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 FLVC1_HUMAN Reviewed; 555 AA. AC Q9Y5Y0; Q1HE16; Q86XY9; Q9NVR9; DT 13-APR-2004, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1999, sequence version 1. DT 28-JAN-2026, entry version 174. DE RecName: Full=Choline/ethanolamine transporter FLVCR1 {ECO:0000305}; DE AltName: Full=Feline leukemia virus subgroup C receptor-related protein 1; DE Short=Feline leukemia virus subgroup C receptor {ECO:0000303|PubMed:11943475}; DE Short=hFLVCR {ECO:0000303|PubMed:11943475}; DE AltName: Full=Heme transporter FLVCR1 {ECO:0000303|PubMed:23187127}; GN Name=FLVCR1 {ECO:0000303|PubMed:16439531, ECO:0000312|HGNC:HGNC:24682}; GN Synonyms=FLVCR {ECO:0000303|PubMed:11943475}; 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), FUNCTION (ISOFORM 1) (MICROBIAL RP INFECTION), CHARACTERIZATION OF FELV-C RECEPTOR FUNCTION, AND TISSUE RP SPECIFICITY. RC TISSUE=Lymphocyte; RX PubMed=10400745; DOI=10.1128/jvi.73.8.6500-6505.1999; RA Tailor C.S., Willett B.J., Kabat D.; RT "A putative cell surface receptor for anemia-inducing feline leukemia virus RT subgroup C is a member of a transporter superfamily."; RL J. Virol. 73:6500-6505(1999). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RG NHLBI resequencing and genotyping service (RS&G); RL Submitted (APR-2006) to the EMBL/GenBank/DDBJ databases. RN [4] 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 (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANTS PRO-52 AND RP MET-544. RC TISSUE=Duodenum; 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 GENE STRUCTURE. RX PubMed=11943475; DOI=10.1016/s0378-1119(02)00457-2; RA Lipovich L., Hughes A.L., King M.-C., Abkowitz J.L., Quigley J.G.; RT "Genomic structure and evolutionary context of the human feline leukemia RT virus subgroup C receptor (hFLVCR) gene: evidence for block duplications RT and de novo gene formation within duplicons of the hFLVCR locus."; RL Gene 286:203-213(2002). RN [7] RP FUNCTION (ISOFORM 1), TRANSPORTER ACTIVITY (ISOFORM 1), SUBCELLULAR RP LOCATION (ISOFORM 1), AND DEVELOPMENTAL STAGE (ISOFORM 1). RX PubMed=15369674; DOI=10.1016/j.cell.2004.08.014; RA Quigley J.G., Yang Z., Worthington M.T., Phillips J.D., Sabo K.M., RA Sabath D.E., Berg C.L., Sassa S., Wood B.L., Abkowitz J.L.; RT "Identification of a human heme exporter that is essential for RT erythropoiesis."; RL Cell 118:757-766(2004). RN [8] RP SUBCELLULAR LOCATION, TOPOLOGY, AND GLYCOSYLATION. RX PubMed=16439531; DOI=10.1128/jvi.80.4.1742-1751.2006; RA Brown J.K., Fung C., Tailor C.S.; RT "Comprehensive mapping of receptor-functioning domains in feline leukemia RT virus subgroup C receptor FLVCR1."; RL J. Virol. 80:1742-1751(2006). RN [9] 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 [10] 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 [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-56, 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 [12] RP FUNCTION (ISOFORM 1), TRANSPORTER ACTIVITY (ISOFORM 1), AND INTERACTION RP WITH HPX. RX PubMed=20610401; DOI=10.1074/jbc.m110.119131; RA Yang Z., Philips J.D., Doty R.T., Giraudi P., Ostrow J.D., Tiribelli C., RA Smith A., Abkowitz J.L.; RT "Kinetics and specificity of feline leukemia virus subgroup C receptor RT (FLVCR) export function and its dependence on hemopexin."; RL J. Biol. Chem. 285:28874-28882(2010). RN [13] 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 [14] 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 [15] RP ALTERNATIVE SPLICING (ISOFORM 2), FUNCTION (ISOFORMS 1 AND 2), AND RP TRANSPORTER ACTIVITY (ISOFORMS 1 AND 2). RX PubMed=23187127; DOI=10.1172/jci62422; RA Chiabrando D., Marro S., Mercurio S., Giorgi C., Petrillo S., Vinchi F., RA Fiorito V., Fagoonee S., Camporeale A., Turco E., Merlo G.R., Silengo L., RA Altruda F., Pinton P., Tolosano E.; RT "The mitochondrial heme exporter FLVCR1b mediates erythroid RT differentiation."; RL J. Clin. Invest. 122:4569-4579(2012). RN [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-536, AND IDENTIFICATION BY RP 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 [17] RP FUNCTION (ISOFORM 1), TRANSPORTER ACTIVITY (ISOFORM 1), INVOLVEMENT IN RP RETSNS, AND VARIANTS RETSNS ARG-192 AND SER-221. RX PubMed=27923065; DOI=10.1371/journal.pgen.1006461; RA Chiabrando D., Castori M., di Rocco M., Ungelenk M., Giesselmann S., RA Di Capua M., Madeo A., Grammatico P., Bartsch S., Huebner C.A., Altruda F., RA Silengo L., Tolosano E., Kurth I.; RT "Mutations in the heme exporter FLVCR1 cause sensory neurodegeneration with RT loss of pain perception."; RL PLoS Genet. 12:E1006461-E1006461(2016). RN [18] RP FUNCTION, TRANSPORTER ACTIVITY, AND SUBCELLULAR LOCATION. RX PubMed=37100056; DOI=10.1016/j.cmet.2023.04.003; RA Kenny T.C., Khan A., Son Y., Yue L., Heissel S., Sharma A., Pasolli H.A., RA Liu Y., Gamazon E.R., Alwaseem H., Hite R.K., Birsoy K.; RT "Integrative genetic analysis identifies FLVCR1 as a plasma-membrane RT choline transporter in mammals."; RL Cell Metab. 35:1057-1071(2023). RN [19] {ECO:0007744|PDB:8UBW, ECO:0007744|PDB:8UBX, ECO:0007744|PDB:8UBY, ECO:0007744|PDB:8UBZ, ECO:0007744|PDB:8UC0} RP STRUCTURE BY ELECTRON MICROSCOPY (2.42 ANGSTROMS) IN COMPLEX WITH CHOLINE RP AND ETHANOLAMINE, FUNCTION, TRANSPORTER ACTIVITY, AND MUTAGENESIS OF RP TRP-125; TYR-153; GLN-214; ASN-245; TYR-349 AND GLN-471. RX PubMed=38693265; DOI=10.1038/s41586-024-07374-4; RA Son Y., Kenny T.C., Khan A., Birsoy K., Hite R.K.; RT "Structural basis of lipid head group entry to the Kennedy pathway by RT FLVCR1."; RL Nature 0:0-0(2024). RN [20] {ECO:0007744|PDB:8QCS, ECO:0007744|PDB:8QCT, ECO:0007744|PDB:8R8T} RP STRUCTURE BY ELECTRON MICROSCOPY (2.60 ANGSTROMS) IN COMPLEX WITH CHOLINE, RP FUNCTION, TRANSPORTER ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND RP SUBCELLULAR LOCATIONMUTAGENESIS OF TRP-125; GLN-214; ASN-245; TYR-349 AND RP GLN-471. RX PubMed=38778100; DOI=10.1038/s41586-024-07444-7; RA Ri K., Weng T.H., Claveras Cabezudo A., Joesting W., Zhang Y., Bazzone A., RA Leong N.C.P., Welsch S., Doty R.T., Gursu G., Lim T.J.Y., Schmidt S.L., RA Abkowitz J.L., Hummer G., Wu D., Nguyen L.N., Safarian S.; RT "Molecular mechanism of choline and ethanolamine transport in humans."; RL Nature 0:0-0(2024). RN [21] RP VARIANTS RETSNS ASP-121; ARG-192 AND THR-241. RX PubMed=21070897; DOI=10.1016/j.ajhg.2010.10.013; RA Rajadhyaksha A.M., Elemento O., Puffenberger E.G., Schierberl K.C., RA Xiang J.Z., Putorti M.L., Berciano J., Poulin C., Brais B., Michaelides M., RA Weleber R.G., Higgins J.J.; RT "Mutations in FLVCR1 cause posterior column ataxia and retinitis RT pigmentosa."; RL Am. J. Hum. Genet. 87:643-654(2010). RN [22] RP VARIANT RETSNS ARG-493. RX PubMed=21267618; DOI=10.1007/s10048-010-0271-4; RA Ishiura H., Fukuda Y., Mitsui J., Nakahara Y., Ahsan B., Takahashi Y., RA Ichikawa Y., Goto J., Sakai T., Tsuji S.; RT "Posterior column ataxia with retinitis pigmentosa in a Japanese family RT with a novel mutation in FLVCR1."; RL Neurogenetics 12:117-121(2011). RN [23] RP FUNCTION, SUBCELLULAR LOCATION, AND CHARACTERIZATION OF VARIANTS RETSNS RP ASP-121; ARG-192; THR-241 AND ARG-493. RX PubMed=22483575; DOI=10.1016/j.bcmd.2012.03.004; RA Yanatori I., Yasui Y., Miura K., Kishi F.; RT "Mutations of FLVCR1 in posterior column ataxia and retinitis pigmentosa RT result in the loss of heme export activity."; RL Blood Cells Mol. Dis. 49:60-66(2012). RN [24] RP VARIANT RETSNS SER-221. RX PubMed=28766925; DOI=10.1002/ajmg.b.32570; RA Castori M., Morlino S., Ungelenk M., Pareyson D., Salsano E., RA Grammatico P., Tolosano E., Kurth I., Chiabrando D.; RT "Posterior column ataxia with retinitis pigmentosa coexisting with sensory- RT autonomic neuropathy and leukemia due to the homozygous p.Pro221Ser FLVCR1 RT mutation."; RL Am. J. Med. Genet. B Neuropsychiatr. Genet. 174:732-739(2017). RN [25] RP VARIANT RETSNS ASP-121. RX PubMed=30444160; DOI=10.1080/13816810.2018.1547913; RA Lee J., Scanga H.L., Dansingani K.K., Taubenslag K.J., Zlotcavitch L., RA Chauhan B.K., Sylvester C.L., Morton D.H., Nischal K.K.; RT "Clinical and imaging characteristics of posterior column ataxia with RT retinitis pigmentosa with a specific FLVCR1 mutation."; RL Ophthalmic Genet. 39:735-740(2018). RN [26] RP VARIANTS NEDMISH VAL-253; ARG-305; PRO-328; ILE-340; 363-TYR--ILE-555 DEL; RP 390-LEU--ILE-555 DEL; 400-GLN--ILE-555 DEL; PRO-409; ALA-412; ASN-421 AND RP SER-464, INVOLVEMENT IN NEDMISH, CHARACTERIZATION OF VARIANTS NEDMISH RP ARG-305; ILE-340; PRO-409; ALA-412; ASN-421 AND SER-464, VARIANTS RETSNS RP ASN-128 AND VAL-168, CHARACTERIZATION OF VARIANT RETSNS ASN-128, VARIANTS RP ARG-192; SER-249 AND THR-343, CHARACTERIZATION OF VARIANT THR-343, RP FUNCTION, AND MUTAGENESIS OF MET-151 AND LEU-443. RX PubMed=39306721; DOI=10.1016/j.gim.2024.101273; RA Calame D.G., Wong J.H., Panda P., Nguyen D.T., Leong N.C.P., Sangermano R., RA Patankar S.G., Abdel-Hamid M.S., AlAbdi L., Safwat S., Flannery K.P., RA Dardas Z., Fatih J.M., Murali C., Kannan V., Lotze T.E., Herman I., RA Ammouri F., Rezich B., Efthymiou S., Alavi S., Murphy D., Firoozfar Z., RA Nasab M.E., Bahreini A., Ghasemi M., Haridy N.A., Goldouzi H.R., Eghbal F., RA Karimiani E.G., Begtrup A., Elloumi H., Srinivasan V.M., Gowda V.K., Du H., RA Jhangiani S.N., Coban-Akdemir Z., Marafi D., Rodan L., Isikay S., RA Rosenfeld J.A., Ramanathan S., Staton M., Oberg K.C., Clark R.D., RA Wenman C., Loughlin S., Saad R., Ashraf T., Male A., Tadros S., RA Boostani R., Abdel-Salam G.M.H., Zaki M., Mardi A., Hashemi-Gorji F., RA Abdalla E., Manzini M.C., Pehlivan D., Posey J.E., Gibbs R.A., Houlden H., RA Alkuraya F.S., Bujakowska K., Maroofian R., Lupski J.R., Nguyen L.N.; RT "Biallelic variation in the choline and ethanolamine transporter FLVCR1 RT underlies a severe developmental disorder spectrum."; RL Genet. Med. 27:101273-101273(2025). CC -!- FUNCTION: Uniporter that mediates the transport of extracellular CC choline and ethanolamine into cells, thereby playing a key role in CC phospholipid biosynthesis (PubMed:37100056, PubMed:38693265, CC PubMed:38778100, PubMed:39306721). Choline and ethanolamine are the CC precursors of phosphatidylcholine and phosphatidylethanolamine, CC respectively, the two most abundant phospholipids (PubMed:38693265, CC PubMed:38778100). Transport is not coupled with proton transport and is CC exclusively driven by the choline (or ethanolamine) gradient across the CC plasma membrane (PubMed:38693265, PubMed:38778100). Also acts as a heme CC b transporter that mediates heme efflux from the cytoplasm to the CC extracellular compartment (PubMed:15369674, PubMed:20610401, CC PubMed:22483575, PubMed:23187127, PubMed:27923065). CC {ECO:0000269|PubMed:15369674, ECO:0000269|PubMed:20610401, CC ECO:0000269|PubMed:22483575, ECO:0000269|PubMed:23187127, CC ECO:0000269|PubMed:27923065, ECO:0000269|PubMed:37100056, CC ECO:0000269|PubMed:38693265, ECO:0000269|PubMed:38778100, CC ECO:0000269|PubMed:39306721}. CC -!- FUNCTION: [Isoform 1]: Uniporter that mediates the transport of CC extracellular choline and ethanolamine into cells (PubMed:37100056, CC PubMed:38693265). Choline and ethanolamine are the precursors of CC phosphatidylcholine and phosphatidylethanolamine, respectively, the two CC most abundant phospholipids (PubMed:38693265). Transport is not coupled CC with proton transport and is exclusively driven by the choline (or CC ethanolamine) gradient across the plasma membrane (PubMed:38693265). CC Also acts as a heme b transporter that mediates heme efflux from the CC cytoplasm to the extracellular compartment (PubMed:15369674, CC PubMed:20610401, PubMed:22483575, PubMed:23187127, PubMed:27923065). CC Heme export depends on the presence of HPX and is required to maintain CC intracellular free heme balance, protecting cells from heme toxicity CC (PubMed:20610401). Heme export provides protection from heme or ferrous CC iron toxicities in liver, brain, sensory neurons and during CC erythropoiesis, a process in which heme synthesis intensifies CC (PubMed:20610401, PubMed:23187127). Possibly export coproporphyrin and CC protoporphyrin IX, which are both intermediate products in the heme CC biosynthetic pathway (PubMed:20610401). Does not export bilirubin CC (PubMed:20610401). The molecular mechanism of heme transport, whether CC electrogenic, electroneutral or coupled to other ions, remains to be CC elucidated (PubMed:20610401, PubMed:23187127). CC {ECO:0000269|PubMed:15369674, ECO:0000269|PubMed:20610401, CC ECO:0000269|PubMed:22483575, ECO:0000269|PubMed:23187127, CC ECO:0000269|PubMed:27923065, ECO:0000269|PubMed:37100056, CC ECO:0000269|PubMed:38693265}. CC -!- FUNCTION: [Isoform 2]: Heme b transporter that promotes heme efflux CC from the mitochondrion to the cytoplasm. Essential for erythroid CC differentiation. {ECO:0000269|PubMed:23187127}. CC -!- FUNCTION: [Isoform 1]: (Microbial infection) Confers susceptibility to CC feline leukemia virus subgroup C (FeLV-C) infection in vitro. CC {ECO:0000269|PubMed:10400745}. CC -!- CATALYTIC ACTIVITY: CC Reaction=choline(out) = choline(in); Xref=Rhea:RHEA:32751, CC ChEBI:CHEBI:15354; Evidence={ECO:0000269|PubMed:37100056, CC ECO:0000269|PubMed:38693265, ECO:0000269|PubMed:38778100}; CC -!- CATALYTIC ACTIVITY: CC Reaction=ethanolamine(in) = ethanolamine(out); Xref=Rhea:RHEA:32747, CC ChEBI:CHEBI:57603; Evidence={ECO:0000269|PubMed:38693265, CC ECO:0000269|PubMed:38778100}; CC -!- CATALYTIC ACTIVITY: CC Reaction=heme b(in) = heme b(out); Xref=Rhea:RHEA:75443, CC ChEBI:CHEBI:60344; Evidence={ECO:0000269|PubMed:15369674, CC ECO:0000269|PubMed:20610401}; CC -!- CATALYTIC ACTIVITY: [Isoform 1]: CC Reaction=choline(out) = choline(in); Xref=Rhea:RHEA:32751, CC ChEBI:CHEBI:15354; Evidence={ECO:0000269|PubMed:37100056, CC ECO:0000269|PubMed:38693265, ECO:0000269|PubMed:38778100}; CC -!- CATALYTIC ACTIVITY: [Isoform 1]: CC Reaction=ethanolamine(in) = ethanolamine(out); Xref=Rhea:RHEA:32747, CC ChEBI:CHEBI:57603; Evidence={ECO:0000269|PubMed:38693265, CC ECO:0000269|PubMed:38778100}; CC -!- CATALYTIC ACTIVITY: [Isoform 1]: CC Reaction=heme b(in) = heme b(out); Xref=Rhea:RHEA:75443, CC ChEBI:CHEBI:60344; Evidence={ECO:0000269|PubMed:15369674, CC ECO:0000269|PubMed:20610401}; CC -!- CATALYTIC ACTIVITY: [Isoform 2]: CC Reaction=heme b(in) = heme b(out); Xref=Rhea:RHEA:75443, CC ChEBI:CHEBI:60344; Evidence={ECO:0000305|PubMed:23187127}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=47.4 uM for choline {ECO:0000269|PubMed:38778100}; CC KM=8.0 uM for ethanolamine {ECO:0000269|PubMed:38778100}; CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane CC {ECO:0000269|PubMed:15369674, ECO:0000269|PubMed:22483575, CC ECO:0000269|PubMed:37100056, ECO:0000269|PubMed:38778100}; Multi-pass CC membrane protein {ECO:0000255}. CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Mitochondrion membrane CC {ECO:0000269|PubMed:23187127}; Multi-pass membrane protein CC {ECO:0000255}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; Synonyms=FLVCR1a {ECO:0000303|PubMed:23187127}; CC IsoId=Q9Y5Y0-1; Sequence=Displayed; CC Name=2; Synonyms=FLVCR1b, mitochondrial {ECO:0000303|PubMed:23187127}; CC IsoId=Q9Y5Y0-2; Sequence=VSP_047866; CC -!- TISSUE SPECIFICITY: Found all hematopoietic tissues including CC peripheral blood lymphocytes. Some expression is found in pancreas and CC kidney. {ECO:0000269|PubMed:10400745}. CC -!- DEVELOPMENTAL STAGE: [Isoform 1]: Down-regulated in haemopoietic CC progenitor cells undergoing differentiation and hemoglobinization. CC Abundant in fetal liver. {ECO:0000269|PubMed:15369674}. CC -!- PTM: N-Glycosylated. {ECO:0000269|PubMed:16439531}. CC -!- DISEASE: Retinopathy-sensory neuropathy syndrome (RETSNS) [MIM:609033]: CC An autosomal recessive neurodegenerative syndrome beginning in infancy CC with areflexia and retinitis pigmentosa. Nyctalopia (night blindness) CC and peripheral visual field loss are usually evident during late CC childhood or teenage years, with subsequent progressive constriction of CC the visual fields and loss of central retinal function over time. A CC sensory ataxia caused by degeneration of the posterior columns of the CC spinal cord results in a loss of proprioceptive sensation that is CC clinically evident in the second decade of life and gradually CC progresses. Scoliosis, camptodactyly, achalasia, gastrointestinal CC dysmotility, and a sensory peripheral neuropathy are variable features CC of the disease. Affected individuals have no clinical or radiological CC evidence of cerebral or cerebellar involvement. Some patients have pain CC insensitivity and commonly manifest self-injury, ulcers and CC amputations. {ECO:0000269|PubMed:21070897, ECO:0000269|PubMed:21267618, CC ECO:0000269|PubMed:22483575, ECO:0000269|PubMed:27923065, CC ECO:0000269|PubMed:28766925, ECO:0000269|PubMed:30444160, CC ECO:0000269|PubMed:39306721}. Note=The disease is caused by variants CC affecting the gene represented in this entry. Defective neuronal heme CC transmembrane export due to FLVCR1 mutations may abrogate the CC neuroprotective effects of neuroglobin and initiate an apoptotic CC cascade that results in the selective degeneration of photoreceptors in CC the neurosensory retina and sensory neurons in the posterior spinal CC cord. {ECO:0000269|PubMed:21070897}. CC -!- DISEASE: Neurodevelopmental disorder with microcephaly, absent speech, CC and hypotonia (NEDMISH) [MIM:621060]: A severe, autosomal recessive CC disorder characterized by profound global developmental delay, impaired CC intellectual development, absent speech, microcephaly, brain CC malformations, epilepsy, spasticity, and premature death. Brain CC malformations range from mild brain volume reduction to CC hydranencephaly. Additional features may include cortical visual CC impairment, sensory neuropathy, limb and digital malformations, and CC macrocytic anemia. {ECO:0000269|PubMed:39306721}. Note=The disease is CC caused by variants affecting the gene represented in this entry. CC -!- MISCELLANEOUS: [Isoform 2]: Has a probable mitochondrial transit CC peptide at positions 1-38. {ECO:0000305}. CC -!- SIMILARITY: Belongs to the major facilitator superfamily. Feline CC leukemia virus subgroup C receptor (TC 2.A.1.28.1) family. CC {ECO:0000305}. 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; AF118637; AAD45243.1; -; mRNA. DR EMBL; AK001419; BAA91679.1; -; mRNA. DR EMBL; DQ496107; ABF47096.1; -; Genomic_DNA. DR EMBL; CH471100; EAW93374.1; -; Genomic_DNA. DR EMBL; BC048312; AAH48312.1; -; mRNA. DR CCDS; CCDS1510.1; -. [Q9Y5Y0-1] DR RefSeq; NP_054772.1; NM_014053.4. [Q9Y5Y0-1] DR PDB; 8QCS; EM; 2.90 A; A=1-555. DR PDB; 8QCT; EM; 2.60 A; A=1-555. DR PDB; 8R8T; EM; 2.90 A; A=1-555. DR PDB; 8UBW; EM; 2.59 A; A=1-555. DR PDB; 8UBX; EM; 2.50 A; A=1-555. DR PDB; 8UBY; EM; 2.67 A; A=1-555. DR PDB; 8UBZ; EM; 3.02 A; A=1-555. DR PDB; 8UC0; EM; 2.42 A; A=1-555. DR PDBsum; 8QCS; -. DR PDBsum; 8QCT; -. DR PDBsum; 8R8T; -. DR PDBsum; 8UBW; -. DR PDBsum; 8UBX; -. DR PDBsum; 8UBY; -. DR PDBsum; 8UBZ; -. DR PDBsum; 8UC0; -. DR AlphaFoldDB; Q9Y5Y0; -. DR EMDB; EMD-18334; -. DR EMDB; EMD-18335; -. DR EMDB; EMD-19009; -. DR EMDB; EMD-42107; -. DR EMDB; EMD-42108; -. DR EMDB; EMD-42109; -. DR EMDB; EMD-42110; -. DR EMDB; EMD-42111; -. DR SMR; Q9Y5Y0; -. DR BioGRID; 118803; 166. DR FunCoup; Q9Y5Y0; 1683. DR MINT; Q9Y5Y0; -. DR STRING; 9606.ENSP00000355938; -. DR TCDB; 2.A.1.28.1; the major facilitator superfamily (mfs). DR GlyCosmos; Q9Y5Y0; 2 sites, No reported glycans. DR GlyGen; Q9Y5Y0; 2 sites, 1 O-linked glycan (1 site). DR iPTMnet; Q9Y5Y0; -. DR PhosphoSitePlus; Q9Y5Y0; -. DR SwissPalm; Q9Y5Y0; -. DR BioMuta; FLVCR1; -. DR DMDM; 46396053; -. DR jPOST; Q9Y5Y0; -. DR MassIVE; Q9Y5Y0; -. DR PaxDb; 9606-ENSP00000355938; -. DR PeptideAtlas; Q9Y5Y0; -. DR ProteomicsDB; 86537; -. [Q9Y5Y0-1] DR Pumba; Q9Y5Y0; -. DR Antibodypedia; 20720; 176 antibodies from 31 providers. DR DNASU; 28982; -. DR Ensembl; ENST00000366971.9; ENSP00000355938.4; ENSG00000162769.14. [Q9Y5Y0-1] DR GeneID; 28982; -. DR KEGG; hsa:28982; -. DR MANE-Select; ENST00000366971.9; ENSP00000355938.4; NM_014053.4; NP_054772.1. DR UCSC; uc001hjt.3; human. [Q9Y5Y0-1] DR AGR; HGNC:24682; -. DR ClinPGx; PA162388695; -. DR CTD; 28982; -. DR DisGeNET; 28982; -. DR GeneCards; FLVCR1; -. DR HGNC; HGNC:24682; FLVCR1. DR HPA; ENSG00000162769; Tissue enhanced (intestine). DR MalaCards; FLVCR1; -. DR MIM; 609033; phenotype. DR MIM; 609144; gene. DR MIM; 621060; phenotype. DR OpenTargets; ENSG00000162769; -. DR Orphanet; 88628; Posterior column ataxia-retinitis pigmentosa syndrome. DR VEuPathDB; HostDB:ENSG00000162769; -. DR eggNOG; KOG2563; Eukaryota. DR GeneTree; ENSGT01030000234625; -. DR InParanoid; Q9Y5Y0; -. DR OMA; LDLMGHN; -. DR OrthoDB; 422206at2759; -. DR PAN-GO; Q9Y5Y0; 6 GO annotations based on evolutionary models. DR PhylomeDB; Q9Y5Y0; -. DR PathwayCommons; Q9Y5Y0; -. DR Reactome; R-HSA-189451; Heme biosynthesis. DR Reactome; R-HSA-917937; Iron uptake and transport. [Q9Y5Y0-1] DR SignaLink; Q9Y5Y0; -. DR Agora; ENSG00000162769; -. DR BioGRID-ORCS; 28982; 32 hits in 1166 CRISPR screens. DR ChiTaRS; FLVCR1; human. DR GeneWiki; FLVCR1; -. DR GenomeRNAi; 28982; -. DR Pharos; Q9Y5Y0; Tbio. DR PRO; PR:Q9Y5Y0; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; Q9Y5Y0; protein. DR Bgee; ENSG00000162769; Expressed in jejunal mucosa and 174 other cell types or tissues. DR ExpressionAtlas; Q9Y5Y0; baseline and differential. DR GO; GO:0016020; C:membrane; IBA:GO_Central. DR GO; GO:0005743; C:mitochondrial inner membrane; TAS:Reactome. DR GO; GO:0005739; C:mitochondrion; IDA:MGI. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0015220; F:choline transmembrane transporter activity; IDA:UniProtKB. DR GO; GO:0034228; F:ethanolamine transmembrane transporter activity; IDA:UniProtKB. DR GO; GO:0020037; F:heme binding; IBA:GO_Central. DR GO; GO:0015232; F:heme transmembrane transporter activity; IDA:UniProtKB. DR GO; GO:0001568; P:blood vessel development; IEA:Ensembl. DR GO; GO:0015871; P:choline transport; IDA:UniProtKB. DR GO; GO:0042733; P:embryonic digit morphogenesis; IEA:Ensembl. DR GO; GO:0048704; P:embryonic skeletal system morphogenesis; IEA:Ensembl. DR GO; GO:0030218; P:erythrocyte differentiation; IDA:MGI. DR GO; GO:0043249; P:erythrocyte maturation; IEA:UniProtKB-KW. DR GO; GO:0060323; P:head morphogenesis; IEA:Ensembl. DR GO; GO:0006783; P:heme biosynthetic process; TAS:Reactome. DR GO; GO:0097037; P:heme export; IMP:UniProtKB. DR GO; GO:0015886; P:heme transport; IMP:MGI. DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl. DR GO; GO:0006879; P:intracellular iron ion homeostasis; TAS:Reactome. DR GO; GO:0006839; P:mitochondrial transport; IDA:MGI. DR GO; GO:0035264; P:multicellular organism growth; IEA:Ensembl. DR GO; GO:0008654; P:phospholipid biosynthetic process; IDA:UniProtKB. DR GO; GO:0046620; P:regulation of organ growth; IEA:Ensembl. DR GO; GO:0048536; P:spleen development; IEA:Ensembl. DR CDD; cd17455; MFS_FLVCR1; 1. DR FunFam; 1.20.1250.20:FF:000184; Feline leukemia virus subgroup C receptor-related protein 1; 1. DR Gene3D; 1.20.1250.20; MFS general substrate transporter like domains; 1. DR InterPro; IPR049680; FLVCR1-2_SLC49-like. DR InterPro; IPR011701; MFS. DR InterPro; IPR020846; MFS_dom. DR InterPro; IPR036259; MFS_trans_sf. DR PANTHER; PTHR10924:SF2; HEME TRANSPORTER FLVCR1; 1. DR PANTHER; PTHR10924; MAJOR FACILITATOR SUPERFAMILY PROTEIN-RELATED; 1. DR Pfam; PF07690; MFS_1; 1. DR SUPFAM; SSF103473; MFS general substrate transporter; 1. DR PROSITE; PS50850; MFS; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell membrane; Disease variant; KW Epilepsy; Erythrocyte maturation; Glycoprotein; Intellectual disability; KW Membrane; Mitochondrion; Neurodegeneration; Neuropathy; Phosphoprotein; KW Proteomics identification; Receptor; Reference proteome; KW Retinitis pigmentosa; Transmembrane; Transmembrane helix; Transport. FT CHAIN 1..555 FT /note="Choline/ethanolamine transporter FLVCR1" FT /id="PRO_0000084844" FT TOPO_DOM 1..99 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:38693265, FT ECO:0000269|PubMed:38778100, ECO:0007744|PDB:8QCS, FT ECO:0007744|PDB:8QCT, ECO:0007744|PDB:8R8T, FT ECO:0007744|PDB:8UBW, ECO:0007744|PDB:8UBX, FT ECO:0007744|PDB:8UBZ" FT TRANSMEM 100..124 FT /note="Helical; Name=TM1" FT /evidence="ECO:0000269|PubMed:38693265, FT ECO:0000269|PubMed:38778100, ECO:0007744|PDB:8QCS, FT ECO:0007744|PDB:8QCT, ECO:0007744|PDB:8R8T, FT ECO:0007744|PDB:8UBW, ECO:0007744|PDB:8UBX, FT ECO:0007744|PDB:8UBZ" FT TOPO_DOM 125..142 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:38693265, FT ECO:0000269|PubMed:38778100, ECO:0007744|PDB:8QCS, FT ECO:0007744|PDB:8QCT, ECO:0007744|PDB:8R8T, FT ECO:0007744|PDB:8UBW, ECO:0007744|PDB:8UBX, FT ECO:0007744|PDB:8UBZ" FT TRANSMEM 143..170 FT /note="Helical; Name=TM2" FT /evidence="ECO:0000269|PubMed:38693265, FT ECO:0000269|PubMed:38778100, ECO:0007744|PDB:8QCS, FT ECO:0007744|PDB:8QCT, ECO:0007744|PDB:8R8T, FT ECO:0007744|PDB:8UBW, ECO:0007744|PDB:8UBX, FT ECO:0007744|PDB:8UBZ" FT TOPO_DOM 171..172 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:38693265, FT ECO:0000269|PubMed:38778100, ECO:0007744|PDB:8QCS, FT ECO:0007744|PDB:8QCT, ECO:0007744|PDB:8R8T, FT ECO:0007744|PDB:8UBW, ECO:0007744|PDB:8UBX, FT ECO:0007744|PDB:8UBZ" FT TRANSMEM 173..192 FT /note="Helical; Name=TM3" FT /evidence="ECO:0000269|PubMed:38693265, FT ECO:0000269|PubMed:38778100, ECO:0007744|PDB:8QCS, FT ECO:0007744|PDB:8QCT, ECO:0007744|PDB:8R8T, FT ECO:0007744|PDB:8UBW, ECO:0007744|PDB:8UBX, FT ECO:0007744|PDB:8UBZ" FT TOPO_DOM 193..199 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:38693265, FT ECO:0000269|PubMed:38778100, ECO:0007744|PDB:8QCS, FT ECO:0007744|PDB:8QCT, ECO:0007744|PDB:8R8T, FT ECO:0007744|PDB:8UBW, ECO:0007744|PDB:8UBX, FT ECO:0007744|PDB:8UBZ" FT TRANSMEM 200..228 FT /note="Helical; Name=TM4" FT /evidence="ECO:0000269|PubMed:38693265, FT ECO:0000269|PubMed:38778100, ECO:0007744|PDB:8QCS, FT ECO:0007744|PDB:8QCT, ECO:0007744|PDB:8R8T, FT ECO:0007744|PDB:8UBW, ECO:0007744|PDB:8UBX, FT ECO:0007744|PDB:8UBZ" FT TOPO_DOM 229..233 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:38693265, FT ECO:0000269|PubMed:38778100, ECO:0007744|PDB:8QCS, FT ECO:0007744|PDB:8QCT, ECO:0007744|PDB:8R8T, FT ECO:0007744|PDB:8UBW, ECO:0007744|PDB:8UBX, FT ECO:0007744|PDB:8UBZ" FT TRANSMEM 234..259 FT /note="Helical; Name=TM5" FT /evidence="ECO:0000269|PubMed:38693265, FT ECO:0000269|PubMed:38778100, ECO:0007744|PDB:8QCS, FT ECO:0007744|PDB:8QCT, ECO:0007744|PDB:8R8T, FT ECO:0007744|PDB:8UBW, ECO:0007744|PDB:8UBX, FT ECO:0007744|PDB:8UBZ" FT TOPO_DOM 260..265 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:38693265, FT ECO:0000269|PubMed:38778100, ECO:0007744|PDB:8QCS, FT ECO:0007744|PDB:8QCT, ECO:0007744|PDB:8R8T, FT ECO:0007744|PDB:8UBW, ECO:0007744|PDB:8UBX, FT ECO:0007744|PDB:8UBZ" FT TRANSMEM 266..295 FT /note="Helical; Name=TM6" FT /evidence="ECO:0000269|PubMed:38693265, FT ECO:0000269|PubMed:38778100, ECO:0007744|PDB:8QCS, FT ECO:0007744|PDB:8QCT, ECO:0007744|PDB:8R8T, FT ECO:0007744|PDB:8UBW, ECO:0007744|PDB:8UBX, FT ECO:0007744|PDB:8UBZ" FT TOPO_DOM 296..331 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:38693265, FT ECO:0000269|PubMed:38778100, ECO:0007744|PDB:8QCS, FT ECO:0007744|PDB:8QCT, ECO:0007744|PDB:8R8T, FT ECO:0007744|PDB:8UBW, ECO:0007744|PDB:8UBX, FT ECO:0007744|PDB:8UBZ" FT TRANSMEM 332..362 FT /note="Helical; Name=TM7" FT /evidence="ECO:0000269|PubMed:38693265, FT ECO:0000269|PubMed:38778100, ECO:0007744|PDB:8QCS, FT ECO:0007744|PDB:8QCT, ECO:0007744|PDB:8R8T, FT ECO:0007744|PDB:8UBW, ECO:0007744|PDB:8UBX, FT ECO:0007744|PDB:8UBZ" FT TOPO_DOM 363..366 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:38693265, FT ECO:0000269|PubMed:38778100, ECO:0007744|PDB:8QCS, FT ECO:0007744|PDB:8QCT, ECO:0007744|PDB:8R8T, FT ECO:0007744|PDB:8UBW, ECO:0007744|PDB:8UBX, FT ECO:0007744|PDB:8UBZ" FT TRANSMEM 367..395 FT /note="Helical; Name=TM8" FT /evidence="ECO:0000269|PubMed:38693265, FT ECO:0000269|PubMed:38778100, ECO:0007744|PDB:8QCS, FT ECO:0007744|PDB:8QCT, ECO:0007744|PDB:8R8T, FT ECO:0007744|PDB:8UBW, ECO:0007744|PDB:8UBX, FT ECO:0007744|PDB:8UBZ" FT TOPO_DOM 396..397 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:38693265, FT ECO:0000269|PubMed:38778100, ECO:0007744|PDB:8QCS, FT ECO:0007744|PDB:8QCT, ECO:0007744|PDB:8R8T, FT ECO:0007744|PDB:8UBW, ECO:0007744|PDB:8UBX, FT ECO:0007744|PDB:8UBZ" FT TRANSMEM 398..420 FT /note="Helical; Name=TM9" FT /evidence="ECO:0000269|PubMed:38693265, FT ECO:0000269|PubMed:38778100, ECO:0007744|PDB:8QCS, FT ECO:0007744|PDB:8QCT, ECO:0007744|PDB:8R8T, FT ECO:0007744|PDB:8UBW, ECO:0007744|PDB:8UBX, FT ECO:0007744|PDB:8UBZ" FT TOPO_DOM 421..423 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:38693265, FT ECO:0000269|PubMed:38778100, ECO:0007744|PDB:8QCS, FT ECO:0007744|PDB:8QCT, ECO:0007744|PDB:8R8T, FT ECO:0007744|PDB:8UBW, ECO:0007744|PDB:8UBX, FT ECO:0007744|PDB:8UBZ" FT TRANSMEM 424..453 FT /note="Helical; Name=TM10" FT /evidence="ECO:0000269|PubMed:38693265, FT ECO:0000269|PubMed:38778100, ECO:0007744|PDB:8QCS, FT ECO:0007744|PDB:8QCT, ECO:0007744|PDB:8R8T, FT ECO:0007744|PDB:8UBW, ECO:0007744|PDB:8UBX, FT ECO:0007744|PDB:8UBZ" FT TOPO_DOM 454..461 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:38693265, FT ECO:0000269|PubMed:38778100, ECO:0007744|PDB:8QCS, FT ECO:0007744|PDB:8QCT, ECO:0007744|PDB:8R8T, FT ECO:0007744|PDB:8UBW, ECO:0007744|PDB:8UBX, FT ECO:0007744|PDB:8UBZ" FT TRANSMEM 462..487 FT /note="Helical; Name=TM11" FT /evidence="ECO:0000269|PubMed:38693265, FT ECO:0000269|PubMed:38778100, ECO:0007744|PDB:8QCS, FT ECO:0007744|PDB:8QCT, ECO:0007744|PDB:8R8T, FT ECO:0007744|PDB:8UBW, ECO:0007744|PDB:8UBX, FT ECO:0007744|PDB:8UBZ" FT TOPO_DOM 488..489 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:38693265, FT ECO:0000269|PubMed:38778100, ECO:0007744|PDB:8QCS, FT ECO:0007744|PDB:8QCT, ECO:0007744|PDB:8R8T, FT ECO:0007744|PDB:8UBW, ECO:0007744|PDB:8UBX, FT ECO:0007744|PDB:8UBZ" FT TRANSMEM 490..512 FT /note="Helical; Name=TM12" FT /evidence="ECO:0000269|PubMed:38693265, FT ECO:0000269|PubMed:38778100, ECO:0007744|PDB:8QCS, FT ECO:0007744|PDB:8QCT, ECO:0007744|PDB:8R8T, FT ECO:0007744|PDB:8UBW, ECO:0007744|PDB:8UBX, FT ECO:0007744|PDB:8UBZ" FT TOPO_DOM 513..555 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:38693265, FT ECO:0000269|PubMed:38778100, ECO:0007744|PDB:8QCS, FT ECO:0007744|PDB:8QCT, ECO:0007744|PDB:8R8T, FT ECO:0007744|PDB:8UBW, ECO:0007744|PDB:8UBX, FT ECO:0007744|PDB:8UBZ" FT REGION 1..52 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 535..555 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 214 FT /ligand="ethanolamine" FT /ligand_id="ChEBI:CHEBI:57603" FT /evidence="ECO:0000269|PubMed:38693265, FT ECO:0000269|PubMed:38778100, ECO:0007744|PDB:8R8T, FT ECO:0007744|PDB:8UBX" FT BINDING 471 FT /ligand="choline" FT /ligand_id="ChEBI:CHEBI:15354" FT /evidence="ECO:0000269|PubMed:38693265, FT ECO:0000269|PubMed:38778100, ECO:0007744|PDB:8QCT, FT ECO:0007744|PDB:8UBX, ECO:0007744|PDB:8UBZ" FT BINDING 471 FT /ligand="ethanolamine" FT /ligand_id="ChEBI:CHEBI:57603" FT /evidence="ECO:0000269|PubMed:38693265, FT ECO:0007744|PDB:8R8T, ECO:0007744|PDB:8UBX" FT MOD_RES 56 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19690332" FT MOD_RES 536 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT CARBOHYD 265 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT VAR_SEQ 1..276 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334" FT /id="VSP_047866" FT VARIANT 52 FT /note="A -> P (in dbSNP:rs11120047)" FT /evidence="ECO:0000269|PubMed:15489334" FT /id="VAR_050297" FT VARIANT 121 FT /note="N -> D (in RETSNS; likely pathogenic; abolished FT localization to the plasma membrane, leading to decreased FT heme exporter activity; dbSNP:rs267606820)" FT /evidence="ECO:0000269|PubMed:21070897, FT ECO:0000269|PubMed:22483575, ECO:0000269|PubMed:30444160" FT /id="VAR_065158" FT VARIANT 128 FT /note="Y -> N (in RETSNS; uncertain significance; decreased FT choline transmembrane transporter activity; decreased FT ethanolamine transmembrane transporter activity)" FT /evidence="ECO:0000269|PubMed:39306721" FT /id="VAR_090360" FT VARIANT 168 FT /note="L -> V (in RETSNS; uncertain significance)" FT /evidence="ECO:0000269|PubMed:39306721" FT /id="VAR_090361" FT VARIANT 192 FT /note="C -> R (in RETSNS; likely pathogenic; also found in FT a patient with mild developmental delay, hypotonia and FT sensory neuropathy without ocular clinical features; FT abolished localization to the plasma membrane, leading to FT decreased heme exporter activity; dbSNP:rs267606821)" FT /evidence="ECO:0000269|PubMed:21070897, FT ECO:0000269|PubMed:22483575, ECO:0000269|PubMed:27923065, FT ECO:0000269|PubMed:39306721" FT /id="VAR_065159" FT VARIANT 221 FT /note="P -> S (in RETSNS; uncertain significance; FT dbSNP:rs753000469)" FT /evidence="ECO:0000269|PubMed:27923065, FT ECO:0000269|PubMed:28766925" FT /id="VAR_077884" FT VARIANT 241 FT /note="A -> T (in RETSNS; likely pathogenic; abolished FT localization to the plasma membrane, leading to decreased FT heme exporter activity; dbSNP:rs267606819)" FT /evidence="ECO:0000269|PubMed:21070897, FT ECO:0000269|PubMed:22483575" FT /id="VAR_065160" FT VARIANT 249 FT /note="T -> S (found in a patient with a mild phenotype FT consisting of hypotonia and sensory and motor neuropathy; FT uncertain significance)" FT /evidence="ECO:0000269|PubMed:39306721" FT /id="VAR_090362" FT VARIANT 253 FT /note="F -> V (in NEDMISH; mild phenotype; uncertain FT significance)" FT /evidence="ECO:0000269|PubMed:39306721" FT /id="VAR_090363" FT VARIANT 305 FT /note="S -> R (in NEDMISH; uncertain significance; FT decreased choline transmembrane transporter activity; FT severely decreased ethanolamine transmembrane transporter FT activity)" FT /evidence="ECO:0000269|PubMed:39306721" FT /id="VAR_090364" FT VARIANT 328 FT /note="L -> P (in NEDMISH; uncertain significance; FT dbSNP:rs1664640662)" FT /evidence="ECO:0000269|PubMed:39306721" FT /id="VAR_090365" FT VARIANT 340 FT /note="T -> I (in NEDMISH; uncertain significance; severely FT decreased choline and ethanolamine transmembrane FT transporter activity; dbSNP:rs754655924)" FT /evidence="ECO:0000269|PubMed:39306721" FT /id="VAR_090366" FT VARIANT 343 FT /note="I -> T (found in patients with sensory neuropathy; FT uncertain significance; decreased choline and ethanolamine FT transmembrane transporter activity; dbSNP:rs774455543)" FT /evidence="ECO:0000269|PubMed:39306721" FT /id="VAR_090367" FT VARIANT 363..555 FT /note="Missing (in NEDMISH; likely pathogenic)" FT /evidence="ECO:0000269|PubMed:39306721" FT /id="VAR_090368" FT VARIANT 390..555 FT /note="Missing (in NEDMISH; likely pathogenic)" FT /evidence="ECO:0000269|PubMed:39306721" FT /id="VAR_090369" FT VARIANT 400..555 FT /note="Missing (in NEDMISH; likely pathogenic)" FT /evidence="ECO:0000269|PubMed:39306721" FT /id="VAR_090370" FT VARIANT 409 FT /note="S -> P (in NEDMISH; uncertain significance; FT decreased choline transmembrane transporter activity; FT severely decreased ethanolamine transmembrane transporter FT activity; dbSNP:rs2102568794)" FT /evidence="ECO:0000269|PubMed:39306721" FT /id="VAR_090371" FT VARIANT 412 FT /note="G -> A (in NEDMISH; likely pathogenic; due to a FT nucleotide substitution that causes missplicing of exon 6 FT or results in missense variant A-412; loss of choline and FT ethanolamine transmembrane transporter activity; FT dbSNP:rs775587493)" FT /evidence="ECO:0000269|PubMed:39306721" FT /id="VAR_090372" FT VARIANT 421 FT /note="D -> N (in NEDMISH; likely pathogenic; due to a FT nucleotide substitution that causes missplicing of exon 6 FT or results in missense variant N-421; missense variant N- FT 421 does not affect choline and ethanolamine transmembrane FT transporter activity; dbSNP:rs2102568834)" FT /evidence="ECO:0000269|PubMed:39306721" FT /id="VAR_090373" FT VARIANT 464 FT /note="G -> S (in NEDMISH; uncertain significance; FT decreased choline and ethanolamine transmembrane FT transporter activity; dbSNP:rs1273394834)" FT /evidence="ECO:0000269|PubMed:39306721" FT /id="VAR_090374" FT VARIANT 493 FT /note="G -> R (in RETSNS; uncertain significance; abolished FT localization to the plasma membrane, leading to decreased FT heme exporter activity; dbSNP:rs1558121050)" FT /evidence="ECO:0000269|PubMed:21267618, FT ECO:0000269|PubMed:22483575" FT /id="VAR_065161" FT VARIANT 544 FT /note="T -> M (in dbSNP:rs3207090)" FT /evidence="ECO:0000269|PubMed:15489334" FT /id="VAR_050298" FT MUTAGEN 125 FT /note="W->A: Reduced transport of choline and FT ethanolamine." FT /evidence="ECO:0000269|PubMed:38693265, FT ECO:0000269|PubMed:38778100" FT MUTAGEN 151 FT /note="M->V: No effect on choline transmembrane transporter FT activity. No effect on ethanolamine transmembrane FT transporter activity." FT /evidence="ECO:0000269|PubMed:39306721" FT MUTAGEN 153 FT /note="Y->A: Reduced transport of choline and FT ethanolamine." FT /evidence="ECO:0000269|PubMed:38693265" FT MUTAGEN 214 FT /note="Q->A: Reduced transport of choline and nearly FT abolished transport of ethanolamine." FT /evidence="ECO:0000269|PubMed:38693265, FT ECO:0000269|PubMed:38778100" FT MUTAGEN 245 FT /note="N->A: Slightly reduced transport of choline and FT ethanolamine." FT /evidence="ECO:0000269|PubMed:38693265, FT ECO:0000269|PubMed:38778100" FT MUTAGEN 349 FT /note="Y->A: Reduced transport of choline and FT ethanolamine." FT /evidence="ECO:0000269|PubMed:38693265, FT ECO:0000269|PubMed:38778100" FT MUTAGEN 443 FT /note="L->P: Decreased choline and ethanolamine FT transmembrane transporter activity." FT /evidence="ECO:0000269|PubMed:39306721" FT MUTAGEN 471 FT /note="Q->A: Slightly reduced transport of choline and FT ethanolamine." FT /evidence="ECO:0000269|PubMed:38693265, FT ECO:0000269|PubMed:38778100" FT HELIX 106..130 FT /evidence="ECO:0007829|PDB:8UC0" FT HELIX 132..139 FT /evidence="ECO:0007829|PDB:8UC0" FT HELIX 143..171 FT /evidence="ECO:0007829|PDB:8UC0" FT HELIX 173..192 FT /evidence="ECO:0007829|PDB:8UC0" FT HELIX 200..218 FT /evidence="ECO:0007829|PDB:8UC0" FT HELIX 220..228 FT /evidence="ECO:0007829|PDB:8UC0" FT TURN 231..233 FT /evidence="ECO:0007829|PDB:8UC0" FT HELIX 234..259 FT /evidence="ECO:0007829|PDB:8UC0" FT HELIX 267..295 FT /evidence="ECO:0007829|PDB:8UC0" FT HELIX 306..313 FT /evidence="ECO:0007829|PDB:8UC0" FT HELIX 316..318 FT /evidence="ECO:0007829|PDB:8QCS" FT HELIX 321..330 FT /evidence="ECO:0007829|PDB:8UC0" FT HELIX 332..362 FT /evidence="ECO:0007829|PDB:8UC0" FT STRAND 363..365 FT /evidence="ECO:0007829|PDB:8UC0" FT HELIX 367..395 FT /evidence="ECO:0007829|PDB:8UC0" FT HELIX 398..419 FT /evidence="ECO:0007829|PDB:8UC0" FT HELIX 420..422 FT /evidence="ECO:0007829|PDB:8UC0" FT HELIX 425..453 FT /evidence="ECO:0007829|PDB:8UC0" FT TURN 454..456 FT /evidence="ECO:0007829|PDB:8UC0" FT HELIX 459..488 FT /evidence="ECO:0007829|PDB:8UC0" FT HELIX 490..510 FT /evidence="ECO:0007829|PDB:8UC0" SQ SEQUENCE 555 AA; 59863 MW; D0EBA9886CC8E747 CRC64; MARPDDEEGA AVAPGHPLAK GYLPLPRGAP VGKESVELQN GPKAGTFPVN GAPRDSLAAA SGVLGGPQTP LAPEEETQAR LLPAGAGAET PGAESSPLPL TALSPRRFVV LLIFSLYSLV NAFQWIQYSI ISNVFEGFYG VTLLHIDWLS MVYMLAYVPL IFPATWLLDT RGLRLTALLG SGLNCLGAWI KCGSVQQHLF WVTMLGQCLC SVAQVFILGL PSRIASVWFG PKEVSTACAT AVLGNQLGTA VGFLLPPVLV PNTQNDTNLL ACNISTMFYG TSAVATLLFI LTAIAFKEKP RYPPSQAQAA LQDSPPEEYS YKKSIRNLFK NIPFVLLLIT YGIMTGAFYS VSTLLNQMIL TYYEGEEVNA GRIGLTLVVA GMVGSILCGL WLDYTKTYKQ TTLIVYILSF IGMVIFTFTL DLRYIIIVFV TGGVLGFFMT GYLPLGFEFA VEITYPESEG TSSGLLNASA QIFGILFTLA QGKLTSDYGP KAGNIFLCVW MFIGIILTAL IKSDLRRHNI NIGITNVDVK AIPADSPTDQ EPKTVMLSKQ SESAI // ID MCL1_HUMAN Reviewed; 350 AA. AC Q07820; B2R6B2; D3DV03; D3DV04; Q9HD91; Q9NRQ3; Q9NRQ4; Q9UHR7; Q9UHR8; AC Q9UHR9; Q9UNJ1; DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot. DT 06-DEC-2005, sequence version 3. DT 28-JAN-2026, entry version 243. DE RecName: Full=Induced myeloid leukemia cell differentiation protein Mcl-1; DE AltName: Full=Bcl-2-like protein 3; DE Short=Bcl2-L-3; DE AltName: Full=Bcl-2-related protein EAT/mcl1; DE AltName: Full=mcl1/EAT; GN Name=MCL1; Synonyms=BCL2L3; 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), AND VARIANT ASP-173. RC TISSUE=Myeloid leukemia cell; RX PubMed=7682708; DOI=10.1073/pnas.90.8.3516; RA Kozopas K.M., Yang T., Buchan H.L., Zhou P., Craig R.W.; RT "MCL1, a gene expressed in programmed myeloid cell differentiation, has RT sequence similarity to BCL2."; RL Proc. Natl. Acad. Sci. U.S.A. 90:3516-3520(1993). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND INDUCTION. RX PubMed=8790944; DOI=10.1247/csf.21.143; RA Umezawa A., Maruyama T., Inazawa J., Imai S., Takano T., Hata J.; RT "Induction of mcl1/EAT, Bcl-2 related gene, by retinoic acid or heat shock RT in the human embryonal carcinoma cells, NCR-G3."; RL Cell Struct. Funct. 21:143-150(1996). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=11130466; DOI=10.1007/pl00000728; RA Akgul C., Turner P.C., White M.R.H., Edwards S.W.; RT "Functional analysis of the human MCL-1 gene."; RL Cell. Mol. Life Sci. 57:684-691(2000). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 2), VARIANT ASP-173, AND RP FUNCTION. RC TISSUE=Myeloid leukemia cell, and Neuroblastoma; RX PubMed=10766760; DOI=10.1074/jbc.m909572199; RA Bingle C.D., Craig R.W., Swales B.M., Singleton V., Zhou P., Whyte M.K.B.; RT "Exon skipping in Mcl-1 results in a Bcl-2 homology domain 3 only gene RT product that promotes cell death."; RL J. Biol. Chem. 275:22136-22146(2000). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), INTERACTION WITH BAX; BAK1 RP AND BCL2L11, AND DIMERIZATION OF ISOFORMS 1 AND 2. RX PubMed=10837489; DOI=10.1074/jbc.m909826199; RA Bae J., Leo C.P., Hsu S.Y., Hsueh A.J.W.; RT "MCL-1S, a splicing variant of the antiapoptotic BCL-2 family member MCL-1, RT encodes a proapoptotic protein possessing only the BH3 domain."; RL J. Biol. Chem. 275:25255-25261(2000). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). 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 (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT VAL-227. RC TISSUE=Thalamus; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [8] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT VAL-227. RG NIEHS SNPs program; RL Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [10] 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 (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [11] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Mammary gland, and Placenta; 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 [12] RP NUCLEOTIDE SEQUENCE [MRNA] OF 182-289 (ISOFORM 1), AND VARIANT VAL-227. RC TISSUE=Ewing sarcoma; RX PubMed=10634649; DOI=10.1016/s0145-2126(99)00137-x; RA Okita H., Umezawa A., Fukuma M., Hata J.; RT "Acute myeloid leukemia possessing jumping translocation is related to RT highly elevated levels of EAT/mcl-1, a Bcl-2 related gene with anti- RT apoptotic functions."; RL Leuk. Res. 24:73-77(2000). RN [13] RP PROTEIN SEQUENCE OF N-TERMINUS OF FRAGMENTS OBTAINED BY CASPASE CLEAVAGE, RP AND MUTAGENESIS OF ASP-127 AND ASP-157. RX PubMed=15122313; DOI=10.1038/sj.onc.1207648; RA Michels J., O'Neill J.W., Dallman C.L., Mouzakiti A., Habens F., RA Brimmell M., Zhang K.Y.J., Craig R.W., Marcusson E.G., Johnson P.W.M., RA Packham G.; RT "Mcl-1 is required for Akata6 B-lymphoma cell survival and is converted to RT a cell death molecule by efficient caspase-mediated cleavage."; RL Oncogene 23:4818-4827(2004). RN [14] RP INDUCTION. RX PubMed=9671497; DOI=10.1128/mcb.18.8.4883; RA Chao J.-R., Wang J.-M., Lee S.-F., Peng H.-W., Lin Y.-H., Chou C.-H., RA Li J.-C., Huang H.-M., Chou C.-K., Kuo M.-L., Yen J.J.-Y., Yang-Yen H.-F.; RT "Mcl-1 is an immediate-early gene activated by the granulocyte-macrophage RT colony-stimulating factor (GM-CSF) signaling pathway and is one component RT of the GM-CSF viability response."; RL Mol. Cell. Biol. 18:4883-4898(1998). RN [15] RP INTERACTION WITH TPT1, AND SUBCELLULAR LOCATION. RX PubMed=12149273; DOI=10.1074/jbc.m207413200; RA Zhang D., Li F., Weidner D., Mnjoyan Z.H., Fujise K.; RT "Physical and functional interaction between myeloid cell leukemia 1 RT protein (MCL1) and fortilin. The potential role of MCL1 as a fortilin RT chaperone."; RL J. Biol. Chem. 277:37430-37438(2002). RN [16] RP PHOSPHORYLATION AT SER-121 AND THR-163. RX PubMed=12223490; DOI=10.1074/jbc.m207951200; RA Inoshita S., Takeda K., Hatai T., Terada Y., Sano M., Hata J., Umezawa A., RA Ichijo H.; RT "Phosphorylation and inactivation of myeloid cell leukemia 1 by JNK in RT response to oxidative stress."; RL J. Biol. Chem. 277:43730-43734(2002). RN [17] RP INTERACTION WITH BAK1, AND SUBCELLULAR LOCATION. RX PubMed=15077116; DOI=10.1038/ncb1123; RA Leu J.I.-J., Dumont P., Hafey M., Murphy M.E., George D.L.; RT "Mitochondrial p53 activates Bak and causes disruption of a Bak-Mcl1 RT complex."; RL Nat. Cell Biol. 6:443-450(2004). RN [18] RP PHOSPHORYLATION AT THR-163, AND MUTAGENESIS OF SER-162 AND THR-163. RX PubMed=15241487; DOI=10.1038/sj.onc.1207692; RA Domina A.M., Vrana J.A., Gregory M.A., Hann S.R., Craig R.W.; RT "MCL1 is phosphorylated in the PEST region and stabilized upon ERK RT activation in viable cells, and at additional sites with cytotoxic okadaic RT acid or taxol."; RL Oncogene 23:5301-5315(2004). RN [19] RP UBIQUITINATION, AND MUTAGENESIS OF LYS-5; LYS-40; LYS-136; LYS-194; RP LYS-197; LYS-208 AND LYS-234. RX PubMed=15989957; DOI=10.1016/j.cell.2005.06.009; RA Zhong Q., Gao W., Du F., Wang X.; RT "Mule/ARF-BP1, a BH3-only E3 ubiquitin ligase, catalyzes the RT polyubiquitination of Mcl-1 and regulates apoptosis."; RL Cell 121:1085-1095(2005). RN [20] RP FUNCTION AS INHIBITOR OF APOPTOSIS, PHOSPHORYLATION AT SER-159 BY RP GSK3-ALPHA AND GSK3-BETA, UBIQUITINATION, AND MUTAGENESIS OF SER-159. RX PubMed=16543145; DOI=10.1016/j.molcel.2006.02.009; RA Maurer U., Charvet C., Wagman A.S., Dejardin E., Green D.R.; RT "Glycogen synthase kinase-3 regulates mitochondrial outer membrane RT permeabilization and apoptosis by destabilization of MCL-1."; RL Mol. Cell 21:749-760(2006). RN [21] 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 [22] RP SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-162 AND THR-163, AND RP MUTAGENESIS OF SER-162. RX PubMed=23024798; DOI=10.1371/journal.pone.0045088; RA Thomas L.W., Lam C., Clark R.E., White M.R., Spiller D.G., Moots R.J., RA Edwards S.W.; RT "Serine 162, an essential residue for the mitochondrial localization, RT stability and anti-apoptotic function of Mcl-1."; RL PLoS ONE 7:E45088-E45088(2012). RN [23] RP INTERACTION WITH RTL10/BOP. RX PubMed=23055042; DOI=10.1007/s13238-012-2069-7; RA Zhang X., Weng C., Li Y., Wang X., Jiang C., Li X., Xu Y., Chen Q., Pan L., RA Tang H.; RT "Human Bop is a novel BH3-only member of the Bcl-2 protein family."; RL Protein Cell 3:790-801(2012). RN [24] RP INTERACTION WITH BCL2L11. RX PubMed=27013495; DOI=10.15252/embr.201541392; RA Weber A., Heinlein M., Dengjel J., Alber C., Singh P.K., Haecker G.; RT "The deubiquitinase Usp27x stabilizes the BH3-only protein Bim and enhances RT apoptosis."; RL EMBO Rep. 17:724-738(2016). RN [25] RP DEUBIQUITINATION BY USP20. RX PubMed=35063767; DOI=10.1016/j.bbrc.2022.01.019; RA Feng J., Liu P., Li X., Zhang D., Lin H., Hou Z., Guo C., Niu Y., Dai B., RA Wang O., Qi M., Wang H., Zhou H.; RT "The deubiquitinating enzyme USP20 regulates the stability of the MCL1 RT protein."; RL Biochem. Biophys. Res. Commun. 593:122-128(2022). RN [26] RP X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 151-307 IN COMPLEXES WITH PMAIP1 RP AND BCL2L11. RX PubMed=17389404; DOI=10.1073/pnas.0701297104; RA Czabotar P.E., Lee E.F., van Delft M.F., Day C.L., Smith B.J., RA Huang D.C.S., Fairlie W.D., Hinds M.G., Colman P.M.; RT "Structural insights into the degradation of Mcl-1 induced by BH3 RT domains."; RL Proc. Natl. Acad. Sci. U.S.A. 104:6217-6222(2007). RN [27] RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 172-327 IN COMPLEX WITH BCL2L11. RX PubMed=20562877; DOI=10.1038/nchembio.391; RA Stewart M.L., Fire E., Keating A.E., Walensky L.D.; RT "The MCL-1 BH3 helix is an exclusive MCL-1 inhibitor and apoptosis RT sensitizer."; RL Nat. Chem. Biol. 6:595-601(2010). RN [28] RP VARIANT [LARGE SCALE ANALYSIS] LEU-231. RX PubMed=18987736; DOI=10.1038/nature07485; RA Ley T.J., Mardis E.R., Ding L., Fulton B., McLellan M.D., Chen K., RA Dooling D., Dunford-Shore B.H., McGrath S., Hickenbotham M., Cook L., RA Abbott R., Larson D.E., Koboldt D.C., Pohl C., Smith S., Hawkins A., RA Abbott S., Locke D., Hillier L.W., Miner T., Fulton L., Magrini V., RA Wylie T., Glasscock J., Conyers J., Sander N., Shi X., Osborne J.R., RA Minx P., Gordon D., Chinwalla A., Zhao Y., Ries R.E., Payton J.E., RA Westervelt P., Tomasson M.H., Watson M., Baty J., Ivanovich J., Heath S., RA Shannon W.D., Nagarajan R., Walter M.J., Link D.C., Graubert T.A., RA DiPersio J.F., Wilson R.K.; RT "DNA sequencing of a cytogenetically normal acute myeloid leukaemia RT genome."; RL Nature 456:66-72(2008). CC -!- FUNCTION: Involved in the regulation of apoptosis versus cell survival, CC and in the maintenance of viability but not of proliferation. Mediates CC its effects by interactions with a number of other regulators of CC apoptosis. Isoform 1 inhibits apoptosis. Isoform 2 promotes apoptosis. CC {ECO:0000269|PubMed:10766760, ECO:0000269|PubMed:16543145}. CC -!- SUBUNIT: Interacts with HIF3A (via C-terminus domain) (By similarity). CC Interacts with BAD, BOK, BIK and BMF (By similarity). Interacts with CC PMAIP1 (PubMed:17389404). Interacts with BBC3 (By similarity). Isoform CC 1 interacts with BAX, BAK1 and TPT1 (PubMed:10837489, PubMed:12149273, CC PubMed:15077116). Heterodimer of isoform 1 and isoform 2. Homodimers of CC isoform 1 or isoform 2 are not detected. Isoform 2 does not interact CC with pro-apoptotic BCL2-related proteins (PubMed:10837489). Interacts CC with RTL10/BOP (PubMed:23055042). Interacts with BCL2L11; may sequester CC BCL2L11 to prevent its pro-apoptotic activity (PubMed:10837489, CC PubMed:17389404, PubMed:20562877, PubMed:27013495). Interacts with CC GIMAP5 and HSPA8/HSC70; the interaction between HSPA8 and MCL1 is CC impaired in the absence of GIMAP5 (By similarity). CC {ECO:0000250|UniProtKB:P97287, ECO:0000250|UniProtKB:Q9Z1P3, CC ECO:0000269|PubMed:10837489, ECO:0000269|PubMed:12149273, CC ECO:0000269|PubMed:15077116, ECO:0000269|PubMed:17389404, CC ECO:0000269|PubMed:20562877, ECO:0000269|PubMed:23055042, CC ECO:0000269|PubMed:27013495}. CC -!- INTERACTION: CC Q07820; P31749: AKT1; NbExp=3; IntAct=EBI-1003422, EBI-296087; CC Q07820; Q16611: BAK1; NbExp=20; IntAct=EBI-1003422, EBI-519866; CC Q07820; Q07812: BAX; NbExp=11; IntAct=EBI-1003422, EBI-516580; CC Q07820; Q9BXH1: BBC3; NbExp=6; IntAct=EBI-1003422, EBI-519884; CC Q07820; Q9BXH1-2: BBC3; NbExp=2; IntAct=EBI-1003422, EBI-519896; CC Q07820; O43521: BCL2L11; NbExp=20; IntAct=EBI-1003422, EBI-526406; CC Q07820; Q14457: BECN1; NbExp=2; IntAct=EBI-1003422, EBI-949378; CC Q07820; P55957: BID; NbExp=3; IntAct=EBI-1003422, EBI-519672; CC Q07820; Q96LC9: BMF; NbExp=3; IntAct=EBI-1003422, EBI-3919268; CC Q07820; Q03135: CAV1; NbExp=3; IntAct=EBI-1003422, EBI-603614; CC Q07820; Q7Z6Z7: HUWE1; NbExp=12; IntAct=EBI-1003422, EBI-625934; CC Q07820; Q9H3M0: KCNF1; NbExp=3; IntAct=EBI-1003422, EBI-6918743; CC Q07820; Q13794: PMAIP1; NbExp=6; IntAct=EBI-1003422, EBI-707392; CC Q07820; Q7L3V2: RTL10; NbExp=2; IntAct=EBI-1003422, EBI-10697720; CC Q07820; Q9UNK0: STX8; NbExp=3; IntAct=EBI-1003422, EBI-727240; CC Q07820; Q93008: USP9X; NbExp=10; IntAct=EBI-1003422, EBI-302524; CC Q07820; P49817: Cav1; Xeno; NbExp=3; IntAct=EBI-1003422, EBI-1161338; CC Q07820; Q9JM54: Pmaip1; Xeno; NbExp=2; IntAct=EBI-1003422, EBI-709183; CC Q07820; Q91AU0; Xeno; NbExp=2; IntAct=EBI-1003422, EBI-9657017; CC Q07820-1; Q07820-2: MCL1; NbExp=4; IntAct=EBI-7173045, EBI-1003451; CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass membrane CC protein {ECO:0000305}. Cytoplasm. Mitochondrion. Nucleus, nucleoplasm. CC Note=Cytoplasmic, associated with mitochondria. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; Synonyms=MCL1L, MCL-1L; CC IsoId=Q07820-1; Sequence=Displayed; CC Name=2; Synonyms=Delta S, MCL-1S, TM; CC IsoId=Q07820-2; Sequence=VSP_000532, VSP_000533; CC -!- INDUCTION: Expression increases early during phorbol ester-induced CC differentiation along the monocyte/macrophage pathway in myeloid CC leukemia cell line ML-1. Rapidly up-regulated by CSF2 in ML-1 cells. CC Up-regulated by heat shock-induced differentiation. Expression CC increases early during retinoic acid-induced differentiation. CC {ECO:0000269|PubMed:8790944, ECO:0000269|PubMed:9671497}. CC -!- PTM: Cleaved by CASP3 during apoptosis. In intact cells cleavage occurs CC preferentially after Asp-127, yielding a pro-apoptotic 28 kDa C- CC terminal fragment. CC -!- PTM: Rapidly degraded in the absence of phosphorylation on Thr-163 in CC the PEST region. {ECO:0000269|PubMed:12223490, CC ECO:0000269|PubMed:15241487, ECO:0000269|PubMed:23024798}. CC -!- PTM: Phosphorylated on Ser-159, by GSK3, in response to CC IL3/interleukin-3 withdrawal. Phosphorylation at Ser-159 induces CC ubiquitination and proteasomal degradation, abrogating the anti- CC apoptotic activity. Treatment with taxol or okadaic acid induces CC phosphorylation on additional sites. {ECO:0000269|PubMed:16543145}. CC -!- PTM: Ubiquitinated. Ubiquitination is induced by phosphorylation at CC Ser-159 (PubMed:16543145). Deubiquitinated by USP20; leading to CC increased stability (PubMed:35063767). {ECO:0000269|PubMed:16543145, CC ECO:0000269|PubMed:35063767}. CC -!- SIMILARITY: Belongs to the Bcl-2 family. {ECO:0000305}. 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; L08246; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; AF118124; AAD13299.1; -; mRNA. DR EMBL; AF147742; AAF74821.1; -; Genomic_DNA. DR EMBL; AF198614; AAF64255.1; -; Genomic_DNA. DR EMBL; AF198614; AAF64256.1; -; Genomic_DNA. DR EMBL; AF162677; AAG00896.1; -; Genomic_DNA. DR EMBL; AF162676; AAG00896.1; JOINED; Genomic_DNA. DR EMBL; AF203373; AAG00904.1; -; mRNA. DR EMBL; BT006640; AAP35286.1; -; mRNA. DR EMBL; AK312508; BAG35409.1; -; mRNA. DR EMBL; DQ088966; AAY68220.1; -; Genomic_DNA. DR EMBL; AL356356; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471121; EAW53538.1; -; Genomic_DNA. DR EMBL; CH471121; EAW53539.1; -; Genomic_DNA. DR EMBL; CH471121; EAW53540.1; -; Genomic_DNA. DR EMBL; CH471121; EAW53541.1; -; Genomic_DNA. DR EMBL; BC017197; AAH17197.1; -; mRNA. DR EMBL; BC071897; AAH71897.1; -; mRNA. DR EMBL; BC107735; AAI07736.1; -; mRNA. DR EMBL; AF118276; AAF15309.1; -; mRNA. DR EMBL; AF118277; AAF15310.1; -; mRNA. DR EMBL; AF118278; AAF15311.1; -; mRNA. DR CCDS; CCDS956.1; -. [Q07820-2] DR CCDS; CCDS957.1; -. [Q07820-1] DR PIR; A47476; A47476. DR RefSeq; NP_001184249.1; NM_001197320.1. DR RefSeq; NP_068779.1; NM_021960.5. [Q07820-1] DR RefSeq; NP_877495.1; NM_182763.3. [Q07820-2] DR PDB; 2KBW; NMR; -; A=163-326. DR PDB; 2MHS; NMR; -; A=171-327. DR PDB; 2NL9; X-ray; 1.55 A; A=209-327. DR PDB; 2NLA; X-ray; 2.80 A; A=209-327. DR PDB; 2PQK; X-ray; 2.00 A; A=172-327. DR PDB; 3D7V; X-ray; 2.03 A; A=209-327. DR PDB; 3IO9; X-ray; 2.40 A; A=209-327. DR PDB; 3KJ0; X-ray; 1.70 A; A=172-327. DR PDB; 3KJ1; X-ray; 1.94 A; A=172-327. DR PDB; 3KJ2; X-ray; 2.35 A; A=172-327. DR PDB; 3KZ0; X-ray; 2.35 A; A/B=172-327. DR PDB; 3MK8; X-ray; 2.32 A; A=172-327, B=208-228. DR PDB; 3PK1; X-ray; 2.49 A; A/C=174-326. DR PDB; 3TWU; X-ray; 1.80 A; B=73-88. DR PDB; 3WIX; X-ray; 1.90 A; A/B/C/D=172-327. DR PDB; 3WIY; X-ray; 2.15 A; A/B/C/D/E/F=172-327. DR PDB; 4BPI; X-ray; 1.98 A; A=209-327. DR PDB; 4BPJ; X-ray; 1.60 A; A=209-327. DR PDB; 4HW2; X-ray; 2.80 A; A/B/C/D/E/F=172-323. DR PDB; 4HW3; X-ray; 2.40 A; A/B/C/D/E/F/G/H/I/J/K/L=172-323. DR PDB; 4HW4; X-ray; 1.53 A; A/B=172-327. DR PDB; 4OQ5; X-ray; 2.86 A; A/B/C/D/E/F=174-326. DR PDB; 4OQ6; X-ray; 1.81 A; A/B=174-326. DR PDB; 4WGI; X-ray; 1.85 A; A=173-321. DR PDB; 4WMR; X-ray; 1.70 A; A=173-321. DR PDB; 4WMS; X-ray; 1.90 A; A=174-321. DR PDB; 4WMT; X-ray; 2.35 A; A=174-321. DR PDB; 4WMU; X-ray; 1.55 A; A=174-321. DR PDB; 4WMV; X-ray; 2.40 A; A=174-321. DR PDB; 4WMW; X-ray; 1.90 A; A=174-321. DR PDB; 4WMX; X-ray; 2.00 A; A=174-321. DR PDB; 4ZBF; X-ray; 2.20 A; A/B/C/D/E/F/G/H/I/J/K/L=172-327. DR PDB; 4ZBI; X-ray; 2.50 A; A/B/C/D/E/F/G/H/I/J/K/L=172-327. DR PDB; 5C3F; X-ray; 1.43 A; A=173-327. DR PDB; 5C6H; X-ray; 2.05 A; A/C/E/G/I/K/M/O/Q/S/U/W=171-327. DR PDB; 5FC4; X-ray; 1.50 A; A=172-320. DR PDB; 5FDO; X-ray; 2.80 A; A/B/C/D=172-320. DR PDB; 5FDR; X-ray; 2.60 A; A/B/C/D=172-327. DR PDB; 5IEZ; X-ray; 2.60 A; A/B/C/D=172-327. DR PDB; 5IF4; X-ray; 2.39 A; A/B=172-327. DR PDB; 5JSB; X-ray; 2.74 A; A/C/E/G/I/K=172-350. DR PDB; 5KU9; X-ray; 2.20 A; A/B=174-219, A/B=258-327. DR PDB; 5LOF; X-ray; 2.20 A; A=173-321. DR PDB; 5MES; X-ray; 2.24 A; A=241-327. DR PDB; 5MEV; X-ray; 2.94 A; A=241-327. DR PDB; 5UUM; X-ray; 2.35 A; A/B=172-325. DR PDB; 5VKC; X-ray; 2.31 A; A/B=174-326. DR PDB; 5VX2; X-ray; 1.85 A; A/C=241-327. DR PDB; 5W89; X-ray; 1.42 A; A=172-321. DR PDB; 5W8F; X-ray; 1.85 A; A=172-320. DR PDB; 6B4L; X-ray; 2.25 A; A/B=174-326. DR PDB; 6B4U; X-ray; 1.95 A; A=174-326. DR PDB; 6BW2; X-ray; 2.75 A; A/B/C/D=172-327. DR PDB; 6BW8; X-ray; 2.90 A; A/B/C/D=172-327. DR PDB; 6FS0; X-ray; 2.25 A; A=174-324. DR PDB; 6FS1; X-ray; 1.60 A; A/B=174-321. DR PDB; 6FS2; X-ray; 2.55 A; A=174-325, B=174-324. DR PDB; 6MBD; X-ray; 1.95 A; A/B=172-324. DR PDB; 6MBE; X-ray; 2.25 A; A=172-323. DR PDB; 6NE5; X-ray; 1.85 A; A/B/C/D=172-328. DR PDB; 6O4U; X-ray; 1.70 A; A/B=172-327. DR PDB; 6O6F; X-ray; 1.60 A; A/B=172-327. DR PDB; 6O6G; X-ray; 2.40 A; A=172-327. DR PDB; 6OQB; X-ray; 1.60 A; A=171-327. DR PDB; 6OQC; X-ray; 1.80 A; A/B=171-327. DR PDB; 6OQD; X-ray; 1.48 A; A=171-327. DR PDB; 6OQN; X-ray; 1.70 A; A/B=171-327. DR PDB; 6OVC; NMR; -; A=171-327. DR PDB; 6P3P; X-ray; 1.61 A; A=172-327. DR PDB; 6QB3; X-ray; 1.90 A; A=174-327. DR PDB; 6QB4; X-ray; 2.38 A; A=174-327. DR PDB; 6QB6; X-ray; 2.24 A; A=174-327. DR PDB; 6QFC; X-ray; 1.96 A; A=174-327. DR PDB; 6QFI; X-ray; 2.40 A; A=171-327. DR PDB; 6QFM; X-ray; 2.00 A; A=171-327. DR PDB; 6QFQ; X-ray; 1.60 A; A=171-327. DR PDB; 6QGD; X-ray; 1.80 A; A=173-321. DR PDB; 6QXJ; X-ray; 1.70 A; A=173-321. DR PDB; 6QYK; X-ray; 2.30 A; A=173-321. DR PDB; 6QYL; X-ray; 2.20 A; A=173-321. DR PDB; 6QYN; X-ray; 2.50 A; A=173-321. DR PDB; 6QYO; X-ray; 2.10 A; A=173-321. DR PDB; 6QYP; X-ray; 2.20 A; A=171-327. DR PDB; 6QZ5; X-ray; 2.00 A; A=171-327. DR PDB; 6QZ6; X-ray; 1.90 A; A=171-327. DR PDB; 6QZ7; X-ray; 2.20 A; A=173-321. DR PDB; 6QZ8; X-ray; 2.15 A; A=171-327. DR PDB; 6QZB; X-ray; 2.00 A; A=171-327. DR PDB; 6STJ; X-ray; 2.20 A; A/B/C/D=173-327. DR PDB; 6U63; X-ray; 2.75 A; A/B/C/D=171-323. DR PDB; 6U64; X-ray; 2.55 A; A=171-320. DR PDB; 6U65; X-ray; 2.09 A; A/B/C/D=171-323. DR PDB; 6U67; X-ray; 1.84 A; A/B=171-323. DR PDB; 6U6F; X-ray; 2.90 A; A/B/C=171-323. DR PDB; 6UA3; X-ray; 1.55 A; A=172-325. DR PDB; 6UAB; X-ray; 2.10 A; A=172-325. DR PDB; 6UD2; X-ray; 1.70 A; A=171-327. DR PDB; 6UDI; X-ray; 1.94 A; A=171-327. DR PDB; 6UDT; X-ray; 1.50 A; A=171-327. DR PDB; 6UDU; X-ray; 1.75 A; A=171-327. DR PDB; 6UDV; X-ray; 1.35 A; A=171-327. DR PDB; 6UDX; X-ray; 1.70 A; A/B=171-327. DR PDB; 6UDY; X-ray; 1.70 A; A/B=171-327. DR PDB; 6VBX; X-ray; 1.95 A; A=172-323. DR PDB; 6YBG; X-ray; 2.10 A; A/B=171-327. DR PDB; 6YBJ; X-ray; 2.50 A; A=173-321. DR PDB; 6YBK; X-ray; 2.00 A; A=173-321. DR PDB; 6YBL; X-ray; 2.10 A; A=173-321. DR PDB; 6ZIE; X-ray; 2.30 A; B=172-327. DR PDB; 7NB4; X-ray; 1.90 A; A=171-327. DR PDB; 7NB7; X-ray; 2.82 A; A/B/C/D=171-327. DR PDB; 7XGE; X-ray; 2.38 A; B/D/F/H=172-321. DR PDB; 8AV9; X-ray; 1.99 A; A=174-327. DR PDB; 8EKX; X-ray; 1.55 A; A=173-321. DR PDB; 8EL0; X-ray; 1.92 A; A=173-321. DR PDB; 8EL1; X-ray; 2.41 A; A/B/C/D=173-321. DR PDB; 8G3S; X-ray; 1.40 A; A=173-321. DR PDB; 8G3T; X-ray; 1.83 A; A=173-321. DR PDB; 8G3U; X-ray; 1.94 A; A=173-321. DR PDB; 8G3W; X-ray; 1.78 A; A=173-321. DR PDB; 8G3X; X-ray; 1.46 A; A=173-321. DR PDB; 8G3Y; X-ray; 1.70 A; A=173-321. DR PDB; 8H7B; X-ray; 1.46 A; A/B=172-322. DR PDB; 8IQM; X-ray; 1.97 A; A=171-327. DR PDB; 8QSO; X-ray; 2.11 A; A=173-321. DR PDB; 8SVY; X-ray; 1.47 A; A=173-321. DR PDB; 8T6F; X-ray; 1.56 A; A=174-321. DR PDB; 8VJP; X-ray; 1.13 A; A=172-323. DR PDB; 8X62; X-ray; 2.80 A; A/B=172-321. DR PDB; 8Y1Y; X-ray; 2.01 A; A=171-327. DR PDB; 8Y1Z; X-ray; 1.91 A; A=171-327. DR PDB; 8Y20; X-ray; 2.23 A; A=173-321. DR PDB; 8ZCS; X-ray; 2.79 A; A/B=173-321. DR PDB; 9BCG; X-ray; 1.90 A; A=173-320. DR PDB; 9CKN; X-ray; 1.50 A; A/B=172-323. DR PDB; 9UGP; X-ray; 1.39 A; A=171-322. DR PDBsum; 2KBW; -. DR PDBsum; 2MHS; -. DR PDBsum; 2NL9; -. DR PDBsum; 2NLA; -. DR PDBsum; 2PQK; -. DR PDBsum; 3D7V; -. DR PDBsum; 3IO9; -. DR PDBsum; 3KJ0; -. DR PDBsum; 3KJ1; -. DR PDBsum; 3KJ2; -. DR PDBsum; 3KZ0; -. DR PDBsum; 3MK8; -. DR PDBsum; 3PK1; -. DR PDBsum; 3TWU; -. DR PDBsum; 3WIX; -. DR PDBsum; 3WIY; -. DR PDBsum; 4BPI; -. DR PDBsum; 4BPJ; -. DR PDBsum; 4HW2; -. DR PDBsum; 4HW3; -. DR PDBsum; 4HW4; -. DR PDBsum; 4OQ5; -. DR PDBsum; 4OQ6; -. DR PDBsum; 4WGI; -. DR PDBsum; 4WMR; -. DR PDBsum; 4WMS; -. DR PDBsum; 4WMT; -. DR PDBsum; 4WMU; -. DR PDBsum; 4WMV; -. DR PDBsum; 4WMW; -. DR PDBsum; 4WMX; -. DR PDBsum; 4ZBF; -. DR PDBsum; 4ZBI; -. DR PDBsum; 5C3F; -. DR PDBsum; 5C6H; -. DR PDBsum; 5FC4; -. DR PDBsum; 5FDO; -. DR PDBsum; 5FDR; -. DR PDBsum; 5IEZ; -. DR PDBsum; 5IF4; -. DR PDBsum; 5JSB; -. DR PDBsum; 5KU9; -. DR PDBsum; 5LOF; -. DR PDBsum; 5MES; -. DR PDBsum; 5MEV; -. DR PDBsum; 5UUM; -. DR PDBsum; 5VKC; -. DR PDBsum; 5VX2; -. DR PDBsum; 5W89; -. DR PDBsum; 5W8F; -. DR PDBsum; 6B4L; -. DR PDBsum; 6B4U; -. DR PDBsum; 6BW2; -. DR PDBsum; 6BW8; -. DR PDBsum; 6FS0; -. DR PDBsum; 6FS1; -. DR PDBsum; 6FS2; -. DR PDBsum; 6MBD; -. DR PDBsum; 6MBE; -. DR PDBsum; 6NE5; -. DR PDBsum; 6O4U; -. DR PDBsum; 6O6F; -. DR PDBsum; 6O6G; -. DR PDBsum; 6OQB; -. DR PDBsum; 6OQC; -. DR PDBsum; 6OQD; -. DR PDBsum; 6OQN; -. DR PDBsum; 6OVC; -. DR PDBsum; 6P3P; -. DR PDBsum; 6QB3; -. DR PDBsum; 6QB4; -. DR PDBsum; 6QB6; -. DR PDBsum; 6QFC; -. DR PDBsum; 6QFI; -. DR PDBsum; 6QFM; -. DR PDBsum; 6QFQ; -. DR PDBsum; 6QGD; -. DR PDBsum; 6QXJ; -. DR PDBsum; 6QYK; -. DR PDBsum; 6QYL; -. DR PDBsum; 6QYN; -. DR PDBsum; 6QYO; -. DR PDBsum; 6QYP; -. DR PDBsum; 6QZ5; -. DR PDBsum; 6QZ6; -. DR PDBsum; 6QZ7; -. DR PDBsum; 6QZ8; -. DR PDBsum; 6QZB; -. DR PDBsum; 6STJ; -. DR PDBsum; 6U63; -. DR PDBsum; 6U64; -. DR PDBsum; 6U65; -. DR PDBsum; 6U67; -. DR PDBsum; 6U6F; -. DR PDBsum; 6UA3; -. DR PDBsum; 6UAB; -. DR PDBsum; 6UD2; -. DR PDBsum; 6UDI; -. DR PDBsum; 6UDT; -. DR PDBsum; 6UDU; -. DR PDBsum; 6UDV; -. DR PDBsum; 6UDX; -. DR PDBsum; 6UDY; -. DR PDBsum; 6VBX; -. DR PDBsum; 6YBG; -. DR PDBsum; 6YBJ; -. DR PDBsum; 6YBK; -. DR PDBsum; 6YBL; -. DR PDBsum; 6ZIE; -. DR PDBsum; 7NB4; -. DR PDBsum; 7NB7; -. DR PDBsum; 7XGE; -. DR PDBsum; 8AV9; -. DR PDBsum; 8EKX; -. DR PDBsum; 8EL0; -. DR PDBsum; 8EL1; -. DR PDBsum; 8G3S; -. DR PDBsum; 8G3T; -. DR PDBsum; 8G3U; -. DR PDBsum; 8G3W; -. DR PDBsum; 8G3X; -. DR PDBsum; 8G3Y; -. DR PDBsum; 8H7B; -. DR PDBsum; 8IQM; -. DR PDBsum; 8QSO; -. DR PDBsum; 8SVY; -. DR PDBsum; 8T6F; -. DR PDBsum; 8VJP; -. DR PDBsum; 8X62; -. DR PDBsum; 8Y1Y; -. DR PDBsum; 8Y1Z; -. DR PDBsum; 8Y20; -. DR PDBsum; 8ZCS; -. DR PDBsum; 9BCG; -. DR PDBsum; 9CKN; -. DR PDBsum; 9UGP; -. DR AlphaFoldDB; Q07820; -. DR SMR; Q07820; -. DR BioGRID; 110338; 147. DR ComplexPortal; CPX-304; MCL1-PMAIP1 complex. DR ComplexPortal; CPX-481; MCL-1-BIM complex. [Q07820-1] DR CORUM; Q07820; -. DR DIP; DIP-231N; -. DR ELM; Q07820; -. DR FunCoup; Q07820; 1501. DR IntAct; Q07820; 90. DR MINT; Q07820; -. DR STRING; 9606.ENSP00000358022; -. DR BindingDB; Q07820; -. DR ChEMBL; CHEMBL4361; -. DR DrugBank; DB04813; Bithionol. DR DrugBank; DB00619; Imatinib. DR DrugBank; DB16770; Morin. DR DrugBank; DB17977; Murizatoclax. DR DrugBank; DB12191; Obatoclax. DR DrugBank; DB16865; Rosmarinic acid. DR DrugBank; DB17166; Tapotoclax. DR DrugBank; DB17059; TW-37. DR DrugCentral; Q07820; -. DR GuidetoPHARMACOLOGY; 2847; -. DR iPTMnet; Q07820; -. DR PhosphoSitePlus; Q07820; -. DR BioMuta; MCL1; -. DR DMDM; 83304396; -. DR jPOST; Q07820; -. DR MassIVE; Q07820; -. DR PaxDb; 9606-ENSP00000358022; -. DR PeptideAtlas; Q07820; -. DR ProteomicsDB; 58540; -. [Q07820-1] DR ProteomicsDB; 58541; -. [Q07820-2] DR Pumba; Q07820; -. DR ABCD; Q07820; 1 sequenced antibody. DR Antibodypedia; 1508; 1455 antibodies from 49 providers. DR DNASU; 4170; -. DR Ensembl; ENST00000307940.3; ENSP00000309973.3; ENSG00000143384.14. [Q07820-2] DR Ensembl; ENST00000369026.3; ENSP00000358022.2; ENSG00000143384.14. [Q07820-1] DR Ensembl; ENST00000678770.1; ENSP00000502859.1; ENSG00000143384.14. [Q07820-1] DR GeneID; 4170; -. DR KEGG; hsa:4170; -. DR MANE-Select; ENST00000369026.3; ENSP00000358022.2; NM_021960.5; NP_068779.1. DR UCSC; uc001euz.4; human. [Q07820-1] DR AGR; HGNC:6943; -. DR CIViC; 4170; 1 evidence item across 1 molecular profile. DR ClinPGx; PA30688; -. DR CTD; 4170; -. DR DisGeNET; 4170; -. DR GeneCards; MCL1; -. DR HGNC; HGNC:6943; MCL1. DR HPA; ENSG00000143384; Tissue enhanced (bone). DR MalaCards; MCL1; -. DR MIM; 159552; gene. DR OpenTargets; ENSG00000143384; -. DR VEuPathDB; HostDB:ENSG00000143384; -. DR eggNOG; KOG4728; Eukaryota. DR GeneTree; ENSGT01130000278292; -. DR HOGENOM; CLU_046711_0_0_1; -. DR InParanoid; Q07820; -. DR OMA; FFAPTRC; -. DR OrthoDB; 8932147at2759; -. DR PAN-GO; Q07820; 6 GO annotations based on evolutionary models. DR PhylomeDB; Q07820; -. DR PathwayCommons; Q07820; -. DR Reactome; R-HSA-6785807; Interleukin-4 and Interleukin-13 signaling. DR Reactome; R-HSA-9725370; Signaling by ALK fusions and activated point mutants. DR SignaLink; Q07820; -. DR SIGNOR; Q07820; -. DR Agora; ENSG00000143384; -. DR BioGRID-ORCS; 4170; 304 hits in 1183 CRISPR screens. DR ChiTaRS; MCL1; human. DR EvolutionaryTrace; Q07820; -. DR GeneWiki; MCL1; -. DR GenomeRNAi; 4170; -. DR Pharos; Q07820; Tchem. DR PRO; PR:Q07820; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; Q07820; protein. DR Bgee; ENSG00000143384; Expressed in visceral pleura and 213 other cell types or tissues. DR ExpressionAtlas; Q07820; baseline and differential. DR GO; GO:0097136; C:Bcl-2 family protein complex; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; TAS:UniProtKB. DR GO; GO:0005829; C:cytosol; ISS:UniProtKB. DR GO; GO:0016020; C:membrane; IDA:MGI. DR GO; GO:0005741; C:mitochondrial outer membrane; IBA:GO_Central. DR GO; GO:0005739; C:mitochondrion; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0005634; C:nucleus; IDA:MGI. DR GO; GO:0051434; F:BH3 domain binding; IPI:BHF-UCL. DR GO; GO:0015267; F:channel activity; IBA:GO_Central. DR GO; GO:0046982; F:protein heterodimerization activity; IPI:UniProtKB. DR GO; GO:0008320; F:protein transmembrane transporter activity; TAS:UniProtKB. DR GO; GO:0001709; P:cell fate determination; NAS:UniProtKB. DR GO; GO:0019725; P:cellular homeostasis; NAS:UniProtKB. DR GO; GO:0006974; P:DNA damage response; IMP:MGI. DR GO; GO:0097192; P:extrinsic apoptotic signaling pathway in absence of ligand; IMP:UniProtKB. DR GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IBA:GO_Central. DR GO; GO:0008053; P:mitochondrial fusion; IBA:GO_Central. DR GO; GO:2000811; P:negative regulation of anoikis; IMP:UniProtKB. DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:BHF-UCL. DR GO; GO:0010507; P:negative regulation of autophagy; IMP:UniProtKB. DR GO; GO:2001240; P:negative regulation of extrinsic apoptotic signaling pathway in absence of ligand; IMP:UniProtKB. DR GO; GO:0043065; P:positive regulation of apoptotic process; IDA:ComplexPortal. DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; IBA:GO_Central. DR GO; GO:1903378; P:positive regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway; IGI:ParkinsonsUK-UCL. DR GO; GO:0042981; P:regulation of apoptotic process; IDA:ComplexPortal. DR GO; GO:0001836; P:release of cytochrome c from mitochondria; IBA:GO_Central. DR GO; GO:0034097; P:response to cytokine; IDA:MGI. DR CDD; cd06845; Bcl-2_like; 1. DR DisProt; DP03697; -. DR FunFam; 1.10.437.10:FF:000002; Induced myeloid leukemia cell differentiation protein Mcl-1; 1. DR Gene3D; 1.10.437.10; Blc2-like; 1. DR InterPro; IPR013281; Apop_reg_Mc1. DR InterPro; IPR036834; Bcl-2-like_sf. DR InterPro; IPR046371; Bcl-2_BH1-3. DR InterPro; IPR026298; Bcl-2_fam. DR InterPro; IPR002475; Bcl2-like. DR InterPro; IPR020717; Bcl2_BH1_motif_CS. DR InterPro; IPR020726; Bcl2_BH2_motif_CS. DR InterPro; IPR020728; Bcl2_BH3_motif_CS. DR PANTHER; PTHR11256; BCL-2 RELATED; 1. DR PANTHER; PTHR11256:SF46; INDUCED MYELOID LEUKEMIA CELL DIFFERENTIATION PROTEIN MCL-1; 1. DR Pfam; PF00452; Bcl-2; 1. DR PRINTS; PR01866; APOPREGMCL1. DR PRINTS; PR01862; BCL2FAMILY. DR SMART; SM00337; BCL; 1. DR SUPFAM; SSF56854; Bcl-2 inhibitors of programmed cell death; 1. DR PROSITE; PS50062; BCL2_FAMILY; 1. DR PROSITE; PS01080; BH1; 1. DR PROSITE; PS01258; BH2; 1. DR PROSITE; PS01259; BH3; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Apoptosis; Cytoplasm; KW Developmental protein; Differentiation; Direct protein sequencing; KW Isopeptide bond; Membrane; Mitochondrion; Nucleus; Phosphoprotein; KW Proteomics identification; Reference proteome; Transmembrane; KW Transmembrane helix; Ubl conjugation. FT CHAIN 1..350 FT /note="Induced myeloid leukemia cell differentiation FT protein Mcl-1" FT /id="PRO_0000143080" FT TRANSMEM 328..348 FT /note="Helical" FT /evidence="ECO:0000255" FT REGION 47..87 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 104..175 FT /note="PEST-like" FT REGION 148..171 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 209..223 FT /note="BH3" FT MOTIF 252..272 FT /note="BH1" FT MOTIF 304..319 FT /note="BH2" FT COMPBIAS 50..61 FT /note="Gly residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 150..161 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT SITE 127..128 FT /note="Cleavage; by caspase-3" FT SITE 157..158 FT /note="Cleavage; by caspase-3" FT MOD_RES 121 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:12223490" FT MOD_RES 159 FT /note="Phosphoserine; by GSK3-alpha and GSK3-beta" FT /evidence="ECO:0000269|PubMed:16543145" FT MOD_RES 162 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:23024798" FT MOD_RES 163 FT /note="Phosphothreonine; by MAPK" FT /evidence="ECO:0000269|PubMed:12223490, FT ECO:0000269|PubMed:15241487, ECO:0000269|PubMed:23024798" FT CROSSLNK 5 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT CROSSLNK 40 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT CROSSLNK 136 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT CROSSLNK 194 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT CROSSLNK 197 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT VAR_SEQ 231..271 FT /note="MLRKLDIKNEDDVKSLSRVMIHVFSDGVTNWGRIVTLISFG -> WVCGVLP FT CRGPRRWHQECAAGFCRCCWSRSWFGISNKIALL (in isoform 2)" FT /evidence="ECO:0000303|PubMed:10837489" FT /id="VSP_000532" FT VAR_SEQ 272..350 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:10837489" FT /id="VSP_000533" FT VARIANT 173 FT /note="E -> D (in dbSNP:rs2737820)" FT /evidence="ECO:0000269|PubMed:10766760, FT ECO:0000269|PubMed:7682708" FT /id="VAR_024021" FT VARIANT 227 FT /note="A -> V (in dbSNP:rs11580946)" FT /evidence="ECO:0000269|PubMed:10634649, FT ECO:0000269|PubMed:14702039, ECO:0000269|Ref.8" FT /id="VAR_024022" FT VARIANT 231 FT /note="M -> L (in dbSNP:rs140449444)" FT /evidence="ECO:0000269|PubMed:18987736" FT /id="VAR_054157" FT MUTAGEN 5 FT /note="K->R: Reduced ubiquitination." FT /evidence="ECO:0000269|PubMed:15989957" FT MUTAGEN 40 FT /note="K->R: Reduced ubiquitination." FT /evidence="ECO:0000269|PubMed:15989957" FT MUTAGEN 127 FT /note="D->A: Abolishes formation of 28 and 17 kDa cleavage FT products by CASP3. Abolishes cleavage by caspase-3; when FT associated with A-157." FT /evidence="ECO:0000269|PubMed:15122313" FT MUTAGEN 136 FT /note="K->R: Reduced ubiquitination." FT /evidence="ECO:0000269|PubMed:15989957" FT MUTAGEN 157 FT /note="D->A: Abolishes formation of 23 and 21 kDa cleavage FT products by CASP3. Abolishes cleavage by caspase-3; when FT associated with A-127." FT /evidence="ECO:0000269|PubMed:15122313" FT MUTAGEN 159 FT /note="S->A: Loss of phosphorylation by GSK3 and loss of FT ubiquitination increasing protein stability." FT /evidence="ECO:0000269|PubMed:16543145" FT MUTAGEN 162 FT /note="S->A: Abolishes mitochondrial localization and FT decreases stability." FT /evidence="ECO:0000269|PubMed:15241487, FT ECO:0000269|PubMed:23024798" FT MUTAGEN 162 FT /note="S->A: No effect." FT /evidence="ECO:0000269|PubMed:15241487, FT ECO:0000269|PubMed:23024798" FT MUTAGEN 163 FT /note="T->A,E: No effect on mitochondrial localization." FT /evidence="ECO:0000269|PubMed:15241487" FT MUTAGEN 163 FT /note="T->A: Abolishes phosphorylation by MAPK. No effect FT on phosphorylation induced by okadaic acid or taxol." FT /evidence="ECO:0000269|PubMed:15241487" FT MUTAGEN 194 FT /note="K->R: Reduced ubiquitination." FT /evidence="ECO:0000269|PubMed:15989957" FT MUTAGEN 197 FT /note="K->R: Reduced ubiquitination." FT /evidence="ECO:0000269|PubMed:15989957" FT MUTAGEN 208 FT /note="K->R: No effect on ubiquitination." FT /evidence="ECO:0000269|PubMed:15989957" FT MUTAGEN 234 FT /note="K->R: No effect on ubiquitination." FT /evidence="ECO:0000269|PubMed:15989957" FT HELIX 173..191 FT /evidence="ECO:0007829|PDB:6UDV" FT STRAND 200..202 FT /evidence="ECO:0007829|PDB:6FS1" FT HELIX 203..223 FT /evidence="ECO:0007829|PDB:6UDV" FT HELIX 225..235 FT /evidence="ECO:0007829|PDB:6UDV" FT HELIX 240..244 FT /evidence="ECO:0007829|PDB:6UDV" FT HELIX 246..253 FT /evidence="ECO:0007829|PDB:6UDV" FT HELIX 254..256 FT /evidence="ECO:0007829|PDB:5C3F" FT HELIX 261..280 FT /evidence="ECO:0007829|PDB:6UDV" FT HELIX 284..286 FT /evidence="ECO:0007829|PDB:6UDV" FT HELIX 287..308 FT /evidence="ECO:0007829|PDB:6UDV" FT HELIX 311..319 FT /evidence="ECO:0007829|PDB:6UDV" FT HELIX 323..325 FT /evidence="ECO:0007829|PDB:6OVC" SQ SEQUENCE 350 AA; 37337 MW; D85821AC59275F1F CRC64; MFGLKRNAVI GLNLYCGGAG LGAGSGGATR PGGRLLATEK EASARREIGG GEAGAVIGGS AGASPPSTLT PDSRRVARPP PIGAEVPDVT ATPARLLFFA PTRRAAPLEE MEAPAADAIM SPEEELDGYE PEPLGKRPAV LPLLELVGES GNNTSTDGSL PSTPPPAEEE EDELYRQSLE IISRYLREQA TGAKDTKPMG RSGATSRKAL ETLRRVGDGV QRNHETAFQG MLRKLDIKNE DDVKSLSRVM IHVFSDGVTN WGRIVTLISF GAFVAKHLKT INQESCIEPL AESITDVLVR TKRDWLVKQR GWDGFVEFFH VEDLEGGIRN VLLAFAGVAG VGAGLAYLIR // 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 //