulation of Wnt signaling pathway, planar cell polarity pathway; IEA:Ensembl. DR GO; GO:0009791; P:post-embryonic development; IEA:Ensembl. DR GO; GO:1904518; P:protein localization to cytoplasmic microtubule plus-end; IMP:UniProtKB. DR GO; GO:0036211; P:protein modification process; NAS:UniProtKB. DR GO; GO:0032956; P:regulation of actin cytoskeleton organization; IMP:UniProtKB. DR GO; GO:0010506; P:regulation of autophagy; TAS:UniProtKB. DR GO; GO:0030516; P:regulation of axon extension; IMP:UniProtKB. DR GO; GO:0032489; P:regulation of Cdc42 protein signal transduction; IMP:BHF-UCL. DR GO; GO:0030155; P:regulation of cell adhesion; TAS:UniProtKB. DR GO; GO:0051726; P:regulation of cell cycle; TAS:ParkinsonsUK-UCL. DR GO; GO:2000145; P:regulation of cell motility; TAS:UniProtKB. DR GO; GO:0006355; P:regulation of DNA-templated transcription; TAS:ProtInc. DR GO; GO:0030100; P:regulation of endocytosis; TAS:UniProtKB. DR GO; GO:1902036; P:regulation of hematopoietic stem cell differentiation; TAS:Reactome. DR GO; GO:0031113; P:regulation of microtubule polymerization; IMP:UniProtKB. DR GO; GO:1905244; P:regulation of modification of synaptic structure; ISS:ARUK-UCL. DR GO; GO:0099150; P:regulation of postsynaptic specialization assembly; IEA:Ensembl. DR GO; GO:0045580; P:regulation of T cell differentiation; ISS:UniProtKB. DR GO; GO:0034976; P:response to endoplasmic reticulum stress; IEA:Ensembl. DR GO; GO:0071871; P:response to epinephrine; IEA:Ensembl. DR GO; GO:0006979; P:response to oxidative stress; IGI:MGI. DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl. DR GO; GO:0042770; P:signal transduction in response to DNA damage; IDA:UniProtKB. DR GO; GO:0048536; P:spleen development; IEA:Ensembl. DR GO; GO:0034446; P:substrate adhesion-dependent cell spreading; IEA:Ensembl. DR GO; GO:0050852; P:T cell receptor signaling pathway; IEA:Ensembl. DR GO; GO:0048538; P:thymus development; IEA:Ensembl. DR GO; GO:0002333; P:transitional one stage B cell differentiation; IEA:Ensembl. DR GO; GO:0097706; P:vascular endothelial cell response to oscillatory fluid shear stress; TAS:Reactome. DR CDD; cd05052; PTKc_Abl; 1. DR CDD; cd09935; SH2_ABL; 1. DR CDD; cd11850; SH3_Abl; 1. DR DisProt; DP03166; -. DR DisProt; DP03168; -. [P00519-2] DR FunFam; 1.10.510.10:FF:002964; Tyrosine-protein kinase; 1. DR FunFam; 1.20.120.330:FF:000003; Tyrosine-protein kinase; 1. DR FunFam; 2.30.30.40:FF:000010; Tyrosine-protein kinase; 1. DR FunFam; 3.30.200.20:FF:000037; Tyrosine-protein kinase; 1. DR FunFam; 3.30.505.10:FF:000004; Tyrosine-protein kinase; 1. DR Gene3D; 1.20.120.330; Nucleotidyltransferases domain 2; 1. DR Gene3D; 3.30.200.20; Phosphorylase Kinase, domain 1; 1. DR Gene3D; 3.30.505.10; SH2 domain; 1. DR Gene3D; 2.30.30.40; SH3 Domains; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. DR IDEAL; IID00645; -. DR InterPro; IPR035837; ABL_SH2. DR InterPro; IPR015015; F-actin-binding. DR InterPro; IPR011009; Kinase-like_dom_sf. DR InterPro; IPR050198; Non-receptor_tyrosine_kinases. DR InterPro; IPR000719; Prot_kinase_dom. DR InterPro; IPR017441; Protein_kinase_ATP_BS. DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom. DR InterPro; IPR000980; SH2. DR InterPro; IPR036860; SH2_dom_sf. DR InterPro; IPR036028; SH3-like_dom_sf. DR InterPro; IPR001452; SH3_domain. DR InterPro; IPR008266; Tyr_kinase_AS. DR InterPro; IPR020635; Tyr_kinase_cat_dom. DR PANTHER; PTHR24418; TYROSINE-PROTEIN KINASE; 1. DR Pfam; PF08919; F_actin_bind; 1. DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1. DR Pfam; PF00017; SH2; 1. DR Pfam; PF00018; SH3_1; 1. DR PRINTS; PR00401; SH2DOMAIN. DR PRINTS; PR00109; TYRKINASE. DR SMART; SM00808; FABD; 1. DR SMART; SM00252; SH2; 1. DR SMART; SM00326; SH3; 1. DR SMART; SM00219; TyrKc; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR SUPFAM; SSF55550; SH2 domain; 1. DR SUPFAM; SSF50044; SH3-domain; 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1. DR PROSITE; PS50001; SH2; 1. DR PROSITE; PS50002; SH3; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Apoptosis; ATP-binding; KW Autophagy; Cell adhesion; Chromosomal rearrangement; Cytoplasm; KW Cytoskeleton; Disease variant; DNA damage; DNA repair; DNA-binding; KW Endocytosis; Kinase; Lipoprotein; Magnesium; Manganese; Membrane; KW Metal-binding; Mitochondrion; Myristate; Nucleotide-binding; Nucleus; KW Phosphoprotein; Proteomics identification; Proto-oncogene; KW Reference proteome; SH2 domain; SH3 domain; Transferase; KW Tyrosine-protein kinase; Ubl conjugation. FT CHAIN 1..1130 FT /note="Tyrosine-protein kinase ABL1" FT /id="PRO_0000088050" FT DOMAIN 61..121 FT /note="SH3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192" FT DOMAIN 127..217 FT /note="SH2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191" FT DOMAIN 242..493 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT REGION 1..60 FT /note="CAP" FT REGION 518..996 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 869..968 FT /note="DNA-binding" FT /evidence="ECO:0000250" FT REGION 953..1130 FT /note="F-actin-binding" FT MOTIF 381..405 FT /note="Kinase activation loop" FT MOTIF 605..609 FT /note="Nuclear localization signal 1" FT /evidence="ECO:0000255" FT MOTIF 709..715 FT /note="Nuclear localization signal 2" FT /evidence="ECO:0000255" FT MOTIF 762..769 FT /note="Nuclear localization signal 3" FT /evidence="ECO:0000255" FT MOTIF 1090..1100 FT /note="Nuclear export signal" FT /evidence="ECO:0000250" FT COMPBIAS 537..566 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 586..597 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 620..640 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 689..698 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 740..752 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 755..774 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 788..802 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 881..891 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 905..915 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 965..975 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 984..993 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 363 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000255|PROSITE-ProRule:PRU10028" FT BINDING 248..256 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT BINDING 271 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT BINDING 316..322 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT SITE 26..27 FT /note="Breakpoint for translocation to form BCR-ABL and FT NUP214-ABL1 fusion proteins" FT /evidence="ECO:0000269|PubMed:15361874, FT ECO:0000269|PubMed:3021337" FT MOD_RES 50 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:16543148, FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:19690332" FT MOD_RES 70 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:16912036, FT ECO:0000269|PubMed:18775435" FT MOD_RES 115 FT /note="Phosphotyrosine" FT /evidence="ECO:0000269|PubMed:16912036" FT MOD_RES 128 FT /note="Phosphotyrosine" FT /evidence="ECO:0000269|PubMed:16912036" FT MOD_RES 139 FT /note="Phosphotyrosine" FT /evidence="ECO:0000269|PubMed:16912036" FT MOD_RES 172 FT /note="Phosphotyrosine" FT /evidence="ECO:0000269|PubMed:16912036" FT MOD_RES 185 FT /note="Phosphotyrosine" FT /evidence="ECO:0000269|PubMed:16912036" FT MOD_RES 215 FT /note="Phosphotyrosine" FT /evidence="ECO:0000269|PubMed:16912036" FT MOD_RES 226 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:16912036" FT MOD_RES 229 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P42684" FT MOD_RES 253 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 257 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 393 FT /note="Phosphotyrosine; by autocatalysis and SRC-type Tyr- FT kinases" FT /evidence="ECO:0000269|PubMed:16912036" FT MOD_RES 413 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 446 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P00520" FT MOD_RES 559 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 569 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17081983, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:18691976, FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569" FT MOD_RES 618 FT /note="Phosphoserine; by PAK2" FT /evidence="ECO:0000269|PubMed:18161990" FT MOD_RES 619 FT /note="Phosphoserine; by PAK2" FT /evidence="ECO:0000269|PubMed:18161990" FT MOD_RES 620 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 659 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18691976" FT MOD_RES 683 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 711 FT /note="N6-acetyllysine; by EP300" FT /evidence="ECO:0000269|PubMed:16648821" FT MOD_RES 718 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 735 FT /note="Phosphothreonine" FT /evidence="ECO:0000269|PubMed:15696159" FT MOD_RES 751 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 781 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 814 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:18691976" FT MOD_RES 823 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 844 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:18691976, FT ECO:0007744|PubMed:23186163" FT MOD_RES 852 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT MOD_RES 855 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 917 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT MOD_RES 977 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18691976" FT VAR_SEQ 1..26 FT /note="MLEICLKLVGCKSKKGLSSSSSCYLE -> MGQQPGKVLGDQRRPSLPALHF FT IKGAGKKESSRHGGPHCNVFVEH (in isoform IB)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_004957" FT VARIANT 47 FT /note="R -> G (in a lung large cell carcinoma sample; FT somatic mutation)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_032676" FT VARIANT 140 FT /note="L -> P (in dbSNP:rs1064152)" FT /evidence="ECO:0000269|PubMed:3021337" FT /id="VAR_051692" FT VARIANT 166 FT /note="R -> K (in a melanoma sample; somatic mutation; FT dbSNP:rs2132958430)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_032677" FT VARIANT 226 FT /note="Y -> C (in CHDSKM; increases kinase activity; no FT effect on protein levels; dbSNP:rs1060499547)" FT /evidence="ECO:0000269|PubMed:28288113" FT /id="VAR_079482" FT VARIANT 247 FT /note="K -> R (in dbSNP:rs34549764)" FT /id="VAR_051693" FT VARIANT 337 FT /note="A -> T (in CHDSKM; increases kinase activity; no FT effect on protein levels; dbSNP:rs1060499548)" FT /evidence="ECO:0000269|PubMed:28288113" FT /id="VAR_079483" FT VARIANT 706 FT /note="G -> V (in dbSNP:rs34634745)" FT /evidence="ECO:0000269|PubMed:17344846, ECO:0000269|Ref.4" FT /id="VAR_025043" FT VARIANT 810 FT /note="P -> L (in dbSNP:rs2229071)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_032678" FT VARIANT 852 FT /note="T -> P (in dbSNP:rs1588283506)" FT /evidence="ECO:0000269|Ref.4" FT /id="VAR_025044" FT VARIANT 900 FT /note="P -> S (in dbSNP:rs35266696)" FT /evidence="ECO:0000269|Ref.4" FT /id="VAR_025045" FT VARIANT 968 FT /note="S -> P (in dbSNP:rs1064165)" FT /id="VAR_051694" FT VARIANT 972 FT /note="S -> L (in dbSNP:rs2229067)" FT /evidence="ECO:0000269|PubMed:17344846, ECO:0000269|Ref.4" FT /id="VAR_025046" FT MUTAGEN 735 FT /note="T->A: Abolishes phosphorylation. Loss of binding FT YWHAS and YWHAZ. Localizes to the nucleus. No effect on FT kinase activity." FT /evidence="ECO:0000269|PubMed:15696159" FT CONFLICT 159 FT /note="G -> S (in Ref. 1; AAA51561)" FT /evidence="ECO:0000305" FT CONFLICT 424..425 FT /note="AF -> GK (in Ref. 9)" FT /evidence="ECO:0000305" FT CONFLICT 445 FT /note="L -> R (in Ref. 1; AAA51561)" FT /evidence="ECO:0000305" FT CONFLICT 459 FT /note="E -> K (in Ref. 1; AAA51561)" FT /evidence="ECO:0000305" FT CONFLICT 520 FT /note="S -> T (in Ref. 1; AAA51561)" FT /evidence="ECO:0000305" FT CONFLICT 719 FT /note="A -> V (in Ref. 1; AAA51561)" FT /evidence="ECO:0000305" FT CONFLICT 837 FT /note="G -> E (in Ref. 2; CAA34438)" FT /evidence="ECO:0000305" FT CONFLICT 837 FT /note="G -> W (in Ref. 1; AAA51561)" FT /evidence="ECO:0000305" FT CONFLICT 863 FT /note="G -> R (in Ref. 1; AAA51561)" FT /evidence="ECO:0000305" FT CONFLICT 894 FT /note="R -> K (in Ref. 1; AAA51561)" FT /evidence="ECO:0000305" FT CONFLICT 917..919 FT /note="SPS -> RPG (in Ref. 1; AAA51561)" FT /evidence="ECO:0000305" FT CONFLICT 952 FT /note="G -> A (in Ref. 1; AAA51561)" FT /evidence="ECO:0000305" FT CONFLICT 967..968 FT /note="QS -> HP (in Ref. 1; AAA51561)" FT /evidence="ECO:0000305" FT CONFLICT 982 FT /note="P -> PL (in Ref. 1; AAA51561)" FT /evidence="ECO:0000305" FT CONFLICT 1022 FT /note="Missing (in Ref. 1; AAA51561)" FT /evidence="ECO:0000305" FT CONFLICT 1045 FT /note="R -> G (in Ref. 1; AAA51561)" FT /evidence="ECO:0000305" FT CONFLICT 1103 FT /note="T -> S (in Ref. 1; AAA51561)" FT /evidence="ECO:0000305" FT STRAND 26..32 FT /evidence="ECO:0007829|PDB:6AMV" FT STRAND 39..44 FT /evidence="ECO:0007829|PDB:6AMV" FT TURN 45..47 FT /evidence="ECO:0007829|PDB:6AMV" FT HELIX 49..53 FT /evidence="ECO:0007829|PDB:2FO0" FT HELIX 58..60 FT /evidence="ECO:0007829|PDB:2FO0" FT STRAND 65..70 FT /evidence="ECO:0007829|PDB:5OAZ" FT STRAND 76..79 FT /evidence="ECO:0007829|PDB:7PW2" FT STRAND 87..93 FT /evidence="ECO:0007829|PDB:5OAZ" FT STRAND 97..104 FT /evidence="ECO:0007829|PDB:5OAZ" FT STRAND 107..112 FT /evidence="ECO:0007829|PDB:5OAZ" FT HELIX 113..115 FT /evidence="ECO:0007829|PDB:5OAZ" FT STRAND 116..118 FT /evidence="ECO:0007829|PDB:5OAZ" FT HELIX 122..124 FT /evidence="ECO:0007829|PDB:5DC4" FT STRAND 128..131 FT /evidence="ECO:0007829|PDB:5DC4" FT HELIX 134..140 FT /evidence="ECO:0007829|PDB:5DC4" FT TURN 141..143 FT /evidence="ECO:0007829|PDB:5DC4" FT STRAND 148..153 FT /evidence="ECO:0007829|PDB:5DC4" FT STRAND 155..157 FT /evidence="ECO:0007829|PDB:5DC4" FT STRAND 161..167 FT /evidence="ECO:0007829|PDB:5DC4" FT STRAND 170..175 FT /evidence="ECO:0007829|PDB:5DC4" FT STRAND 177..179 FT /evidence="ECO:0007829|PDB:4XEY" FT TURN 180..182 FT /evidence="ECO:0007829|PDB:4XEY" FT STRAND 184..187 FT /evidence="ECO:0007829|PDB:5DC4" FT STRAND 190..194 FT /evidence="ECO:0007829|PDB:5DC4" FT HELIX 195..202 FT /evidence="ECO:0007829|PDB:5DC4" FT STRAND 209..211 FT /evidence="ECO:0007829|PDB:5DC4" FT STRAND 226..228 FT /evidence="ECO:0007829|PDB:5MO4" FT STRAND 229..231 FT /evidence="ECO:0007829|PDB:2GQG" FT TURN 233..235 FT /evidence="ECO:0007829|PDB:2G1T" FT HELIX 239..241 FT /evidence="ECO:0007829|PDB:5HU9" FT STRAND 242..247 FT /evidence="ECO:0007829|PDB:5HU9" FT HELIX 248..251 FT /evidence="ECO:0007829|PDB:5HU9" FT STRAND 254..261 FT /evidence="ECO:0007829|PDB:5HU9" FT HELIX 262..264 FT /evidence="ECO:0007829|PDB:5HU9" FT STRAND 266..271 FT /evidence="ECO:0007829|PDB:5HU9" FT TURN 275..277 FT /evidence="ECO:0007829|PDB:5HU9" FT HELIX 280..290 FT /evidence="ECO:0007829|PDB:5HU9" FT STRAND 301..305 FT /evidence="ECO:0007829|PDB:5HU9" FT STRAND 307..310 FT /evidence="ECO:0007829|PDB:5HU9" FT STRAND 312..316 FT /evidence="ECO:0007829|PDB:5HU9" FT STRAND 319..322 FT /evidence="ECO:0007829|PDB:2HZI" FT HELIX 323..329 FT /evidence="ECO:0007829|PDB:5HU9" FT TURN 332..334 FT /evidence="ECO:0007829|PDB:5HU9" FT HELIX 337..356 FT /evidence="ECO:0007829|PDB:5HU9" FT STRAND 359..361 FT /evidence="ECO:0007829|PDB:2G2H" FT HELIX 366..368 FT /evidence="ECO:0007829|PDB:5HU9" FT STRAND 369..371 FT /evidence="ECO:0007829|PDB:5HU9" FT HELIX 373..375 FT /evidence="ECO:0007829|PDB:5HU9" FT STRAND 377..379 FT /evidence="ECO:0007829|PDB:5HU9" FT HELIX 381..383 FT /evidence="ECO:0007829|PDB:2G2F" FT HELIX 384..387 FT /evidence="ECO:0007829|PDB:2G1T" FT HELIX 390..392 FT /evidence="ECO:0007829|PDB:2G1T" FT STRAND 393..396 FT /evidence="ECO:0007829|PDB:3QRJ" FT STRAND 399..401 FT /evidence="ECO:0007829|PDB:5HU9" FT HELIX 403..405 FT /evidence="ECO:0007829|PDB:5HU9" FT HELIX 408..413 FT /evidence="ECO:0007829|PDB:5HU9" FT HELIX 418..433 FT /evidence="ECO:0007829|PDB:5HU9" FT HELIX 445..447 FT /evidence="ECO:0007829|PDB:5HU9" FT HELIX 448..453 FT /evidence="ECO:0007829|PDB:5HU9" FT HELIX 466..475 FT /evidence="ECO:0007829|PDB:5HU9" FT HELIX 480..482 FT /evidence="ECO:0007829|PDB:5HU9" FT HELIX 486..496 FT /evidence="ECO:0007829|PDB:5HU9" FT STRAND 498..500 FT /evidence="ECO:0007829|PDB:1OPL" FT HELIX 503..506 FT /evidence="ECO:0007829|PDB:2G1T" FT TURN 510..512 FT /evidence="ECO:0007829|PDB:2F4J" FT HELIX 1029..1045 FT /evidence="ECO:0007829|PDB:1ZZP" FT TURN 1046..1048 FT /evidence="ECO:0007829|PDB:1ZZP" FT HELIX 1053..1070 FT /evidence="ECO:0007829|PDB:1ZZP" FT HELIX 1071..1073 FT /evidence="ECO:0007829|PDB:1ZZP" FT HELIX 1080..1097 FT /evidence="ECO:0007829|PDB:1ZZP" FT STRAND 1101..1104 FT /evidence="ECO:0007829|PDB:1ZZP" FT STRAND 1106..1108 FT /evidence="ECO:0007829|PDB:1ZZP" FT HELIX 1115..1128 FT /evidence="ECO:0007829|PDB:1ZZP" FT LIPID P00519-2:2 FT /note="N-myristoyl glycine" FT /evidence="ECO:0000305" SQ SEQUENCE 1130 AA; 122873 MW; 85FE6C1C0E483EA2 CRC64; MLEICLKLVG CKSKKGLSSS SSCYLEEALQ RPVASDFEPQ GLSEAARWNS KENLLAGPSE NDPNLFVALY DFVASGDNTL SITKGEKLRV LGYNHNGEWC EAQTKNGQGW VPSNYITPVN SLEKHSWYHG PVSRNAAEYL LSSGINGSFL VRESESSPGQ RSISLRYEGR VYHYRINTAS DGKLYVSSES RFNTLAELVH HHSTVADGLI TTLHYPAPKR NKPTVYGVSP NYDKWEMERT DITMKHKLGG GQYGEVYEGV WKKYSLTVAV KTLKEDTMEV EEFLKEAAVM KEIKHPNLVQ LLGVCTREPP FYIITEFMTY GNLLDYLREC NRQEVNAVVL LYMATQISSA MEYLEKKNFI HRDLAARNCL VGENHLVKVA DFGLSRLMTG DTYTAHAGAK FPIKWTAPES LAYNKFSIKS DVWAFGVLLW EIATYGMSPY PGIDLSQVYE LLEKDYRMER PEGCPEKVYE LMRACWQWNP SDRPSFAEIH QAFETMFQES SISDEVEKEL GKQGVRGAVS TLLQAPELPT KTRTSRRAAE HRDTTDVPEM PHSKGQGESD PLDHEPAVSP LLPRKERGPP EGGLNEDERL LPKDKKTNLF SALIKKKKKT APTPPKRSSS FREMDGQPER RGAGEEEGRD ISNGALAFTP LDTADPAKSP KPSNGAGVPN GALRESGGSG FRSPHLWKKS STLTSSRLAT GEEEGGGSSS KRFLRSCSAS CVPHGAKDTE WRSVTLPRDL QSTGRQFDSS TFGGHKSEKP ALPRKRAGEN RSDQVTRGTV TPPPRLVKKN EEAADEVFKD IMESSPGSSP PNLTPKPLRR QVTVAPASGL PHKEEAGKGS ALGTPAAAEP VTPTSKAGSG APGGTSKGPA EESRVRRHKH SSESPGRDKG KLSRLKPAPP PPPAASAGKA GGKPSQSPSQ EAAGEAVLGA KTKATSLVDA VNSDAAKPSQ PGEGLKKPVL PATPKPQSAK PSGTPISPAP VPSTLPSASS ALAGDQPSST AFIPLISTRV SLRKTRQPPE RIASGAITKG VVLDSTEALC LAISRNSEQM ASHSAVLEAG KNLYTFCVSY VDSIQQMRNK FAFREAINKL ENNLRELQIC PATAGSGPAA TQDFSKLLSS VKEISDIVQR // ID BCR_HUMAN Reviewed; 1271 AA. AC P11274; P78501; Q12842; Q4LE80; Q6NZI3; DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot. DT 03-APR-2007, sequence version 2. DT 28-JAN-2026, entry version 260. DE RecName: Full=Breakpoint cluster region protein {ECO:0000305}; DE EC=2.7.11.1 {ECO:0000269|PubMed:1657398}; DE AltName: Full=Renal carcinoma antigen NY-REN-26; GN Name=BCR {ECO:0000312|HGNC:HGNC:1014}; Synonyms=BCR1, D22S11; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND VARIANT SER-796. RX PubMed=3285291; RA Lifshitz B., Fainstein E., Marcelle C., Shtivelman E., Amson R., Gale R.P., RA Canaani E.; RT "bcr genes and transcripts."; RL Oncogene 2:113-117(1988). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND CHROMOSOMAL TRANSLOCATION. RX PubMed=7665185; DOI=10.1006/geno.1995.1008; RA Chissoe S.L., Bodenteich A., Wang Y.-F., Wang Y.-P., Burian D., RA Clifton S.W., Crabtree J., Freeman A., Iyer K., Jian L., Ma Y., RA McLaury H.-J., Pan H.-Q., Sarhan O.H., Toth S., Wang Z., Zhang G., RA Heisterkamp N., Groffen J., Roe B.A.; RT "Sequence and analysis of the human ABL gene, the BCR gene, and regions RT involved in the Philadelphia chromosomal translocation."; RL Genomics 27:67-82(1995). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT SER-796. RC TISSUE=Brain; RA Nakajima D., Saito K., Yamakawa H., Kikuno R.F., Nakayama M., Ohara R., RA Okazaki N., Koga H., Nagase T., Ohara O.; RT "Preparation of a set of expression-ready clones of mammalian long cDNAs RT encoding large proteins by the ORF trap cloning method."; RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-872, CHROMOSOMAL TRANSLOCATION, INVOLVEMENT RP IN CML, AND VARIANT SER-796. RX PubMed=3107980; DOI=10.1002/j.1460-2075.1987.tb04727.x; RA Hariharan I.K., Adams J.M.; RT "cDNA sequence for human bcr, the gene that translocates to the abl RT oncogene in chronic myeloid leukaemia."; RL EMBO J. 6:115-119(1987). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-693, AND INVOLVEMENT IN CML. RX PubMed=3540951; DOI=10.1073/pnas.83.24.9768; RA Mes-Masson A.-M., McLaughlin J., Daley G.Q., Paskind M., Witte O.N.; RT "Overlapping cDNA clones define the complete coding region for the P210c- RT abl gene product associated with chronic myelogenous leukemia cells RT containing the Philadelphia chromosome."; RL Proc. Natl. Acad. Sci. U.S.A. 83:9768-9772(1986). RN [6] RP ERRATUM OF PUBMED:3540951, AND SEQUENCE REVISION. RA Mes-Masson A.M., McLaughlin J., Daley G.Q., Paskind M., Witte O.N.; RL Proc. Natl. Acad. Sci. U.S.A. 84:2507-2507(1987). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] OF 683-1271 (ISOFORM 1). RX PubMed=2989703; DOI=10.1038/315758a0; RA Heisterkamp N., Stam K., Groffen J., de Klein A., Grosveld G.; RT "Structural organization of the bcr gene and its role in the Ph' RT translocation."; RL Nature 315:758-761(1985). RN [8] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-46 AND 275-426. RX PubMed=2263470; DOI=10.1093/nar/18.23.7119; RA Zhu Q.S., Heisterkamp N., Groffen J.; RT "Unique organization of the human BCR gene promoter."; RL Nucleic Acids Res. 18:7119-7125(1990). RN [9] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 56-426. RX PubMed=2825022; DOI=10.1038/330386a0; RA Fainstein E., Marcelle C., Rosner A., Canaani E., Gale R.P., Dreazen O., RA Smith S.D., Croce C.M.; RT "A new fused transcript in Philadelphia chromosome positive acute RT lymphocytic leukaemia."; RL Nature 330:386-388(1987). RN [10] RP NUCLEOTIDE SEQUENCE [MRNA] OF 362-438, AND ALTERNATIVE SPLICING. RX PubMed=2915904; RA Romero P., Beran M., Shtalrid M., Andersson B., Talpaz M., Blick M.; RT "Alternative 5' end of the bcr-abl transcript in chronic myelogenous RT leukemia."; RL Oncogene 4:93-98(1989). RN [11] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 670-842, INVOLVEMENT IN CML, AND RP VARIANT SER-796. RX PubMed=2407300; RA Selleri L., von Lindern M., Hermans A., Meijer D., Torelli G., Grosveld G.; RT "Chronic myeloid leukemia may be associated with several bcr-abl RT transcripts including the acute lymphoid leukemia-type 7 kb transcript."; RL Blood 75:1146-1153(1990). RN [12] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-4. RX PubMed=1900918; DOI=10.1128/mcb.11.4.1854-1860.1991; RA Shah N.P., Witte O.N., Denny C.T.; RT "Characterization of the BCR promoter in Philadelphia chromosome-positive RT and -negative cell lines."; RL Mol. Cell. Biol. 11:1854-1860(1991). RN [13] RP FUNCTION. RX PubMed=1903516; DOI=10.1038/351400a0; RA Diekmann D., Brill S., Garrett M.D., Totty N., Hsuan J., Monfries C., RA Hall C., Lim L., Hall A.; RT "Bcr encodes a GTPase-activating protein for p21rac."; RL Nature 351:400-402(1991). RN [14] RP INTERACTION WITH ABL1 SH2-DOMAIN. RX PubMed=1712671; DOI=10.1016/0092-8674(91)90148-r; RA Pendergast A.M., Muller A.J., Havlik M.H., Maru Y., Witte O.N.; RT "BCR sequences essential for transformation by the BCR-ABL oncogene bind to RT the ABL SH2 regulatory domain in a non-phosphotyrosine-dependent manner."; RL Cell 66:161-171(1991). RN [15] RP FUNCTION AS PROTEIN KINASE, AND CATALYTIC ACTIVITY. RX PubMed=1657398; DOI=10.1016/0092-8674(91)90521-y; RA Maru Y., Witte O.N.; RT "The BCR gene encodes a novel serine/threonine kinase activity within a RT single exon."; RL Cell 67:459-468(1991). RN [16] RP FUNCTION, AND DOMAIN. RX PubMed=7479768; DOI=10.1073/pnas.92.22.10282; RA Chuang T.H., Xu X., Kaartinen V., Heisterkamp N., Groffen J., Bokoch G.M.; RT "Abr and Bcr are multifunctional regulators of the Rho GTP-binding protein RT family."; RL Proc. Natl. Acad. Sci. U.S.A. 92:10282-10286(1995). RN [17] RP PHOSPHORYLATION AT TYR-177 BY HCK, MUTAGENESIS OF TYR-177, AND INTERACTION RP WITH HCK AND GRB2. RX PubMed=9407116; DOI=10.1074/jbc.272.52.33260; RA Warmuth M., Bergmann M., Priess A., Hauslmann K., Emmerich B., Hallek M.; RT "The Src family kinase Hck interacts with Bcr-Abl by a kinase-independent RT mechanism and phosphorylates the Grb2-binding site of Bcr."; RL J. Biol. Chem. 272:33260-33270(1997). RN [18] RP IDENTIFICATION AS A RENAL CANCER ANTIGEN. RC TISSUE=Renal cell carcinoma; RX PubMed=10508479; RX DOI=10.1002/(sici)1097-0215(19991112)83:4<456::aid-ijc4>3.0.co;2-5; RA Scanlan M.J., Gordan J.D., Williamson B., Stockert E., Bander N.H., RA Jongeneel C.V., Gure A.O., Jaeger D., Jaeger E., Knuth A., Chen Y.-T., RA Old L.J.; RT "Antigens recognized by autologous antibody in patients with renal-cell RT carcinoma."; RL Int. J. Cancer 83:456-464(1999). RN [19] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1264, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=15144186; DOI=10.1021/ac035352d; RA Brill L.M., Salomon A.R., Ficarro S.B., Mukherji M., Stettler-Gill M., RA Peters E.C.; RT "Robust phosphoproteomic profiling of tyrosine phosphorylation sites from RT human T cells using immobilized metal affinity chromatography and tandem RT mass spectrometry."; RL Anal. Chem. 76:2763-2772(2004). RN [20] RP INTERACTION WITH FES/FPS; ABL1; PIK3R1 AND GRB2, MUTAGENESIS OF TYR-177, RP PHOSPHORYLATION AT TYR-246, AND FUNCTION. RX PubMed=15302586; DOI=10.1016/j.yexcr.2004.05.010; RA Laurent C.E., Smithgall T.E.; RT "The c-Fes tyrosine kinase cooperates with the breakpoint cluster region RT protein (Bcr) to induce neurite extension in a Rac- and Cdc42-dependent RT manner."; RL Exp. Cell Res. 299:188-198(2004). RN [21] RP INTERACTION WITH PDZK1, AND MUTAGENESIS OF 1269-THR--GLU-1271 AND VAL-1271. RX PubMed=15494376; DOI=10.1242/jcs.01472; RA Malmberg E.K., Andersson C.X., Gentzsch M., Chen J.H., Mengos A., Cui L., RA Hansson G.C., Riordan J.R.; RT "Bcr (breakpoint cluster region) protein binds to PDZ-domains of scaffold RT protein PDZK1 and vesicle coat protein Mint3."; RL J. Cell Sci. 117:5535-5541(2004). RN [22] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling RT networks."; RL Cell 127:635-648(2006). RN [23] RP FUNCTION, AND MUTAGENESIS OF ARG-1090 AND ASN-1202. RX PubMed=17116687; DOI=10.1128/mcb.00756-06; RA Cho Y.J., Cunnick J.M., Yi S.J., Kaartinen V., Groffen J., Heisterkamp N.; RT "Abr and Bcr, two homologous Rac GTPase-activating proteins, control RT multiple cellular functions of murine macrophages."; RL Mol. Cell. Biol. 27:899-911(2007). RN [24] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Platelet; RX PubMed=18088087; DOI=10.1021/pr0704130; RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., RA Schuetz C., Walter U., Gambaryan S., Sickmann A.; RT "Phosphoproteome of resting human platelets."; RL J. Proteome Res. 7:526-534(2008). RN [25] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-459, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [26] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-177; SER-459 AND SER-1264, RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [27] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [28] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-122; SER-215 AND SER-459, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [29] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22223895; DOI=10.1074/mcp.m111.015131; RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., RA Giglione C.; RT "Comparative large-scale characterisation of plant vs. mammal proteins RT reveals similar and idiosyncratic N-alpha acetylation features."; RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012). RN [30] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-122; SER-139; SER-202; RP SER-215; SER-222; SER-356; SER-377; SER-459; SER-463; SER-473; SER-488; RP TYR-554; THR-641; TYR-644; THR-693 AND SER-894, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [31] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-459, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [32] RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 3-72, AND HOMOTETRAMERIZATION. RX PubMed=11780146; DOI=10.1038/nsb747; RA Zhao X., Ghaffari S., Lodish H., Malashkevich V.N., Kim P.S.; RT "Structure of the Bcr-Abl oncoprotein oligomerization domain."; RL Nat. Struct. Biol. 9:117-120(2002). RN [33] RP FUNCTION, INTERACTION WITH DLG4, AND MUTAGENESIS OF VAL-1271. RX PubMed=20962234; DOI=10.1523/jneurosci.1711-10.2010; RA Oh D., Han S., Seo J., Lee J.R., Choi J., Groffen J., Kim K., Cho Y.S., RA Choi H.S., Shin H., Woo J., Won H., Park S.K., Kim S.Y., Jo J., RA Whitcomb D.J., Cho K., Kim H., Bae Y.C., Heisterkamp N., Choi S.Y., Kim E.; RT "Regulation of synaptic Rac1 activity, long-term potentiation maintenance, RT and learning and memory by BCR and ABR Rac GTPase-activating proteins."; RL J. Neurosci. 30:14134-14144(2010). RN [34] RP FUNCTION, AND MUTAGENESIS OF 689-ASN-GLU-690. RX PubMed=23940119; DOI=10.1083/jcb.201304133; RA Dubash A.D., Koetsier J.L., Amargo E.V., Najor N.A., Harmon R.M., RA Green K.J.; RT "The GEF Bcr activates RhoA/MAL signaling to promote keratinocyte RT differentiation via desmoglein-1."; RL J. Cell Biol. 202:653-666(2013). RN [35] RP INTERACTION WITH SH2D5. RX PubMed=25331951; DOI=10.1074/jbc.m114.615112; RA Gray E.J., Petsalaki E., James D.A., Bagshaw R.D., Stacey M.M., Rocks O., RA Gingras A.C., Pawson T.; RT "src homology 2 domain containing protein 5 (sh2d5) binds the breakpoint RT cluster region protein, BCR, and regulates levels of Rac1-GTP."; RL J. Biol. Chem. 289:35397-35408(2014). RN [36] RP VARIANTS [LARGE SCALE ANALYSIS] PRO-400; MET-413; GLU-752; SER-796; RP CYS-910; ILE-949; LYS-1037; MET-1091; ALA-1096; GLY-1104; ASN-1106; RP THR-1149; LYS-1161; GLU-1187; MET-1189; GLY-1204 AND ARG-1235. RX PubMed=17344846; DOI=10.1038/nature05610; RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G., RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., RA Futreal P.A., Stratton M.R.; RT "Patterns of somatic mutation in human cancer genomes."; RL Nature 446:153-158(2007). CC -!- FUNCTION: Protein with a unique structure having two opposing CC regulatory activities toward small GTP-binding proteins. The C-terminus CC is a GTPase-activating protein (GAP) domain which stimulates GTP CC hydrolysis by RAC1, RAC2 and CDC42. Accelerates the intrinsic rate of CC GTP hydrolysis of RAC1 or CDC42, leading to down-regulation of the CC active GTP-bound form (PubMed:17116687, PubMed:1903516, CC PubMed:7479768). The central Dbl homology (DH) domain functions as CC guanine nucleotide exchange factor (GEF) that modulates the GTPases CC CDC42, RHOA and RAC1. Promotes the conversion of CDC42, RHOA and RAC1 CC from the GDP-bound to the GTP-bound form (PubMed:23940119, CC PubMed:7479768). The amino terminus contains an intrinsic kinase CC activity (PubMed:1657398). Functions as an important negative regulator CC of neuronal RAC1 activity (By similarity). Regulates macrophage CC functions such as CSF1-directed motility and phagocytosis through the CC modulation of RAC1 activity (PubMed:17116687). Plays a major role as a CC RHOA GEF in keratinocytes being involved in focal adhesion formation CC and keratinocyte differentiation (PubMed:23940119). CC {ECO:0000250|UniProtKB:Q6PAJ1, ECO:0000269|PubMed:1657398, CC ECO:0000269|PubMed:17116687, ECO:0000269|PubMed:1903516, CC ECO:0000269|PubMed:23940119, ECO:0000269|PubMed:7479768}. CC -!- CATALYTIC ACTIVITY: CC Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + CC H(+); Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA- CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1; CC Evidence={ECO:0000269|PubMed:1657398}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17990; CC Evidence={ECO:0000269|PubMed:1657398}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + CC ADP + H(+); Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA- CC COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.1; CC Evidence={ECO:0000269|PubMed:1657398}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46609; CC Evidence={ECO:0000269|PubMed:1657398}; CC -!- SUBUNIT: Homotetramer. Interacts with PDZK1 (PubMed:15494376). May CC interact with CCPG1 (By similarity). Interacts with FES/FPS, ABL1, CC PIK3R1 and GRB2 (PubMed:15302586, PubMed:1712671, PubMed:9407116). CC Interacts with HCK (PubMed:9407116). Interacts with SH2D5 CC (PubMed:25331951). Interacts with DLG4 (PubMed:20962234). CC {ECO:0000250|UniProtKB:Q6PAJ1, ECO:0000269|PubMed:15302586, CC ECO:0000269|PubMed:15494376, ECO:0000269|PubMed:1712671, CC ECO:0000269|PubMed:20962234, ECO:0000269|PubMed:25331951, CC ECO:0000269|PubMed:9407116}. CC -!- INTERACTION: CC P11274; O96018: APBA3; NbExp=5; IntAct=EBI-712838, EBI-6115839; CC P11274; Q12959: DLG1; NbExp=3; IntAct=EBI-712838, EBI-357481; CC P11274; Q15700: DLG2; NbExp=2; IntAct=EBI-712838, EBI-80426; CC P11274; Q92796: DLG3; NbExp=2; IntAct=EBI-712838, EBI-80440; CC P11274; P78352: DLG4; NbExp=2; IntAct=EBI-712838, EBI-80389; CC P11274; P62993: GRB2; NbExp=13; IntAct=EBI-712838, EBI-401755; CC P11274; Q86UL8: MAGI2; NbExp=3; IntAct=EBI-712838, EBI-311035; CC P11274; Q8NI35: PATJ; NbExp=5; IntAct=EBI-712838, EBI-724390; CC P11274; Q5T2W1: PDZK1; NbExp=8; IntAct=EBI-712838, EBI-349819; CC P11274; Q14160: SCRIB; NbExp=3; IntAct=EBI-712838, EBI-357345; CC P11274; Q6ZV89-1: SH2D5; NbExp=2; IntAct=EBI-712838, EBI-15101685; CC P11274; Q9H2K2: TNKS2; NbExp=3; IntAct=EBI-712838, EBI-4398527; CC P11274; A2AM67: Sh2d5; Xeno; NbExp=7; IntAct=EBI-712838, EBI-15101945; CC P11274; Q8JZW5: Sh2d5; Xeno; NbExp=2; IntAct=EBI-712838, EBI-15101675; CC P11274-1; P18031: PTPN1; NbExp=3; IntAct=EBI-8658094, EBI-968788; CC -!- SUBCELLULAR LOCATION: Postsynaptic density CC {ECO:0000250|UniProtKB:Q6PAJ1}. Cell projection, dendritic spine CC {ECO:0000250|UniProtKB:Q6PAJ1}. Cell projection, axon CC {ECO:0000250|UniProtKB:Q6PAJ1}. Synapse {ECO:0000250|UniProtKB:F1LXF1}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P11274-1; Sequence=Displayed; CC Name=2; CC IsoId=P11274-2; Sequence=VSP_024352; CC -!- DOMAIN: The region involved in binding to ABL1 SH2-domain is rich in CC serine residues and needs to be Ser/Thr phosphorylated prior to SH2 CC binding. This region is essential for the activation of the ABL1 CC tyrosine kinase and transforming potential of the chimeric BCR-ABL CC oncogene. CC -!- DOMAIN: The DH domain is involved in interaction with CCPG1. CC {ECO:0000250|UniProtKB:Q6PAJ1}. CC -!- DOMAIN: The amino terminus contains an intrinsic kinase activity. The CC central Dbl homology (DH) domain functions as a guanine nucleotide CC exchange factor (GEF) that modulates the GTPases CDC42, RHOA and RAC1. CC Promotes the conversion of CDC42, RHOA and RAC1 from the GDP-bound to CC the GTP-bound form. The C-terminus is a Rho-GAP domain which stimulates CC GTP hydrolysis by RAC1, RAC2 and CDC42. The protein has a unique CC structure having two opposing regulatory activities toward small GTP- CC binding proteins. {ECO:0000305|PubMed:7479768}. CC -!- PTM: Autophosphorylated. Phosphorylated by FES/FPS on tyrosine CC residues, leading to down-regulation of the BCR kinase activity. CC Phosphorylation at Tyr-177 by HCK is important for interaction with CC GRB2. {ECO:0000269|PubMed:15302586, ECO:0000269|PubMed:9407116}. CC -!- DISEASE: Leukemia, chronic myeloid (CML) [MIM:608232]: A clonal CC myeloproliferative disorder of a pluripotent stem cell with a specific CC cytogenetic abnormality, the Philadelphia chromosome (Ph), involving CC myeloid, erythroid, megakaryocytic, B-lymphoid, and sometimes T- CC lymphoid cells, but not marrow fibroblasts. CC {ECO:0000269|PubMed:2407300, ECO:0000269|PubMed:3107980, CC ECO:0000269|PubMed:3540951}. Note=The gene represented in this entry is CC involved in disease pathogenesis. CC -!- DISEASE: Note=A chromosomal aberration involving BCR has been found in CC patients with chronic myeloid leukemia. Translocation t(9;22)(q34;q11) CC with ABL1. The translocation produces a BCR-ABL found also in acute CC myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). CC {ECO:0000269|PubMed:3107980, ECO:0000269|PubMed:7665185}. CC -!- SEQUENCE CAUTION: CC Sequence=BAE06073.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/55/BCR"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; Y00661; CAA68676.1; -; mRNA. DR EMBL; U07000; AAB60388.1; -; Genomic_DNA. DR EMBL; AB209991; BAE06073.1; ALT_INIT; mRNA. DR EMBL; X02596; CAA26441.1; -; mRNA. DR EMBL; M15025; AAA35594.1; -; Genomic_DNA. DR EMBL; X52828; CAA37010.1; -; Genomic_DNA. DR EMBL; X52829; CAA37011.1; -; Genomic_DNA. DR EMBL; X14676; CAA32806.1; -; mRNA. DR EMBL; M64437; -; NOT_ANNOTATED_CDS; mRNA. DR CCDS; CCDS13806.1; -. [P11274-1] DR CCDS; CCDS13807.1; -. [P11274-2] DR PIR; A26664; TVHUA2. DR PIR; A91064; TVHUBR. DR RefSeq; NP_004318.3; NM_004327.3. [P11274-1] DR RefSeq; NP_067585.2; NM_021574.3. [P11274-2] DR PDB; 1K1F; X-ray; 2.20 A; A/B/C/D/E/F/G/H=1-72. DR PDB; 2AIN; NMR; -; B=1266-1271. DR PDB; 5N6R; NMR; -; A=487-702. DR PDB; 5N7E; X-ray; 1.65 A; B=487-702. DR PDB; 5OC7; X-ray; 1.65 A; A/D=704-893. DR PDBsum; 1K1F; -. DR PDBsum; 2AIN; -. DR PDBsum; 5N6R; -. DR PDBsum; 5N7E; -. DR PDBsum; 5OC7; -. DR AlphaFoldDB; P11274; -. DR SASBDB; P11274; -. DR SMR; P11274; -. DR BioGRID; 107083; 230. DR CORUM; P11274; -. DR ELM; P11274; -. DR FunCoup; P11274; 1481. DR IntAct; P11274; 222. DR MINT; P11274; -. DR STRING; 9606.ENSP00000303507; -. DR BindingDB; P11274; -. DR ChEMBL; CHEMBL5146; -. DR DrugBank; DB01254; Dasatinib. DR DrugBank; DB00619; Imatinib. DR DrugBank; DB08901; Ponatinib. DR DrugCentral; P11274; -. DR GlyCosmos; P11274; 1 site, 1 glycan. DR GlyGen; P11274; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P11274; -. DR MetOSite; P11274; -. DR PhosphoSitePlus; P11274; -. DR BioMuta; BCR; -. DR DMDM; 143811366; -. DR jPOST; P11274; -. DR MassIVE; P11274; -. DR PaxDb; 9606-ENSP00000303507; -. DR PeptideAtlas; P11274; -. DR ProteomicsDB; 52729; -. [P11274-1] DR ProteomicsDB; 52730; -. [P11274-2] DR Pumba; P11274; -. DR ABCD; P11274; 2 sequenced antibodies. DR Antibodypedia; 9277; 677 antibodies from 41 providers. DR DNASU; 613; -. DR Ensembl; ENST00000305877.13; ENSP00000303507.8; ENSG00000186716.22. [P11274-1] DR Ensembl; ENST00000359540.7; ENSP00000352535.3; ENSG00000186716.22. [P11274-2] DR GeneID; 613; -. DR KEGG; hsa:613; -. DR MANE-Select; ENST00000305877.13; ENSP00000303507.8; NM_004327.4; NP_004318.3. DR UCSC; uc002zww.4; human. [P11274-1] DR AGR; HGNC:1014; -. DR ClinPGx; PA25321; -. DR CTD; 613; -. DR DisGeNET; 613; -. DR GeneCards; BCR; -. DR HGNC; HGNC:1014; BCR. DR HPA; ENSG00000186716; Low tissue specificity. DR MalaCards; BCR; -. DR MIM; 151410; gene. DR MIM; 608232; phenotype. DR OpenTargets; ENSG00000186716; -. DR Orphanet; 585909; B-lymphoblastic leukemia/lymphoma with t(9;22)(q34.1;q11.2). DR Orphanet; 521; Chronic myeloid leukemia. DR Orphanet; 261330; Distal 22q11.2 microdeletion syndrome. DR Orphanet; 99861; Precursor T-cell acute lymphoblastic leukemia. DR VEuPathDB; HostDB:ENSG00000186716; -. DR eggNOG; KOG4269; Eukaryota. DR GeneTree; ENSGT00940000153491; -. DR HOGENOM; CLU_004164_0_0_1; -. DR InParanoid; P11274; -. DR OMA; HDLMPFI; -. DR OrthoDB; 2155291at2759; -. DR PAN-GO; P11274; 1 GO annotation based on evolutionary models. DR PhylomeDB; P11274; -. DR PathwayCommons; P11274; -. DR Reactome; R-HSA-1839117; Signaling by cytosolic FGFR1 fusion mutants. DR Reactome; R-HSA-5655302; Signaling by FGFR1 in disease. DR Reactome; R-HSA-8980692; RHOA GTPase cycle. DR Reactome; R-HSA-9013026; RHOB GTPase cycle. DR Reactome; R-HSA-9013106; RHOC GTPase cycle. DR Reactome; R-HSA-9013148; CDC42 GTPase cycle. DR Reactome; R-HSA-9013149; RAC1 GTPase cycle. DR Reactome; R-HSA-9013404; RAC2 GTPase cycle. DR Reactome; R-HSA-9013423; RAC3 GTPase cycle. DR SignaLink; P11274; -. DR SIGNOR; P11274; -. DR Agora; ENSG00000186716; -. DR BioGRID-ORCS; 613; 37 hits in 1202 CRISPR screens. DR CD-CODE; FB4E32DD; Presynaptic clusters and postsynaptic densities. DR ChiTaRS; BCR; human. DR EvolutionaryTrace; P11274; -. DR GeneWiki; BCR_(gene); -. DR GenomeRNAi; 613; -. DR Pharos; P11274; Tclin. DR PRO; PR:P11274; -. DR Proteomes; UP000005640; Chromosome 22. DR RNAct; P11274; protein. DR Bgee; ENSG00000186716; Expressed in nucleus accumbens and 182 other cell types or tissues. DR ExpressionAtlas; P11274; baseline and differential. DR GO; GO:0030424; C:axon; IEA:UniProtKB-SubCell. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0043197; C:dendritic spine; IEA:UniProtKB-SubCell. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0098978; C:glutamatergic synapse; ISS:UniProtKB. DR GO; GO:0016020; C:membrane; HDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IEA:Ensembl. DR GO; GO:0014069; C:postsynaptic density; IEA:UniProtKB-SubCell. DR GO; GO:0032991; C:protein-containing complex; IDA:MGI. DR GO; GO:0098685; C:Schaffer collateral - CA1 synapse; ISS:UniProtKB. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0005096; F:GTPase activator activity; IDA:UniProtKB. DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IDA:UniProtKB. DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA. DR GO; GO:0004674; F:protein serine/threonine kinase activity; TAS:ProtInc. DR GO; GO:0004713; F:protein tyrosine kinase activity; TAS:Reactome. DR GO; GO:0030036; P:actin cytoskeleton organization; IEA:Ensembl. DR GO; GO:0090630; P:activation of GTPase activity; IDA:UniProtKB. DR GO; GO:0007420; P:brain development; IEA:Ensembl. DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IEA:Ensembl. DR GO; GO:0060216; P:definitive hemopoiesis; IEA:Ensembl. DR GO; GO:0048041; P:focal adhesion assembly; IMP:UniProtKB. DR GO; GO:0048872; P:homeostasis of number of cells; IEA:Ensembl. DR GO; GO:0042472; P:inner ear morphogenesis; IEA:Ensembl. DR GO; GO:0065002; P:intracellular protein transmembrane transport; IEA:Ensembl. DR GO; GO:0030216; P:keratinocyte differentiation; IMP:UniProtKB. DR GO; GO:1905517; P:macrophage migration; IEA:Ensembl. DR GO; GO:0050804; P:modulation of chemical synaptic transmission; ISS:UniProtKB. DR GO; GO:0060313; P:negative regulation of blood vessel remodeling; IEA:Ensembl. DR GO; GO:0002692; P:negative regulation of cellular extravasation; IEA:Ensembl. DR GO; GO:0050728; P:negative regulation of inflammatory response; IEA:Ensembl. DR GO; GO:1905522; P:negative regulation of macrophage migration; IEA:Ensembl. DR GO; GO:0043314; P:negative regulation of neutrophil degranulation; IEA:Ensembl. DR GO; GO:2000378; P:negative regulation of reactive oxygen species metabolic process; IEA:Ensembl. DR GO; GO:0060268; P:negative regulation of respiratory burst; IEA:Ensembl. DR GO; GO:0050885; P:neuromuscular process controlling balance; IEA:Ensembl. DR GO; GO:0043312; P:neutrophil degranulation; IEA:Ensembl. DR GO; GO:0006909; P:phagocytosis; IEA:Ensembl. DR GO; GO:0050766; P:positive regulation of phagocytosis; IEA:Ensembl. DR GO; GO:0006468; P:protein phosphorylation; TAS:ProtInc. DR GO; GO:0051726; P:regulation of cell cycle; IEA:Ensembl. DR GO; GO:0035023; P:regulation of Rho protein signal transduction; IMP:UniProtKB. DR GO; GO:0051056; P:regulation of small GTPase mediated signal transduction; TAS:Reactome. DR GO; GO:0043114; P:regulation of vascular permeability; IEA:Ensembl. DR GO; GO:0003014; P:renal system process; IEA:Ensembl. DR GO; GO:0007165; P:signal transduction; TAS:ProtInc. DR GO; GO:0007264; P:small GTPase-mediated signal transduction; IMP:UniProtKB. DR CDD; cd08686; C2_ABR; 1. DR CDD; cd13367; PH_BCR_vertebrate; 1. DR CDD; cd04387; RhoGAP_Bcr; 1. DR CDD; cd00160; RhoGEF; 1. DR DisProt; DP03016; -. DR FunFam; 2.60.40.150:FF:000057; active breakpoint cluster region-related protein isoform X1; 1. DR FunFam; 1.20.900.10:FF:000014; active breakpoint cluster region-related protein isoform X2; 1. DR FunFam; 1.10.555.10:FF:000004; active breakpoint cluster region-related protein-like; 1. DR Gene3D; 4.10.280.30; Bcr-Abl oncoprotein oligomerisation domain; 1. DR Gene3D; 2.60.40.150; C2 domain; 1. DR Gene3D; 1.20.900.10; Dbl homology (DH) domain; 1. DR Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 1. DR Gene3D; 1.10.555.10; Rho GTPase activation protein; 1. DR InterPro; IPR037769; Abr/Bcr. DR InterPro; IPR015123; Bcr-Abl_oncoprot_oligo. DR InterPro; IPR036481; Bcr-Abl_oncoprot_oligo_sf. DR InterPro; IPR000008; C2_dom. DR InterPro; IPR035892; C2_domain_sf. DR InterPro; IPR035899; DBL_dom_sf. DR InterPro; IPR000219; DH_dom. DR InterPro; IPR001331; GDS_CDC24_CS. DR InterPro; IPR011993; PH-like_dom_sf. DR InterPro; IPR001849; PH_domain. DR InterPro; IPR008936; Rho_GTPase_activation_prot. DR InterPro; IPR000198; RhoGAP_dom. DR PANTHER; PTHR23182:SF3; BREAKPOINT CLUSTER REGION PROTEIN; 1. DR PANTHER; PTHR23182; BREAKPOINT CLUSTER REGION PROTEIN BCR; 1. DR Pfam; PF09036; Bcr-Abl_Oligo; 1. DR Pfam; PF00168; C2; 1. DR Pfam; PF19057; PH_19; 1. DR Pfam; PF00620; RhoGAP; 1. DR Pfam; PF00621; RhoGEF; 1. DR SMART; SM00239; C2; 1. DR SMART; SM00233; PH; 1. DR SMART; SM00324; RhoGAP; 1. DR SMART; SM00325; RhoGEF; 1. DR SUPFAM; SSF69036; Bcr-Abl oncoprotein oligomerization domain; 1. DR SUPFAM; SSF49562; C2 domain (Calcium/lipid-binding domain, CaLB); 1. DR SUPFAM; SSF48065; DBL homology domain (DH-domain); 1. DR SUPFAM; SSF48350; GTPase activation domain, GAP; 1. DR SUPFAM; SSF50729; PH domain-like; 1. DR PROSITE; PS50004; C2; 1. DR PROSITE; PS00741; DH_1; 1. DR PROSITE; PS50010; DH_2; 1. DR PROSITE; PS50003; PH_DOMAIN; 1. DR PROSITE; PS50238; RHOGAP; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; ATP-binding; KW Cell projection; Chromosomal rearrangement; Coiled coil; GTPase activation; KW Guanine-nucleotide releasing factor; Kinase; Methylation; KW Nucleotide-binding; Phosphoprotein; Proteomics identification; KW Proto-oncogene; Reference proteome; Serine/threonine-protein kinase; KW Synapse; Transferase. FT CHAIN 1..1271 FT /note="Breakpoint cluster region protein" FT /id="PRO_0000080933" FT DOMAIN 498..691 FT /note="DH" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00062" FT DOMAIN 708..866 FT /note="PH" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145" FT DOMAIN 893..1020 FT /note="C2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041" FT DOMAIN 1054..1248 FT /note="Rho-GAP" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00172" FT REGION 1..426 FT /note="Kinase" FT REGION 67..173 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 185..247 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 197..385 FT /note="Binding to ABL SH2-domain" FT REGION 286..392 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 416..476 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COILED 28..55 FT /evidence="ECO:0000255" FT COMPBIAS 87..105 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 123..138 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 185..198 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 199..208 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 346..356 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 369..382 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 441..451 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT SITE 426..427 FT /note="Breakpoint for translocation to form BCR-ABL FT oncogene" FT SITE 1090 FT /note="Arginine finger; crucial for GTP hydrolysis by FT stabilizing the transition state" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00172" FT MOD_RES 1 FT /note="N-acetylmethionine" FT /evidence="ECO:0007744|PubMed:22223895" FT MOD_RES 122 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163" FT MOD_RES 139 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 177 FT /note="Phosphotyrosine; by HCK" FT /evidence="ECO:0000269|PubMed:9407116, FT ECO:0007744|PubMed:19690332" FT MOD_RES 202 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 215 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163" FT MOD_RES 222 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 236 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q6PAJ1" FT MOD_RES 246 FT /note="Phosphotyrosine; by FES" FT /evidence="ECO:0000269|PubMed:15302586" FT MOD_RES 356 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 377 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 382 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q6PAJ1" FT MOD_RES 385 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q6PAJ1" FT MOD_RES 459 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569" FT MOD_RES 463 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 471 FT /note="Omega-N-methylarginine" FT /evidence="ECO:0000250|UniProtKB:Q6PAJ1" FT MOD_RES 473 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 488 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 554 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 641 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 644 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 693 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 894 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 1264 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:15144186, FT ECO:0007744|PubMed:19690332" FT VAR_SEQ 961..1004 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:3285291" FT /id="VSP_024352" FT VARIANT 400 FT /note="S -> P (in a bladder transitional cell carcinoma FT sample; somatic mutation)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041883" FT VARIANT 413 FT /note="I -> M (in dbSNP:rs56321828)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041884" FT VARIANT 558 FT /note="K -> T (in dbSNP:rs4437065)" FT /id="VAR_051983" FT VARIANT 752 FT /note="D -> E (in dbSNP:rs12484731)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041885" FT VARIANT 796 FT /note="N -> S (in dbSNP:rs140504)" FT /evidence="ECO:0000269|PubMed:17344846, FT ECO:0000269|PubMed:2407300, ECO:0000269|PubMed:3107980, FT ECO:0000269|PubMed:3285291, ECO:0000269|Ref.3" FT /id="VAR_031552" FT VARIANT 910 FT /note="Y -> C (in dbSNP:rs35537221)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041886" FT VARIANT 949 FT /note="V -> I (in dbSNP:rs2229038)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041887" FT VARIANT 1037 FT /note="E -> K (in dbSNP:rs776552570)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_031553" FT VARIANT 1091 FT /note="V -> M (in dbSNP:rs778229520)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041888" FT VARIANT 1096 FT /note="T -> A (in dbSNP:rs745459086)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041889" FT VARIANT 1104 FT /note="A -> G (in dbSNP:rs11558696)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041890" FT VARIANT 1106 FT /note="D -> N (in dbSNP:rs879255379)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041891" FT VARIANT 1127 FT /note="T -> M (in dbSNP:rs35812689)" FT /id="VAR_031554" FT VARIANT 1149 FT /note="A -> T (in dbSNP:rs200099830)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041892" FT VARIANT 1161 FT /note="E -> K (in dbSNP:rs2074037194)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041893" FT VARIANT 1187 FT /note="K -> E (in dbSNP:rs1195127922)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041894" FT VARIANT 1189 FT /note="V -> M (in dbSNP:rs55816482)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041895" FT VARIANT 1204 FT /note="A -> G (in dbSNP:rs56265970)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041896" FT VARIANT 1235 FT /note="W -> R (in dbSNP:rs55719322)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041897" FT MUTAGEN 177 FT /note="Y->F: Abolishes interaction with FES and GRB2." FT /evidence="ECO:0000269|PubMed:15302586, FT ECO:0000269|PubMed:9407116" FT MUTAGEN 689..690 FT /note="NE->AA: Loss of RHOA GEF activity." FT /evidence="ECO:0000269|PubMed:23940119" FT MUTAGEN 1090 FT /note="R->A: Loss of GAP activity. Loss of GAP activity; FT when associated with A-1202." FT /evidence="ECO:0000269|PubMed:17116687" FT MUTAGEN 1202 FT /note="N->A: Loss of GAP activity; when associated with A- FT 1090." FT /evidence="ECO:0000269|PubMed:17116687" FT MUTAGEN 1269..1271 FT /note="Missing: Abolishes interaction with PDZK1." FT /evidence="ECO:0000269|PubMed:15494376" FT MUTAGEN 1271 FT /note="V->A: Reduces interaction with PDZK1. Abolishes FT interaction with DLG4. No effect on synaptic localization." FT /evidence="ECO:0000269|PubMed:15494376, FT ECO:0000269|PubMed:20962234" FT CONFLICT 287 FT /note="M -> I (in Ref. 1; CAA68676)" FT /evidence="ECO:0000305" FT CONFLICT 418 FT /note="G -> D (in Ref. 1; CAA68676)" FT /evidence="ECO:0000305" FT CONFLICT 483 FT /note="E -> K (in Ref. 1; CAA68676)" FT /evidence="ECO:0000305" FT CONFLICT 560 FT /note="F -> S (in Ref. 1; CAA68676)" FT /evidence="ECO:0000305" FT CONFLICT 690 FT /note="E -> D (in Ref. 11)" FT /evidence="ECO:0000305" FT CONFLICT 733 FT /note="D -> E (in Ref. 4; CAA26441)" FT /evidence="ECO:0000305" FT HELIX 4..14 FT /evidence="ECO:0007829|PDB:1K1F" FT HELIX 28..64 FT /evidence="ECO:0007829|PDB:1K1F" FT HELIX 492..521 FT /evidence="ECO:0007829|PDB:5N7E" FT HELIX 524..531 FT /evidence="ECO:0007829|PDB:5N7E" FT STRAND 533..535 FT /evidence="ECO:0007829|PDB:5N7E" FT HELIX 540..546 FT /evidence="ECO:0007829|PDB:5N7E" FT TURN 547..549 FT /evidence="ECO:0007829|PDB:5N7E" FT HELIX 550..569 FT /evidence="ECO:0007829|PDB:5N7E" FT HELIX 578..586 FT /evidence="ECO:0007829|PDB:5N7E" FT HELIX 588..611 FT /evidence="ECO:0007829|PDB:5N7E" FT HELIX 613..618 FT /evidence="ECO:0007829|PDB:5N7E" FT STRAND 630..634 FT /evidence="ECO:0007829|PDB:5N6R" FT HELIX 639..651 FT /evidence="ECO:0007829|PDB:5N7E" FT HELIX 653..661 FT /evidence="ECO:0007829|PDB:5N7E" FT HELIX 670..687 FT /evidence="ECO:0007829|PDB:5N7E" FT STRAND 694..697 FT /evidence="ECO:0007829|PDB:5N6R" FT STRAND 709..719 FT /evidence="ECO:0007829|PDB:5OC7" FT STRAND 722..740 FT /evidence="ECO:0007829|PDB:5OC7" FT STRAND 751..758 FT /evidence="ECO:0007829|PDB:5OC7" FT HELIX 759..761 FT /evidence="ECO:0007829|PDB:5OC7" FT STRAND 762..767 FT /evidence="ECO:0007829|PDB:5OC7" FT STRAND 830..838 FT /evidence="ECO:0007829|PDB:5OC7" FT STRAND 843..847 FT /evidence="ECO:0007829|PDB:5OC7" FT HELIX 851..865 FT /evidence="ECO:0007829|PDB:5OC7" FT HELIX 876..885 FT /evidence="ECO:0007829|PDB:5OC7" FT STRAND 1268..1271 FT /evidence="ECO:0007829|PDB:2AIN" SQ SEQUENCE 1271 AA; 142819 MW; 4BF66FA1E9D205FE CRC64; MVDPVGFAEA WKAQFPDSEP PRMELRSVGD IEQELERCKA SIRRLEQEVN QERFRMIYLQ TLLAKEKKSY DRQRWGFRRA AQAPDGASEP RASASRPQPA PADGADPPPA EEPEARPDGE GSPGKARPGT ARRPGAAASG ERDDRGPPAS VAALRSNFER IRKGHGQPGA DAEKPFYVNV EFHHERGLVK VNDKEVSDRI SSLGSQAMQM ERKKSQHGAG SSVGDASRPP YRGRSSESSC GVDGDYEDAE LNPRFLKDNL IDANGGSRPP WPPLEYQPYQ SIYVGGMMEG EGKGPLLRSQ STSEQEKRLT WPRRSYSPRS FEDCGGGYTP DCSSNENLTS SEEDFSSGQS SRVSPSPTTY RMFRDKSRSP SQNSQQSFDS SSPPTPQCHK RHRHCPVVVS EATIVGVRKT GQIWPNDGEG AFHGDADGSF GTPPGYGCAA DRAEEQRRHQ DGLPYIDDSP SSSPHLSSKG RGSRDALVSG ALESTKASEL DLEKGLEMRK WVLSGILASE ETYLSHLEAL LLPMKPLKAA ATTSQPVLTS QQIETIFFKV PELYEIHKEF YDGLFPRVQQ WSHQQRVGDL FQKLASQLGV YRAFVDNYGV AMEMAEKCCQ ANAQFAEISE NLRARSNKDA KDPTTKNSLE TLLYKPVDRV TRSTLVLHDL LKHTPASHPD HPLLQDALRI SQNFLSSINE EITPRRQSMT VKKGEHRQLL KDSFMVELVE GARKLRHVFL FTDLLLCTKL KKQSGGKTQQ YDCKWYIPLT DLSFQMVDEL EAVPNIPLVP DEELDALKIK ISQIKNDIQR EKRANKGSKA TERLKKKLSE QESLLLLMSP SMAFRVHSRN GKSYTFLISS DYERAEWREN IREQQKKCFR SFSLTSVELQ MLTNSCVKLQ TVHSIPLTIN KEDDESPGLY GFLNVIVHSA TGFKQSSNLY CTLEVDSFGY FVNKAKTRVY RDTAEPNWNE EFEIELEGSQ TLRILCYEKC YNKTKIPKED GESTDRLMGK GQVQLDPQAL QDRDWQRTVI AMNGIEVKLS VKFNSREFSL KRMPSRKQTG VFGVKIAVVT KRERSKVPYI VRQCVEEIER RGMEEVGIYR VSGVATDIQA LKAAFDVNNK DVSVMMSEMD VNAIAGTLKL YFRELPEPLF TDEFYPNFAE GIALSDPVAK ESCMLNLLLS LPEANLLTFL FLLDHLKRVA EKEAVNKMSL HNLATVFGPT LLRPSEKESK LPANPSQPIT MTDSWSLEVM SQVQVLLYFL QLEAIPAPDS KRQSILFSTE V // ID CBL_HUMAN Reviewed; 906 AA. AC P22681; A3KMP8; DT 01-AUG-1991, integrated into UniProtKB/Swiss-Prot. DT 07-JUL-2009, sequence version 2. DT 28-JAN-2026, entry version 262. DE RecName: Full=E3 ubiquitin-protein ligase CBL; DE EC=2.3.2.27 {ECO:0000269|PubMed:10514377, ECO:0000269|PubMed:14661060, ECO:0000269|PubMed:17509076, ECO:0000269|PubMed:40101708}; DE AltName: Full=Casitas B-lineage lymphoma proto-oncogene; DE AltName: Full=Proto-oncogene c-Cbl; DE AltName: Full=RING finger protein 55; DE AltName: Full=RING-type E3 ubiquitin transferase CBL {ECO:0000305}; DE AltName: Full=Signal transduction protein CBL; GN Name=CBL; Synonyms=CBL2, RNF55; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=2030914; RA Blake T.J., Shapiro M., Morse H.C. III, Langdon W.Y.; RT "The sequences of the human and mouse c-cbl proto-oncogenes show v-cbl was RT generated by a large truncation encompassing a proline-rich domain and a RT leucine zipper-like motif."; RL Oncogene 6:653-657(1991). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16554811; DOI=10.1038/nature04632; RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G., RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., RA Hattori M., Rogers J., Lander E.S., Sakaki Y.; RT "Human chromosome 11 DNA sequence and analysis including novel gene RT identification."; RL Nature 440:497-500(2006). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP INTERACTION WITH BLK. RX PubMed=8083187; DOI=10.1016/s0021-9258(17)31595-8; RA Donovan J.A., Wange R.L., Langdon W.Y., Samelson L.E.; RT "The protein product of the c-cbl protooncogene is the 120-kDa tyrosine- RT phosphorylated protein in Jurkat cells activated via the T cell antigen RT receptor."; RL J. Biol. Chem. 269:22921-22924(1994). RN [5] RP PHOSPHORYLATION BY EGFR, AND INTERACTION WITH EGFR. RX PubMed=7657591; DOI=10.1074/jbc.270.35.20242; RA Galisteo M.L., Dikic I., Batzer A.G., Langdon W.Y., Schlessinger J.; RT "Tyrosine phosphorylation of the c-cbl proto-oncogene protein product and RT association with epidermal growth factor (EGF) receptor upon EGF RT stimulation."; RL J. Biol. Chem. 270:20242-20245(1995). RN [6] RP INTERACTION WITH ZAP70. RX PubMed=9407100; DOI=10.1074/jbc.272.52.33140; RA Lupher M.L. Jr., Songyang Z., Shoelson S.E., Cantley L.C., Band H.; RT "The Cbl phosphotyrosine-binding domain selects a D(N/D)XpY motif and binds RT to the Tyr292 negative regulatory phosphorylation site of ZAP-70."; RL J. Biol. Chem. 272:33140-33144(1997). RN [7] RP PHOSPHORYLATION BY SYK AND FYN. RX PubMed=9535867; DOI=10.1074/jbc.273.15.8867; RA Deckert M., Elly C., Altman A., Liu Y.C.; RT "Coordinated regulation of the tyrosine phosphorylation of Cbl by Fyn and RT Syk tyrosine kinases."; RL J. Biol. Chem. 273:8867-8874(1998). RN [8] RP PHOSPHORYLATION BY HCK, AND INTERACTION WITH HCK. RX PubMed=10092522; DOI=10.1006/bbrc.1999.0427; RA Howlett C.J., Bisson S.A., Resek M.E., Tigley A.W., Robbins S.M.; RT "The proto-oncogene p120(Cbl) is a downstream substrate of the Hck protein- RT tyrosine kinase."; RL Biochem. Biophys. Res. Commun. 257:129-138(1999). RN [9] RP INTERACTION WITH SH2B2. RX PubMed=10374881; DOI=10.1038/sj.leu.2401397; RA Wakioka T., Sasaki A., Mitsui K., Yokouchi M., Inoue A., Komiya S., RA Yoshimura A.; RT "APS, an adaptor protein containing pleckstrin homology (PH) and Src RT homology-2 (SH2) domains inhibits the JAK-STAT pathway in collaboration RT with c-Cbl."; RL Leukemia 13:760-767(1999). RN [10] RP INTERACTION WITH SH2B2. RX PubMed=9989826; DOI=10.1038/sj.onc.1202326; RA Yokouchi M., Wakioka T., Sakamoto H., Yasukawa H., Ohtsuka S., Sasaki A., RA Ohtsubo M., Valius M., Inoue A., Komiya S., Yoshimura A.; RT "APS, an adaptor protein containing PH and SH2 domains, is associated with RT the PDGF receptor and c-Cbl and inhibits PDGF-induced mitogenesis."; RL Oncogene 18:759-767(1999). RN [11] RP INTERACTION WITH SLA AND ZAP70, AND MUTAGENESIS OF GLY-306. RX PubMed=10449770; DOI=10.1073/pnas.96.17.9775; RA Tang J., Sawasdikosol S., Chang J.-H., Burakoff S.J.; RT "SLAP, a dimeric adapter protein, plays a functional role in T cell RT receptor signaling."; RL Proc. Natl. Acad. Sci. U.S.A. 96:9775-9780(1999). RN [12] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=10514377; DOI=10.1126/science.286.5438.309; RA Joazeiro C.A., Wing S.S., Huang H.-K., Leverson J.D., Hunter T., Liu Y.-C.; RT "The tyrosine kinase negative regulator c-Cbl as a RING-type, E2-dependent RT ubiquitin-protein ligase."; RL Science 286:309-312(1999). RN [13] RP INTERACTION WITH CD2AP. RX PubMed=11067845; DOI=10.1074/jbc.m005784200; RA Kirsch K.H., Georgescu M.M., Shishido T., Langdon W.Y., Birge R.B., RA Hanafusa H.; RT "The adapter type protein CMS/CD2AP binds to the proto-oncogenic protein c- RT Cbl through a tyrosine phosphorylation-regulated Src homology 3 domain RT interaction."; RL J. Biol. Chem. 276:4957-4963(2001). RN [14] RP INTERACTION WITH SLA2. RX PubMed=11696592; DOI=10.1084/jem.194.9.1263; RA Holland S.J., Liao X.C., Mendenhall M.K., Zhou X., Pardo J., Chu P., RA Spencer C., Fu A.C., Sheng N., Yu P., Pali E., Nagin A., Shen M., Yu S., RA Chan E., Wu X., Li C., Woisetschlager M., Aversa G., Kolbinger F., RA Bennett M.K., Molineaux S., Luo Y., Payan D.G., Mancebo H.S.Y., Wu J.; RT "Functional cloning of Src-like adapter protein-2 (SLAP-2), a novel RT inhibitor of antigen receptor signaling."; RL J. Exp. Med. 194:1263-1276(2001). RN [15] RP INTERACTION WITH LAT2. RX PubMed=12486104; DOI=10.1084/jem.20021405; RA Brdicka T., Imrich M., Angelisova P., Brdickova N., Horvath O., Spicka J., RA Hilgert I., Luskova P., Draber P., Novak P., Engels N., Wienands J., RA Simeoni L., Oesterreicher J., Aguado E., Malissen M., Schraven B., RA Horejsi V.; RT "Non-T cell activation linker (NTAL): a transmembrane adaptor protein RT involved in immunoreceptor signaling."; RL J. Exp. Med. 196:1617-1626(2002). RN [16] RP INTERACTION WITH SH2B2, MUTAGENESIS OF TYR-371; TYR-700; TYR-731 AND RP TYR-774, AND PHOSPHORYLATION AT TYR-371; TYR-700 AND TYR-774. RX PubMed=11997497; DOI=10.1128/mcb.22.11.3599-3609.2002; RA Liu J., Kimura A., Baumann C.A., Saltiel A.R.; RT "APS facilitates c-Cbl tyrosine phosphorylation and GLUT4 translocation in RT response to insulin in 3T3-L1 adipocytes."; RL Mol. Cell. Biol. 22:3599-3609(2002). RN [17] RP FUNCTION, SUBCELLULAR LOCATION, UBIQUITINATION, MUTAGENESIS OF CYS-381, AND RP INTERACTION WITH HCK. RX PubMed=11896602; DOI=10.1038/sj.onc.1205228; RA Howlett C.J., Robbins S.M.; RT "Membrane-anchored Cbl suppresses Hck protein-tyrosine kinase mediated RT cellular transformation."; RL Oncogene 21:1707-1716(2002). RN [18] RP INTERACTION WITH CSF1R, AND PHOSPHORYLATION. RX PubMed=11850825; DOI=10.1038/sj.onc.1205166; RA Wilhelmsen K., Burkhalter S., van der Geer P.; RT "C-Cbl binds the CSF-1 receptor at tyrosine 973, a novel phosphorylation RT site in the receptor's carboxy-terminus."; RL Oncogene 21:1079-1089(2002). RN [19] RP INTERACTION WITH INPPL1. RX PubMed=12504111; DOI=10.1016/s0006-291x(02)02894-2; RA Vandenbroere I., Paternotte N., Dumont J.E., Erneux C., Pirson I.; RT "The c-Cbl-associated protein and c-Cbl are two new partners of the SH2- RT containing inositol polyphosphate 5-phosphatase SHIP2."; RL Biochem. Biophys. Res. Commun. 300:494-500(2003). RN [20] RP INTERACTION WITH FGR, AND PHOSPHORYLATION BY FGR. RX PubMed=12435267; DOI=10.1042/bj20021201; RA Melander F., Andersson T., Dib K.; RT "Fgr but not Syk tyrosine kinase is a target for beta 2 integrin-induced c- RT Cbl-mediated ubiquitination in adherent human neutrophils."; RL Biochem. J. 370:687-694(2003). RN [21] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=12522270; DOI=10.1073/pnas.2436191100; RA Salomon A.R., Ficarro S.B., Brill L.M., Brinker A., Phung Q.T., Ericson C., RA Sauer K., Brock A., Horn D.M., Schultz P.G., Peters E.C.; RT "Profiling of tyrosine phosphorylation pathways in human cells using mass RT spectrometry."; RL Proc. Natl. Acad. Sci. U.S.A. 100:443-448(2003). RN [22] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=15144186; DOI=10.1021/ac035352d; RA Brill L.M., Salomon A.R., Ficarro S.B., Mukherji M., Stettler-Gill M., RA Peters E.C.; RT "Robust phosphoproteomic profiling of tyrosine phosphorylation sites from RT human T cells using immobilized metal affinity chromatography and tandem RT mass spectrometry."; RL Anal. Chem. 76:2763-2772(2004). RN [23] RP REVIEW ON ROLE IN KIT SIGNALING AND KIT DEGRADATION. RX PubMed=15526160; DOI=10.1007/s00018-004-4189-6; RA Ronnstrand L.; RT "Signal transduction via the stem cell factor receptor/c-Kit."; RL Cell. Mol. Life Sci. 61:2535-2548(2004). RN [24] RP PHOSPHORYLATION AT TYR-700. RX PubMed=15556646; DOI=10.1016/j.febslet.2004.10.054; RA Grossmann A.H., Kolibaba K.S., Willis S.G., Corbin A.S., Langdon W.S., RA Deininger M.W., Druker B.J.; RT "Catalytic domains of tyrosine kinases determine the phosphorylation sites RT within c-Cbl."; RL FEBS Lett. 577:555-562(2004). RN [25] RP FUNCTION, PHOSPHORYLATION, AND INTERACTION WITH FGFR2; LYN AND FYN. RX PubMed=15190072; DOI=10.1074/jbc.m402469200; RA Kaabeche K., Lemonnier J., Le Mee S., Caverzasio J., Marie P.J.; RT "Cbl-mediated degradation of Lyn and Fyn induced by constitutive fibroblast RT growth factor receptor-2 activation supports osteoblast differentiation."; RL J. Biol. Chem. 279:36259-36267(2004). RN [26] RP FUNCTION, PHOSPHORYLATION AT TYR-731, AND MUTAGENESIS OF TYR-731. RX PubMed=14739300; DOI=10.1074/jbc.m311032200; RA Miyazaki T., Sanjay A., Neff L., Tanaka S., Horne W.C., Baron R.; RT "Src kinase activity is essential for osteoclast function."; RL J. Biol. Chem. 279:17660-17666(2004). RN [27] RP INTERACTION WITH ALK, AND PHOSPHORYLATION BY ALK. RX PubMed=15226403; DOI=10.1242/jcs.01183; RA Motegi A., Fujimoto J., Kotani M., Sakuraba H., Yamamoto T.; RT "ALK receptor tyrosine kinase promotes cell growth and neurite outgrowth."; RL J. Cell Sci. 117:3319-3329(2004). RN [28] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=14661060; DOI=10.1038/sj.onc.1207298; RA Kim M., Tezuka T., Tanaka K., Yamamoto T.; RT "Cbl-c suppresses v-Src-induced transformation through ubiquitin-dependent RT protein degradation."; RL Oncogene 23:1645-1655(2004). RN [29] RP REVIEW ON ROLE IN KIT SIGNALING AND KIT DEGRADATION. RX PubMed=16129412; DOI=10.1016/j.bbrc.2005.08.055; RA Roskoski R. Jr.; RT "Signaling by Kit protein-tyrosine kinase--the stem cell factor receptor."; RL Biochem. Biophys. Res. Commun. 337:1-13(2005). RN [30] RP INTERACTION WITH AXL. RX PubMed=15958209; DOI=10.1016/j.bbrc.2005.05.086; RA Valverde P.; RT "Effects of Gas6 and hydrogen peroxide in Axl ubiquitination and RT downregulation."; RL Biochem. Biophys. Res. Commun. 333:180-185(2005). RN [31] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=15592455; DOI=10.1038/nbt1046; RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., RA Zha X.-M., Polakiewicz R.D., Comb M.J.; RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells."; RL Nat. Biotechnol. 23:94-101(2005). RN [32] RP FUNCTION, AND MUTAGENESIS OF GLY-306. RX PubMed=17094949; DOI=10.1016/j.bbrc.2006.10.150; RA Lock P., I S.T.T., Straffon A.F., Schieb H., Hovens C.M., Stylli S.S.; RT "Spred-2 steady-state levels are regulated by phosphorylation and Cbl- RT mediated ubiquitination."; RL Biochem. Biophys. Res. Commun. 351:1018-1023(2006). RN [33] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-900, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=16964243; DOI=10.1038/nbt1240; RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.; RT "A probability-based approach for high-throughput protein phosphorylation RT analysis and site localization."; RL Nat. Biotechnol. 24:1285-1292(2006). RN [34] RP FUNCTION, CATALYTIC ACTIVITY, AND PHOSPHORYLATION. RX PubMed=17509076; DOI=10.1111/j.1742-4658.2007.05835.x; RA Bonaventure J., Horne W.C., Baron R.; RT "The localization of FGFR3 mutations causing thanatophoric dysplasia type I RT differentially affects phosphorylation, processing and ubiquitylation of RT the receptor."; RL FEBS J. 274:3078-3093(2007). RN [35] RP INTERACTION WITH PDGFRB. RX PubMed=17620338; DOI=10.1074/jbc.m701797200; RA Reddi A.L., Ying G., Duan L., Chen G., Dimri M., Douillard P., Druker B.J., RA Naramura M., Band V., Band H.; RT "Binding of Cbl to a phospholipase Cgamma1-docking site on platelet-derived RT growth factor receptor beta provides a dual mechanism of negative RT regulation."; RL J. Biol. Chem. 282:29336-29347(2007). RN [36] RP INTERACTION WITH LYN. RX PubMed=18235045; DOI=10.1182/blood-2007-08-109330; RA Wu J., Meng F., Lu H., Kong L., Bornmann W., Peng Z., Talpaz M., RA Donato N.J.; RT "Lyn regulates BCR-ABL and Gab2 tyrosine phosphorylation and c-Cbl protein RT stability in imatinib-resistant chronic myelogenous leukemia cells."; RL Blood 111:3821-3829(2008). RN [37] RP FUNCTION, INTERACTION WITH FGFR2, AND SUBCELLULAR LOCATION. RX PubMed=18374639; DOI=10.1016/j.bone.2008.02.009; RA Dufour C., Guenou H., Kaabeche K., Bouvard D., Sanjay A., Marie P.J.; RT "FGFR2-Cbl interaction in lipid rafts triggers attenuation of PI3K/Akt RT signaling and osteoblast survival."; RL Bone 42:1032-1039(2008). RN [38] RP FUNCTION, AND INTERACTION WITH SPRY2. RX PubMed=17974561; DOI=10.1074/jbc.m705457200; RA Chandramouli S., Yu C.Y., Yusoff P., Lao D.H., Leong H.F., Mizuno K., RA Guy G.R.; RT "Tesk1 interacts with Spry2 to abrogate its inhibition of ERK RT phosphorylation downstream of receptor tyrosine kinase signaling."; RL J. Biol. Chem. 283:1679-1691(2008). RN [39] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [40] RP INTERACTION WITH EPHB1, AND PHOSPHORYLATION. RX PubMed=18034775; DOI=10.1111/j.1600-0854.2007.00679.x; RA Fasen K., Cerretti D.P., Huynh-Do U.; RT "Ligand binding induces Cbl-dependent EphB1 receptor degradation through RT the lysosomal pathway."; RL Traffic 9:251-266(2008). RN [41] RP INTERACTION WITH TEK/TIE2, AND FUNCTION. RX PubMed=19689429; DOI=10.1042/bj20091010; RA Wehrle C., Van Slyke P., Dumont D.J.; RT "Angiopoietin-1-induced ubiquitylation of Tie2 by c-Cbl is required for RT internalization and degradation."; RL Biochem. J. 423:375-380(2009). RN [42] RP INTERACTION WITH EGFR. RX PubMed=19836242; DOI=10.1016/j.cub.2009.09.048; RA Tarcic G., Boguslavsky S.K., Wakim J., Kiuchi T., Liu A., Reinitz F., RA Nathanson D., Takahashi T., Mischel P.S., Ng T., Yarden Y.; RT "An unbiased screen identifies DEP-1 tumor suppressor as a phosphatase RT controlling EGFR endocytosis."; RL Curr. Biol. 19:1788-1798(2009). RN [43] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-452, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [44] RP INTERACTION WITH PDGFRB, AND PHOSPHORYLATION. RX PubMed=20494825; DOI=10.1016/j.cellsig.2010.05.004; RA Wardega P., Heldin C.H., Lennartsson J.; RT "Mutation of tyrosine residue 857 in the PDGF beta-receptor affects cell RT proliferation but not migration."; RL Cell. Signal. 22:1363-1368(2010). RN [45] RP REVIEW ON FUNCTION IN FGF SIGNALING, AND UBIQUITINATION OF FGFR1. RX PubMed=20094046; DOI=10.1038/nrc2780; RA Turner N., Grose R.; RT "Fibroblast growth factor signalling: from development to cancer."; RL Nat. Rev. Cancer 10:116-129(2010). RN [46] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [47] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [48] RP FUNCTION, AND INTERACTION WITH FGFR2. RX PubMed=21596750; DOI=10.1074/jbc.m110.197525; RA Severe N., Miraoui H., Marie P.J.; RT "The Casitas B lineage lymphoma (Cbl) mutant G306E enhances osteogenic RT differentiation in human mesenchymal stromal cells in part by decreased RT Cbl-mediated platelet-derived growth factor receptor alpha and fibroblast RT growth factor receptor 2 ubiquitination."; RL J. Biol. Chem. 286:24443-24450(2011). RN [49] RP INTERACTION WITH TNS4 AND EGFR, AND MUTAGENESIS OF TYR-674; TYR-700; RP TYR-731 AND TYR-774. RX PubMed=23774213; DOI=10.1158/0008-5472.can-12-4441; RA Hong S.Y., Shih Y.P., Li T., Carraway K.L. III, Lo S.H.; RT "CTEN prolongs signaling by EGFR through reducing its ligand-induced RT degradation."; RL Cancer Res. 73:5266-5276(2013). RN [50] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-439; SER-483 AND SER-669, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [51] RP INTERACTION WITH CD5. RX PubMed=23376399; DOI=10.1016/j.bbrc.2013.01.086; RA Roa N.S., Ordonez-Rueda D., Chavez-Rios J.R., Raman C., Garcia-Zepeda E.A., RA Lozano F., Soldevila G.; RT "The carboxy-terminal region of CD5 is required for c-CBL mediated TCR RT signaling downmodulation in thymocytes."; RL Biochem. Biophys. Res. Commun. 432:52-59(2013). RN [52] RP SUBCELLULAR LOCATION, INTERACTION WITH CD93, AND PHOSPHORYLATION AT RP TYR-774. RX PubMed=26848865; DOI=10.18632/oncotarget.7136; RA Galvagni F., Nardi F., Maida M., Bernardini G., Vannuccini S., RA Petraglia F., Santucci A., Orlandini M.; RT "CD93 and dystroglycan cooperation in human endothelial cell adhesion and RT migration adhesion and migration."; RL Oncotarget 7:10090-10103(2016). RN [53] RP FUNCTION, AND PATHWAY. RX PubMed=28381567; DOI=10.1128/jvi.00393-17; RA Deschamps T., Dogrammatzis C., Mullick R., Kalamvoki M.; RT "Cbl E3 Ligase Mediates the Removal of Nectin-1 from the Surface of Herpes RT Simplex Virus 1-Infected Cells."; RL J. Virol. 91:0-0(2017). RN [54] RP SUBUNIT, INTERACTION WITH IFT20 AND CBLB, UBIQUITINATION, AND SUBCELLULAR RP LOCATION. RX PubMed=29237719; DOI=10.1083/jcb.201611050; RA Schmid F.M., Schou K.B., Vilhelm M.J., Holm M.S., Breslin L., Farinelli P., RA Larsen L.A., Andersen J.S., Pedersen L.B., Christensen S.T.; RT "IFT20 modulates ciliary PDGFRalpha signaling by regulating the stability RT of Cbl E3 ubiquitin ligases."; RL J. Cell Biol. 217:151-161(2018). RN [55] RP INTERACTION WITH MYCOBACTERIUM TUBERCULOSIS LPQN (MICROBIAL INFECTION). RX PubMed=30118682; DOI=10.1016/j.molcel.2018.07.010; RA Penn B.H., Netter Z., Johnson J.R., Von Dollen J., Jang G.M., Johnson T., RA Ohol Y.M., Maher C., Bell S.L., Geiger K., Golovkine G., Du X., Choi A., RA Parry T., Mohapatra B.C., Storck M.D., Band H., Chen C., Jaeger S., RA Shales M., Portnoy D.A., Hernandez R., Coscoy L., Cox J.S., Krogan N.J.; RT "An Mtb-human protein-protein interaction map identifies a switch between RT host antiviral and antibacterial responses."; RL Mol. Cell 71:637-648(2018). RN [56] RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND SUBCELLULAR LOCATION. RX PubMed=40101708; DOI=10.1016/j.cell.2025.02.014; RA Jiang Y., Dai A., Huang Y., Li H., Cui J., Yang H., Si L., Jiao T., Ren Z., RA Zhang Z., Mou S., Zhu H., Guo W., Huang Q., Li Y., Xue M., Jiang J., RA Wang F., Li L., Zhong Q., Wang K., Liu B., Wang J., Fan G., Guo J., RA Chen L., Workman C.J., Shen Z., Kong Y., Vignali D.A.A., Xu C., Wang H.; RT "Ligand-induced ubiquitination unleashes LAG3 immune checkpoint function by RT hindering membrane sequestration of signaling motifs."; RL Cell 188:2354-2371(2025). RN [57] {ECO:0007744|PDB:1B47, ECO:0007744|PDB:2CBL} RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 47-350 IN COMPLEX WITH ZAP70 RP PEPTIDE AND CALCIUM IONS, CALCIUM-BINDING SITE, AND MUTAGENESIS OF SER-80; RP PRO-82; ASP-229; GLU-240; ARG-294 AND GLY-306. RX PubMed=10078535; DOI=10.1038/18050; RA Meng W., Sawasdikosol S., Burakoff S.J., Eck M.J.; RT "Structure of the amino-terminal domain of Cbl complexed to its binding RT site on ZAP-70 kinase."; RL Nature 398:84-90(1999). RN [58] RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 47-434 IN COMPLEX WITH ZAP70 AND RP UBE2L3. RX PubMed=10966114; DOI=10.1016/s0092-8674(00)00057-x; RA Zheng N., Wang P., Jeffrey P.D., Pavletich N.P.; RT "Structure of a c-Cbl-UbcH7 complex: RING domain function in ubiquitin- RT protein ligases."; RL Cell 102:533-539(2000). RN [59] RP VARIANTS NSLL PRO-367; GLU-382; TYR-390 AND GLN-420, AND CHARACTERIZATION RP OF VARIANTS NSLL TYR-390 AND GLN-420. RX PubMed=20619386; DOI=10.1016/j.ajhg.2010.06.015; RA Martinelli S., De Luca A., Stellacci E., Rossi C., Checquolo S., Lepri F., RA Caputo V., Silvano M., Buscherini F., Consoli F., Ferrara G., Digilio M.C., RA Cavaliere M.L., van Hagen J.M., Zampino G., van der Burgt I., Ferrero G.B., RA Mazzanti L., Screpanti I., Yntema H.G., Nillesen W.M., Savarirayan R., RA Zenker M., Dallapiccola B., Gelb B.D., Tartaglia M.; RT "Heterozygous germline mutations in the CBL tumor-suppressor gene cause a RT Noonan syndrome-like phenotype."; RL Am. J. Hum. Genet. 87:250-257(2010). RN [60] RP VARIANTS ARG-287; SER-LYS-365 INS; HIS-371 AND LEU-499, CHARACTERIZATION OF RP VARIANTS SER-LYS-365 INS AND HIS-371, AND PHOSPHORYLATION AT TYR-674; RP TYR-700 AND TYR-774. RX PubMed=20622007; DOI=10.1074/jbc.m110.106161; RA Fernandes M.S., Reddy M.M., Croteau N.J., Walz C., Weisbach H., Podar K., RA Band H., Carroll M., Reiter A., Larson R.A., Salgia R., Griffin J.D., RA Sattler M.; RT "Novel oncogenic mutations of CBL in human acute myeloid leukemia that RT activate growth and survival pathways depend on increased metabolism."; RL J. Biol. Chem. 285:32596-32605(2010). RN [61] RP CHARACTERIZATION OF VARIANTS NSLL GLU-382; TYR-390 AND GLN-420. RX PubMed=25178484; DOI=10.1002/humu.22682; RA Brand K., Kentsch H., Glashoff C., Rosenberger G.; RT "RASopathy-associated CBL germline mutations cause aberrant ubiquitylation RT and trafficking of EGFR."; RL Hum. Mutat. 35:1372-1381(2014). CC -!- FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator CC of many signaling pathways by mediating ubiquitination of cell surface CC receptors (PubMed:10514377, PubMed:11896602, PubMed:14661060, CC PubMed:14739300, PubMed:15190072, PubMed:17509076, PubMed:18374639, CC PubMed:19689429, PubMed:21596750, PubMed:28381567, PubMed:40101708). CC Accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, and CC then transfers it to substrates promoting their degradation by the CC proteasome (PubMed:10514377, PubMed:14661060, PubMed:14739300, CC PubMed:17094949, PubMed:17509076, PubMed:17974561). Recognizes CC activated receptor tyrosine kinases, including KIT, FLT1, FGFR1, FGFR2, CC PDGFRA, PDGFRB, CSF1R, EPHA8 and KDR and mediates their ubiquitination CC to terminate signaling (PubMed:15190072, PubMed:18374639, CC PubMed:21596750). Recognizes membrane-bound HCK, SRC and other kinases CC of the SRC family and mediates their ubiquitination and degradation CC (PubMed:11896602). Ubiquitinates EGFR and SPRY2 (PubMed:17094949, CC PubMed:17974561). Involved in LAG3-mediated inhibition of TCR CC signaling: following ligand-binding to LAG3, catalyzes 'Lys-63'-linked CC ubiquitination of LAG3, unleashing the LAG3 C-terminus from the CC membrane, and initiating a signaling that prevents TCR activation CC (PubMed:40101708). Ubiquitinates NECTIN1 following association between CC NECTIN1 and herpes simplex virus 1/HHV-1 envelope glycoprotein D, CC leading to NECTIN1 removal from cell surface (PubMed:28381567). CC Participates in signal transduction in hematopoietic cells. Plays an CC important role in the regulation of osteoblast differentiation and CC apoptosis (PubMed:15190072, PubMed:18374639). Essential for CC osteoclastic bone resorption (PubMed:14739300). The 'Tyr-731' CC phosphorylated form induces the activation and recruitment of CC phosphatidylinositol 3-kinase to the cell membrane in a signaling CC pathway that is critical for osteoclast function (PubMed:14739300). In CC association with CBLB, required for proper feedback inhibition of CC ciliary platelet-derived growth factor receptor-alpha (PDGFRA) CC signaling pathway via ubiquitination and internalization of PDGFRA (By CC similarity). {ECO:0000250|UniProtKB:P22682, CC ECO:0000269|PubMed:10514377, ECO:0000269|PubMed:11896602, CC ECO:0000269|PubMed:14661060, ECO:0000269|PubMed:14739300, CC ECO:0000269|PubMed:15190072, ECO:0000269|PubMed:17094949, CC ECO:0000269|PubMed:17509076, ECO:0000269|PubMed:17974561, CC ECO:0000269|PubMed:18374639, ECO:0000269|PubMed:19689429, CC ECO:0000269|PubMed:21596750, ECO:0000269|PubMed:28381567, CC ECO:0000269|PubMed:40101708}. CC -!- CATALYTIC ACTIVITY: CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L- CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.; CC EC=2.3.2.27; Evidence={ECO:0000269|PubMed:10514377, CC ECO:0000269|PubMed:14661060, ECO:0000269|PubMed:17509076, CC ECO:0000269|PubMed:40101708}; CC -!- PATHWAY: Protein modification; protein ubiquitination. CC {ECO:0000269|PubMed:10514377, ECO:0000269|PubMed:14661060, CC ECO:0000269|PubMed:17509076, ECO:0000269|PubMed:28381567, CC ECO:0000269|PubMed:40101708}. CC -!- SUBUNIT: Forms homodimers; IFT20 promotes the formation of stable CC homodimers (PubMed:29237719). Interacts (phosphorylated at Tyr-731) CC with PIK3R1. Associates with NCK via its SH3 domain. The phosphorylated CC C-terminus interacts with CD2AP via its second SH3 domain. Binds to CC UBE2L3. Interacts with adapters SLA, SLA2 and with the phosphorylated CC C-terminus of SH2B2. Interacts with EGFR, SYK and ZAP70 via the highly CC conserved Cbl-N region. Also interacts with SORBS1 and INPPL1/SHIP2. CC Interacts with phosphorylated LAT2 (By similarity). Interacts with CBLB CC (PubMed:29237719). Interacts with ALK, AXL, BLK, FGR and FGFR2. CC Interacts with CSF1R, EPHB1, FLT1, KDR, PDGFRA and PDGFRB; regulates CC receptor degradation through ubiquitination. Interacts with HCK and CC LYN. Interacts with ATX2 (By similarity). Interacts with TEK/TIE2 CC (tyrosine phosphorylated). Interacts with SH3KBP1 and this interaction CC is inhibited in the presence of SHKBP1 or ARAP1 (By similarity). CC Interacts with SIGLEC10 (By similarity). Interacts with IFT20 CC (PubMed:29237719). Interacts with SPRY2; the interaction inhibits CBL- CC mediated ubiquitination of EGFR (PubMed:17974561). Interacts CC (phosphorylated at Tyr-774) with tensin TNS4 (via SH2 domain); the CC interaction is enhanced in the presence of EGF and reduces interaction CC of CBL with EGFR (PubMed:23774213). Interacts with EGFR; the CC interaction is reduced in the presence of TNS4 (PubMed:23774213). CC Interacts with CD5 (PubMed:23376399). Interacts with CD93 CC (PubMed:26848865). {ECO:0000250|UniProtKB:P22682, CC ECO:0000269|PubMed:10078535, ECO:0000269|PubMed:10092522, CC ECO:0000269|PubMed:10374881, ECO:0000269|PubMed:10449770, CC ECO:0000269|PubMed:10966114, ECO:0000269|PubMed:11067845, CC ECO:0000269|PubMed:11696592, ECO:0000269|PubMed:11850825, CC ECO:0000269|PubMed:11896602, ECO:0000269|PubMed:11997497, CC ECO:0000269|PubMed:12435267, ECO:0000269|PubMed:12486104, CC ECO:0000269|PubMed:12504111, ECO:0000269|PubMed:15190072, CC ECO:0000269|PubMed:15226403, ECO:0000269|PubMed:15958209, CC ECO:0000269|PubMed:17620338, ECO:0000269|PubMed:17974561, CC ECO:0000269|PubMed:18034775, ECO:0000269|PubMed:18235045, CC ECO:0000269|PubMed:18374639, ECO:0000269|PubMed:19689429, CC ECO:0000269|PubMed:19836242, ECO:0000269|PubMed:20494825, CC ECO:0000269|PubMed:21596750, ECO:0000269|PubMed:23376399, CC ECO:0000269|PubMed:23774213, ECO:0000269|PubMed:26848865, CC ECO:0000269|PubMed:29237719, ECO:0000269|PubMed:7657591, CC ECO:0000269|PubMed:8083187, ECO:0000269|PubMed:9407100, CC ECO:0000269|PubMed:9989826}. CC -!- SUBUNIT: (Microbial infection) Interacts with M.tuberculosis LpqN, CC which influences the balance between intrinsic antibacterial and CC antiviral defense. {ECO:0000269|PubMed:30118682}. CC -!- INTERACTION: CC P22681; Q8IZP0-2: ABI1; NbExp=3; IntAct=EBI-518228, EBI-7358775; CC P22681; Q14155: ARHGEF7; NbExp=9; IntAct=EBI-518228, EBI-717515; CC P22681; P54253: ATXN1; NbExp=3; IntAct=EBI-518228, EBI-930964; CC P22681; Q9Y5K6: CD2AP; NbExp=7; IntAct=EBI-518228, EBI-298152; CC P22681; P46108: CRK; NbExp=13; IntAct=EBI-518228, EBI-886; CC P22681; P46109: CRKL; NbExp=9; IntAct=EBI-518228, EBI-910; CC P22681; P00533: EGFR; NbExp=26; IntAct=EBI-518228, EBI-297353; CC P22681; P55085: F2RL1; NbExp=3; IntAct=EBI-518228, EBI-4303189; CC P22681; P17948: FLT1; NbExp=2; IntAct=EBI-518228, EBI-1026718; CC P22681; P06241: FYN; NbExp=6; IntAct=EBI-518228, EBI-515315; CC P22681; P62993: GRB2; NbExp=20; IntAct=EBI-518228, EBI-401755; CC P22681; P08631-2: HCK; NbExp=2; IntAct=EBI-518228, EBI-9834454; CC P22681; P42858: HTT; NbExp=18; IntAct=EBI-518228, EBI-466029; CC P22681; Q15811: ITSN1; NbExp=12; IntAct=EBI-518228, EBI-602041; CC P22681; P06239: LCK; NbExp=4; IntAct=EBI-518228, EBI-1348; CC P22681; Q96JA1: LRIG1; NbExp=2; IntAct=EBI-518228, EBI-2865191; CC P22681; P07948: LYN; NbExp=2; IntAct=EBI-518228, EBI-79452; CC P22681; P45983: MAPK8; NbExp=2; IntAct=EBI-518228, EBI-286483; CC P22681; P08581: MET; NbExp=17; IntAct=EBI-518228, EBI-1039152; CC P22681; P16333: NCK1; NbExp=5; IntAct=EBI-518228, EBI-389883; CC P22681; P04629: NTRK1; NbExp=2; IntAct=EBI-518228, EBI-1028226; CC P22681; Q13196: p72syk; NbExp=2; IntAct=EBI-518228, EBI-8609796; CC P22681; P27986: PIK3R1; NbExp=16; IntAct=EBI-518228, EBI-79464; CC P22681; O00459: PIK3R2; NbExp=4; IntAct=EBI-518228, EBI-346930; CC P22681; Q92569: PIK3R3; NbExp=4; IntAct=EBI-518228, EBI-79893; CC P22681; P07949: RET; NbExp=8; IntAct=EBI-518228, EBI-2480756; CC P22681; P31947: SFN; NbExp=2; IntAct=EBI-518228, EBI-476295; CC P22681; O14492: SH2B2; NbExp=7; IntAct=EBI-518228, EBI-7507432; CC P22681; Q99962: SH3GL2; NbExp=2; IntAct=EBI-518228, EBI-77938; CC P22681; Q96B97: SH3KBP1; NbExp=29; IntAct=EBI-518228, EBI-346595; CC P22681; P29353: SHC1; NbExp=5; IntAct=EBI-518228, EBI-78835; CC P22681; O43597: SPRY2; NbExp=17; IntAct=EBI-518228, EBI-742487; CC P22681; Q9C004: SPRY4; NbExp=9; IntAct=EBI-518228, EBI-354861; CC P22681; P12931: SRC; NbExp=8; IntAct=EBI-518228, EBI-621482; CC P22681; P43405: SYK; NbExp=7; IntAct=EBI-518228, EBI-78302; CC P22681; P62837: UBE2D2; NbExp=4; IntAct=EBI-518228, EBI-347677; CC P22681; P31946: YWHAB; NbExp=5; IntAct=EBI-518228, EBI-359815; CC P22681; P62258: YWHAE; NbExp=6; IntAct=EBI-518228, EBI-356498; CC P22681; P61981: YWHAG; NbExp=5; IntAct=EBI-518228, EBI-359832; CC P22681; Q04917: YWHAH; NbExp=5; IntAct=EBI-518228, EBI-306940; CC P22681; P27348: YWHAQ; NbExp=7; IntAct=EBI-518228, EBI-359854; CC P22681; P63104: YWHAZ; NbExp=4; IntAct=EBI-518228, EBI-347088; CC P22681; P43403: ZAP70; NbExp=3; IntAct=EBI-518228, EBI-1211276; CC P22681; P39688: Fyn; Xeno; NbExp=3; IntAct=EBI-518228, EBI-524514; CC P22681; P62994: Grb2; Xeno; NbExp=5; IntAct=EBI-518228, EBI-401775; CC P22681; P06240: Lck; Xeno; NbExp=2; IntAct=EBI-518228, EBI-1401; CC P22681; F1SDV6: PLCG1; Xeno; NbExp=2; IntAct=EBI-518228, EBI-15628084; CC P22681; P08487: PLCG1; Xeno; NbExp=3; IntAct=EBI-518228, EBI-8013886; CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cell membrane CC {ECO:0000269|PubMed:40101708}. Cell projection, cilium CC {ECO:0000269|PubMed:29237719}. Golgi apparatus CC {ECO:0000269|PubMed:29237719}. Note=Colocalizes with FGFR2 in lipid CC rafts at the cell membrane. CC -!- DOMAIN: The RING-type zinc finger domain mediates binding to an E2 CC ubiquitin-conjugating enzyme. CC -!- DOMAIN: The N-terminus is composed of the phosphotyrosine binding (PTB) CC domain, a short linker region and the RING-type zinc finger. The PTB CC domain, which is also called TKB (tyrosine kinase binding) domain, is CC composed of three different subdomains: a four-helix bundle (4H), a CC calcium-binding EF hand and a divergent SH2 domain. CC -!- PTM: Phosphorylated on tyrosine residues by ALK, EGFR, SYK, FYN and CC ZAP70 (By similarity). Phosphorylated on tyrosine residues in response CC to FLT1 and KIT signaling. Phosphorylated on tyrosine residues by INSR CC and FGR. Phosphorylated on several tyrosine residues by constitutively CC activated FGFR3. Not phosphorylated at Tyr-731 by FGFR3. Phosphorylated CC on tyrosine residues by activated CSF1R, PDGFRA and PDGFRB. CC Phosphorylated on tyrosine residues by HCK. {ECO:0000250, CC ECO:0000269|PubMed:10092522, ECO:0000269|PubMed:11850825, CC ECO:0000269|PubMed:11997497, ECO:0000269|PubMed:12435267, CC ECO:0000269|PubMed:14739300, ECO:0000269|PubMed:15190072, CC ECO:0000269|PubMed:15226403, ECO:0000269|PubMed:15556646, CC ECO:0000269|PubMed:17509076, ECO:0000269|PubMed:18034775, CC ECO:0000269|PubMed:20494825, ECO:0000269|PubMed:20622007, CC ECO:0000269|PubMed:26848865, ECO:0000269|PubMed:7657591, CC ECO:0000269|PubMed:9535867}. CC -!- PTM: Ubiquitinated, leading to its degradation via the proteasome CC (PubMed:11896602, PubMed:20094046). Ubiquitination is negatively CC regulated by IFT20 (PubMed:29237719). {ECO:0000269|PubMed:11896602, CC ECO:0000269|PubMed:20094046, ECO:0000269|PubMed:29237719}. CC -!- DISEASE: Noonan syndrome-like disorder with or without juvenile CC myelomonocytic leukemia (NSLL) [MIM:613563]: A syndrome characterized CC by a phenotype reminiscent of Noonan syndrome. Clinical features are CC highly variable, including facial dysmorphism, short neck, CC developmental delay, hyperextensible joints and thorax abnormalities CC with widely spaced nipples. The facial features consist of triangular CC face with hypertelorism, large low-set ears, ptosis, and flat nasal CC bridge. Some patients manifest cardiac defects. Some have an increased CC risk for certain malignancies, particularly juvenile myelomonocytic CC leukemia. {ECO:0000269|PubMed:20619386, ECO:0000269|PubMed:25178484}. CC Note=The disease is caused by variants affecting the gene represented CC in this entry. CC -!- MISCELLANEOUS: This protein has one functional calcium-binding site. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/171/CBL"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X57110; CAA40393.1; -; mRNA. DR EMBL; AP002956; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC132733; AAI32734.1; -; mRNA. DR EMBL; BC136463; AAI36464.1; -; mRNA. DR CCDS; CCDS8418.1; -. DR PIR; A43817; A43817. DR RefSeq; NP_005179.2; NM_005188.3. DR PDB; 1B47; X-ray; 2.20 A; A/B/C=47-350. DR PDB; 1FBV; X-ray; 2.90 A; A=47-434. DR PDB; 1YVH; X-ray; 2.05 A; A=25-351. DR PDB; 2CBL; X-ray; 2.10 A; A=47-351. DR PDB; 2JUJ; NMR; -; A=851-906. DR PDB; 2K4D; NMR; -; A=358-437. DR PDB; 2OO9; X-ray; 2.10 A; A/B/C=856-895. DR PDB; 2Y1M; X-ray; 2.67 A; A/B/C/D/E/F=47-435. DR PDB; 2Y1N; X-ray; 2.00 A; A/C=47-435. DR PDB; 3BUM; X-ray; 2.00 A; B=25-351. DR PDB; 3BUN; X-ray; 2.00 A; B=25-351. DR PDB; 3BUO; X-ray; 2.60 A; B/D=25-351. DR PDB; 3BUW; X-ray; 1.45 A; B/D=25-351. DR PDB; 3BUX; X-ray; 1.35 A; B/D=25-351. DR PDB; 3OB1; X-ray; 2.20 A; B=25-351. DR PDB; 3OB2; X-ray; 2.10 A; B=25-351. DR PDB; 3PLF; X-ray; 1.92 A; B/D=25-351. DR PDB; 4A49; X-ray; 2.21 A; A=354-435. DR PDB; 4A4B; X-ray; 2.79 A; A=47-435. DR PDB; 4A4C; X-ray; 2.70 A; A=47-435. DR PDB; 4GPL; X-ray; 3.00 A; B=47-351. DR PDB; 5HKW; X-ray; 2.25 A; A/B/C=47-351. DR PDB; 5HKX; X-ray; 1.85 A; A=47-435. DR PDB; 5HKY; X-ray; 1.80 A; A=47-351. DR PDB; 5HKZ; X-ray; 1.80 A; A=47-351. DR PDB; 5HL0; X-ray; 2.20 A; A=47-351. DR PDB; 5J3X; X-ray; 2.82 A; A/B/C/D/E/F=47-435. DR PDB; 5O76; X-ray; 2.47 A; A/C=47-435. DR PDB; 6O02; X-ray; 2.95 A; A=47-353. DR PDB; 6O03; X-ray; 3.30 A; A/B=47-353. DR PDB; 6XAR; X-ray; 2.50 A; A/B=25-357. DR PDB; 7SIY; X-ray; 1.48 A; A=48-351. DR PDB; 9ERZ; X-ray; 2.02 A; A/C=47-355. DR PDBsum; 1B47; -. DR PDBsum; 1FBV; -. DR PDBsum; 1YVH; -. DR PDBsum; 2CBL; -. DR PDBsum; 2JUJ; -. DR PDBsum; 2K4D; -. DR PDBsum; 2OO9; -. DR PDBsum; 2Y1M; -. DR PDBsum; 2Y1N; -. DR PDBsum; 3BUM; -. DR PDBsum; 3BUN; -. DR PDBsum; 3BUO; -. DR PDBsum; 3BUW; -. DR PDBsum; 3BUX; -. DR PDBsum; 3OB1; -. DR PDBsum; 3OB2; -. DR PDBsum; 3PLF; -. DR PDBsum; 4A49; -. DR PDBsum; 4A4B; -. DR PDBsum; 4A4C; -. DR PDBsum; 4GPL; -. DR PDBsum; 5HKW; -. DR PDBsum; 5HKX; -. DR PDBsum; 5HKY; -. DR PDBsum; 5HKZ; -. DR PDBsum; 5HL0; -. DR PDBsum; 5J3X; -. DR PDBsum; 5O76; -. DR PDBsum; 6O02; -. DR PDBsum; 6O03; -. DR PDBsum; 6XAR; -. DR PDBsum; 7SIY; -. DR PDBsum; 9ERZ; -. DR AlphaFoldDB; P22681; -. DR BMRB; P22681; -. DR SMR; P22681; -. DR BioGRID; 107315; 517. DR CORUM; P22681; -. DR DIP; DIP-189N; -. DR FunCoup; P22681; 2642. DR IntAct; P22681; 135. DR MINT; P22681; -. DR STRING; 9606.ENSP00000264033; -. DR GlyCosmos; P22681; 7 sites, 2 glycans. DR GlyGen; P22681; 13 sites, 2 O-linked glycans (12 sites). DR iPTMnet; P22681; -. DR MetOSite; P22681; -. DR PhosphoSitePlus; P22681; -. DR BioMuta; CBL; -. DR DMDM; 251757253; -. DR CPTAC; CPTAC-1567; -. DR jPOST; P22681; -. DR MassIVE; P22681; -. DR PaxDb; 9606-ENSP00000264033; -. DR PeptideAtlas; P22681; -. DR ProteomicsDB; 54017; -. DR Pumba; P22681; -. DR Antibodypedia; 3815; 1158 antibodies from 49 providers. DR DNASU; 867; -. DR Ensembl; ENST00000264033.6; ENSP00000264033.3; ENSG00000110395.8. DR GeneID; 867; -. DR KEGG; hsa:867; -. DR MANE-Select; ENST00000264033.6; ENSP00000264033.3; NM_005188.4; NP_005179.2. DR UCSC; uc001pwe.5; human. DR AGR; HGNC:1541; -. DR CIViC; 867; 9 evidence items across 10 molecular profiles. DR ClinPGx; PA26115; -. DR CTD; 867; -. DR DisGeNET; 867; -. DR GeneCards; CBL; -. DR HGNC; HGNC:1541; CBL. DR HPA; ENSG00000110395; Low tissue specificity. DR MalaCards; CBL; -. DR MIM; 165360; gene. DR MIM; 613563; phenotype. DR OpenTargets; ENSG00000110395; -. DR Orphanet; 98850; Aggressive systemic mastocytosis. DR Orphanet; 86834; Juvenile myelomonocytic leukemia. DR Orphanet; 648; Noonan syndrome. DR Orphanet; 363972; Noonan syndrome-like disorder with juvenile myelomonocytic leukemia. DR VEuPathDB; HostDB:ENSG00000110395; -. DR eggNOG; KOG1785; Eukaryota. DR GeneTree; ENSGT00940000155772; -. DR HOGENOM; CLU_013535_3_0_1; -. DR InParanoid; P22681; -. DR OMA; GCMYEAM; -. DR OrthoDB; 7237699at2759; -. DR PAN-GO; P22681; 7 GO annotations based on evolutionary models. DR PhylomeDB; P22681; -. DR BRENDA; 2.3.2.27; 2681. DR PathwayCommons; P22681; -. DR Reactome; R-HSA-1059683; Interleukin-6 signaling. DR Reactome; R-HSA-1236382; Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants. DR Reactome; R-HSA-1295596; Spry regulation of FGF signaling. DR Reactome; R-HSA-1433559; Regulation of KIT signaling. DR Reactome; R-HSA-182971; EGFR downregulation. DR Reactome; R-HSA-2173789; TGF-beta receptor signaling activates SMADs. DR Reactome; R-HSA-5637810; Constitutive Signaling by EGFRvIII. DR Reactome; R-HSA-5654726; Negative regulation of FGFR1 signaling. DR Reactome; R-HSA-5654727; Negative regulation of FGFR2 signaling. DR Reactome; R-HSA-5654732; Negative regulation of FGFR3 signaling. DR Reactome; R-HSA-5654733; Negative regulation of FGFR4 signaling. DR Reactome; R-HSA-6807004; Negative regulation of MET activity. DR Reactome; R-HSA-8849469; PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1. DR Reactome; R-HSA-8856825; Cargo recognition for clathrin-mediated endocytosis. DR Reactome; R-HSA-8856828; Clathrin-mediated endocytosis. DR Reactome; R-HSA-8875360; InlB-mediated entry of Listeria monocytogenes into host cell. DR Reactome; R-HSA-912631; Regulation of signaling by CBL. DR Reactome; R-HSA-9680350; Signaling by CSF1 (M-CSF) in myeloid cells. DR Reactome; R-HSA-9706369; Negative regulation of FLT3. DR Reactome; R-HSA-9706377; FLT3 signaling by CBL mutants. DR SignaLink; P22681; -. DR SIGNOR; P22681; -. DR UniPathway; UPA00143; -. DR Agora; ENSG00000110395; Agora Nominated Target for Alzheimer's Disease. DR BioGRID-ORCS; 867; 32 hits in 1216 CRISPR screens. DR ChiTaRS; CBL; human. DR EvolutionaryTrace; P22681; -. DR GeneWiki; CBL_(gene); -. DR GenomeRNAi; 867; -. DR Pharos; P22681; Tbio. DR PRO; PR:P22681; -. DR Proteomes; UP000005640; Chromosome 11. DR RNAct; P22681; protein. DR Bgee; ENSG00000110395; Expressed in primordial germ cell in gonad and 187 other cell types or tissues. DR ExpressionAtlas; P22681; baseline and differential. DR GO; GO:0005929; C:cilium; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0016600; C:flotillin complex; ISS:BHF-UCL. DR GO; GO:0005925; C:focal adhesion; IEA:Ensembl. DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB. DR GO; GO:0030426; C:growth cone; IEA:Ensembl. DR GO; GO:0045121; C:membrane raft; IBA:GO_Central. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl. DR GO; GO:0005886; C:plasma membrane; IDA:HGNC-UCL. DR GO; GO:0097229; C:sperm end piece; IDA:HPA. DR GO; GO:0045296; F:cadherin binding; HDA:BHF-UCL. DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro. DR GO; GO:0046875; F:ephrin receptor binding; IPI:UniProtKB. DR GO; GO:0036312; F:phosphatidylinositol 3-kinase regulatory subunit binding; IEA:Ensembl. DR GO; GO:0001784; F:phosphotyrosine residue binding; IEA:InterPro. DR GO; GO:0030971; F:receptor tyrosine kinase binding; IBA:GO_Central. DR GO; GO:0017124; F:SH3 domain binding; IPI:BHF-UCL. DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:UniProtKB. DR GO; GO:0004842; F:ubiquitin-protein transferase activity; TAS:HGNC-UCL. DR GO; GO:0008270; F:zinc ion binding; IEA:UniProtKB-KW. DR GO; GO:0071456; P:cellular response to hypoxia; IEA:Ensembl. DR GO; GO:1990090; P:cellular response to nerve growth factor stimulus; IEA:Ensembl. DR GO; GO:0036120; P:cellular response to platelet-derived growth factor stimulus; IEA:Ensembl. DR GO; GO:0019221; P:cytokine-mediated signaling pathway; TAS:Reactome. DR GO; GO:0006974; P:DNA damage response; IEA:Ensembl. DR GO; GO:0008584; P:male gonad development; IEA:Ensembl. DR GO; GO:0043303; P:mast cell degranulation; IEA:Ensembl. DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB. DR GO; GO:0042059; P:negative regulation of epidermal growth factor receptor signaling pathway; IMP:UniProtKB. DR GO; GO:0050868; P:negative regulation of T cell activation; IDA:UniProtKB. DR GO; GO:0050860; P:negative regulation of T cell receptor signaling pathway; IDA:UniProtKB. DR GO; GO:0045742; P:positive regulation of epidermal growth factor receptor signaling pathway; TAS:Reactome. DR GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; IMP:BHF-UCL. DR GO; GO:0048260; P:positive regulation of receptor-mediated endocytosis; IMP:UniProtKB. DR GO; GO:0051865; P:protein autoubiquitination; IEA:Ensembl. DR GO; GO:0070534; P:protein K63-linked ubiquitination; IDA:UniProtKB. DR GO; GO:0006513; P:protein monoubiquitination; IEA:Ensembl. DR GO; GO:0050821; P:protein stabilization; IDA:UniProtKB. DR GO; GO:0016567; P:protein ubiquitination; IDA:UniProtKB. DR GO; GO:2000583; P:regulation of platelet-derived growth factor receptor-alpha signaling pathway; ISS:UniProtKB. DR GO; GO:0032487; P:regulation of Rap protein signal transduction; IEA:Ensembl. DR GO; GO:0014823; P:response to activity; IEA:Ensembl. DR GO; GO:0045471; P:response to ethanol; IEA:Ensembl. DR GO; GO:0010332; P:response to gamma radiation; IEA:Ensembl. DR GO; GO:0042594; P:response to starvation; IEA:Ensembl. DR GO; GO:0033574; P:response to testosterone; IEA:Ensembl. DR GO; GO:0007165; P:signal transduction; IBA:GO_Central. DR GO; GO:0046718; P:symbiont entry into host cell; TAS:Reactome. DR GO; GO:0070086; P:ubiquitin-dependent endocytosis; IEA:Ensembl. DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IMP:UniProtKB. DR CDD; cd16708; RING-HC_Cbl; 1. DR CDD; cd09920; SH2_Cbl-b_TKB; 1. DR CDD; cd14393; UBA_c-Cbl; 1. DR FunFam; 1.10.238.10:FF:000022; E3 ubiquitin-protein ligase CBL; 1. DR FunFam; 1.10.8.10:FF:000030; E3 ubiquitin-protein ligase CBL; 1. DR FunFam; 1.20.930.20:FF:000001; E3 ubiquitin-protein ligase CBL; 1. DR FunFam; 3.30.40.10:FF:000015; E3 ubiquitin-protein ligase CBL; 1. DR FunFam; 3.30.505.10:FF:000154; E3 ubiquitin-protein ligase CBL; 1. DR Gene3D; 1.20.930.20; Adaptor protein Cbl, N-terminal domain; 1. DR Gene3D; 1.10.8.10; DNA helicase RuvA subunit, C-terminal domain; 1. DR Gene3D; 1.10.238.10; EF-hand; 1. DR Gene3D; 3.30.505.10; SH2 domain; 1. DR Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 1. DR IDEAL; IID00300; -. DR InterPro; IPR024162; Adaptor_Cbl. DR InterPro; IPR014741; Adaptor_Cbl_EF_hand-like. DR InterPro; IPR036537; Adaptor_Cbl_N_dom_sf. DR InterPro; IPR003153; Adaptor_Cbl_N_hlx. DR InterPro; IPR014742; Adaptor_Cbl_SH2-like. DR InterPro; IPR024159; Cbl_PTB. DR InterPro; IPR011992; EF-hand-dom_pair. DR InterPro; IPR036860; SH2_dom_sf. DR InterPro; IPR015940; UBA. DR InterPro; IPR009060; UBA-like_sf. DR InterPro; IPR018957; Znf_C3HC4_RING-type. DR InterPro; IPR001841; Znf_RING. DR InterPro; IPR013083; Znf_RING/FYVE/PHD. DR InterPro; IPR017907; Znf_RING_CS. DR PANTHER; PTHR23007; CBL; 1. DR PANTHER; PTHR23007:SF5; E3 UBIQUITIN-PROTEIN LIGASE CBL; 1. DR Pfam; PF02262; Cbl_N; 1. DR Pfam; PF02761; Cbl_N2; 1. DR Pfam; PF02762; Cbl_N3; 1. DR Pfam; PF00627; UBA; 1. DR Pfam; PF00097; zf-C3HC4; 1. DR SMART; SM00184; RING; 1. DR SMART; SM00165; UBA; 1. DR SUPFAM; SSF47473; EF-hand; 1. DR SUPFAM; SSF47668; N-terminal domain of cbl (N-cbl); 1. DR SUPFAM; SSF57850; RING/U-box; 1. DR SUPFAM; SSF55550; SH2 domain; 1. DR SUPFAM; SSF46934; UBA-like; 1. DR PROSITE; PS51506; CBL_PTB; 1. DR PROSITE; PS50030; UBA; 1. DR PROSITE; PS00518; ZF_RING_1; 1. DR PROSITE; PS50089; ZF_RING_2; 1. PE 1: Evidence at protein level; KW 3D-structure; Calcium; Cell membrane; Cell projection; Cytoplasm; KW Disease variant; Golgi apparatus; Membrane; Metal-binding; Phosphoprotein; KW Proteomics identification; Proto-oncogene; Reference proteome; Repeat; KW Transferase; Ubl conjugation; Ubl conjugation pathway; Zinc; Zinc-finger. FT CHAIN 1..906 FT /note="E3 ubiquitin-protein ligase CBL" FT /id="PRO_0000055858" FT DOMAIN 47..351 FT /note="Cbl-PTB" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00839" FT DOMAIN 856..895 FT /note="UBA" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00212" FT ZN_FING 381..420 FT /note="RING-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175" FT REGION 1..357 FT /note="Sufficient for interaction with EPHB1" FT /evidence="ECO:0000269|PubMed:18034775" FT REGION 1..21 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 47..175 FT /note="4H" FT REGION 176..248 FT /note="EF-hand-like" FT REGION 249..351 FT /note="SH2-like" FT REGION 352..380 FT /note="Linker" FT REGION 358..906 FT /note="Required for ubiquitination of SPRED2" FT /evidence="ECO:0000269|PubMed:17094949" FT REGION 432..462 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 477..498 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 519..667 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 648..906 FT /note="Interaction with CD2AP" FT /evidence="ECO:0000269|PubMed:11067845" FT REGION 680..719 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 743..781 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 799..854 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 10..21 FT /note="Gly residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 533..550 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 639..653 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 765..774 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 838..854 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 229 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0007744|PDB:1B47, ECO:0007744|PDB:2CBL" FT BINDING 231 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0007744|PDB:1B47, ECO:0007744|PDB:2CBL" FT BINDING 233 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0007744|PDB:1B47, ECO:0007744|PDB:2CBL" FT BINDING 235 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0007744|PDB:1B47, ECO:0007744|PDB:2CBL" FT BINDING 240 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0007744|PDB:1B47, ECO:0007744|PDB:2CBL" FT BINDING 294 FT /ligand="4-O-phospho-L-tyrosine" FT /ligand_id="ChEBI:CHEBI:62338" FT /evidence="ECO:0000250" FT MOD_RES 371 FT /note="Phosphotyrosine; by INSR" FT /evidence="ECO:0000269|PubMed:11997497" FT MOD_RES 439 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 452 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19690332" FT MOD_RES 483 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 619 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P22682" FT MOD_RES 642 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P22682" FT MOD_RES 668 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P22682" FT MOD_RES 669 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 674 FT /note="Phosphotyrosine" FT /evidence="ECO:0000269|PubMed:20622007" FT MOD_RES 700 FT /note="Phosphotyrosine; by ABL1" FT /evidence="ECO:0000269|PubMed:11997497, FT ECO:0000269|PubMed:15556646, ECO:0000269|PubMed:20622007" FT MOD_RES 731 FT /note="Phosphotyrosine; by SRC" FT /evidence="ECO:0000269|PubMed:14739300" FT MOD_RES 774 FT /note="Phosphotyrosine" FT /evidence="ECO:0000269|PubMed:11997497, FT ECO:0000269|PubMed:20622007, ECO:0000269|PubMed:26848865" FT MOD_RES 900 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:16964243" FT VARIANT 287 FT /note="K -> R (found in patients with acute myeloid FT leukemia; uncertain significance)" FT /evidence="ECO:0000269|PubMed:20622007" FT /id="VAR_071040" FT VARIANT 365 FT /note="Q -> QSK (found in patients with acute myeloid FT leukemia; uncertain significance; loss of the ability to FT negatively regulate signaling pathways; promotes cell cycle FT progression; decreases apoptosis)" FT /id="VAR_071041" FT VARIANT 367 FT /note="Q -> P (in NSLL; dbSNP:rs267606704)" FT /evidence="ECO:0000269|PubMed:20619386" FT /id="VAR_064332" FT VARIANT 371 FT /note="Y -> H (found in patients with acute myeloid FT leukemia; uncertain significance; loss of the ability to FT negatively regulate signaling pathways; promotes cell cycle FT progression; decreases apoptosis; dbSNP:rs267606706)" FT /evidence="ECO:0000269|PubMed:20622007" FT /id="VAR_071042" FT VARIANT 382 FT /note="K -> E (in NSLL; dominant-negative; impairs CBL- FT mediated ubiquitination, internalization and degradation of FT the EGF receptor/EGFR; decreases the ability to negatively FT regulate EGFR signaling; dbSNP:rs267606705)" FT /evidence="ECO:0000269|PubMed:25178484" FT /id="VAR_064333" FT VARIANT 390 FT /note="D -> Y (in NSLL; dominant-negative; impairs CBL- FT mediated ubiquitination, internalization and degradation of FT the EGF receptor/EGFR; decreases the ability to negatively FT regulate EGFR signaling; dbSNP:rs267606707)" FT /evidence="ECO:0000269|PubMed:20619386, FT ECO:0000269|PubMed:25178484" FT /id="VAR_064334" FT VARIANT 420 FT /note="R -> Q (in NSLL; dominant-negative; impairs CBL- FT mediated ubiquitination, internalization and degradation of FT the EGF receptor/EGFR; decreases the ability to negatively FT regulate EGFR signaling; dbSNP:rs267606708)" FT /evidence="ECO:0000269|PubMed:20619386, FT ECO:0000269|PubMed:25178484" FT /id="VAR_064335" FT VARIANT 499 FT /note="R -> L (found in patients with acute myeloid FT leukemia; uncertain significance)" FT /evidence="ECO:0000269|PubMed:20622007" FT /id="VAR_071043" FT VARIANT 620 FT /note="L -> F (in dbSNP:rs2227988)" FT /id="VAR_057211" FT VARIANT 782 FT /note="P -> L (in dbSNP:rs2229073)" FT /id="VAR_057212" FT VARIANT 904 FT /note="V -> I (in dbSNP:rs17122769)" FT /id="VAR_057213" FT MUTAGEN 80 FT /note="S->D: Abolishes interaction with ZAP70." FT /evidence="ECO:0000269|PubMed:10078535" FT MUTAGEN 82 FT /note="P->A: Abolishes interaction with ZAP70." FT /evidence="ECO:0000269|PubMed:10078535" FT MUTAGEN 229 FT /note="D->Q: Abolishes interaction with ZAP70." FT /evidence="ECO:0000269|PubMed:10078535" FT MUTAGEN 240 FT /note="E->S: Abolishes interaction with ZAP70." FT /evidence="ECO:0000269|PubMed:10078535" FT MUTAGEN 294 FT /note="R->K: Abolishes interaction with ZAP70." FT /evidence="ECO:0000269|PubMed:10078535" FT MUTAGEN 306 FT /note="G->E: Abolishes interaction with ZAP70 and EPHB1, FT but does not affect interaction with SLA. Reduces FT ubiquitination and therefore proteasomal degradation of FT SPRED2." FT /evidence="ECO:0000269|PubMed:10078535, FT ECO:0000269|PubMed:10449770, ECO:0000269|PubMed:17094949" FT MUTAGEN 371 FT /note="Y->F: Strongly reduces tyrosine phosphorylation by FT INSR; when associated with F-700 and F-774." FT /evidence="ECO:0000269|PubMed:11997497" FT MUTAGEN 381 FT /note="C->A: Loss of ubiquitin ligase activity." FT /evidence="ECO:0000269|PubMed:11896602" FT MUTAGEN 674 FT /note="Y->F: Does not affect interaction with TNS4 FT following EGF stimulation." FT /evidence="ECO:0000269|PubMed:23774213" FT MUTAGEN 700 FT /note="Y->F: Does not affect interaction with TNS4 FT following EGF stimulation. Strongly reduces tyrosine FT phosphorylation by INSR; when associated with F-371 and F- FT 774." FT /evidence="ECO:0000269|PubMed:11997497, FT ECO:0000269|PubMed:23774213" FT MUTAGEN 731 FT /note="Y->F: No effect on tyrosine phosphorylation by INSR. FT Loss of phosphorylation by SRC. Inhibition of bone FT resorption. Abolishes interaction with PIK3R1. Does not FT affect interaction with TNS4 following EGF stimulation." FT /evidence="ECO:0000269|PubMed:11997497, FT ECO:0000269|PubMed:14739300, ECO:0000269|PubMed:23774213" FT MUTAGEN 774 FT /note="Y->F: Loss of interaction with TNS4 following EGF FT stimulation. Strongly reduces tyrosine phosphorylation by FT INSR; when associated with F-371 and F-700." FT /evidence="ECO:0000269|PubMed:11997497, FT ECO:0000269|PubMed:23774213" FT CONFLICT 15 FT /note="S -> T (in Ref. 1; CAA40393)" FT /evidence="ECO:0000305" FT HELIX 53..70 FT /evidence="ECO:0007829|PDB:3BUX" FT HELIX 73..75 FT /evidence="ECO:0007829|PDB:3BUX" FT STRAND 79..82 FT /evidence="ECO:0007829|PDB:7SIY" FT HELIX 84..101 FT /evidence="ECO:0007829|PDB:3BUX" FT TURN 102..104 FT /evidence="ECO:0007829|PDB:7SIY" FT HELIX 106..111 FT /evidence="ECO:0007829|PDB:3BUX" FT HELIX 113..136 FT /evidence="ECO:0007829|PDB:3BUX" FT HELIX 137..141 FT /evidence="ECO:0007829|PDB:3BUX" FT STRAND 142..144 FT /evidence="ECO:0007829|PDB:6XAR" FT HELIX 146..168 FT /evidence="ECO:0007829|PDB:3BUX" FT HELIX 170..172 FT /evidence="ECO:0007829|PDB:3BUX" FT HELIX 176..178 FT /evidence="ECO:0007829|PDB:3BUX" FT HELIX 184..194 FT /evidence="ECO:0007829|PDB:3BUX" FT STRAND 198..201 FT /evidence="ECO:0007829|PDB:3BUX" FT HELIX 202..212 FT /evidence="ECO:0007829|PDB:3BUX" FT HELIX 218..228 FT /evidence="ECO:0007829|PDB:3BUX" FT STRAND 233..237 FT /evidence="ECO:0007829|PDB:3BUX" FT HELIX 238..247 FT /evidence="ECO:0007829|PDB:3BUX" FT HELIX 251..253 FT /evidence="ECO:0007829|PDB:3BUX" FT HELIX 254..261 FT /evidence="ECO:0007829|PDB:3BUX" FT TURN 262..264 FT /evidence="ECO:0007829|PDB:2Y1M" FT STRAND 268..271 FT /evidence="ECO:0007829|PDB:5HKX" FT HELIX 274..281 FT /evidence="ECO:0007829|PDB:3BUX" FT HELIX 282..284 FT /evidence="ECO:0007829|PDB:3BUX" FT STRAND 290..295 FT /evidence="ECO:0007829|PDB:3BUX" FT STRAND 297..299 FT /evidence="ECO:0007829|PDB:3BUX" FT STRAND 302..308 FT /evidence="ECO:0007829|PDB:3BUX" FT TURN 310..312 FT /evidence="ECO:0007829|PDB:3BUO" FT STRAND 314..317 FT /evidence="ECO:0007829|PDB:3BUX" FT STRAND 320..322 FT /evidence="ECO:0007829|PDB:3BUW" FT HELIX 324..333 FT /evidence="ECO:0007829|PDB:3BUX" FT HELIX 350..352 FT /evidence="ECO:0007829|PDB:5HKX" FT STRAND 354..356 FT /evidence="ECO:0007829|PDB:1FBV" FT STRAND 360..362 FT /evidence="ECO:0007829|PDB:4A49" FT HELIX 365..378 FT /evidence="ECO:0007829|PDB:5HKX" FT TURN 382..384 FT /evidence="ECO:0007829|PDB:5HKX" FT STRAND 385..388 FT /evidence="ECO:0007829|PDB:5HKX" FT STRAND 391..394 FT /evidence="ECO:0007829|PDB:5HKX" FT STRAND 398..400 FT /evidence="ECO:0007829|PDB:2K4D" FT HELIX 402..410 FT /evidence="ECO:0007829|PDB:5HKX" FT TURN 417..419 FT /evidence="ECO:0007829|PDB:5HKX" FT STRAND 425..428 FT /evidence="ECO:0007829|PDB:5HKX" FT STRAND 430..432 FT /evidence="ECO:0007829|PDB:4A49" FT HELIX 856..866 FT /evidence="ECO:0007829|PDB:2OO9" FT HELIX 871..880 FT /evidence="ECO:0007829|PDB:2OO9" FT TURN 881..883 FT /evidence="ECO:0007829|PDB:2OO9" FT HELIX 885..895 FT /evidence="ECO:0007829|PDB:2OO9" SQ SEQUENCE 906 AA; 99633 MW; 1AA6BF67377322CA CRC64; MAGNVKKSSG AGGGSGSGGS GSGGLIGLMK DAFQPHHHHH HHLSPHPPGT VDKKMVEKCW KLMDKVVRLC QNPKLALKNS PPYILDLLPD TYQHLRTILS RYEGKMETLG ENEYFRVFME NLMKKTKQTI SLFKEGKERM YEENSQPRRN LTKLSLIFSH MLAELKGIFP SGLFQGDTFR ITKADAAEFW RKAFGEKTIV PWKSFRQALH EVHPISSGLE AMALKSTIDL TCNDYISVFE FDIFTRLFQP WSSLLRNWNS LAVTHPGYMA FLTYDEVKAR LQKFIHKPGS YIFRLSCTRL GQWAIGYVTA DGNILQTIPH NKPLFQALID GFREGFYLFP DGRNQNPDLT GLCEPTPQDH IKVTQEQYEL YCEMGSTFQL CKICAENDKD VKIEPCGHLM CTSCLTSWQE SEGQGCPFCR CEIKGTEPIV VDPFDPRGSG SLLRQGAEGA PSPNYDDDDD ERADDTLFMM KELAGAKVER PPSPFSMAPQ ASLPPVPPRL DLLPQRVCVP SSASALGTAS KAASGSLHKD KPLPVPPTLR DLPPPPPPDR PYSVGAESRP QRRPLPCTPG DCPSRDKLPP VPSSRLGDSW LPRPIPKVPV SAPSSSDPWT GRELTNRHSL PFSLPSQMEP RPDVPRLGST FSLDTSMSMN SSPLVGPECD HPKIKPSSSA NAIYSLAARP LPVPKLPPGE QCEGEEDTEY MTPSSRPLRP LDTSQSSRAC DCDQQIDSCT YEAMYNIQSQ APSITESSTF GEGNLAAAHA NTGPEESENE DDGYDVPKPP VPAVLARRTL SDISNASSSF GWLSLDGDPT TNVTEGSQVP ERPPKPFPRR INSERKAGSC QQGSGPAASA ATASPQLSSE IENLMSQGYS YQDIQKALVI AQNNIEMAKN ILREFVSISS PAHVAT // ID CEBPA_HUMAN Reviewed; 358 AA. AC P49715; A7LNP2; P78319; Q05CA4; DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot. DT 05-FEB-2008, sequence version 3. DT 28-JAN-2026, entry version 220. DE RecName: Full=CCAAT/enhancer-binding protein alpha {ECO:0000312|HGNC:HGNC:1833}; DE Short=C/EBP alpha {ECO:0000312|HGNC:HGNC:1833}; GN Name=CEBPA {ECO:0000312|HGNC:HGNC:1833}; GN Synonyms=CEBP {ECO:0000312|HGNC:HGNC:1833}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC TISSUE=Umbilical cord; RX PubMed=7575576; DOI=10.1006/bbrc.1995.2439; RA Antonson P., Xanthopoulos K.G.; RT "Molecular cloning, sequence, and expression patterns of the human gene RT encoding CCAAT/enhancer binding protein alpha (C/EBP alpha)."; RL Biochem. Biophys. Res. Commun. 215:106-113(1995). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Liver; RA Swart G.W.M., van Groningen J.J.M., van Ruissen F., Bergers M., RA Schalwijk J.; RT "Transcription factor C/EBP-alpha: novel sites of expression and cloning of RT the human gene."; RL Biol. Chem. Hoppe-Seyler 378:373-379(1997). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RG SeattleSNPs variation discovery resource; RL Submitted (JUL-2007) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15057824; DOI=10.1038/nature02399; RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A., RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., RA Rubin E.M., Lucas S.M.; RT "The DNA sequence and biology of human chromosome 19."; RL Nature 428:529-535(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-133. RC TISSUE=Pancreas; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP INTERACTION WITH HBV PROTEIN X (MICROBIAL INFECTION). RX PubMed=9915821; DOI=10.1074/jbc.274.5.2858; RA Choi B.H., Park G.T., Rho H.M.; RT "Interaction of hepatitis B viral X protein and CCAAT/enhancer-binding RT protein alpha synergistically activates the hepatitis B viral enhancer RT II/pregenomic promoter."; RL J. Biol. Chem. 274:2858-2865(1999). RN [7] RP INTERACTION WITH UBN1. RX PubMed=10725330; DOI=10.1083/jcb.148.6.1165; RA Aho S., Buisson M., Pajunen T., Ryoo Y.W., Giot J.-F., Gruffat H., RA Sergeant A., Uitto J.; RT "Ubinuclein, a novel nuclear protein interacting with cellular and viral RT transcription factors."; RL J. Cell Biol. 148:1165-1176(2000). RN [8] RP INVOLVEMENT IN AML. RX PubMed=12661007; DOI=10.1002/gcc.10185; RA Snaddon J., Smith M.L., Neat M., Cambal-Parrales M., Dixon-McIver A., RA Arch R., Amess J.A., Rohatiner A.Z., Lister T.A., Fitzgibbon J.; RT "Mutations of CEBPA in acute myeloid leukemia FAB types M1 and M2."; RL Genes Chromosomes Cancer 37:72-78(2003). RN [9] RP INTERACTION WITH CDK2; CDK4; E2F4; RB1 AND SMARCA2, AND PHOSPHORYLATION AT RP SER-190. RX PubMed=15107404; DOI=10.1101/gad.1183304; RA Wang G.L., Iakova P., Wilde M., Awad S., Timchenko N.A.; RT "Liver tumors escape negative control of proliferation via PI3K/Akt- RT mediated block of C/EBP alpha growth inhibitory activity."; RL Genes Dev. 18:912-925(2004). RN [10] RP INTERACTION WITH EPSTEIN-BARR VIRUS BZLF1 PROTEIN (MICROBIAL INFECTION). RX PubMed=15078966; DOI=10.1128/jvi.78.9.4847-4865.2004; RA Wu F.Y., Wang S.E., Chen H., Wang L., Hayward S.D., Hayward G.S.; RT "CCAAT/enhancer binding protein alpha binds to the Epstein-Barr virus (EBV) RT ZTA protein through oligomeric interactions and contributes to cooperative RT transcriptional activation of the ZTA promoter through direct binding to RT the ZII and ZIIIB motifs during induction of the EBV lytic cycle."; RL J. Virol. 78:4847-4865(2004). RN [11] RP FUNCTION (ISOFORMS 1 AND 3). RX PubMed=14660596; DOI=10.1074/jbc.m312709200; RA Muller C., Calkhoven C.F., Sha X., Leutz A.; RT "The CCAAT enhancer-binding protein alpha (C/EBPalpha) requires a SWI/SNF RT complex for proliferation arrest."; RL J. Biol. Chem. 279:7353-7358(2004). RN [12] RP INVOLVEMENT IN AML. RX PubMed=15575056; DOI=10.1056/nejmoa041331; RA Smith M.L., Cavenagh J.D., Lister T.A., Fitzgibbon J.; RT "Mutation of CEBPA in familial acute myeloid leukemia."; RL N. Engl. J. Med. 351:2403-2407(2004). RN [13] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-161, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., RA Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [14] RP INTERACTION WITH TRIB1. RX PubMed=20410507; DOI=10.1182/blood-2009-07-229450; RA Dedhia P.H., Keeshan K., Uljon S., Xu L., Vega M.E., Shestova O., RA Zaks-Zilberman M., Romany C., Blacklow S.C., Pear W.S.; RT "Differential ability of Tribbles family members to promote degradation of RT C/EBPalpha and induce acute myelogenous leukemia."; RL Blood 116:1321-1328(2010). RN [15] RP FUNCTION (ISOFORM 4), ALTERNATIVE INITIATION, IDENTIFICATION OF RP NON-CANONICAL INITIATION CODON, SUBCELLULAR LOCATION (ISOFORM 4), AND RP INTERACTION WITH NPM1; TAF1A AND UBTF. RX PubMed=20075868; DOI=10.1038/emboj.2009.404; RA Muller C., Bremer A., Schreiber S., Eichwald S., Calkhoven C.F.; RT "Nucleolar retention of a translational C/EBPalpha isoform stimulates rDNA RT transcription and cell size."; RL EMBO J. 29:897-909(2010). RN [16] RP INTERACTION WITH TFDP1; TFDP2 AND E2F1. RX PubMed=20176812; DOI=10.1128/mcb.01619-09; RA Zaragoza K., Begay V., Schuetz A., Heinemann U., Leutz A.; RT "Repression of transcriptional activity of C/EBPalpha by E2F-dimerization RT partner complexes."; RL Mol. Cell. Biol. 30:2293-2304(2010). RN [17] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-161, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25218447; DOI=10.1038/nsmb.2890; RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M., RA Vertegaal A.C.; RT "Uncovering global SUMOylation signaling networks in a site-specific RT manner."; RL Nat. Struct. Mol. Biol. 21:927-936(2014). RN [18] RP INTERACTION WITH TRIB1, DOMAIN, AND MUTAGENESIS OF ILE-55; GLU-57; HIS-58; RP GLU-59; SER-61; ILE-62; ASP-63; ILE-64; SER-65; TYR-67; ILE-68 AND ASP-69. RX PubMed=26455797; DOI=10.1016/j.str.2015.08.017; RA Murphy J.M., Nakatani Y., Jamieson S.A., Dai W., Lucet I.S., Mace P.D.; RT "Molecular mechanism of CCAAT-enhancer binding protein recruitment by the RT TRIB1 pseudokinase."; RL Structure 23:2111-2121(2015). RN [19] RP INTERACTION WITH SIX1. RX PubMed=27923061; DOI=10.1371/journal.pgen.1006474; RA Brunmeir R., Wu J., Peng X., Kim S.Y., Julien S.G., Zhang Q., Xie W., RA Xu F.; RT "Comparative Transcriptomic and Epigenomic Analyses Reveal New Regulators RT of Murine Brown Adipogenesis."; RL PLoS Genet. 12:E1006474-E1006474(2016). RN [20] RP UBIQUITINATION. RX PubMed=27041596; DOI=10.1016/j.str.2016.03.002; RA Uljon S., Xu X., Durzynska I., Stein S., Adelmant G., Marto J.A., RA Pear W.S., Blacklow S.C.; RT "Structural basis for substrate selectivity of the E3 ligase COP1."; RL Structure 24:687-696(2016). RN [21] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-161, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=28112733; DOI=10.1038/nsmb.3366; RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C., RA Nielsen M.L.; RT "Site-specific mapping of the human SUMO proteome reveals co-modification RT with phosphorylation."; RL Nat. Struct. Mol. Biol. 24:325-336(2017). RN [22] RP VARIANTS AML LEU-84 AND LYS-312 INS, CHARACTERIZATION OF VARIANTS AML RP LEU-84 AND LYS-312 INS, INVOLVEMENT IN AML, FUNCTION, SUBCELLULAR LOCATION, RP ALTERNATIVE TRANSLATIONAL INITIATION, AND DNA-BINDING. RX PubMed=11242107; DOI=10.1038/85820; RA Pabst T., Mueller B.U., Zhang P., Radomska H.S., Narravula S., RA Schnittger S., Behre G., Hiddemann W., Tenen D.G.; RT "Dominant-negative mutations of CEBPA, encoding CCAAT/enhancer binding RT protein-alpha (C/EBPalpha), in acute myeloid leukemia."; RL Nat. Genet. 27:263-270(2001). CC -!- FUNCTION: Transcription factor that coordinates proliferation arrest CC and the differentiation of myeloid progenitors, adipocytes, CC hepatocytes, and cells of the lung and the placenta. Binds directly to CC the consensus DNA sequence 5'-T[TG]NNGNAA[TG]-3' acting as an activator CC on distinct target genes (PubMed:11242107). During early embryogenesis, CC plays essential and redundant functions with CEBPB. Essential for the CC transition from common myeloid progenitors (CMP) to CC granulocyte/monocyte progenitors (GMP). Critical for the proper CC development of the liver and the lung (By similarity). Necessary for CC terminal adipocyte differentiation, is required for postnatal CC maintenance of systemic energy homeostasis and lipid storage (By CC similarity). To regulate these different processes at the proper moment CC and tissue, interplays with other transcription factors and modulators. CC Down-regulates the expression of genes that maintain cells in an CC undifferentiated and proliferative state through E2F1 repression, which CC is critical for its ability to induce adipocyte and granulocyte CC terminal differentiation. Reciprocally E2F1 blocks adipocyte CC differentiation by binding to specific promoters and repressing CEBPA CC binding to its target gene promoters. Proliferation arrest also depends CC on a functional binding to SWI/SNF complex (PubMed:14660596). In liver, CC regulates gluconeogenesis and lipogenesis through different mechanisms. CC To regulate gluconeogenesis, functionally cooperates with FOXO1 binding CC to IRE-controlled promoters and regulating the expression of target CC genes such as PCK1 or G6PC1. To modulate lipogenesis, interacts and CC transcriptionally synergizes with SREBF1 in promoter activation of CC specific lipogenic target genes such as ACAS2. In adipose tissue, seems CC to act as FOXO1 coactivator accessing to ADIPOQ promoter through FOXO1 CC binding sites (By similarity). {ECO:0000250|UniProtKB:P05554, CC ECO:0000250|UniProtKB:P53566, ECO:0000269|PubMed:11242107, CC ECO:0000269|PubMed:14660596}. CC -!- FUNCTION: [Isoform 3]: Can act as dominant-negative. Binds DNA and have CC transctivation activity, even if much less efficiently than isoform 2. CC Does not inhibit cell proliferation (PubMed:14660596). CC {ECO:0000250|UniProtKB:P05554, ECO:0000250|UniProtKB:P53566, CC ECO:0000269|PubMed:14660596}. CC -!- FUNCTION: [Isoform 4]: Directly and specifically enhances ribosomal DNA CC transcription interacting with RNA polymerase I-specific cofactors and CC inducing histone acetylation. {ECO:0000269|PubMed:20075868}. CC -!- SUBUNIT: Binds DNA as a homodimer and as a heterodimer. Can form stable CC heterodimers with CEBPB, CEBPD, CEBPE and CEBPG (By similarity). CC Interacts with PRDM16 (By similarity). Interacts with UBN1 CC (PubMed:10725330). Interacts with ZNF638; this interaction increases CC transcriptional activation (By similarity). Interacts with the complex CC TFDP2:E2F1; the interaction prevents CEBPA binding to target gene CC promoters and represses its transcriptional activity (PubMed:20176812). CC Interacts with RB1 (PubMed:15107404). Interacts (when phosphorylated at CC Ser-190) with CDK2, CDK4, E2F4 and SMARCA2 (PubMed:15107404). Interacts CC with SREBPF1 (By similarity). Interacts with FOXO1 (via the Fork-head CC domain); the interaction increases when FOXO1 is deacetylated (By CC similarity). Interacts with SIX1 (PubMed:27923061). Interacts (via CC recognition sequence) with TRIB1 (PubMed:20410507, PubMed:26455797). CC Interacts (via bZIP domain) with OVOL2 (via zinc-finger domains); the CC interaction inhibits the transcription factor activity of CEBPA and is CC required to repress adipogenesis (By similarity). CC {ECO:0000250|UniProtKB:P05554, ECO:0000250|UniProtKB:P53566, CC ECO:0000269|PubMed:10725330, ECO:0000269|PubMed:15107404, CC ECO:0000269|PubMed:20075868, ECO:0000269|PubMed:20176812, CC ECO:0000269|PubMed:20410507, ECO:0000269|PubMed:26455797, CC ECO:0000269|PubMed:27923061}. CC -!- SUBUNIT: [Isoform 1]: Interacts with TAF1A and UBTF. CC {ECO:0000269|PubMed:20075868}. CC -!- SUBUNIT: [Isoform 4]: Interacts with TAF1A and UBTF (PubMed:20075868). CC Interacts with NPM1 (PubMed:20075868). {ECO:0000269|PubMed:20075868}. CC -!- SUBUNIT: (Microbial infection) Interacts with HBV protein X. CC {ECO:0000269|PubMed:9915821}. CC -!- SUBUNIT: (Microbial infection) Interacts with Epstein-Barr virus lytic CC switch protein BZLF1; this interaction induces G1 cell cycle arrest. CC {ECO:0000269|PubMed:15078966}. CC -!- INTERACTION: CC P49715; P18847: ATF3; NbExp=2; IntAct=EBI-1172054, EBI-712767; CC P49715; P18848: ATF4; NbExp=4; IntAct=EBI-1172054, EBI-492498; CC P49715; Q9Y2D1: ATF5; NbExp=2; IntAct=EBI-1172054, EBI-492509; CC P49715; Q16520: BATF; NbExp=3; IntAct=EBI-1172054, EBI-749503; CC P49715; Q8N1L9: BATF2; NbExp=2; IntAct=EBI-1172054, EBI-742695; CC P49715; Q9NR55: BATF3; NbExp=2; IntAct=EBI-1172054, EBI-10312707; CC P49715; P47902: CDX1; NbExp=3; IntAct=EBI-1172054, EBI-8514176; CC P49715; P49715: CEBPA; NbExp=2; IntAct=EBI-1172054, EBI-1172054; CC P49715; P17676: CEBPB; NbExp=2; IntAct=EBI-1172054, EBI-969696; CC P49715; P49716: CEBPD; NbExp=2; IntAct=EBI-1172054, EBI-7962058; CC P49715; Q15744: CEBPE; NbExp=2; IntAct=EBI-1172054, EBI-3907048; CC P49715; P53567: CEBPG; NbExp=4; IntAct=EBI-1172054, EBI-740209; CC P49715; P35638: DDIT3; NbExp=5; IntAct=EBI-1172054, EBI-742651; CC P49715; P01100: FOS; NbExp=2; IntAct=EBI-1172054, EBI-852851; CC P49715; P24001-2: IL32; NbExp=7; IntAct=EBI-1172054, EBI-8800907; CC P49715; P09874: PARP1; NbExp=2; IntAct=EBI-1172054, EBI-355676; CC P49715; P03122: E2; Xeno; NbExp=2; IntAct=EBI-1172054, EBI-7028618; CC P49715; P06422: E2; Xeno; NbExp=4; IntAct=EBI-1172054, EBI-7136851; CC P49715-1; Q96RU8-1: TRIB1; NbExp=2; IntAct=EBI-16180754, EBI-16180744; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11242107}. CC -!- SUBCELLULAR LOCATION: [Isoform 4]: Nucleus, nucleolus CC {ECO:0000269|PubMed:20075868}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative initiation; Named isoforms=4; CC Name=1; CC IsoId=P49715-1; Sequence=Displayed; CC Name=2; Synonyms=C/EBPalpha-p42 {ECO:0000303|PubMed:11242107}; CC IsoId=P49715-2; Sequence=VSP_057548; CC Name=3; Synonyms=C/EBPalpha-p30 {ECO:0000303|PubMed:11242107}; CC IsoId=P49715-3; Sequence=VSP_057547; CC Name=4; Synonyms=extended-C/EBPalpha {ECO:0000303|PubMed:20075868}; CC IsoId=P49715-4; Sequence=VSP_057607; CC -!- DOMAIN: The recognition sequence (54-72) is required for interaction CC with TRIB1. {ECO:0000269|PubMed:26455797}. CC -!- PTM: Phosphorylation at Ser-190 is required for interaction with CDK2, CC CDK4 and SWI/SNF complex leading to cell cycle inhibition. CC Dephosphorylated at Ser-190 by protein phosphatase 2A (PP2A) through CC PI3K/AKT signaling pathway regulation (PubMed:15107404). CC Phosphorylation at Thr-226 and Thr-230 by GSK3 is constitutive in CC adipose tissue and lung. In liver, both Thr-226 and Thr-230 are CC phosphorylated only during feeding but not during fasting. CC Phosphorylation of the GSK3 consensus sites selectively decreases CC transactivation activity on IRE-controlled promoters. CC {ECO:0000250|UniProtKB:P53566}. CC -!- PTM: Sumoylated, sumoylation blocks the inhibitory effect on cell CC proliferation by disrupting the interaction with SMARCA2. CC {ECO:0000250|UniProtKB:P05554}. CC -!- PTM: Ubiquitinated by COP1 upon interaction with TRIB1. CC {ECO:0000303|PubMed:27041596}. CC -!- DISEASE: Leukemia, acute myelogenous (AML) [MIM:601626]: A subtype of CC acute leukemia, a cancer of the white blood cells. AML is a malignant CC disease of bone marrow characterized by maturational arrest of CC hematopoietic precursors at an early stage of development. Clonal CC expansion of myeloid blasts occurs in bone marrow, blood, and other CC tissue. Myelogenous leukemias develop from changes in cells that CC normally produce neutrophils, basophils, eosinophils and monocytes. CC {ECO:0000269|PubMed:11242107, ECO:0000269|PubMed:12661007, CC ECO:0000269|PubMed:15575056}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the bZIP family. C/EBP subfamily. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/40050/CEBPA"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U34070; AAC50235.1; -; Genomic_DNA. DR EMBL; Y11525; CAA72289.1; -; mRNA. DR EMBL; EU048234; ABS82765.1; -; Genomic_DNA. DR EMBL; AC008738; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC027902; AAH27902.1; -; mRNA. DR CCDS; CCDS54243.1; -. [P49715-1] DR PIR; JC4311; JC4311. DR RefSeq; NP_001272758.1; NM_001285829.2. [P49715-3] DR RefSeq; NP_001274353.1; NM_001287424.2. [P49715-4] DR RefSeq; NP_001274364.1; NM_001287435.2. [P49715-2] DR RefSeq; NP_004355.2; NM_004364.4. [P49715-1] DR PDB; 6DC0; X-ray; 2.80 A; A/B=51-75. DR PDB; 8K8C; X-ray; 2.06 A; A/B=281-340. DR PDBsum; 6DC0; -. DR PDBsum; 8K8C; -. DR AlphaFoldDB; P49715; -. DR SMR; P49715; -. DR BioGRID; 107479; 1174. DR ComplexPortal; CPX-509; bZIP transcription factor complex, CEBPA-CEBPB. DR ComplexPortal; CPX-6469; bZIP transcription factor complex, ATF3-CEBPA. DR ComplexPortal; CPX-6525; bZIP transcription factor complex, ATF4-CEBPA. DR ComplexPortal; CPX-6586; bZIP transcription factor complex, ATF5-CEBPA. DR ComplexPortal; CPX-69; bZIP transcription factor complex, CEBPA-DDIT3. DR ComplexPortal; CPX-7006; bZIP transcription factor complex, BATF-CEBPA. DR ComplexPortal; CPX-7065; bZIP transcription factor complex, BATF2-CEBPA. DR ComplexPortal; CPX-7095; bZIP transcription factor complex, BATF3-CEBPA. DR ComplexPortal; CPX-71; bZIP transcription factor complex, CEBPA-CEBPA. DR CORUM; P49715; -. DR DIP; DIP-37882N; -. DR ELM; P49715; -. DR FunCoup; P49715; 2543. DR IntAct; P49715; 36. DR MINT; P49715; -. DR STRING; 9606.ENSP00000427514; -. DR GlyGen; P49715; 3 sites. DR iPTMnet; P49715; -. DR PhosphoSitePlus; P49715; -. DR BioMuta; CEBPA; -. DR DMDM; 166898082; -. DR jPOST; P49715; -. DR MassIVE; P49715; -. DR PaxDb; 9606-ENSP00000427514; -. DR PeptideAtlas; P49715; -. DR ProteomicsDB; 56054; -. DR Antibodypedia; 38083; 714 antibodies from 42 providers. DR DNASU; 1050; -. DR Ensembl; ENST00000498907.3; ENSP00000427514.1; ENSG00000245848.3. [P49715-1] DR GeneID; 1050; -. DR KEGG; hsa:1050; -. DR MANE-Select; ENST00000498907.3; ENSP00000427514.1; NM_004364.5; NP_004355.2. DR UCSC; uc002nun.4; human. [P49715-1] DR AGR; HGNC:1833; -. DR CIViC; 1050; 1 clinical assertion and 15 evidence items across 4 molecular profiles. DR ClinPGx; PA26376; -. DR CTD; 1050; -. DR DisGeNET; 1050; -. DR GeneCards; CEBPA; -. DR GeneReviews; CEBPA; -. DR HGNC; HGNC:1833; CEBPA. DR HPA; ENSG00000245848; Group enriched (adipose tissue, breast, liver, skin). DR MalaCards; CEBPA; -. DR MIM; 116897; gene. DR MIM; 601626; phenotype. DR OpenTargets; ENSG00000245848; -. DR Orphanet; 319480; Acute myeloid leukemia with CEBPA somatic mutations. DR Orphanet; 102724; Acute myeloid leukemia with t(8;21)(q22;q22) translocation. DR Orphanet; 319465; Inherited acute myeloid leukemia. DR VEuPathDB; HostDB:ENSG00000245848; -. DR eggNOG; KOG3119; Eukaryota. DR GeneTree; ENSGT00940000162646; -. DR HOGENOM; CLU_043327_2_0_1; -. DR InParanoid; P49715; -. DR OMA; QMPHLQY; -. DR OrthoDB; 10032067at2759; -. DR PAN-GO; P49715; 4 GO annotations based on evolutionary models. DR PhylomeDB; P49715; -. DR PathwayCommons; P49715; -. DR Reactome; R-HSA-381340; Transcriptional regulation of white adipocyte differentiation. DR Reactome; R-HSA-9616222; Transcriptional regulation of granulopoiesis. DR Reactome; R-HSA-9841922; MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis. DR SignaLink; P49715; -. DR SIGNOR; P49715; -. DR Agora; ENSG00000245848; -. DR BioGRID-ORCS; 1050; 82 hits in 1196 CRISPR screens. DR CD-CODE; 91857CE7; Nucleolus. DR ChiTaRS; CEBPA; human. DR GeneWiki; CEBPA; -. DR GenomeRNAi; 1050; -. DR Pharos; P49715; Tbio. DR PRO; PR:P49715; -. DR Proteomes; UP000005640; Chromosome 19. DR RNAct; P49715; protein. DR Bgee; ENSG00000245848; Expressed in nipple and 187 other cell types or tissues. DR GO; GO:1990647; C:C/EBP complex; IPI:ComplexPortal. DR GO; GO:0036488; C:CHOP-C/EBP complex; IPI:ComplexPortal. DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB. DR GO; GO:0016363; C:nuclear matrix; IEA:Ensembl. DR GO; GO:0005730; C:nucleolus; IDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0035189; C:Rb-E2F complex; IEA:Ensembl. DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; IMP:BHF-UCL. DR GO; GO:0005667; C:transcription regulator complex; IDA:ARUK-UCL. DR GO; GO:0031490; F:chromatin DNA binding; IEA:Ensembl. DR GO; GO:0003677; F:DNA binding; TAS:ProtInc. DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IMP:BHF-UCL. DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:UniProtKB. DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB. DR GO; GO:0042826; F:histone deacetylase binding; IEA:Ensembl. DR GO; GO:0071837; F:HMG box domain binding; IEA:Ensembl. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0019900; F:kinase binding; IPI:UniProtKB. DR GO; GO:0046982; F:protein heterodimerization activity; IEA:Ensembl. DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB. DR GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl. DR GO; GO:0001163; F:RNA polymerase I transcription regulatory region sequence-specific DNA binding; IDA:UniProtKB. DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central. DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:ARUK-UCL. DR GO; GO:0097677; F:STAT family protein binding; IPI:UniProtKB. DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:UniProtKB. DR GO; GO:0006953; P:acute-phase response; IEA:Ensembl. DR GO; GO:0031100; P:animal organ regeneration; IEA:Ensembl. DR GO; GO:0050873; P:brown fat cell differentiation; IEA:Ensembl. DR GO; GO:0071285; P:cellular response to lithium ion; IEA:Ensembl. DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IEA:Ensembl. DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; IEA:Ensembl. DR GO; GO:0008203; P:cholesterol metabolic process; IEA:Ensembl. DR GO; GO:0019221; P:cytokine-mediated signaling pathway; NAS:UniProtKB. DR GO; GO:0006351; P:DNA-templated transcription; IEA:InterPro. DR GO; GO:0001892; P:embryonic placenta development; IEA:Ensembl. DR GO; GO:0097009; P:energy homeostasis; IEA:Ensembl. DR GO; GO:0002070; P:epithelial cell maturation; IEA:Ensembl. DR GO; GO:0045444; P:fat cell differentiation; ISS:UniProtKB. DR GO; GO:0006091; P:generation of precursor metabolites and energy; TAS:ProtInc. DR GO; GO:0042593; P:glucose homeostasis; ISS:UniProtKB. DR GO; GO:0030851; P:granulocyte differentiation; ISS:UniProtKB. DR GO; GO:0071425; P:hematopoietic stem cell proliferation; IEA:Ensembl. DR GO; GO:0048839; P:inner ear development; IEA:Ensembl. DR GO; GO:0140467; P:integrated stress response signaling; NAS:ComplexPortal. DR GO; GO:0070102; P:interleukin-6-mediated signaling pathway; IDA:ARUK-UCL. DR GO; GO:0055088; P:lipid homeostasis; ISS:UniProtKB. DR GO; GO:0001889; P:liver development; ISS:UniProtKB. DR GO; GO:0030324; P:lung development; ISS:UniProtKB. DR GO; GO:0030225; P:macrophage differentiation; IEA:Ensembl. DR GO; GO:0007613; P:memory; IEA:Ensembl. DR GO; GO:0007005; P:mitochondrion organization; IEA:Ensembl. DR GO; GO:0030099; P:myeloid cell differentiation; IBA:GO_Central. DR GO; GO:0045786; P:negative regulation of cell cycle; IEA:Ensembl. DR GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:UniProtKB. DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; ISS:UniProtKB. DR GO; GO:1902034; P:negative regulation of hematopoietic stem cell proliferation; IEA:Ensembl. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:ComplexPortal. DR GO; GO:0007219; P:Notch signaling pathway; IEA:Ensembl. DR GO; GO:0002076; P:osteoblast development; IEA:Ensembl. DR GO; GO:2000144; P:positive regulation of DNA-templated transcription initiation; IDA:UniProtKB. DR GO; GO:0045600; P:positive regulation of fat cell differentiation; IEA:Ensembl. DR GO; GO:0010628; P:positive regulation of gene expression; IEA:Ensembl. DR GO; GO:0050729; P:positive regulation of inflammatory response; ISS:ARUK-UCL. DR GO; GO:0043032; P:positive regulation of macrophage activation; ISS:ARUK-UCL. DR GO; GO:0045669; P:positive regulation of osteoblast differentiation; IEA:Ensembl. DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; TAS:ParkinsonsUK-UCL. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB. DR GO; GO:0051726; P:regulation of cell cycle; TAS:ParkinsonsUK-UCL. DR GO; GO:0006355; P:regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central. DR GO; GO:0071548; P:response to dexamethasone; IEA:Ensembl. DR GO; GO:0080184; P:response to phenylpropanoid; IEA:Ensembl. DR GO; GO:0033274; P:response to vitamin B2; IEA:Ensembl. DR GO; GO:0006360; P:transcription by RNA polymerase I; IDA:UniProtKB. DR GO; GO:0000050; P:urea cycle; IEA:Ensembl. DR GO; GO:0050872; P:white fat cell differentiation; IEA:Ensembl. DR GO; GO:0070343; P:white fat cell proliferation; ISS:UniProt. DR CDD; cd14711; bZIP_CEBPA; 1. DR FunFam; 1.20.5.170:FF:000028; CCAAT/enhancer-binding protein beta; 1. DR Gene3D; 1.20.5.170; -; 1. DR InterPro; IPR004827; bZIP. DR InterPro; IPR046347; bZIP_sf. DR InterPro; IPR031106; C/EBP. DR InterPro; IPR016468; C/EBP_chordates. DR PANTHER; PTHR23334; CCAAT/ENHANCER BINDING PROTEIN; 1. DR PANTHER; PTHR23334:SF5; CCAAT_ENHANCER-BINDING PROTEIN ALPHA; 1. DR Pfam; PF07716; bZIP_2; 1. DR PIRSF; PIRSF005879; CCAAT/enhancer-binding; 1. DR SMART; SM00338; BRLZ; 1. DR SUPFAM; SSF57959; Leucine zipper domain; 1. DR PROSITE; PS50217; BZIP; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Activator; Alternative initiation; KW Developmental protein; Disease variant; DNA-binding; KW Host-virus interaction; Isopeptide bond; Nucleus; Phosphoprotein; KW Proteomics identification; Reference proteome; Transcription; KW Transcription regulation; Ubl conjugation. FT CHAIN 1..358 FT /note="CCAAT/enhancer-binding protein alpha" FT /id="PRO_0000076613" FT DOMAIN 282..345 FT /note="bZIP" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978" FT DNA_BIND 285..300 FT /evidence="ECO:0000250|UniProtKB:P05554" FT REGION 1..70 FT /note="Required to repress E2F1:TFDP1-mediated FT transcription, to inhibit cell cycle and to induce FT adipocyte differentiation" FT /evidence="ECO:0000250|UniProtKB:P05554" FT REGION 1..55 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 54..72 FT /note="Required for interaction with TRIB1" FT /evidence="ECO:0000269|PubMed:26455797" FT REGION 128..204 FT /note="Required to induce adipocyte differentiation" FT /evidence="ECO:0000250|UniProtKB:P05554" FT REGION 178..201 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 182..198 FT /note="Required to functionally cooperate with SREBF1 in FT promoter activation" FT /evidence="ECO:0000250|UniProtKB:P53566" FT REGION 217..291 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 244..358 FT /note="Interaction with FOXO1" FT /evidence="ECO:0000250|UniProtKB:P53566" FT REGION 286..313 FT /note="Basic motif" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978" FT REGION 317..345 FT /note="Leucine-zipper" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978" FT COMPBIAS 29..39 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 40..49 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 181..199 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 224..238 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 239..259 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 276..291 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 161 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 190 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:15107404" FT MOD_RES 226 FT /note="Phosphothreonine; by GSK3" FT /evidence="ECO:0000250|UniProtKB:P53566" FT MOD_RES 230 FT /note="Phosphothreonine; by GSK3" FT /evidence="ECO:0000250|UniProtKB:P53566" FT MOD_RES 234 FT /note="Phosphoserine; by GSK3" FT /evidence="ECO:0000250|UniProtKB:P53566" FT CROSSLNK 161 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0007744|PubMed:25218447, FT ECO:0007744|PubMed:28112733" FT VAR_SEQ 1..119 FT /note="Missing (in isoform 3)" FT /id="VSP_057547" FT VAR_SEQ 1..14 FT /note="Missing (in isoform 2)" FT /id="VSP_057548" FT VAR_SEQ 1 FT /note="M -> MRGRGRAGSPGGRRRRPAQAGGRRGSPCRENSNSPM (in FT isoform 4)" FT /id="VSP_057607" FT VARIANT 84 FT /note="H -> L (in AML; no effect on expression; no effect FT on DNA-binding or transactivation activity; FT dbSNP:rs28931590)" FT /evidence="ECO:0000269|PubMed:11242107" FT /id="VAR_072677" FT VARIANT 312 FT /note="Q -> QK (in AML; nuclear; no effect on expression; FT loss of DNA-binding and transactivation activity)" FT /evidence="ECO:0000269|PubMed:11242107" FT /id="VAR_072678" FT MUTAGEN 55 FT /note="I->A: Decreased interaction with TRIB1." FT /evidence="ECO:0000269|PubMed:26455797" FT MUTAGEN 57 FT /note="E->T: No effect on interaction with TRIB1." FT /evidence="ECO:0000269|PubMed:26455797" FT MUTAGEN 58 FT /note="H->D: No effect on interaction with TRIB1." FT /evidence="ECO:0000269|PubMed:26455797" FT MUTAGEN 59 FT /note="E->A: Decreased interaction with TRIB1." FT /evidence="ECO:0000269|PubMed:26455797" FT MUTAGEN 61 FT /note="S->A: Decreased interaction with TRIB1." FT /evidence="ECO:0000269|PubMed:26455797" FT MUTAGEN 62 FT /note="I->A: Decreased interaction with TRIB1." FT /evidence="ECO:0000269|PubMed:26455797" FT MUTAGEN 63 FT /note="D->A: No effect on interaction with TRIB1." FT /evidence="ECO:0000269|PubMed:26455797" FT MUTAGEN 64 FT /note="I->A: Decreased interaction with TRIB1." FT /evidence="ECO:0000269|PubMed:26455797" FT MUTAGEN 65 FT /note="S->A: No effect on interaction with TRIB1." FT /evidence="ECO:0000269|PubMed:26455797" FT MUTAGEN 67 FT /note="Y->A: Decreased interaction with TRIB1." FT /evidence="ECO:0000269|PubMed:26455797" FT MUTAGEN 67 FT /note="Y->F: No effect on interaction with TRIB1." FT /evidence="ECO:0000269|PubMed:26455797" FT MUTAGEN 68 FT /note="I->A: Decreased interaction with TRIB1." FT /evidence="ECO:0000269|PubMed:26455797" FT MUTAGEN 69 FT /note="D->A: No effect on interaction with TRIB1." FT /evidence="ECO:0000269|PubMed:26455797" FT CONFLICT 40..41 FT /note="AQ -> PK (in Ref. 1; AAC50235)" FT /evidence="ECO:0000305" FT CONFLICT 95..98 FT /note="VGPT -> WAH (in Ref. 2; CAA72289)" FT /evidence="ECO:0000305" FT CONFLICT 241 FT /note="L -> V (in Ref. 2; CAA72289)" FT /evidence="ECO:0000305" FT CONFLICT 248..250 FT /note="GPG -> ALA (in Ref. 2; CAA72289)" FT /evidence="ECO:0000305" FT CONFLICT 269 FT /note="S -> T (in Ref. 1; AAC50235)" FT /evidence="ECO:0000305" FT HELIX 64..66 FT /evidence="ECO:0007829|PDB:6DC0" FT HELIX 70..73 FT /evidence="ECO:0007829|PDB:6DC0" FT HELIX 284..338 FT /evidence="ECO:0007829|PDB:8K8C" SQ SEQUENCE 358 AA; 37561 MW; 574C0A049E25BCAC CRC64; MESADFYEAE PRPPMSSHLQ SPPHAPSSAA FGFPRGAGPA QPPAPPAAPE PLGGICEHET SIDISAYIDP AAFNDEFLAD LFQHSRQQEK AKAAVGPTGG GGGGDFDYPG APAGPGGAVM PGGAHGPPPG YGCAAAGYLD GRLEPLYERV GAPALRPLVI KQEPREEDEA KQLALAGLFP YQPPPPPPPS HPHPHPPPAH LAAPHLQFQI AHCGQTTMHL QPGHPTPPPT PVPSPHPAPA LGAAGLPGPG SALKGLGAAH PDLRASGGSG AGKAKKSVDK NSNEYRVRRE RNNIAVRKSR DKAKQRNVET QQKVLELTSD NDRLRKRVEQ LSRELDTLRG IFRQLPESSL VKAMGNCA // ID KMT2A_HUMAN Reviewed; 3969 AA. AC Q03164; E9PQG7; Q13743; Q13744; Q14845; Q16364; Q59FF2; Q6UBD1; Q9HBJ3; AC Q9UD94; Q9UMA3; DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-2007, sequence version 5. DT 28-JAN-2026, entry version 267. DE RecName: Full=Histone-lysine N-methyltransferase 2A; DE Short=Lysine N-methyltransferase 2A; DE EC=2.1.1.364 {ECO:0000269|PubMed:12453419, ECO:0000269|PubMed:19187761, ECO:0000269|PubMed:19556245, ECO:0000269|PubMed:24235145, ECO:0000269|PubMed:25561738, ECO:0000269|PubMed:26886794}; DE AltName: Full=ALL-1 {ECO:0000303|PubMed:12453419}; DE AltName: Full=CXXC-type zinc finger protein 7; DE AltName: Full=Cysteine methyltransferase KMT2A {ECO:0000305}; DE EC=2.1.1.- {ECO:0000269|PubMed:24235145}; DE AltName: Full=Myeloid/lymphoid or mixed-lineage leukemia; DE AltName: Full=Myeloid/lymphoid or mixed-lineage leukemia protein 1; DE AltName: Full=Trithorax-like protein; DE AltName: Full=Zinc finger protein HRX; DE Contains: DE RecName: Full=MLL cleavage product N320; DE AltName: Full=N-terminal cleavage product of 320 kDa; DE Short=p320; DE Contains: DE RecName: Full=MLL cleavage product C180; DE AltName: Full=C-terminal cleavage product of 180 kDa; DE Short=p180; GN Name=KMT2A; Synonyms=ALL1, CXXC7, HRX, HTRX, MLL, MLL1, TRX1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=1423624; DOI=10.1016/0092-8674(92)90602-9; RA Tkachuk D.C., Kohler S., Cleary M.L.; RT "Involvement of a homolog of Drosophila trithorax by 11q23 chromosomal RT translocations in acute leukemias."; RL Cell 71:691-700(1992). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 3), AND VARIANT GLY-30. RX PubMed=8703835; DOI=10.1046/j.1365-2141.1996.d01-1748.x; RA Nilson I., Loechner K., Siegler G., Greil J., Beck J.D., Fey G.H., RA Marschalek R.; RT "Exon/intron structure of the human ALL-1 (MLL) gene involved in RT translocations to chromosomal region 11q23 and acute leukaemias."; RL Br. J. Haematol. 93:966-972(1996). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS VAL-53; LYS-502; THR-2319; RP ARG-2354; ARG-2387; ILE-3714 AND ALA-3773. RG NIEHS SNPs program; RL Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16554811; DOI=10.1038/nature04632; RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G., RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., RA Hattori M., Rogers J., Lander E.S., Sakaki Y.; RT "Human chromosome 11 DNA sequence and analysis including novel gene RT identification."; RL Nature 440:497-500(2006). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-1909. RX PubMed=8378076; RA Yamamoto K., Seto M., Komatsu H., Iida S., Akao Y., Kojima S., Kodera Y., RA Nakazawa S., Ariyoshi Y., Takahashi T., Ueda R.; RT "Two distinct portions of LTG19/ENL at 19p13 are involved in t(11;19) RT leukemia."; RL Oncogene 8:2617-2625(1993). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] OF 63-3969 (ISOFORM 3), AND CHROMOSOMAL RP TRANSLOCATION WITH AFF1/MLLT2. RX PubMed=1423625; DOI=10.1016/0092-8674(92)90603-a; RA Gu Y., Nakamura T., Alder H., Prasad R., Canaani O., Cimino G., Croce C.M., RA Canaani E.; RT "The t(4;11) chromosome translocation of human acute leukemias fuses the RT ALL-1 gene, related to Drosophila trithorax, to the AF-4 gene."; RL Cell 71:701-708(1992). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 812-3969. RC TISSUE=Brain; RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., RA Ohara O., Nagase T., Kikuno R.F.; RT "Homo sapiens protein coding cDNA."; RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1112-1140 AND 1552-162, AND NUCLEOTIDE RP SEQUENCE [MRNA] OF 1317-2328. RC TISSUE=Brain; RX PubMed=1303259; DOI=10.1038/ng1092-113; RA Djabali M., Selleri L., Parry P., Bower M., Young B.D., Evans G.A.; RT "A trithorax-like gene is interrupted by chromosome 11q23 translocations in RT acute leukaemias."; RL Nat. Genet. 2:113-118(1992). RN [9] RP ERRATUM OF PUBMED:1303259. RX PubMed=8401594; DOI=10.1038/ng0893-431; RA Djabali M., Selleri L., Parry P., Bower M., Young B., Evans G.A.; RL Nat. Genet. 4:431-431(1993). RN [10] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1212-1603 (ISOFORM 3). RX PubMed=7794749; DOI=10.1111/j.1365-2141.1995.tb05151.x; RA Marschalek R., Greil J., Lochner K., Nilson I., Siegler G., RA Zweckbronner I., Beck J.D., Fey G.H.; RT "Molecular analysis of the chromosomal breakpoint and fusion transcripts in RT the acute lymphoblastic SEM cell line with chromosomal translocation RT t(4;11)."; RL Br. J. Haematol. 90:308-320(1995). RN [11] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1251-1654 (ISOFORM 2). RX PubMed=7598802; DOI=10.1089/dna.1995.14.475; RA Mbangkollo D., Burnett R., McCabe N., Thirman M., Gill H., Yu H., RA Rowley J.D., Diaz M.O.; RT "The human MLL gene: nucleotide sequence, homology to the Drosophila trx RT zinc-finger domain, and alternative splicing."; RL DNA Cell Biol. 14:475-483(1995). RN [12] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1251-1538. RX PubMed=8162575; RA Gu Y., Alder H., Nakamura T., Schichman S.A., Prasad R., Canaani O., RA Saito H., Croce C.M., Canaani E.; RT "Sequence analysis of the breakpoint cluster region in the ALL-1 gene RT involved in acute leukemia."; RL Cancer Res. 54:2327-2330(1994). RN [13] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1311-1687 (ISOFORM 3), AND CHROMOSOMAL RP TRANSLOCATION WITH GAS7. RX PubMed=10706619; DOI=10.1073/pnas.050397097; RA Megonigal M.D., Cheung N.-K.V., Rappaport E.F., Nowell P.C., Wilson R.B., RA Jones D.H., Addya K., Leonard D.G.B., Kushner B.H., Williams T.M., RA Lange B.J., Felix C.A.; RT "Detection of leukemia-associated MLL-GAS7 translocation early during RT chemotherapy with DNA topoisomerase II inhibitors."; RL Proc. Natl. Acad. Sci. U.S.A. 97:2814-2819(2000). RN [14] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1421-1540. RX PubMed=8414518; RA Forster A., Rabbitts T.H.; RT "A method for identifying genes within yeast artificial chromosomes: RT application to isolation of MLL fusion cDNAs from acute leukaemia RT translocations."; RL Oncogene 8:3157-3160(1993). RN [15] RP PROTEIN SEQUENCE OF 2719-2730, CLEAVAGE, SUBUNIT, SUBCELLULAR LOCATION, AND RP MUTAGENESIS OF 2718-ASP--VAL-2720. RX PubMed=12482972; DOI=10.1128/mcb.23.1.186-194.2003; RA Hsieh J.J.-D., Ernst P., Erdjument-Bromage H., Tempst P., Korsmeyer S.J.; RT "Proteolytic cleavage of MLL generates a complex of N- and C-terminal RT fragments that confers protein stability and subnuclear localization."; RL Mol. Cell. Biol. 23:186-194(2003). RN [16] RP CHROMOSOMAL TRANSLOCATION WITH CENPK. RX PubMed=8950979; RA Taki T., Hayashi Y., Taniwaki M., Seto M., Ueda R., Hanada R., Suzukawa K., RA Yokota J., Morishita K.; RT "Fusion of the MLL gene with two different genes, AF-6 and AF-5alpha, by a RT complex translocation involving chromosomes 5, 6, 8 and 11 in infant RT leukemia."; RL Oncogene 13:2121-2130(1996). RN [17] RP CHROMOSOMAL TRANSLOCATION WITH ABI1. RX PubMed=9694699; RA Taki T., Shibuya N., Taniwaki M., Hanada R., Morishita K., Bessho F., RA Yanagisawa M., Hayashi Y.; RT "ABI-1, a human homolog to mouse Abl-interactor 1, fuses the MLL gene in RT acute myeloid leukemia with t(10;11)(p11.2;q23)."; RL Blood 92:1125-1130(1998). RN [18] RP INTERACTION WITH SBF1. RX PubMed=9537414; DOI=10.1038/ng0498-331; RA Cui X., De Vivo I., Slany R., Miyamoto A., Firestein R., Cleary M.L.; RT "Association of SET domain and myotubularin-related proteins modulates RT growth control."; RL Nat. Genet. 18:331-337(1998). RN [19] RP INTERACTION WITH PPP1R15A, DISEASE, AND FUNCTION. RX PubMed=10490642; DOI=10.1128/mcb.19.10.7050; RA Adler H.T., Chinery R., Wu D.Y., Kussick S.J., Payne J.M., RA Fornace A.J. Jr., Tkachuk D.C.; RT "Leukemic HRX fusion proteins inhibit GADD34-induced apoptosis and RT associate with the GADD34 and hSNF5/INI1 proteins."; RL Mol. Cell. Biol. 19:7050-7060(1999). RN [20] RP CHROMOSOMAL TRANSLOCATION WITH AFF4. RC TISSUE=Placenta; RX PubMed=10588740; DOI=10.1073/pnas.96.25.14535; RA Taki T., Kano H., Taniwaki M., Sako M., Yanagisawa M., Hayashi Y.; RT "AF5q31, a newly identified AF4-related gene, is fused to MLL in infant RT acute lymphoblastic leukemia with ins(5;11)(q31;q13q23)."; RL Proc. Natl. Acad. Sci. U.S.A. 96:14535-14540(1999). RN [21] RP CHROMOSOMAL TRANSLOCATION WITH NCKIPSD/AF3P21. RX PubMed=10648423; RA Sano K., Hayakawa A., Piao J.-H., Kosaka Y., Nakamura H.; RT "Novel SH3 protein encoded by the AF3p21 gene is fused to the mixed lineage RT leukemia protein in a therapy-related leukemia with t(3;11)(p21;q23)."; RL Blood 95:1066-1068(2000). RN [22] RP CHROMOSOMAL TRANSLOCATION WITH GMPS. RX PubMed=11110714; RA Pegram L.D., Megonigal M.D., Lange B.J., Nowell P.C., Rowley J.D., RA Rappaport E.F., Felix C.A.; RT "t(3;11) translocation in treatment-related acute myeloid leukemia fuses RT MLL with the GMPS (guanosine 5-prime monophosphate synthetase) gene."; RL Blood 96:4360-4362(2000). RN [23] RP CHROMOSOMAL TRANSLOCATION WITH LPP. RX PubMed=11433529; DOI=10.1002/gcc.1157; RA Daheron L., Veinstein A., Brizard F., Drabkin H., Lacotte L., Guilhot F., RA Larsen C.J., Brizard A., Roche J.; RT "Human LPP gene is fused to MLL in a secondary acute leukemia with a RT t(3;11) (q28;q23)."; RL Genes Chromosomes Cancer 31:382-389(2001). RN [24] RP CHROMOSOMAL TRANSLOCATION WITH TET1. RX PubMed=12124344; RA Ono R., Taki T., Taketani T., Taniwaki M., Kobayashi H., Hayashi Y.; RT "LCX, leukemia-associated protein with a CXXC domain, is fused to MLL in RT acute myeloid leukemia with trilineage dysplasia having RT t(10;11)(q22;q23)."; RL Cancer Res. 62:4075-4080(2002). RN [25] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=12453419; DOI=10.1016/s1097-2765(02)00740-2; RA Nakamura T., Mori T., Tada S., Krajewski W., Rozovskaia T., Wassell R., RA Dubois G., Mazo A., Croce C.M., Canaani E.; RT "ALL-1 is a histone methyltransferase that assembles a supercomplex of RT proteins involved in transcriptional regulation."; RL Mol. Cell 10:1119-1128(2002). RN [26] RP CLEAVAGE, INTERACTION WITH TASP1, AND MUTAGENESIS OF 2666-ASP-GLY-2667 AND RP 2718-ASP--VAL-2720. RX PubMed=14636557; DOI=10.1016/s0092-8674(03)00816-x; RA Hsieh J.J.-D., Cheng E.H.-Y., Korsmeyer S.J.; RT "Taspase1: a threonine aspartase required for cleavage of MLL and proper RT HOX gene expression."; RL Cell 115:293-303(2003). RN [27] RP CHROMOSOMAL TRANSLOCATION WITH ZFYVE19 AND KNL1. RX PubMed=12618766; DOI=10.1038/sj.onc.1206273; RA Chinwalla V., Chien A., Odero M., Neilly M.B., Zeleznik-Le N.J., RA Rowley J.D.; RT "A t(11;15) fuses MLL to two different genes, AF15q14 and a novel gene RT MPFYVE on chromosome 15."; RL Oncogene 22:1400-1410(2003). RN [28] RP CHROMOSOMAL TRANSLOCATION WITH KNL1. RX PubMed=12618768; DOI=10.1038/sj.onc.1206272; RA Kuefer M.U., Chinwalla V., Zeleznik-Le N.J., Behm F.G., Naeve C.W., RA Rakestraw K.M., Mukatira S.T., Raimondi S.C., Morris S.W.; RT "Characterization of the MLL partner gene AF15q14 involved in RT t(11;15)(q23;q14)."; RL Oncogene 22:1418-1424(2003). RN [29] RP CHROMOSOMAL TRANSLOCATION WITH DAB2IP. RX PubMed=14978793; DOI=10.1002/gcc.20004; RA von Bergh A.R.M., Wijers P.M., Groot A.J., van Zelderen-Bhola S., RA Falkenburg J.H.F., Kluin P.M., Schuuring E.; RT "Identification of a novel RAS GTPase-activating protein (RASGAP) gene at RT 9q34 as an MLL fusion partner in a patient with de novo acute myeloid RT leukemia."; RL Genes Chromosomes Cancer 39:324-334(2004). RN [30] RP CHROMOSOMAL TRANSLOCATION WITH SEPT11. RX PubMed=14999297; DOI=10.1038/sj.leu.2403334; RA Kojima K., Sakai I., Hasegawa A., Niiya H., Azuma T., Matsuo Y., Fujii N., RA Tanimoto M., Fujita S.; RT "FLJ10849, a septin family gene, fuses MLL in a novel leukemia cell line RT CNLBC1 derived from chronic neutrophilic leukemia in transformation with RT t(4;11)(q21;q23)."; RL Leukemia 18:998-1005(2004). RN [31] RP IDENTIFICATION IN THE MLL1/MLL COMPLEX. RX PubMed=15199122; DOI=10.1128/mcb.24.13.5639-5649.2004; RA Yokoyama A., Wang Z., Wysocka J., Sanyal M., Aufiero D.J., Kitabayashi I., RA Herr W., Cleary M.L.; RT "Leukemia proto-oncoprotein MLL forms a SET1-like histone methyltransferase RT complex with menin to regulate Hox gene expression."; RL Mol. Cell. Biol. 24:5639-5649(2004). RN [32] RP CHROMOSOMAL TRANSLOCATION WITH FRYL. RX PubMed=16061630; DOI=10.1158/0008-5472.can-05-1325; RA Hayette S., Cornillet-Lefebvre P., Tigaud I., Struski S., Forissier S., RA Berchet A., Doll D., Gillot L., Brahim W., Delabesse E., Magaud J.-P., RA Rimokh R.; RT "AF4p12, a human homologue to the furry gene of Drosophila, as a novel MLL RT fusion partner."; RL Cancer Res. 65:6521-6525(2005). RN [33] RP FUNCTION, IDENTIFICATION IN THE MLL1/MLL COMPLEX, AND INTERACTION WITH RP KAT8. RX PubMed=15960975; DOI=10.1016/j.cell.2005.04.031; RA Dou Y., Milne T.A., Tackett A.J., Smith E.R., Fukuda A., Wysocka J., RA Allis C.D., Chait B.T., Hess J.L., Roeder R.G.; RT "Physical association and coordinate function of the H3 K4 RT methyltransferase MLL1 and the H4 K16 acetyltransferase MOF."; RL Cell 121:873-885(2005). RN [34] RP DOMAIN 9AATAD. RX PubMed=17467953; DOI=10.1016/j.ygeno.2007.02.003; RA Piskacek S., Gregor M., Nemethova M., Grabner M., Kovarik P., Piskacek M.; RT "Nine-amino-acid transactivation domain: establishment and prediction RT utilities."; RL Genomics 89:756-768(2007). RN [35] RP IDENTIFICATION IN THE MLL1/MLL COMPLEX. RX PubMed=17500065; DOI=10.1074/jbc.m701574200; RA Cho Y.-W., Hong T., Hong S., Guo H., Yu H., Kim D., Guszczynski T., RA Dressler G.R., Copeland T.D., Kalkum M., Ge K.; RT "PTIP associates with MLL3- and MLL4-containing histone H3 lysine 4 RT methyltransferase complex."; RL J. Biol. Chem. 282:20395-20406(2007). RN [36] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-153; SER-197; SER-518; RP SER-680; THR-840; SER-1056; THR-1845; SER-2098; THR-2147; SER-2151; RP THR-2525; SER-2955; SER-3036; THR-3372 AND SER-3511, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [37] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [38] RP FUNCTION, CATALYTIC ACTIVITY, CHARACTERIZATION OF THE MLL1/MLL COMPLEX, RP INTERACTION WITH WDR5, AND MUTAGENESIS OF ASN-3906 AND TYR-3942. RX PubMed=19556245; DOI=10.1074/jbc.m109.014498; RA Patel A., Dharmarajan V., Vought V.E., Cosgrove M.S.; RT "On the mechanism of multiple lysine methylation by the human mixed lineage RT leukemia protein-1 (MLL1) core complex."; RL J. Biol. Chem. 284:24242-24256(2009). RN [39] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1858, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200; RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., RA Mann M., Daub H.; RT "Large-scale proteomics analysis of the human kinome."; RL Mol. Cell. Proteomics 8:1751-1764(2009). RN [40] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-153; SER-2098 AND SER-3515, RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [41] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-636; LYS-1130 AND LYS-1235, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., RA Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [42] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-153; SER-197; SER-926; RP SER-2955 AND THR-3372, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [43] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2201, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [44] RP IDENTIFICATION IN MLL1 COMPLEX. RX PubMed=23508102; DOI=10.1128/mcb.01742-12; RA van Nuland R., Smits A.H., Pallaki P., Jansen P.W., Vermeulen M., RA Timmers H.T.; RT "Quantitative dissection and stoichiometry determination of the human RT SET1/MLL histone methyltransferase complexes."; RL Mol. Cell. Biol. 33:2067-2077(2013). RN [45] RP SUBCELLULAR LOCATION. RX PubMed=25593309; DOI=10.1101/gad.252189.114; RA Gong F., Chiu L.Y., Cox B., Aymard F., Clouaire T., Leung J.W., RA Cammarata M., Perez M., Agarwal P., Brodbelt J.S., Legube G., Miller K.M.; RT "Screen identifies bromodomain protein ZMYND8 in chromatin recognition of RT transcription-associated DNA damage that promotes homologous RT recombination."; RL Genes Dev. 29:197-211(2015). RN [46] RP FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, AND MUTAGENESIS OF ASN-3906. RX PubMed=25561738; DOI=10.1074/jbc.m114.627646; RA Shinsky S.A., Monteith K.E., Viggiano S., Cosgrove M.S.; RT "Biochemical reconstitution and phylogenetic comparison of human SET1 RT family core complexes involved in histone methylation."; RL J. Biol. Chem. 290:6361-6375(2015). RN [47] RP INVOLVEMENT IN WDSTS. RX PubMed=22795537; DOI=10.1016/j.ajhg.2012.06.008; RA Jones W.D., Dafou D., McEntagart M., Woollard W.J., Elmslie F.V., RA Holder-Espinasse M., Irving M., Saggar A.K., Smithson S., Trembath R.C., RA Deshpande C., Simpson M.A.; RT "De novo mutations in MLL cause Wiedemann-Steiner syndrome."; RL Am. J. Hum. Genet. 91:358-364(2012). RN [48] RP INTERACTION WITH ZNF335. RX PubMed=23178126; DOI=10.1016/j.cell.2012.10.043; RA Yang Y.J., Baltus A.E., Mathew R.S., Murphy E.A., Evrony G.D., RA Gonzalez D.M., Wang E.P., Marshall-Walker C.A., Barry B.J., Murn J., RA Tatarakis A., Mahajan M.A., Samuels H.H., Shi Y., Golden J.A., Mahajnah M., RA Shenhav R., Walsh C.A.; RT "Microcephaly gene links trithorax and REST/NRSF to control neural stem RT cell proliferation and differentiation."; RL Cell 151:1097-1112(2012). RN [49] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1858; SER-2098; THR-2525; RP SER-2611; SER-2796; SER-2955; SER-3036; SER-3511 AND SER-3527, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [50] RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, METHYLATION AT RP CYS-3882, AND MUTAGENESIS OF CYS-3882. RX PubMed=24235145; DOI=10.1074/jbc.m113.501064; RA Patel A., Vought V.E., Swatkoski S., Viggiano S., Howard B., RA Dharmarajan V., Monteith K.E., Kupakuwana G., Namitz K.E., Shinsky S.A., RA Cotter R.J., Cosgrove M.S.; RT "Automethylation activities within the mixed lineage leukemia-1 (MLL1) core RT complex reveal evidence supporting a 'two-active site' model for multiple RT histone H3 lysine 4 methylation."; RL J. Biol. Chem. 289:868-884(2014). RN [51] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1837, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [52] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-2528, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=28112733; DOI=10.1038/nsmb.3366; RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C., RA Nielsen M.L.; RT "Site-specific mapping of the human SUMO proteome reveals co-modification RT with phosphorylation."; RL Nat. Struct. Mol. Biol. 24:325-336(2017). RN [53] RP INTERACTION WITH HUMAN HERPESVIRUS 8/HHV-8 PROTEIN LANA1, AND SUBCELLULAR RP LOCATION. RX PubMed=34850113; DOI=10.1093/nar/gkab1094; RA Tan M., Li S., Juillard F., Chitas R., Custodio T.F., Xue H., Szymula A., RA Sun Q., Liu B., Alvarez A.L., Chen S., Huang J., Simas J.P., McVey C.E., RA Kaye K.M.; RT "MLL1 is regulated by KSHV LANA and is important for virus latency."; RL Nucleic Acids Res. 49:12895-12911(2021). RN [54] RP STRUCTURE BY NMR OF 1146-1214 IN COMPLEX WITH ZINC, DOMAIN CXXC-TYPE RP ZINC-FINGER, DNA-BINDING, AND MUTAGENESIS OF ARG-1151; ARG-1153; ARG-1154; RP CYS-1155; CYS-1158; CYS-1161; GLN-1162; ASP-1166; CYS-1167; CYS-1170; RP ASN-1172; CYS-1173; ASP-1175; LYS-1176; 1178-LYS--GLY-1181; LYS-1178; RP PHE-1179; ASN-1183; LYS-1185; LYS-1186; GLN-1187; CYS-1188; CYS-1189; RP ARG-1192; LYS-1193; CYS-1194; GLN-1195 AND ASN-1196. RX PubMed=16990798; DOI=10.1038/sj.emboj.7601340; RA Allen M.D., Grummitt C.G., Hilcenko C., Min S.Y., Tonkin L.M., RA Johnson C.M., Freund S.M., Bycroft M., Warren A.J.; RT "Solution structure of the nonmethyl-CpG-binding CXXC domain of the RT leukaemia-associated MLL histone methyltransferase."; RL EMBO J. 25:4503-4512(2006). RN [55] RP STRUCTURE BY NMR OF 2842-2869 IN COMPLEX WITH CREBBP. RX PubMed=16253272; DOI=10.1016/j.jmb.2005.09.059; RA De Guzman R.N., Goto N.K., Dyson H.J., Wright P.E.; RT "Structural basis for cooperative transcription factor binding to the CBP RT coactivator."; RL J. Mol. Biol. 355:1005-1013(2006). RN [56] {ECO:0007744|PDB:2JYI} RP STRUCTURE BY NMR OF 1147-1203. RA Cierpicki T., Riesbeck L.E., Grembecka J., Lukasik S.M., Omonkowska M., RA Shultis D., Zeleznik-Le N.J., Bushweller J.H.; RT "Structural basis for maintenance of unmethylated CpG elements by the CXXC RT domain of MLL and its critical contributions to MLL-AF9 immortalization RT activity."; RL Submitted (DEC-2007) to the PDB data bank. RN [57] RP X-RAY CRYSTALLOGRAPHY (1.37 ANGSTROMS) OF 3764-3776 IN COMPLEX WITH WDR5, RP AND INTERACTION WITH WDR5. RX PubMed=18829459; DOI=10.1074/jbc.c800164200; RA Patel A., Dharmarajan V., Cosgrove M.S.; RT "Structure of WDR5 bound to mixed lineage leukemia protein-1 peptide."; RL J. Biol. Chem. 283:32158-32161(2008). RN [58] {ECO:0007744|PDB:3EMH} RP X-RAY CRYSTALLOGRAPHY (1.37 ANGSTROMS) OF 3764-3776 IN COMPLEX WITH WDR5, RP INTERACTION WITH WDR5, AND MUTAGENESIS OF ARG-3765 AND HIS-3769. RX PubMed=18840606; DOI=10.1074/jbc.m806900200; RA Song J.J., Kingston R.E.; RT "WDR5 interacts with mixed lineage leukemia (MLL) protein via the histone RT H3-binding pocket."; RL J. Biol. Chem. 283:35258-35264(2008). RN [59] RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 3785-3969 IN COMPLEX WITH ZINC; RP S-ADENOSYL-L-HOMOCYSTEINE AND HISTONE H3 PEPTIDE, FUNCTION, CATALYTIC RP ACTIVITY, DOMAIN SET, INTERACTION WITH ASH2L AND RBBP5, AND MUTAGENESIS OF RP TYR-3858; GLN-3867; ASP-3869; ARG-3871; GLU-3872; TYR-3874; LYS-3878 AND RP TYR-3942. RX PubMed=19187761; DOI=10.1016/j.molcel.2008.12.029; RA Southall S.M., Wong P.S., Odho Z., Roe S.M., Wilson J.R.; RT "Structural basis for the requirement of additional factors for MLL1 SET RT domain activity and recognition of epigenetic marks."; RL Mol. Cell 33:181-191(2009). RN [60] {ECO:0007744|PDB:2KYU} RP STRUCTURE BY NMR OF 1564-1628 IN COMPLEX WITH ZINC, FUNCTION, DOMAIN, RP MUTAGENESIS OF TRP-1594; VAL-1617 AND TYR-1619, AND INTERACTION WITH PPIE. RX PubMed=20677832; DOI=10.1021/bi1009387; RA Park S., Osmers U., Raman G., Schwantes R.H., Diaz M.O., Bushweller J.H.; RT "The PHD3 domain of MLL acts as a CYP33-regulated switch between MLL- RT mediated activation and repression."; RL Biochemistry 49:6576-6586(2010). RN [61] {ECO:0007744|PDB:2KU7, ECO:0007744|PDB:3LQH, ECO:0007744|PDB:3LQI, ECO:0007744|PDB:3LQJ} RP X-RAY CRYSTALLOGRAPHY (1.72 ANGSTROMS) OF 1566-1784 IN COMPLEX WITH ZINC RP AND METHYLATED HISTONE H3, INTERACTION WITH PPIE, DOMAIN, AND MUTAGENESIS RP OF TYR-1581; GLN-1587 AND TRP-1594. RX PubMed=20541251; DOI=10.1016/j.cell.2010.05.016; RA Wang Z., Song J., Milne T.A., Wang G.G., Li H., Allis C.D., Patel D.J.; RT "Pro isomerization in MLL1 PHD3-bromo cassette connects H3K4me readout to RT CyP33 and HDAC-mediated repression."; RL Cell 141:1183-1194(2010). RN [62] {ECO:0007744|PDB:2KKF} RP STRUCTURE BY NMR OF 1147-1203 IN COMPLEX WITH ZINC AND TARGET DNA, RP FUNCTION, DOMAIN CXXC-TYPE ZINC-FINGER, AND MUTAGENESIS OF ARG-1150; RP ARG-1154; LYS-1185; GLN-1187; CYS-1188; LYS-1193; LEU-1197 AND MET-1200. RX PubMed=20010842; DOI=10.1038/nsmb.1714; RA Cierpicki T., Risner L.E., Grembecka J., Lukasik S.M., Popovic R., RA Omonkowska M., Shultis D.D., Zeleznik-Le N.J., Bushweller J.H.; RT "Structure of the MLL CXXC domain-DNA complex and its functional role in RT MLL-AF9 leukemia."; RL Nat. Struct. Mol. Biol. 17:62-68(2010). RN [63] {ECO:0007744|PDB:3P4F} RP X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 3761-3770 IN COMPLEX WITH RBBP5 RP AND WDR5, AND FUNCTION. RX PubMed=21220120; DOI=10.1016/j.str.2010.09.022; RA Avdic V., Zhang P., Lanouette S., Groulx A., Tremblay V., Brunzelle J., RA Couture J.F.; RT "Structural and biochemical insights into MLL1 core complex assembly."; RL Structure 19:101-108(2011). RN [64] {ECO:0007744|PDB:4GQ6} RP X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 6-15 IN COMPLEX WITH MEN1, RP INTERACTION WITH MEN1, AND INTERACTION OF FUSION PROTEIN KMT2A-MLLT3 WITH RP MEN1. RX PubMed=22936661; DOI=10.1182/blood-2012-05-429274; RA Shi A., Murai M.J., He S., Lund G., Hartley T., Purohit T., Reddy G., RA Chruszcz M., Grembecka J., Cierpicki T.; RT "Structural insights into inhibition of the bivalent menin-MLL interaction RT by small molecules in leukemia."; RL Blood 120:4461-4469(2012). RN [65] {ECO:0007744|PDB:4ESG} RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 3755-3771 IN COMPLEX WITH WDR5, RP INTERACTION WITH THE WRAD COMPLEX, INTERACTION WITH WDR5, MUTAGENESIS OF RP SER-3763; ARG-3765 AND HIS-3769, AND MOTIF WIN. RX PubMed=22665483; DOI=10.1074/jbc.m112.364125; RA Dharmarajan V., Lee J.H., Patel A., Skalnik D.G., Cosgrove M.S.; RT "Structural basis for WDR5 interaction (Win) motif recognition in human RT SET1 family histone methyltransferases."; RL J. Biol. Chem. 287:27275-27289(2012). RN [66] {ECO:0007744|PDB:3U85, ECO:0007744|PDB:3U88} RP X-RAY CRYSTALLOGRAPHY (3.00 ANGSTROMS) OF 6-25 AND 103-153 IN COMPLEX WITH RP MEN1 AND PSIP1, INTERACTION WITH MEN1, INTERACTION OF KMT2A-MEN1 COMPLEX RP WITH PSIP1, MOTIF MBM, AND MUTAGENESIS OF ARG-6; TRP-7; ARG-8; PHE-9; RP PRO-10; ALA-11; ARG-12; PRO-13; ARG-24 AND ARG-25. RX PubMed=22327296; DOI=10.1038/nature10806; RA Huang J., Gurung B., Wan B., Matkar S., Veniaminova N.A., Wan K., RA Merchant J.L., Hua X., Lei M.; RT "The same pocket in menin binds both MLL and JUND but has opposite effects RT on transcription."; RL Nature 482:542-546(2012). RN [67] {ECO:0007744|PDB:2LXS, ECO:0007744|PDB:2LXT} RP STRUCTURE BY NMR OF 2840-2858 IN COMPLEX WITH CREBBP AND CREB1. RX PubMed=23651431; DOI=10.1021/cb4002188; RA Bruschweiler S., Konrat R., Tollinger M.; RT "Allosteric communication in the KIX domain proceeds through dynamic RT repacking of the hydrophobic core."; RL ACS Chem. Biol. 8:1600-1610(2013). RN [68] {ECO:0007744|PDB:2MTN} RP STRUCTURE BY NMR OF 110-160 IN COMPLEX WITH PSIP1, DOMAIN IBM MOTIF, RP INTERACTION WITH PSIP1 AND MEN1, INTERACTION OF FUSION PROTEIN KMT2A-MLLT3 RP WITH PSIP1 AND MEN1, AND MUTAGENESIS OF PHE-129; PHE-148 AND LEU-149. RX PubMed=25305204; DOI=10.1182/blood-2014-01-550079; RA Murai M.J., Pollock J., He S., Miao H., Purohit T., Yokom A., Hess J.L., RA Muntean A.G., Grembecka J., Cierpicki T.; RT "The same site on the integrase-binding domain of lens epithelium-derived RT growth factor is a therapeutic target for MLL leukemia and HIV."; RL Blood 124:3730-3737(2014). RN [69] {ECO:0007744|PDB:2MSR} RP STRUCTURE BY NMR OF 140-160 IN COMPLEX WITH PSIP1, INTERACTION WITH PSIP1, RP AND MUTAGENESIS OF PHE-129; PHE-133; GLU-144; GLU-146; PHE-148 AND PHE-151. RX PubMed=25082813; DOI=10.1158/0008-5472.can-13-3602; RA Cermakova K., Tesina P., Demeulemeester J., El Ashkar S., Mereau H., RA Schwaller J., Rezacova P., Veverka V., De Rijck J.; RT "Validation and structural characterization of the LEDGF/p75-MLL interface RT as a new target for the treatment of MLL-dependent leukemia."; RL Cancer Res. 74:5139-5151(2014). RN [70] {ECO:0007744|PDB:5F5E, ECO:0007744|PDB:5F6L} RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 3813-3969 IN COMPLEX WITH RP S-ADENOSYL-L-HOMOCYSTEINE AND ZINC, FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, RP DOMAIN, AND MUTAGENESIS OF ASN-3861; ARG-3864 AND GLN-3867. RX PubMed=26886794; DOI=10.1038/nature16952; RA Li Y., Han J., Zhang Y., Cao F., Liu Z., Li S., Wu J., Hu C., Wang Y., RA Shuai J., Chen J., Cao L., Li D., Shi P., Tian C., Zhang J., Dou Y., Li G., RA Chen Y., Lei M.; RT "Structural basis for activity regulation of MLL family RT methyltransferases."; RL Nature 530:447-452(2016). RN [71] {ECO:0007744|PDB:5SVH} RP X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS) OF 2839-2869. RA Langelaan D.N., Smith S.P.; RT "Design of a nanomolar affinity ligand to the KIX domain of CBP."; RL Submitted (AUG-2016) to the PDB data bank. RN [72] {ECO:0007744|PDB:6EMQ} RP STRUCTURE BY NMR OF 111-160 IN COMPLEX WITH PSIP1, INTERACTION WITH PSIP1, RP DOMAIN IBM MOTIF, MUTAGENESIS OF VAL-132; PHE-133; SER-136 AND SER-142, AND RP PHOSPHORYLATION AT SER-136; SER-142 AND SER-153. RX PubMed=29997176; DOI=10.1073/pnas.1803909115; RA Sharma S., Cermakova K., De Rijck J., Demeulemeester J., Fabry M., RA El Ashkar S., Van Belle S., Lepsik M., Tesina P., Duchoslav V., Novak P., RA Hubalek M., Srb P., Christ F., Rezacova P., Hodges H.C., Debyser Z., RA Veverka V.; RT "Affinity switching of the LEDGF/p75 IBD interactome is governed by kinase- RT dependent phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 115:E7053-E7062(2018). RN [73] {ECO:0007744|PDB:4NW3} RP X-RAY CRYSTALLOGRAPHY (2.82 ANGSTROMS) OF 1147-1204 IN COMPLEX WITH CPG RP DNA, DOMAIN CXXC-TYPE ZINC-FINGER, AND ZINC-BINDING. RX PubMed=29276034; DOI=10.1016/j.str.2017.11.022; RA Xu C., Liu K., Lei M., Yang A., Li Y., Hughes T.R., Min J.; RT "DNA Sequence Recognition of Human CXXC Domains and Their Structural RT Determinants."; RL Structure 26:85-95.e3(2018). CC -!- FUNCTION: Histone methyltransferase that plays an essential role in CC early development and hematopoiesis (PubMed:12453419, PubMed:15960975, CC PubMed:19187761, PubMed:19556245, PubMed:20677832, PubMed:21220120, CC PubMed:26886794). Catalytic subunit of the MLL1/MLL complex, a CC multiprotein complex that mediates both methylation of 'Lys-4' of CC histone H3 (H3K4me) complex and acetylation of 'Lys-16' of histone H4 CC (H4K16ac) (PubMed:12453419, PubMed:15960975, PubMed:19187761, CC PubMed:19556245, PubMed:20677832, PubMed:21220120, PubMed:24235145, CC PubMed:26886794). Catalyzes methyl group transfer from S-adenosyl-L- CC methionine to the epsilon-amino group of 'Lys-4' of histone H3 (H3K4) CC via a non-processive mechanism. Part of chromatin remodeling machinery CC predominantly forms H3K4me1 and H3K4me2 methylation marks at active CC chromatin sites where transcription and DNA repair take place CC (PubMed:12453419, PubMed:15960975, PubMed:19187761, PubMed:19556245, CC PubMed:20677832, PubMed:21220120, PubMed:25561738, PubMed:26886794). CC Has weak methyltransferase activity by itself, and requires other CC component of the MLL1/MLL complex to obtain full methyltransferase CC activity (PubMed:19187761, PubMed:26886794). Has no activity toward CC histone H3 phosphorylated on 'Thr-3', less activity toward H3 CC dimethylated on 'Arg-8' or 'Lys-9', while it has higher activity toward CC H3 acetylated on 'Lys-9' (PubMed:19187761). Binds to unmethylated CpG CC elements in the promoter of target genes and helps maintain them in the CC nonmethylated state (PubMed:20010842). Required for transcriptional CC activation of HOXA9 (PubMed:12453419, PubMed:20010842, CC PubMed:20677832). Promotes PPP1R15A-induced apoptosis CC (PubMed:10490642). Plays a critical role in the control of circadian CC gene expression and is essential for the transcriptional activation CC mediated by the CLOCK-BMAL1 heterodimer (By similarity). Establishes a CC permissive chromatin state for circadian transcription by mediating a CC rhythmic methylation of 'Lys-4' of histone H3 (H3K4me) and this histone CC modification directs the circadian acetylation at H3K9 and H3K14 CC allowing the recruitment of CLOCK-BMAL1 to chromatin (By similarity). CC Also has auto-methylation activity on Cys-3882 in absence of histone H3 CC substrate (PubMed:24235145). {ECO:0000250|UniProtKB:P55200, CC ECO:0000269|PubMed:10490642, ECO:0000269|PubMed:12453419, CC ECO:0000269|PubMed:15960975, ECO:0000269|PubMed:19187761, CC ECO:0000269|PubMed:19556245, ECO:0000269|PubMed:20010842, CC ECO:0000269|PubMed:21220120, ECO:0000269|PubMed:24235145, CC ECO:0000269|PubMed:26886794, ECO:0000305|PubMed:20677832}. CC -!- CATALYTIC ACTIVITY: CC Reaction=L-lysyl(4)-[histone H3] + S-adenosyl-L-methionine = N(6)- CC methyl-L-lysyl(4)-[histone H3] + S-adenosyl-L-homocysteine + H(+); CC Xref=Rhea:RHEA:60264, Rhea:RHEA-COMP:15543, Rhea:RHEA-COMP:15547, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856, CC ChEBI:CHEBI:59789, ChEBI:CHEBI:61929; EC=2.1.1.364; CC Evidence={ECO:0000269|PubMed:12453419, ECO:0000269|PubMed:19187761, CC ECO:0000269|PubMed:19556245, ECO:0000269|PubMed:24235145, CC ECO:0000269|PubMed:25561738, ECO:0000269|PubMed:26886794}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60265; CC Evidence={ECO:0000305|PubMed:19556245, ECO:0000305|PubMed:25561738}; CC -!- CATALYTIC ACTIVITY: CC Reaction=N(6)-methyl-L-lysyl(4)-[histone H3] + S-adenosyl-L-methionine CC = N(6),N(6)-dimethyl-L-lysyl(4)-[histone H3] + S-adenosyl-L- CC homocysteine + H(+); Xref=Rhea:RHEA:60268, Rhea:RHEA-COMP:15540, CC Rhea:RHEA-COMP:15543, ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, CC ChEBI:CHEBI:59789, ChEBI:CHEBI:61929, ChEBI:CHEBI:61976; CC Evidence={ECO:0000269|PubMed:19187761, ECO:0000269|PubMed:24235145, CC ECO:0000269|PubMed:25561738, ECO:0000269|PubMed:26886794}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60269; CC Evidence={ECO:0000305|PubMed:25561738}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-cysteinyl-[protein] + S-adenosyl-L-methionine = S-methyl-L- CC cysteinyl-[protein] + S-adenosyl-L-homocysteine + H(+); CC Xref=Rhea:RHEA:66544, Rhea:RHEA-COMP:10131, Rhea:RHEA-COMP:10132, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29950, ChEBI:CHEBI:57856, CC ChEBI:CHEBI:59789, ChEBI:CHEBI:82612; CC Evidence={ECO:0000269|PubMed:24235145}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66545; CC Evidence={ECO:0000269|PubMed:24235145}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=10.4 uM for S-adenosyl-L-methionine (for histone-lysine N- CC methyltransferase activity) {ECO:0000269|PubMed:24235145}; CC KM=6.5 uM for S-adenosyl-L-methionine (for protein-cysteine CC methyltransferase) {ECO:0000269|PubMed:24235145}; CC -!- SUBUNIT: MLL cleavage product N320 heterodimerizes with MLL cleavage CC product C180 (via SET and FYRC domains). Component of some MLL1/MLL CC complex, at least composed of the core components KMT2A/MLL1, ASH2L, CC HCFC1/HCF1, HCFC2, WDR5, DPY30 and RBBP5, as well as the facultative CC components BACC1, CHD8, E2F6, HSP70, INO80C, KANSL1, LAS1L, MAX, MCRS1, CC MEN1, MGA, KAT8/MOF, PELP1, PHF20, PRP31, RING2, RUVB1/TIP49A, CC RUVB2/TIP49B, SENP3, TAF1, TAF4, TAF6, TAF7, TAF9 and TEX10 CC (PubMed:15199122, PubMed:15960975, PubMed:17500065, PubMed:19187761, CC PubMed:19556245, PubMed:23508102, PubMed:26886794). Forms a core CC complex with the evolutionary conserved subcomplex WRAD composed of CC WDR5, RBBP5, ASH2L/ASH2 and DPY30 subunits; WRAD differentially CC stimulates the methyltransferase activity (PubMed:25561738). Interacts CC (via WIN motif) with WDR5; the interaction is direct (PubMed:18829459, CC PubMed:18840606, PubMed:19556245, PubMed:22665483). Interaction with CC WDR5 is required for stable interaction with ASH2L and RBBP5, and CC thereby also for optimal histone methyltransferase activity CC (PubMed:26886794). Interacts with KAT8/MOF; the interaction is direct CC (PubMed:15960975). Interacts with SBF1 and PPP1R15A (PubMed:10490642, CC PubMed:9537414). Interacts with ZNF335 (PubMed:23178126). Interacts CC with CLOCK and BMAL1 in a circadian manner (By similarity). Interacts CC with PPIE; this results in decreased histone H3 methyltransferase CC activity (PubMed:20541251, PubMed:20677832). Interacts with CREBBP CC (PubMed:16253272). Interacts with the WRAD complex composed of WDR5, CC RBBP5, ASH2L and DPY30 (PubMed:22665483). Interacts (via MBM motif) CC with MEN1 (PubMed:22327296, PubMed:22936661, PubMed:25305204). CC Interacts (via IBM motifs) with PSIP1 (via IBD domain) with moderate CC affinity whereas the KMT2A-MEN1 complex interacts with a greater CC affinity; MEN1 enhances interaction of KMT2A with PSIP1 CC (PubMed:22327296, PubMed:25082813, PubMed:25305204, PubMed:29997176). CC Phosphorylation increases its affinity for PSIP1 (PubMed:29997176). CC Forms a complex with CREBBP and CREB1 (PubMed:23651431). CC {ECO:0000250|UniProtKB:P55200, ECO:0000269|PubMed:10490642, CC ECO:0000269|PubMed:12482972, ECO:0000269|PubMed:14636557, CC ECO:0000269|PubMed:15199122, ECO:0000269|PubMed:15960975, CC ECO:0000269|PubMed:16253272, ECO:0000269|PubMed:16990798, CC ECO:0000269|PubMed:17500065, ECO:0000269|PubMed:18829459, CC ECO:0000269|PubMed:18840606, ECO:0000269|PubMed:19187761, CC ECO:0000269|PubMed:19556245, ECO:0000269|PubMed:20541251, CC ECO:0000269|PubMed:20677832, ECO:0000269|PubMed:21220120, CC ECO:0000269|PubMed:22327296, ECO:0000269|PubMed:22665483, CC ECO:0000269|PubMed:23178126, ECO:0000269|PubMed:23651431, CC ECO:0000269|PubMed:25082813, ECO:0000269|PubMed:25305204, CC ECO:0000269|PubMed:25561738, ECO:0000269|PubMed:26886794, CC ECO:0000269|PubMed:29997176, ECO:0000269|PubMed:9537414}. CC -!- SUBUNIT: (Microbial infection) Interacts with herpes virus 8/HHV-8 CC protein LANA1; this interaction regulates the MLL1 histone CC methyltransferase activity on viral DNA. {ECO:0000269|PubMed:34850113}. CC -!- INTERACTION: CC Q03164; P10275: AR; NbExp=4; IntAct=EBI-591370, EBI-608057; CC Q03164; Q9UBL3-3: ASH2L; NbExp=4; IntAct=EBI-591370, EBI-16130425; CC Q03164; Q6P1J9: CDC73; NbExp=4; IntAct=EBI-591370, EBI-930143; CC Q03164; Q6PD62: CTR9; NbExp=5; IntAct=EBI-591370, EBI-1019583; CC Q03164; P68431: H3C12; NbExp=11; IntAct=EBI-591370, EBI-79722; CC Q03164; Q9H7Z6: KAT8; NbExp=3; IntAct=EBI-591370, EBI-896414; CC Q03164; Q03164: KMT2A; NbExp=5; IntAct=EBI-591370, EBI-591370; CC Q03164; O00255-2: MEN1; NbExp=12; IntAct=EBI-591370, EBI-9869387; CC Q03164; Q8N7H5: PAF1; NbExp=4; IntAct=EBI-591370, EBI-2607770; CC Q03164; Q9UNP9: PPIE; NbExp=4; IntAct=EBI-591370, EBI-591818; CC Q03164; Q15291: RBBP5; NbExp=12; IntAct=EBI-591370, EBI-592823; CC Q03164; P26373: RPL13; NbExp=2; IntAct=EBI-591370, EBI-356849; CC Q03164; Q96EB6: SIRT1; NbExp=5; IntAct=EBI-591370, EBI-1802965; CC Q03164; Q13309-1: SKP2; NbExp=2; IntAct=EBI-591370, EBI-15490084; CC Q03164; P61964: WDR5; NbExp=17; IntAct=EBI-591370, EBI-540834; CC Q03164; Q9WTL8: Bmal1; Xeno; NbExp=3; IntAct=EBI-591370, EBI-644534; CC Q03164; O08785: Clock; Xeno; NbExp=3; IntAct=EBI-591370, EBI-79859; CC Q03164; P45481: Crebbp; Xeno; NbExp=7; IntAct=EBI-591370, EBI-296306; CC PRO_0000390949; Q02548: PAX5; NbExp=2; IntAct=EBI-2610266, EBI-296331; CC PRO_0000390950; Q92794: KAT6A; NbExp=10; IntAct=EBI-2638616, EBI-948013; CC PRO_0000390950; P61964: WDR5; NbExp=2; IntAct=EBI-2638616, EBI-540834; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:12482972, CC ECO:0000269|PubMed:25593309, ECO:0000269|PubMed:34850113}. CC -!- SUBCELLULAR LOCATION: [MLL cleavage product N320]: Nucleus. CC -!- SUBCELLULAR LOCATION: [MLL cleavage product C180]: Nucleus. CC Note=Localizes to a diffuse nuclear pattern when not associated with CC MLL cleavage product N320. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q03164-1; Sequence=Displayed; CC Name=2; Synonyms=14P-18B; CC IsoId=Q03164-2; Sequence=VSP_006666; CC Name=3; CC IsoId=Q03164-3; Sequence=VSP_046879; CC -!- TISSUE SPECIFICITY: Heart, lung, brain and T- and B-lymphocytes. CC -!- DOMAIN: The 9aaTAD motif is a transactivation domain present in a large CC number of yeast and animal transcription factors. CC {ECO:0000269|PubMed:17467953}. CC -!- DOMAIN: The SET domain structure is atypical and is not in an optimal CC position to have methyltransferase activity. It requires other CC components of the MLL1/MLL complex, such as ASH2L or RBBP5, to order CC the active site and obtain optimal histone methyltransferase activity. CC {ECO:0000269|PubMed:19187761, ECO:0000269|PubMed:26886794}. CC -!- DOMAIN: The CXXC-type zinc finger binds to DNA sequence elements CC containing unnmethylated CpG dinucleotides. CC {ECO:0000269|PubMed:16990798, ECO:0000269|PubMed:20010842, CC ECO:0000269|PubMed:29276034}. CC -!- DOMAIN: The third PHD-type zinc-finger binds both trimethylated histone CC H3K4me3 and PPIE; histone and PPIE bind to distinct surfaces CC (PubMed:20541251, PubMed:20677832). Nevertheless, PPIE binding and CC histone binding are mutually inhibitory (PubMed:20677832). CC Isomerization of a peptidylproline bond in the linker between the third CC PHD-type zinc-finger and the bromo domain disrupts the interaction CC between the bromo domain and the third PHD-type zinc-finger, and CC thereby facilitates interaction with PPIE (PubMed:20541251). CC {ECO:0000269|PubMed:20541251, ECO:0000269|PubMed:20677832}. CC -!- PTM: Proteolytic cleavage by TASP1 generates MLL cleavage product N320 CC and MLL cleavage product C180, which reassemble through a non-covalent CC association. 2 cleavage sites exist, cleavage site 1 (CS1) and cleavage CC site 2 (CS2), to generate MLL cleavage products N320 and C180. CS2 is CC the major site. {ECO:0000269|PubMed:12482972, CC ECO:0000269|PubMed:14636557}. CC -!- PTM: Phosphorylation increases its interaction with PSIP1. CC {ECO:0000269|PubMed:29997176}. CC -!- PTM: Auto-methylated at Cys-3882: auto-methylation is inhibited by the CC WRAD complex and unmodified histone H3. {ECO:0000269|PubMed:24235145}. CC -!- DISEASE: Wiedemann-Steiner syndrome (WDSTS) [MIM:605130]: A syndrome CC characterized by hairy elbows (hypertrichosis cubiti), intellectual CC disability, a distinctive facial appearance, and short stature. Facial CC characteristics include long eyelashes, thick or arched eyebrows with a CC lateral flare, and downslanting and vertically narrow palpebral CC fissures. {ECO:0000269|PubMed:22795537}. Note=The disease is caused by CC variants affecting the gene represented in this entry. CC -!- DISEASE: Note=Chromosomal aberrations involving KMT2A are a cause of CC acute leukemias. Translocation t(1;11)(q21;q23) with MLLT11/AF1Q; CC translocation t(3;11)(p21;q23) with NCKIPSD/AF3p21; translocation CC t(3,11)(q25,q23) with GMPS; translocation t(4;11)(q21;q23) with CC AFF1/MLLT2/AF4; insertion ins(5;11)(q31;q13q23) with AFF4/AF5Q31; CC translocation t(5;11)(q12;q23) with AF5-alpha/CENPK; translocation CC t(6;11)(q27;q23) with AFDN; translocation t(9;11)(p22;q23) with CC MLLT3/AF9; translocation t(10;11)(p11.2;q23) with ABI1; translocation CC t(10;11)(p12;q23) with MLLT10/AF10; t(11;15)(q23;q14) with KNL1 and CC ZFYVE19; translocation t(11;17)(q23;q21) with MLLT6/AF17; translocation CC t(11;19)(q23;p13.3) with ELL; translocation t(11;19)(q23;p13.3) with CC MLLT1/ENL; translocation t(11;19)(q23;p23) with GAS7; translocation CC t(X;11)(q13;q23) with FOXO4/AFX1. Translocation t(3;11)(q28;q23) with CC LPP. Translocation t(10;11)(q22;q23) with TET1. Translocation CC t(9;11)(q34;q23) with DAB2IP. Translocation t(4;11)(p12;q23) with FRYL. CC Fusion proteins KMT2A-MLLT1, KMT2A-MLLT3 and KMT2A-ELL interact with CC PPP1R15A and, on the contrary to unfused KMT2A, inhibit PPP1R15A- CC induced apoptosis. Fusion protein KMT2A-MLLT3 interacts with MEN1 and CC PSIP1 (PubMed:22936661, PubMed:25305204). {ECO:0000269|PubMed:10490642, CC ECO:0000269|PubMed:22936661, ECO:0000269|PubMed:25305204}. CC -!- DISEASE: Note=A chromosomal aberration involving KMT2A may be a cause CC of chronic neutrophilic leukemia. Translocation t(4;11)(q21;q23) with CC SEPT11. {ECO:0000269|PubMed:10490642}. CC -!- SIMILARITY: Belongs to the class V-like SAM-binding methyltransferase CC superfamily. Histone-lysine methyltransferase family. TRX/MLL CC subfamily. {ECO:0000255|PROSITE-ProRule:PRU00190}. CC -!- SEQUENCE CAUTION: CC Sequence=AAA58669.1; Type=Frameshift; Evidence={ECO:0000305}; CC Sequence=AAG26332.2; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305}; CC Sequence=BAD92745.1; Type=Frameshift; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/13/kmt2a"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; L04284; AAA58669.1; ALT_FRAME; mRNA. DR EMBL; Z69744; CAA93625.1; -; Genomic_DNA. DR EMBL; Z69745; CAA93625.1; JOINED; Genomic_DNA. DR EMBL; Z69746; CAA93625.1; JOINED; Genomic_DNA. DR EMBL; Z69747; CAA93625.1; JOINED; Genomic_DNA. DR EMBL; Z69748; CAA93625.1; JOINED; Genomic_DNA. DR EMBL; Z69749; CAA93625.1; JOINED; Genomic_DNA. DR EMBL; Z69750; CAA93625.1; JOINED; Genomic_DNA. DR EMBL; Z69751; CAA93625.1; JOINED; Genomic_DNA. DR EMBL; Z69752; CAA93625.1; JOINED; Genomic_DNA. DR EMBL; Z69753; CAA93625.1; JOINED; Genomic_DNA. DR EMBL; Z69754; CAA93625.1; JOINED; Genomic_DNA. DR EMBL; Z69755; CAA93625.1; JOINED; Genomic_DNA. DR EMBL; Z69756; CAA93625.1; JOINED; Genomic_DNA. DR EMBL; Z69757; CAA93625.1; JOINED; Genomic_DNA. DR EMBL; Z69758; CAA93625.1; JOINED; Genomic_DNA. DR EMBL; Z69759; CAA93625.1; JOINED; Genomic_DNA. DR EMBL; Z69760; CAA93625.1; JOINED; Genomic_DNA. DR EMBL; Z69761; CAA93625.1; JOINED; Genomic_DNA. DR EMBL; Z69762; CAA93625.1; JOINED; Genomic_DNA. DR EMBL; Z69763; CAA93625.1; JOINED; Genomic_DNA. DR EMBL; Z69764; CAA93625.1; JOINED; Genomic_DNA. DR EMBL; Z69765; CAA93625.1; JOINED; Genomic_DNA. DR EMBL; Z69766; CAA93625.1; JOINED; Genomic_DNA. DR EMBL; Z69767; CAA93625.1; JOINED; Genomic_DNA. DR EMBL; Z69768; CAA93625.1; JOINED; Genomic_DNA. DR EMBL; Z69769; CAA93625.1; JOINED; Genomic_DNA. DR EMBL; Z69770; CAA93625.1; JOINED; Genomic_DNA. DR EMBL; Z69772; CAA93625.1; JOINED; Genomic_DNA. DR EMBL; Z69773; CAA93625.1; JOINED; Genomic_DNA. DR EMBL; Z69774; CAA93625.1; JOINED; Genomic_DNA. DR EMBL; Z69775; CAA93625.1; JOINED; Genomic_DNA. DR EMBL; Z69776; CAA93625.1; JOINED; Genomic_DNA. DR EMBL; Z69777; CAA93625.1; JOINED; Genomic_DNA. DR EMBL; Z69778; CAA93625.1; JOINED; Genomic_DNA. DR EMBL; Z69779; CAA93625.1; JOINED; Genomic_DNA. DR EMBL; Z69780; CAA93625.1; JOINED; Genomic_DNA. DR EMBL; AY373585; AAQ63624.1; -; Genomic_DNA. DR EMBL; AP000941; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AP001267; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; D14540; BAA03407.1; -; mRNA. DR EMBL; AB209508; BAD92745.1; ALT_FRAME; mRNA. DR EMBL; L04731; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; L01986; AAA92511.1; -; mRNA. DR EMBL; X83604; CAA58584.1; -; Genomic_DNA. DR EMBL; S78570; AAB34770.1; -; mRNA. DR EMBL; U04737; AAA18644.1; -; Genomic_DNA. DR EMBL; S66432; AAB28545.1; -; mRNA. DR EMBL; AF232001; AAG26335.2; -; mRNA. DR EMBL; AF231998; AAG26332.2; ALT_SEQ; mRNA. DR CCDS; CCDS31686.1; -. [Q03164-1] DR CCDS; CCDS55791.1; -. [Q03164-3] DR PIR; A44265; A44265. DR PIR; I52578; I52578. DR PIR; I53035; I53035. DR RefSeq; NP_001184033.1; NM_001197104.2. [Q03164-3] DR RefSeq; NP_005924.2; NM_005933.4. [Q03164-1] DR PDB; 2AGH; NMR; -; C=2840-2869. DR PDB; 2J2S; NMR; -; A=1143-1214. DR PDB; 2JYI; NMR; -; A=1147-1203. DR PDB; 2KKF; NMR; -; A=1147-1203. DR PDB; 2KU7; NMR; -; A=1585-1628. DR PDB; 2KYU; NMR; -; A=1564-1628. DR PDB; 2LXS; NMR; -; B=2840-2858. DR PDB; 2LXT; NMR; -; B=2840-2858. DR PDB; 2MSR; NMR; -; A=140-160. DR PDB; 2MTN; NMR; -; A=110-160. DR PDB; 2W5Y; X-ray; 2.00 A; A=3785-3969. DR PDB; 2W5Z; X-ray; 2.20 A; A=3785-3969. DR PDB; 3EG6; X-ray; 1.72 A; C=3762-3773. DR PDB; 3EMH; X-ray; 1.37 A; B=3764-3776. DR PDB; 3LQH; X-ray; 1.72 A; A=1566-1784. DR PDB; 3LQI; X-ray; 1.92 A; A/B/C=1566-1784. DR PDB; 3LQJ; X-ray; 1.90 A; A/B=1566-1784. DR PDB; 3P4F; X-ray; 2.35 A; C=3761-3770. DR PDB; 3U85; X-ray; 3.00 A; B=6-25. DR PDB; 3U88; X-ray; 3.00 A; M/N=103-153. DR PDB; 4ESG; X-ray; 1.70 A; C/D=3755-3771. DR PDB; 4GQ6; X-ray; 1.55 A; B=6-15. DR PDB; 4NW3; X-ray; 2.82 A; A=1147-1204. DR PDB; 5F5E; X-ray; 1.80 A; A=3813-3969. DR PDB; 5F6L; X-ray; 1.90 A; A=3813-3969. DR PDB; 5SVH; X-ray; 2.05 A; B=2839-2869. DR PDB; 6EMQ; NMR; -; A=111-160. DR PDB; 6KIU; EM; 3.20 A; K=3754-3969. DR PDB; 6KIV; EM; 4.00 A; K=3754-3969. DR PDB; 6KIX; EM; 4.10 A; K=3754-3969. DR PDB; 6KIZ; EM; 4.50 A; K=3754-3969. DR PDB; 6PWV; EM; 6.20 A; C=3762-3969. DR PDB; 6PWW; EM; 4.40 A; C=3762-3969. DR PDB; 6U9K; X-ray; 2.00 A; A/B=3813-3969. DR PDB; 6U9M; X-ray; 2.05 A; A/B=3813-3969. DR PDB; 6U9N; X-ray; 1.95 A; A/B=3813-3969. DR PDB; 6U9R; X-ray; 2.10 A; A/B=3813-3969. DR PDB; 6W5I; EM; 6.90 A; C=3762-3969. DR PDB; 6W5M; EM; 4.60 A; C=3762-3969. DR PDB; 6W5N; EM; 6.00 A; C=3762-3969. DR PDB; 7MBM; EM; -; C=3762-3969. DR PDB; 7MBN; EM; -; C=3762-3969. DR PDB; 7RZD; X-ray; 1.82 A; C=747-755. DR PDB; 7RZJ; X-ray; 1.80 A; E=747-755. DR PDB; 7S79; X-ray; 1.53 A; E=747-755. DR PDB; 7S7D; X-ray; 1.56 A; E=747-755. DR PDB; 7S8A; X-ray; 2.10 A; C=747-755. DR PDB; 7S8E; X-ray; 1.60 A; E=747-755. DR PDB; 7S8F; X-ray; 1.80 A; C=747-755. DR PDB; 7U5V; X-ray; 2.59 A; A=3811-3969. DR PDB; 7W67; X-ray; 2.19 A; C=3813-3969. DR PDB; 7W6A; X-ray; 2.21 A; C=3813-3969. DR PDB; 7W6I; X-ray; 2.56 A; C=3813-3969. DR PDB; 7W6J; X-ray; 2.68 A; C=3813-3969. DR PDB; 7ZEY; NMR; -; B=1564-1627. DR PDB; 7ZEZ; NMR; -; B=1564-1627. DR PDB; 9C4S; X-ray; 1.54 A; B=4-15. DR PDB; 9C4T; X-ray; 1.46 A; B=4-15. DR PDB; 9C4U; X-ray; 1.57 A; B=4-15. DR PDB; 9C4V; X-ray; 1.47 A; B=4-15. DR PDBsum; 2AGH; -. DR PDBsum; 2J2S; -. DR PDBsum; 2JYI; -. DR PDBsum; 2KKF; -. DR PDBsum; 2KU7; -. DR PDBsum; 2KYU; -. DR PDBsum; 2LXS; -. DR PDBsum; 2LXT; -. DR PDBsum; 2MSR; -. DR PDBsum; 2MTN; -. DR PDBsum; 2W5Y; -. DR PDBsum; 2W5Z; -. DR PDBsum; 3EG6; -. DR PDBsum; 3EMH; -. DR PDBsum; 3LQH; -. DR PDBsum; 3LQI; -. DR PDBsum; 3LQJ; -. DR PDBsum; 3P4F; -. DR PDBsum; 3U85; -. DR PDBsum; 3U88; -. DR PDBsum; 4ESG; -. DR PDBsum; 4GQ6; -. DR PDBsum; 4NW3; -. DR PDBsum; 5F5E; -. DR PDBsum; 5F6L; -. DR PDBsum; 5SVH; -. DR PDBsum; 6EMQ; -. DR PDBsum; 6KIU; -. DR PDBsum; 6KIV; -. DR PDBsum; 6KIX; -. DR PDBsum; 6KIZ; -. DR PDBsum; 6PWV; -. DR PDBsum; 6PWW; -. DR PDBsum; 6U9K; -. DR PDBsum; 6U9M; -. DR PDBsum; 6U9N; -. DR PDBsum; 6U9R; -. DR PDBsum; 6W5I; -. DR PDBsum; 6W5M; -. DR PDBsum; 6W5N; -. DR PDBsum; 7MBM; -. DR PDBsum; 7MBN; -. DR PDBsum; 7RZD; -. DR PDBsum; 7RZJ; -. DR PDBsum; 7S79; -. DR PDBsum; 7S7D; -. DR PDBsum; 7S8A; -. DR PDBsum; 7S8E; -. DR PDBsum; 7S8F; -. DR PDBsum; 7U5V; -. DR PDBsum; 7W67; -. DR PDBsum; 7W6A; -. DR PDBsum; 7W6I; -. DR PDBsum; 7W6J; -. DR PDBsum; 7ZEY; -. DR PDBsum; 7ZEZ; -. DR PDBsum; 9C4S; -. DR PDBsum; 9C4T; -. DR PDBsum; 9C4U; -. DR PDBsum; 9C4V; -. DR BMRB; Q03164; -. DR EMDB; EMD-0694; -. DR EMDB; EMD-0695; -. DR EMDB; EMD-20512; -. DR EMDB; EMD-20513; -. DR EMDB; EMD-21542; -. DR EMDB; EMD-21543; -. DR EMDB; EMD-21544; -. DR EMDB; EMD-23738; -. DR EMDB; EMD-23739; -. DR EMDB; EMD-9998; -. DR EMDB; EMD-9999; -. DR SASBDB; Q03164; -. DR SMR; Q03164; -. DR BioGRID; 110443; 318. DR ComplexPortal; CPX-5850; Histone-lysine N-methyltransferase complex, KMT2A variant. DR CORUM; Q03164; -. DR DIP; DIP-29221N; -. DR ELM; Q03164; -. DR FunCoup; Q03164; 3961. DR IntAct; Q03164; 132. DR MINT; Q03164; -. DR STRING; 9606.ENSP00000436786; -. DR BindingDB; Q03164; -. DR ChEMBL; CHEMBL1293299; -. DR CarbonylDB; Q03164; -. DR GlyConnect; 2046; 1 N-Linked glycan (1 site). DR GlyCosmos; Q03164; 17 sites, 4 glycans. DR GlyGen; Q03164; 46 sites, 4 N-linked glycans (3 sites), 2 O-linked glycans (34 sites). DR iPTMnet; Q03164; -. DR PhosphoSitePlus; Q03164; -. DR SwissPalm; Q03164; -. DR BioMuta; KMT2A; -. DR DMDM; 146345435; -. DR jPOST; Q03164; -. DR MassIVE; Q03164; -. DR PaxDb; 9606-ENSP00000436786; -. DR PeptideAtlas; Q03164; -. DR ProteomicsDB; 23014; -. DR ProteomicsDB; 58195; -. [Q03164-1] DR ProteomicsDB; 58196; -. [Q03164-2] DR Pumba; Q03164; -. DR Antibodypedia; 18629; 476 antibodies from 36 providers. DR DNASU; 4297; -. DR Ensembl; ENST00000389506.10; ENSP00000374157.5; ENSG00000118058.26. [Q03164-1] DR Ensembl; ENST00000534358.8; ENSP00000436786.2; ENSG00000118058.26. [Q03164-3] DR Ensembl; ENST00000649699.1; ENSP00000496927.1; ENSG00000118058.26. [Q03164-2] DR GeneID; 4297; -. DR KEGG; hsa:4297; -. DR MANE-Select; ENST00000534358.8; ENSP00000436786.2; NM_001197104.2; NP_001184033.1. [Q03164-3] DR UCSC; uc001pta.4; human. [Q03164-1] DR AGR; HGNC:7132; -. DR CIViC; 4297; 1 clinical assertion and 7 evidence items across 7 molecular profiles. DR ClinPGx; PA241; -. DR CTD; 4297; -. DR DisGeNET; 4297; -. DR GeneCards; KMT2A; -. DR GeneReviews; KMT2A; -. DR HGNC; HGNC:7132; KMT2A. DR HPA; ENSG00000118058; Low tissue specificity. DR MalaCards; KMT2A; -. DR MIM; 159555; gene+phenotype. DR MIM; 605130; phenotype. DR OpenTargets; ENSG00000118058; -. DR Orphanet; 98831; Acute myeloid leukemia with 11q23 abnormalities. DR Orphanet; 402017; Acute myeloid leukemia with t(9;11)(p22;q23). DR Orphanet; 98835; Acute undifferentiated leukemia. DR Orphanet; 585918; B-lymphoblastic leukemia/lymphoma with t(v;11q23.3). DR Orphanet; 589534; Mixed phenotype acute leukemia with t(9;22)(q34.1;q11.2). DR Orphanet; 589595; Mixed phenotype acute leukemia with t(v;11q23.3). DR Orphanet; 319182; Wiedemann-Steiner syndrome. DR VEuPathDB; HostDB:ENSG00000118058; -. DR eggNOG; KOG1084; Eukaryota. DR GeneTree; ENSGT00940000160099; -. DR HOGENOM; CLU_000208_2_0_1; -. DR InParanoid; Q03164; -. DR OMA; VVRSQQW; -. DR OrthoDB; 308383at2759; -. DR PAN-GO; Q03164; 4 GO annotations based on evolutionary models. DR PhylomeDB; Q03164; -. DR BioCyc; MetaCyc:HS04188-MONOMER; -. DR PathwayCommons; Q03164; -. DR Reactome; R-HSA-3214841; PKMTs methylate histone lysines. DR Reactome; R-HSA-8936459; RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function. DR Reactome; R-HSA-8939236; RUNX1 regulates transcription of genes involved in differentiation of HSCs. DR Reactome; R-HSA-9616222; Transcriptional regulation of granulopoiesis. DR Reactome; R-HSA-9772755; Formation of WDR5-containing histone-modifying complexes. DR Reactome; R-HSA-9931510; Phosphorylated BMAL1:CLOCK (ARNTL:CLOCK) activates expression of core clock genes. DR Reactome; R-HSA-9931512; Phosphorylation of CLOCK, acetylation of BMAL1 (ARNTL) at target gene promoters. DR Reactome; R-HSA-9931521; The CRY:PER:kinase complex represses transactivation by the BMAL:CLOCK (ARNTL:CLOCK) complex. DR SignaLink; Q03164; -. DR SIGNOR; Q03164; -. DR Agora; ENSG00000118058; -. DR BioGRID-ORCS; 4297; 127 hits in 1158 CRISPR screens. DR CD-CODE; 91857CE7; Nucleolus. DR ChiTaRS; KMT2A; human. DR EvolutionaryTrace; Q03164; -. DR GeneWiki; MLL_(gene); -. DR GenomeRNAi; 4297; -. DR Pharos; Q03164; Tchem. DR PRO; PR:Q03164; -. DR Proteomes; UP000005640; Chromosome 11. DR RNAct; Q03164; protein. DR Bgee; ENSG00000118058; Expressed in ventricular zone and 215 other cell types or tissues. DR ExpressionAtlas; Q03164; baseline and differential. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0035097; C:histone methyltransferase complex; IDA:UniProtKB. DR GO; GO:0071339; C:MLL1 complex; IDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0003682; F:chromatin binding; IEA:Ensembl. DR GO; GO:0042800; F:histone H3K4 methyltransferase activity; IDA:UniProtKB. DR GO; GO:0140945; F:histone H3K4 monomethyltransferase activity; IEA:UniProtKB-EC. DR GO; GO:0140999; F:histone H3K4 trimethyltransferase activity; IDA:BHF-UCL. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0003680; F:minor groove of adenine-thymine-rich DNA binding; NAS:UniProtKB. DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB. DR GO; GO:0106363; F:protein-cysteine methyltransferase activity; IDA:UniProtKB. DR GO; GO:0045322; F:unmethylated CpG binding; IDA:UniProtKB. DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB. DR GO; GO:0009952; P:anterior/posterior pattern specification; IEA:Ensembl. DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW. DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; IEA:Ensembl. DR GO; GO:0032922; P:circadian regulation of gene expression; ISS:UniProtKB. DR GO; GO:0060216; P:definitive hemopoiesis; IEA:Ensembl. DR GO; GO:0035162; P:embryonic hemopoiesis; TAS:UniProtKB. DR GO; GO:0035640; P:exploration behavior; IEA:Ensembl. DR GO; GO:0048144; P:fibroblast proliferation; IEA:Ensembl. DR GO; GO:0048873; P:homeostasis of number of cells within a tissue; IEA:Ensembl. DR GO; GO:0051899; P:membrane depolarization; IEA:Ensembl. DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW. DR GO; GO:0090310; P:negative regulation of DNA methylation-dependent heterochromatin formation; IMP:UniProtKB. DR GO; GO:0048147; P:negative regulation of fibroblast proliferation; IEA:Ensembl. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IMP:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL. DR GO; GO:0009791; P:post-embryonic development; IEA:Ensembl. DR GO; GO:0065003; P:protein-containing complex assembly; IDA:UniProtKB. DR GO; GO:0048172; P:regulation of short-term neuronal synaptic plasticity; IEA:Ensembl. DR GO; GO:0035864; P:response to potassium ion; IEA:Ensembl. DR GO; GO:0048536; P:spleen development; IEA:Ensembl. DR GO; GO:0045064; P:T-helper 2 cell differentiation; IDA:UniProtKB. DR GO; GO:0045815; P:transcription initiation-coupled chromatin remodeling; IDA:UniProtKB. DR GO; GO:0008542; P:visual learning; IEA:Ensembl. DR CDD; cd05493; Bromo_ALL-1; 1. DR CDD; cd15693; ePHD_KMT2A; 1. DR CDD; cd15588; PHD1_KMT2A; 1. DR CDD; cd15590; PHD2_KMT2A; 1. DR CDD; cd15592; PHD3_KMT2A; 1. DR CDD; cd19170; SET_KMT2A_2B; 1. DR DisProt; DP01116; -. DR FunFam; 3.30.160.360:FF:000002; Histone-lysine N-methyltransferase; 1. DR FunFam; 3.30.160.360:FF:000003; Histone-lysine N-methyltransferase; 1. DR FunFam; 3.30.40.10:FF:000002; Histone-lysine N-methyltransferase; 1. DR FunFam; 3.30.40.10:FF:000071; Histone-lysine N-methyltransferase; 1. DR FunFam; 3.30.40.10:FF:000089; Histone-lysine N-methyltransferase; 1. DR FunFam; 2.170.270.10:FF:000149; Myeloid/lymphoid or mixed-lineage leukemia; 1. DR Gene3D; 3.30.160.360; -; 2. DR Gene3D; 6.10.250.2390; -; 1. DR Gene3D; 1.20.920.10; Bromodomain-like; 1. DR Gene3D; 2.170.270.10; SET domain; 1. DR Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 3. DR IDEAL; IID00379; -. DR InterPro; IPR001487; Bromodomain. DR InterPro; IPR036427; Bromodomain-like_sf. DR InterPro; IPR034732; EPHD. DR InterPro; IPR003889; FYrich_C. DR InterPro; IPR003888; FYrich_N. DR InterPro; IPR047219; KMT2A_2B_SET. DR InterPro; IPR041958; KMT2A_ePHD. DR InterPro; IPR042023; KMT2A_PHD1. DR InterPro; IPR042025; KMT2A_PHD2. DR InterPro; IPR044133; KMT2A_PHD3. DR InterPro; IPR016569; MeTrfase_trithorax. DR InterPro; IPR003616; Post-SET_dom. DR InterPro; IPR001214; SET_dom. DR InterPro; IPR046341; SET_dom_sf. DR InterPro; IPR002857; Znf_CXXC. DR InterPro; IPR011011; Znf_FYVE_PHD. DR InterPro; IPR001965; Znf_PHD. DR InterPro; IPR019787; Znf_PHD-finger. DR InterPro; IPR013083; Znf_RING/FYVE/PHD. DR PANTHER; PTHR45838:SF2; HISTONE-LYSINE N-METHYLTRANSFERASE 2A; 1. DR PANTHER; PTHR45838; HISTONE-LYSINE-N-METHYLTRANSFERASE 2 KMT2 FAMILY MEMBER; 1. DR Pfam; PF05965; FYRC; 1. DR Pfam; PF05964; FYRN; 1. DR Pfam; PF00628; PHD; 2. DR Pfam; PF00856; SET; 1. DR Pfam; PF02008; zf-CXXC; 1. DR Pfam; PF13771; zf-HC5HC2H; 1. DR PIRSF; PIRSF010354; Methyltransferase_trithorax; 1. DR SMART; SM00297; BROMO; 1. DR SMART; SM00542; FYRC; 1. DR SMART; SM00541; FYRN; 1. DR SMART; SM00249; PHD; 4. DR SMART; SM00508; PostSET; 1. DR SMART; SM00317; SET; 1. DR SUPFAM; SSF47370; Bromodomain; 1. DR SUPFAM; SSF57903; FYVE/PHD zinc finger; 2. DR SUPFAM; SSF82199; SET domain; 1. DR PROSITE; PS50014; BROMODOMAIN_2; 1. DR PROSITE; PS51805; EPHD; 1. DR PROSITE; PS51543; FYRC; 1. DR PROSITE; PS51542; FYRN; 1. DR PROSITE; PS50868; POST_SET; 1. DR PROSITE; PS50280; SET; 1. DR PROSITE; PS51058; ZF_CXXC; 1. DR PROSITE; PS01359; ZF_PHD_1; 3. DR PROSITE; PS50016; ZF_PHD_2; 3. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Apoptosis; KW Biological rhythms; Bromodomain; Chromatin regulator; KW Chromosomal rearrangement; Direct protein sequencing; DNA-binding; KW Host-virus interaction; Isopeptide bond; Metal-binding; Methylation; KW Methyltransferase; Nucleus; Phosphoprotein; Proteomics identification; KW Proto-oncogene; Reference proteome; Repeat; S-adenosyl-L-methionine; KW Transcription; Transcription regulation; Transferase; Ubl conjugation; KW Zinc; Zinc-finger. FT CHAIN 1..3969 FT /note="Histone-lysine N-methyltransferase 2A" FT /id="PRO_0000124876" FT CHAIN 1..2718 FT /note="MLL cleavage product N320" FT /evidence="ECO:0000305|PubMed:12482972, FT ECO:0000305|PubMed:14636557" FT /id="PRO_0000390949" FT CHAIN 2719..3969 FT /note="MLL cleavage product C180" FT /evidence="ECO:0000305|PubMed:12482972, FT ECO:0000305|PubMed:14636557" FT /id="PRO_0000390950" FT DOMAIN 1635..1765 FT /note="Bromo" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00035" FT DOMAIN 2018..2074 FT /note="FYR N-terminal" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00875" FT DOMAIN 3666..3747 FT /note="FYR C-terminal" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00876" FT DOMAIN 3829..3945 FT /note="SET" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190" FT DOMAIN 3953..3969 FT /note="Post-SET" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00155" FT DNA_BIND 169..180 FT /note="A.T hook 1" FT DNA_BIND 217..227 FT /note="A.T hook 2" FT DNA_BIND 301..309 FT /note="A.T hook 3" FT ZN_FING 1147..1195 FT /note="CXXC-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509, FT ECO:0000269|PubMed:29276034" FT ZN_FING 1431..1482 FT /note="PHD-type 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00146" FT ZN_FING 1479..1533 FT /note="PHD-type 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00146" FT ZN_FING 1566..1627 FT /note="PHD-type 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00146" FT ZN_FING 1870..1910 FT /note="C2HC pre-PHD-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01146" FT ZN_FING 1931..1978 FT /note="PHD-type 4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01146" FT REGION 1..108 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 132..253 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 301..352 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 445..585 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 713..780 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 798..949 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1038..1066 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1106..1166 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1200..1375 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1584..1600 FT /note="Interaction with histone H3K4me3" FT /evidence="ECO:0000269|PubMed:20677832" FT REGION 1663..1713 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1806..1869 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 2081..2133 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 2145..2232 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 2275..2333 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 2373..2460 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 2475..2618 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 2647..2675 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 2713..2821 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 2961..3064 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 3166..3244 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 3464..3608 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 3620..3643 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 3785..3808 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 6..25 FT /note="Menin-binding motif (MBM)" FT /evidence="ECO:0000269|PubMed:22327296" FT MOTIF 123..134 FT /note="Integrase domain-binding motif 1 (IBM1)" FT /evidence="ECO:0000269|PubMed:25305204" FT MOTIF 147..152 FT /note="Integrase domain-binding motif 2 (IBM2)" FT /evidence="ECO:0000269|PubMed:25305204" FT MOTIF 2847..2855 FT /note="9aaTAD" FT /evidence="ECO:0000269|PubMed:17467953" FT MOTIF 3762..3767 FT /note="WDR5 interaction motif (WIN)" FT /evidence="ECO:0000269|PubMed:18829459, FT ECO:0000269|PubMed:22665483" FT COMPBIAS 15..29 FT /note="Gly residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 59..69 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 77..104 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 202..220 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 237..253 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 323..347 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 452..491 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 546..559 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 560..573 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 716..732 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 762..780 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 798..808 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 820..841 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 846..890 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1043..1062 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1220..1232 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1233..1243 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1248..1273 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1284..1300 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1304..1313 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1826..1847 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 2095..2115 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 2214..2232 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 2283..2302 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 2310..2319 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 2406..2421 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 2432..2442 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 2543..2563 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 2573..2592 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 2726..2741 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 2744..2782 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 2784..2795 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 2796..2805 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 2812..2821 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 2963..2972 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 3016..3030 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 3039..3064 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 3171..3182 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 3198..3216 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 3218..3233 FT /note="Basic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 3476..3489 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 3508..3529 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 3591..3603 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 1155 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509, FT ECO:0000269|PubMed:29276034, ECO:0007744|PDB:4NW3" FT BINDING 1158 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509, FT ECO:0000269|PubMed:29276034, ECO:0007744|PDB:4NW3" FT BINDING 1161 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509, FT ECO:0000269|PubMed:29276034, ECO:0007744|PDB:4NW3" FT BINDING 1167 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509, FT ECO:0000269|PubMed:29276034, ECO:0007744|PDB:4NW3" FT BINDING 1170 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509, FT ECO:0000269|PubMed:29276034, ECO:0007744|PDB:4NW3" FT BINDING 1173 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509, FT ECO:0000269|PubMed:29276034, ECO:0007744|PDB:4NW3" FT BINDING 1189 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509, FT ECO:0000269|PubMed:29276034, ECO:0007744|PDB:4NW3" FT BINDING 1194 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509, FT ECO:0000269|PubMed:29276034, ECO:0007744|PDB:4NW3" FT BINDING 3839 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190, FT ECO:0000269|PubMed:19187761, ECO:0000269|PubMed:26886794, FT ECO:0007744|PDB:2W5Y, ECO:0007744|PDB:5F5E, FT ECO:0007744|PDB:5F6L" FT BINDING 3841 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190, FT ECO:0000269|PubMed:19187761, ECO:0000269|PubMed:26886794, FT ECO:0007744|PDB:2W5Y, ECO:0007744|PDB:5F5E, FT ECO:0007744|PDB:5F6L" FT BINDING 3883 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190, FT ECO:0000269|PubMed:19187761, ECO:0000269|PubMed:26886794, FT ECO:0007744|PDB:2W5Z, ECO:0007744|PDB:5F5E" FT BINDING 3906..3907 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000269|PubMed:19187761, FT ECO:0000269|PubMed:26886794, ECO:0007744|PDB:2W5Y, FT ECO:0007744|PDB:5F5E, ECO:0007744|PDB:5F6L" FT BINDING 3909 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000269|PubMed:16990798, FT ECO:0000269|PubMed:19187761, ECO:0007744|PDB:2W5Y, FT ECO:0007744|PDB:2W5Z, ECO:0007744|PDB:5F5E, FT ECO:0007744|PDB:5F6L" FT BINDING 3957 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000269|PubMed:16990798, FT ECO:0000269|PubMed:19187761, ECO:0007744|PDB:2W5Y, FT ECO:0007744|PDB:2W5Z, ECO:0007744|PDB:5F5E, FT ECO:0007744|PDB:5F6L" FT BINDING 3958 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190, FT ECO:0000269|PubMed:19187761, ECO:0000269|PubMed:26886794, FT ECO:0007744|PDB:2W5Y, ECO:0007744|PDB:5F5E, FT ECO:0007744|PDB:5F6L" FT BINDING 3959 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000269|PubMed:16990798, FT ECO:0000269|PubMed:19187761, ECO:0007744|PDB:2W5Y, FT ECO:0007744|PDB:2W5Z, ECO:0007744|PDB:5F5E, FT ECO:0007744|PDB:5F6L" FT BINDING 3964 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000269|PubMed:16990798, FT ECO:0000269|PubMed:19187761, ECO:0007744|PDB:2W5Y, FT ECO:0007744|PDB:2W5Z, ECO:0007744|PDB:5F6L" FT SITE 1334..1335 FT /note="Breakpoint for translocation to form KMT2A-ZFYVE19 FT oncogene" FT SITE 1362..1363 FT /note="Breakpoint for translocation to form KMT2A-AF3P21 FT and KMT2A-KNL1 oncogenes" FT SITE 1362..1363 FT /note="Breakpoint for translocation to form KMT2A-CENPK FT oncogene" FT SITE 1362 FT /note="Breakpoint for translocation to form KMT2A-FRYL FT fusion protein" FT SITE 1406..1407 FT /note="Breakpoint for translocation to form KMT2A-AFF4 FT fusion protein" FT SITE 1444..1445 FT /note="Breakpoint for translocation to form KMT2A-GAS7 FT oncogene" FT SITE 1444..1445 FT /note="Breakpoint for translocation to form KMT2A-LPP" FT SITE 2666..2667 FT /note="Cleavage; by TASP1, site 1" FT /evidence="ECO:0000269|PubMed:14636557" FT SITE 2718..2719 FT /note="Cleavage; by TASP1, site 2" FT /evidence="ECO:0000269|PubMed:14636557" FT SITE 3765 FT /note="Important for WDR5-recognition and binding" FT /evidence="ECO:0000269|PubMed:19556245" FT MOD_RES 136 FT /note="Phosphoserine; by CK2" FT /evidence="ECO:0000269|PubMed:29997176" FT MOD_RES 142 FT /note="Phosphoserine; by CK2" FT /evidence="ECO:0000269|PubMed:29997176" FT MOD_RES 153 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:29997176, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:20068231" FT MOD_RES 197 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:20068231" FT MOD_RES 239 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P55200" FT MOD_RES 373 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P55200" FT MOD_RES 518 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 636 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 680 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 840 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 926 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231" FT MOD_RES 1056 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 1130 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 1235 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 1837 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 1845 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 1858 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19369195, FT ECO:0007744|PubMed:23186163" FT MOD_RES 2098 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163" FT MOD_RES 2147 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 2151 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 2201 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692" FT MOD_RES 2525 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT MOD_RES 2611 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 2796 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 2955 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163" FT MOD_RES 2958 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P55200" FT MOD_RES 3036 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT MOD_RES 3372 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:20068231" FT MOD_RES 3462 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P55200" FT MOD_RES 3511 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT MOD_RES 3515 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19690332" FT MOD_RES 3527 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 3882 FT /note="S-methylcysteine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:24235145" FT CROSSLNK 2528 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT VAR_SEQ 1407..1444 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:7598802" FT /id="VSP_006666" FT VAR_SEQ 1603 FT /note="S -> SGTE (in isoform 3)" FT /evidence="ECO:0000303|PubMed:10706619, FT ECO:0000303|PubMed:1423625" FT /id="VSP_046879" FT VARIANT 30 FT /note="A -> G (in dbSNP:rs9332745)" FT /evidence="ECO:0000269|PubMed:8703835" FT /id="VAR_021317" FT VARIANT 53 FT /note="A -> V (in dbSNP:rs9332747)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_021318" FT VARIANT 502 FT /note="E -> K (in dbSNP:rs9332772)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_021319" FT VARIANT 1975 FT /note="Q -> P (in dbSNP:rs693598)" FT /id="VAR_052652" FT VARIANT 2319 FT /note="S -> T (in dbSNP:rs9332837)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_021320" FT VARIANT 2354 FT /note="P -> R (in dbSNP:rs9332838)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_021321" FT VARIANT 2387 FT /note="Q -> R (in dbSNP:rs9332839)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_021322" FT VARIANT 3714 FT /note="V -> I (in dbSNP:rs9332859)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_021323" FT VARIANT 3773 FT /note="S -> A (in dbSNP:rs9332861)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_021324" FT MUTAGEN 6 FT /note="R->A: Reduced interaction with MEN1." FT /evidence="ECO:0000269|PubMed:22327296" FT MUTAGEN 7 FT /note="W->A: Reduced interaction with MEN1." FT /evidence="ECO:0000269|PubMed:22327296" FT MUTAGEN 8 FT /note="R->A: Reduced interaction with MEN1." FT /evidence="ECO:0000269|PubMed:22327296" FT MUTAGEN 9 FT /note="F->A: Loss of interaction with MEN1." FT /evidence="ECO:0000269|PubMed:22327296" FT MUTAGEN 9 FT /note="F->H,Y: Reduced interaction with MEN1." FT /evidence="ECO:0000269|PubMed:22327296" FT MUTAGEN 10 FT /note="P->A: Reduced interaction with MEN1." FT /evidence="ECO:0000269|PubMed:22327296" FT MUTAGEN 11 FT /note="A->R: Reduced interaction with MEN1." FT /evidence="ECO:0000269|PubMed:22327296" FT MUTAGEN 12 FT /note="R->A: Reduced interaction with MEN1." FT /evidence="ECO:0000269|PubMed:22327296" FT MUTAGEN 13 FT /note="P->A: Reduced interaction with MEN1." FT /evidence="ECO:0000269|PubMed:22327296" FT MUTAGEN 24 FT /note="R->E: Reduced interaction with MEN1; when associated FT with E-25." FT /evidence="ECO:0000269|PubMed:22327296" FT MUTAGEN 25 FT /note="R->E: Reduced interaction with MEN1; when associated FT with E-24." FT /evidence="ECO:0000269|PubMed:22327296" FT MUTAGEN 129 FT /note="F->A: Weakly affects interaction with PSIP1 whereas FT significantly decreases interaction of KMT2A-MEN1 complex FT with PSIP1. Reduced interaction with PSIP1; when associated FT with A-133." FT /evidence="ECO:0000269|PubMed:25082813, FT ECO:0000269|PubMed:25305204" FT MUTAGEN 132 FT /note="V->A: Reduced interaction with PSIP1; when FT associated with A-133." FT /evidence="ECO:0000269|PubMed:29997176" FT MUTAGEN 133 FT /note="F->A: Reduced interaction with PSIP1; when FT associated with A-129 or A-132." FT /evidence="ECO:0000269|PubMed:25082813, FT ECO:0000269|PubMed:29997176" FT MUTAGEN 136 FT /note="S->D: Phosphomimetic mutant. Significant increase in FT interaction with PSIP1; when associated with D-142." FT /evidence="ECO:0000269|PubMed:29997176" FT MUTAGEN 142 FT /note="S->D: Phosphomimetic mutant. Significant increase in FT interaction with PSIP1; when associated with D-136." FT /evidence="ECO:0000269|PubMed:29997176" FT MUTAGEN 144 FT /note="E->Q: Loss of interaction with PSIP1; when FT associated with Q-146 and A-148." FT /evidence="ECO:0000269|PubMed:25082813" FT MUTAGEN 146 FT /note="E->Q: Loss of interaction with PSIP1; when FT associated with Q-144 and A-148." FT /evidence="ECO:0000269|PubMed:25082813" FT MUTAGEN 148 FT /note="F->A: Reduced interaction with PSIP1. Loss of FT interaction with PSIP1; when associated with A-149 or Q-144 FT and Q-146." FT /evidence="ECO:0000269|PubMed:25082813, FT ECO:0000269|PubMed:25305204" FT MUTAGEN 149 FT /note="L->A: Loss of interaction with PSIP1; when FT associated with A-148." FT /evidence="ECO:0000269|PubMed:25305204" FT MUTAGEN 151 FT /note="F->A: Reduced interaction with PSIP1." FT /evidence="ECO:0000269|PubMed:25082813" FT MUTAGEN 1150 FT /note="R->A: Impairs DNA-binding." FT /evidence="ECO:0000269|PubMed:20010842" FT MUTAGEN 1151 FT /note="R->A: Impairs DNA-binding." FT /evidence="ECO:0000269|PubMed:16990798" FT MUTAGEN 1153 FT /note="R->A: No effect on stability or DNA-binding." FT /evidence="ECO:0000269|PubMed:16990798" FT MUTAGEN 1154 FT /note="R->A: Impairs DNA-binding." FT /evidence="ECO:0000269|PubMed:16990798, FT ECO:0000269|PubMed:20010842" FT MUTAGEN 1155 FT /note="C->A: Abolishes zinc-binding and stability of the FT CXXC-type zinc finger and causes loss of DNA-binding." FT /evidence="ECO:0000269|PubMed:16990798" FT MUTAGEN 1158 FT /note="C->A: Abolishes zinc-binding and stability of the FT CXXC-type zinc finger and causes loss of DNA-binding." FT /evidence="ECO:0000269|PubMed:16990798" FT MUTAGEN 1161 FT /note="C->A: Abolishes zinc-binding and stability of the FT CXXC-type zinc finger and causes loss of DNA-binding." FT /evidence="ECO:0000269|PubMed:16990798" FT MUTAGEN 1162 FT /note="Q->A: No effect on stability or DNA-binding." FT /evidence="ECO:0000269|PubMed:16990798" FT MUTAGEN 1166 FT /note="D->A: Abolishes zinc-binding and stability of the FT CXXC-type zinc finger and causes loss of DNA-binding." FT /evidence="ECO:0000269|PubMed:16990798" FT MUTAGEN 1167 FT /note="C->A: Abolishes zinc-binding and stability of the FT CXXC-type zinc finger and causes loss of DNA-binding." FT /evidence="ECO:0000269|PubMed:16990798" FT MUTAGEN 1170 FT /note="C->A: Abolishes zinc-binding and stability of the FT CXXC-type zinc finger and causes loss of DNA-binding." FT /evidence="ECO:0000269|PubMed:16990798" FT MUTAGEN 1172 FT /note="N->A: No effect on stability or DNA-binding." FT /evidence="ECO:0000269|PubMed:16990798" FT MUTAGEN 1173 FT /note="C->A: Abolishes zinc-binding and stability of the FT CXXC-type zinc finger and causes loss of DNA-binding." FT /evidence="ECO:0000269|PubMed:16990798" FT MUTAGEN 1175 FT /note="D->A: Impairs DNA-binding." FT /evidence="ECO:0000269|PubMed:16990798" FT MUTAGEN 1176 FT /note="K->A: Impairs DNA-binding." FT /evidence="ECO:0000269|PubMed:16990798" FT MUTAGEN 1178..1181 FT /note="KFGG->AAAA: Abolishes zinc-binding and stability of FT the CXXC-type zinc finger and causes loss of DNA-binding." FT /evidence="ECO:0000269|PubMed:16990798" FT MUTAGEN 1178 FT /note="K->A: Impairs DNA-binding." FT /evidence="ECO:0000269|PubMed:16990798" FT MUTAGEN 1179 FT /note="F->A: Impairs DNA-binding." FT /evidence="ECO:0000269|PubMed:16990798" FT MUTAGEN 1183 FT /note="N->A: Impairs DNA-binding." FT /evidence="ECO:0000269|PubMed:16990798" FT MUTAGEN 1185 FT /note="K->A: Impairs DNA-binding." FT /evidence="ECO:0000269|PubMed:16990798, FT ECO:0000269|PubMed:20010842" FT MUTAGEN 1186 FT /note="K->A: Impairs DNA-binding." FT /evidence="ECO:0000269|PubMed:16990798" FT MUTAGEN 1187 FT /note="Q->A: Impairs DNA-binding." FT /evidence="ECO:0000269|PubMed:16990798, FT ECO:0000269|PubMed:20010842" FT MUTAGEN 1188 FT /note="C->A: No effect on stability or DNA-binding." FT /evidence="ECO:0000269|PubMed:16990798, FT ECO:0000269|PubMed:20010842" FT MUTAGEN 1188 FT /note="C->D: Abolishes DNA-binding and increases CpG FT methylation of the HOXA9 promoter region. Does not lead to FT the development of leukemia when overexpressed in mice as FT gene fusion with MLLT3." FT /evidence="ECO:0000269|PubMed:20010842" FT MUTAGEN 1189 FT /note="C->A: Abolishes zinc-binding and stability of the FT CXXC-type zinc finger and causes loss of DNA-binding." FT /evidence="ECO:0000269|PubMed:16990798" FT MUTAGEN 1192 FT /note="R->A: Abolishes zinc-binding and stability of the FT CXXC-type zinc finger and causes loss of DNA-binding." FT /evidence="ECO:0000269|PubMed:16990798" FT MUTAGEN 1193 FT /note="K->A: Impairs DNA-binding." FT /evidence="ECO:0000269|PubMed:16990798, FT ECO:0000269|PubMed:20010842" FT MUTAGEN 1194 FT /note="C->A: Impairs zinc-binding and stability of the FT CXXC-type zinc finger and causes loss of DNA-binding." FT /evidence="ECO:0000269|PubMed:16990798" FT MUTAGEN 1195 FT /note="Q->A: No effect on stability or DNA-binding." FT /evidence="ECO:0000269|PubMed:16990798" FT MUTAGEN 1196 FT /note="N->A: No effect on stability or DNA-binding." FT /evidence="ECO:0000269|PubMed:16990798" FT MUTAGEN 1197 FT /note="L->A: Mildly decreases DNA-binding." FT /evidence="ECO:0000269|PubMed:20010842" FT MUTAGEN 1200 FT /note="M->A: No effect on DNA-binding." FT /evidence="ECO:0000269|PubMed:20010842" FT MUTAGEN 1581 FT /note="Y->A: Decreases affinity for histone H3K4me3." FT /evidence="ECO:0000269|PubMed:20541251" FT MUTAGEN 1587 FT /note="Q->A: Decreases affinity for histone H3K4me3." FT /evidence="ECO:0000269|PubMed:20541251" FT MUTAGEN 1594 FT /note="W->A: Abolishes interaction with histone H3K4me3." FT /evidence="ECO:0000269|PubMed:20677832" FT MUTAGEN 1594 FT /note="W->E: Decreases affinity for histone H3K4me3." FT /evidence="ECO:0000269|PubMed:20541251" FT MUTAGEN 1617 FT /note="V->A: Decreases binding affinity for PPIE." FT /evidence="ECO:0000269|PubMed:20677832" FT MUTAGEN 1619 FT /note="Y->A: May perturb protein folding and thereby FT decrease binding affinity for PPIE." FT /evidence="ECO:0000269|PubMed:20677832" FT MUTAGEN 2666..2667 FT /note="DG->AA: Reduces cleavage without abolishing it. FT Abolishes cleavage by TASP1; when associated with 2718-A-- FT A-2720." FT /evidence="ECO:0000269|PubMed:14636557" FT MUTAGEN 2718..2720 FT /note="DGV->AAA: Abolishes cleavage by TASP1; when FT associated with 2666-A-A-2667." FT /evidence="ECO:0000269|PubMed:12482972, FT ECO:0000269|PubMed:14636557" FT MUTAGEN 3763 FT /note="S->A: Increased interaction with WDR5." FT /evidence="ECO:0000269|PubMed:22665483" FT MUTAGEN 3765 FT /note="R->A: Loss of interaction with the WRAD complex and FT WDR5." FT /evidence="ECO:0000269|PubMed:18840606, FT ECO:0000269|PubMed:22665483" FT MUTAGEN 3769 FT /note="H->A,F: Slight decrease in interaction with WDR5." FT /evidence="ECO:0000269|PubMed:18840606" FT MUTAGEN 3769 FT /note="H->Y: Increased interaction with WDR5." FT /evidence="ECO:0000269|PubMed:22665483" FT MUTAGEN 3858 FT /note="Y->A: Impairs methyltransferase activity toward FT unmodified or monomethylated H3K4me." FT /evidence="ECO:0000269|PubMed:19187761" FT MUTAGEN 3858 FT /note="Y->F: Slightly affects methyltransferase activity FT toward unmodified or monomethylated H3K4me." FT /evidence="ECO:0000269|PubMed:19187761" FT MUTAGEN 3861 FT /note="N->I: Leads to stable interaction with ASH2L and FT RBBP5 in the absence of WDR5; when associated with L-3867." FT /evidence="ECO:0000269|PubMed:26886794" FT MUTAGEN 3861 FT /note="N->T: Leads to stable interaction with ASH2L and FT RBBP5 in the absence of WDR5; when associated with V-3867." FT /evidence="ECO:0000269|PubMed:26886794" FT MUTAGEN 3864 FT /note="R->A: Disrupts interaction with ASH2L and RBBP5 and FT nearly abolishes histone methyltransferase activity." FT /evidence="ECO:0000269|PubMed:26886794" FT MUTAGEN 3867 FT /note="Q->A: Slightly affects methyltransferase activity of FT the enzyme alone, while it impairs methyltransferase FT activity in complex; when associated with A-3871." FT /evidence="ECO:0000269|PubMed:19187761" FT MUTAGEN 3867 FT /note="Q->L: Leads to stable interaction with ASH2L and FT RBBP5 in the absence of WDR5; when associated with I-3861." FT /evidence="ECO:0000269|PubMed:26886794" FT MUTAGEN 3867 FT /note="Q->V: Leads to stable interaction with ASH2L and FT RBBP5 in the absence of WDR5; when associated with T-3861." FT /evidence="ECO:0000269|PubMed:26886794" FT MUTAGEN 3869 FT /note="D->A: Does not affect methyltransferase activity of FT the enzyme alone or in complex; when associated with A- FT 3872." FT /evidence="ECO:0000269|PubMed:19187761" FT MUTAGEN 3871 FT /note="R->A: Slightly affects methyltransferase activity of FT the enzyme alone, while it impairs methyltransferase FT activity in complex; when associated with A-3867." FT /evidence="ECO:0000269|PubMed:19187761" FT MUTAGEN 3872 FT /note="E->A: Does not affect methyltransferase activity of FT the enzyme alone or in complex; when associated with A- FT 3869." FT /evidence="ECO:0000269|PubMed:19187761" FT MUTAGEN 3874 FT /note="Y->A: Affects methyltransferase activity of the FT enzyme alone, while it does not affect methyltransferase FT activity in complex; when associated with A-3878." FT /evidence="ECO:0000269|PubMed:19187761" FT MUTAGEN 3878 FT /note="K->A: Affects methyltransferase activity of the FT enzyme alone, while it does not affect methyltransferase FT activity in complex; when associated with A-3874." FT /evidence="ECO:0000269|PubMed:19187761" FT MUTAGEN 3882 FT /note="C->A,S: Abolished auto-methylation." FT /evidence="ECO:0000269|PubMed:24235145" FT MUTAGEN 3906 FT /note="N->A: Loss of the histone H3 methyltransferase FT activity. Abolishes interaction with S-adenosyl-L- FT methionine." FT /evidence="ECO:0000269|PubMed:19556245, FT ECO:0000269|PubMed:25561738" FT MUTAGEN 3942 FT /note="Y->A,F: Impairs methyltransferase activity toward FT unmodified or monomethylated H3K4me." FT /evidence="ECO:0000269|PubMed:19187761, FT ECO:0000269|PubMed:19556245" FT MUTAGEN 3942 FT /note="Y->F: Shifts from a specific monomethyltransferase FT to a di- and trimethyltransferase activity." FT /evidence="ECO:0000269|PubMed:19187761, FT ECO:0000269|PubMed:19556245" FT CONFLICT 144 FT /note="E -> ELTTQIPCSWRTKGHIHDKKTEPFRLLAWSWCLN (in Ref. 2; FT CAA93625)" FT /evidence="ECO:0000305" FT CONFLICT 556 FT /note="Q -> E (in Ref. 2; CAA93625 and 6; L04731)" FT /evidence="ECO:0000305" FT CONFLICT 1347 FT /note="V -> A (in Ref. 13; AAG26335)" FT /evidence="ECO:0000305" FT CONFLICT 1487 FT /note="R -> G (in Ref. 12; AAA18644)" FT /evidence="ECO:0000305" FT CONFLICT 1490 FT /note="Q -> R (in Ref. 13; AAG26335)" FT /evidence="ECO:0000305" FT CONFLICT 1507 FT /note="P -> L (in Ref. 13; AAG26335)" FT /evidence="ECO:0000305" FT CONFLICT 1513 FT /note="N -> T (in Ref. 13; AAG26335)" FT /evidence="ECO:0000305" FT CONFLICT 1600 FT /note="E -> G (in Ref. 13; AAG26335)" FT /evidence="ECO:0000305" FT CONFLICT 1616 FT /note="S -> C (in Ref. 11; AAB34770)" FT /evidence="ECO:0000305" FT CONFLICT 1937 FT /note="Q -> H (in Ref. 8; AAA92511)" FT /evidence="ECO:0000305" FT CONFLICT 2181 FT /note="P -> S (in Ref. 8; AAA92511)" FT /evidence="ECO:0000305" FT CONFLICT 3556 FT /note="K -> N (in Ref. 6; L04731)" FT /evidence="ECO:0000305" FT CONFLICT 3718 FT /note="R -> G (in Ref. 2; CAA93625)" FT /evidence="ECO:0000305" FT CONFLICT 3759 FT /note="N -> D (in Ref. 2; CAA93625)" FT /evidence="ECO:0000305" FT CONFLICT 3813 FT /note="D -> G (in Ref. 2; CAA93625)" FT /evidence="ECO:0000305" FT CONFLICT 3901 FT /note="A -> R (in Ref. 1; AAA58669)" FT /evidence="ECO:0000305" FT HELIX 114..133 FT /evidence="ECO:0007829|PDB:3U88" FT STRAND 135..138 FT /evidence="ECO:0007829|PDB:2MTN" FT STRAND 140..145 FT /evidence="ECO:0007829|PDB:6EMQ" FT STRAND 150..152 FT /evidence="ECO:0007829|PDB:2MSR" FT STRAND 1151..1154 FT /evidence="ECO:0007829|PDB:2J2S" FT STRAND 1156..1158 FT /evidence="ECO:0007829|PDB:4NW3" FT HELIX 1159..1162 FT /evidence="ECO:0007829|PDB:4NW3" FT STRAND 1168..1170 FT /evidence="ECO:0007829|PDB:4NW3" FT HELIX 1171..1175 FT /evidence="ECO:0007829|PDB:4NW3" FT HELIX 1177..1179 FT /evidence="ECO:0007829|PDB:4NW3" FT STRAND 1183..1185 FT /evidence="ECO:0007829|PDB:2J2S" FT TURN 1190..1192 FT /evidence="ECO:0007829|PDB:4NW3" FT STRAND 1197..1200 FT /evidence="ECO:0007829|PDB:2J2S" FT TURN 1204..1206 FT /evidence="ECO:0007829|PDB:2J2S" FT STRAND 1566..1568 FT /evidence="ECO:0007829|PDB:3LQI" FT TURN 1570..1572 FT /evidence="ECO:0007829|PDB:3LQH" FT STRAND 1575..1577 FT /evidence="ECO:0007829|PDB:3LQI" FT TURN 1578..1582 FT /evidence="ECO:0007829|PDB:2KYU" FT STRAND 1585..1587 FT /evidence="ECO:0007829|PDB:3LQH" FT TURN 1589..1591 FT /evidence="ECO:0007829|PDB:3LQH" FT STRAND 1594..1596 FT /evidence="ECO:0007829|PDB:3LQH" FT HELIX 1597..1599 FT /evidence="ECO:0007829|PDB:3LQH" FT HELIX 1604..1612 FT /evidence="ECO:0007829|PDB:3LQH" FT HELIX 1614..1617 FT /evidence="ECO:0007829|PDB:3LQH" FT TURN 1622..1624 FT /evidence="ECO:0007829|PDB:3LQH" FT STRAND 1627..1629 FT /evidence="ECO:0007829|PDB:3LQH" FT HELIX 1631..1652 FT /evidence="ECO:0007829|PDB:3LQH" FT HELIX 1655..1661 FT /evidence="ECO:0007829|PDB:3LQH" FT HELIX 1708..1716 FT /evidence="ECO:0007829|PDB:3LQH" FT HELIX 1723..1740 FT /evidence="ECO:0007829|PDB:3LQH" FT HELIX 1745..1765 FT /evidence="ECO:0007829|PDB:3LQH" FT HELIX 1771..1773 FT /evidence="ECO:0007829|PDB:3LQH" FT HELIX 2847..2855 FT /evidence="ECO:0007829|PDB:5SVH" FT HELIX 3764..3766 FT /evidence="ECO:0007829|PDB:4ESG" FT HELIX 3796..3799 FT /evidence="ECO:0007829|PDB:2W5Y" FT HELIX 3809..3811 FT /evidence="ECO:0007829|PDB:2W5Y" FT HELIX 3816..3820 FT /evidence="ECO:0007829|PDB:5F5E" FT HELIX 3823..3830 FT /evidence="ECO:0007829|PDB:5F5E" FT STRAND 3831..3835 FT /evidence="ECO:0007829|PDB:5F5E" FT STRAND 3837..3847 FT /evidence="ECO:0007829|PDB:5F5E" FT STRAND 3854..3857 FT /evidence="ECO:0007829|PDB:5F5E" FT STRAND 3860..3864 FT /evidence="ECO:0007829|PDB:5F5E" FT HELIX 3865..3867 FT /evidence="ECO:0007829|PDB:5F5E" FT HELIX 3868..3877 FT /evidence="ECO:0007829|PDB:5F5E" FT STRAND 3884..3886 FT /evidence="ECO:0007829|PDB:5F5E" FT STRAND 3888..3894 FT /evidence="ECO:0007829|PDB:5F5E" FT TURN 3896..3898 FT /evidence="ECO:0007829|PDB:5F5E" FT HELIX 3901..3904 FT /evidence="ECO:0007829|PDB:5F5E" FT STRAND 3912..3920 FT /evidence="ECO:0007829|PDB:5F5E" FT STRAND 3923..3932 FT /evidence="ECO:0007829|PDB:5F5E" FT STRAND 3939..3942 FT /evidence="ECO:0007829|PDB:5F5E" FT HELIX 3951..3953 FT /evidence="ECO:0007829|PDB:7W67" SQ SEQUENCE 3969 AA; 431764 MW; 1150F37EAB1430D3 CRC64; MAHSCRWRFP ARPGTTGGGG GGGRRGLGGA PRQRVPALLL PPGPPVGGGG PGAPPSPPAV AAAAAAAGSS GAGVPGGAAA ASAASSSSAS SSSSSSSSAS SGPALLRVGP GFDAALQVSA AIGTNLRRFR AVFGESGGGG GSGEDEQFLG FGSDEEVRVR SPTRSPSVKT SPRKPRGRPR SGSDRNSAIL SDPSVFSPLN KSETKSGDKI KKKDSKSIEK KRGRPPTFPG VKIKITHGKD ISELPKGNKE DSLKKIKRTP SATFQQATKI KKLRAGKLSP LKSKFKTGKL QIGRKGVQIV RRRGRPPSTE RIKTPSGLLI NSELEKPQKV RKDKEGTPPL TKEDKTVVRQ SPRRIKPVRI IPSSKRTDAT IAKQLLQRAK KGAQKKIEKE AAQLQGRKVK TQVKNIRQFI MPVVSAISSR IIKTPRRFIE DEDYDPPIKI ARLESTPNSR FSAPSCGSSE KSSAASQHSS QMSSDSSRSS SPSVDTSTDS QASEEIQVLP EERSDTPEVH PPLPISQSPE NESNDRRSRR YSVSERSFGS RTTKKLSTLQ SAPQQQTSSS PPPPLLTPPP PLQPASSISD HTPWLMPPTI PLASPFLPAS TAPMQGKRKS ILREPTFRWT SLKHSRSEPQ YFSSAKYAKE GLIRKPIFDN FRPPPLTPED VGFASGFSAS GTAASARLFS PLHSGTRFDM HKRSPLLRAP RFTPSEAHSR IFESVTLPSN RTSAGTSSSG VSNRKRKRKV FSPIRSEPRS PSHSMRTRSG RLSSSELSPL TPPSSVSSSL SISVSPLATS ALNPTFTFPS HSLTQSGESA EKNQRPRKQT SAPAEPFSSS SPTPLFPWFT PGSQTERGRN KDKAPEELSK DRDADKSVEK DKSRERDRER EKENKRESRK EKRKKGSEIQ SSSALYPVGR VSKEKVVGED VATSSSAKKA TGRKKSSSHD SGTDITSVTL GDTTAVKTKI LIKKGRGNLE KTNLDLGPTA PSLEKEKTLC LSTPSSSTVK HSTSSIGSML AQADKLPMTD KRVASLLKKA KAQLCKIEKS KSLKQTDQPK AQGQESDSSE TSVRGPRIKH VCRRAAVALG RKRAVFPDDM PTLSALPWEE REKILSSMGN DDKSSIAGSE DAEPLAPPIK PIKPVTRNKA PQEPPVKKGR RSRRCGQCPG CQVPEDCGVC TNCLDKPKFG GRNIKKQCCK MRKCQNLQWM PSKAYLQKQA KAVKKKEKKS KTSEKKDSKE SSVVKNVVDS SQKPTPSARE DPAPKKSSSE PPPRKPVEEK SEEGNVSAPG PESKQATTPA SRKSSKQVSQ PALVIPPQPP TTGPPRKEVP KTTPSEPKKK QPPPPESGPE QSKQKKVAPR PSIPVKQKPK EKEKPPPVNK QENAGTLNIL STLSNGNSSK QKIPADGVHR IRVDFKEDCE AENVWEMGGL GILTSVPITP RVVCFLCASS GHVEFVYCQV CCEPFHKFCL EENERPLEDQ LENWCCRRCK FCHVCGRQHQ ATKQLLECNK CRNSYHPECL GPNYPTKPTK KKKVWICTKC VRCKSCGSTT PGKGWDAQWS HDFSLCHDCA KLFAKGNFCP LCDKCYDDDD YESKMMQCGK CDRWVHSKCE NLSDEMYEIL SNLPESVAYT CVNCTERHPA EWRLALEKEL QISLKQVLTA LLNSRTTSHL LRYRQAAKPP DLNPETEESI PSRSSPEGPD PPVLTEVSKQ DDQQPLDLEG VKRKMDQGNY TSVLEFSDDI VKIIQAAINS DGGQPEIKKA NSMVKSFFIR QMERVFPWFS VKKSRFWEPN KVSSNSGMLP NAVLPPSLDH NYAQWQEREE NSHTEQPPLM KKIIPAPKPK GPGEPDSPTP LHPPTPPILS TDRSREDSPE LNPPPGIEDN RQCALCLTYG DDSANDAGRL LYIGQNEWTH VNCALWSAEV FEDDDGSLKN VHMAVIRGKQ LRCEFCQKPG ATVGCCLTSC TSNYHFMCSR AKNCVFLDDK KVYCQRHRDL IKGEVVPENG FEVFRRVFVD FEGISLRRKF LNGLEPENIH MMIGSMTIDC LGILNDLSDC EDKLFPIGYQ CSRVYWSTTD ARKRCVYTCK IVECRPPVVE PDINSTVEHD ENRTIAHSPT SFTESSSKES QNTAEIISPP SPDRPPHSQT SGSCYYHVIS KVPRIRTPSY SPTQRSPGCR PLPSAGSPTP TTHEIVTVGD PLLSSGLRSI GSRRHSTSSL SPQRSKLRIM SPMRTGNTYS RNNVSSVSTT GTATDLESSA KVVDHVLGPL NSSTSLGQNT STSSNLQRTV VTVGNKNSHL DGSSSSEMKQ SSASDLVSKS SSLKGEKTKV LSSKSSEGSA HNVAYPGIPK LAPQVHNTTS RELNVSKIGS FAEPSSVSFS SKEALSFPHL HLRGQRNDRD QHTDSTQSAN SSPDEDTEVK TLKLSGMSNR SSIINEHMGS SSRDRRQKGK KSCKETFKEK HSSKSFLEPG QVTTGEEGNL KPEFMDEVLT PEYMGQRPCN NVSSDKIGDK GLSMPGVPKA PPMQVEGSAK ELQAPRKRTV KVTLTPLKME NESQSKNALK ESSPASPLQI ESTSPTEPIS ASENPGDGPV AQPSPNNTSC QDSQSNNYQN LPVQDRNLML PDGPKPQEDG SFKRRYPRRS ARARSNMFFG LTPLYGVRSY GEEDIPFYSS STGKKRGKRS AEGQVDGADD LSTSDEDDLY YYNFTRTVIS SGGEERLASH NLFREEEQCD LPKISQLDGV DDGTESDTSV TATTRKSSQI PKRNGKENGT ENLKIDRPED AGEKEHVTKS SVGHKNEPKM DNCHSVSRVK TQGQDSLEAQ LSSLESSRRV HTSTPSDKNL LDTYNTELLK SDSDNNNSDD CGNILPSDIM DFVLKNTPSM QALGESPESS SSELLNLGEG LGLDSNREKD MGLFEVFSQQ LPTTEPVDSS VSSSISAEEQ FELPLELPSD LSVLTTRSPT VPSQNPSRLA VISDSGEKRV TITEKSVASS ESDPALLSPG VDPTPEGHMT PDHFIQGHMD ADHISSPPCG SVEQGHGNNQ DLTRNSSTPG LQVPVSPTVP IQNQKYVPNS TDSPGPSQIS NAAVQTTPPH LKPATEKLIV VNQNMQPLYV LQTLPNGVTQ KIQLTSSVSS TPSVMETNTS VLGPMGGGLT LTTGLNPSLP TSQSLFPSAS KGLLPMSHHQ HLHSFPAATQ SSFPPNISNP PSGLLIGVQP PPDPQLLVSE SSQRTDLSTT VATPSSGLKK RPISRLQTRK NKKLAPSSTP SNIAPSDVVS NMTLINFTPS QLPNHPSLLD LGSLNTSSHR TVPNIIKRSK SSIMYFEPAP LLPQSVGGTA ATAAGTSTIS QDTSHLTSGS VSGLASSSSV LNVVSMQTTT TPTSSASVPG HVTLTNPRLL GTPDIGSISN LLIKASQQSL GIQDQPVALP PSSGMFPQLG TSQTPSTAAI TAASSICVLP STQTTGITAA SPSGEADEHY QLQHVNQLLA SKTGIHSSQR DLDSASGPQV SNFTQTVDAP NSMGLEQNKA LSSAVQASPT SPGGSPSSPS SGQRSASPSV PGPTKPKPKT KRFQLPLDKG NGKKHKVSHL RTSSSEAHIP DQETTSLTSG TGTPGAEAEQ QDTASVEQSS QKECGQPAGQ VAVLPEVQVT QNPANEQESA EPKTVEEEES NFSSPLMLWL QQEQKRKESI TEKKPKKGLV FEISSDDGFQ ICAESIEDAW KSLTDKVQEA RSNARLKQLS FAGVNGLRML GILHDAVVFL IEQLSGAKHC RNYKFRFHKP EEANEPPLNP HGSARAEVHL RKSAFDMFNF LASKHRQPPE YNPNDEEEEE VQLKSARRAT SMDLPMPMRF RHLKKTSKEA VGVYRSPIHG RGLFCKRNID AGEMVIEYAG NVIRSIQTDK REKYYDSKGI GCYMFRIDDS EVVDATMHGN AARFINHSCE PNCYSRVINI DGQKHIVIFA MRKIYRGEEL TYDYKFPIED ASNKLPCNCG AKKCRKFLN // ID PML_HUMAN Reviewed; 882 AA. AC P29590; E9PBR7; P29591; P29592; P29593; Q00755; Q15959; Q59FP9; Q8WUA0; AC Q96S41; Q9BPW2; Q9BWP7; Q9BZX6; Q9BZX7; Q9BZX8; Q9BZX9; Q9BZY0; Q9BZY2; AC Q9BZY3; DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot. DT 25-NOV-2008, sequence version 3. DT 28-JAN-2026, entry version 269. DE RecName: Full=Protein PML; DE AltName: Full=E3 SUMO-protein ligase PML; DE EC=2.3.2.- {ECO:0000269|PubMed:20972456, ECO:0000269|PubMed:28250117}; DE AltName: Full=Promyelocytic leukemia protein; DE AltName: Full=RING finger protein 71; DE AltName: Full=RING-type E3 SUMO transferase PML {ECO:0000305}; DE AltName: Full=Tripartite motif-containing protein 19; DE Short=TRIM19; GN Name=PML; Synonyms=MYL, PP8675, RNF71, TRIM19; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PML-3), AND DISEASE. RX PubMed=1652369; DOI=10.1016/0092-8674(91)90113-d; RA de The H., Lavau C., Marchio A., Chomienne C., Degos L., Dejean A.; RT "The PML-RAR alpha fusion mRNA generated by the t(15;17) translocation in RT acute promyelocytic leukemia encodes a functionally altered RAR."; RL Cell 66:675-684(1991). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS PML-1; PML-5 AND PML-8), CHROMOSOMAL RP TRANSLOCATION WITH RARA, DISEASE, AND VARIANT LEU-645. RX PubMed=1720570; DOI=10.1126/science.1720570; RA Goddard A.D., Borrow J., Freemont P.S., Solomon E.; RT "Characterization of a zinc finger gene disrupted by the t(15;17) in acute RT promyelocytic leukemia."; RL Science 254:1371-1374(1991). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PML-4). RX PubMed=1311253; DOI=10.1002/j.1460-2075.1992.tb05095.x; RA Kastner P., Perez A., Lutz Y., Rochette-Egly C., Gaub M.P., Durand B., RA Lanotte M., Berger R., Chambon P.; RT "Structure, localization and transcriptional properties of two classes of RT retinoic acid receptor alpha fusion proteins in acute promyelocytic RT leukemia (APL): structural similarities with a new family of RT oncoproteins."; RL EMBO J. 11:629-642(1992). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PML-6). RX PubMed=1652368; DOI=10.1016/0092-8674(91)90112-c; RA Kakizuka A., Miller W.H. Jr., Umenono K., Warrell R.P. Jr., Frankel S.R., RA Murty V.V., Dmitrovsky E., Evans R.M.; RT "Chromosomal translocation t(15;17) in human acute promyelocytic leukemia RT fuses RAR alpha with a novel putative transcription factor, PML."; RL Cell 66:663-674(1991). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS PML-1; PML-2; PML-4; PML-5; PML-6; RP PML-7; PML-8; PML-12 AND PML-14), AND VARIANT LEU-645. RX PubMed=11331580; DOI=10.1093/emboj/20.9.2140; RA Reymond A., Meroni G., Fantozzi A., Merla G., Cairo S., Luzi L., RA Riganelli D., Zanaria E., Messali S., Cainarca S., Guffanti A., Minucci S., RA Pelicci P.G., Ballabio A.; RT "The tripartite motif family identifies cell compartments."; RL EMBO J. 20:2140-2151(2001). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PML-6). RA Goddard A.D., Solomon E.; RL Submitted (JAN-1992) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM PML-13). RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; RL Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM PML-11). RC TISSUE=Brain; RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., RA Ohara O., Nagase T., Kikuno R.F.; RT "Homo sapiens protein coding cDNA."; RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16572171; DOI=10.1038/nature04601; RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S., RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.; RT "Analysis of the DNA sequence and duplication history of human chromosome RT 15."; RL Nature 440:671-675(2006). RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM PML-13). RC TISSUE=Kidney; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [11] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 419-466, AND CHROMOSOMAL TRANSLOCATION RP WITH RARA. RX PubMed=1312695; RA Tong J.H., Dong S., Geng J.P., Huang W., Wang Z.Y., Sun G.L., Chen S.J., RA Chen Z., Larsen C.-J., Berger R.; RT "Molecular rearrangements of the MYL gene in acute promyelocytic leukemia RT (APL, M3) define a breakpoint cluster region as well as some molecular RT variants."; RL Oncogene 7:311-316(1992). RN [12] RP NUCLEOTIDE SEQUENCE [MRNA] OF 454-503, AND CHROMOSOMAL TRANSLOCATION WITH RP RARA. RX PubMed=12691149; DOI=10.1080/1042819021000040305; RA Fujita K., Oba R., Harada H., Mori H., Niikura H., Isoyama K., Omine M.; RT "Cytogenetics, FISH and RT-PCR analysis of acute promyelocytic leukemia: RT structure of the fusion point in a case lacking classic t(15;17) RT translocation."; RL Leuk. Lymphoma 44:111-115(2003). RN [13] RP SUMOYLATION AT LYS-65; LYS-160 AND LYS-490, MUTAGENESIS OF LYS-65; LYS-133; RP LYS-150; LYS-160 AND LYS-490, SUBCELLULAR LOCATION, AND FUNCTION. RX PubMed=9756909; DOI=10.1074/jbc.273.41.26675; RA Kamitani T., Kito K., Nguyen H.P., Wada H., Fukuda-Kamitani T., Yeh E.T.H.; RT "Identification of three major sentrinization sites in PML."; RL J. Biol. Chem. 273:26675-26682(1998). RN [14] RP INTERACTION WITH TRIM27. RX PubMed=9570750; DOI=10.1242/jcs.111.10.1319; RA Cao T., Duprez E., Borden K.L., Freemont P.S., Etkin L.D.; RT "Ret finger protein is a normal component of PML nuclear bodies and RT interacts directly with PML."; RL J. Cell Sci. 111:1319-1329(1998). RN [15] RP INTERACTION WITH LASSA VIRUS Z PROTEIN (MICROBIAL INFECTION). RX PubMed=9420283; DOI=10.1128/jvi.72.1.758-766.1998; RA Borden K.L., Campbell-Dwyer E.J., Salvato M.S.; RT "An arenavirus RING (zinc-binding) protein binds the oncoprotein RT promyelocyte leukemia protein (PML) and relocates PML nuclear bodies to the RT cytoplasm."; RL J. Virol. 72:758-766(1998). RN [16] RP INHIBITION OF SUMOYLATION BY HHV-5 (MICROBIAL INFECTION). RX PubMed=10233977; DOI=10.1128/jvi.73.6.5137-5143.1999; RA Mueller S., Dejean A.; RT "Viral immediate-early proteins abrogate the modification by SUMO-1 of PML RT and Sp100 proteins, correlating with nuclear body disruption."; RL J. Virol. 73:5137-5143(1999). RN [17] RP FUNCTION, AND INTERACTION WITH RARA; RXRA AND TRIM24. RX PubMed=10610177; DOI=10.1038/15463; RA Zhong S., Delva L., Rachez C., Cenciarelli C., Gandini D., Zhang H., RA Kalantry S., Freedman L.P., Pandolfi P.P.; RT "A RA-dependent, tumour-growth suppressive transcription complex is the RT target of the PML-RARalpha and T18 oncoproteins."; RL Nat. Genet. 23:287-295(1999). RN [18] RP SUMOYLATION AT LYS-65; LYS-160 AND LYS-490. RX PubMed=10779416; RA Zhong S., Muller S., Ronchetti S., Freemont P.S., Dejean A., Pandolfi P.P.; RT "Role of SUMO-1-modified PML in nuclear body formation."; RL Blood 95:2748-2752(2000). RN [19] RP FUNCTION, AND INTERACTION WITH DAXX. RX PubMed=10684855; DOI=10.1084/jem.191.4.631; RA Zhong S., Salomoni P., Ronchetti S., Guo A., Ruggero D., Pandolfi P.P.; RT "Promyelocytic leukemia protein (PML) and Daxx participate in a novel RT nuclear pathway for apoptosis."; RL J. Exp. Med. 191:631-640(2000). RN [20] RP INTERACTION WITH DAXX, AND SUBCELLULAR LOCATION. RX PubMed=10669754; DOI=10.1128/mcb.20.5.1784-1796.2000; RA Li H., Leo C., Zhu J., Wu X., O'Neil J., Park E.-J., Chen J.D.; RT "Sequestration and inhibition of Daxx-mediated transcriptional repression RT by PML."; RL Mol. Cell. Biol. 20:1784-1796(2000). RN [21] RP FUNCTION, INTERACTION WITH TP53, AND SUBCELLULAR LOCATION. RX PubMed=11025664; DOI=10.1038/35036365; RA Guo A., Salomoni P., Luo J., Shih A., Zhong S., Gu W., Pandolfi P.P.; RT "The function of PML in p53-dependent apoptosis."; RL Nat. Cell Biol. 2:730-736(2000). RN [22] RP FUNCTION IN HUMAN FOAMY VIRUS RESTRICTION, INTERACTION WITH HUMAN FOAMY RP VIRUS BEL1 AND BET (MICROBIAL INFECTION), AND SUBCELLULAR LOCATION. RX PubMed=11432836; DOI=10.1093/emboj/20.13.3495; RA Regad T., Saib A., Lallemand-Breitenbach V., Pandolfi P.P., de The H., RA Chelbi-Alix M.K.; RT "PML mediates the interferon-induced antiviral state against a complex RT retrovirus via its association with the viral transactivator."; RL EMBO J. 20:3495-3505(2001). RN [23] RP FUNCTION, AND INTERACTION WITH EIF4E. RX PubMed=11500381; DOI=10.1093/emboj/20.16.4547; RA Cohen N., Sharma M., Kentsis A., Perez J.M., Strudwick S., Borden K.L.; RT "PML RING suppresses oncogenic transformation by reducing the affinity of RT eIF4E for mRNA."; RL EMBO J. 20:4547-4559(2001). RN [24] RP FUNCTION, AND INTERACTION WITH EIF4E. RX PubMed=11575918; DOI=10.1006/jmbi.2001.5003; RA Kentsis A., Dwyer E.C., Perez J.M., Sharma M., Chen A., Pan Z.Q., RA Borden K.L.; RT "The RING domains of the promyelocytic leukemia protein PML and the RT arenaviral protein Z repress translation by directly inhibiting translation RT initiation factor eIF4E."; RL J. Mol. Biol. 312:609-623(2001). RN [25] RP NOMENCLATURE OF ISOFORMS PML-1 THROUGH PML-7. RX PubMed=11704850; DOI=10.1038/sj.onc.1204765; RA Jensen K., Shiels C., Freemont P.S.; RT "PML protein isoforms and the RBCC/TRIM motif."; RL Oncogene 20:7223-7233(2001). RN [26] RP INTERACTION WITH SIRT1. RX PubMed=12006491; DOI=10.1093/emboj/21.10.2383; RA Langley E., Pearson M., Faretta M., Bauer U.-M., Frye R.A., Minucci S., RA Pelicci P.G., Kouzarides T.; RT "Human SIR2 deacetylates p53 and antagonizes PML/p53-induced cellular RT senescence."; RL EMBO J. 21:2383-2396(2002). RN [27] RP SUMOYLATION, AND DESUMOYLATION BY SENP2. RX PubMed=12419228; DOI=10.1016/s1097-2765(02)00699-8; RA Best J.L., Ganiatsas S., Agarwal S., Changou A., Salomoni P., Shirihai O., RA Meluh P.B., Pandolfi P.P., Zon L.I.; RT "SUMO-1 protease-1 regulates gene transcription through PML."; RL Mol. Cell 10:843-855(2002). RN [28] RP FUNCTION IN DNA REPAIR, PHOSPHORYLATION AT SER-117 BY CHEK2, AND RP INTERACTION WITH CHEK2. RX PubMed=12402044; DOI=10.1038/ncb869; RA Yang S., Kuo C., Bisi J.E., Kim M.K.; RT "PML-dependent apoptosis after DNA damage is regulated by the checkpoint RT kinase hCds1/Chk2."; RL Nat. Cell Biol. 4:865-870(2002). RN [29] RP INTERACTION WITH RABIES VIRUS PHOSPHOPROTEINS, SUBCELLULAR LOCATION, AND RP FUNCTION. RX PubMed=12439746; DOI=10.1038/sj.onc.1205931; RA Blondel D., Regad T., Poisson N., Pavie B., Harper F., Pandolfi P.P., RA De The H., Chelbi-Alix M.K.; RT "Rabies virus P and small P products interact directly with PML and RT reorganize PML nuclear bodies."; RL Oncogene 21:7957-7970(2002). RN [30] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH CHEK2 AND TP53. RX PubMed=12810724; DOI=10.1074/jbc.m301264200; RA Louria-Hayon I., Grossman T., Sionov R.V., Alsheich O., Pandolfi P.P., RA Haupt Y.; RT "The promyelocytic leukemia protein protects p53 from Mdm2-mediated RT inhibition and degradation."; RL J. Biol. Chem. 278:33134-33141(2003). RN [31] RP INTERACTION WITH TOPBP1. RX PubMed=12773567; DOI=10.1128/mcb.23.12.4247-4256.2003; RA Xu Z.-X., Timanova-Atanasova A., Zhao R.-X., Chang K.-S.; RT "PML colocalizes with and stabilizes the DNA damage response protein RT TopBP1."; RL Mol. Cell. Biol. 23:4247-4256(2003). RN [32] RP INTERACTION WITH SIAH1, AND DEGRADATION. RX PubMed=14645235; DOI=10.1074/jbc.m306407200; RA Fanelli M., Fantozzi A., De Luca P., Caprodossi S., Matsuzawa S., RA Lazar M.A., Pelicci P.G., Minucci S.; RT "The coiled-coil domain is the structural determinant for mammalian RT homologues of Drosophila Sina-mediated degradation of promyelocytic RT leukemia protein and other tripartite motif proteins by the proteasome."; RL J. Biol. Chem. 279:5374-5379(2004). RN [33] RP INHIBITION OF SUMOYLATION BY HHV-5 (MICROBIAL INFECTION), AND INTERACTION RP WITH HHV-5 IMMEDIATE EARLY PROTEIN IE1 (MICROBIAL INFECTION). RX PubMed=15163746; DOI=10.1128/jvi.78.12.6527-6542.2004; RA Lee H.R., Kim D.J., Lee J.M., Choi C.Y., Ahn B.Y., Hayward G.S., Ahn J.H.; RT "Ability of the human cytomegalovirus IE1 protein to modulate sumoylation RT of PML correlates with its functional activities in transcriptional RT regulation and infectivity in cultured fibroblast cells."; RL J. Virol. 78:6527-6542(2004). RN [34] RP FUNCTION, INTERACTION WITH ELF4, AND SUBCELLULAR LOCATION. RX PubMed=14976184; DOI=10.1074/jbc.m312439200; RA Suico M.A., Yoshida H., Seki Y., Uchikawa T., Lu Z., Shuto T., RA Matsuzaki K., Nakao M., Li J.-D., Kai H.; RT "Myeloid Elf-1-like factor, an ETS transcription factor, up-regulates RT lysozyme transcription in epithelial cells through interaction with RT promyelocytic leukemia protein."; RL J. Biol. Chem. 279:19091-19098(2004). RN [35] RP INTERACTION WITH ANKRD2. RX PubMed=15136035; DOI=10.1016/j.jmb.2004.03.071; RA Kojic S., Medeot E., Guccione E., Krmac H., Zara I., Martinelli V., RA Valle G., Faulkner G.; RT "The Ankrd2 protein, a link between the sarcomere and the nucleus in RT skeletal muscle."; RL J. Mol. Biol. 339:313-325(2004). RN [36] RP FUNCTION, INTERACTION WITH MDM2 AND RPL11, PHOSPHORYLATION BY ATR IN RP RESPONSE TO DNA DAMAGE, AND SUBCELLULAR LOCATION. RX PubMed=15195100; DOI=10.1038/ncb1147; RA Bernardi R., Scaglioni P.P., Bergmann S., Horn H.F., Vousden K.H., RA Pandolfi P.P.; RT "PML regulates p53 stability by sequestering Mdm2 to the nucleolus."; RL Nat. Cell Biol. 6:665-672(2004). RN [37] RP SUBCELLULAR LOCATION, AND INTERACTION WITH CHFR. RX PubMed=15467728; DOI=10.1038/nsmb837; RA Daniels M.J., Marson A., Venkitaraman A.R.; RT "PML bodies control the nuclear dynamics and function of the CHFR mitotic RT checkpoint protein."; RL Nat. Struct. Mol. Biol. 11:1114-1121(2004). RN [38] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH TGFBR1; TGFBR2; SMAD2; RP SMAD3 AND ZFYVE9/SARA. RX PubMed=15356634; DOI=10.1038/nature02783; RA Lin H.K., Bergmann S., Pandolfi P.P.; RT "Cytoplasmic PML function in TGF-beta signalling."; RL Nature 431:205-211(2004). RN [39] RP INTERACTION OF PML-RARALPHA ONCOPROTEIN WITH UBE2I, SUBCELLULAR LOCATION, RP SUMOYLATION, AND MUTAGENESIS OF CYS-88 AND PRO-89. RX PubMed=15809060; DOI=10.1016/j.bbrc.2005.03.052; RA Kim Y.E., Kim D.Y., Lee J.M., Kim S.T., Han T.H., Ahn J.H.; RT "Requirement of the coiled-coil domain of PML-RARalpha oncoprotein for RT localization, sumoylation, and inhibition of monocyte differentiation."; RL Biochem. Biophys. Res. Commun. 330:746-754(2005). RN [40] RP SUBCELLULAR LOCATION. RX PubMed=16778193; DOI=10.1158/0008-5472.can-05-3792; RA Condemine W., Takahashi Y., Zhu J., Puvion-Dutilleul F., Guegan S., RA Janin A., de The H.; RT "Characterization of endogenous human promyelocytic leukemia isoforms."; RL Cancer Res. 66:6192-6198(2006). RN [41] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-403; SER-518; SER-527 AND RP SER-530, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-565 (ISOFORM PML-5), RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-518; SER-527 AND SER-530 RP (ISOFORM PML-6), AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling RT networks."; RL Cell 127:635-648(2006). RN [42] RP FUNCTION. RX PubMed=17030982; DOI=10.1083/jcb.200604009; RA Dellaire G., Ching R.W., Ahmed K., Jalali F., Tse K.C., Bristow R.G., RA Bazett-Jones D.P.; RT "Promyelocytic leukemia nuclear bodies behave as DNA damage sensors whose RT response to DNA double-strand breaks is regulated by NBS1 and the kinases RT ATM, Chk2, and ATR."; RL J. Cell Biol. 175:55-66(2006). RN [43] RP FUNCTION IN POLIOVIRUS RESTRICTION. RX PubMed=16912307; DOI=10.1128/jvi.00031-06; RA Pampin M., Simonin Y., Blondel B., Percherancier Y., Chelbi-Alix M.K.; RT "Cross talk between PML and p53 during poliovirus infection: implications RT for antiviral defense."; RL J. Virol. 80:8582-8592(2006). RN [44] RP SUBUNIT, SUMOYLATION, SUMO-BINDING MOTIF, MUTAGENESIS OF CYS-57 AND CYS-60, RP AND SUBCELLULAR LOCATION. RX PubMed=17081985; DOI=10.1016/j.molcel.2006.09.013; RA Shen T.H., Lin H.K., Scaglioni P.P., Yung T.M., Pandolfi P.P.; RT "The mechanisms of PML-nuclear body formation."; RL Mol. Cell 24:331-339(2006). RN [45] RP INTERACTION WITH PKM, FUNCTION, SUBCELLULAR LOCATION, DOMAIN, AND RP MUTAGENESIS OF LYS-487 AND LYS-490. RX PubMed=18298799; DOI=10.1111/j.1365-2443.2008.01165.x; RA Shimada N., Shinagawa T., Ishii S.; RT "Modulation of M2-type pyruvate kinase activity by the cytoplasmic PML RT tumor suppressor protein."; RL Genes Cells 13:245-254(2008). RN [46] RP ACETYLATION AT LYS-487 AND LYS-515, AND MUTAGENESIS OF LYS-487 AND LYS-515. RX PubMed=18621739; DOI=10.1074/jbc.m802217200; RA Hayakawa F., Abe A., Kitabayashi I., Pandolfi P.P., Naoe T.; RT "Acetylation of PML is involved in histone deacetylase inhibitor-mediated RT apoptosis."; RL J. Biol. Chem. 283:24420-24425(2008). RN [47] RP FUNCTION IN HHV-5 RESTRICTION. RX PubMed=17942542; DOI=10.1128/jvi.01685-07; RA Tavalai N., Papior P., Rechter S., Stamminger T.; RT "Nuclear domain 10 components promyelocytic leukemia protein and hDaxx RT independently contribute to an intrinsic antiviral defense against human RT cytomegalovirus infection."; RL J. Virol. 82:126-137(2008). RN [48] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=18716620; DOI=10.1038/nature07290; RA Song M.S., Salmena L., Carracedo A., Egia A., Lo-Coco F., RA Teruya-Feldstein J., Pandolfi P.P.; RT "The deubiquitinylation and localization of PTEN are regulated by a HAUSP- RT PML network."; RL Nature 455:813-817(2008). RN [49] RP POLYUBIQUITINATION AT LYS-380; LYS-400; LYS-401 AND LYS-476 BY RNF4, RP PROTEASOMAL DEGRADATION, AND SUMOYLATION. RX PubMed=18408734; DOI=10.1038/ncb1716; RA Tatham M.H., Geoffroy M.C., Shen L., Plechanovova A., Hattersley N., RA Jaffray E.G., Palvimo J.J., Hay R.T.; RT "RNF4 is a poly-SUMO-specific E3 ubiquitin ligase required for arsenic- RT induced PML degradation."; RL Nat. Cell Biol. 10:538-546(2008). RN [50] RP FUNCTION, AND INTERACTION WITH SATB1. RX PubMed=17173041; DOI=10.1038/ncb1516; RA Kumar P.P., Bischof O., Purbey P.K., Notani D., Urlaub H., Dejean A., RA Galande S.; RT "Functional interaction between PML and SATB1 regulates chromatin-loop RT architecture and transcription of the MHC class I locus."; RL Nat. Cell Biol. 9:45-56(2007). RN [51] RP FUNCTION. RX PubMed=18391071; DOI=10.1083/jcb.200707018; RA Culjkovic B., Tan K., Orolicki S., Amri A., Meloche S., Borden K.L.; RT "The eIF4E RNA regulon promotes the Akt signaling pathway."; RL J. Cell Biol. 181:51-63(2008). RN [52] RP FUNCTION IN HHV-1 RESTRICTION, AND SUBCELLULAR LOCATION. RX PubMed=18509536; DOI=10.1371/journal.pone.0002277; RA McNally B.A., Trgovcich J., Maul G.G., Liu Y., Zheng P.; RT "A role for cytoplasmic PML in cellular resistance to viral infection."; RL PLoS ONE 3:E2277-E2277(2008). RN [53] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-403; SER-518; SER-527 AND RP SER-530, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [54] RP FUNCTION IN INFLUENZA A VIRUS RESTRICTION. RX PubMed=19703418; DOI=10.1016/j.bbrc.2009.08.091; RA Li W., Wang G., Zhang H., Zhang D., Zeng J., Chen X., Xu Y., Li K.; RT "Differential suppressive effect of promyelocytic leukemia protein on the RT replication of different subtypes/strains of influenza A virus."; RL Biochem. Biophys. Res. Commun. 389:84-89(2009). RN [55] RP FUNCTION, AND INTERACTION WITH TERT. RX PubMed=19567472; DOI=10.1242/jcs.048066; RA Oh W., Ghim J., Lee E.W., Yang M.R., Kim E.T., Ahn J.H., Song J.; RT "PML-IV functions as a negative regulator of telomerase by interacting with RT TERT."; RL J. Cell Sci. 122:2613-2622(2009). RN [56] RP PHOSPHORYLATION AT SER-8 AND SER-38 BY HIPK2, AND INTERACTION WITH HIPK2. RX PubMed=19015637; DOI=10.1038/onc.2008.420; RA Gresko E., Ritterhoff S., Sevilla-Perez J., Roscic A., Froebius K., RA Kotevic I., Vichalkovski A., Hess D., Hemmings B.A., Schmitz M.L.; RT "PML tumor suppressor is regulated by HIPK2-mediated phosphorylation in RT response to DNA damage."; RL Oncogene 28:698-708(2009). RN [57] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-530, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [58] RP INTERACTION WITH MORC3, AND SUBCELLULAR LOCATION. RX PubMed=20501696; DOI=10.1242/jcs.063586; RA Mimura Y., Takahashi K., Kawata K., Akazawa T., Inoue N.; RT "Two-step colocalization of MORC3 with PML nuclear bodies."; RL J. Cell Sci. 123:2014-2024(2010). RN [59] RP FUNCTION IN RABIES VIRUS RESTRICTION. RX PubMed=20702643; DOI=10.1128/jvi.01286-10; RA Blondel D., Kheddache S., Lahaye X., Dianoux L., Chelbi-Alix M.K.; RT "Resistance to rabies virus infection conferred by the PMLIV isoform."; RL J. Virol. 84:10719-10726(2010). RN [60] RP PHOSPHORYLATION BY CK2 (MICROBIAL INFECTION), AND SUBCELLULAR LOCATION. RX PubMed=20719947; DOI=10.1128/jvi.01183-10; RA Sivachandran N., Cao J.Y., Frappier L.; RT "Epstein-Barr virus nuclear antigen 1 Hijacks the host kinase CK2 to RT disrupt PML nuclear bodies."; RL J. Virol. 84:11113-11123(2010). RN [61] RP INTERACTION OF PML-4 AND PML-5 WITH HADV5 E1B-55K (MICROBIAL INFECTION). RX PubMed=20639899; DOI=10.1038/onc.2010.284; RA Wimmer P., Schreiner S., Everett R.D., Sirma H., Groitl P., Dobner T.; RT "SUMO modification of E1B-55K oncoprotein regulates isoform-specific RT binding to the tumour suppressor protein PML."; RL Oncogene 29:5511-5522(2010). RN [62] RP SUMOYLATION, AND UBIQUITINATION. RX PubMed=20943951; DOI=10.1091/mbc.e10-05-0449; RA Geoffroy M.C., Jaffray E.G., Walker K.J., Hay R.T.; RT "Arsenic-induced SUMO-dependent recruitment of RNF4 into PML nuclear RT bodies."; RL Mol. Biol. Cell 21:4227-4239(2010). RN [63] RP INTERACTION WITH CSNK2A1 AND CSNK2A3. RX PubMed=20625391; DOI=10.1371/journal.pone.0011418; RA Hung M.S., Lin Y.C., Mao J.H., Kim I.J., Xu Z., Yang C.T., Jablons D.M., RA You L.; RT "Functional polymorphism of the CK2alpha intronless gene plays oncogenic RT roles in lung cancer."; RL PLoS ONE 5:E11418-E11418(2010). RN [64] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-518 AND SER-527, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [65] RP INTERACTION WITH UBC9, SUBUNIT, UBIQUITINATION, SUMOYLATION, ARSENIC RP BINDING, DOMAIN, AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=20378816; DOI=10.1126/science.1183424; RA Zhang X.W., Yan X.J., Zhou Z.R., Yang F.F., Wu Z.Y., Sun H.B., Liang W.X., RA Song A.X., Lallemand-Breitenbach V., Jeanne M., Zhang Q.Y., Yang H.Y., RA Huang Q.H., Zhou G.B., Tong J.H., Zhang Y., Wu J.H., Hu H.Y., de The H., RA Chen S.J., Chen Z.; RT "Arsenic trioxide controls the fate of the PML-RARalpha oncoprotein by RT directly binding PML."; RL Science 328:240-243(2010). RN [66] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [67] RP FUNCTION, AND INTERACTION WITH WRN. RX PubMed=21639834; DOI=10.1134/s000629791105004x; RA Liu J., Song Y., Qian J., Liu B., Dong Y., Tian B., Sun Z.; RT "Promyelocytic leukemia protein interacts with werner syndrome helicase and RT regulates double-strand break repair in gamma-irradiation-induced DNA RT damage responses."; RL Biochemistry (Mosc.) 76:550-554(2011). RN [68] RP UBIQUITINATION, PHOSPHORYLATION AT SER-518, AND MUTAGENESIS OF SER-518. RX PubMed=21840486; DOI=10.1016/j.ccr.2011.07.008; RA Yuan W.C., Lee Y.R., Huang S.F., Lin Y.M., Chen T.Y., Chung H.C., RA Tsai C.H., Chen H.Y., Chiang C.T., Lai C.K., Lu L.T., Chen C.H., Gu D.L., RA Pu Y.S., Jou Y.S., Lu K.P., Hsiao P.W., Shih H.M., Chen R.H.; RT "A Cullin3-KLHL20 Ubiquitin ligase-dependent pathway targets PML to RT potentiate HIF-1 signaling and prostate cancer progression."; RL Cancer Cell 20:214-228(2011). RN [69] RP REVIEW ON FUNCTION. RX PubMed=21475307; DOI=10.1038/cdd.2011.31; RA Pinton P., Giorgi C., Pandolfi P.P.; RT "The role of PML in the control of apoptotic cell fate: a new key player at RT ER-mitochondria sites."; RL Cell Death Differ. 18:1450-1456(2011). RN [70] RP REVIEW ON FUNCTION. RX PubMed=21501958; DOI=10.1016/j.ceb.2011.03.011; RA Carracedo A., Ito K., Pandolfi P.P.; RT "The nuclear bodies inside out: PML conquers the cytoplasm."; RL Curr. Opin. Cell Biol. 23:360-366(2011). RN [71] RP PHOSPHORYLATION AT SER-403; SER-505; SER-518 AND SER-527, AND INTERACTION RP WITH PIN1 AND MAPK1. RX PubMed=22033920; DOI=10.1074/jbc.m111.289512; RA Lim J.H., Liu Y., Reineke E., Kao H.Y.; RT "Mitogen-activated protein kinase extracellular signal-regulated kinase 2 RT phosphorylates and promotes Pin1 protein-dependent promyelocytic leukemia RT protein turnover."; RL J. Biol. Chem. 286:44403-44411(2011). RN [72] RP FUNCTION IN HSV-1 RESTRICTION. RX PubMed=21172801; DOI=10.1242/jcs.075390; RA Cuchet D., Sykes A., Nicolas A., Orr A., Murray J., Sirma H., Heeren J., RA Bartelt A., Everett R.D.; RT "PML isoforms I and II participate in PML-dependent restriction of HSV-1 RT replication."; RL J. Cell Sci. 124:280-291(2011). RN [73] RP REVIEW ON FUNCTION IN ANTIVIRAL DEFENSE. RX PubMed=21198351; DOI=10.1089/jir.2010.0111; RA Geoffroy M.C., Chelbi-Alix M.K.; RT "Role of promyelocytic leukemia protein in host antiviral defense."; RL J. Interferon Cytokine Res. 31:145-158(2011). RN [74] RP FUNCTION IN EMCV RESTRICTION, AND INTERACTION WITH EMCV P3D-POL (MICROBIAL RP INFECTION). RX PubMed=21994459; DOI=10.1128/jvi.05808-11; RA Maroui M.A., Pampin M., Chelbi-Alix M.K.; RT "Promyelocytic leukemia isoform IV confers resistance to RT encephalomyocarditis virus via the sequestration of 3D polymerase in RT nuclear bodies."; RL J. Virol. 85:13164-13173(2011). RN [75] RP SUMOYLATION, AND DESUMOYLATION BY SENP6. RX PubMed=21148299; DOI=10.1091/mbc.e10-06-0504; RA Hattersley N., Shen L., Jaffray E.G., Hay R.T.; RT "The SUMO protease SENP6 is a direct regulator of PML nuclear bodies."; RL Mol. Biol. Cell 22:78-90(2011). RN [76] RP REVIEW ON FUNCTION. RX PubMed=21161613; DOI=10.1007/s12035-010-8156-y; RA Salomoni P., Betts-Henderson J.; RT "The role of PML in the nervous system."; RL Mol. Neurobiol. 43:114-123(2011). RN [77] RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY. RX PubMed=20972456; DOI=10.1038/onc.2010.462; RA Chu Y., Yang X.; RT "SUMO E3 ligase activity of TRIM proteins."; RL Oncogene 30:1108-1116(2011). RN [78] RP FUNCTION IN VARICELLA ZOSTER RESTRICTION, SUBCELLULAR LOCATION, AND RP INTERACTION WITH VZV VP26 (MICROBIAL INFECTION). RX PubMed=21304940; DOI=10.1371/journal.ppat.1001266; RA Reichelt M., Wang L., Sommer M., Perrino J., Nour A.M., Sen N., Baiker A., RA Zerboni L., Arvin A.M.; RT "Entrapment of viral capsids in nuclear PML cages is an intrinsic antiviral RT host defense against Varicella-Zoster virus."; RL PLoS Pathog. 7:E1001266-E1001266(2011). RN [79] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-518; SER-527 AND SER-530, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [80] RP SUMOYLATION AT LYS-65 AND LYS-160, PHOSPHORYLATION AT SER-565, SUBCELLULAR RP LOCATION, AND INTERACTION WITH PIAS1; PIAS2 AND CSNK2A1. RX PubMed=22406621; DOI=10.1158/0008-5472.can-11-3159; RA Rabellino A., Carter B., Konstantinidou G., Wu S.Y., Rimessi A., RA Byers L.A., Heymach J.V., Girard L., Chiang C.M., Teruya-Feldstein J., RA Scaglioni P.P.; RT "The SUMO E3-ligase PIAS1 regulates the tumor suppressor PML and its RT oncogenic counterpart PML-RARA."; RL Cancer Res. 72:2275-2284(2012). RN [81] RP SUBCELLULAR LOCATION, AND INTERACTION WITH MAGEA2. RX PubMed=22117195; DOI=10.1038/cdd.2011.173; RA Peche L.Y., Scolz M., Ladelfa M.F., Monte M., Schneider C.; RT "MageA2 restrains cellular senescence by targeting the function of RT PMLIV/p53 axis at the PML-NBs."; RL Cell Death Differ. 19:926-936(2012). RN [82] RP REVIEW ON FUNCTION. RX PubMed=22237204; DOI=10.1038/cddis.2011.122; RA Salomoni P., Dvorkina M., Michod D.; RT "Role of the promyelocytic leukaemia protein in cell death regulation."; RL Cell Death Dis. 3:E247-E247(2012). RN [83] RP FUNCTION, AND INTERACTION WITH TBX2; TBX3; E2F4 AND RBL2. RX PubMed=22002537; DOI=10.1038/emboj.2011.370; RA Martin N., Benhamed M., Nacerddine K., Demarque M.D., van Lohuizen M., RA Dejean A., Bischof O.; RT "Physical and functional interaction between PML and TBX2 in the RT establishment of cellular senescence."; RL EMBO J. 31:95-109(2012). RN [84] RP FUNCTION IN CIRCADIAN CLOCK, SUBCELLULAR LOCATION, INTERACTION WITH PER2, RP ACETYLATION AT LYS-487, AND DEACETYLATION BY SIRT1. RX PubMed=22274616; DOI=10.1038/emboj.2012.1; RA Miki T., Xu Z., Chen-Goodspeed M., Liu M., Van Oort-Jansen A., Rea M.A., RA Zhao Z., Lee C.C., Chang K.S.; RT "PML regulates PER2 nuclear localization and circadian function."; RL EMBO J. 31:1427-1439(2012). RN [85] RP REVIEW ON PTM. RX PubMed=23316480; DOI=10.3389/fonc.2012.00210; RA Cheng X., Kao H.Y.; RT "Post-translational modifications of PML: consequences and implications."; RL Front. Oncol. 2:210-210(2012). RN [86] RP FUNCTION, SUBCELLULAR LOCATION, SUMOYLATION AT LYS-490, AND INTERACTION RP WITH HDAC7; RANBP2 AND CTNNB1-TCF7L2 COMPLEX. RX PubMed=22155184; DOI=10.1053/j.gastro.2011.11.041; RA Satow R., Shitashige M., Jigami T., Fukami K., Honda K., Kitabayashi I., RA Yamada T.; RT "Beta-catenin inhibits promyelocytic leukemia protein tumor suppressor RT function in colorectal cancer cells."; RL Gastroenterology 142:572-581(2012). RN [87] RP INTERACTION WITH MOMLV IN AND RT (MICROBIAL INFECTION), AND SUBCELLULAR RP LOCATION. RX PubMed=22685230; DOI=10.1093/jb/mvs063; RA Okino Y., Inayoshi Y., Kojima Y., Kidani S., Kaneoka H., Honkawa A., RA Higuchi H., Nishijima K., Miyake K., Iijima S.; RT "Moloney murine leukemia virus integrase and reverse transcriptase interact RT with PML proteins."; RL J. Biochem. 152:161-169(2012). RN [88] RP FUNCTION. RX PubMed=22589541; DOI=10.1074/jbc.m112.340505; RA Cheng X., Liu Y., Chu H., Kao H.Y.; RT "Promyelocytic leukemia protein (PML) regulates endothelial cell network RT formation and migration in response to tumor necrosis factor alpha RT (TNFalpha) and interferon alpha (IFNalpha)."; RL J. Biol. Chem. 287:23356-23367(2012). RN [89] RP DOMAIN C-TERMINAL. RX PubMed=22773875; DOI=10.1074/jbc.m112.374769; RA Geng Y., Monajembashi S., Shao A., Cui D., He W., Chen Z., Hemmerich P., RA Tang J.; RT "Contribution of the C-terminal regions of promyelocytic leukemia protein RT (PML) isoforms II and V to PML nuclear body formation."; RL J. Biol. Chem. 287:30729-30742(2012). RN [90] RP REVIEW ON UBIQUITINATION. RX PubMed=22935031; DOI=10.1186/1423-0127-19-81; RA Chen R.H., Lee Y.R., Yuan W.C.; RT "The role of PML ubiquitination in human malignancies."; RL J. Biomed. Sci. 19:81-81(2012). RN [91] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH CIITA. RX PubMed=23007646; DOI=10.1083/jcb.201112015; RA Ulbricht T., Alzrigat M., Horch A., Reuter N., von Mikecz A., Steimle V., RA Schmitt E., Kraemer O.H., Stamminger T., Hemmerich P.; RT "PML promotes MHC class II gene expression by stabilizing the class II RT transactivator."; RL J. Cell Biol. 199:49-63(2012). RN [92] RP FUNCTION, AND TISSUE SPECIFICITY. RX PubMed=22886304; DOI=10.1172/jci62129; RA Carracedo A., Weiss D., Leliaert A.K., Bhasin M., de Boer V.C., Laurent G., RA Adams A.C., Sundvall M., Song S.J., Ito K., Finley L.S., Egia A., RA Libermann T., Gerhart-Hines Z., Puigserver P., Haigis M.C., RA Maratos-Flier E., Richardson A.L., Schafer Z.T., Pandolfi P.P.; RT "A metabolic prosurvival role for PML in breast cancer."; RL J. Clin. Invest. 122:3088-3100(2012). RN [93] RP INTERACTION WITH HHV-1 ICP0 (MICROBIAL INFECTION). RX PubMed=22875967; DOI=10.1128/jvi.01145-12; RA Cuchet-Lourenco D., Vanni E., Glass M., Orr A., Everett R.D.; RT "Herpes simplex virus 1 ubiquitin ligase ICP0 interacts with PML isoform I RT and induces its SUMO-independent degradation."; RL J. Virol. 86:11209-11222(2012). RN [94] RP INTERACTION WITH TRIM16. RX PubMed=22629402; DOI=10.1371/journal.pone.0037470; RA Bell J.L., Malyukova A., Holien J.K., Koach J., Parker M.W., Kavallaris M., RA Marshall G.M., Cheung B.B.; RT "TRIM16 acts as an E3 ubiquitin ligase and can heterodimerize with other RT TRIM family members."; RL PLoS ONE 7:E37470-E37470(2012). RN [95] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-36; SER-38; SER-48; SER-403; RP SER-505; SER-512; SER-518; SER-527; SER-530 AND THR-867, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [96] RP SUBCELLULAR LOCATION, AND INTERACTION WITH MDM2 AND MAPK7. RX PubMed=22869143; DOI=10.1038/onc.2012.332; RA Yang Q., Liao L., Deng X., Chen R., Gray N.S., Yates J.R. III, Lee J.D.; RT "BMK1 is involved in the regulation of p53 through disrupting the PML-MDM2 RT interaction."; RL Oncogene 32:3156-3164(2013). RN [97] RP UBIQUITINATION BY UHRF1. RX PubMed=22945642; DOI=10.1038/onc.2012.406; RA Guan D., Factor D., Liu Y., Wang Z., Kao H.Y.; RT "The epigenetic regulator UHRF1 promotes ubiquitination-mediated RT degradation of the tumor-suppressor protein promyelocytic leukemia RT protein."; RL Oncogene 32:3819-3828(2013). RN [98] RP SUMOYLATION, INTERACTION WITH RNF4, AND DOMAIN SIM. RX PubMed=23028697; DOI=10.1371/journal.pone.0044949; RA Maroui M.A., Kheddache-Atmane S., El Asmi F., Dianoux L., Aubry M., RA Chelbi-Alix M.K.; RT "Requirement of PML SUMO interacting motif for RNF4- or arsenic trioxide- RT induced degradation of nuclear PML isoforms."; RL PLoS ONE 7:E44949-E44949(2012). RN [99] RP FUNCTION. RX PubMed=23219818; DOI=10.1016/j.bbrc.2012.11.108; RA Kuroki M., Ariumi Y., Hijikata M., Ikeda M., Dansako H., Wakita T., RA Shimotohno K., Kato N.; RT "PML tumor suppressor protein is required for HCV production."; RL Biochem. Biophys. Res. Commun. 430:592-597(2013). RN [100] RP INTERACTION WITH NLRP3. RX PubMed=23430110; DOI=10.1182/blood-2012-05-432104; RA Lo Y.H., Huang Y.W., Wu Y.H., Tsai C.S., Lin Y.C., Mo S.T., Kuo W.C., RA Chuang Y.T., Jiang S.T., Shih H.M., Lai M.Z.; RT "Selective inhibition of the NLRP3 inflammasome by targeting to RT promyelocytic leukemia protein in mouse and human."; RL Blood 121:3185-3194(2013). RN [101] RP FUNCTION, AND INTERACTION WITH HUMAN ADENOVIRUS 2 E1A (MICROBIAL RP INFECTION). RX PubMed=23135708; DOI=10.1128/jvi.02023-12; RA Berscheminski J., Groitl P., Dobner T., Wimmer P., Schreiner S.; RT "The adenoviral oncogene E1A-13S interacts with a specific isoform of the RT tumor suppressor PML to enhance viral transcription."; RL J. Virol. 87:965-977(2013). RN [102] RP FUNCTION, AND INTERACTION WITH KAT6A. RX PubMed=23431171; DOI=10.1073/pnas.1300490110; RA Rokudai S., Laptenko O., Arnal S.M., Taya Y., Kitabayashi I., Prives C.; RT "MOZ increases p53 acetylation and premature senescence through its complex RT formation with PML."; RL Proc. Natl. Acad. Sci. U.S.A. 110:3895-3900(2013). RN [103] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-8; SER-36; SER-403; SER-518; RP SER-527 AND SER-530, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [104] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-65; LYS-380 AND LYS-490, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25218447; DOI=10.1038/nsmb.2890; RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M., RA Vertegaal A.C.; RT "Uncovering global SUMOylation signaling networks in a site-specific RT manner."; RL Nat. Struct. Mol. Biol. 21:927-936(2014). RN [105] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-65; LYS-160 AND LYS-490, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25772364; DOI=10.1016/j.celrep.2015.02.033; RA Hendriks I.A., Treffers L.W., Verlaan-de Vries M., Olsen J.V., RA Vertegaal A.C.; RT "SUMO-2 orchestrates chromatin modifiers in response to DNA damage."; RL Cell Rep. 10:1778-1791(2015). RN [106] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-65; LYS-160; LYS-380; LYS-394; RP LYS-478 AND LYS-490, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RX PubMed=25755297; DOI=10.1074/mcp.o114.044792; RA Xiao Z., Chang J.G., Hendriks I.A., Sigurdsson J.O., Olsen J.V., RA Vertegaal A.C.; RT "System-wide analysis of SUMOylation dynamics in response to replication RT stress reveals novel small ubiquitin-like modified target proteins and RT acceptor lysines relevant for genome stability."; RL Mol. Cell. Proteomics 14:1419-1434(2015). RN [107] RP INTERACTION OF PML-4 AND PML-5 WITH HADV5 E1B-55K (MICROBIAL INFECTION). RX PubMed=25772236; DOI=10.1038/onc.2015.63; RA Wimmer P., Berscheminski J., Blanchette P., Groitl P., Branton P.E., RA Hay R.T., Dobner T., Schreiner S.; RT "PML isoforms IV and V contribute to adenovirus-mediated oncogenic RT transformation by functionally inhibiting the tumor-suppressor p53."; RL Oncogene 35:69-82(2016). RN [108] RP SUMOYLATION AT LYS-160; LYS-380; LYS-400; LYS-490 AND LYS-497, MUTAGENESIS RP OF LYS-65; LYS-160; LYS-380; LYS-400; LYS-490 AND LYS-497, AND SUBCELLULAR RP LOCATION. RX PubMed=27211601; DOI=10.1038/srep26509; RA Liang Y.C., Lee C.C., Yao Y.L., Lai C.C., Schmitz M.L., Yang W.M.; RT "SUMO5, a novel poly-sumo isoform, regulates pml nuclear bodies."; RL Sci. Rep. 6:26509-26509(2016). RN [109] RP INTERACTION WITH PRDM1. RX PubMed=28842558; DOI=10.1038/s41467-017-00476-w; RA Wang W.F., Yan L., Liu Z., Liu L.X., Lin J., Liu Z.Y., Chen X.P., Zhang W., RA Xu Z.Z., Shi T., Li J.M., Zhao Y.L., Meng G., Xia Y., Li J.Y., Zhu J.; RT "HSP70-Hrd1 axis precludes the oncorepressor potential of N-terminal RT misfolded Blimp-1s in lymphoma cells."; RL Nat. Commun. 8:363-363(2017). RN [110] RP INHIBITION OF SUMOYLATION BY HHV-5 (MICROBIAL INFECTION), AND INTERACTION RP WITH HHV-5 IMMEDIATE EARLY PROTEIN IE1 (MICROBIAL INFECTION). RX PubMed=27903803; DOI=10.1128/jvi.02049-16; RA Schilling E.M., Scherer M., Reuter N., Schweininger J., Muller Y.A., RA Stamminger T.; RT "The Human Cytomegalovirus IE1 Protein Antagonizes PML Nuclear Body- RT Mediated Intrinsic Immunity via the Inhibition of PML De Novo RT SUMOylation."; RL J. Virol. 91:0-0(2017). RN [111] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-65; LYS-160; LYS-380; LYS-394; RP LYS-401; LYS-460; LYS-476; LYS-478; LYS-487; LYS-490 AND LYS-497, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=28112733; DOI=10.1038/nsmb.3366; RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C., RA Nielsen M.L.; RT "Site-specific mapping of the human SUMO proteome reveals co-modification RT with phosphorylation."; RL Nat. Struct. Mol. Biol. 24:325-336(2017). RN [112] RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND INTERACTION WITH HHV-5 IMMEDIATE RP EARLY PROTEIN IE1 (MICROBIAL INFECTION). RX PubMed=28250117; DOI=10.1128/jvi.02335-16; RA Reuter N., Schilling E.M., Scherer M., Mueller R., Stamminger T.; RT "The ND10 Component Promyelocytic Leukemia Protein Acts as an E3 Ligase for RT SUMOylation of the Major Immediate Early Protein IE1 of Human RT Cytomegalovirus."; RL J. Virol. 91:0-0(2017). RN [113] RP CLEAVAGE BY ENTEROVIRUS 71 PROTEASE 3C (MICROBIAL INFECTION), CLEAVAGE RP SITE, AND MUTAGENESIS OF GLN-430 AND GLN-444. RX PubMed=34930370; DOI=10.1186/s12985-021-01725-7; RA Li Z., Wu Y., Li H., Li W., Tan J., Qiao W.; RT "3C protease of enterovirus 71 cleaves promyelocytic leukemia protein and RT impairs PML-NBs production."; RL Virol. J. 18:255-255(2021). RN [114] RP SUBCELLULAR LOCATION. RX PubMed=36373674; DOI=10.7554/elife.79676; RA Oravcova M., Nie M., Zilio N., Maeda S., Jami-Alahmadi Y., RA Lazzerini-Denchi E., Wohlschlegel J.A., Ulrich H.D., Otomo T., Boddy M.N.; RT "The Nse5/6-like SIMC1-SLF2 complex localizes SMC5/6 to viral replication RT centers."; RL Elife 11:0-0(2022). RN [115] RP STRUCTURE BY NMR OF 49-104. RX PubMed=7729428; DOI=10.1002/j.1460-2075.1995.tb07139.x; RA Borden K.L.B., Boddy M.N., Lally J., O'Reilly N.J., Martin S., Howe K., RA Solomon E., Freemont P.S.; RT "The solution structure of the RING finger domain from the acute RT promyelocytic leukaemia proto-oncoprotein PML."; RL EMBO J. 14:1532-1541(1995). CC -!- FUNCTION: Functions via its association with PML-nuclear bodies (PML- CC NBs) in a wide range of important cellular processes, including tumor CC suppression, transcriptional regulation, apoptosis, senescence, DNA CC damage response, and viral defense mechanisms. Acts as the scaffold of CC PML-NBs allowing other proteins to shuttle in and out, a process which CC is regulated by SUMO-mediated modifications and interactions. Inhibits CC EIF4E-mediated mRNA nuclear export by reducing EIF4E affinity for the CC 5' 7-methylguanosine (m7G) cap of target mRNAs (PubMed:11500381, CC PubMed:11575918, PubMed:18391071). Isoform PML-4 has a multifaceted CC role in the regulation of apoptosis and growth suppression: activates CC RB1 and inhibits AKT1 via interactions with PP1 and PP2A phosphatases CC respectively, negatively affects the PI3K pathway by inhibiting MTOR CC and activating PTEN, and positively regulates p53/TP53 by acting at CC different levels (by promoting its acetylation and phosphorylation and CC by inhibiting its MDM2-dependent degradation). Isoform PML-4 also: acts CC as a transcriptional repressor of TBX2 during cellular senescence and CC the repression is dependent on a functional RBL2/E2F4 repressor CC complex, regulates double-strand break repair in gamma-irradiation- CC induced DNA damage responses via its interaction with WRN, acts as a CC negative regulator of telomerase by interacting with TERT, and CC regulates PER2 nuclear localization and circadian function. Isoform CC PML-6 inhibits specifically the activity of the tetrameric form of PKM. CC The nuclear isoforms (isoform PML-1, isoform PML-2, isoform PML-3, CC isoform PML-4 and isoform PML-5) in concert with SATB1 are involved in CC local chromatin-loop remodeling and gene expression regulation at the CC MHC-I locus. Isoform PML-2 is required for efficient IFN-gamma induced CC MHC II gene transcription via regulation of CIITA. Cytoplasmic PML is CC involved in the regulation of the TGF-beta signaling pathway. PML also CC regulates transcription activity of ELF4 and can act as an important CC mediator for TNF- and IFN-alpha-mediated inhibition of endothelial cell CC network formation and migration. {ECO:0000269|PubMed:11500381, CC ECO:0000269|PubMed:11575918, ECO:0000269|PubMed:18391071}. CC -!- FUNCTION: Exhibits antiviral activity against both DNA and RNA viruses. CC The antiviral activity can involve one or several isoform(s) and can be CC enhanced by the permanent PML-NB-associated protein DAXX or by the CC recruitment of p53/TP53 within these structures. Isoform PML-4 CC restricts varicella zoster virus (VZV) via sequestration of virion CC capsids in PML-NBs thereby preventing their nuclear egress and CC inhibiting formation of infectious virus particles. The sumoylated CC isoform PML-4 restricts rabies virus by inhibiting viral mRNA and CC protein synthesis. The cytoplasmic isoform PML-14 can restrict herpes CC simplex virus-1 (HHV-1) replication by sequestering the viral E3 CC ubiquitin-protein ligase ICP0 in the cytoplasm. Isoform PML-6 shows CC restriction activity towards human cytomegalovirus (HHV-5) and CC influenza A virus strains PR8(H1N1) and ST364(H3N2). Sumoylated isoform CC PML-4 and isoform PML-12 show antiviral activity against CC encephalomyocarditis virus (EMCV) by promoting nuclear sequestration of CC viral polymerase (P3D-POL) within PML NBs. Isoform PML-3 exhibits CC antiviral activity against poliovirus by inducing apoptosis in infected CC cells through the recruitment and the activation of p53/TP53 in the CC PML-NBs. Isoform PML-3 represses human foamy virus (HFV) transcription CC by complexing the HFV transactivator, bel1/tas, preventing its binding CC to viral DNA. PML may positively regulate infectious hepatitis C viral CC (HCV) production and isoform PML-2 may enhance adenovirus CC transcription. Functions as an E3 SUMO-protein ligase that sumoylates CC (HHV-5) immediate early protein IE1, thereby participating in the CC antiviral response (PubMed:20972456, PubMed:28250117). Isoforms PML-3 CC and PML-6 display the highest levels of sumoylation activity CC (PubMed:20972456, PubMed:28250117). {ECO:0000269|PubMed:20972456, CC ECO:0000269|PubMed:28250117}. CC -!- PATHWAY: Protein modification; protein sumoylation. CC {ECO:0000269|PubMed:20972456, ECO:0000269|PubMed:28250117}. CC -!- SUBUNIT: Key component of PML bodies. PML bodies are formed by the CC interaction of PML homodimers (via SUMO-binding motif) with sumoylated CC PML, leading to the assembly of higher oligomers. Several types of PML CC bodies have been observed. PML bodies can form hollow spheres that can CC sequester target proteins inside. Interacts (via SUMO-binding motif) CC with sumoylated proteins. Interacts (via C-terminus) with p53/TP53. CC Recruits p53/TP53 and CHEK2 into PML bodies, which promotes p53/TP53 CC phosphorylation at 'Ser-20' and prevents its proteasomal degradation. CC Interacts with MDM2, and sequesters MDM2 in the nucleolus, thereby CC preventing ubiquitination of p53/TP53. Interaction with PML-RARA CC oncoprotein and certain viral proteins causes disassembly of PML bodies CC and abolishes the normal PML function. Interacts with HIPK2, TERT, CC SIRT1, TOPBP1, TRIM27 and TRIM69. Interacts with ELF4 (via C-terminus). CC Interacts with ITPR3. Interacts (in the cytoplasm) with TGFBR1, TGFBR2 CC and PKM. Interacts (via the coiled-coil domain and when sumoylated) CC with SATB1. Interacts with UBE2I; the interaction is enhanced by CC arsenic binding. Interacts (PML-RARA oncoprotein, via the coiled-coil CC domain) with UBE2I; the interaction is enhanced by arsenic binding and CC is required for PML-RARA oncoprotein sumoylation and inhibition of RARA CC transactivational activity. Interacts with RB1, PPP1A, SMAD2, SMAD3, CC DAXX, RPL11 and MTOR. Interacts with PPARGC1A and KAT2A. Interacts with CC CSNK2A1 and CSNK2A3. Interacts with ANKRD2; the interaction is direct. CC Interacts (via SUMO-interacting motif) with sumoylated MORC3 CC (PubMed:20501696). Isoform PML-1, isoform PML-2, isoform PML-3, isoform CC PML-4, isoform PML-5 and isoform PML-6 interact with RNF4. Isoform PML- CC 1 interacts with NLRP3. Isoform PML-1, isoform PML-2, isoform PML-3, CC isoform PML-4 and isoform PML-5 interact with MAGEA2, RBL2, PER2 and CC E2F4. Isoform PML-2 interacts with CIITA. Isoform PML-2, isoform PML-3 CC and isoform PML-4 interact with TBX2. Isoform PML-4 interacts with CC RANBP2, HDAC7, KAT6A, WRN, PIN1, TBX3 and phosphorylated MAPK1/ERK2. CC Isoform PML-4 interacts with the CTNNB1 and TCF7L2/TCF4 complex. CC Isoform PML-4 preferentially interacts with MAPK7/BMK1 although other CC isoforms (isoform PML-1, isoform PML-2, isoform PML-3 and isoform PML- CC 6) also interact with it. Isoform PML-12 interacts with PIAS1, PIAS2 CC (isoform PIAS2-alpha) and CSNK2A1/CK2. Interacts with TRIM16. Interacts CC with PRDM1/Blimp-1 (PubMed:28842558). Interacts (via RING-type zinc CC finger) with EIF4E; the interaction results in conformational changes CC of both interacting proteins and reduces EIF4E affinity for the 5' m7G CC cap of mRNA, thus reducing EIF4E-mediated mRNA nuclear export CC (PubMed:11500381, PubMed:11575918). {ECO:0000269|PubMed:10610177, CC ECO:0000269|PubMed:10669754, ECO:0000269|PubMed:10684855, CC ECO:0000269|PubMed:11025664, ECO:0000269|PubMed:11500381, CC ECO:0000269|PubMed:11575918, ECO:0000269|PubMed:12006491, CC ECO:0000269|PubMed:12402044, ECO:0000269|PubMed:12439746, CC ECO:0000269|PubMed:12773567, ECO:0000269|PubMed:12810724, CC ECO:0000269|PubMed:14645235, ECO:0000269|PubMed:14976184, CC ECO:0000269|PubMed:15136035, ECO:0000269|PubMed:15195100, CC ECO:0000269|PubMed:15356634, ECO:0000269|PubMed:15467728, CC ECO:0000269|PubMed:15809060, ECO:0000269|PubMed:17081985, CC ECO:0000269|PubMed:17173041, ECO:0000269|PubMed:18298799, CC ECO:0000269|PubMed:19015637, ECO:0000269|PubMed:19567472, CC ECO:0000269|PubMed:20378816, ECO:0000269|PubMed:20501696, CC ECO:0000269|PubMed:20625391, ECO:0000269|PubMed:21639834, CC ECO:0000269|PubMed:22002537, ECO:0000269|PubMed:22033920, CC ECO:0000269|PubMed:22117195, ECO:0000269|PubMed:22155184, CC ECO:0000269|PubMed:22274616, ECO:0000269|PubMed:22406621, CC ECO:0000269|PubMed:22629402, ECO:0000269|PubMed:22869143, CC ECO:0000269|PubMed:23007646, ECO:0000269|PubMed:23028697, CC ECO:0000269|PubMed:23430110, ECO:0000269|PubMed:23431171, CC ECO:0000269|PubMed:28842558, ECO:0000269|PubMed:9570750}. CC -!- SUBUNIT: (Microbial infection) Interacts with Lassa virus Z protein and CC rabies virus phosphoprotein. {ECO:0000269|PubMed:9420283}. CC -!- SUBUNIT: (Microbial infection) Isoform PML-1 interacts with herpes CC simplex virus-1/HHV-1 ICP0. {ECO:0000269|PubMed:22875967}. CC -!- SUBUNIT: (Microbial infection) Isoform PML-2 interacts with human CC adenovirus 2 E1A and this interaction stimulates E1A-dependent CC transcriptional activation. {ECO:0000269|PubMed:23135708}. CC -!- SUBUNIT: (Microbial infection) Isoform PML-4 interacts with VZV capsid CC protein VP26/ORF23 capsid protein. {ECO:0000269|PubMed:21304940}. CC -!- SUBUNIT: (Microbial infection) The sumoylated isoform PML-4 interacts CC with encephalomyocarditis virus (EMCV) RNA-directed RNA polymerase 3D- CC POL (P3D-POL). {ECO:0000269|PubMed:21994459}. CC -!- SUBUNIT: (Microbial infection) Isoform PML-6 interacts with moloney CC murine leukemia virus (MoMLV) integrase (IN) and reverse transcriptase CC (RT). {ECO:0000269|PubMed:22685230}. CC -!- SUBUNIT: (Microbial infection) Isoform PML-4 and isoform PML-5 interact CC with human adenovirus 5 E1B-55K protein; these interactions promote CC efficient subnuclear targeting of E1B-55K to PML nuclear bodies. CC {ECO:0000269|PubMed:20639899, ECO:0000269|PubMed:23135708, CC ECO:0000269|PubMed:25772236}. CC -!- SUBUNIT: (Microbial infection) Isoform PML-3 interacts (via RING-type CC zinc finger) with human foamy virus bel1/tas and bet. CC {ECO:0000269|PubMed:11432836}. CC -!- SUBUNIT: (Microbial infection) Interacts with human cytomegalovirus CC (HHV-5) immediate early protein IE1; this interaction mediates PML CC desumoylation and PML-mediated sumoylation of IE1. CC {ECO:0000269|PubMed:27903803, ECO:0000269|PubMed:28250117, CC ECO:0000305|PubMed:15163746}. CC -!- INTERACTION: CC P29590; P68400: CSNK2A1; NbExp=2; IntAct=EBI-295890, EBI-347804; CC P29590; Q9UER7: DAXX; NbExp=6; IntAct=EBI-295890, EBI-77321; CC P29590; P06730: EIF4E; NbExp=5; IntAct=EBI-295890, EBI-73440; CC P29590; P25445: FAS; NbExp=4; IntAct=EBI-295890, EBI-494743; CC P29590; Q9Y2M5: KLHL20; NbExp=11; IntAct=EBI-295890, EBI-714379; CC P29590; Q13164: MAPK7; NbExp=6; IntAct=EBI-295890, EBI-1213983; CC P29590; Q00987: MDM2; NbExp=6; IntAct=EBI-295890, EBI-389668; CC P29590; O15055: PER2; NbExp=3; IntAct=EBI-295890, EBI-1054296; CC P29590; P25788: PSMA3; NbExp=2; IntAct=EBI-295890, EBI-348380; CC P29590; P63165: SUMO1; NbExp=6; IntAct=EBI-295890, EBI-80140; CC P29590; Q13207: TBX2; NbExp=2; IntAct=EBI-295890, EBI-2853051; CC P29590; Q6N021: TET2; NbExp=2; IntAct=EBI-295890, EBI-310727; CC P29590; Q15583: TGIF1; NbExp=3; IntAct=EBI-295890, EBI-714215; CC P29590; P04637: TP53; NbExp=4; IntAct=EBI-295890, EBI-366083; CC P29590; P62258: YWHAE; NbExp=2; IntAct=EBI-295890, EBI-356498; CC P29590; Q05516: ZBTB16; NbExp=7; IntAct=EBI-295890, EBI-711925; CC P29590; Q8UN00: gag-pro-pol; Xeno; NbExp=4; IntAct=EBI-295890, EBI-6692904; CC P29590; P03243-1; Xeno; NbExp=3; IntAct=EBI-295890, EBI-1927377; CC P29590; PRO_0000037566 [P27958]; Xeno; NbExp=6; IntAct=EBI-295890, EBI-6377335; CC P29590-1; Q9Y2M5: KLHL20; NbExp=3; IntAct=EBI-303992, EBI-714379; CC P29590-2; P03243-1; Xeno; NbExp=3; IntAct=EBI-303996, EBI-1927377; CC P29590-3; P04489; Xeno; NbExp=4; IntAct=EBI-8099068, EBI-6398911; CC P29590-5; Q00987: MDM2; NbExp=6; IntAct=EBI-304008, EBI-389668; CC P29590-5; O14746: TERT; NbExp=7; IntAct=EBI-304008, EBI-1772203; CC P29590-5; Q05516: ZBTB16; NbExp=2; IntAct=EBI-304008, EBI-711925; CC P29590-5; P03243-1; Xeno; NbExp=3; IntAct=EBI-304008, EBI-1927377; CC P29590-5; PRO_0000039791 [P03304]; Xeno; NbExp=3; IntAct=EBI-304008, EBI-6726189; CC P29590-13; P29590-13: PML; NbExp=3; IntAct=EBI-12368281, EBI-12368281; CC -!- SUBCELLULAR LOCATION: Nucleus. Nucleus, nucleoplasm. Cytoplasm CC {ECO:0000269|PubMed:27211601}. Nucleus, PML body CC {ECO:0000269|PubMed:20501696, ECO:0000269|PubMed:20719947, CC ECO:0000269|PubMed:27211601, ECO:0000269|PubMed:36373674}. Nucleus, CC nucleolus. Endoplasmic reticulum membrane {ECO:0000250}; Peripheral CC membrane protein {ECO:0000250}; Cytoplasmic side {ECO:0000250}. Early CC endosome membrane; Peripheral membrane protein; Cytoplasmic side. CC Note=Isoform PML-1 can shuttle between the nucleus and cytoplasm. CC Isoform PML-2, isoform PML-3, isoform PML-4, isoform PML-5 and isoform CC PML-6 are nuclear isoforms whereas isoform PML-7 and isoform PML-14 CC lacking the nuclear localization signal are cytoplasmic isoforms. CC Detected in the nucleolus after DNA damage. Acetylation at Lys-487 is CC essential for its nuclear localization. Within the nucleus, most of PML CC is expressed in the diffuse nuclear fraction of the nucleoplasm and CC only a small fraction is found in the matrix-associated nuclear bodies CC (PML-NBs). The transfer of PML from the nucleoplasm to PML-NBs depends CC on its phosphorylation and sumoylation. The B1 box and the RING finger CC are also required for the localization in PML-NBs. Also found in CC specific membrane structures termed mitochondria-associated membranes CC (MAMs) which connect the endoplasmic reticulum (ER) and the CC mitochondria. Sequestered in the cytoplasm by interaction with rabies CC virus phosphoprotein. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=12; CC Name=PML-1; Synonyms=PML-I, TRIM19alpha; CC IsoId=P29590-1; Sequence=Displayed; CC Name=PML-2; Synonyms=PML-II, TRIM19kappa; CC IsoId=P29590-8; Sequence=VSP_040595; CC Name=PML-3; Synonyms=PML-III; CC IsoId=P29590-9; Sequence=VSP_040596, VSP_040597; CC Name=PML-4; Synonyms=PML-IV, PML-X, TRIM19zeta; CC IsoId=P29590-5; Sequence=VSP_005744, VSP_005745; CC Name=PML-5; Synonyms=PML-2, PML-V, TRIM19beta; CC IsoId=P29590-2; Sequence=VSP_005739, VSP_005740; CC Name=PML-6; Synonyms=PML-3B, PML-VI, TRIM19epsilon; CC IsoId=P29590-4; Sequence=VSP_005742, VSP_005743; CC Name=PML-7; Synonyms=PML-VII, TRIM19theta; CC IsoId=P29590-10; Sequence=VSP_040591, VSP_040594; CC Name=PML-8; Synonyms=PML-2G, PML-IIG, TRIM19gamma; CC IsoId=P29590-3; Sequence=VSP_005741; CC Name=PML-11; Synonyms=PML-1A, PML-IA; CC IsoId=P29590-11; Sequence=VSP_040590; CC Name=PML-12; Synonyms=PML-4A, PML-IVA, TRIM19lambda; CC IsoId=P29590-12; Sequence=VSP_040590, VSP_005744, VSP_005745; CC Name=PML-13; Synonyms=PML-2A, PML-IIA; CC IsoId=P29590-13; Sequence=VSP_040590, VSP_040595; CC Name=PML-14; Synonyms=PML-6B, PML-VIB, TRIM19eta, TRIM19iota; CC IsoId=P29590-14; Sequence=VSP_040592, VSP_040593; CC -!- INDUCTION: By interferons alpha, beta and gamma. Up-regulated by IRF3 CC and p53/TP53. CC -!- DOMAIN: The coiled-coil domain mediates a strong homo/multidimerization CC activity essential for core assembly of PML-NBs. Interacts with PKM via CC its coiled-coil domain (PubMed:18298799). CC {ECO:0000269|PubMed:18298799}. CC -!- DOMAIN: The B box-type zinc binding domain and the coiled-coil domain CC mediate its interaction with PIAS1. {ECO:0000269|PubMed:22406621}. CC -!- DOMAIN: Binds arsenic via the RING-type zinc finger. CC {ECO:0000269|PubMed:20378816}. CC -!- DOMAIN: (Microbial infection) The RING-type zinc finger is necessary CC for the sumoylation of human cytomegalovirus (HHV-5) immediate early CC protein IE1. {ECO:0000269|PubMed:28250117}. CC -!- DOMAIN: The unique C-terminal domains of isoform PML-2 and isoform PML- CC 5 play an important role in regulating the localization, assembly CC dynamics, and functions of PML-NBs. {ECO:0000269|PubMed:22773875}. CC -!- DOMAIN: The Sumo interaction motif (SIM) is required for efficient CC ubiquitination, recruitment of proteasome components within PML-NBs and CC PML degradation in response to arsenic trioxide. CC {ECO:0000269|PubMed:23028697}. CC -!- PTM: Ubiquitinated; mediated by RNF4, RNF111, UHRF1, UBE3A/E6AP, CC BCR(KLHL20) E3 ubiquitin ligase complex E3 ligase complex, SIAH1 or CC SIAH2 and leading to subsequent proteasomal degradation CC (PubMed:18408734, PubMed:21840486, PubMed:22033920). Ubiquitination by CC BCR(KLHL20) E3 ubiquitin ligase complex E3 ligase complex requires CC CDK1/2-mediated phosphorylation at Ser-518 which in turn is recognized CC by prolyl-isopeptidase PIN1 and PIN1-catalyzed isomerization further CC potentiates PML interaction with KLHL20 (PubMed:21840486, CC PubMed:22033920). 'Lys-6'-, 'Lys-11'-, 'Lys-48'- and 'Lys-63'-linked CC polyubiquitination by RNF4 is polysumoylation-dependent CC (PubMed:18408734). Ubiquitination by RNF111 is polysumoylation- CC dependent (By similarity). {ECO:0000250|UniProtKB:Q60953, CC ECO:0000269|PubMed:18408734, ECO:0000269|PubMed:21840486, CC ECO:0000269|PubMed:22033920}. CC -!- PTM: Sumoylation regulates PML's: stability in response to CC extracellular or intracellular stimuli, transcription directly and CC indirectly, through sequestration of or dissociation of the CC transcription factors from PML-NBs, ability to regulate apoptosis and CC its anti-viral activities. It is also essential for: maintaining proper CC PML nuclear bodies (PML-NBs) structure and normal function, recruitment CC of components of PML-NBs, the turnover and retention of PML in PML-NBs CC and the integrity of PML-NBs. Undergoes 'Lys-11'-linked sumoylation. CC Sumoylation on all three sites (Lys-65, Lys-160 and Lys-490) is CC required for nuclear body formation. Sumoylation on Lys-160 is a CC prerequisite for sumoylation on Lys-65. Lys-65 and Lys-160 are CC sumoylated by PISA1 and PIAS2. PIAS1-mediated sumoylation of PML CC promotes its interaction with CSNK2A1/CK2 and phosphorylation at Ser- CC 565 which in turn triggers its ubiquitin-mediated degradation. PIAS1- CC mediated sumoylation of PML-RARA promotes its ubiquitin-mediated CC degradation. The PML-RARA fusion protein requires the coiled-coil CC domain for sumoylation. Sumoylation at Lys-490 by RANBP2 is essential CC for the proper assembly of PML-NBs. SUMO1P1/SUMO5 conjugated PML at CC Lys-160, Lys-380, Lys-400, Lys-490 and Lys-497, but Lys-380, Lys-400 CC and Lys-497 are not key acceptor lysines. SUMO1P1/SUMO5 forms polymeric CC chain on Lys-160 of PML by successive conjugation at 'Lys-18'; CC facilitating recruitment of PML-NB components, which enlarges PML. CC SUMO1P1/SUMO5 conjugation of PML increases SUMO2/3 conjugation, which CC leads to the recruitment of RNF4 and ubiquitin-dependent disintegration CC of PML-NBs. SUMO1P1/SUMO5 monoconjugated Lys-490 (PubMed:27211601). DNA CC damage triggers its sumoylation while some but not all viral infections CC can abolish sumoylation. Desumoylated by SENP1, SENP2, SENP3, SENP5 and CC SENP6 (PubMed:12419228, PubMed:21148299, PubMed:27211601). Arsenic CC induces PML and PML-RARA polysumoylation and their subsequent RNF4- CC dependent ubiquitination and proteasomal degradation, and is used as CC treatment in acute promyelocytic leukemia (APL). The nuclear isoforms CC (isoform PML-1, isoform PML-2, isoform PML-3, isoform PML-4, isoform CC PML-5 and isoform PML-6) show an increased sumoylation in response to CC arsenic trioxide. The cytoplasmic isoform PML-7 is not sumoylated. CC {ECO:0000269|PubMed:12419228, ECO:0000269|PubMed:18408734, CC ECO:0000269|PubMed:21148299, ECO:0000269|PubMed:22155184, CC ECO:0000269|PubMed:22406621, ECO:0000269|PubMed:27211601, CC ECO:0000269|PubMed:9756909}. CC -!- PTM: Phosphorylation is a major regulatory mechanism that controls PML CC protein abundance and the number and size of PML nuclear bodies (PML- CC NBs). Phosphorylated in response to DNA damage, probably by ATR CC (PubMed:15195100). HIPK2-mediated phosphorylation at Ser-8, Ser-36 and CC Ser-38 leads to increased accumulation of PML protein and its CC sumoylation and is required for the maximal pro-apoptotic activity of CC PML after DNA damage (PubMed:19015637). CHEK2-mediated phosphorylation CC at Ser-117 is important for PML-mediated apoptosis following DNA damage CC (PubMed:12402044). MAPK1-mediated phosphorylations at Ser-403, Ser-505, CC Ser-527 and Ser-530 and CDK1/2-mediated phosphorylation at Ser-518 CC promote PIN1-dependent PML degradation (PubMed:21840486, CC PubMed:22033920). CK2-mediated phosphorylation at Ser-565 primes PML CC ubiquitination via an unidentified ubiquitin ligase (PubMed:20719947, CC PubMed:22406621). {ECO:0000269|PubMed:12402044, CC ECO:0000269|PubMed:15195100, ECO:0000269|PubMed:19015637, CC ECO:0000269|PubMed:20719947, ECO:0000269|PubMed:21840486, CC ECO:0000269|PubMed:22033920, ECO:0000269|PubMed:22406621}. CC -!- PTM: (Microbial infection) Upon infection with Epstein-Barr virus, CC phosphorylated by CK2. Viral EBNA1 increases the association of CK2 CC with PML proteins, which increases PML phosphorylation by CK2, CC triggering the USP7-dependent polyubiquitylation and degradation of CC PML. {ECO:0000269|PubMed:20719947}. CC -!- PTM: Acetylation at Lys-487 is essential for its nuclear localization. CC Deacetylated at Lys-487 by SIRT1 and this deacetylation promotes PML CC control of PER2 nuclear localization. {ECO:0000269|PubMed:18621739, CC ECO:0000269|PubMed:22274616}. CC -!- PTM: (Microbial infection) Immediate early protein IE1 of human CC cytomegalovirus (HHV-5) interferes with the sumoylation of PML CC (PubMed:10233977, PubMed:15163746, PubMed:27903803). Immediate early CC protein IE1 inhibits PML de novo sumoylation (PubMed:27903803). CC {ECO:0000269|PubMed:10233977, ECO:0000269|PubMed:15163746, CC ECO:0000269|PubMed:27903803}. CC -!- PTM: (Microbial infection) Cleaved at two different sites by CC enterovirus 71 protease 3C, leading to impaired PML-Nuclear bodies CC formation. {ECO:0000269|PubMed:34930370}. CC -!- DISEASE: Note=A chromosomal aberration involving PML may be a cause of CC acute promyelocytic leukemia (APL). Translocation t(15;17)(q21;q21) CC with RARA. The PML breakpoints (type A and type B) lie on either side CC of an alternatively spliced exon. {ECO:0000269|PubMed:1652369, CC ECO:0000269|PubMed:1720570}. CC -!- MISCELLANEOUS: [Isoform PML-8]: Non-canonical splice sites. Might CC alternatively represent a polymorphic variation. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAA60351.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=AAA60352.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=AAA60388.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=AAA60390.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=BAB62809.1; Type=Miscellaneous discrepancy; Note=Chimeric cDNA.; Evidence={ECO:0000305}; CC Sequence=BAD92648.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/41/PML"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; S50913; AAB19601.2; -; mRNA. DR EMBL; M79462; AAA60388.1; ALT_INIT; mRNA. DR EMBL; M79463; AAA60351.1; ALT_INIT; mRNA. DR EMBL; M79464; AAA60390.1; ALT_INIT; mRNA. DR EMBL; X63131; CAA44841.1; -; mRNA. DR EMBL; M73778; AAA60125.1; -; mRNA. DR EMBL; M80185; AAA60352.1; ALT_INIT; mRNA. DR EMBL; AF230401; AAG50180.1; -; mRNA. DR EMBL; AF230402; AAG50181.1; -; mRNA. DR EMBL; AF230403; AAG50182.1; -; mRNA. DR EMBL; AF230405; AAG50184.1; -; mRNA. DR EMBL; AF230406; AAG50185.1; -; mRNA. DR EMBL; AF230407; AAG50186.1; -; mRNA. DR EMBL; AF230408; AAG50187.1; -; mRNA. DR EMBL; AF230409; AAG50188.1; -; mRNA. DR EMBL; AF230410; AAG50189.1; -; mRNA. DR EMBL; AF230411; AAG50190.1; -; mRNA. DR EMBL; BT009911; AAP88913.1; -; mRNA. DR EMBL; AB209411; BAD92648.1; ALT_INIT; mRNA. DR EMBL; AC013486; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC108137; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC000080; AAH00080.2; -; mRNA. DR EMBL; BC020994; AAH20994.1; -; mRNA. DR EMBL; X64800; CAA46026.1; -; Genomic_DNA. DR EMBL; AB067754; BAB62809.1; ALT_SEQ; mRNA. DR CCDS; CCDS10255.1; -. [P29590-1] DR CCDS; CCDS10256.1; -. [P29590-10] DR CCDS; CCDS10257.1; -. [P29590-8] DR CCDS; CCDS10258.1; -. [P29590-13] DR CCDS; CCDS45297.1; -. [P29590-5] DR CCDS; CCDS45298.1; -. [P29590-2] DR CCDS; CCDS45299.1; -. [P29590-4] DR CCDS; CCDS45300.1; -. [P29590-14] DR CCDS; CCDS58386.1; -. [P29590-12] DR PIR; A40044; A40044. DR PIR; I38054; I38054. DR PIR; S19244; S19244. DR PIR; S42516; S42516. DR PIR; S44381; S44381. DR RefSeq; NP_002666.1; NM_002675.4. [P29590-5] DR RefSeq; NP_150241.2; NM_033238.3. [P29590-1] DR RefSeq; NP_150242.1; NM_033239.3. [P29590-8] DR RefSeq; NP_150243.2; NM_033240.3. [P29590-2] DR RefSeq; NP_150247.2; NM_033244.4. [P29590-4] DR RefSeq; NP_150249.1; NM_033246.3. [P29590-14] DR RefSeq; NP_150250.2; NM_033247.3. [P29590-10] DR RefSeq; NP_150252.1; NM_033249.3. [P29590-12] DR RefSeq; NP_150253.2; NM_033250.3. [P29590-13] DR PDB; 1BOR; NMR; -; A=49-104. DR PDB; 2MVW; NMR; -; A/B=120-168. DR PDB; 2MWX; NMR; -; A=49-104. DR PDB; 4WJN; X-ray; 1.50 A; B=547-573. DR PDB; 4WJO; X-ray; 1.46 A; B=547-573. DR PDB; 5YUF; X-ray; 1.60 A; A/B/C/D=49-99. DR PDB; 6IMQ; X-ray; 2.06 A; A/B/C/D=120-168. DR PDB; 6UYO; X-ray; 1.64 A; B/D=547-574. DR PDB; 6UYP; X-ray; 1.42 A; B=547-574. DR PDB; 6UYQ; X-ray; 1.50 A; B=547-574. DR PDB; 6UYR; X-ray; 1.30 A; B=547-574. DR PDB; 6UYS; X-ray; 1.59 A; B/D=547-574. DR PDB; 6UYT; X-ray; 1.66 A; B=547-574. DR PDB; 6UYU; X-ray; 1.66 A; B/D=547-574. DR PDB; 6UYV; X-ray; 1.40 A; B=547-574. DR PDB; 8DJH; X-ray; 1.77 A; B=546-573. DR PDB; 8DJI; X-ray; 1.97 A; B=547-574. DR PDB; 8J25; X-ray; 2.60 A; A=183-236. DR PDB; 8J2P; X-ray; 2.09 A; A/E=183-236. DR PDB; 8YTC; EM; 5.30 A; A/B=46-256. DR PDBsum; 1BOR; -. DR PDBsum; 2MVW; -. DR PDBsum; 2MWX; -. DR PDBsum; 4WJN; -. DR PDBsum; 4WJO; -. DR PDBsum; 5YUF; -. DR PDBsum; 6IMQ; -. DR PDBsum; 6UYO; -. DR PDBsum; 6UYP; -. DR PDBsum; 6UYQ; -. DR PDBsum; 6UYR; -. DR PDBsum; 6UYS; -. DR PDBsum; 6UYT; -. DR PDBsum; 6UYU; -. DR PDBsum; 6UYV; -. DR PDBsum; 8DJH; -. DR PDBsum; 8DJI; -. DR PDBsum; 8J25; -. DR PDBsum; 8J2P; -. DR PDBsum; 8YTC; -. DR AlphaFoldDB; P29590; -. DR BMRB; P29590; -. DR EMDB; EMD-39571; -. DR SMR; P29590; -. DR BioGRID; 111384; 962. DR CORUM; P29590; -. DR DIP; DIP-33053N; -. DR FunCoup; P29590; 2387. DR IntAct; P29590; 193. DR MINT; P29590; -. DR STRING; 9606.ENSP00000268058; -. DR DrugBank; DB01169; Arsenic trioxide. DR GlyGen; P29590; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P29590; -. DR PhosphoSitePlus; P29590; -. DR SwissPalm; P29590; -. DR BioMuta; PML; -. DR DMDM; 215274219; -. DR jPOST; P29590; -. DR MassIVE; P29590; -. DR PaxDb; 9606-ENSP00000268058; -. DR PeptideAtlas; P29590; -. DR ProteomicsDB; 19281; -. DR ProteomicsDB; 54589; -. [P29590-1] DR ProteomicsDB; 54590; -. [P29590-10] DR ProteomicsDB; 54591; -. [P29590-11] DR ProteomicsDB; 54592; -. [P29590-12] DR ProteomicsDB; 54593; -. [P29590-13] DR ProteomicsDB; 54594; -. [P29590-14] DR ProteomicsDB; 54595; -. [P29590-2] DR ProteomicsDB; 54596; -. [P29590-3] DR ProteomicsDB; 54597; -. [P29590-4] DR ProteomicsDB; 54598; -. [P29590-5] DR ProteomicsDB; 54599; -. [P29590-8] DR ProteomicsDB; 54600; -. [P29590-9] DR Pumba; P29590; -. DR Antibodypedia; 1737; 602 antibodies from 45 providers. DR DNASU; 5371; -. DR Ensembl; ENST00000268058.8; ENSP00000268058.3; ENSG00000140464.21. [P29590-1] DR Ensembl; ENST00000268059.10; ENSP00000268059.6; ENSG00000140464.21. [P29590-8] DR Ensembl; ENST00000354026.10; ENSP00000315434.8; ENSG00000140464.21. [P29590-13] DR Ensembl; ENST00000359928.8; ENSP00000353004.4; ENSG00000140464.21. [P29590-14] DR Ensembl; ENST00000395132.6; ENSP00000378564.2; ENSG00000140464.21. [P29590-10] DR Ensembl; ENST00000395135.7; ENSP00000378567.3; ENSG00000140464.21. [P29590-5] DR Ensembl; ENST00000435786.6; ENSP00000395576.2; ENSG00000140464.21. [P29590-2] DR Ensembl; ENST00000436891.7; ENSP00000394642.3; ENSG00000140464.21. [P29590-4] DR Ensembl; ENST00000564428.5; ENSP00000457023.1; ENSG00000140464.21. [P29590-12] DR Ensembl; ENST00000565898.5; ENSP00000455838.1; ENSG00000140464.21. [P29590-11] DR Ensembl; ENST00000567543.5; ENSP00000456277.1; ENSG00000140464.21. [P29590-14] DR Ensembl; ENST00000569477.5; ENSP00000455612.1; ENSG00000140464.21. [P29590-9] DR Ensembl; ENST00000569965.5; ENSP00000456486.1; ENSG00000140464.21. [P29590-4] DR GeneID; 5371; -. DR KEGG; hsa:5371; -. DR MANE-Select; ENST00000268058.8; ENSP00000268058.3; NM_033238.3; NP_150241.2. DR UCSC; uc002awk.4; human. [P29590-1] DR AGR; HGNC:9113; -. DR CIViC; 5371; 7 evidence items across 10 molecular profiles. DR ClinPGx; PA33439; -. DR CTD; 5371; -. DR DisGeNET; 5371; -. DR GeneCards; PML; -. DR HGNC; HGNC:9113; PML. DR HPA; ENSG00000140464; Low tissue specificity. DR MalaCards; PML; -. DR MIM; 102578; gene. DR OpenTargets; ENSG00000140464; -. DR Orphanet; 520; Acute promyelocytic leukemia. DR VEuPathDB; HostDB:ENSG00000140464; -. DR eggNOG; KOG2177; Eukaryota. DR GeneTree; ENSGT00510000048454; -. DR HOGENOM; CLU_009136_1_0_1; -. DR InParanoid; P29590; -. DR OrthoDB; 10250935at2759; -. DR PAN-GO; P29590; 7 GO annotations based on evolutionary models. DR PhylomeDB; P29590; -. DR PathwayCommons; P29590; -. DR Reactome; R-HSA-3108214; SUMOylation of DNA damage response and repair proteins. DR Reactome; R-HSA-3232142; SUMOylation of ubiquitinylation proteins. DR Reactome; R-HSA-6804758; Regulation of TP53 Activity through Acetylation. DR Reactome; R-HSA-877300; Interferon gamma signaling. DR Reactome; R-HSA-8934593; Regulation of RUNX1 Expression and Activity. DR Reactome; R-HSA-8948747; Regulation of PTEN localization. DR Reactome; R-HSA-9609690; HCMV Early Events. DR Reactome; R-HSA-9616222; Transcriptional regulation of granulopoiesis. [P29590-4] DR SignaLink; P29590; -. DR SIGNOR; P29590; -. DR UniPathway; UPA00886; -. DR Agora; ENSG00000140464; -. DR BioGRID-ORCS; 5371; 21 hits in 1215 CRISPR screens. DR CD-CODE; 8C2F96ED; Centrosome. DR CD-CODE; B5B9A610; PML body. DR ChiTaRS; PML; human. DR EvolutionaryTrace; P29590; -. DR GeneWiki; Promyelocytic_leukemia_protein; -. DR GenomeRNAi; 5371; -. DR Pharos; P29590; Tbio. DR PRO; PR:P29590; -. DR Proteomes; UP000005640; Chromosome 15. DR RNAct; P29590; protein. DR Bgee; ENSG00000140464; Expressed in omental fat pad and 171 other cell types or tissues. DR ExpressionAtlas; P29590; baseline and differential. DR GO; GO:0000781; C:chromosome, telomeric region; IDA:BHF-UCL. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; ISS:UniProtKB. DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell. DR GO; GO:0016363; C:nuclear matrix; IDA:UniProtKB. DR GO; GO:0031965; C:nuclear membrane; IDA:UniProtKB. DR GO; GO:0005730; C:nucleolus; IDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:UniProtKB. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0016605; C:PML body; IDA:UniProtKB. DR GO; GO:0050897; F:cobalt ion binding; IDA:UniProtKB. DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0060090; F:molecular adaptor activity; IDA:UniProt. DR GO; GO:0046982; F:protein heterodimerization activity; IDA:UniProtKB. DR GO; GO:0042803; F:protein homodimerization activity; IPI:BHF-UCL. DR GO; GO:0046332; F:SMAD binding; IEA:Ensembl. DR GO; GO:0032183; F:SUMO binding; IPI:UniProtKB. DR GO; GO:0019789; F:SUMO transferase activity; EXP:Reactome. DR GO; GO:0003713; F:transcription coactivator activity; IDA:UniProtKB. DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB. DR GO; GO:0061659; F:ubiquitin-like protein ligase activity; IBA:GO_Central. DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB. DR GO; GO:0006915; P:apoptotic process; IDA:UniProtKB. DR GO; GO:0060444; P:branching involved in mammary gland duct morphogenesis; IEA:Ensembl. DR GO; GO:0045165; P:cell fate commitment; IEA:Ensembl. DR GO; GO:0071353; P:cellular response to interleukin-4; IEA:Ensembl. DR GO; GO:1990830; P:cellular response to leukemia inhibitory factor; IEA:Ensembl. DR GO; GO:0090398; P:cellular senescence; IDA:UniProtKB. DR GO; GO:0006338; P:chromatin remodeling; IDA:UniProtKB. DR GO; GO:0032922; P:circadian regulation of gene expression; ISS:UniProtKB. DR GO; GO:0030330; P:DNA damage response, signal transduction by p53 class mediator; ISS:UniProtKB. DR GO; GO:0032469; P:endoplasmic reticulum calcium ion homeostasis; ISS:UniProtKB. DR GO; GO:0043153; P:entrainment of circadian clock by photoperiod; ISS:UniProtKB. DR GO; GO:0097191; P:extrinsic apoptotic signaling pathway; IEA:Ensembl. DR GO; GO:0010761; P:fibroblast migration; IEA:Ensembl. DR GO; GO:0045087; P:innate immune response; IDA:UniProtKB. DR GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IDA:UniProtKB. DR GO; GO:0042771; P:intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; ISS:UniProtKB. DR GO; GO:0070059; P:intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress; IEA:Ensembl. DR GO; GO:0008631; P:intrinsic apoptotic signaling pathway in response to oxidative stress; IEA:Ensembl. DR GO; GO:0051457; P:maintenance of protein location in nucleus; IDA:MGI. DR GO; GO:0030099; P:myeloid cell differentiation; IEA:Ensembl. DR GO; GO:0016525; P:negative regulation of angiogenesis; IMP:UniProtKB. DR GO; GO:0030308; P:negative regulation of cell growth; IDA:UniProtKB. DR GO; GO:0008285; P:negative regulation of cell population proliferation; IMP:BHF-UCL. DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:0032691; P:negative regulation of interleukin-1 beta production; IEA:Ensembl. DR GO; GO:0045930; P:negative regulation of mitotic cell cycle; IDA:UniProtKB. DR GO; GO:0032211; P:negative regulation of telomere maintenance via telomerase; IMP:UniProtKB. DR GO; GO:0032938; P:negative regulation of translation in response to oxidative stress; IDA:UniProtKB. DR GO; GO:2000059; P:negative regulation of ubiquitin-dependent protein catabolic process; IMP:UniProtKB. DR GO; GO:0090402; P:oncogene-induced cell senescence; IEA:Ensembl. DR GO; GO:0030578; P:PML body organization; IDA:UniProtKB. DR GO; GO:0060058; P:positive regulation of apoptotic process involved in mammary gland involution; IDA:UniProtKB. DR GO; GO:0002230; P:positive regulation of defense response to virus by host; IMP:UniProtKB. DR GO; GO:2001238; P:positive regulation of extrinsic apoptotic signaling pathway; IMP:UniProtKB. DR GO; GO:0048146; P:positive regulation of fibroblast proliferation; IEA:Ensembl. DR GO; GO:1904816; P:positive regulation of protein localization to chromosome, telomeric region; IDA:BHF-UCL. DR GO; GO:1901798; P:positive regulation of signal transduction by p53 class mediator; IEA:Ensembl. DR GO; GO:0032206; P:positive regulation of telomere maintenance; IMP:BHF-UCL. DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IDA:UniProtKB. DR GO; GO:0006606; P:protein import into nucleus; IEA:Ensembl. DR GO; GO:0050821; P:protein stabilization; IDA:UniProtKB. DR GO; GO:0016925; P:protein sumoylation; TAS:Reactome. DR GO; GO:0006605; P:protein targeting; IDA:UniProtKB. DR GO; GO:0065003; P:protein-containing complex assembly; IDA:UniProtKB. DR GO; GO:0031503; P:protein-containing complex localization; IEA:Ensembl. DR GO; GO:0010522; P:regulation of calcium ion transport into cytosol; ISS:UniProtKB. DR GO; GO:0030155; P:regulation of cell adhesion; IEA:Ensembl. DR GO; GO:0051726; P:regulation of cell cycle; IDA:UniProtKB. DR GO; GO:0042752; P:regulation of circadian rhythm; ISS:UniProtKB. DR GO; GO:0006355; P:regulation of DNA-templated transcription; IMP:UniProtKB. DR GO; GO:2000779; P:regulation of double-strand break repair; IMP:UniProtKB. DR GO; GO:0034097; P:response to cytokine; IDA:BHF-UCL. DR GO; GO:0010332; P:response to gamma radiation; IEA:Ensembl. DR GO; GO:0001666; P:response to hypoxia; IDA:UniProtKB. DR GO; GO:0009411; P:response to UV; IEA:Ensembl. DR GO; GO:0048384; P:retinoic acid receptor signaling pathway; IEA:Ensembl. DR GO; GO:0060395; P:SMAD protein signal transduction; IEA:Ensembl. DR GO; GO:0044790; P:suppression of viral release by host; IDA:UniProtKB. DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; IEA:Ensembl. DR CDD; cd19804; Bbox1_TRIM19_C-V; 1. DR CDD; cd19770; Bbox2_TRIM19_C-V; 1. DR CDD; cd16579; RING-HC_PML_C-V; 1. DR DisProt; DP03104; -. DR FunFam; 3.30.40.10:FF:000178; PML isoform 6; 1. DR Gene3D; 3.30.160.60; Classic Zinc Finger; 1. DR Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 1. DR InterPro; IPR021978; PML-like_CC. DR InterPro; IPR057617; PML_C. DR InterPro; IPR047153; TRIM45/56/19-like. DR InterPro; IPR000315; Znf_B-box. DR InterPro; IPR018957; Znf_C3HC4_RING-type. DR InterPro; IPR001841; Znf_RING. DR InterPro; IPR013083; Znf_RING/FYVE/PHD. DR InterPro; IPR017907; Znf_RING_CS. DR PANTHER; PTHR25462; BONUS, ISOFORM C-RELATED; 1. DR PANTHER; PTHR25462:SF302; PROTEIN PML; 1. DR Pfam; PF22586; ANCHR-like_BBOX; 1. DR Pfam; PF25244; PML_C; 1. DR Pfam; PF12126; PML_CC; 1. DR Pfam; PF00097; zf-C3HC4; 1. DR SMART; SM00336; BBOX; 1. DR SMART; SM00184; RING; 1. DR SUPFAM; SSF57850; RING/U-box; 1. DR PROSITE; PS50119; ZF_BBOX; 2. DR PROSITE; PS00518; ZF_RING_1; 1. DR PROSITE; PS50089; ZF_RING_2; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Activator; Alternative splicing; KW Antiviral defense; Apoptosis; Biological rhythms; KW Chromosomal rearrangement; Coiled coil; Cytoplasm; DNA-binding; KW Endoplasmic reticulum; Endosome; Host-virus interaction; Immunity; KW Innate immunity; Isopeptide bond; Membrane; Metal-binding; Nucleus; KW Phosphoprotein; Proteomics identification; Proto-oncogene; KW Reference proteome; Repeat; Transcription; Transcription regulation; KW Transferase; Tumor suppressor; Ubl conjugation; Zinc; Zinc-finger. FT CHAIN 1..882 FT /note="Protein PML" FT /id="PRO_0000056001" FT ZN_FING 57..92 FT /note="RING-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175" FT ZN_FING 124..166 FT /note="B box-type 1; atypical" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024" FT ZN_FING 183..236 FT /note="B box-type 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024" FT REGION 1..48 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 448..555 FT /note="Interaction with PER2" FT /evidence="ECO:0000269|PubMed:22274616" FT REGION 467..589 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 556..562 FT /note="Sumo interaction motif (SIM)" FT COILED 228..253 FT /evidence="ECO:0000255" FT MOTIF 476..490 FT /note="Nuclear localization signal" FT COMPBIAS 468..484 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 489..501 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 505..516 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 57 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT BINDING 60 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT BINDING 72 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT BINDING 74 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT BINDING 77 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT BINDING 80 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT BINDING 88 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT BINDING 91 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT BINDING 129 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024" FT BINDING 132 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024" FT BINDING 151 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024" FT BINDING 155 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024" FT BINDING 189 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024" FT BINDING 194 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024" FT BINDING 215 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024" FT BINDING 222 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024" FT SITE 394..395 FT /note="Breakpoint for translocation to form PML-RARA FT oncogene in type A APL" FT SITE 430..431 FT /note="(Microbial infection) Cleavage by protease 3C of FT enterovirus 71" FT /evidence="ECO:0000269|PubMed:34930370" FT SITE 444..445 FT /note="(Microbial infection) Cleavage by protease 3C of FT enterovirus 71" FT /evidence="ECO:0000269|PubMed:34930370" FT SITE 552..553 FT /note="Breakpoint for translocation to form PML-RARA FT oncogene in type B APL" FT MOD_RES 8 FT /note="Phosphoserine; by HIPK2" FT /evidence="ECO:0000269|PubMed:19015637, FT ECO:0007744|PubMed:24275569" FT MOD_RES 36 FT /note="Phosphoserine; by HIPK2 and MAPK1" FT /evidence="ECO:0007744|PubMed:23186163, FT ECO:0007744|PubMed:24275569" FT MOD_RES 38 FT /note="Phosphoserine; by HIPK2 and MAPK1" FT /evidence="ECO:0000269|PubMed:19015637, FT ECO:0007744|PubMed:23186163" FT MOD_RES 48 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 117 FT /note="Phosphoserine; by CHEK2" FT /evidence="ECO:0000269|PubMed:12402044" FT MOD_RES 403 FT /note="Phosphoserine; by MAPK1 and MAPK7" FT /evidence="ECO:0000269|PubMed:22033920, FT ECO:0007744|PubMed:17081983, ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569" FT MOD_RES 487 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000269|PubMed:18621739, FT ECO:0000269|PubMed:22274616" FT MOD_RES 493 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q60953" FT MOD_RES 504 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q60953" FT MOD_RES 505 FT /note="Phosphoserine; by MAPK1" FT /evidence="ECO:0000269|PubMed:22033920, FT ECO:0007744|PubMed:23186163" FT MOD_RES 512 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 515 FT /note="N6-acetyllysine" FT /evidence="ECO:0000305|PubMed:18621739" FT MOD_RES 518 FT /note="Phosphoserine; by CDK1 and CDK2" FT /evidence="ECO:0000269|PubMed:21840486, FT ECO:0000269|PubMed:22033920, ECO:0007744|PubMed:17081983, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163, FT ECO:0007744|PubMed:24275569" FT MOD_RES 527 FT /note="Phosphoserine; by MAPK1" FT /evidence="ECO:0000269|PubMed:22033920, FT ECO:0007744|PubMed:17081983, ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569" FT MOD_RES 530 FT /note="Phosphoserine; by MAPK1" FT /evidence="ECO:0007744|PubMed:17081983, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163, FT ECO:0007744|PubMed:24275569" FT MOD_RES 565 FT /note="Phosphoserine; by CK2" FT /evidence="ECO:0000269|PubMed:22406621" FT MOD_RES 867 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:23186163" FT CROSSLNK 65 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO1); alternate" FT /evidence="ECO:0000269|PubMed:10779416" FT CROSSLNK 65 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0007744|PubMed:25218447, FT ECO:0007744|PubMed:25755297, ECO:0007744|PubMed:25772364, FT ECO:0007744|PubMed:28112733" FT CROSSLNK 160 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO1); alternate" FT /evidence="ECO:0000269|PubMed:10779416" FT CROSSLNK 160 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO1P1/SUMO5); alternate" FT /evidence="ECO:0000269|PubMed:27211601" FT CROSSLNK 160 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0007744|PubMed:25755297, FT ECO:0007744|PubMed:25772364, ECO:0007744|PubMed:28112733" FT CROSSLNK 380 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in /SUMO5); alternate" FT /evidence="ECO:0000269|PubMed:27211601" FT CROSSLNK 380 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0007744|PubMed:25218447, FT ECO:0007744|PubMed:25755297, ECO:0007744|PubMed:28112733" FT CROSSLNK 380 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin); alternate" FT /evidence="ECO:0000269|PubMed:18408734" FT CROSSLNK 394 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:25755297, FT ECO:0007744|PubMed:28112733" FT CROSSLNK 400 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO1P1/SUMO5); alternate" FT /evidence="ECO:0000269|PubMed:27211601" FT CROSSLNK 400 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin); alternate" FT /evidence="ECO:0000269|PubMed:18408734" FT CROSSLNK 401 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 401 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin); alternate" FT /evidence="ECO:0000269|PubMed:18408734" FT CROSSLNK 460 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 476 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 476 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin); alternate" FT /evidence="ECO:0000269|PubMed:18408734" FT CROSSLNK 478 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:25755297, FT ECO:0007744|PubMed:28112733" FT CROSSLNK 487 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 490 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO1); alternate" FT /evidence="ECO:0000269|PubMed:10779416" FT CROSSLNK 490 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO1P1/SUMO5); alternate" FT /evidence="ECO:0000269|PubMed:27211601" FT CROSSLNK 490 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0007744|PubMed:25218447, FT ECO:0007744|PubMed:25755297, ECO:0007744|PubMed:25772364, FT ECO:0007744|PubMed:28112733" FT CROSSLNK 497 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO1); alternate" FT CROSSLNK 497 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO1P1/SUMO5); alternate" FT /evidence="ECO:0000269|PubMed:27211601" FT CROSSLNK 497 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0007744|PubMed:28112733" FT VAR_SEQ 419..466 FT /note="Missing (in isoform PML-11, isoform PML-12 and FT isoform PML-13)" FT /evidence="ECO:0000303|PubMed:11331580, FT ECO:0000303|PubMed:15489334, ECO:0000303|Ref.7, FT ECO:0000303|Ref.8" FT /id="VSP_040590" FT VAR_SEQ 419..435 FT /note="PEEAERVKAQVQALGLA -> LPPPAHALTGPAQSSTH (in isoform FT PML-7)" FT /evidence="ECO:0000303|PubMed:11331580" FT /id="VSP_040591" FT VAR_SEQ 419..423 FT /note="PEEAE -> RNALW (in isoform PML-14)" FT /evidence="ECO:0000303|PubMed:11331580" FT /id="VSP_040592" FT VAR_SEQ 424..882 FT /note="Missing (in isoform PML-14)" FT /evidence="ECO:0000303|PubMed:11331580" FT /id="VSP_040593" FT VAR_SEQ 436..882 FT /note="Missing (in isoform PML-7)" FT /evidence="ECO:0000303|PubMed:11331580" FT /id="VSP_040594" FT VAR_SEQ 553..560 FT /note="EERVVVIS -> GRERNALW (in isoform PML-6)" FT /evidence="ECO:0000303|PubMed:11331580, FT ECO:0000303|PubMed:1652368, ECO:0000303|Ref.6" FT /id="VSP_005742" FT VAR_SEQ 561..882 FT /note="Missing (in isoform PML-6)" FT /evidence="ECO:0000303|PubMed:11331580, FT ECO:0000303|PubMed:1652368, ECO:0000303|Ref.6" FT /id="VSP_005743" FT VAR_SEQ 571..882 FT /note="SSRELDDSSSESSDLQLEGPSTLRVLDENLADPQAEDRPLVFFDLKIDNETQ FT KISQLAAVNRESKFRVVIQPEAFFSIYSKAVSLEVGLQHFLSFLSSMRRPILACYKLWG FT PGLPNFFRALEDINRLWEFQEAISGFLAALPLIRERVPGASSFKLKNLAQTYLARNMSE FT RSAMAAVLAMRDLCRLLEVSPGPQLAQHVYPFSSLQCFASLQPLVQAAVLPRAEARLLA FT LHNVSFMELLSAHRRDRQGGLKKYSRYLSLQTTTLPPAQPAFNLQALGTYFEGLLEGPA FT LARAEGVSTPLAGRGLAERASQQS -> CMEPMETAEPQSSPAHSSPAHSSPAHSSPVQ FT SLLRAQGASSLPCGTYHPPAWPPHQPAEQAATPDAEPHSEPPDHQERPAVHRGIRYLLY FT RAQRAIRLRHALRLHPQLHRAPIRTWSPHVVQASTPAITGPLNHPANAQEHPAQLQRGI FT SPPHRIRGAVRSRSRSLRGSSHLSQWLNNFFALPFSSMASQLDMSSVVGAGESRAQTLG FT AGVPPGDSVRGSMEASQVQVPLEASPITFPPPCAPERPPISPVPGARQAGL (in FT isoform PML-2 and isoform PML-13)" FT /evidence="ECO:0000303|PubMed:11331580, FT ECO:0000303|PubMed:15489334, ECO:0000303|Ref.7" FT /id="VSP_040595" FT VAR_SEQ 571..882 FT /note="SSRELDDSSSESSDLQLEGPSTLRVLDENLADPQAEDRPLVFFDLKIDNETQ FT KISQLAAVNRESKFRVVIQPEAFFSIYSKAVSLEVGLQHFLSFLSSMRRPILACYKLWG FT PGLPNFFRALEDINRLWEFQEAISGFLAALPLIRERVPGASSFKLKNLAQTYLARNMSE FT RSAMAAVLAMRDLCRLLEVSPGPQLAQHVYPFSSLQCFASLQPLVQAAVLPRAEARLLA FT LHNVSFMELLSAHRRDRQGGLKKYSRYLSLQTTTLPPAQPAFNLQALGTYFEGLLEGPA FT LARAEGVSTPLAGRGLAERASQQS -> CMEPMETAEPQSSPAHSSPAHSSPVQSLLRA FT QGASSLPCGTYHPPAWPPHQPAEQAATPDAEPHSEPPDHQERPAVHRGIRYLLYRAQRA FT IRLRHALRLHPQLHRAPIRTWSPHVVQASTPAITGPLNHPANAQEHPAQLQRGISPPHR FT IRGAVRSRSRSLRGSSHLSQWLNNFFALPFSSMASQLDMSSVVGAGESRAQTLGAGVPP FT GDSVRGSMEASQVQVPLEASPITFPPPCAPERPPISPVPGARQAGL (in isoform FT PML-8)" FT /evidence="ECO:0000303|PubMed:11331580, FT ECO:0000303|PubMed:1720570" FT /id="VSP_005741" FT VAR_SEQ 571..641 FT /note="SSRELDDSSSESSDLQLEGPSTLRVLDENLADPQAEDRPLVFFDLKIDNETQ FT KISQLAAVNRESKFRVVIQ -> VSSSPQSEVLYWKVHGAHGDRRATVLASPLLASPLL FT ASPLLASPVSAESTRSLQPALWHIPPPSLASPPAR (in isoform PML-3)" FT /evidence="ECO:0000303|PubMed:1652369" FT /id="VSP_040596" FT VAR_SEQ 571..611 FT /note="SSRELDDSSSESSDLQLEGPSTLRVLDENLADPQAEDRPLV -> VSGPEVQ FT PRTPASPHFRSQGAQPQQVTLRLALRLGNFPVRH (in isoform PML-5)" FT /evidence="ECO:0000303|PubMed:11331580, FT ECO:0000303|PubMed:1720570" FT /id="VSP_005739" FT VAR_SEQ 612..882 FT /note="Missing (in isoform PML-5)" FT /evidence="ECO:0000303|PubMed:11331580, FT ECO:0000303|PubMed:1720570" FT /id="VSP_005740" FT VAR_SEQ 621..633 FT /note="TQKISQLAAVNRE -> SGFSWGYPHPFLI (in isoform PML-4 and FT isoform PML-12)" FT /evidence="ECO:0000303|PubMed:11331580, FT ECO:0000303|PubMed:1311253" FT /id="VSP_005744" FT VAR_SEQ 634..882 FT /note="Missing (in isoform PML-4 and isoform PML-12)" FT /evidence="ECO:0000303|PubMed:11331580, FT ECO:0000303|PubMed:1311253" FT /id="VSP_005745" FT VAR_SEQ 642..882 FT /note="Missing (in isoform PML-3)" FT /evidence="ECO:0000303|PubMed:1652369" FT /id="VSP_040597" FT VARIANT 645 FT /note="F -> L (in dbSNP:rs5742915)" FT /evidence="ECO:0000269|PubMed:11331580, FT ECO:0000269|PubMed:1720570" FT /id="VAR_052090" FT MUTAGEN 57 FT /note="C->S: Strongly reduced sumoylation; when associated FT with S-60." FT /evidence="ECO:0000269|PubMed:17081985" FT MUTAGEN 60 FT /note="C->S: Strongly reduced sumoylation; when associated FT with S-57." FT /evidence="ECO:0000269|PubMed:17081985" FT MUTAGEN 65 FT /note="K->R: Loss of one sumoylation. No effect on nuclear FT body formation. Loss of 2 sumoylations; when associated FT with R-490 with or without R-133 or R-150. No effect on FT nuclear body formation; when associated with R-490. Loss FT the ability to be conjugated by SUMO1P1/SUMO5 but could be FT conjugated by SUMO1; when associated with R-160 and R-490." FT /evidence="ECO:0000269|PubMed:27211601, FT ECO:0000269|PubMed:9756909" FT MUTAGEN 65 FT /note="K->R: Loss of one sumoylation. No effect on nuclear FT body formation. Loss of 2 sumoylations; when associated FT with R-490 with or without R-133 or R-150. No effect on FT nuclear body formation; when associated with R-490. No FT sumoylation nor nuclear body formation; when associated FT with R-160 and R-490." FT /evidence="ECO:0000269|PubMed:9756909" FT MUTAGEN 68 FT /note="K->R: No effect on sumoylation levels." FT MUTAGEN 88 FT /note="C->S: No nuclear microspeckle location, no FT sumoylation and loss of intrinsic transcriptional repressor FT activity of PML-RARA oncoprotein; when associated with R- FT 89." FT /evidence="ECO:0000269|PubMed:15809060" FT MUTAGEN 89 FT /note="P->R: No nuclear microspeckle location, no FT sumoylation and loss of intrinsic transcriptional repressor FT activity of PML-RARA oncoprotein; when associated with S- FT 88." FT /evidence="ECO:0000269|PubMed:15809060" FT MUTAGEN 133 FT /note="K->R: Loss of 2 sumoylations; when associated with FT R-65 and R-490." FT /evidence="ECO:0000269|PubMed:9756909" FT MUTAGEN 150 FT /note="K->R: Loss of 2 sumoylations; when associated with FT R-65 and R-490." FT /evidence="ECO:0000269|PubMed:9756909" FT MUTAGEN 160 FT /note="K->R: Compromised the formation of high molecular FT weight species of SUMO1P1/SUMO5 conjugation on PML. Loss of FT 2 sumoylations; when associated with or without R-65. No FT sumoylation nor nuclear body formation; when associated FT with or without R-65 and R-490. Loss the ability to be FT conjugated by SUMO1P1/SUMO5 but could be conjugated by FT SUMO1; when associated with R-65 and R-490." FT /evidence="ECO:0000269|PubMed:27211601, FT ECO:0000269|PubMed:9756909" FT MUTAGEN 160 FT /note="K->R: Loss of 2 sumoylations; when associated with FT or without R-65. No sumoylation nor nuclear body formation; FT when associated with or without R-65 and R-490." FT /evidence="ECO:0000269|PubMed:9756909" FT MUTAGEN 380 FT /note="K->R: Does not affect SUMO1P1/SUMO5 conjugation." FT /evidence="ECO:0000269|PubMed:27211601" FT MUTAGEN 400 FT /note="K->R: Does not affect SUMO1P1/SUMO5 conjugation." FT /evidence="ECO:0000269|PubMed:27211601" FT MUTAGEN 430 FT /note="Q->A: Loss of cleavage by enterovirus 71 protease FT 3C." FT /evidence="ECO:0000269|PubMed:34930370" FT MUTAGEN 444 FT /note="Q->A: Loss of cleavage by enterovirus 71 protease FT 3C." FT /evidence="ECO:0000269|PubMed:34930370" FT MUTAGEN 487 FT /note="K->A: Loss of nuclear localization; when associated FT with A-490." FT /evidence="ECO:0000269|PubMed:18298799, FT ECO:0000269|PubMed:18621739" FT MUTAGEN 487 FT /note="K->R: Loss of nuclear localization. Reduced FT acetylation. Further decrease in acetylation; when FT associated with R-515." FT /evidence="ECO:0000269|PubMed:18298799, FT ECO:0000269|PubMed:18621739" FT MUTAGEN 490 FT /note="K->A: Loss of nuclear localization; when associated FT with A-487." FT /evidence="ECO:0000269|PubMed:18298799, FT ECO:0000269|PubMed:9756909" FT MUTAGEN 490 FT /note="K->R: Abolished conjugation of one SUMO1P1/SUMO5. FT Loss of 2 sumoylations; when associated with R-65 with or FT without R-133. No effect on nuclear body formation; when FT associated with R-65. No sumoylation nor nuclear body FT formation; when associated with R-65 and R-160. Loss the FT ability to be conjugated by SUMO1P1/SUMO5 but could be FT conjugated by SUMO1; when associated with R-65 and R-160." FT /evidence="ECO:0000269|PubMed:18298799, FT ECO:0000269|PubMed:27211601, ECO:0000269|PubMed:9756909" FT MUTAGEN 490 FT /note="K->R: Loss of 2 sumoylations; when associated with FT R-65 with or without R-133. No effect on nuclear body FT formation; when associated with R-65. No sumoylation nor FT nuclear body formation; when associated with R-65 and R- FT 160." FT /evidence="ECO:0000269|PubMed:18298799, FT ECO:0000269|PubMed:9756909" FT MUTAGEN 497 FT /note="K->R: Does not affect SUMO1P1/SUMO5 conjugation." FT /evidence="ECO:0000269|PubMed:27211601" FT MUTAGEN 515 FT /note="K->R: Slightly reduced acetylation. Further decrease FT in acetylation; when associated with R-487." FT /evidence="ECO:0000269|PubMed:18621739" FT MUTAGEN 518 FT /note="S->A: Abolishes ubiquitination by the BCR(KLHL20) E3 FT ubiquitin ligase complex." FT /evidence="ECO:0000269|PubMed:21840486" FT MUTAGEN 556..559 FT /note="VVVI->AAAS: Abolishes SUMO1 binding." FT CONFLICT 224 FT /note="E -> D (in Ref. 7; AAP88913 and 10; AAH00080/ FT AAH20994)" FT /evidence="ECO:0000305" FT CONFLICT 419 FT /note="P -> A (in Ref. 2; AAA60351/AAA60388/AAA60390, 4; FT AAA60352 and 5; AAG50182/AAG50184/AAG50185)" FT /evidence="ECO:0000305" FT STRAND 54..56 FT /evidence="ECO:0007829|PDB:5YUF" FT TURN 58..60 FT /evidence="ECO:0007829|PDB:5YUF" FT STRAND 62..66 FT /evidence="ECO:0007829|PDB:5YUF" FT HELIX 78..82 FT /evidence="ECO:0007829|PDB:5YUF" FT TURN 89..91 FT /evidence="ECO:0007829|PDB:5YUF" FT STRAND 93..96 FT /evidence="ECO:0007829|PDB:1BOR" FT STRAND 121..126 FT /evidence="ECO:0007829|PDB:6IMQ" FT TURN 130..132 FT /evidence="ECO:0007829|PDB:6IMQ" FT STRAND 138..140 FT /evidence="ECO:0007829|PDB:6IMQ" FT TURN 141..144 FT /evidence="ECO:0007829|PDB:6IMQ" FT STRAND 145..147 FT /evidence="ECO:0007829|PDB:6IMQ" FT HELIX 149..158 FT /evidence="ECO:0007829|PDB:6IMQ" FT STRAND 163..165 FT /evidence="ECO:0007829|PDB:6IMQ" FT STRAND 202..204 FT /evidence="ECO:0007829|PDB:8J2P" FT TURN 205..207 FT /evidence="ECO:0007829|PDB:8J2P" FT HELIX 213..218 FT /evidence="ECO:0007829|PDB:8J2P" FT STRAND 556..558 FT /evidence="ECO:0007829|PDB:6UYR" FT MOD_RES P29590-2:565 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17081983" FT CONFLICT P29590-2:578 FT /note="P -> A (in Ref. 5; AAG50181)" FT /evidence="ECO:0000305" FT MOD_RES P29590-4:518 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17081983" FT MOD_RES P29590-4:527 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17081983" FT MOD_RES P29590-4:530 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17081983" FT CONFLICT P29590-10:419 FT /note="L -> V (in Ref. 5; AAG50187)" FT /evidence="ECO:0000305" SQ SEQUENCE 882 AA; 97551 MW; D50968A977E34287 CRC64; MEPAPARSPR PQQDPARPQE PTMPPPETPS EGRQPSPSPS PTERAPASEE EFQFLRCQQC QAEAKCPKLL PCLHTLCSGC LEASGMQCPI CQAPWPLGAD TPALDNVFFE SLQRRLSVYR QIVDAQAVCT RCKESADFWC FECEQLLCAK CFEAHQWFLK HEARPLAELR NQSVREFLDG TRKTNNIFCS NPNHRTPTLT SIYCRGCSKP LCCSCALLDS SHSELKCDIS AEIQQRQEEL DAMTQALQEQ DSAFGAVHAQ MHAAVGQLGR ARAETEELIR ERVRQVVAHV RAQERELLEA VDARYQRDYE EMASRLGRLD AVLQRIRTGS ALVQRMKCYA SDQEVLDMHG FLRQALCRLR QEEPQSLQAA VRTDGFDEFK VRLQDLSSCI TQGKDAAVSK KASPEAASTP RDPIDVDLPE EAERVKAQVQ ALGLAEAQPM AVVQSVPGAH PVPVYAFSIK GPSYGEDVSN TTTAQKRKCS QTQCPRKVIK MESEEGKEAR LARSSPEQPR PSTSKAVSPP HLDGPPSPRS PVIGSEVFLP NSNHVASGAG EAEERVVVIS SSEDSDAENS SSRELDDSSS ESSDLQLEGP STLRVLDENL ADPQAEDRPL VFFDLKIDNE TQKISQLAAV NRESKFRVVI QPEAFFSIYS KAVSLEVGLQ HFLSFLSSMR RPILACYKLW GPGLPNFFRA LEDINRLWEF QEAISGFLAA LPLIRERVPG ASSFKLKNLA QTYLARNMSE RSAMAAVLAM RDLCRLLEVS PGPQLAQHVY PFSSLQCFAS LQPLVQAAVL PRAEARLLAL HNVSFMELLS AHRRDRQGGL KKYSRYLSLQ TTTLPPAQPA FNLQALGTYF EGLLEGPALA RAEGVSTPLA GRGLAERASQ QS // ID ZBT16_HUMAN Reviewed; 673 AA. AC Q05516; Q8TAL4; DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot. DT 07-MAR-2006, sequence version 2. DT 28-JAN-2026, entry version 244. DE RecName: Full=Zinc finger and BTB domain-containing protein 16; DE AltName: Full=Promyelocytic leukemia zinc finger protein; DE AltName: Full=Zinc finger protein 145; DE AltName: Full=Zinc finger protein PLZF; GN Name=ZBTB16; Synonyms=PLZF, ZNF145; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PLZFB), ALTERNATIVE SPLICING, AND RP CHROMOSOMAL TRANSLOCATION WITH RARA. RC TISSUE=Heart ventricle; RX PubMed=8384553; DOI=10.1002/j.1460-2075.1993.tb05757.x; RA Chen Z., Brand N.J., Chen A., Chen S.-J., Tong J.-H., Wang Z.-Y., RA Waxman S., Zelent A.; RT "Fusion between a novel Kruppel-like zinc finger gene and the retinoic acid RT receptor-alpha locus due to a variant t(11;17) translocation associated RT with acute promyelocytic leukaemia."; RL EMBO J. 12:1161-1167(1993). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=10500192; DOI=10.1073/pnas.96.20.11422; RA Zhang T., Xiong H., Kan L.-X., Zhang C.-K., Jiao X.-F., Fu G., Zhang Q.-H., RA Lu L., Tong J.-H., Gu B.-W., Yu M., Liu J.-X., Licht J., Waxman S., RA Zelent A., Chen E., Chen S.-J.; RT "Genomic sequence, structural organization, molecular evolution, and RT aberrant rearrangement of promyelocytic leukemia zinc finger gene."; RL Proc. Natl. Acad. Sci. U.S.A. 96:11422-11427(1999). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM PLZFB). RC TISSUE=Brain; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 424-455. RX PubMed=8387545; DOI=10.1172/jci116453; RA Chen S.-J., Zelent A., Tong J.-H., Yu H.-Q., Wang Z.-Y., Derre J., RA Berger R., Waxman S., Chen Z.; RT "Rearrangements of the retinoic acid receptor alpha and promyelocytic RT leukemia zinc finger genes resulting from t(11;17)(q23;q21) in a patient RT with acute promyelocytic leukemia."; RL J. Clin. Invest. 91:2260-2267(1993). RN [5] RP INTERACTION WITH ZBTB32. RX PubMed=10572087; RA Hoatlin M.E., Zhi Y., Ball H., Silvey K., Melnick A., Stone S., Arai S., RA Hawe N., Owen G., Zelent A., Licht J.D.; RT "A novel BTB/POZ transcriptional repressor protein interacts with the RT Fanconi anemia group C protein and PLZF."; RL Blood 94:3737-3747(1999). RN [6] RP FUNCTION, AND INTERACTION WITH RUNX1T1. RX PubMed=10688654; DOI=10.1128/mcb.20.6.2075-2086.2000; RA Melnick A.M., Westendorf J.J., Polinger A., Carlile G.W., Arai S., RA Ball H.J., Lutterbach B., Hiebert S.W., Licht J.D.; RT "The ETO protein disrupted in t(8;21)-associated acute myeloid leukemia is RT a corepressor for the promyelocytic leukemia zinc finger protein."; RL Mol. Cell. Biol. 20:2075-2086(2000). RN [7] RP INTERACTION WITH EPN1. RX PubMed=11161217; DOI=10.1126/science.291.5506.1047; RA Itoh T., Koshiba S., Kigawa T., Kikuchi A., Yokoyama S., Takenawa T.; RT "Role of the ENTH domain in phosphatidylinositol-4,5-bisphosphate binding RT and endocytosis."; RL Science 291:1047-1051(2001). RN [8] RP FUNCTION AS AN E3 UBIQUITIN-PROTEIN LIGASE, AND INTERACTION WITH CUL3. RX PubMed=14528312; DOI=10.1038/ncb1056; RA Furukawa M., He Y.J., Borchers C., Xiong Y.; RT "Targeting of protein ubiquitination by BTB-Cullin 3-Roc1 ubiquitin RT ligases."; RL Nat. Cell Biol. 5:1001-1007(2003). RN [9] RP INTERACTION WITH ATP7B. RX PubMed=16676348; DOI=10.1002/jcb.20980; RA Ko J.H., Son W., Bae G.Y., Kang J.H., Oh W., Yoo O.J.; RT "A new hepatocytic isoform of PLZF lacking the BTB domain interacts with RT ATP7B, the Wilson disease protein, and positively regulates ERK signal RT transduction."; RL J. Cell. Biochem. 99:719-734(2006). RN [10] RP FUNCTION, INTERACTION WITH RNF112, AND SUBCELLULAR LOCATION. RX PubMed=24359566; DOI=10.1186/1423-0127-20-98; RA Lin D.Y., Huang C.C., Hsieh Y.T., Lin H.C., Pao P.C., Tsou J.H., Lai C.Y., RA Hung L.Y., Wang J.M., Chang W.C., Lee Y.C.; RT "Analysis of the interaction between Zinc finger protein 179 (Znf179) and RT promyelocytic leukemia zinc finger (Plzf)."; RL J. Biomed. Sci. 20:98-98(2013). RN [11] RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 6-126. RX PubMed=9770450; DOI=10.1073/pnas.95.21.12123; RA Ahmad K.F., Engel C.K., Prive G.G.; RT "Crystal structure of the BTB domain from PLZF."; RL Proc. Natl. Acad. Sci. U.S.A. 95:12123-12128(1998). RN [12] RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 7-122. RX PubMed=10537309; RA Li X., Peng H., Schultz D.C., Lopez-Guisa J.M., Rauscher F.J. III, RA Marmorstein R.; RT "Structure-function studies of the BTB/POZ transcriptional repression RT domain from the promyelocytic leukemia zinc finger oncoprotein."; RL Cancer Res. 59:5275-5282(1999). RN [13] RP VARIANT SGYMR VAL-617. RX PubMed=18611983; DOI=10.1136/jmg.2008.059451; RA Fischer S., Kohlhase J., Boehm D., Schweiger B., Hoffmann D., Heitmann M., RA Horsthemke B., Wieczorek D.; RT "Biallelic loss of function of the promyelocytic leukaemia zinc finger RT (PLZF) gene causes severe skeletal defects and genital hypoplasia."; RL J. Med. Genet. 45:731-737(2008). CC -!- FUNCTION: Acts as a transcriptional repressor (PubMed:10688654, CC PubMed:24359566). Transcriptional repression may be mediated through CC recruitment of histone deacetylases to target promoters CC (PubMed:10688654). May play a role in myeloid maturation and in the CC development and/or maintenance of other differentiated tissues. CC Probable substrate-recognition component of an E3 ubiquitin-protein CC ligase complex which mediates the ubiquitination and subsequent CC proteasomal degradation of target proteins (PubMed:14528312). CC {ECO:0000269|PubMed:10688654, ECO:0000269|PubMed:14528312, CC ECO:0000269|PubMed:24359566}. CC -!- PATHWAY: Protein modification; protein ubiquitination. CC -!- SUBUNIT: Binds EPN1 (PubMed:11161217). Interacts with ZBTB32 and CUL3 CC (PubMed:10572087, PubMed:14528312). Interacts with ATP7B CC (PubMed:16676348). Interacts with transcriptional corepressor RUNX1T1 CC (via its N-terminus); the interaction increases the transcription CC repression activity of ZBTB16 (PubMed:10688654). Interacts (via C2H2- CC type zinc finger domains 1 and 2) with RNF112 (PubMed:24359566). CC {ECO:0000269|PubMed:10572087, ECO:0000269|PubMed:10688654, CC ECO:0000269|PubMed:11161217, ECO:0000269|PubMed:14528312, CC ECO:0000269|PubMed:16676348, ECO:0000269|PubMed:24359566}. CC -!- INTERACTION: CC Q05516; Q9Y2J4: AMOTL2; NbExp=3; IntAct=EBI-711925, EBI-746752; CC Q05516; Q9H2G9: BLZF1; NbExp=3; IntAct=EBI-711925, EBI-2548012; CC Q05516; Q9H257-2: CARD9; NbExp=3; IntAct=EBI-711925, EBI-11530605; CC Q05516; Q8TD31-3: CCHCR1; NbExp=3; IntAct=EBI-711925, EBI-10175300; CC Q05516; Q8NHQ1: CEP70; NbExp=4; IntAct=EBI-711925, EBI-739624; CC Q05516; Q9Y2V7: COG6; NbExp=5; IntAct=EBI-711925, EBI-3866319; CC Q05516; Q9GZU7: CTDSP1; NbExp=3; IntAct=EBI-711925, EBI-751587; CC Q05516; P68104: EEF1A1; NbExp=4; IntAct=EBI-711925, EBI-352162; CC Q05516; Q5JST6: EFHC2; NbExp=3; IntAct=EBI-711925, EBI-2349927; CC Q05516; Q9NTX9: FAM217B; NbExp=3; IntAct=EBI-711925, EBI-19153639; CC Q05516; Q86YD7: FAM90A1; NbExp=3; IntAct=EBI-711925, EBI-6658203; CC Q05516; Q5TD97: FHL5; NbExp=3; IntAct=EBI-711925, EBI-750641; CC Q05516; Q08379: GOLGA2; NbExp=8; IntAct=EBI-711925, EBI-618309; CC Q05516; A6NEM1: GOLGA6L9; NbExp=3; IntAct=EBI-711925, EBI-5916454; CC Q05516; O95872: GPANK1; NbExp=3; IntAct=EBI-711925, EBI-751540; CC Q05516; Q13547: HDAC1; NbExp=6; IntAct=EBI-711925, EBI-301834; CC Q05516; P07686: HEXB; NbExp=3; IntAct=EBI-711925, EBI-7133736; CC Q05516; P49639: HOXA1; NbExp=3; IntAct=EBI-711925, EBI-740785; CC Q05516; Q00444: HOXC5; NbExp=3; IntAct=EBI-711925, EBI-11955357; CC Q05516; O75031: HSF2BP; NbExp=3; IntAct=EBI-711925, EBI-7116203; CC Q05516; P42858: HTT; NbExp=4; IntAct=EBI-711925, EBI-466029; CC Q05516; Q9BVG8-5: KIFC3; NbExp=3; IntAct=EBI-711925, EBI-14069005; CC Q05516; Q6A162: KRT40; NbExp=9; IntAct=EBI-711925, EBI-10171697; CC Q05516; O43504: LAMTOR5; NbExp=8; IntAct=EBI-711925, EBI-713382; CC Q05516; O95751: LDOC1; NbExp=4; IntAct=EBI-711925, EBI-740738; CC Q05516; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-711925, EBI-16439278; CC Q05516; Q9UJV3-2: MID2; NbExp=3; IntAct=EBI-711925, EBI-10172526; CC Q05516; Q5JR59-3: MTUS2; NbExp=3; IntAct=EBI-711925, EBI-11522433; CC Q05516; Q8WY64: MYLIP; NbExp=3; IntAct=EBI-711925, EBI-6952711; CC Q05516; Q8NI38: NFKBID; NbExp=3; IntAct=EBI-711925, EBI-10271199; CC Q05516; O00746: NME4; NbExp=3; IntAct=EBI-711925, EBI-744871; CC Q05516; Q9H4L5: OSBPL3; NbExp=3; IntAct=EBI-711925, EBI-1051317; CC Q05516; O43189: PHF1; NbExp=3; IntAct=EBI-711925, EBI-530034; CC Q05516; O75928-2: PIAS2; NbExp=3; IntAct=EBI-711925, EBI-348567; CC Q05516; Q4G0R1: PIBF1; NbExp=3; IntAct=EBI-711925, EBI-14066006; CC Q05516; P29590: PML; NbExp=7; IntAct=EBI-711925, EBI-295890; CC Q05516; P29590-5: PML; NbExp=2; IntAct=EBI-711925, EBI-304008; CC Q05516; P31321: PRKAR1B; NbExp=3; IntAct=EBI-711925, EBI-2805516; CC Q05516; Q96QF0-7: RAB3IP; NbExp=3; IntAct=EBI-711925, EBI-11984839; CC Q05516; Q04864-2: REL; NbExp=3; IntAct=EBI-711925, EBI-10829018; CC Q05516; Q6NUQ1: RINT1; NbExp=3; IntAct=EBI-711925, EBI-726876; CC Q05516; Q9H788-2: SH2D4A; NbExp=3; IntAct=EBI-711925, EBI-10308083; CC Q05516; Q9NYJ8: TAB2; NbExp=3; IntAct=EBI-711925, EBI-358708; CC Q05516; Q08117-2: TLE5; NbExp=3; IntAct=EBI-711925, EBI-11741437; CC Q05516; Q13077: TRAF1; NbExp=5; IntAct=EBI-711925, EBI-359224; CC Q05516; Q12933: TRAF2; NbExp=5; IntAct=EBI-711925, EBI-355744; CC Q05516; Q9BUZ4: TRAF4; NbExp=3; IntAct=EBI-711925, EBI-3650647; CC Q05516; P19474: TRIM21; NbExp=3; IntAct=EBI-711925, EBI-81290; CC Q05516; P36406: TRIM23; NbExp=3; IntAct=EBI-711925, EBI-740098; CC Q05516; P14373: TRIM27; NbExp=5; IntAct=EBI-711925, EBI-719493; CC Q05516; Q9BYV2: TRIM54; NbExp=6; IntAct=EBI-711925, EBI-2130429; CC Q05516; Q5W5X9-3: TTC23; NbExp=3; IntAct=EBI-711925, EBI-9090990; CC Q05516; Q7KZS0: UBE2I; NbExp=3; IntAct=EBI-711925, EBI-10180829; CC Q05516; Q9NP79: VTA1; NbExp=4; IntAct=EBI-711925, EBI-740160; CC Q05516; P62258: YWHAE; NbExp=2; IntAct=EBI-711925, EBI-356498; CC Q05516; Q05516: ZBTB16; NbExp=8; IntAct=EBI-711925, EBI-711925; CC Q05516; B2RXF5: ZBTB42; NbExp=3; IntAct=EBI-711925, EBI-12287587; CC Q05516; Q9H707: ZNF552; NbExp=3; IntAct=EBI-711925, EBI-2555731; CC Q05516; Q6ZNG0: ZNF620; NbExp=3; IntAct=EBI-711925, EBI-4395669; CC Q05516; Q8N720: ZNF655; NbExp=3; IntAct=EBI-711925, EBI-625509; CC Q05516; O35826: Gne; Xeno; NbExp=2; IntAct=EBI-711925, EBI-7109445; CC Q05516; P09022: Hoxa1; Xeno; NbExp=3; IntAct=EBI-711925, EBI-3957603; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:24359566}. Nucleus, CC nuclear body {ECO:0000269|PubMed:24359566}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=PLZFB; CC IsoId=Q05516-1; Sequence=Displayed; CC Name=PLZFA; CC IsoId=Q05516-2; Sequence=VSP_006896; CC -!- TISSUE SPECIFICITY: Within the hematopoietic system, PLZF is expressed CC in bone marrow, early myeloid cell lines and peripheral blood CC mononuclear cells. Also expressed in the ovary, and at lower levels, in CC the kidney and lung. CC -!- INDUCTION: By retinoic acid. CC -!- DISEASE: Skeletal defects, genital hypoplasia, and impaired CC intellectual development (SGYMR) [MIM:612447]: A disorder characterized CC by intellectual disability, craniofacial dysmorphism, microcephaly and CC short stature. Additional features include absence of the thumbs, CC hypoplasia of the radii and ulnae, additional vertebrae and ribs, CC retarded bone age and genital hypoplasia. CC {ECO:0000269|PubMed:18611983}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Note=A chromosomal aberration involving ZBTB16 may be a cause CC of acute promyelocytic leukemia (APL). Translocation t(11;17)(q32;q21) CC with RARA. {ECO:0000269|PubMed:8384553}. CC -!- SIMILARITY: Belongs to the krueppel C2H2-type zinc-finger protein CC family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/37/PLZF"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; Z19002; CAA79489.1; -; mRNA. DR EMBL; AF060568; AAD03619.1; -; Genomic_DNA. DR EMBL; BC026902; AAH26902.1; -; mRNA. DR EMBL; BC029812; AAH29812.1; -; mRNA. DR EMBL; S60093; AAC60590.2; -; Genomic_DNA. DR CCDS; CCDS8367.1; -. [Q05516-1] DR PIR; S36336; S36336. DR RefSeq; NP_001018011.1; NM_001018011.3. [Q05516-1] DR RefSeq; NP_001341679.1; NM_001354750.2. [Q05516-1] DR RefSeq; NP_001341680.1; NM_001354751.2. [Q05516-1] DR RefSeq; NP_005997.2; NM_006006.4. [Q05516-1] DR RefSeq; XP_054225863.1; XM_054369888.1. [Q05516-1] DR PDB; 1BUO; X-ray; 1.90 A; A=6-126. DR PDB; 1CS3; X-ray; 2.00 A; A=7-122. DR PDB; 8YTH; X-ray; 2.40 A; B=285-292. DR PDBsum; 1BUO; -. DR PDBsum; 1CS3; -. DR PDBsum; 8YTH; -. DR AlphaFoldDB; Q05516; -. DR SMR; Q05516; -. DR BioGRID; 113498; 182. DR CORUM; Q05516; -. DR DIP; DIP-2654N; -. DR FunCoup; Q05516; 566. DR IntAct; Q05516; 127. DR MINT; Q05516; -. DR STRING; 9606.ENSP00000338157; -. DR BindingDB; Q05516; -. DR ChEMBL; CHEMBL4105726; -. DR MoonDB; Q05516; Predicted. DR iPTMnet; Q05516; -. DR PhosphoSitePlus; Q05516; -. DR BioMuta; ZBTB16; -. DR DMDM; 90109930; -. DR jPOST; Q05516; -. DR MassIVE; Q05516; -. DR PaxDb; 9606-ENSP00000338157; -. DR PeptideAtlas; Q05516; -. DR ProteomicsDB; 58332; -. [Q05516-1] DR ProteomicsDB; 58333; -. [Q05516-2] DR ABCD; Q05516; 3 sequenced antibodies. DR Antibodypedia; 897; 397 antibodies from 38 providers. DR DNASU; 7704; -. DR Ensembl; ENST00000335953.9; ENSP00000338157.4; ENSG00000109906.16. [Q05516-1] DR Ensembl; ENST00000392996.2; ENSP00000376721.2; ENSG00000109906.16. [Q05516-1] DR Ensembl; ENST00000682278.1; ENSP00000506794.1; ENSG00000109906.16. [Q05516-1] DR Ensembl; ENST00000682697.1; ENSP00000506924.1; ENSG00000109906.16. [Q05516-1] DR Ensembl; ENST00000682971.1; ENSP00000506894.1; ENSG00000109906.16. [Q05516-1] DR Ensembl; ENST00000683318.1; ENSP00000508351.1; ENSG00000109906.16. [Q05516-1] DR Ensembl; ENST00000683554.1; ENSP00000506953.1; ENSG00000109906.16. [Q05516-1] DR Ensembl; ENST00000684295.1; ENSP00000507788.1; ENSG00000109906.16. [Q05516-1] DR GeneID; 7704; -. DR KEGG; hsa:7704; -. DR MANE-Select; ENST00000335953.9; ENSP00000338157.4; NM_006006.6; NP_005997.2. DR UCSC; uc001pop.4; human. [Q05516-1] DR AGR; HGNC:12930; -. DR ClinPGx; PA37517; -. DR CTD; 7704; -. DR DisGeNET; 7704; -. DR GeneCards; ZBTB16; -. DR HGNC; HGNC:12930; ZBTB16. DR HPA; ENSG00000109906; Low tissue specificity. DR MalaCards; ZBTB16; -. DR MIM; 176797; gene. DR MIM; 612447; phenotype. DR OpenTargets; ENSG00000109906; -. DR Orphanet; 520; Acute promyelocytic leukemia. DR Orphanet; 99861; Precursor T-cell acute lymphoblastic leukemia. DR VEuPathDB; HostDB:ENSG00000109906; -. DR eggNOG; KOG1721; Eukaryota. DR GeneTree; ENSGT00940000154616; -. DR HOGENOM; CLU_026420_0_0_1; -. DR InParanoid; Q05516; -. DR OMA; NDTEANM; -. DR OrthoDB; 8922241at2759; -. DR PAN-GO; Q05516; 5 GO annotations based on evolutionary models. DR PhylomeDB; Q05516; -. DR PathwayCommons; Q05516; -. DR Reactome; R-HSA-8951664; Neddylation. DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation. DR SignaLink; Q05516; -. DR SIGNOR; Q05516; -. DR UniPathway; UPA00143; -. DR Agora; ENSG00000109906; Agora Nominated Target for Alzheimer's Disease. DR BioGRID-ORCS; 7704; 12 hits in 1214 CRISPR screens. DR ChiTaRS; ZBTB16; human. DR EvolutionaryTrace; Q05516; -. DR GeneWiki; Zinc_finger_and_BTB_domain-containing_protein_16; -. DR GenomeRNAi; 7704; -. DR Pharos; Q05516; Tbio. DR PRO; PR:Q05516; -. DR Proteomes; UP000005640; Chromosome 11. DR RNAct; Q05516; protein. DR Bgee; ENSG00000109906; Expressed in skin of hip and 205 other cell types or tissues. DR ExpressionAtlas; Q05516; baseline and differential. DR GO; GO:0000785; C:chromatin; ISS:UniProt. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0001673; C:male germ cell nucleus; IEA:Ensembl. DR GO; GO:0016604; C:nuclear body; IDA:UniProtKB. DR GO; GO:0016607; C:nuclear speck; IDA:UniProtKB. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0016605; C:PML body; IDA:UniProtKB. DR GO; GO:0032991; C:protein-containing complex; IMP:UniProtKB. DR GO; GO:0017053; C:transcription repressor complex; IDA:MGI. DR GO; GO:0003677; F:DNA binding; IDA:MGI. DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IBA:GO_Central. DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IDA:NTNU_SB. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0019904; F:protein domain specific binding; IEA:Ensembl. DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB. DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:UniProtKB. DR GO; GO:0003712; F:transcription coregulator activity; ISS:UniProt. DR GO; GO:0001222; F:transcription corepressor binding; IPI:UniProtKB. DR GO; GO:0031703; F:type 2 angiotensin receptor binding; IEA:Ensembl. DR GO; GO:0008270; F:zinc ion binding; IEA:UniProtKB-KW. DR GO; GO:0009952; P:anterior/posterior pattern specification; IEA:Ensembl. DR GO; GO:0006915; P:apoptotic process; NAS:UniProtKB. DR GO; GO:0051216; P:cartilage development; IDA:UniProtKB. DR GO; GO:0008283; P:cell population proliferation; IEA:Ensembl. DR GO; GO:0007417; P:central nervous system development; ISS:UniProtKB. DR GO; GO:0042733; P:embryonic digit morphogenesis; IEA:Ensembl. DR GO; GO:0035116; P:embryonic hindlimb morphogenesis; IEA:Ensembl. DR GO; GO:0009880; P:embryonic pattern specification; IEA:Ensembl. DR GO; GO:0035136; P:forelimb morphogenesis; IEA:Ensembl. DR GO; GO:0030097; P:hemopoiesis; IDA:UniProtKB. DR GO; GO:0048133; P:male germ-line stem cell asymmetric division; IEA:Ensembl. DR GO; GO:0001823; P:mesonephros development; ISS:UniProtKB. DR GO; GO:0030099; P:myeloid cell differentiation; TAS:UniProtKB. DR GO; GO:0008285; P:negative regulation of cell population proliferation; IEA:Ensembl. DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:0045638; P:negative regulation of myeloid cell differentiation; ISS:UniProtKB. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:UniProtKB. DR GO; GO:0043931; P:ossification involved in bone maturation; IEA:Ensembl. DR GO; GO:0043065; P:positive regulation of apoptotic process; IEA:Ensembl. DR GO; GO:0061036; P:positive regulation of cartilage development; IDA:UniProtKB. DR GO; GO:0032332; P:positive regulation of chondrocyte differentiation; IMP:UniProtKB. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:0045600; P:positive regulation of fat cell differentiation; IMP:UniProtKB. DR GO; GO:0051138; P:positive regulation of NK T cell differentiation; IEA:Ensembl. DR GO; GO:0045778; P:positive regulation of ossification; IDA:UniProtKB. DR GO; GO:0034504; P:protein localization to nucleus; IEA:Ensembl. DR GO; GO:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central. DR GO; GO:0045066; P:regulatory T cell differentiation; ISS:UniProt. DR GO; GO:0002394; P:tolerance induction in gut-associated lymphoid tissue; ISS:UniProt. DR CDD; cd18205; BTB_POZ_ZBTB16_PLZF; 1. DR FunFam; 3.30.160.60:FF:001818; GDNF-inducible zinc finger protein 1 isoform X1; 1. DR FunFam; 3.30.160.60:FF:000553; Zinc finger and BTB domain-containing protein 16; 1. DR FunFam; 3.30.160.60:FF:000792; Zinc finger and BTB domain-containing protein 16; 1. DR FunFam; 3.30.160.60:FF:001013; Zinc finger and BTB domain-containing protein 16; 1. DR FunFam; 3.30.160.60:FF:002171; Zinc finger and BTB domain-containing protein 16; 1. DR FunFam; 3.30.710.10:FF:000059; Zinc finger and BTB domain-containing protein 16; 1. DR FunFam; 3.30.160.60:FF:001082; zinc finger and BTB domain-containing protein 16; 1. DR Gene3D; 3.30.160.60; Classic Zinc Finger; 7. DR Gene3D; 3.30.710.10; Potassium Channel Kv1.1, Chain A; 1. DR InterPro; IPR000210; BTB/POZ_dom. DR InterPro; IPR011333; SKP1/BTB/POZ_sf. DR InterPro; IPR036236; Znf_C2H2_sf. DR InterPro; IPR013087; Znf_C2H2_type. DR PANTHER; PTHR24390:SF159; GROWTH FACTOR INDEPENDENT 1 TRANSCRIPTIONAL REPRESSOR; 1. DR PANTHER; PTHR24390; ZINC FINGER PROTEIN; 1. DR Pfam; PF00651; BTB; 1. DR Pfam; PF00096; zf-C2H2; 2. DR Pfam; PF13912; zf-C2H2_6; 2. DR SMART; SM00225; BTB; 1. DR SMART; SM00355; ZnF_C2H2; 9. DR SUPFAM; SSF57667; beta-beta-alpha zinc fingers; 4. DR SUPFAM; SSF54695; POZ domain; 1. DR PROSITE; PS50097; BTB; 1. DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 8. DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 9. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Chromosomal rearrangement; KW Disease variant; DNA-binding; Intellectual disability; Metal-binding; KW Nucleus; Phosphoprotein; Proteomics identification; Proto-oncogene; KW Reference proteome; Repeat; Repressor; Transcription; KW Transcription regulation; Ubl conjugation pathway; Zinc; Zinc-finger. FT CHAIN 1..673 FT /note="Zinc finger and BTB domain-containing protein 16" FT /id="PRO_0000047729" FT DOMAIN 34..96 FT /note="BTB" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00037" FT ZN_FING 404..426 FT /note="C2H2-type 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042" FT ZN_FING 432..454 FT /note="C2H2-type 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042" FT ZN_FING 461..483 FT /note="C2H2-type 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042" FT ZN_FING 490..512 FT /note="C2H2-type 4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042" FT ZN_FING 518..540 FT /note="C2H2-type 5" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042" FT ZN_FING 546..568 FT /note="C2H2-type 6" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042" FT ZN_FING 574..596 FT /note="C2H2-type 7" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042" FT ZN_FING 602..624 FT /note="C2H2-type 8" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042" FT ZN_FING 630..652 FT /note="C2H2-type 9" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042" FT REGION 200..300 FT /note="Interaction with RUNX1T1" FT /evidence="ECO:0000269|PubMed:10688654" FT REGION 215..236 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 249..332 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 293..302 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 319..331 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT SITE 394..395 FT /note="Breakpoint for translocation to form PLZF-RAR-alpha FT oncogene" FT MOD_RES 76 FT /note="Phosphoserine; by PDPK1" FT /evidence="ECO:0000255" FT MOD_RES 184 FT /note="Phosphoserine; by PDPK1" FT /evidence="ECO:0000255" FT MOD_RES 197 FT /note="Phosphoserine; by PDPK1" FT /evidence="ECO:0000255" FT MOD_RES 256 FT /note="Phosphoserine; by PDPK1" FT /evidence="ECO:0000255" FT MOD_RES 282 FT /note="Phosphothreonine; by PDPK1" FT /evidence="ECO:0000255" FT MOD_RES 628 FT /note="Phosphoserine; by PDPK1" FT /evidence="ECO:0000255" FT VAR_SEQ 255..377 FT /note="Missing (in isoform PLZFA)" FT /evidence="ECO:0000305" FT /id="VSP_006896" FT VARIANT 617 FT /note="M -> V (in SGYMR; dbSNP:rs121434606)" FT /evidence="ECO:0000269|PubMed:18611983" FT /id="VAR_054912" FT CONFLICT 580 FT /note="G -> D (in Ref. 1; CAA79489)" FT /evidence="ECO:0000305" FT HELIX 16..30 FT /evidence="ECO:0007829|PDB:1BUO" FT TURN 31..33 FT /evidence="ECO:0007829|PDB:1BUO" FT STRAND 36..42 FT /evidence="ECO:0007829|PDB:1BUO" FT STRAND 44..47 FT /evidence="ECO:0007829|PDB:1BUO" FT HELIX 49..55 FT /evidence="ECO:0007829|PDB:1BUO" FT HELIX 57..62 FT /evidence="ECO:0007829|PDB:1BUO" FT HELIX 63..65 FT /evidence="ECO:0007829|PDB:1CS3" FT STRAND 68..72 FT /evidence="ECO:0007829|PDB:1BUO" FT HELIX 77..89 FT /evidence="ECO:0007829|PDB:1BUO" FT HELIX 96..98 FT /evidence="ECO:0007829|PDB:1BUO" FT HELIX 99..109 FT /evidence="ECO:0007829|PDB:1BUO" FT HELIX 112..125 FT /evidence="ECO:0007829|PDB:1BUO" FT STRAND 288..290 FT /evidence="ECO:0007829|PDB:8YTH" SQ SEQUENCE 673 AA; 74274 MW; 51F8E361FA31239E CRC64; MDLTKMGMIQ LQNPSHPTGL LCKANQMRLA GTLCDVVIMV DSQEFHAHRT VLACTSKMFE ILFHRNSQHY TLDFLSPKTF QQILEYAYTA TLQAKAEDLD DLLYAAEILE IEYLEEQCLK MLETIQASDD NDTEATMADG GAEEEEDRKA RYLKNIFISK HSSEESGYAS VAGQSLPGPM VDQSPSVSTS FGLSAMSPTK AAVDSLMTIG QSLLQGTLQP PAGPEEPTLA GGGRHPGVAE VKTEMMQVDE VPSQDSPGAA ESSISGGMGD KVEERGKEGP GTPTRSSVIT SARELHYGRE ESAEQVPPPA EAGQAPTGRP EHPAPPPEKH LGIYSVLPNH KADAVLSMPS SVTSGLHVQP ALAVSMDFST YGGLLPQGFI QRELFSKLGE LAVGMKSESR TIGEQCSVCG VELPDNEAVE QHRKLHSGMK TYGCELCGKR FLDSLRLRMH LLAHSAGAKA FVCDQCGAQF SKEDALETHR QTHTGTDMAV FCLLCGKRFQ AQSALQQHME VHAGVRSYIC SECNRTFPSH TALKRHLRSH TGDHPYECEF CGSCFRDEST LKSHKRIHTG EKPYECNGCG KKFSLKHQLE THYRVHTGEK PFECKLCHQR SRDYSAMIKH LRTHNGASPY QCTICTEYCP SLSSMQKHMK GHKPEEIPPD WRIEKTYLYL CYV //