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 ATM_HUMAN Reviewed; 3056 AA. AC Q13315; B2RNX5; O15429; Q12758; Q16551; Q93007; Q9NP02; Q9UCX7; DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot. DT 22-JAN-2014, sequence version 4. DT 28-JAN-2026, entry version 269. DE RecName: Full=Serine-protein kinase ATM; DE EC=2.7.11.1 {ECO:0000269|PubMed:15448695, ECO:0000269|PubMed:15790808, ECO:0000269|PubMed:16858402, ECO:0000269|PubMed:28508083, ECO:0000269|PubMed:30886146, ECO:0000269|PubMed:8988033, ECO:0000269|PubMed:9843217}; DE AltName: Full=Ataxia telangiectasia mutated; DE Short=A-T mutated; GN Name=ATM; 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], AND VARIANT AT ASP-3003. RX PubMed=8589678; DOI=10.1093/hmg/4.11.2025; RA Savitsky K., Sfez S., Tagle D.A., Ziv Y., Sartiel A., Collins F.S., RA Shiloh Y., Rotman G.; RT "The complete sequence of the coding region of the ATM gene reveals RT similarity to cell cycle regulators in different species."; RL Hum. Mol. Genet. 4:2025-2032(1995). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], VARIANT AT ASP-3003, AND VARIANTS RP CYS-49; ARG-1054; PHE-1420; ILE-2079 AND ALA-2287. RX PubMed=8665503; RA Vorechovsky I., Rasio D., Luo L., Monaco C., Hammarstroem L., RA Webster A.D.B., Zaloudik J., Barbanti-Brodano G., James M.R., Russo G., RA Croce C.M., Negrini M.; RT "The ATM gene and susceptibility to breast cancer: analysis of 38 breast RT tumors reveals no evidence for mutation."; RL Cancer Res. 56:2726-2732(1996). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=9199932; DOI=10.1101/gr.7.6.592; RA Platzer M., Rotman G., Bauer D., Uziel T., Savitsky K., Bar-Shira A., RA Gilad S., Shiloh Y., Rosenthal A.; RT "Ataxia-telangiectasia locus: sequence analysis of 184 kb of human genomic RT DNA containing the entire ATM gene."; RL Genome Res. 7:592-605(1997). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT ASN-1983. RX PubMed=16554811; DOI=10.1038/nature04632; RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G., RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., RA Hattori M., Rogers J., Lander E.S., Sakaki Y.; RT "Human chromosome 11 DNA sequence and analysis including novel gene RT identification."; RL Nature 440:497-500(2006). RN [5] RP NUCLEOTIDE SEQUENCE [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 [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-2756. RG NIEHS SNPs program; RL Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-1369, AND VARIANT AT 2546-SER--ILE-2548 RP DEL. RX PubMed=8789452; DOI=10.1093/hmg/5.1.145; RA Byrd P.J., McConville C.M., Cooper P., Parkhill J., Stankovic T., RA McGuire G.M., Thick J.A., Taylor A.M.R.; RT "Mutations revealed by sequencing the 5' half of the gene for ataxia RT telangiectasia."; RL Hum. Mol. Genet. 5:145-149(1996). RN [8] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-24. RX PubMed=9108147; DOI=10.1093/nar/25.9.1678; RA Savitsky K., Platzer M., Uziel T., Gilad S., Sartiel A., Rosenthal A., RA Elroy-Stein O., Shiloh Y., Rotman G.; RT "Ataxia-telangiectasia: structural diversity of untranslated sequences RT suggests complex post-transcriptional regulation of ATM gene expression."; RL Nucleic Acids Res. 25:1678-1684(1997). RN [9] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1332-3056, AND VARIANTS 2427-LEU-ARG-2428 RP DEL; 2546-SER--ILE-2548 DEL; SER-2860 DEL AND ASP-3003. RC TISSUE=Fibroblast; RX PubMed=7792600; DOI=10.1126/science.7792600; RA Savitsky K., Bar-Shira A., Gilad S., Rotman G., Ziv Y., Vanagaite L., RA Tagle D.A., Smith S., Uziel T., Sfez S., Ashkenazi M., Pecker I., RA Frydman M., Harnik R., Patanjali S.R., Simmons A., Clines G.A., Sartiel A., RA Gatti R.A., Chessa L., Sanal O., Lavin M.F., Jaspers N.G.J., Taylor A.M.R., RA Arlett C.F., Miki T., Weissman S.M., Lovett M., Collins F.S., Shiloh Y.; RT "A single ataxia telangiectasia gene with a product similar to PI-3 RT kinase."; RL Science 268:1749-1753(1995). RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1332-3056. RC TISSUE=Brain; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [11] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1349-3056. RX PubMed=8521392; RA Rasio D., Negrini M., Croce C.M.; RT "Genomic organization of the ATM locus involved in ataxia-telangiectasia."; RL Cancer Res. 55:6053-6057(1995). RN [12] RP PHOSPHORYLATION. RX PubMed=8969240; DOI=10.1074/jbc.271.52.33693; RA Chen G., Lee E.Y.-H.P.; RT "The product of the ATM gene is a 370-kDa nuclear phosphoprotein."; RL J. Biol. Chem. 271:33693-33697(1996). RN [13] RP SUBCELLULAR LOCATION. RX PubMed=9050866; DOI=10.1073/pnas.94.5.1840; RA Brown K.D., Ziv Y., Sadanandan S.N., Chessa L., Collins F.S., Shiloh Y., RA Tagle D.A.; RT "The ataxia-telangiectasia gene product, a constitutively expressed nuclear RT protein that is not up-regulated following genome damage."; RL Proc. Natl. Acad. Sci. U.S.A. 94:1840-1845(1997). RN [14] RP SUBCELLULAR LOCATION, AND VARIANTS 2546-SER--ILE-2548 DEL AND TYR-2824. RX PubMed=9150358; DOI=10.1038/sj.onc.1201037; RA Watters D., Khanna K.K., Beamish H., Birrell G., Spring K., Kedar P., RA Gatei M., Stenzel D., Hobson K., Kozlov S., Zhang N., Farrell A., RA Ramsay J., Gatti R.A., Lavin M.F.; RT "Cellular localisation of the ataxia-telangiectasia (ATM) gene product and RT discrimination between mutated and normal forms."; RL Oncogene 14:1911-1921(1997). RN [15] RP CATALYTIC ACTIVITY. RX PubMed=8988033; RA Jung M., Kondratyev A., Lee S.A., Dimtchev A., Dritschilo A.; RT "ATM gene product phosphorylates I kappa B-alpha."; RL Cancer Res. 57:24-27(1997). RN [16] RP INTERACTION WITH ABL1. RX PubMed=9168117; DOI=10.1038/387520a0; RA Shafman T., Khanna K.K., Kedar P., Spring K., Kozlov S., Yen T., Hobson K., RA Gatei M., Zhang N., Watters D., Egerton M., Shiloh Y., Kharbanda S., RA Kufe D., Lavin M.F.; RT "Interaction between ATM protein and c-Abl in response to DNA damage."; RL Nature 387:520-523(1997). RN [17] RP ACTIVITY REGULATION. RX PubMed=9766667; RA Sarkaria J.N., Tibbetts R.S., Busby E.C., Kennedy A.P., Hill D.E., RA Abraham R.T.; RT "Inhibition of phosphoinositide 3-kinase related kinases by the RT radiosensitizing agent wortmannin."; RL Cancer Res. 58:4375-4382(1998). RN [18] RP FUNCTION, INTERACTION WITH TP53, AND CATALYTIC ACTIVITY. RX PubMed=9843217; DOI=10.1038/3882; RA Khanna K.K., Keating K.E., Kozlov S., Scott S., Gatei M., Hobson K., RA Taya Y., Gabrielli B., Chan D., Lees-Miller S.P., Lavin M.F.; RT "ATM associates with and phosphorylates p53: mapping the region of RT interaction."; RL Nat. Genet. 20:398-400(1998). RN [19] RP SUBCELLULAR LOCATION. RX PubMed=9707615; DOI=10.1073/pnas.95.17.10146; RA Lim D.-S., Kirsch D.G., Canman C.E., Ahn J.-H., Ziv Y., Newman L.S., RA Darnell R.B., Shiloh Y., Kastan M.B.; RT "ATM binds to beta-adaptin in cytoplasmic vesicles."; RL Proc. Natl. Acad. Sci. U.S.A. 95:10146-10151(1998). RN [20] RP FUNCTION IN PHOSPHORYLATION OF TP53. RX PubMed=9733514; DOI=10.1126/science.281.5383.1674; RA Banin S., Moyal L., Shieh S.-Y., Taya Y., Anderson C.W., Chessa L., RA Smorodinsky N.I., Prives C., Reiss Y., Shiloh Y., Ziv Y.; RT "Enhanced phosphorylation of p53 by ATM in response to DNA damage."; RL Science 281:1674-1677(1998). RN [21] RP FUNCTION IN PHOSPHORYLATION OF TP53, AND MUTAGENESIS OF ASP-2870 AND RP ASN-2875. RX PubMed=9733515; DOI=10.1126/science.281.5383.1677; RA Canman C.E., Lim D.-S., Cimprich K.A., Taya Y., Tamai K., Sakaguchi K., RA Appella E., Kastan M.B., Siliciano J.D.; RT "Activation of the ATM kinase by ionizing radiation and phosphorylation of RT p53."; RL Science 281:1677-1679(1998). RN [22] RP DNA-BINDING. RX PubMed=10500142; DOI=10.1073/pnas.96.20.11134; RA Smith G.C.M., Cary R.B., Lakin N.D., Hann B.C., Teo S.-H., Chen D.J., RA Jackson S.P.; RT "Purification and DNA binding properties of the ataxia-telangiectasia gene RT product ATM."; RL Proc. Natl. Acad. Sci. U.S.A. 96:11134-11139(1999). RN [23] RP FUNCTION IN PHOSPHORYLATION OF BRCA1. RX PubMed=10550055; DOI=10.1126/science.286.5442.1162; RA Cortez D., Wang Y., Qin J., Elledge S.J.; RT "Requirement of ATM-dependent phosphorylation of brca1 in the DNA damage RT response to double-strand breaks."; RL Science 286:1162-1166(1999). RN [24] RP IDENTIFICATION OF ATM AS MEMBER OF BASC. RX PubMed=10783165; RA Wang Y., Cortez D., Yazdi P., Neff N., Elledge S.J., Qin J.; RT "BASC, a super complex of BRCA1-associated proteins involved in the RT recognition and repair of aberrant DNA structures."; RL Genes Dev. 14:927-939(2000). RN [25] RP FUNCTION IN PHOSPHORYLATION OF NBN. RX PubMed=10766245; DOI=10.1038/35007091; RA Lim D.-S., Kim S.-T., Xu B., Maser R.S., Lin J., Petrini J.H.J., RA Kastan M.B.; RT "ATM phosphorylates p95/nbs1 in an S-phase checkpoint pathway."; RL Nature 404:613-617(2000). RN [26] RP FUNCTION IN PHOSPHORYLATION OF NBN. RX PubMed=10839545; DOI=10.1038/35013089; RA Wu X., Ranganathan V., Weisman D.S., Heine W.F., Ciccone D.N., RA O'Neill T.B., Crick K.E., Pierce K.A., Lane W.S., Rathbun G., RA Livingston D.M., Weaver D.T.; RT "ATM phosphorylation of Nijmegen breakage syndrome protein is required in a RT DNA damage response."; RL Nature 405:477-482(2000). RN [27] RP FUNCTION IN PHOSPHORYLATION OF CTIP. RX PubMed=10910365; DOI=10.1038/35018134; RA Li S., Ting N.S.Y., Zheng L., Chen P.-L., Ziv Y., Shiloh Y., Lee E.Y.-H.P., RA Lee W.-H.; RT "Functional link of BRCA1 and ataxia telangiectasia gene product in DNA RT damage response."; RL Nature 406:210-215(2000). RN [28] RP FUNCTION IN PHOSPHORYLATION OF NBN. RX PubMed=10802669; DOI=10.1038/75508; RA Gatei M., Young D., Cerosaletti K.M., Desai-Mehta A., Spring K., Kozlov S., RA Lavin M.F., Gatti R.A., Concannon P., Khanna K.K.; RT "ATM-dependent phosphorylation of nibrin in response to radiation RT exposure."; RL Nat. Genet. 25:115-119(2000). RN [29] RP FUNCTION IN PHOSPHORYLATION OF CHEK2. RX PubMed=10973490; DOI=10.1073/pnas.190030497; RA Matsuoka S., Rotman G., Ogawa A., Shiloh Y., Tamai K., Elledge S.J.; RT "Ataxia telangiectasia-mutated phosphorylates Chk2 in vivo and in vitro."; RL Proc. Natl. Acad. Sci. U.S.A. 97:10389-10394(2000). RN [30] RP FUNCTION IN PHOSPHORYLATION OF TERF1. RX PubMed=11375976; DOI=10.1074/jbc.m011534200; RA Kishi S., Zhou X.Z., Ziv Y., Khoo C., Hill D.E., Shiloh Y., Lu K.P.; RT "Telomeric protein Pin2/TRF1 as an important ATM target in response to RT double strand DNA breaks."; RL J. Biol. Chem. 276:29282-29291(2001). RN [31] RP INTERACTION WITH RAD17. RX PubMed=11418864; DOI=10.1038/35082110; RA Bao S., Tibbetts R.S., Brumbaugh K.M., Fang Y., Richardson D.A., Ali A., RA Chen S.M., Abraham R.T., Wang X.-F.; RT "ATR/ATM-mediated phosphorylation of human Rad17 is required for genotoxic RT stress responses."; RL Nature 411:969-974(2001). RN [32] RP FUNCTION IN PHOSPHORYLATION OF FANCD2. RX PubMed=12086603; DOI=10.1016/s0092-8674(02)00747-x; RA Taniguchi T., Garcia-Higuera I., Xu B., Andreassen P.R., Gregory R.C., RA Kim S.-T., Lane W.S., Kastan M.B., D'Andrea A.D.; RT "Convergence of the Fanconi anemia and ataxia telangiectasia signaling RT pathways."; RL Cell 109:459-472(2002). RN [33] RP PHOSPHORYLATION BY NUAK1. RX PubMed=12409306; DOI=10.1074/jbc.m206025200; RA Suzuki A., Kusakai G., Kishimoto A., Lu J., Ogura T., Lavin M.F., Esumi H.; RT "Identification of a novel protein kinase mediating Akt survival signaling RT to the ATM protein."; RL J. Biol. Chem. 278:48-53(2003). RN [34] RP PHOSPHORYLATION AT SER-1981, SUBUNIT, FUNCTION, AND MUTAGENESIS OF RP SER-1981. RX PubMed=12556884; DOI=10.1038/nature01368; RA Bakkenist C.J., Kastan M.B.; RT "DNA damage activates ATM through intermolecular autophosphorylation and RT dimer dissociation."; RL Nature 421:499-506(2003). RN [35] RP FUNCTION IN DNA DAMAGE RESPONSE. RX PubMed=14871926; DOI=10.1101/gad.1176004; RA Ali A., Zhang J., Bao S., Liu I., Otterness D., Dean N.M., Abraham R.T., RA Wang X.F.; RT "Requirement of protein phosphatase 5 in DNA-damage-induced ATM RT activation."; RL Genes Dev. 18:249-254(2004). RN [36] RP FUNCTION IN PHOSPHORYLATION OF DCLRE1C. RX PubMed=15456891; DOI=10.1128/mcb.24.20.9207-9220.2004; RA Zhang X., Succi J., Feng Z., Prithivirajsingh S., Story M.D., RA Legerski R.J.; RT "Artemis is a phosphorylation target of ATM and ATR and is involved in the RT G2/M DNA damage checkpoint response."; RL Mol. Cell. Biol. 24:9207-9220(2004). RN [37] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=15448695; DOI=10.1038/ncb1170; RA Demonacos C., Krstic-Demonacos M., Smith L., Xu D., O'Connor D.P., RA Jansson M., La Thangue N.B.; RT "A new effector pathway links ATM kinase with the DNA damage response."; RL Nat. Cell Biol. 6:968-976(2004). RN [38] RP FUNCTION, AND ACTIVITY REGULATION. RX PubMed=15064416; DOI=10.1126/science.1091496; RA Lee J.-H., Paull T.T.; RT "Direct activation of the ATM protein kinase by the Mre11/Rad50/Nbs1 RT complex."; RL Science 304:93-96(2004). RN [39] RP INTERACTION WITH EEF1E1. RX PubMed=15680327; DOI=10.1016/j.cell.2004.11.054; RA Park B.-J., Kang J.W., Lee S.W., Choi S.-J., Shin Y.K., Ahn Y.H., RA Choi Y.H., Choi D., Lee K.S., Kim S.; RT "The haploinsufficient tumor suppressor p18 upregulates p53 via RT interactions with ATM/ATR."; RL Cell 120:209-221(2005). RN [40] RP FUNCTION. RX PubMed=15916964; DOI=10.1016/j.molcel.2005.04.015; RA Bhoumik A., Takahashi S., Breitweiser W., Shiloh Y., Jones N., Ronai Z.; RT "ATM-dependent phosphorylation of ATF2 is required for the DNA damage RT response."; RL Mol. Cell 18:577-587(2005). RN [41] RP INTERACTION WITH KAT8. RX PubMed=15923642; DOI=10.1128/mcb.25.12.5292-5305.2005; RA Gupta A., Sharma G.G., Young C.S.H., Agarwal M., Smith E.R., Paull T.T., RA Lucchesi J.C., Khanna K.K., Ludwig T., Pandita T.K.; RT "Involvement of human MOF in ATM function."; RL Mol. Cell. Biol. 25:5292-5305(2005). RN [42] RP FUNCTION IN HISTONE MRNA DEGRADATION ACTIVITY. RX PubMed=16086026; DOI=10.1038/nsmb972; RA Kaygun H., Marzluff W.F.; RT "Regulated degradation of replication-dependent histone mRNAs requires both RT ATR and Upf1."; RL Nat. Struct. Mol. Biol. 12:794-800(2005). RN [43] RP PHOSPHORYLATION AT SER-1981, AND ACETYLATION. RX PubMed=16141325; DOI=10.1073/pnas.0504211102; RA Sun Y., Jiang X., Chen S., Fernandes N., Price B.D.; RT "A role for the Tip60 histone acetyltransferase in the acetylation and RT activation of ATM."; RL Proc. Natl. Acad. Sci. U.S.A. 102:13182-13187(2005). RN [44] RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, SUBUNIT, AND RP PHOSPHORYLATION AT SER-1981. RX PubMed=15790808; DOI=10.1126/science.1108297; RA Lee J.H., Paull T.T.; RT "ATM activation by DNA double-strand breaks through the Mre11-Rad50-Nbs1 RT complex."; RL Science 308:551-554(2005). RN [45] RP PHOSPHORYLATION AT SER-367; SER-1893 AND SER-1981, FUNCTION, CATALYTIC RP ACTIVITY, MUTAGENESIS OF SER-367; SER-1893 AND SER-1981, AND IDENTIFICATION RP BY MASS SPECTROMETRY. RX PubMed=16858402; DOI=10.1038/sj.emboj.7601231; RA Kozlov S.V., Graham M.E., Peng C., Chen P., Robinson P.J., Lavin M.F.; RT "Involvement of novel autophosphorylation sites in ATM activation."; RL EMBO J. 25:3504-3514(2006). RN [46] RP INTERACTION WITH ATMIN. RX PubMed=17525732; DOI=10.1038/sj.emboj.7601733; RA Kanu N., Behrens A.; RT "ATMIN defines an NBS1-independent pathway of ATM signalling."; RL EMBO J. 26:2933-2941(2007). RN [47] RP ACETYLATION AT LYS-3016, FUNCTION, AND MUTAGENESIS OF LYS-3016 AND RP LYS-3018. RX PubMed=17923702; DOI=10.1128/mcb.01382-07; RA Sun Y., Xu Y., Roy K., Price B.D.; RT "DNA damage-induced acetylation of lysine 3016 of ATM activates ATM kinase RT activity."; RL Mol. Cell. Biol. 27:8502-8509(2007). RN [48] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1981 AND SER-1983, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic kidney; RX PubMed=17525332; DOI=10.1126/science.1140321; RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., RA Gygi S.P., Elledge S.J.; RT "ATM and ATR substrate analysis reveals extensive protein networks RT responsive to DNA damage."; RL Science 316:1160-1166(2007). RN [49] RP INTERACTION WITH CEP164. RX PubMed=18283122; DOI=10.1101/gad.1627708; RA Sivasubramaniam S., Sun X., Pan Y.R., Wang S., Lee E.Y.; RT "Cep164 is a mediator protein required for the maintenance of genomic RT stability through modulation of MDC1, RPA, and CHK1."; RL Genes Dev. 22:587-600(2008). RN [50] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2996, AND IDENTIFICATION BY RP MASS SPECTROMETRY [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 [51] RP INTERACTION WITH NABP2. RX PubMed=18449195; DOI=10.1038/nature06883; RA Richard D.J., Bolderson E., Cubeddu L., Wadsworth R.I.M., Savage K., RA Sharma G.G., Nicolette M.L., Tsvetanov S., McIlwraith M.J., Pandita R.K., RA Takeda S., Hay R.T., Gautier J., West S.C., Paull T.T., Pandita T.K., RA White M.F., Khanna K.K.; RT "Single-stranded DNA-binding protein hSSB1 is critical for genomic RT stability."; RL Nature 453:677-681(2008). RN [52] RP INTERACTION WITH DDX1. RX PubMed=18710941; DOI=10.1128/mcb.01053-08; RA Li L., Monckton E.A., Godbout R.; RT "A role for DEAD box 1 at DNA double-strand breaks."; RL Mol. Cell. Biol. 28:6413-6425(2008). RN [53] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2996, 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 [54] RP FUNCTION AS DYRK2 KINASE. RX PubMed=19965871; DOI=10.1074/jbc.m109.042341; RA Taira N., Yamamoto H., Yamaguchi T., Miki Y., Yoshida K.; RT "ATM augments nuclear stabilization of DYRK2 by inhibiting MDM2 in the RT apoptotic response to DNA damage."; RL J. Biol. Chem. 285:4909-4919(2010). RN [55] RP INTERACTION WITH TTI1. RX PubMed=20810650; DOI=10.1101/gad.1934210; RA Hurov K.E., Cotta-Ramusino C., Elledge S.J.; RT "A genetic screen identifies the Triple T complex required for DNA damage RT signaling and ATM and ATR stability."; RL Genes Dev. 24:1939-1950(2010). RN [56] RP INTERACTION WITH TELO2. RX PubMed=20801936; DOI=10.1101/gad.1956410; RA Takai H., Xie Y., de Lange T., Pavletich N.P.; RT "Tel2 structure and function in the Hsp90-dependent maturation of mTOR and RT ATR complexes."; RL Genes Dev. 24:2019-2030(2010). RN [57] RP INTERACTION WITH TELO2 AND TTI1. RX PubMed=20427287; DOI=10.1074/jbc.m110.121699; RA Kaizuka T., Hara T., Oshiro N., Kikkawa U., Yonezawa K., Takehana K., RA Iemura S., Natsume T., Mizushima N.; RT "Tti1 and Tel2 are critical factors in mammalian target of rapamycin RT complex assembly."; RL J. Biol. Chem. 285:20109-20116(2010). RN [58] 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 [59] RP PHOSPHORYLATION AT SER-1981. RX PubMed=21144835; DOI=10.1016/j.bbrc.2010.12.005; RA Kang Y., Cheong H.M., Lee J.H., Song P.I., Lee K.H., Kim S.Y., Jun J.Y., RA You H.J.; RT "Protein phosphatase 5 is necessary for ATR-mediated DNA repair."; RL Biochem. Biophys. Res. Commun. 404:476-481(2011). RN [60] RP INTERACTION WITH BRAT1. RX PubMed=22977523; DOI=10.3892/etm.2011.232; RA So E.Y., Ouchi T.; RT "Functional interaction of BRCA1/ATM-associated BAAT1 with the DNA-PK RT catalytic subunit."; RL Exp. Ther. Med. 2:443-447(2011). RN [61] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=21757780; DOI=10.1074/jbc.m111.258152; RA Gatei M., Jakob B., Chen P., Kijas A.W., Becherel O.J., Gueven N., RA Birrell G., Lee J.H., Paull T.T., Lerenthal Y., Fazry S., RA Taucher-Scholz G., Kalb R., Schindler D., Waltes R., Doerk T., Lavin M.F.; RT "ATM protein-dependent phosphorylation of Rad50 protein regulates DNA RT repair and cell cycle control."; RL J. Biol. Chem. 286:31542-31556(2011). RN [62] RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=22223895; DOI=10.1074/mcp.m111.015131; RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., RA Giglione C.; RT "Comparative large-scale characterisation of plant vs. mammal proteins RT reveals similar and idiosyncratic N-alpha acetylation features."; RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012). RN [63] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [64] RP FUNCTION. RX PubMed=24534091; DOI=10.1002/embj.201386064; RA Wang Q., Goldstein M., Alexander P., Wakeman T.P., Sun T., Feng J., Lou Z., RA Kastan M.B., Wang X.F.; RT "Rad17 recruits the MRE11-RAD50-NBS1 complex to regulate the cellular RT response to DNA double-strand breaks."; RL EMBO J. 33:862-877(2014). RN [65] RP IDENTIFICATION BY 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 [66] RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, INTERACTION WITH PEX5, RP AND MUTAGENESIS OF ARG-3047. RX PubMed=26344566; DOI=10.1038/ncb3230; RA Zhang J., Tripathi D.N., Jing J., Alexander A., Kim J., Powell R.T., RA Dere R., Tait-Mulder J., Lee J.H., Paull T.T., Pandita R.K., Charaka V.K., RA Pandita T.K., Kastan M.B., Walker C.L.; RT "ATM functions at the peroxisome to induce pexophagy in response to ROS."; RL Nat. Cell Biol. 17:1259-1269(2015). RN [67] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=26240375; DOI=10.1093/nar/gkv754; RA Kijas A.W., Lim Y.C., Bolderson E., Cerosaletti K., Gatei M., Jakob B., RA Tobias F., Taucher-Scholz G., Gueven N., Oakley G., Concannon P., RA Wolvetang E., Khanna K.K., Wiesmueller L., Lavin M.F.; RT "ATM-dependent phosphorylation of MRE11 controls extent of resection during RT homology directed repair by signalling through Exonuclease 1."; RL Nucleic Acids Res. 43:8352-8367(2015). RN [68] RP FUNCTION IN PHOSPHORYLATION OF FBXW7. RX PubMed=26774286; DOI=10.1016/j.molcel.2015.12.010; RA Zhang Q., Karnak D., Tan M., Lawrence T.S., Morgan M.A., Sun Y.; RT "FBXW7 facilitates nonhomologous end-joining via K63-linked RT polyubiquitylation of XRCC4."; RL Mol. Cell 61:419-433(2016). RN [69] RP FUNCTION. RX PubMed=29203878; DOI=10.1038/s41467-017-02114-x; RA Batenburg N.L., Walker J.R., Noordermeer S.M., Moatti N., Durocher D., RA Zhu X.D.; RT "ATM and CDK2 control chromatin remodeler CSB to inhibit RIF1 in DSB repair RT pathway choice."; RL Nat. Commun. 8:1921-1921(2017). RN [70] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=30171069; DOI=10.1074/jbc.ra118.005354; RA Choppara S., Ganga S., Manne R., Dutta P., Singh S., Santra M.K.; RT "The SCFFBXO46 ubiquitin ligase complex mediates degradation of the tumor RT suppressor FBXO31 and thereby prevents premature cellular senescence."; RL J. Biol. Chem. 293:16291-16306(2018). RN [71] RP FUNCTION. RX PubMed=30612738; DOI=10.1016/j.cell.2018.11.024; RA Jachimowicz R.D., Beleggia F., Isensee J., Velpula B.B., Goergens J., RA Bustos M.A., Doll M.A., Shenoy A., Checa-Rodriguez C., Wiederstein J.L., RA Baranes-Bachar K., Bartenhagen C., Hertwig F., Teper N., Nishi T., RA Schmitt A., Distelmaier F., Luedecke H.J., Albrecht B., Krueger M., RA Schumacher B., Geiger T., Hoon D.S.B., Huertas P., Fischer M., Hucho T., RA Peifer M., Ziv Y., Reinhardt H.C., Wieczorek D., Shiloh Y.; RT "UBQLN4 represses homologous recombination and is overexpressed in RT aggressive tumors."; RL Cell 0:0-0(2019). RN [72] RP FUNCTION IN PHOSPHORYLATION OF UFL1, AND CATALYTIC ACTIVITY. RX PubMed=30886146; DOI=10.1038/s41467-019-09175-0; RA Qin B., Yu J., Nowsheen S., Wang M., Tu X., Liu T., Li H., Wang L., Lou Z.; RT "UFL1 promotes histone H4 ufmylation and ATM activation."; RL Nat. Commun. 10:1242-1242(2019). RN [73] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=30952868; DOI=10.1038/s41467-019-09641-9; RA Ha G.H., Ji J.H., Chae S., Park J., Kim S., Lee J.K., Kim Y., Min S., RA Park J.M., Kang T.H., Lee H., Cho H., Lee C.W.; RT "Pellino1 regulates reversible ATM activation via NBS1 ubiquitination at RT DNA double-strand breaks."; RL Nat. Commun. 10:1577-1577(2019). RN [74] RP ACETYLATION AT LYS-3016, PHOSPHORYLATION AT SER-1981, AND MUTAGENESIS OF RP LYS-3016. RX PubMed=30944854; DOI=10.1126/sciadv.aav1118; RA Tang M., Li Z., Zhang C., Lu X., Tu B., Cao Z., Li Y., Chen Y., Jiang L., RA Wang H., Wang L., Wang J., Liu B., Xu X., Wang H., Zhu W.G.; RT "SIRT7-mediated ATM deacetylation is essential for its deactivation and DNA RT damage repair."; RL Sci. Adv. 5:EAAV1118-EAAV1118(2019). RN [75] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=38128537; DOI=10.1016/j.cell.2023.11.022; RA Chen Y., Wu J., Zhai L., Zhang T., Yin H., Gao H., Zhao F., Wang Z., RA Yang X., Jin M., Huang B., Ding X., Li R., Yang J., He Y., Wang Q., RA Wang W., Kloeber J.A., Li Y., Hao B., Zhang Y., Wang J., Tan M., Li K., RA Wang P., Lou Z., Yuan J.; RT "Metabolic regulation of homologous recombination repair by MRE11 RT lactylation."; RL Cell 187:294-311(2024). RN [76] {ECO:0007744|PDB:5NP0, ECO:0007744|PDB:5NP1} RP STRUCTURE BY ELECTRON MICROSCOPY (5.70 ANGSTROMS), CATALYTIC ACTIVITY, AND RP SUBUNIT. RX PubMed=28508083; DOI=10.1126/sciadv.1700933; RA Baretic D., Pollard H.K., Fisher D.I., Johnson C.M., Santhanam B., RA Truman C.M., Kouba T., Fersht A.R., Phillips C., Williams R.L.; RT "Structures of closed and open conformations of dimeric human ATM."; RL Sci. Adv. 3:E1700933-E1700933(2017). RN [77] {ECO:0007744|PDB:7SIC, ECO:0007744|PDB:7SID} RP STRUCTURE BY ELECTRON MICROSCOPY (2.51 ANGSTROMS) IN COMPLEX WITH NBN, RP FUNCTION, INTERACTION WITH NBN, AND ACTIVITY REGULATION. RX PubMed=35076389; DOI=10.7554/elife.74218; RA Warren C., Pavletich N.P.; RT "Structure of the human ATM kinase and mechanism of Nbs1 binding."; RL Elife 11:0-0(2022). RN [78] RP VARIANTS GLY-2424; 2546-SER--ILE-2548 DEL AND CYS-2827. RX PubMed=8755918; RA McConville C.M., Stankovic T., Byrd P.J., McGuire G.M., Yao Q.-Y., RA Lennox G.G., Taylor A.M.R.; RT "Mutations associated with variant phenotypes in ataxia-telangiectasia."; RL Am. J. Hum. Genet. 59:320-330(1996). RN [79] RP VARIANT AT 2546-SER--ILE-2548 DEL, AND VARIANT ILE-2438. RX PubMed=8808599; RA Wright J., Teraoka S., Onengut S., Tolun A., Gatti R.A., Ochs H.D., RA Concannon P.; RT "A high frequency of distinct ATM gene mutations in ataxia- RT telangiectasia."; RL Am. J. Hum. Genet. 59:839-846(1996). RN [80] RP VARIANTS 705-TYR--SER-707 DELINS PHE-ILE-PRO AND 2546-SER--ILE-2548 DEL, RP AND VARIANTS CYS-49; LEU-858; ARG-1054; PHE-1420 AND ARG-1691. RX PubMed=8797579; RA Vorechovsky I., Luo L., Lindblom A., Negrini M., Webster A.D.B., RA Croce C.M., Hammarstroem L.; RT "ATM mutations in cancer families."; RL Cancer Res. 56:4130-4133(1996). RN [81] RP VARIANT AT 705-TYR--SER-707 DELINS PHE-ILE-PRO, AND VARIANTS LEU-858 AND RP ARG-1054. RX PubMed=9043869; DOI=10.1159/000472231; RA Vorechovsky I., Luo L., Prudente S., Chessa L., Russo G., Kanariou M., RA James M.R., Negrini M., Webster A.D.B., Hammarstroem L.; RT "Exon-scanning mutation analysis of the ATM gene in patients with ataxia- RT telangiectasia."; RL Eur. J. Hum. Genet. 4:352-355(1996). RN [82] RP VARIANT AT ARG-2867. RX PubMed=8698354; DOI=10.1007/s004390050202; RA Baumer A., Bernthaler U., Wolz W., Hoehn H., Schindler D.; RT "New mutations in the ataxia telangiectasia gene."; RL Hum. Genet. 98:246-249(1996). RN [83] RP VARIANTS 2427-LEU-ARG-2428 DEL; 2546-SER--ILE-2548 DEL; SER-2860 DEL AND RP GLY-2904. RX PubMed=8845835; DOI=10.1093/hmg/5.4.433; RA Gilad S., Khosravi R., Shkedy D., Uziel T., Ziv Y., Savitsky K., Rotman G., RA Smith S., Chessa L., Jorgensen T.J., Harnik R., Frydman M., Sanal O., RA Portnoi S., Goldwicz Z., Jaspers N.G.J., Gatti R.A., Lenoir G., Lavin M.F., RA Tatsumi K., Wegner R.-D., Shiloh Y., Bar-Shira A.; RT "Predominance of null mutations in ataxia-telangiectasia."; RL Hum. Mol. Genet. 5:433-439(1996). RN [84] RP POSSIBLE INVOLVEMENT IN TPLL AND BNHL, AND VARIANTS VAL-1040; THR-1407; RP SER-1463; HIS-1682; HIS-1910; LYS-2164; SER-2396; GLY-2424; PRO-2442; RP 2546-SER--ILE-2548 DEL; ALA-2695; ARG-2722; VAL-2725; LEU-2732; LYS-2810 RP DEL; CYS-2832 AND 2871-ARG-HIS-2872 DELINS SER AND VAL-2890. RX PubMed=9288106; DOI=10.1038/ng0997-96; RA Vorechovsky I., Luo L., Dyer M.J.S., Catovsky D., Amlot P.L., Yaxley J.C., RA Foroni L., Hammarstroem L., Webster A.D.B., Yuille M.A.R.; RT "Clustering of missense mutations in the ataxia-telangiectasia gene in a RT sporadic T-cell leukaemia."; RL Nat. Genet. 17:96-99(1997). RN [85] RP POSSIBLE INVOLVEMENT IN TPLL, AND VARIANTS GLY-2725; PRO-3006 AND CYS-3008. RX PubMed=9334731; DOI=10.1038/nm1097-1155; RA Stilgenbauer S., Schaffner C., Litterst A., Liebisch P., Gilad S., RA Bar-Shira A., James M.R., Lichter P., Doehner H.; RT "Biallelic mutations in the ATM gene in T-prolymphocytic leukemia."; RL Nat. Med. 3:1155-1159(1997). RN [86] RP VARIANT AT CYS-2832. RX PubMed=9443866; DOI=10.1086/301673; RA Telatar M., Teraoka S., Wang Z., Chun H.H., Liang T., Castellvi-Bel S., RA Udar N., Boerresen-Dale A.-L., Chessa L., Bernatowska-Matuszkiewicz E., RA Porras O., Watanabe M., Junker A., Concannon P., Gatti R.A.; RT "Ataxia-telangiectasia: identification and detection of founder-effect RT mutations in the ATM gene in ethnic populations."; RL Am. J. Hum. Genet. 62:86-97(1998). RN [87] RP POSSIBLE INVOLVEMENT IN TALL, AND VARIANTS AT LEU-292; ASP-768; GLN-1001; RP ARG-1691; ILE-1743; GLY-2424; 2427-LEU-ARG-2428 DEL; 2546-SER--ILE-2548 RP DEL; ASP-2554; GLY-2668 AND CYS-2827. RX PubMed=9463314; DOI=10.1086/301706; RA Stankovic T., Kidd A.M.J., Sutcliffe A., McGuire G.M., Robinson P., RA Weber P., Bedenham T., Bradwell A.R., Easton D.F., Lennox G.G., Haites N., RA Byrd P.J., Taylor A.M.R.; RT "ATM mutations and phenotypes in ataxia-telangiectasia families in the RT British Isles: expression of mutant ATM and the risk of leukemia, lymphoma, RT and breast cancer."; RL Am. J. Hum. Genet. 62:334-345(1998). RN [88] RP VARIANT AT 1812-ALA-PHE-1813 DELINS VAL. RX PubMed=9497252; DOI=10.1086/301755; RA Gilad S., Chessa L., Khosravi R., Russell P., Galanty Y., Piane M., RA Gatti R.A., Jorgensen T.J., Shiloh Y., Bar-Shira A.; RT "Genotype-phenotype relationships in ataxia-telangiectasia and variants."; RL Am. J. Hum. Genet. 62:551-561(1998). RN [89] RP VARIANT AT PRO-2656. RX PubMed=9450874; RX DOI=10.1002/(sici)1096-8628(19980113)75:2<141::aid-ajmg4>3.3.co;2-8; RA Toyoshima M., Hara T., Zhang H., Yamamoto T., Akaboshi S., Nanba E., RA Ohno K., Hori N., Sato K., Takeshita K.; RT "Ataxia-telangiectasia without immunodeficiency: novel point mutations RT within and adjacent to the phosphatidylinositol 3-kinase-like domain."; RL Am. J. Med. Genet. 75:141-144(1998). RN [90] RP VARIANT TPLL GLY-2486. RX PubMed=9573030; RA Stoppa-Lyonnet D., Soulier J., Lauge A., Dastot H., Garand R., Sigaux F., RA Stern M.-H.; RT "Inactivation of the ATM gene in T-cell prolymphocytic leukemias."; RL Blood 91:3920-3926(1998). RN [91] RP VARIANTS 2855-SER-VAL-2856 DELINS ARG-ILE AND CYS-3008, AND VARIANT RP VAL-1853. RX PubMed=9872980; DOI=10.1101/gr.8.12.1245; RA Hacia J.G., Sun B., Hunt N., Edgemon K., Mosbrook D., Robbins C., RA Fodor S.P.A., Tagle D.A., Collins F.S.; RT "Strategies for mutational analysis of the large multiexon ATM gene using RT high-density oligonucleotide arrays."; RL Genome Res. 8:1245-1258(1998). RN [92] RP VARIANT AT 2625-ASP-ALA-2626 DELINS GLU-PRO. RX PubMed=9521587; DOI=10.1007/s004390050675; RA van Belzen M.J., Hiel J.A.P., Weemaes C.M.R., Gabreeels F.J.M., RA van Engelen B.G.M., Smeets D.F.C.M., van den Heuvel L.P.W.J.; RT "A double missense mutation in the ATM gene of a Dutch family with ataxia RT telangiectasia."; RL Hum. Genet. 102:187-191(1998). RN [93] RP VARIANT AT LEU-2829, AND VARIANTS GLU-126; ASP-514 AND ASN-1853. RX PubMed=9711876; RX DOI=10.1002/(sici)1098-1004(1998)12:3<186::aid-humu6>3.0.co;2-f; RA Sasaki T., Tian H., Kukita Y., Inazuka M., Tahira T., Imai T., Yamauchi M., RA Saito T., Hori T., Hashimoto-Tamaoki T., Komatsu K., Nikaido O., RA Hayashi K.; RT "ATM mutations in patients with ataxia telangiectasia screened by a RT hierarchical strategy."; RL Hum. Mutat. 12:186-195(1998). RN [94] RP VARIANTS AT LEU-858; ARG-1054; ASP-1091 AND ARG-1566. RX PubMed=9792409; RX DOI=10.1002/(sici)1098-1004(1998)12:5<330::aid-humu6>3.0.co;2-h; RA Broeks A., de Klein A., Floore A.N., Muijtjens M., Kleijer W.J., RA Jaspers N.G.J., van 't Veer L.J.; RT "ATM germline mutations in classical ataxia-telangiectasia patients in the RT Dutch population."; RL Hum. Mutat. 12:330-337(1998). RN [95] RP VARIANTS AT ARG-2491 AND GLY-2909. RX PubMed=9792410; RX DOI=10.1002/(sici)1098-1004(1998)12:5<338::aid-humu7>3.0.co;2-9; RA Fukao T., Song X.-Q., Yoshida T., Tashita H., Kaneko H., Teramoto T., RA Inoue R., Katamura K., Mayumi M., Hiratani M., Taniguchi N., Arai J., RA Wakiguchi H., Bar-Shira A., Shiloh Y., Kondo N.; RT "Ataxia-telangiectasia in the Japanese population: identification of RT R1917X, W2491R, R2909G, IVS33+2T-->A, and 7883del5, the latter two being RT relatively common mutations."; RL Hum. Mutat. 12:338-343(1998). RN [96] RP VARIANTS TPLL GLY-2139; VAL-2890 AND CYS-3008. RX PubMed=9488043; DOI=10.1038/sj.onc.1201603; RA Yuille M.A.R., Coignet L.J.A., Abraham S.M., Yaqub F., Luo L., Matutes E., RA Brito-Babapulle V., Vorechovsky I., Dyer M.J.S., Catovsky D.; RT "ATM is usually rearranged in T-cell prolymphocytic leukaemia."; RL Oncogene 16:789-796(1998). RN [97] RP ERRATUM OF PUBMED:9488043. RA Yuille M.A.R., Coignet L.J.A., Abraham S.M., Yaqub F., Luo L., Matutes E., RA Brito-Babapulle V., Vorechovsky I., Dyer M.J.S., Catovsky D.; RL Oncogene 16:2955-2955(1998). RN [98] RP POSSIBLE INVOLVEMENT IN BCLL AND MCL, AND VARIANTS ASN-1853; VAL-1853; RP ARG-1953; LYS-2418 INS; PRO-2420; GLY-2423; HIS-3008 AND ASN-3018. RX PubMed=10397742; RA Schaffner C., Stilgenbauer S., Rappold G.A., Doehner H., Lichter P.; RT "Somatic ATM mutations indicate a pathogenic role of ATM in B-cell chronic RT lymphocytic leukemia."; RL Blood 94:748-753(1999). RN [99] RP POSSIBLE INVOLVEMENT IN BCLL, AND VARIANTS CYS-332; ARG-1691 AND GLY-2424. RX PubMed=9892178; RA Bullrich F., Rasio D., Kitada S., Starostik P., Kipps T., Keating M., RA Albitar M., Reed J.C., Croce C.M.; RT "ATM mutations in B-cell chronic lymphocytic leukemia."; RL Cancer Res. 59:24-27(1999). RN [100] RP VARIANT AT PRO-1465. RX PubMed=10234507; DOI=10.1038/sj.ejhg.5200288; RA Izatt L., Vessey C., Hodgson S.V., Solomon E.; RT "Rapid and efficient ATM mutation detection by fluorescent chemical RT cleavage of mismatch: identification of four novel mutations."; RL Eur. J. Hum. Genet. 7:310-320(1999). RN [101] RP VARIANTS CYS-49; LEU-182; PRO-707; LEU-858; PHE-1420; ALA-1570; ASN-1853 RP AND SER-2765. RX PubMed=10534763; RX DOI=10.1002/(sici)1098-2264(199912)26:4<286::aid-gcc2>3.3.co;2-o; RA Izatt L., Greenman J., Hodgson S.V., Ellis D., Watts S., Scott G., RA Jacobs C., Liebmann R., Zvelebil M.J., Mathew C., Solomon E.; RT "Identification of germline missense mutations and rare allelic variants in RT the ATM gene in early-onset breast cancer."; RL Genes Chromosomes Cancer 26:286-294(1999). RN [102] RP VARIANTS AT SER-570; CYS-785; GLY-1913; GLY-2016; ASP-2067; CYS-2227; RP ASP-2470; VAL-2662 DEL; PRO-2849 AND ARG-2867, AND VARIANTS CYS-49; RP LEU-858; ARG-1054; ASN-1853 AND VAL-1853. RX PubMed=9887333; DOI=10.1093/hmg/8.1.69; RA Sandoval N., Platzer M., Rosenthal A., Doerk T., Bendix R., Skawran B., RA Stuhrmann M., Wegner R.-D., Sperling K., Banin S., Shiloh Y., Baumer A., RA Bernthaler U., Sennefelder H., Brohm M., Weber B.H.F., Schindler D.; RT "Characterization of ATM gene mutations in 66 ataxia telangiectasia RT families."; RL Hum. Mol. Genet. 8:69-79(1999). RN [103] RP VARIANTS AT 375-GLN--VAL-3056 DEL; 1466-ARG--VAL-3056 DEL; RP 1730-ARG--VAL-3056 DEL; GLY-2016; 2224-MET--ARG-2227 DELINS ILE-SER; RP 2246-CYS--THR-2252 DELINS HIS; VAL-2664 DEL; VAL-2726; 2849-ARG--VAL-3056 RP DEL AND ARG-2855, AND VARIANT CYS-49. RX PubMed=10425038; RX DOI=10.1002/(sici)1098-1004(1999)14:2<156::aid-humu7>3.0.co;2-e; RA Castellvi-Bel S., Sheikhavandi S., Telatar M., Tai L.-Q., Hwang M.J., RA Wang Z., Yang Z., Cheng R., Gatti R.A.; RT "New mutations, polymorphisms, and rare variants in the ATM gene detected RT by a novel SSCP strategy."; RL Hum. Mutat. 14:156-162(1999). RN [104] RP POSSIBLE INVOLVEMENT IN BCLL, AND VARIANTS THR-350; THR-352; ARG-1054; RP THR-2274 AND ALA-2695. RX PubMed=10023947; DOI=10.1016/s0140-6736(98)10117-4; RA Stankovic T., Weber P., Stewart G., Bedenham T., Murray J., Byrd P.J., RA Moss P.A.H., Taylor A.M.R.; RT "Inactivation of ataxia telangiectasia mutated gene in B-cell chronic RT lymphocytic leukaemia."; RL Lancet 353:26-29(1999). RN [105] RP VARIANT ARG-1054. RX PubMed=10217116; DOI=10.1016/s0140-6736(05)75199-0; RA Vorechovsky I., Luo L., Ortmann E., Steinmann D., Doerk T.; RT "Missense mutations at ATM gene and cancer risk."; RL Lancet 353:1276-1276(1999). RN [106] RP ERRATUM OF PUBMED:10217116. RA Vorechovsky I., Luo L., Ortmann E., Steinmann D., Doerk T.; RL Lancet 354:780-780(1999). RN [107] RP VARIANTS AT GLU-224; VAL-323; PRO-1420; CYS-2218; 2546-SER--ILE-2548 DEL; RP GLN-2625; CYS-2832; 2855-SER-VAL-2856 DELINS ARG-ILE AND CYS-3008, AND RP VARIANTS VAL-1853 AND ILE-2438. RX PubMed=10817650; RX DOI=10.1002/(sici)1096-8628(20000529)92:3<170::aid-ajmg3>3.0.co;2-#; RA Li A., Swift M.; RT "Mutations at the ataxia-telangiectasia locus and clinical phenotypes of A- RT T patients."; RL Am. J. Med. Genet. 92:170-177(2000). RN [108] RP VARIANTS AT 35-ARG--VAL-3056 DEL; LEU-292; 393-TRP--VAL-3056 DEL; ARG-950; RP LEU-1082; 1171-GLN--VAL-3056 DEL; 1839-GLN--VAL-3056 DEL; GLU-2063; RP CYS-2227; 2246-CYS--THR-2252 DELINS HIS; 2547-ARG--SER-2549 DEL; GLU-2625; RP PRO-2626 AND ARG-2702, AND VARIANT CYS-49. RX PubMed=10873394; DOI=10.1006/mgme.2000.2998; RA Becker-Catania S.G., Chen G., Hwang M.J., Wang Z., Sun X., Sanal O., RA Bernatowska-Matuszkiewicz E., Chessa L., Lee E.Y.-H.P., Gatti R.A.; RT "Ataxia-telangiectasia: phenotype/genotype studies of ATM protein RT expression, mutations, and radiosensitivity."; RL Mol. Genet. Metab. 70:122-133(2000). RN [109] RP VARIANTS MCL LYS-2418 INS; GLY-2423 AND CYS-3008. RX PubMed=10706620; DOI=10.1073/pnas.050400997; RA Schaffner C., Idler I., Stilgenbauer S., Doehner H., Lichter P.; RT "Mantle cell lymphoma is characterized by inactivation of the ATM gene."; RL Proc. Natl. Acad. Sci. U.S.A. 97:2773-2778(2000). RN [110] RP VARIANTS TRP-45 AND CYS-49. RX PubMed=11897822; DOI=10.1136/jmg.39.3.192; RA Allinen M., Launonen V., Laake K., Jansen L., Huusko P., Kaeaeriaeinen H., RA Boerresen-Dale A.L., Winqvist R.; RT "ATM mutations in Finnish breast cancer patients."; RL J. Med. Genet. 39:192-196(2002). RN [111] RP VARIANTS [LARGE SCALE ANALYSIS] GLN-23; CYS-49; GLU-126; HIS-140; GLN-250; RP PHE-333; CYS-337; HIS-337; ALA-410; SER-504; ASP-514; TYR-540; VAL-546; RP LEU-582; PRO-707; GLN-848; LEU-858; SER-872; TRP-924; ALA-935; ARG-1054; RP PHE-1179; ILE-1321; TYR-1380; SER-1382; PHE-1420; MET-1469; CYS-1475; RP SER-1650; THR-1739; ASN-1853; VAL-1853; ILE-1916; THR-1945; CYS-1961; RP ASP-1991; PHE-2307; PRO-2332; PHE-2356; LEU-2408; PRO-2442; GLN-2443; RP ARG-2464; ARG-2492; ALA-2666; HIS-2719; ARG-2842 AND ASN-2870. 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 [112] RP VARIANTS CYS-49; LEU-858; ARG-1054; VAL-1255; ASN-1853; THR-2105; SER-2396 RP AND HIS-2719. RX PubMed=18384426; DOI=10.1111/j.1399-0004.2008.00987.x; RA Brunet J., Gutierrez-Enriquez S., Torres A., Berez V., Sanjose S., RA Galceran J., Izquierdo A., Menendez J.A., Guma J., Borras J.; RT "ATM germline mutations in Spanish early-onset breast cancer patients RT negative for BRCA1/BRCA2 mutations."; RL Clin. Genet. 73:465-473(2008). RN [113] RP FUNCTION, CHARACTERIZATION OF VARIANTS AT LEU-292; PRO-1465; ILE-1743; RP THR-2274; GLY-2424; 2427-LEU-ARG-2428 DEL; 2546-SER--ILE-2548 DEL; RP ASP-2554; GLY-2668; CYS-2827; 2855-SER-VAL-2856 DELINS ARG-ILE AND RP CYS-3008, CHARACTERIZATION OF VARIANTS VAL-546; ARG-1054; ILE-1322; RP ARG-1691; CYS-1961 AND SER-2765, VARIANT ILE-1322, AND MUTAGENESIS OF RP LYS-1807; VAL-1941; TYR-2019; GLU-2039; LEU-2338; SER-2394; LEU-2452; RP SER-2685; PRO-2699; ASP-2708 AND GLN-2730. RX PubMed=19431188; DOI=10.1002/humu.21034; RA Barone G., Groom A., Reiman A., Srinivasan V., Byrd P.J., Taylor A.M.; RT "Modeling ATM mutant proteins from missense changes confirms retained RT kinase activity."; RL Hum. Mutat. 30:1222-1230(2009). RN [114] RP VARIANTS ALA-661; PRO-707; LEU-858; TRP-924; ARG-1054; ARG-1691 AND RP VAL-1853. RX PubMed=28202063; DOI=10.1186/s12920-017-0244-7; RA Jalkh N., Chouery E., Haidar Z., Khater C., Atallah D., Ali H., RA Marafie M.J., Al-Mulla M.R., Al-Mulla F., Megarbane A.; RT "Next-generation sequencing in familial breast cancer patients from RT Lebanon."; RL BMC Med. Genomics 10:8-8(2017). RN [115] RP VARIANTS AT VAL-323; PRO-1046; ARG-2023; SER-2068; ASP-2080; HIS-2627; RP LEU-2834 AND ASP-3003, CHARACTERIZATION OF VARIANTS AT VAL-323; PRO-1046; RP ARG-2023; SER-2068; ASP-2080; HIS-2627; LEU-2834 AND ASP-3003, AND RP PHOSPHORYLATION. RX PubMed=27664052; DOI=10.1007/s12017-016-8440-8; RA Carranza D., Vega A.K., Torres-Rusillo S., Montero E., Martinez L.J., RA Santamaria M., Santos J.L., Molina I.J.; RT "Molecular and functional characterization of a cohort of Spanish patients RT with ataxia-telangiectasia."; RL NeuroMolecular Med. 19:161-174(2017). RN [116] RP VARIANTS VAL-68; ILE-341; LEU-597; GLY-699; GLY-759; SER-813; GLY-869; RP ILE-897; ASP-1474; VAL-1488; CYS-1961; ALA-2287; PHE-2307; ARG-2464; RP PRO-2524; THR-2531; GLN-2810; HIS-2832; LEU-2974; ASP-3029 AND LEU-3056. RX PubMed=28726808; DOI=10.1038/gim.2017.85; RA Chaffee K.G., Oberg A.L., McWilliams R.R., Majithia N., Allen B.A., RA Kidd J., Singh N., Hartman A.R., Wenstrup R.J., Petersen G.M.; RT "Prevalence of germ-line mutations in cancer genes among pancreatic cancer RT patients with a positive family history."; RL Genet. Med. 20:119-127(2018). CC -!- FUNCTION: Serine/threonine protein kinase which activates checkpoint CC signaling upon double strand breaks (DSBs), apoptosis and genotoxic CC stresses such as ionizing ultraviolet A light (UVA), thereby acting as CC a DNA damage sensor (PubMed:10550055, PubMed:10839545, PubMed:10910365, CC PubMed:12556884, PubMed:14871926, PubMed:15064416, PubMed:15448695, CC PubMed:15456891, PubMed:15790808, PubMed:15916964, PubMed:17923702, CC PubMed:21757780, PubMed:24534091, PubMed:35076389, PubMed:9733514). CC Recognizes the substrate consensus sequence [ST]-Q (PubMed:10550055, CC PubMed:10839545, PubMed:10910365, PubMed:12556884, PubMed:14871926, CC PubMed:15448695, PubMed:15456891, PubMed:15916964, PubMed:17923702, CC PubMed:24534091, PubMed:9733514). Phosphorylates 'Ser-139' of histone CC variant H2AX at double strand breaks (DSBs), thereby regulating DNA CC damage response mechanism (By similarity). Also plays a role in pre-B CC cell allelic exclusion, a process leading to expression of a single CC immunoglobulin heavy chain allele to enforce clonality and monospecific CC recognition by the B-cell antigen receptor (BCR) expressed on CC individual B-lymphocytes. After the introduction of DNA breaks by the CC RAG complex on one immunoglobulin allele, acts by mediating a CC repositioning of the second allele to pericentromeric heterochromatin, CC preventing accessibility to the RAG complex and recombination of the CC second allele. Also involved in signal transduction and cell cycle CC control. May function as a tumor suppressor. Necessary for activation CC of ABL1 and SAPK. Phosphorylates DYRK2, CHEK2, p53/TP53, FBXW7, FANCD2, CC NFKBIA, BRCA1, CREBBP/CBP, RBBP8/CTIP, FBXO46, MRE11, nibrin (NBN), CC RAD50, RAD17, PELI1, TERF1, UFL1, RAD9, UBQLN4 and DCLRE1C CC (PubMed:10550055, PubMed:10766245, PubMed:10802669, PubMed:10839545, CC PubMed:10910365, PubMed:10973490, PubMed:11375976, PubMed:12086603, CC PubMed:15456891, PubMed:19965871, PubMed:21757780, PubMed:24534091, CC PubMed:26240375, PubMed:26774286, PubMed:30171069, PubMed:30612738, CC PubMed:30886146, PubMed:30952868, PubMed:38128537, PubMed:9733515, CC PubMed:9843217). May play a role in vesicle and/or protein transport. CC Could play a role in T-cell development, gonad and neurological CC function. Plays a role in replication-dependent histone mRNA CC degradation. Binds DNA ends. Phosphorylation of DYRK2 in nucleus in CC response to genotoxic stress prevents its MDM2-mediated ubiquitination CC and subsequent proteasome degradation (PubMed:19965871). Phosphorylates CC ATF2 which stimulates its function in DNA damage response CC (PubMed:15916964). Phosphorylates ERCC6 which is essential for its CC chromatin remodeling activity at DNA double-strand breaks CC (PubMed:29203878). Phosphorylates TTC5/STRAP at 'Ser-203' in the CC cytoplasm in response to DNA damage, which promotes TTC5/STRAP nuclear CC localization (PubMed:15448695). Also involved in pexophagy by mediating CC phosphorylation of PEX5: translocated to peroxisomes in response to CC reactive oxygen species (ROS), and catalyzes phosphorylation of PEX5, CC promoting PEX5 ubiquitination and induction of pexophagy CC (PubMed:26344566). {ECO:0000250|UniProtKB:Q62388, CC ECO:0000269|PubMed:10550055, ECO:0000269|PubMed:10766245, CC ECO:0000269|PubMed:10802669, ECO:0000269|PubMed:10839545, CC ECO:0000269|PubMed:10910365, ECO:0000269|PubMed:10973490, CC ECO:0000269|PubMed:11375976, ECO:0000269|PubMed:12086603, CC ECO:0000269|PubMed:12556884, ECO:0000269|PubMed:14871926, CC ECO:0000269|PubMed:15448695, ECO:0000269|PubMed:15456891, CC ECO:0000269|PubMed:15916964, ECO:0000269|PubMed:16086026, CC ECO:0000269|PubMed:16858402, ECO:0000269|PubMed:17923702, CC ECO:0000269|PubMed:19431188, ECO:0000269|PubMed:19965871, CC ECO:0000269|PubMed:21757780, ECO:0000269|PubMed:24534091, CC ECO:0000269|PubMed:26240375, ECO:0000269|PubMed:26344566, CC ECO:0000269|PubMed:26774286, ECO:0000269|PubMed:29203878, CC ECO:0000269|PubMed:30171069, ECO:0000269|PubMed:30612738, CC ECO:0000269|PubMed:30886146, ECO:0000269|PubMed:30952868, CC ECO:0000269|PubMed:35076389, ECO:0000269|PubMed:38128537, CC ECO:0000269|PubMed:9733514, ECO:0000269|PubMed:9733515, CC ECO:0000269|PubMed:9843217}. CC -!- CATALYTIC ACTIVITY: CC Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + CC H(+); Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA- CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1; CC Evidence={ECO:0000269|PubMed:15448695, ECO:0000269|PubMed:15790808, CC ECO:0000269|PubMed:16858402, ECO:0000269|PubMed:26240375, CC ECO:0000269|PubMed:26344566, ECO:0000269|PubMed:28508083, CC ECO:0000269|PubMed:30171069, ECO:0000269|PubMed:30886146, CC ECO:0000269|PubMed:30952868, ECO:0000269|PubMed:38128537, CC ECO:0000269|PubMed:8988033, ECO:0000269|PubMed:9843217}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17990; CC Evidence={ECO:0000269|PubMed:15790808, ECO:0000269|PubMed:21757780, CC ECO:0000269|PubMed:26240375, ECO:0000269|PubMed:30952868, CC ECO:0000269|PubMed:9843217, ECO:0000305|PubMed:15448695}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + CC ADP + H(+); Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA- CC COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.1; CC Evidence={ECO:0000269|PubMed:24534091, ECO:0000269|PubMed:28508083, CC ECO:0000269|PubMed:30952868, ECO:0000269|PubMed:8988033, CC ECO:0000269|PubMed:9843217}; CC -!- ACTIVITY REGULATION: Activated by the MRN (MRE11-RAD50-NBS1) complex in CC response to DNA double strand breaks (DSBs), which recruits ATM to DSBs CC and promotes its activation (PubMed:15064416, PubMed:15790808, CC PubMed:35076389). Inhibited by wortmannin (PubMed:9766667). CC {ECO:0000269|PubMed:15064416, ECO:0000269|PubMed:15790808, CC ECO:0000269|PubMed:35076389, ECO:0000269|PubMed:9766667}. CC -!- SUBUNIT: Homodimer (PubMed:12556884, PubMed:15790808, PubMed:28508083). CC Dimers or tetramers in inactive state (PubMed:12556884, CC PubMed:15790808, PubMed:28508083). On DNA damage, autophosphorylation CC dissociates ATM into monomers rendering them catalytically active CC (PubMed:12556884, PubMed:28508083). Binds p53/TP53, ABL1, BRCA1 and CC TERF1 (PubMed:15790808, PubMed:9168117, PubMed:9843217). Interacts with CC NBN (via FxF/Y motif) (PubMed:35076389). Part of the BRCA1-associated CC genome surveillance complex (BASC), which contains BRCA1, MSH2, MSH6, CC MLH1, ATM, BLM, PMS2 and the RAD50-MRE11-NBN protein complex CC (PubMed:10783165). This association could be a dynamic process changing CC throughout the cell cycle and within subnuclear domains CC (PubMed:10783165). Interacts with RAD17; DNA damage promotes the CC association (PubMed:11418864). Interacts with EEF1E1; the interaction, CC induced on DNA damage, up-regulates TP53 (PubMed:15680327). Interacts CC with KAT8, NABP2, ATMIN and CEP164 (PubMed:15923642, PubMed:17525732, CC PubMed:18283122, PubMed:18449195). Interacts with AP2B1 and AP3B2; the CC interaction occurs in cytoplasmic vesicles (By similarity). Interacts CC with TELO2 and TTI1 (PubMed:20427287, PubMed:20801936, CC PubMed:20810650). Interacts with DDX1 (PubMed:18710941). Interacts with CC BRAT1 (PubMed:22977523). Interacts with CYREN (via XLF motif) (By CC similarity). Interacts (via microbody targeting signal) with PEX5; CC promoting translocation to peroxisomes in response to reactive oxygen CC species (ROS) (PubMed:26344566). {ECO:0000250|UniProtKB:Q62388, CC ECO:0000269|PubMed:10783165, ECO:0000269|PubMed:11418864, CC ECO:0000269|PubMed:12556884, ECO:0000269|PubMed:15680327, CC ECO:0000269|PubMed:15790808, ECO:0000269|PubMed:15923642, CC ECO:0000269|PubMed:17525732, ECO:0000269|PubMed:18283122, CC ECO:0000269|PubMed:18449195, ECO:0000269|PubMed:18710941, CC ECO:0000269|PubMed:20427287, ECO:0000269|PubMed:20801936, CC ECO:0000269|PubMed:20810650, ECO:0000269|PubMed:22977523, CC ECO:0000269|PubMed:26344566, ECO:0000269|PubMed:28508083, CC ECO:0000269|PubMed:35076389, ECO:0000269|PubMed:9168117, CC ECO:0000269|PubMed:9843217}. CC -!- INTERACTION: CC Q13315; Q9NY61: AATF; NbExp=3; IntAct=EBI-495465, EBI-372428; CC Q13315; P00519: ABL1; NbExp=4; IntAct=EBI-495465, EBI-375543; CC Q13315; P31749: AKT1; NbExp=5; IntAct=EBI-495465, EBI-296087; CC Q13315; O43313: ATMIN; NbExp=5; IntAct=EBI-495465, EBI-7422202; CC Q13315; Q6PJG6: BRAT1; NbExp=3; IntAct=EBI-495465, EBI-10826195; CC Q13315; P62508-3: ESRRG; NbExp=3; IntAct=EBI-495465, EBI-12001340; CC Q13315; Q5XUX0: FBXO31; NbExp=2; IntAct=EBI-495465, EBI-6162477; CC Q13315; Q9Y6K9: IKBKG; NbExp=4; IntAct=EBI-495465, EBI-81279; CC Q13315; Q13007: IL24; NbExp=2; IntAct=EBI-495465, EBI-3915542; CC Q13315; Q14676: MDC1; NbExp=3; IntAct=EBI-495465, EBI-495644; CC Q13315; Q9BQ15: NABP2; NbExp=4; IntAct=EBI-495465, EBI-2120336; CC Q13315; P11245: NAT2; NbExp=2; IntAct=EBI-495465, EBI-9057228; CC Q13315; O60934: NBN; NbExp=2; IntAct=EBI-495465, EBI-494844; CC Q13315; P46531: NOTCH1; NbExp=8; IntAct=EBI-495465, EBI-636374; CC Q13315; Q9BZ95: NSD3; NbExp=3; IntAct=EBI-495465, EBI-3390132; CC Q13315; Q7LG56: RRM2B; NbExp=3; IntAct=EBI-495465, EBI-9009083; CC Q13315; Q9Y4R8: TELO2; NbExp=4; IntAct=EBI-495465, EBI-1043674; CC Q13315; P54274: TERF1; NbExp=3; IntAct=EBI-495465, EBI-710997; CC Q13315; P54274-2: TERF1; NbExp=5; IntAct=EBI-495465, EBI-711018; CC Q13315; Q15554: TERF2; NbExp=2; IntAct=EBI-495465, EBI-706637; CC Q13315; Q12888: TP53BP1; NbExp=2; IntAct=EBI-495465, EBI-396540; CC Q13315; O43156: TTI1; NbExp=5; IntAct=EBI-495465, EBI-1055680; CC Q13315; PRO_0000037577 [P27958]; Xeno; NbExp=3; IntAct=EBI-495465, EBI-6904388; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:9050866, CC ECO:0000269|PubMed:9150358}. Cytoplasmic vesicle CC {ECO:0000269|PubMed:9050866, ECO:0000269|PubMed:9150358}. Cytoplasm, CC cytoskeleton, microtubule organizing center, centrosome CC {ECO:0000250|UniProtKB:Q62388}. Peroxisome matrix CC {ECO:0000269|PubMed:26344566}. Note=Primarily nuclear (PubMed:9050866, CC PubMed:9150358). Found also in endocytic vesicles in association with CC beta-adaptin (PubMed:9707615). Translocated to peroxisomes in response CC to reactive oxygen species (ROS) by PEX5 (PubMed:26344566). CC {ECO:0000269|PubMed:26344566, ECO:0000269|PubMed:9050866, CC ECO:0000269|PubMed:9150358, ECO:0000269|PubMed:9707615}. CC -!- TISSUE SPECIFICITY: Found in pancreas, kidney, skeletal muscle, liver, CC lung, placenta, brain, heart, spleen, thymus, testis, ovary, small CC intestine, colon and leukocytes. CC -!- INDUCTION: By ionizing radiation. CC -!- DOMAIN: The FATC domain is required for interaction with KAT5. CC {ECO:0000269|PubMed:16141325}. CC -!- PTM: Phosphorylated by NUAK1/ARK5 (PubMed:12409306). CC Autophosphorylation on Ser-367, Ser-1893, Ser-1981 correlates with DNA CC damage-mediated activation of the kinase (PubMed:12556884, CC PubMed:15790808, PubMed:16141325, PubMed:16858402, PubMed:21144835, CC PubMed:27664052). During the late stages of DNA damage response, CC dephosphorylated following deacetylation by SIRT7, leading to ATM CC deactivation (PubMed:30944854). {ECO:0000269|PubMed:12409306, CC ECO:0000269|PubMed:12556884, ECO:0000269|PubMed:15790808, CC ECO:0000269|PubMed:16141325, ECO:0000269|PubMed:16858402, CC ECO:0000269|PubMed:21144835, ECO:0000269|PubMed:27664052, CC ECO:0000269|PubMed:30944854}. CC -!- PTM: Acetylation, on DNA damage, is required for activation of the CC kinase activity, dimer-monomer transition, and subsequent CC autophosphorylation on Ser-1981 (PubMed:12556884, PubMed:16141325, CC PubMed:16858402, PubMed:17923702, PubMed:21144835). Acetylated in vitro CC by KAT5/TIP60 (PubMed:16141325). Deacetylated by SIRT7 during the late CC stages of DNA damage response, promoting ATM dephosphorylation and CC subsequent deactivation (PubMed:30944854). CC {ECO:0000269|PubMed:12556884, ECO:0000269|PubMed:16141325, CC ECO:0000269|PubMed:16858402, ECO:0000269|PubMed:17923702, CC ECO:0000269|PubMed:21144835, ECO:0000269|PubMed:30944854}. CC -!- DISEASE: Ataxia telangiectasia (AT) [MIM:208900]: A rare recessive CC disorder characterized by progressive cerebellar ataxia, dilation of CC the blood vessels in the conjunctiva and eyeballs, immunodeficiency, CC growth retardation and sexual immaturity. Patients have a strong CC predisposition to cancer; about 30% of patients develop tumors, CC particularly lymphomas and leukemias. Cells from affected individuals CC are highly sensitive to damage by ionizing radiation and resistant to CC inhibition of DNA synthesis following irradiation. CC {ECO:0000269|PubMed:10234507, ECO:0000269|PubMed:10425038, CC ECO:0000269|PubMed:10817650, ECO:0000269|PubMed:10873394, CC ECO:0000269|PubMed:19431188, ECO:0000269|PubMed:27664052, CC ECO:0000269|PubMed:7792600, ECO:0000269|PubMed:8589678, CC ECO:0000269|PubMed:8665503, ECO:0000269|PubMed:8698354, CC ECO:0000269|PubMed:8755918, ECO:0000269|PubMed:8789452, CC ECO:0000269|PubMed:8797579, ECO:0000269|PubMed:8808599, CC ECO:0000269|PubMed:8845835, ECO:0000269|PubMed:9043869, CC ECO:0000269|PubMed:9150358, ECO:0000269|PubMed:9443866, CC ECO:0000269|PubMed:9450874, ECO:0000269|PubMed:9463314, CC ECO:0000269|PubMed:9497252, ECO:0000269|PubMed:9521587, CC ECO:0000269|PubMed:9711876, ECO:0000269|PubMed:9792409, CC ECO:0000269|PubMed:9792410, ECO:0000269|PubMed:9872980, CC ECO:0000269|PubMed:9887333}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Note=Defects in ATM may contribute to T-cell acute CC lymphoblastic leukemia (TALL) and T-prolymphocytic leukemia (TPLL). CC TPLL is characterized by a high white blood cell count, with a CC predominance of prolymphocytes, marked splenomegaly, lymphadenopathy, CC skin lesions and serous effusion. The clinical course is highly CC aggressive, with poor response to chemotherapy and short survival time. CC TPLL occurs both in adults as a sporadic disease and in younger AT CC patients. {ECO:0000269|PubMed:9288106, ECO:0000269|PubMed:9334731, CC ECO:0000269|PubMed:9463314, ECO:0000269|PubMed:9488043, CC ECO:0000269|PubMed:9573030}. CC -!- DISEASE: Note=Defects in ATM may contribute to B-cell non-Hodgkin CC lymphomas (BNHL), including mantle cell lymphoma (MCL). CC {ECO:0000269|PubMed:10397742, ECO:0000269|PubMed:10706620, CC ECO:0000269|PubMed:9288106}. CC -!- DISEASE: Note=Defects in ATM may contribute to B-cell chronic CC lymphocytic leukemia (BCLL). BCLL is the commonest form of leukemia in CC the elderly. It is characterized by the accumulation of mature CD5+ B- CC lymphocytes, lymphadenopathy, immunodeficiency and bone marrow failure. CC {ECO:0000269|PubMed:10023947, ECO:0000269|PubMed:10397742, CC ECO:0000269|PubMed:9892178}. CC -!- SIMILARITY: Belongs to the PI3/PI4-kinase family. ATM subfamily. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAA86520.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=AAA86520.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact.; Evidence={ECO:0000305}; CC Sequence=AAI37170.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=AAI37170.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact.; Evidence={ECO:0000305}; CC Sequence=EAW67111.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/123/ATM"; CC -!- WEB RESOURCE: Name=Wikipedia; Note=Ataxia telangiectasia mutated entry; CC URL="https://en.wikipedia.org/wiki/Ataxia_telangiectasia_mutated"; 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; U33841; AAC50289.1; -; mRNA. DR EMBL; U55757; AAB38309.1; -; Genomic_DNA. DR EMBL; U55704; AAB38309.1; JOINED; Genomic_DNA. DR EMBL; U55705; AAB38309.1; JOINED; Genomic_DNA. DR EMBL; U55707; AAB38309.1; JOINED; Genomic_DNA. DR EMBL; U55708; AAB38309.1; JOINED; Genomic_DNA. DR EMBL; U55709; AAB38309.1; JOINED; Genomic_DNA. DR EMBL; U55710; AAB38309.1; JOINED; Genomic_DNA. DR EMBL; U55711; AAB38309.1; JOINED; Genomic_DNA. DR EMBL; U55712; AAB38309.1; JOINED; Genomic_DNA. DR EMBL; U55713; AAB38309.1; JOINED; Genomic_DNA. DR EMBL; U55714; AAB38309.1; JOINED; Genomic_DNA. DR EMBL; U55715; AAB38309.1; JOINED; Genomic_DNA. DR EMBL; U55716; AAB38309.1; JOINED; Genomic_DNA. DR EMBL; U55717; AAB38309.1; JOINED; Genomic_DNA. DR EMBL; U55718; AAB38309.1; JOINED; Genomic_DNA. DR EMBL; U55719; AAB38309.1; JOINED; Genomic_DNA. DR EMBL; U55720; AAB38309.1; JOINED; Genomic_DNA. DR EMBL; U55721; AAB38309.1; JOINED; Genomic_DNA. DR EMBL; U55722; AAB38309.1; JOINED; Genomic_DNA. DR EMBL; U55723; AAB38309.1; JOINED; Genomic_DNA. DR EMBL; U55724; AAB38309.1; JOINED; Genomic_DNA. DR EMBL; U55725; AAB38309.1; JOINED; Genomic_DNA. DR EMBL; U55726; AAB38309.1; JOINED; Genomic_DNA. DR EMBL; U55727; AAB38309.1; JOINED; Genomic_DNA. DR EMBL; U55728; AAB38309.1; JOINED; Genomic_DNA. DR EMBL; U55729; AAB38309.1; JOINED; Genomic_DNA. DR EMBL; U55730; AAB38309.1; JOINED; Genomic_DNA. DR EMBL; U55731; AAB38309.1; JOINED; Genomic_DNA. DR EMBL; U55732; AAB38309.1; JOINED; Genomic_DNA. DR EMBL; U55733; AAB38309.1; JOINED; Genomic_DNA. DR EMBL; U55734; AAB38309.1; JOINED; Genomic_DNA. DR EMBL; U55735; AAB38309.1; JOINED; Genomic_DNA. DR EMBL; U55736; AAB38309.1; JOINED; Genomic_DNA. DR EMBL; U55737; AAB38309.1; JOINED; Genomic_DNA. DR EMBL; U55738; AAB38309.1; JOINED; Genomic_DNA. DR EMBL; U55739; AAB38309.1; JOINED; Genomic_DNA. DR EMBL; U55740; AAB38309.1; JOINED; Genomic_DNA. DR EMBL; U55741; AAB38309.1; JOINED; Genomic_DNA. DR EMBL; U55742; AAB38309.1; JOINED; Genomic_DNA. DR EMBL; U55743; AAB38309.1; JOINED; Genomic_DNA. DR EMBL; U55744; AAB38309.1; JOINED; Genomic_DNA. DR EMBL; U55745; AAB38309.1; JOINED; Genomic_DNA. DR EMBL; U55746; AAB38309.1; JOINED; Genomic_DNA. DR EMBL; U55747; AAB38309.1; JOINED; Genomic_DNA. DR EMBL; U55748; AAB38309.1; JOINED; Genomic_DNA. DR EMBL; U55749; AAB38309.1; JOINED; Genomic_DNA. DR EMBL; U55750; AAB38309.1; JOINED; Genomic_DNA. DR EMBL; U55751; AAB38309.1; JOINED; Genomic_DNA. DR EMBL; U55752; AAB38309.1; JOINED; Genomic_DNA. DR EMBL; U55753; AAB38309.1; JOINED; Genomic_DNA. DR EMBL; U55754; AAB38309.1; JOINED; Genomic_DNA. DR EMBL; U55755; AAB38309.1; JOINED; Genomic_DNA. DR EMBL; U55756; AAB38309.1; JOINED; Genomic_DNA. DR EMBL; U55757; AAB38310.1; -; Genomic_DNA. DR EMBL; U55726; AAB38310.1; JOINED; Genomic_DNA. DR EMBL; U55727; AAB38310.1; JOINED; Genomic_DNA. DR EMBL; U55728; AAB38310.1; JOINED; Genomic_DNA. DR EMBL; U55729; AAB38310.1; JOINED; Genomic_DNA. DR EMBL; U55730; AAB38310.1; JOINED; Genomic_DNA. DR EMBL; U55731; AAB38310.1; JOINED; Genomic_DNA. DR EMBL; U55732; AAB38310.1; JOINED; Genomic_DNA. DR EMBL; U55733; AAB38310.1; JOINED; Genomic_DNA. DR EMBL; U55734; AAB38310.1; JOINED; Genomic_DNA. DR EMBL; U55735; AAB38310.1; JOINED; Genomic_DNA. DR EMBL; U55736; AAB38310.1; JOINED; Genomic_DNA. DR EMBL; U55737; AAB38310.1; JOINED; Genomic_DNA. DR EMBL; U55738; AAB38310.1; JOINED; Genomic_DNA. DR EMBL; U55739; AAB38310.1; JOINED; Genomic_DNA. DR EMBL; U55740; AAB38310.1; JOINED; Genomic_DNA. DR EMBL; U55741; AAB38310.1; JOINED; Genomic_DNA. DR EMBL; U55742; AAB38310.1; JOINED; Genomic_DNA. DR EMBL; U55743; AAB38310.1; JOINED; Genomic_DNA. DR EMBL; U55744; AAB38310.1; JOINED; Genomic_DNA. DR EMBL; U55745; AAB38310.1; JOINED; Genomic_DNA. DR EMBL; U55746; AAB38310.1; JOINED; Genomic_DNA. DR EMBL; U55747; AAB38310.1; JOINED; Genomic_DNA. DR EMBL; U55748; AAB38310.1; JOINED; Genomic_DNA. DR EMBL; U55749; AAB38310.1; JOINED; Genomic_DNA. DR EMBL; U55750; AAB38310.1; JOINED; Genomic_DNA. DR EMBL; U55751; AAB38310.1; JOINED; Genomic_DNA. DR EMBL; U55752; AAB38310.1; JOINED; Genomic_DNA. DR EMBL; U55753; AAB38310.1; JOINED; Genomic_DNA. DR EMBL; U55754; AAB38310.1; JOINED; Genomic_DNA. DR EMBL; U55755; AAB38310.1; JOINED; Genomic_DNA. DR EMBL; U55756; AAB38310.1; JOINED; Genomic_DNA. DR EMBL; U82828; AAB65827.1; -; Genomic_DNA. DR EMBL; AP001925; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AP005718; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; KF455499; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471065; EAW67111.1; ALT_SEQ; Genomic_DNA. DR EMBL; X91196; CAA62603.1; -; mRNA. DR EMBL; U67092; AAC51298.1; -; Genomic_DNA. DR EMBL; AY220758; AAO26044.1; -; Genomic_DNA. DR EMBL; U26455; AAA86520.1; ALT_SEQ; mRNA. DR EMBL; BC137169; AAI37170.1; ALT_SEQ; mRNA. DR CCDS; CCDS31669.1; -. DR PIR; A43100; A43100. DR RefSeq; NP_000042.3; NM_000051.3. DR RefSeq; NP_001338763.1; NM_001351834.2. DR RefSeq; XP_005271619.2; XM_005271562.6. DR RefSeq; XP_006718906.1; XM_006718843.5. DR RefSeq; XP_006718908.1; XM_006718845.1. DR RefSeq; XP_011541142.1; XM_011542840.4. DR RefSeq; XP_016873279.1; XM_017017790.3. DR RefSeq; XP_047282931.1; XM_047426975.1. DR RefSeq; XP_047282932.1; XM_047426976.1. DR RefSeq; XP_054224846.1; XM_054368871.1. DR RefSeq; XP_054224847.1; XM_054368872.1. DR RefSeq; XP_054224848.1; XM_054368873.1. DR RefSeq; XP_054224849.1; XM_054368874.1. DR RefSeq; XP_054224850.1; XM_054368875.1. DR RefSeq; XP_054224851.1; XM_054368876.1. DR PDB; 5NP0; EM; 5.70 A; A/B=1-3056. DR PDB; 5NP1; EM; 5.70 A; A=1-3056. DR PDB; 6HKA; NMR; -; A=3024-3056. DR PDB; 6K9K; EM; 7.82 A; A=1-3056. DR PDB; 6K9L; EM; 4.27 A; A/B=1-3056. DR PDB; 7NI4; EM; 3.00 A; A/B=1-3056. DR PDB; 7NI5; EM; 2.78 A; A/B=1-3056. DR PDB; 7NI6; EM; 2.80 A; A/B=1-3056. DR PDB; 7SIC; EM; 2.51 A; A/B=1-3056. DR PDB; 7SID; EM; 2.53 A; A/C=1-3056. DR PDB; 8OXM; EM; 3.30 A; A/B=1-3056. DR PDB; 8OXO; EM; 3.00 A; A/B=1-3056. DR PDB; 8OXP; EM; 2.60 A; A/B=1-3056. DR PDB; 8OXQ; EM; 2.50 A; A/B=1-3056. DR PDBsum; 5NP0; -. DR PDBsum; 5NP1; -. DR PDBsum; 6HKA; -. DR PDBsum; 6K9K; -. DR PDBsum; 6K9L; -. DR PDBsum; 7NI4; -. DR PDBsum; 7NI5; -. DR PDBsum; 7NI6; -. DR PDBsum; 7SIC; -. DR PDBsum; 7SID; -. DR PDBsum; 8OXM; -. DR PDBsum; 8OXO; -. DR PDBsum; 8OXP; -. DR PDBsum; 8OXQ; -. DR EMDB; EMD-12350; -. DR EMDB; EMD-12351; -. DR EMDB; EMD-12352; -. DR EMDB; EMD-17265; -. DR EMDB; EMD-17266; -. DR EMDB; EMD-17267; -. DR EMDB; EMD-17268; -. DR EMDB; EMD-25140; -. DR EMDB; EMD-25141; -. DR EMDB; EMD-3669; -. DR EMDB; EMD-3672; -. DR EMDB; EMD-9949; -. DR EMDB; EMD-9950; -. DR SMR; Q13315; -. DR BioGRID; 106962; 345. DR CORUM; Q13315; -. DR DIP; DIP-182N; -. DR FunCoup; Q13315; 3527. DR IntAct; Q13315; 175. DR MINT; Q13315; -. DR STRING; 9606.ENSP00000278616; -. DR BindingDB; Q13315; -. DR ChEMBL; CHEMBL3797; -. DR DrugBank; DB02289; 2-Aminopropanedioic Acid. DR DrugBank; DB00201; Caffeine. DR GuidetoPHARMACOLOGY; 1934; -. DR GlyCosmos; Q13315; 4 sites, 2 glycans. DR GlyGen; Q13315; 7 sites, 2 O-linked glycans (6 sites). DR iPTMnet; Q13315; -. DR PhosphoSitePlus; Q13315; -. DR BioMuta; ATM; -. DR DMDM; 317373479; -. DR CPTAC; CPTAC-2874; -. DR CPTAC; CPTAC-2875; -. DR CPTAC; CPTAC-2876; -. DR CPTAC; CPTAC-3210; -. DR CPTAC; CPTAC-3211; -. DR CPTAC; CPTAC-3212; -. DR CPTAC; CPTAC-3213; -. DR CPTAC; CPTAC-5976; -. DR CPTAC; CPTAC-5977; -. DR CPTAC; CPTAC-5978; -. DR CPTAC; CPTAC-5979; -. DR CPTAC; CPTAC-912; -. DR CPTAC; CPTAC-913; -. DR jPOST; Q13315; -. DR MassIVE; Q13315; -. DR PaxDb; 9606-ENSP00000278616; -. DR PeptideAtlas; Q13315; -. DR ProteomicsDB; 59303; -. DR Pumba; Q13315; -. DR Antibodypedia; 3596; 1462 antibodies from 49 providers. DR CPTC; Q13315; 4 antibodies. DR DNASU; 472; -. DR Ensembl; ENST00000278616.10; ENSP00000278616.4; ENSG00000149311.23. DR Ensembl; ENST00000452508.7; ENSP00000388058.2; ENSG00000149311.23. DR Ensembl; ENST00000601453.3; ENSP00000469471.2; ENSG00000149311.23. DR Ensembl; ENST00000675843.1; ENSP00000501606.1; ENSG00000149311.23. DR Ensembl; ENST00000713844.1; ENSP00000519149.1; ENSG00000149311.23. DR GeneID; 472; -. DR KEGG; hsa:472; -. DR MANE-Select; ENST00000675843.1; ENSP00000501606.1; NM_000051.4; NP_000042.3. DR UCSC; uc001pkb.1; human. DR AGR; HGNC:795; -. DR CIViC; 472; 50 evidence items across 37 molecular profiles. DR ClinPGx; PA61; -. DR CTD; 472; -. DR DisGeNET; 472; -. DR GeneCards; ATM; -. DR GeneReviews; ATM; -. DR HGNC; HGNC:795; ATM. DR HPA; ENSG00000149311; Low tissue specificity. DR MalaCards; ATM; -. DR MIM; 208900; phenotype. DR MIM; 607585; gene. DR OpenTargets; ENSG00000149311; -. DR Orphanet; 100; Ataxia-telangiectasia. DR Orphanet; 370109; Ataxia-telangiectasia variant. DR Orphanet; 67038; B-cell chronic lymphocytic leukemia. DR Orphanet; 440437; Familial colorectal cancer Type X. DR Orphanet; 1331; Familial prostate cancer. DR Orphanet; 145; Hereditary breast and/or ovarian cancer syndrome. DR Orphanet; 227535; Hereditary breast cancer. DR Orphanet; 52416; Mantle cell lymphoma. DR VEuPathDB; HostDB:ENSG00000149311; -. DR eggNOG; KOG0892; Eukaryota. DR GeneTree; ENSGT00670000098061; -. DR HOGENOM; CLU_000178_3_1_1; -. DR InParanoid; Q13315; -. DR OMA; SEVYMKW; -. DR OrthoDB; 381190at2759; -. DR PAN-GO; Q13315; 7 GO annotations based on evolutionary models. DR PhylomeDB; Q13315; -. DR BRENDA; 2.7.11.1; 2681. DR PathwayCommons; Q13315; -. DR Reactome; R-HSA-2559586; DNA Damage/Telomere Stress Induced Senescence. DR Reactome; R-HSA-3371453; Regulation of HSF1-mediated heat shock response. DR Reactome; R-HSA-349425; Autodegradation of the E3 ubiquitin ligase COP1. DR Reactome; R-HSA-5685938; HDR through Single Strand Annealing (SSA). DR Reactome; R-HSA-5685942; HDR through Homologous Recombination (HRR). DR Reactome; R-HSA-5693548; Sensing of DNA Double Strand Breaks. DR Reactome; R-HSA-5693554; Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA). DR Reactome; R-HSA-5693565; Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks. DR Reactome; R-HSA-5693568; Resolution of D-loop Structures through Holliday Junction Intermediates. DR Reactome; R-HSA-5693571; Nonhomologous End-Joining (NHEJ). DR Reactome; R-HSA-5693579; Homologous DNA Pairing and Strand Exchange. DR Reactome; R-HSA-5693607; Processing of DNA double-strand break ends. DR Reactome; R-HSA-5693616; Presynaptic phase of homologous DNA pairing and strand exchange. DR Reactome; R-HSA-6796648; TP53 Regulates Transcription of DNA Repair Genes. DR Reactome; R-HSA-6803204; TP53 Regulates Transcription of Genes Involved in Cytochrome C Release. DR Reactome; R-HSA-6803207; TP53 Regulates Transcription of Caspase Activators and Caspases. DR Reactome; R-HSA-6804756; Regulation of TP53 Activity through Phosphorylation. DR Reactome; R-HSA-6804757; Regulation of TP53 Degradation. DR Reactome; R-HSA-6804760; Regulation of TP53 Activity through Methylation. DR Reactome; R-HSA-69473; G2/M DNA damage checkpoint. DR Reactome; R-HSA-69541; Stabilization of p53. DR Reactome; R-HSA-912446; Meiotic recombination. DR Reactome; R-HSA-9664873; Pexophagy. DR Reactome; R-HSA-9701192; Defective homologous recombination repair (HRR) due to BRCA1 loss of function. DR Reactome; R-HSA-9704331; Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function. DR Reactome; R-HSA-9704646; Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function. DR Reactome; R-HSA-9709570; Impaired BRCA2 binding to RAD51. DR Reactome; R-HSA-9709603; Impaired BRCA2 binding to PALB2. DR SignaLink; Q13315; -. DR SIGNOR; Q13315; -. DR Agora; ENSG00000149311; -. DR BioGRID-ORCS; 472; 54 hits in 1215 CRISPR screens. DR CD-CODE; 8C2F96ED; Centrosome. DR CD-CODE; 91857CE7; Nucleolus. DR CD-CODE; A0DCDA94; DNA damage foci. DR ChiTaRS; ATM; human. DR GeneWiki; Ataxia_telangiectasia_mutated; -. DR GenomeRNAi; 472; -. DR Pharos; Q13315; Tchem. DR PRO; PR:Q13315; -. DR Proteomes; UP000005640; Chromosome 11. DR RNAct; Q13315; protein. DR Bgee; ENSG00000149311; Expressed in calcaneal tendon and 207 other cell types or tissues. DR ExpressionAtlas; Q13315; baseline and differential. DR GO; GO:0005813; C:centrosome; ISS:UniProtKB. DR GO; GO:0005694; C:chromosome; IBA:GO_Central. DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:1990391; C:DNA repair complex; IDA:MGI. DR GO; GO:0098850; C:extrinsic component of synaptic vesicle membrane; IEA:Ensembl. DR GO; GO:0005730; C:nucleolus; IDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:ParkinsonsUK-UCL. DR GO; GO:0005782; C:peroxisomal matrix; IDA:UniProtKB. DR GO; GO:0035861; C:site of double-strand break; IDA:UniProtKB. DR GO; GO:0005819; C:spindle; IEA:Ensembl. DR GO; GO:0016303; F:1-phosphatidylinositol-3-kinase activity; IMP:UniProtKB. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW. DR GO; GO:0004677; F:DNA-dependent protein kinase activity; IDA:BHF-UCL. DR GO; GO:0035979; F:histone H2AXS139 kinase activity; ISS:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:BHF-UCL. DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA. DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB. DR GO; GO:0044877; F:protein-containing complex binding; IDA:BHF-UCL. DR GO; GO:0007420; P:brain development; IEA:Ensembl. DR GO; GO:0071480; P:cellular response to gamma radiation; IDA:CAFA. DR GO; GO:0071500; P:cellular response to nitrosative stress; IDA:ParkinsonsUK-UCL. DR GO; GO:0034614; P:cellular response to reactive oxygen species; IDA:UniProt. DR GO; GO:0071300; P:cellular response to retinoic acid; ISS:ARUK-UCL. DR GO; GO:0033554; P:cellular response to stress; IDA:UniProt. DR GO; GO:0071481; P:cellular response to X-ray; IDA:ParkinsonsUK-UCL. DR GO; GO:0090398; P:cellular senescence; TAS:Reactome. DR GO; GO:0008340; P:determination of adult lifespan; IEA:Ensembl. DR GO; GO:0000077; P:DNA damage checkpoint signaling; IDA:UniProtKB. DR GO; GO:0006974; P:DNA damage response; IDA:CAFA. DR GO; GO:0030330; P:DNA damage response, signal transduction by p53 class mediator; TAS:Reactome. DR GO; GO:0000729; P:DNA double-strand break processing; IDA:UniProt. DR GO; GO:0006302; P:double-strand break repair; IDA:UniProtKB. DR GO; GO:0000724; P:double-strand break repair via homologous recombination; IDA:UniProt. DR GO; GO:0006303; P:double-strand break repair via nonhomologous end joining; TAS:Reactome. DR GO; GO:0097695; P:establishment of protein-containing complex localization to telomere; IMP:BHF-UCL. DR GO; GO:0097694; P:establishment of RNA localization to telomere; IMP:BHF-UCL. DR GO; GO:0007143; P:female meiotic nuclear division; IEA:Ensembl. DR GO; GO:0007507; P:heart development; IEA:Ensembl. DR GO; GO:0071044; P:histone mRNA catabolic process; IDA:UniProtKB. DR GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IBA:GO_Central. DR GO; GO:0042159; P:lipoprotein catabolic process; IEA:Ensembl. DR GO; GO:0007140; P:male meiotic nuclear division; IEA:Ensembl. DR GO; GO:0045141; P:meiotic telomere clustering; IEA:Ensembl. DR GO; GO:0007095; P:mitotic G2 DNA damage checkpoint signaling; IMP:BHF-UCL. DR GO; GO:0007094; P:mitotic spindle assembly checkpoint signaling; IMP:UniProtKB. DR GO; GO:0035264; P:multicellular organism growth; IEA:Ensembl. DR GO; GO:0030889; P:negative regulation of B cell proliferation; IMP:UniProtKB. DR GO; GO:1904354; P:negative regulation of telomere capping; IMP:BHF-UCL. DR GO; GO:1904262; P:negative regulation of TORC1 signaling; IMP:ParkinsonsUK-UCL. DR GO; GO:0051402; P:neuron apoptotic process; IEA:Ensembl. DR GO; GO:0048599; P:oocyte development; IEA:Ensembl. DR GO; GO:0001541; P:ovarian follicle development; IEA:Ensembl. DR GO; GO:0036289; P:peptidyl-serine autophosphorylation; IMP:MGI. DR GO; GO:0000425; P:pexophagy; IDA:UniProtKB. DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:UniProtKB. DR GO; GO:0045785; P:positive regulation of cell adhesion; ISS:ARUK-UCL. DR GO; GO:0030335; P:positive regulation of cell migration; IMP:BHF-UCL. DR GO; GO:0043517; P:positive regulation of DNA damage response, signal transduction by p53 class mediator; IMP:BHF-UCL. DR GO; GO:2000781; P:positive regulation of double-strand break repair; IMP:BHF-UCL. DR GO; GO:0010628; P:positive regulation of gene expression; IMP:BHF-UCL. DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; IEA:Ensembl. DR GO; GO:1904884; P:positive regulation of telomerase catalytic core complex assembly; IMP:BHF-UCL. DR GO; GO:0032212; P:positive regulation of telomere maintenance via telomerase; ISS:BHF-UCL. DR GO; GO:1904358; P:positive regulation of telomere maintenance via telomere lengthening; IMP:BHF-UCL. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:ARUK-UCL. DR GO; GO:0009791; P:post-embryonic development; IEA:Ensembl. DR GO; GO:0002331; P:pre-B cell allelic exclusion; ISS:UniProtKB. DR GO; GO:0046777; P:protein autophosphorylation; IMP:UniProtKB. DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB. DR GO; GO:0050821; P:protein stabilization; IDA:UniProt. DR GO; GO:0007131; P:reciprocal meiotic recombination; TAS:ProtInc. DR GO; GO:0042981; P:regulation of apoptotic process; TAS:Reactome. DR GO; GO:2000785; P:regulation of autophagosome assembly; IC:UniProt. DR GO; GO:0010506; P:regulation of autophagy; IMP:ParkinsonsUK-UCL. DR GO; GO:0051726; P:regulation of cell cycle; IMP:BHF-UCL. DR GO; GO:1900034; P:regulation of cellular response to heat; TAS:Reactome. DR GO; GO:1901796; P:regulation of signal transduction by p53 class mediator; TAS:Reactome. DR GO; GO:0032210; P:regulation of telomere maintenance via telomerase; IGI:BHF-UCL. DR GO; GO:0090399; P:replicative senescence; IMP:BHF-UCL. DR GO; GO:0010212; P:response to ionizing radiation; IDA:UniProtKB. DR GO; GO:0007165; P:signal transduction; TAS:ProtInc. DR GO; GO:0042770; P:signal transduction in response to DNA damage; IDA:UniProtKB. DR GO; GO:0001756; P:somitogenesis; IEA:Ensembl. DR GO; GO:0000723; P:telomere maintenance; IBA:GO_Central. DR GO; GO:0048538; P:thymus development; IEA:Ensembl. DR GO; GO:0033151; P:V(D)J recombination; IEA:Ensembl. DR CDD; cd05171; PIKKc_ATM; 1. DR FunFam; 1.10.1070.11:FF:000011; Serine-protein kinase ATM; 1. DR FunFam; 3.30.1010.10:FF:000015; Serine-protein kinase ATM; 1. DR Gene3D; 1.10.1070.11; Phosphatidylinositol 3-/4-kinase, catalytic domain; 1. DR Gene3D; 3.30.1010.10; Phosphatidylinositol 3-kinase Catalytic Subunit, Chain A, domain 4; 1. DR InterPro; IPR016024; ARM-type_fold. DR InterPro; IPR038980; ATM_plant. DR InterPro; IPR003152; FATC_dom. DR InterPro; IPR011009; Kinase-like_dom_sf. DR InterPro; IPR000403; PI3/4_kinase_cat_dom. DR InterPro; IPR036940; PI3/4_kinase_cat_sf. DR InterPro; IPR018936; PI3/4_kinase_CS. DR InterPro; IPR003151; PIK-rel_kinase_FAT. DR InterPro; IPR014009; PIK_FAT. DR InterPro; IPR044107; PIKKc_ATM. DR InterPro; IPR021668; TAN. DR PANTHER; PTHR37079; SERINE/THREONINE-PROTEIN KINASE ATM; 1. DR PANTHER; PTHR37079:SF4; SERINE_THREONINE-PROTEIN KINASE ATM; 1. DR Pfam; PF02259; FAT; 1. DR Pfam; PF02260; FATC; 1. DR Pfam; PF00454; PI3_PI4_kinase; 1. DR Pfam; PF11640; TAN; 1. DR SMART; SM01343; FATC; 1. DR SMART; SM00146; PI3Kc; 1. DR SMART; SM01342; TAN; 1. DR SUPFAM; SSF48371; ARM repeat; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR PROSITE; PS51189; FAT; 1. DR PROSITE; PS51190; FATC; 1. DR PROSITE; PS00915; PI3_4_KINASE_1; 1. DR PROSITE; PS00916; PI3_4_KINASE_2; 1. DR PROSITE; PS50290; PI3_4_KINASE_3; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; ATP-binding; Cell cycle; Cytoplasm; KW Cytoplasmic vesicle; Cytoskeleton; Disease variant; DNA damage; KW DNA-binding; Kinase; Neurodegeneration; Nucleotide-binding; Nucleus; KW Peroxisome; Phosphoprotein; Proteomics identification; Reference proteome; KW Serine/threonine-protein kinase; Transferase; Tumor suppressor. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0007744|PubMed:22223895" FT CHAIN 2..3056 FT /note="Serine-protein kinase ATM" FT /id="PRO_0000088840" FT DOMAIN 1940..2566 FT /note="FAT" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00534" FT DOMAIN 2686..2998 FT /note="PI3K/PI4K catalytic" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269" FT DOMAIN 3024..3056 FT /note="FATC" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00534, FT ECO:0000255|PROSITE-ProRule:PRU00535" FT REGION 1373..1382 FT /note="Interaction with ABL1" FT /evidence="ECO:0000269|PubMed:9168117" FT REGION 2692..2698 FT /note="G-loop" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269" FT REGION 2867..2875 FT /note="Catalytic loop" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269" FT REGION 2887..2911 FT /note="Activation loop" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269" FT MOTIF 3046..3048 FT /note="Microbody targeting signal; atypical" FT /evidence="ECO:0000269|PubMed:26344566" FT MOD_RES 2 FT /note="N-acetylserine" FT /evidence="ECO:0007744|PubMed:22223895" FT MOD_RES 367 FT /note="Phosphoserine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:16858402" FT MOD_RES 1893 FT /note="Phosphoserine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:16858402" FT MOD_RES 1981 FT /note="Phosphoserine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:12556884, FT ECO:0000269|PubMed:15790808, ECO:0000269|PubMed:16141325, FT ECO:0000269|PubMed:16858402, ECO:0000269|PubMed:21144835, FT ECO:0000269|PubMed:30944854, ECO:0007744|PubMed:17525332" FT MOD_RES 1983 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17525332" FT MOD_RES 2996 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18691976, FT ECO:0007744|PubMed:19369195" FT MOD_RES 3016 FT /note="N6-acetyllysine" FT /evidence="ECO:0000269|PubMed:17923702, FT ECO:0000269|PubMed:30944854" FT VARIANT 23 FT /note="R -> Q (in a colorectal adenocarcinoma sample; FT somatic mutation; dbSNP:rs587779858)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041545" FT VARIANT 35..3056 FT /note="Missing (in AT; dbSNP:rs55861249)" FT /evidence="ECO:0000269|PubMed:10873394" FT /id="VAR_085060" FT VARIANT 45 FT /note="R -> W (found in a patient with breast cancer; FT uncertain significance; dbSNP:rs3218684)" FT /evidence="ECO:0000269|PubMed:11897822" FT /id="VAR_056678" FT VARIANT 49 FT /note="S -> C (in dbSNP:rs1800054)" FT /evidence="ECO:0000269|PubMed:10425038, FT ECO:0000269|PubMed:10534763, ECO:0000269|PubMed:10873394, FT ECO:0000269|PubMed:11897822, ECO:0000269|PubMed:17344846, FT ECO:0000269|PubMed:18384426, ECO:0000269|PubMed:8665503, FT ECO:0000269|PubMed:8797579, ECO:0000269|PubMed:9887333" FT /id="VAR_010798" FT VARIANT 68 FT /note="I -> V (found in a patient with familial pancreatic FT cancer; uncertain significance)" FT /evidence="ECO:0000269|PubMed:28726808" FT /id="VAR_083373" FT VARIANT 126 FT /note="D -> E (in dbSNP:rs2234997)" FT /evidence="ECO:0000269|PubMed:17344846, FT ECO:0000269|PubMed:9711876" FT /id="VAR_010799" FT VARIANT 140 FT /note="D -> H (in dbSNP:rs55633650)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041546" FT VARIANT 182 FT /note="V -> L (in dbSNP:rs3218707)" FT /evidence="ECO:0000269|PubMed:10534763" FT /id="VAR_010800" FT VARIANT 224 FT /note="K -> E (in AT; uncertain significance; FT dbSNP:rs145053092)" FT /evidence="ECO:0000269|PubMed:10817650" FT /id="VAR_010801" FT VARIANT 250 FT /note="R -> Q (in dbSNP:rs56123940)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041547" FT VARIANT 292 FT /note="P -> L (in AT; decrease phosphorylation of target FT proteins; increases protein abundance; dbSNP:rs747727055)" FT /evidence="ECO:0000269|PubMed:10873394, FT ECO:0000269|PubMed:19431188, ECO:0000269|PubMed:9463314" FT /id="VAR_010802" FT VARIANT 323 FT /note="I -> V (in AT; loss of protein expression; FT dbSNP:rs587781511)" FT /evidence="ECO:0000269|PubMed:10817650, FT ECO:0000269|PubMed:27664052" FT /id="VAR_010803" FT VARIANT 332 FT /note="Y -> C (in B-cell chronic lymphocytic leukemia)" FT /evidence="ECO:0000269|PubMed:9892178" FT /id="VAR_010804" FT VARIANT 333 FT /note="S -> F (in dbSNP:rs28904919)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041548" FT VARIANT 337 FT /note="R -> C (in a colorectal adenocarcinoma sample; FT somatic mutation; dbSNP:rs138398778)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041549" FT VARIANT 337 FT /note="R -> H (in a colorectal adenocarcinoma sample; FT somatic mutation; dbSNP:rs202160435)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041550" FT VARIANT 341 FT /note="V -> I (found in a patient with familial pancreatic FT cancer; uncertain significance)" FT /evidence="ECO:0000269|PubMed:28726808" FT /id="VAR_083374" FT VARIANT 350 FT /note="A -> T (in B-cell chronic lymphocytic leukemia; FT dbSNP:rs371713984)" FT /evidence="ECO:0000269|PubMed:10023947" FT /id="VAR_010805" FT VARIANT 352 FT /note="I -> T (in B-cell chronic lymphocytic leukemia; FT dbSNP:rs369203092)" FT /evidence="ECO:0000269|PubMed:10023947" FT /id="VAR_010806" FT VARIANT 374..3056 FT /note="Missing (in AT; uncertain significance)" FT /evidence="ECO:0000269|PubMed:10425038" FT /id="VAR_085061" FT VARIANT 393..3056 FT /note="Missing (in AT; uncertain significance; FT dbSNP:rs587776547)" FT /evidence="ECO:0000269|PubMed:10873394" FT /id="VAR_085062" FT VARIANT 410 FT /note="V -> A (in dbSNP:rs56128736)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041551" FT VARIANT 504 FT /note="N -> S (in dbSNP:rs56365018)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041552" FT VARIANT 514 FT /note="G -> D (in dbSNP:rs2235000)" FT /evidence="ECO:0000269|PubMed:17344846, FT ECO:0000269|PubMed:9711876" FT /id="VAR_010807" FT VARIANT 540 FT /note="C -> Y (in a colorectal adenocarcinoma sample; FT somatic mutation)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041553" FT VARIANT 546 FT /note="L -> V (no effect on phosphorylation of target FT proteins; dbSNP:rs2227924)" FT /evidence="ECO:0000269|PubMed:17344846, FT ECO:0000269|PubMed:19431188" FT /id="VAR_041554" FT VARIANT 570 FT /note="F -> S (in AT; dbSNP:rs777301065)" FT /evidence="ECO:0000269|PubMed:9887333" FT /id="VAR_010808" FT VARIANT 582 FT /note="F -> L (in dbSNP:rs2235006)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041555" FT VARIANT 597 FT /note="P -> L (found in a patient with familial pancreatic FT cancer; uncertain significance)" FT /evidence="ECO:0000269|PubMed:28726808" FT /id="VAR_083375" FT VARIANT 661 FT /note="D -> A (found in a patient with familial breast FT cancer; uncertain significance)" FT /evidence="ECO:0000269|PubMed:28202063" FT /id="VAR_083376" FT VARIANT 699 FT /note="E -> G (found in a patient with familial pancreatic FT cancer; uncertain significance)" FT /evidence="ECO:0000269|PubMed:28726808" FT /id="VAR_083377" FT VARIANT 705..707 FT /note="YSS -> FIP (in AT)" FT /evidence="ECO:0000269|PubMed:8797579, FT ECO:0000269|PubMed:9043869" FT /id="VAR_010809" FT VARIANT 707 FT /note="S -> P (in dbSNP:rs4986761)" FT /evidence="ECO:0000269|PubMed:10534763, FT ECO:0000269|PubMed:17344846, ECO:0000269|PubMed:28202063" FT /id="VAR_010810" FT VARIANT 759 FT /note="S -> G (found in a patient with familial pancreatic FT cancer; uncertain significance)" FT /evidence="ECO:0000269|PubMed:28726808" FT /id="VAR_083378" FT VARIANT 761 FT /note="T -> S (in dbSNP:rs2235011)" FT /id="VAR_056679" FT VARIANT 768 FT /note="N -> D (in AT)" FT /evidence="ECO:0000269|PubMed:9463314" FT /id="VAR_010812" FT VARIANT 785 FT /note="R -> C (in AT; dbSNP:rs587778065)" FT /evidence="ECO:0000269|PubMed:9887333" FT /id="VAR_010813" FT VARIANT 788 FT /note="S -> R (in dbSNP:rs641252)" FT /id="VAR_056680" FT VARIANT 813 FT /note="N -> S (found in a patient with familial pancreatic FT cancer; uncertain significance)" FT /evidence="ECO:0000269|PubMed:28726808" FT /id="VAR_083379" FT VARIANT 814 FT /note="D -> E (in dbSNP:rs3218695)" FT /id="VAR_056681" FT VARIANT 848 FT /note="E -> Q (in a lung adenocarcinoma sample; somatic FT mutation; dbSNP:rs879254046)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041556" FT VARIANT 858 FT /note="F -> L (in dbSNP:rs1800056)" FT /evidence="ECO:0000269|PubMed:10534763, FT ECO:0000269|PubMed:17344846, ECO:0000269|PubMed:18384426, FT ECO:0000269|PubMed:28202063, ECO:0000269|PubMed:8797579, FT ECO:0000269|PubMed:9043869, ECO:0000269|PubMed:9792409, FT ECO:0000269|PubMed:9887333" FT /id="VAR_010814" FT VARIANT 869 FT /note="A -> G (found in a patient with familial pancreatic FT cancer; uncertain significance)" FT /evidence="ECO:0000269|PubMed:28726808" FT /id="VAR_083380" FT VARIANT 872 FT /note="P -> S (in dbSNP:rs3218673)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041557" FT VARIANT 897 FT /note="F -> I (found in a patient with familial pancreatic FT cancer; uncertain significance)" FT /evidence="ECO:0000269|PubMed:28726808" FT /id="VAR_083381" FT VARIANT 924 FT /note="R -> W (found in a patient with familial breast FT cancer; uncertain significance; dbSNP:rs55723361)" FT /evidence="ECO:0000269|PubMed:17344846, FT ECO:0000269|PubMed:28202063" FT /id="VAR_041558" FT VARIANT 935 FT /note="T -> A (in dbSNP:rs35813135)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041559" FT VARIANT 935 FT /note="T -> M (in dbSNP:rs3218708)" FT /id="VAR_056682" FT VARIANT 942 FT /note="L -> F (in dbSNP:rs3218688)" FT /id="VAR_056683" FT VARIANT 950 FT /note="L -> R (in AT; dbSNP:rs786203054)" FT /evidence="ECO:0000269|PubMed:10873394" FT /id="VAR_010815" FT VARIANT 1001 FT /note="L -> Q (in AT; risk factor for T-cell acute FT lymphoblastic leukemia)" FT /evidence="ECO:0000269|PubMed:9463314" FT /id="VAR_010816" FT VARIANT 1040 FT /note="M -> V (in dbSNP:rs3092857)" FT /evidence="ECO:0000269|PubMed:9288106" FT /id="VAR_010817" FT VARIANT 1046 FT /note="L -> P (in AT; loss of protein expression; FT dbSNP:rs568461905)" FT /evidence="ECO:0000269|PubMed:27664052" FT /id="VAR_077237" FT VARIANT 1054 FT /note="P -> R (in AT; likely benign; no effect on FT phosphorylation of target proteins; dbSNP:rs1800057)" FT /evidence="ECO:0000269|PubMed:10023947, FT ECO:0000269|PubMed:10217116, ECO:0000269|PubMed:17344846, FT ECO:0000269|PubMed:18384426, ECO:0000269|PubMed:19431188, FT ECO:0000269|PubMed:28202063, ECO:0000269|PubMed:8665503, FT ECO:0000269|PubMed:8797579, ECO:0000269|PubMed:9043869, FT ECO:0000269|PubMed:9792409, ECO:0000269|PubMed:9887333" FT /id="VAR_010818" FT VARIANT 1082 FT /note="H -> L (in AT; uncertain significance)" FT /evidence="ECO:0000269|PubMed:10873394" FT /id="VAR_010819" FT VARIANT 1091 FT /note="E -> D (in AT)" FT /evidence="ECO:0000269|PubMed:9792409" FT /id="VAR_010820" FT VARIANT 1171..3056 FT /note="Missing (in AT; uncertain significance; increases FT protein abundance)" FT /evidence="ECO:0000269|PubMed:10873394" FT /id="VAR_085063" FT VARIANT 1179 FT /note="S -> F (in a gastric adenocarcinoma sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041560" FT VARIANT 1255 FT /note="L -> V (found in a patient with early-onset breast FT cancer; uncertain significance)" FT /evidence="ECO:0000269|PubMed:18384426" FT /id="VAR_083382" FT VARIANT 1313 FT /note="E -> Q (in dbSNP:rs3092841)" FT /id="VAR_056684" FT VARIANT 1321 FT /note="M -> I (in dbSNP:rs35184530)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041561" FT VARIANT 1322 FT /note="L -> I (no effect on phosphorylation of target FT proteins; dbSNP:rs144535256)" FT /evidence="ECO:0000269|PubMed:19431188" FT /id="VAR_080300" FT VARIANT 1380 FT /note="H -> Y (in dbSNP:rs3092856)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041562" FT VARIANT 1382 FT /note="P -> S (in dbSNP:rs55859590)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041563" FT VARIANT 1407 FT /note="I -> T (in T-prolymphocytic leukemia; FT dbSNP:rs1234250980)" FT /evidence="ECO:0000269|PubMed:9288106" FT /id="VAR_010821" FT VARIANT 1420 FT /note="L -> F (in dbSNP:rs1800058)" FT /evidence="ECO:0000269|PubMed:10534763, FT ECO:0000269|PubMed:17344846, ECO:0000269|PubMed:8665503, FT ECO:0000269|PubMed:8797579" FT /id="VAR_010822" FT VARIANT 1420 FT /note="L -> P (in AT)" FT /evidence="ECO:0000269|PubMed:10817650" FT /id="VAR_010823" FT VARIANT 1427 FT /note="A -> T (in dbSNP:rs2229021)" FT /id="VAR_056685" FT VARIANT 1463 FT /note="F -> S (found in B-cell non-Hodgkin lymphoma; FT uncertain significance)" FT /evidence="ECO:0000269|PubMed:9288106" FT /id="VAR_010825" FT VARIANT 1465 FT /note="L -> P (in AT; decreased phosphorylation of target FT proteins; dbSNP:rs730881391)" FT /evidence="ECO:0000269|PubMed:10234507, FT ECO:0000269|PubMed:19431188" FT /id="VAR_010826" FT VARIANT 1466..3056 FT /note="Missing (in AT; uncertain significance; FT dbSNP:rs730881369)" FT /evidence="ECO:0000269|PubMed:10425038" FT /id="VAR_085064" FT VARIANT 1469 FT /note="I -> M (in a renal papillary cancer sample; somatic FT mutation; dbSNP:rs775047783)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041564" FT VARIANT 1474 FT /note="H -> D (found in a patient with familial pancreatic FT cancer; uncertain significance)" FT /evidence="ECO:0000269|PubMed:28726808" FT /id="VAR_083383" FT VARIANT 1475 FT /note="Y -> C (in dbSNP:rs34640941)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041565" FT VARIANT 1488 FT /note="L -> V (found in a patient with familial pancreatic FT cancer; uncertain significance)" FT /evidence="ECO:0000269|PubMed:28726808" FT /id="VAR_083384" FT VARIANT 1541 FT /note="L -> F (in dbSNP:rs3092849)" FT /id="VAR_056686" FT VARIANT 1566 FT /note="P -> R (in AT)" FT /evidence="ECO:0000269|PubMed:9792409" FT /id="VAR_010827" FT VARIANT 1570 FT /note="V -> A (in dbSNP:rs140856217)" FT /evidence="ECO:0000269|PubMed:10534763" FT /id="VAR_010828" FT VARIANT 1650 FT /note="N -> S (in dbSNP:rs55870064)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041566" FT VARIANT 1682 FT /note="D -> H (in T-prolymphocytic leukemia; FT dbSNP:rs121434217)" FT /evidence="ECO:0000269|PubMed:9288106" FT /id="VAR_010829" FT VARIANT 1691 FT /note="S -> R (in AT, B-cell chronic lymphocytic leukemia FT and familial cancer patients; no effect on phosphorylation FT of target proteins; dbSNP:rs1800059)" FT /evidence="ECO:0000269|PubMed:19431188, FT ECO:0000269|PubMed:28202063, ECO:0000269|PubMed:8797579, FT ECO:0000269|PubMed:9463314, ECO:0000269|PubMed:9892178" FT /id="VAR_010830" FT VARIANT 1729 FT /note="V -> L (in dbSNP:rs3092907)" FT /id="VAR_056687" FT VARIANT 1730..3056 FT /note="Missing (in AT; uncertain significance; FT dbSNP:rs764389018)" FT /evidence="ECO:0000269|PubMed:10425038" FT /id="VAR_085065" FT VARIANT 1739 FT /note="N -> T (in a colorectal adenocarcinoma sample; FT somatic mutation)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041567" FT VARIANT 1743 FT /note="T -> I (in AT; decreased phosphorylation of target FT proteins; dbSNP:rs587779844)" FT /evidence="ECO:0000269|PubMed:19431188, FT ECO:0000269|PubMed:9463314" FT /id="VAR_010831" FT VARIANT 1812..1813 FT /note="AF -> V (in AT)" FT /evidence="ECO:0000269|PubMed:9497252" FT /id="VAR_010832" FT VARIANT 1839..3056 FT /note="Missing (in AT; uncertain significance; reduces FT protein abundance)" FT /evidence="ECO:0000269|PubMed:10873394" FT /id="VAR_085066" FT VARIANT 1853 FT /note="D -> N (in dbSNP:rs1801516)" FT /evidence="ECO:0000269|PubMed:10397742, FT ECO:0000269|PubMed:10425038, ECO:0000269|PubMed:10534763, FT ECO:0000269|PubMed:17344846, ECO:0000269|PubMed:18384426, FT ECO:0000269|PubMed:9711876, ECO:0000269|PubMed:9887333" FT /id="VAR_010833" FT VARIANT 1853 FT /note="D -> V (might contribute to B-cell chronic FT lymphocytic leukemia; dbSNP:rs1801673)" FT /evidence="ECO:0000269|PubMed:10397742, FT ECO:0000269|PubMed:10817650, ECO:0000269|PubMed:17344846, FT ECO:0000269|PubMed:28202063, ECO:0000269|PubMed:9872980, FT ECO:0000269|PubMed:9887333" FT /id="VAR_010834" FT VARIANT 1910 FT /note="L -> H (in T-prolymphocytic leukemia)" FT /evidence="ECO:0000269|PubMed:9288106" FT /id="VAR_010835" FT VARIANT 1913 FT /note="V -> G (in AT; dbSNP:rs1060501688)" FT /evidence="ECO:0000269|PubMed:9887333" FT /id="VAR_010836" FT VARIANT 1916 FT /note="M -> I (in a breast pleomorphic lobular carcinoma FT sample; somatic mutation)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041568" FT VARIANT 1945 FT /note="A -> T (in a colorectal adenocarcinoma sample; FT somatic mutation)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041569" FT VARIANT 1953 FT /note="T -> R (in B-cell chronic lymphocytic leukemia)" FT /evidence="ECO:0000269|PubMed:10397742" FT /id="VAR_010837" FT VARIANT 1961 FT /note="Y -> C (found in a patient with familial pancreatic FT cancer; uncertain significance; also found in a lung FT adenocarcinoma sample; uncertain significance; decreased FT phosphorylation of target proteins; dbSNP:rs56399311)" FT /evidence="ECO:0000269|PubMed:17344846, FT ECO:0000269|PubMed:19431188, ECO:0000269|PubMed:28726808" FT /id="VAR_041570" FT VARIANT 1983 FT /note="S -> N (in dbSNP:rs659243)" FT /evidence="ECO:0000269|PubMed:16554811" FT /id="VAR_041571" FT VARIANT 1991 FT /note="E -> D (in a renal clear cell carcinoma sample; FT somatic mutation; dbSNP:rs587782274)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041572" FT VARIANT 2016 FT /note="D -> G (in AT; uncertain significance; FT dbSNP:rs587781302)" FT /evidence="ECO:0000269|PubMed:10425038, FT ECO:0000269|PubMed:9887333" FT /id="VAR_010838" FT VARIANT 2023 FT /note="G -> R (in AT; loss of protein expression; FT dbSNP:rs11212587)" FT /evidence="ECO:0000269|PubMed:27664052" FT /id="VAR_077238" FT VARIANT 2034 FT /note="R -> Q (in dbSNP:rs3218670)" FT /id="VAR_056688" FT VARIANT 2063 FT /note="G -> E (in AT; uncertain significance; reduces FT protein abundance; dbSNP:rs866290641)" FT /evidence="ECO:0000269|PubMed:10873394" FT /id="VAR_010839" FT VARIANT 2067 FT /note="A -> D (in AT; dbSNP:rs397514577)" FT /evidence="ECO:0000269|PubMed:9887333" FT /id="VAR_010840" FT VARIANT 2068 FT /note="L -> S (in AT; decreased protein abundance; loss of FT DNA damage induced protein autophosphorylation; FT dbSNP:rs1555114558)" FT /evidence="ECO:0000269|PubMed:27664052" FT /id="VAR_077239" FT VARIANT 2079 FT /note="V -> I (in dbSNP:rs1800060)" FT /evidence="ECO:0000269|PubMed:8665503" FT /id="VAR_010841" FT VARIANT 2080 FT /note="Y -> D (in AT; loss of DNA damage induced protein FT autophosphorylation; dbSNP:rs1064795467)" FT /evidence="ECO:0000269|PubMed:27664052" FT /id="VAR_077240" FT VARIANT 2105 FT /note="R -> T (found in a patient with early-onset breast FT cancer; uncertain significance)" FT /evidence="ECO:0000269|PubMed:18384426" FT /id="VAR_083385" FT VARIANT 2139 FT /note="E -> G (in T-prolymphocytic leukemia; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:9488043" FT /id="VAR_010842" FT VARIANT 2164 FT /note="E -> K (in T-prolymphocytic leukemia; FT dbSNP:rs1317619286)" FT /evidence="ECO:0000269|PubMed:9288106" FT /id="VAR_010843" FT VARIANT 2218 FT /note="S -> C (in AT)" FT /evidence="ECO:0000269|PubMed:10817650" FT /id="VAR_010844" FT VARIANT 2224..2227 FT /note="MALR -> IS (in AT; uncertain significance)" FT /evidence="ECO:0000269|PubMed:10425038" FT /id="VAR_010845" FT VARIANT 2227 FT /note="R -> C (in AT; uncertain significance; reduces FT protein abundance; dbSNP:rs564652222)" FT /evidence="ECO:0000269|PubMed:10873394, FT ECO:0000269|PubMed:9887333" FT /id="VAR_010846" FT VARIANT 2246..2252 FT /note="CIKDILT -> H (in AT; uncertain significance)" FT /evidence="ECO:0000269|PubMed:10425038, FT ECO:0000269|PubMed:10873394" FT /id="VAR_010847" FT VARIANT 2274 FT /note="A -> T (in B-cell chronic lymphocytic leukemia; FT uncertain significance; no effect on phosphorylation of FT target proteins; dbSNP:rs567060474)" FT /evidence="ECO:0000269|PubMed:10023947, FT ECO:0000269|PubMed:19431188" FT /id="VAR_010848" FT VARIANT 2287 FT /note="G -> A (found in a patient with familial pancreatic FT cancer; uncertain significance; dbSNP:rs1800061)" FT /evidence="ECO:0000269|PubMed:28726808, FT ECO:0000269|PubMed:8665503" FT /id="VAR_010849" FT VARIANT 2307 FT /note="L -> F (found in patients with familial pancreatic FT cancer; uncertain significance; also found in a lung FT adenocarcinoma sample; uncertain significance; FT dbSNP:rs56009889)" FT /evidence="ECO:0000269|PubMed:17344846, FT ECO:0000269|PubMed:28726808" FT /id="VAR_041573" FT VARIANT 2332 FT /note="L -> P (in dbSNP:rs4988111)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041574" FT VARIANT 2335 FT /note="T -> K (in dbSNP:rs3092831)" FT /id="VAR_056689" FT VARIANT 2356 FT /note="I -> F (in a renal clear cell carcinoma sample; FT somatic mutation; dbSNP:rs876658517)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041575" FT VARIANT 2396 FT /note="T -> S (found in a patient with T-prolymphocytic FT leukemia; uncertain significance; also found in a patient FT with early-onset breast cancer; uncertain significance; FT dbSNP:rs370559102)" FT /evidence="ECO:0000269|PubMed:18384426, FT ECO:0000269|PubMed:9288106" FT /id="VAR_010850" FT VARIANT 2408 FT /note="S -> L (in a colorectal adenocarcinoma sample; FT somatic mutation; dbSNP:rs730881315)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041576" FT VARIANT 2418 FT /note="K -> KK (in mantle cell lymphoma)" FT /evidence="ECO:0000269|PubMed:10397742, FT ECO:0000269|PubMed:10706620" FT /id="VAR_010851" FT VARIANT 2420 FT /note="A -> P (in B-cell chronic lymphocytic leukemia)" FT /evidence="ECO:0000269|PubMed:10397742" FT /id="VAR_010852" FT VARIANT 2423 FT /note="E -> G (in mantle cell lymphoma; dbSNP:rs121434221)" FT /evidence="ECO:0000269|PubMed:10397742, FT ECO:0000269|PubMed:10706620" FT /id="VAR_010853" FT VARIANT 2424 FT /note="V -> G (in AT; also found in B-cell chronic FT lymphocytic leukemia and T-prolymphocytic leukemia; risk FT factor for breast cancer; decreased phosphorylation of FT target proteins; dbSNP:rs28904921)" FT /evidence="ECO:0000269|PubMed:19431188, FT ECO:0000269|PubMed:8755918, ECO:0000269|PubMed:9288106, FT ECO:0000269|PubMed:9463314, ECO:0000269|PubMed:9892178" FT /id="VAR_010854" FT VARIANT 2427..2428 FT /note="Missing (in AT; also found in T-prolymphocytic FT leukemia; lack of phosphorylation of target proteins)" FT /evidence="ECO:0000269|PubMed:19431188, FT ECO:0000269|PubMed:7792600, ECO:0000269|PubMed:8845835, FT ECO:0000269|PubMed:9463314" FT /id="VAR_010855" FT VARIANT 2438 FT /note="T -> I (in dbSNP:rs147604227)" FT /evidence="ECO:0000269|PubMed:10817650, FT ECO:0000269|PubMed:8808599" FT /id="VAR_010856" FT VARIANT 2442 FT /note="Q -> P (in T-prolymphocytic leukemia; also in a lung FT adenocarcinoma sample; somatic mutation)" FT /evidence="ECO:0000269|PubMed:17344846, FT ECO:0000269|PubMed:9288106" FT /id="VAR_010857" FT VARIANT 2443 FT /note="R -> Q (in a colorectal adenocarcinoma sample; FT somatic mutation; dbSNP:rs587782310)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041577" FT VARIANT 2464 FT /note="C -> R (found in patients with familial pancreatic FT cancer; uncertain significance; also found in a small cell FT lung cancer sample; uncertain significance; FT dbSNP:rs55801750)" FT /evidence="ECO:0000269|PubMed:17344846, FT ECO:0000269|PubMed:28726808" FT /id="VAR_041578" FT VARIANT 2470 FT /note="Y -> D (in AT; dbSNP:rs876659365)" FT /evidence="ECO:0000269|PubMed:9887333" FT /id="VAR_010858" FT VARIANT 2486 FT /note="R -> G (in T-prolymphocytic leukemia)" FT /evidence="ECO:0000269|PubMed:9573030" FT /id="VAR_010859" FT VARIANT 2491 FT /note="W -> R (in AT)" FT /evidence="ECO:0000269|PubMed:9792410" FT /id="VAR_010860" FT VARIANT 2492 FT /note="L -> R (in dbSNP:rs56399857)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041579" FT VARIANT 2524 FT /note="A -> P (found in a patient with familial pancreatic FT cancer; uncertain significance)" FT /evidence="ECO:0000269|PubMed:28726808" FT /id="VAR_083386" FT VARIANT 2531 FT /note="M -> T (found in patients with familial pancreatic FT cancer; uncertain significance)" FT /evidence="ECO:0000269|PubMed:28726808" FT /id="VAR_083387" FT VARIANT 2546..2548 FT /note="Missing (in AT; also found in T-prolymphocytic FT leukemia and T-cell acute lymphoblastic leukemia; lack of FT phosphorylation of target proteins)" FT /evidence="ECO:0000269|PubMed:10817650, FT ECO:0000269|PubMed:19431188, ECO:0000269|PubMed:7792600, FT ECO:0000269|PubMed:8755918, ECO:0000269|PubMed:8789452, FT ECO:0000269|PubMed:8797579, ECO:0000269|PubMed:8808599, FT ECO:0000269|PubMed:8845835, ECO:0000269|PubMed:9150358, FT ECO:0000269|PubMed:9288106, ECO:0000269|PubMed:9463314" FT /id="VAR_010861" FT VARIANT 2547..2549 FT /note="Missing (in AT; dbSNP:rs587776547)" FT /evidence="ECO:0000269|PubMed:10873394" FT /id="VAR_085067" FT VARIANT 2554 FT /note="H -> D (in AT; lack of phosphorylation of target FT proteins)" FT /evidence="ECO:0000269|PubMed:19431188, FT ECO:0000269|PubMed:9463314" FT /id="VAR_010862" FT VARIANT 2570 FT /note="E -> G (in dbSNP:rs28904920)" FT /id="VAR_056690" FT VARIANT 2625..2626 FT /note="DA -> EP (in AT; dbSNP:rs267606668)" FT /evidence="ECO:0000269|PubMed:9521587" FT /id="VAR_010864" FT VARIANT 2625 FT /note="D -> E (in AT; uncertain significance; FT dbSNP:rs1196903858)" FT /evidence="ECO:0000269|PubMed:10873394" FT /id="VAR_085068" FT VARIANT 2625 FT /note="D -> Q (in AT; requires 2 nucleotide substitutions)" FT /evidence="ECO:0000269|PubMed:10817650" FT /id="VAR_010863" FT VARIANT 2626 FT /note="A -> P (in AT; uncertain significance; FT dbSNP:rs267606669)" FT /evidence="ECO:0000269|PubMed:10873394" FT /id="VAR_085069" FT VARIANT 2627 FT /note="Y -> H (in AT; loss of protein expression)" FT /evidence="ECO:0000269|PubMed:27664052" FT /id="VAR_077241" FT VARIANT 2640 FT /note="T -> I (in dbSNP:rs4988125)" FT /id="VAR_056691" FT VARIANT 2656 FT /note="L -> P (in AT; dbSNP:rs121434218)" FT /evidence="ECO:0000269|PubMed:9450874" FT /id="VAR_010865" FT VARIANT 2662 FT /note="Missing (in AT)" FT /evidence="ECO:0000269|PubMed:9887333" FT /id="VAR_010866" FT VARIANT 2664 FT /note="Missing (in AT; uncertain significance; FT dbSNP:rs1471563800)" FT /evidence="ECO:0000269|PubMed:10425038" FT /id="VAR_085070" FT VARIANT 2666 FT /note="T -> A (in a lung adenocarcinoma sample; somatic FT mutation; dbSNP:rs745775382)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041580" FT VARIANT 2668 FT /note="E -> G (in AT; uncertain significance; no effect on FT phosphorylation of target proteins)" FT /evidence="ECO:0000269|PubMed:19431188, FT ECO:0000269|PubMed:9463314" FT /id="VAR_010868" FT VARIANT 2695 FT /note="G -> A (in T-prolymphocytic leukemia and B-cell FT chronic lymphocytic leukemia)" FT /evidence="ECO:0000269|PubMed:10023947, FT ECO:0000269|PubMed:9288106" FT /id="VAR_010869" FT VARIANT 2702 FT /note="I -> R (in AT; dbSNP:rs876659735)" FT /evidence="ECO:0000269|PubMed:10873394" FT /id="VAR_010870" FT VARIANT 2709 FT /note="G -> S (in dbSNP:rs3218680)" FT /id="VAR_056692" FT VARIANT 2719 FT /note="R -> H (found in a patient with early-onset breast FT cancer; uncertain significance; dbSNP:rs55982963)" FT /evidence="ECO:0000269|PubMed:17344846, FT ECO:0000269|PubMed:18384426" FT /id="VAR_041581" FT VARIANT 2722 FT /note="L -> R (in T-prolymphocytic leukemia)" FT /evidence="ECO:0000269|PubMed:9288106" FT /id="VAR_010871" FT VARIANT 2725 FT /note="D -> G (found in T-prolymphocytic leukemia; FT uncertain significance; dbSNP:rs1555128314)" FT /evidence="ECO:0000269|PubMed:9334731" FT /id="VAR_010872" FT VARIANT 2725 FT /note="D -> V (in T-prolymphocytic leukemia)" FT /evidence="ECO:0000269|PubMed:9288106" FT /id="VAR_010873" FT VARIANT 2726 FT /note="A -> V (in AT; uncertain significance)" FT /evidence="ECO:0000269|PubMed:10425038" FT /id="VAR_010874" FT VARIANT 2732 FT /note="F -> L (in T-prolymphocytic leukemia; FT dbSNP:rs876659619)" FT /evidence="ECO:0000269|PubMed:9288106" FT /id="VAR_010875" FT VARIANT 2765 FT /note="G -> S (may contribute to breast cancer; lack of FT phosphorylation of target proteins; dbSNP:rs748634900)" FT /evidence="ECO:0000269|PubMed:10534763, FT ECO:0000269|PubMed:19431188" FT /id="VAR_010876" FT VARIANT 2810 FT /note="K -> Q (found in a patient with familial pancreatic FT cancer; uncertain significance)" FT /evidence="ECO:0000269|PubMed:28726808" FT /id="VAR_083388" FT VARIANT 2810 FT /note="Missing (in T-prolymphocytic leukemia)" FT /evidence="ECO:0000269|PubMed:9288106" FT /id="VAR_010877" FT VARIANT 2824 FT /note="C -> Y (in AT; dbSNP:rs876660927)" FT /evidence="ECO:0000269|PubMed:9150358" FT /id="VAR_010878" FT VARIANT 2827 FT /note="F -> C (in AT; mild; decreased phosphorylation of FT target proteins; dbSNP:rs121434216)" FT /evidence="ECO:0000269|PubMed:19431188, FT ECO:0000269|PubMed:8755918, ECO:0000269|PubMed:9463314" FT /id="VAR_010879" FT VARIANT 2829 FT /note="P -> L (in AT; dbSNP:rs938431501)" FT /evidence="ECO:0000269|PubMed:9711876" FT /id="VAR_010880" FT VARIANT 2832 FT /note="R -> C (in AT; also found in B-cell non-Hodgkin FT lymphoma; increases protein abundance; dbSNP:rs587779872)" FT /evidence="ECO:0000269|PubMed:10817650, FT ECO:0000269|PubMed:10873394, ECO:0000269|PubMed:9288106, FT ECO:0000269|PubMed:9443866" FT /id="VAR_010881" FT VARIANT 2832 FT /note="R -> H (found in a patient with familial pancreatic FT cancer; uncertain significance)" FT /evidence="ECO:0000269|PubMed:28726808" FT /id="VAR_083389" FT VARIANT 2834 FT /note="F -> L (in AT; decreased protein abundance)" FT /evidence="ECO:0000269|PubMed:27664052" FT /id="VAR_077242" FT VARIANT 2842 FT /note="P -> R (in a lung adenocarcinoma sample; somatic FT mutation; dbSNP:rs879254065)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041582" FT VARIANT 2849..3056 FT /note="Missing (in AT; uncertain significance; FT dbSNP:rs587778080)" FT /evidence="ECO:0000269|PubMed:10425038" FT /id="VAR_085071" FT VARIANT 2849 FT /note="R -> P (in AT; dbSNP:rs587782202)" FT /evidence="ECO:0000269|PubMed:9887333" FT /id="VAR_010882" FT VARIANT 2855..2856 FT /note="SV -> RI (in AT; lack of phosphorylation of target FT proteins; dbSNP:rs587781353)" FT /evidence="ECO:0000269|PubMed:10817650, FT ECO:0000269|PubMed:19431188, ECO:0000269|PubMed:9872980" FT /id="VAR_010884" FT VARIANT 2855 FT /note="S -> R (in AT; uncertain significance; FT dbSNP:rs780905851)" FT /evidence="ECO:0000269|PubMed:10425038" FT /id="VAR_010883" FT VARIANT 2860 FT /note="Missing (in AT)" FT /evidence="ECO:0000269|PubMed:7792600, FT ECO:0000269|PubMed:8845835" FT /id="VAR_010885" FT VARIANT 2867 FT /note="G -> R (in AT)" FT /evidence="ECO:0000269|PubMed:8698354, FT ECO:0000269|PubMed:9887333" FT /id="VAR_010886" FT VARIANT 2870 FT /note="D -> N (in dbSNP:rs55798854)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041583" FT VARIANT 2871..2872 FT /note="RH -> S (in T-prolymphocytic leukemia)" FT /evidence="ECO:0000269|PubMed:9288106" FT /id="VAR_010887" FT VARIANT 2890 FT /note="L -> V (in T-prolymphocytic leukemia; FT dbSNP:rs587779874)" FT /evidence="ECO:0000269|PubMed:9288106, FT ECO:0000269|PubMed:9488043" FT /id="VAR_010888" FT VARIANT 2904 FT /note="E -> G (in AT; dbSNP:rs786202826)" FT /evidence="ECO:0000269|PubMed:8845835" FT /id="VAR_010889" FT VARIANT 2909 FT /note="R -> G (in AT)" FT /evidence="ECO:0000269|PubMed:9792410" FT /id="VAR_010890" FT VARIANT 2974 FT /note="P -> L (found in a patient with familial pancreatic FT cancer; uncertain significance)" FT /evidence="ECO:0000269|PubMed:28726808" FT /id="VAR_083390" FT VARIANT 3003 FT /note="N -> D (in AT; decreased protein abundance; FT dbSNP:rs1137889)" FT /evidence="ECO:0000269|PubMed:27664052, FT ECO:0000269|PubMed:7792600, ECO:0000269|PubMed:8589678, FT ECO:0000269|PubMed:8665503" FT /id="VAR_077243" FT VARIANT 3006 FT /note="A -> P (found in T-prolymphocytic leukemia; FT uncertain significance; dbSNP:rs876658767)" FT /evidence="ECO:0000269|PubMed:9334731" FT /id="VAR_010892" FT VARIANT 3008 FT /note="R -> C (in AT; also found in T-prolymphocytic FT leukemia and mantle cell lymphoma; lack of phosphorylation FT of target proteins; dbSNP:rs587782292)" FT /evidence="ECO:0000269|PubMed:10706620, FT ECO:0000269|PubMed:10817650, ECO:0000269|PubMed:19431188, FT ECO:0000269|PubMed:9334731, ECO:0000269|PubMed:9488043, FT ECO:0000269|PubMed:9872980" FT /id="VAR_010893" FT VARIANT 3008 FT /note="R -> H (in B-cell chronic lymphocytic leukemia; FT dbSNP:rs587781894)" FT /evidence="ECO:0000269|PubMed:10397742" FT /id="VAR_010894" FT VARIANT 3018 FT /note="K -> N (in B-cell chronic lymphocytic leukemia)" FT /evidence="ECO:0000269|PubMed:10397742" FT /id="VAR_010895" FT VARIANT 3029 FT /note="G -> D (found in a patient with familial pancreatic FT cancer; uncertain significance)" FT /evidence="ECO:0000269|PubMed:28726808" FT /id="VAR_083391" FT VARIANT 3056 FT /note="V -> L (found in a patient with familial pancreatic FT cancer; uncertain significance)" FT /evidence="ECO:0000269|PubMed:28726808" FT /id="VAR_083392" FT MUTAGEN 367 FT /note="S->A: Loss of IR-induced S-367 autophosphorylation. FT Reduced correction of cell cycle checkpoint defects and FT DNA-repair activity. No effect on S-1893 nor S-1981 FT autophosphorylation." FT /evidence="ECO:0000269|PubMed:16858402" FT MUTAGEN 1807 FT /note="K->E: Decreased phosphorylation of target proteins." FT /evidence="ECO:0000269|PubMed:19431188" FT MUTAGEN 1893 FT /note="S->A: Loss of IR-induced S-1893 autophosphorylation. FT Reduced correction of cell cycle checkpoint defects and FT DNA-repair activity. No effect on S-367 nor S-1981 FT autophosphorylation." FT /evidence="ECO:0000269|PubMed:16858402" FT MUTAGEN 1941 FT /note="V->L: Decreased phosphorylation of target proteins." FT /evidence="ECO:0000269|PubMed:19431188" FT MUTAGEN 1981 FT /note="S->A: Loss of IR-induced S-1981 autophosphorylation. FT Reduced correction of cell cycle checkpoint defects and FT DNA-repair activity. No effect on S-367 nor S-1893 FT autophosphorylation. No dimer disruption." FT /evidence="ECO:0000269|PubMed:12556884, FT ECO:0000269|PubMed:16858402" FT MUTAGEN 1981 FT /note="S->D,E: Disrupts the dimer." FT /evidence="ECO:0000269|PubMed:12556884, FT ECO:0000269|PubMed:16858402" FT MUTAGEN 2019 FT /note="Y->C: Loss of phosphorylation of target proteins." FT /evidence="ECO:0000269|PubMed:19431188" FT MUTAGEN 2039 FT /note="E->K: Decreased phosphorylation of target proteins." FT /evidence="ECO:0000269|PubMed:19431188" FT MUTAGEN 2338 FT /note="L->P: Loss of phosphorylation of target proteins." FT /evidence="ECO:0000269|PubMed:19431188" FT MUTAGEN 2394 FT /note="S->L: Loss of phosphorylation of target proteins." FT /evidence="ECO:0000269|PubMed:19431188" FT MUTAGEN 2452 FT /note="L->P: Loss of phosphorylation of target proteins." FT /evidence="ECO:0000269|PubMed:19431188" FT MUTAGEN 2685 FT /note="S->T: No effect on phosphorylation of target FT proteins." FT /evidence="ECO:0000269|PubMed:19431188" FT MUTAGEN 2699 FT /note="P->L: Loss of phosphorylation of target proteins." FT /evidence="ECO:0000269|PubMed:19431188" FT MUTAGEN 2708 FT /note="D->N: Decreased phosphorylation of target proteins." FT /evidence="ECO:0000269|PubMed:19431188" FT MUTAGEN 2730 FT /note="Q->P: Loss of phosphorylation of target proteins." FT /evidence="ECO:0000269|PubMed:19431188" FT MUTAGEN 2870 FT /note="D->A: Loss of kinase activity." FT /evidence="ECO:0000269|PubMed:9733515" FT MUTAGEN 2875 FT /note="N->K: Loss of kinase activity." FT /evidence="ECO:0000269|PubMed:9733515" FT MUTAGEN 3016 FT /note="K->Q: Mimics acetylation, preventing FT dephosphorylation and subsequent ATM deactivation during FT the late stage of DNA damage response." FT /evidence="ECO:0000269|PubMed:30944854" FT MUTAGEN 3016 FT /note="K->R: Loss of DNA damage-inducible acetylation. FT Retains constitutive kinase activity, but blocks DNA FT damage-induced kinase activation. Disrupts dimer and FT abolishes S-1981 autophosphorylation." FT /evidence="ECO:0000269|PubMed:17923702" FT MUTAGEN 3018 FT /note="K->R: Retains DNA damage-inducible acetylation and FT S-1981 autophosphorylation." FT /evidence="ECO:0000269|PubMed:17923702" FT MUTAGEN 3047 FT /note="R->Q: Abolished interaction with PEX5 and FT translocation to peroxisomes in response to reactive oxygen FT species (ROS)." FT /evidence="ECO:0000269|PubMed:26344566" FT CONFLICT 46 FT /note="H -> N (in Ref. 7; CAA62603)" FT /evidence="ECO:0000305" FT CONFLICT 56 FT /note="N -> I (in Ref. 7; CAA62603)" FT /evidence="ECO:0000305" FT CONFLICT 313 FT /note="Y -> N (in Ref. 7; CAA62603)" FT /evidence="ECO:0000305" FT CONFLICT 488 FT /note="W -> G (in Ref. 7; CAA62603)" FT /evidence="ECO:0000305" FT CONFLICT 554 FT /note="T -> A (in Ref. 1; AAC50289)" FT /evidence="ECO:0000305" FT CONFLICT 750 FT /note="K -> N (in Ref. 1; AAC50289)" FT /evidence="ECO:0000305" FT CONFLICT 754 FT /note="Q -> K (in Ref. 7; CAA62603)" FT /evidence="ECO:0000305" FT CONFLICT 887 FT /note="E -> G (in Ref. 7; CAA62603)" FT /evidence="ECO:0000305" FT CONFLICT 1003 FT /note="Q -> L (in Ref. 7; CAA62603)" FT /evidence="ECO:0000305" FT CONFLICT 1049 FT /note="L -> W (in Ref. 7; CAA62603)" FT /evidence="ECO:0000305" FT CONFLICT 1089 FT /note="A -> V (in Ref. 7; CAA62603)" FT /evidence="ECO:0000305" FT HELIX 6..17 FT /evidence="ECO:0007829|PDB:7SIC" FT HELIX 20..33 FT /evidence="ECO:0007829|PDB:7SIC" FT HELIX 36..41 FT /evidence="ECO:0007829|PDB:7SIC" FT HELIX 57..73 FT /evidence="ECO:0007829|PDB:7SIC" FT HELIX 90..108 FT /evidence="ECO:0007829|PDB:7SIC" FT STRAND 109..112 FT /evidence="ECO:0007829|PDB:7SIC" FT HELIX 117..129 FT /evidence="ECO:0007829|PDB:7SIC" FT STRAND 130..133 FT /evidence="ECO:0007829|PDB:7SIC" FT HELIX 135..148 FT /evidence="ECO:0007829|PDB:7SIC" FT TURN 149..151 FT /evidence="ECO:0007829|PDB:7SIC" FT HELIX 153..158 FT /evidence="ECO:0007829|PDB:7SIC" FT HELIX 161..176 FT /evidence="ECO:0007829|PDB:7SIC" FT HELIX 183..201 FT /evidence="ECO:0007829|PDB:7SIC" FT HELIX 207..209 FT /evidence="ECO:0007829|PDB:7SIC" FT HELIX 210..222 FT /evidence="ECO:0007829|PDB:7SIC" FT STRAND 223..225 FT /evidence="ECO:0007829|PDB:7NI5" FT HELIX 229..242 FT /evidence="ECO:0007829|PDB:7SIC" FT STRAND 244..246 FT /evidence="ECO:0007829|PDB:7SIC" FT HELIX 248..268 FT /evidence="ECO:0007829|PDB:7SIC" FT HELIX 273..290 FT /evidence="ECO:0007829|PDB:7SIC" FT HELIX 292..294 FT /evidence="ECO:0007829|PDB:7SIC" FT HELIX 298..300 FT /evidence="ECO:0007829|PDB:7SIC" FT HELIX 306..323 FT /evidence="ECO:0007829|PDB:7SIC" FT STRAND 324..326 FT /evidence="ECO:0007829|PDB:7SIC" FT HELIX 343..356 FT /evidence="ECO:0007829|PDB:7SIC" FT HELIX 393..402 FT /evidence="ECO:0007829|PDB:7SIC" FT TURN 407..409 FT /evidence="ECO:0007829|PDB:7SIC" FT HELIX 410..422 FT /evidence="ECO:0007829|PDB:7SIC" FT HELIX 424..426 FT /evidence="ECO:0007829|PDB:7SIC" FT HELIX 429..431 FT /evidence="ECO:0007829|PDB:7SID" FT HELIX 432..442 FT /evidence="ECO:0007829|PDB:7SIC" FT STRAND 445..447 FT /evidence="ECO:0007829|PDB:7SIC" FT HELIX 452..466 FT /evidence="ECO:0007829|PDB:7SIC" FT HELIX 474..492 FT /evidence="ECO:0007829|PDB:7SIC" FT TURN 493..496 FT /evidence="ECO:0007829|PDB:7SIC" FT HELIX 498..500 FT /evidence="ECO:0007829|PDB:7SID" FT HELIX 501..513 FT /evidence="ECO:0007829|PDB:7SIC" FT HELIX 521..524 FT /evidence="ECO:0007829|PDB:7SIC" FT TURN 525..527 FT /evidence="ECO:0007829|PDB:7SIC" FT HELIX 528..530 FT /evidence="ECO:0007829|PDB:7NI5" FT HELIX 536..548 FT /evidence="ECO:0007829|PDB:7SIC" FT HELIX 572..580 FT /evidence="ECO:0007829|PDB:7SIC" FT HELIX 597..600 FT /evidence="ECO:0007829|PDB:7SIC" FT TURN 605..607 FT /evidence="ECO:0007829|PDB:7SIC" FT HELIX 608..615 FT /evidence="ECO:0007829|PDB:7SIC" FT STRAND 617..619 FT /evidence="ECO:0007829|PDB:7SIC" FT HELIX 620..628 FT /evidence="ECO:0007829|PDB:7SIC" FT TURN 634..636 FT /evidence="ECO:0007829|PDB:7NI5" FT HELIX 646..655 FT /evidence="ECO:0007829|PDB:7SIC" FT HELIX 684..704 FT /evidence="ECO:0007829|PDB:7SIC" FT TURN 707..709 FT /evidence="ECO:0007829|PDB:7SIC" FT HELIX 713..731 FT /evidence="ECO:0007829|PDB:7SIC" FT STRAND 732..735 FT /evidence="ECO:0007829|PDB:8OXP" FT HELIX 737..741 FT /evidence="ECO:0007829|PDB:7SIC" FT HELIX 744..765 FT /evidence="ECO:0007829|PDB:7SIC" FT HELIX 771..786 FT /evidence="ECO:0007829|PDB:7SIC" FT STRAND 792..794 FT /evidence="ECO:0007829|PDB:7NI5" FT HELIX 795..806 FT /evidence="ECO:0007829|PDB:7SIC" FT HELIX 809..822 FT /evidence="ECO:0007829|PDB:7SIC" FT HELIX 887..889 FT /evidence="ECO:0007829|PDB:7SIC" FT HELIX 892..911 FT /evidence="ECO:0007829|PDB:7SIC" FT HELIX 920..930 FT /evidence="ECO:0007829|PDB:7SIC" FT TURN 933..935 FT /evidence="ECO:0007829|PDB:7SIC" FT HELIX 941..953 FT /evidence="ECO:0007829|PDB:7SIC" FT STRAND 957..959 FT /evidence="ECO:0007829|PDB:7SIC" FT HELIX 963..970 FT /evidence="ECO:0007829|PDB:7SIC" FT HELIX 973..979 FT /evidence="ECO:0007829|PDB:7SIC" FT TURN 980..982 FT /evidence="ECO:0007829|PDB:7SIC" FT HELIX 984..994 FT /evidence="ECO:0007829|PDB:7SIC" FT HELIX 995..997 FT /evidence="ECO:0007829|PDB:7SIC" FT HELIX 998..1002 FT /evidence="ECO:0007829|PDB:7SIC" FT HELIX 1009..1030 FT /evidence="ECO:0007829|PDB:7SIC" FT TURN 1031..1033 FT /evidence="ECO:0007829|PDB:7NI5" FT HELIX 1036..1052 FT /evidence="ECO:0007829|PDB:7SIC" FT STRAND 1060..1063 FT /evidence="ECO:0007829|PDB:7SIC" FT STRAND 1066..1069 FT /evidence="ECO:0007829|PDB:7SIC" FT HELIX 1070..1076 FT /evidence="ECO:0007829|PDB:7SIC" FT HELIX 1077..1079 FT /evidence="ECO:0007829|PDB:7SIC" FT HELIX 1083..1092 FT /evidence="ECO:0007829|PDB:7SIC" FT HELIX 1093..1096 FT /evidence="ECO:0007829|PDB:7SIC" FT HELIX 1113..1132 FT /evidence="ECO:0007829|PDB:7SIC" FT STRAND 1136..1138 FT /evidence="ECO:0007829|PDB:7NI5" FT HELIX 1144..1164 FT /evidence="ECO:0007829|PDB:7SIC" FT HELIX 1169..1181 FT /evidence="ECO:0007829|PDB:7SIC" FT HELIX 1187..1201 FT /evidence="ECO:0007829|PDB:7SIC" FT HELIX 1206..1212 FT /evidence="ECO:0007829|PDB:7SIC" FT HELIX 1214..1223 FT /evidence="ECO:0007829|PDB:7SIC" FT HELIX 1227..1229 FT /evidence="ECO:0007829|PDB:7NI5" FT TURN 1231..1233 FT /evidence="ECO:0007829|PDB:7SID" FT HELIX 1236..1238 FT /evidence="ECO:0007829|PDB:7SIC" FT HELIX 1244..1261 FT /evidence="ECO:0007829|PDB:7SIC" FT HELIX 1265..1275 FT /evidence="ECO:0007829|PDB:7SIC" FT HELIX 1279..1285 FT /evidence="ECO:0007829|PDB:7SIC" FT HELIX 1287..1294 FT /evidence="ECO:0007829|PDB:7SIC" FT HELIX 1295..1297 FT /evidence="ECO:0007829|PDB:7SIC" FT TURN 1299..1303 FT /evidence="ECO:0007829|PDB:8OXM" FT HELIX 1306..1322 FT /evidence="ECO:0007829|PDB:7SIC" FT TURN 1325..1327 FT /evidence="ECO:0007829|PDB:7SIC" FT HELIX 1328..1330 FT /evidence="ECO:0007829|PDB:7SIC" FT HELIX 1332..1338 FT /evidence="ECO:0007829|PDB:7SIC" FT HELIX 1340..1348 FT /evidence="ECO:0007829|PDB:7SIC" FT HELIX 1383..1396 FT /evidence="ECO:0007829|PDB:7SIC" FT STRAND 1397..1399 FT /evidence="ECO:0007829|PDB:7SIC" FT HELIX 1404..1408 FT /evidence="ECO:0007829|PDB:7SIC" FT HELIX 1413..1428 FT /evidence="ECO:0007829|PDB:8OXQ" FT HELIX 1432..1450 FT /evidence="ECO:0007829|PDB:8OXQ" FT HELIX 1453..1455 FT /evidence="ECO:0007829|PDB:7SID" FT TURN 1456..1460 FT /evidence="ECO:0007829|PDB:7NI5" FT HELIX 1461..1477 FT /evidence="ECO:0007829|PDB:8OXQ" FT HELIX 1485..1508 FT /evidence="ECO:0007829|PDB:8OXQ" FT HELIX 1513..1515 FT /evidence="ECO:0007829|PDB:8OXQ" FT HELIX 1517..1527 FT /evidence="ECO:0007829|PDB:8OXQ" FT TURN 1528..1530 FT /evidence="ECO:0007829|PDB:7SID" FT HELIX 1532..1545 FT /evidence="ECO:0007829|PDB:8OXQ" FT TURN 1546..1551 FT /evidence="ECO:0007829|PDB:8OXQ" FT HELIX 1553..1560 FT /evidence="ECO:0007829|PDB:8OXQ" FT STRAND 1567..1569 FT /evidence="ECO:0007829|PDB:8OXQ" FT HELIX 1572..1582 FT /evidence="ECO:0007829|PDB:8OXQ" FT TURN 1583..1585 FT /evidence="ECO:0007829|PDB:7NI6" FT HELIX 1590..1601 FT /evidence="ECO:0007829|PDB:8OXQ" FT HELIX 1607..1610 FT /evidence="ECO:0007829|PDB:8OXQ" FT HELIX 1611..1623 FT /evidence="ECO:0007829|PDB:8OXQ" FT HELIX 1625..1634 FT /evidence="ECO:0007829|PDB:8OXQ" FT STRAND 1635..1637 FT /evidence="ECO:0007829|PDB:8OXP" FT HELIX 1639..1641 FT /evidence="ECO:0007829|PDB:7SIC" FT HELIX 1643..1658 FT /evidence="ECO:0007829|PDB:8OXQ" FT STRAND 1661..1663 FT /evidence="ECO:0007829|PDB:8OXM" FT HELIX 1664..1677 FT /evidence="ECO:0007829|PDB:8OXQ" FT HELIX 1694..1702 FT /evidence="ECO:0007829|PDB:8OXQ" FT HELIX 1706..1721 FT /evidence="ECO:0007829|PDB:8OXQ" FT STRAND 1723..1725 FT /evidence="ECO:0007829|PDB:8OXO" FT HELIX 1727..1742 FT /evidence="ECO:0007829|PDB:8OXQ" FT HELIX 1744..1753 FT /evidence="ECO:0007829|PDB:8OXQ" FT STRAND 1754..1756 FT /evidence="ECO:0007829|PDB:7NI4" FT HELIX 1759..1763 FT /evidence="ECO:0007829|PDB:8OXQ" FT TURN 1764..1767 FT /evidence="ECO:0007829|PDB:8OXQ" FT TURN 1785..1789 FT /evidence="ECO:0007829|PDB:8OXQ" FT HELIX 1792..1795 FT /evidence="ECO:0007829|PDB:8OXQ" FT HELIX 1802..1815 FT /evidence="ECO:0007829|PDB:8OXQ" FT HELIX 1822..1825 FT /evidence="ECO:0007829|PDB:8OXQ" FT HELIX 1828..1831 FT /evidence="ECO:0007829|PDB:8OXQ" FT HELIX 1835..1851 FT /evidence="ECO:0007829|PDB:8OXQ" FT HELIX 1857..1874 FT /evidence="ECO:0007829|PDB:8OXQ" FT HELIX 1903..1917 FT /evidence="ECO:0007829|PDB:8OXQ" FT STRAND 1922..1924 FT /evidence="ECO:0007829|PDB:8OXQ" FT HELIX 1927..1930 FT /evidence="ECO:0007829|PDB:8OXQ" FT HELIX 1938..1947 FT /evidence="ECO:0007829|PDB:8OXQ" FT HELIX 1951..1973 FT /evidence="ECO:0007829|PDB:8OXQ" FT HELIX 1986..1997 FT /evidence="ECO:0007829|PDB:8OXQ" FT HELIX 2001..2012 FT /evidence="ECO:0007829|PDB:8OXQ" FT HELIX 2016..2019 FT /evidence="ECO:0007829|PDB:8OXQ" FT STRAND 2023..2028 FT /evidence="ECO:0007829|PDB:7SIC" FT HELIX 2029..2038 FT /evidence="ECO:0007829|PDB:8OXQ" FT HELIX 2042..2051 FT /evidence="ECO:0007829|PDB:8OXQ" FT HELIX 2057..2070 FT /evidence="ECO:0007829|PDB:8OXQ" FT HELIX 2074..2087 FT /evidence="ECO:0007829|PDB:8OXQ" FT HELIX 2093..2105 FT /evidence="ECO:0007829|PDB:8OXQ" FT HELIX 2124..2136 FT /evidence="ECO:0007829|PDB:8OXQ" FT HELIX 2140..2159 FT /evidence="ECO:0007829|PDB:8OXQ" FT HELIX 2166..2168 FT /evidence="ECO:0007829|PDB:8OXQ" FT HELIX 2170..2190 FT /evidence="ECO:0007829|PDB:8OXQ" FT HELIX 2195..2210 FT /evidence="ECO:0007829|PDB:8OXQ" FT TURN 2211..2214 FT /evidence="ECO:0007829|PDB:8OXQ" FT HELIX 2217..2236 FT /evidence="ECO:0007829|PDB:8OXQ" FT STRAND 2240..2242 FT /evidence="ECO:0007829|PDB:8OXP" FT HELIX 2245..2264 FT /evidence="ECO:0007829|PDB:8OXQ" FT HELIX 2269..2281 FT /evidence="ECO:0007829|PDB:8OXQ" FT HELIX 2290..2301 FT /evidence="ECO:0007829|PDB:8OXQ" FT HELIX 2305..2322 FT /evidence="ECO:0007829|PDB:8OXQ" FT HELIX 2328..2348 FT /evidence="ECO:0007829|PDB:8OXQ" FT HELIX 2353..2359 FT /evidence="ECO:0007829|PDB:8OXQ" FT HELIX 2361..2370 FT /evidence="ECO:0007829|PDB:8OXQ" FT HELIX 2377..2406 FT /evidence="ECO:0007829|PDB:8OXQ" FT HELIX 2408..2421 FT /evidence="ECO:0007829|PDB:8OXQ" FT HELIX 2437..2475 FT /evidence="ECO:0007829|PDB:8OXQ" FT HELIX 2481..2483 FT /evidence="ECO:0007829|PDB:8OXQ" FT HELIX 2484..2493 FT /evidence="ECO:0007829|PDB:8OXQ" FT TURN 2494..2496 FT /evidence="ECO:0007829|PDB:8OXQ" FT HELIX 2498..2507 FT /evidence="ECO:0007829|PDB:8OXQ" FT HELIX 2508..2510 FT /evidence="ECO:0007829|PDB:8OXQ" FT HELIX 2513..2516 FT /evidence="ECO:0007829|PDB:8OXQ" FT HELIX 2520..2525 FT /evidence="ECO:0007829|PDB:8OXQ" FT STRAND 2529..2531 FT /evidence="ECO:0007829|PDB:7SID" FT STRAND 2533..2535 FT /evidence="ECO:0007829|PDB:8OXQ" FT HELIX 2537..2551 FT /evidence="ECO:0007829|PDB:8OXQ" FT HELIX 2553..2564 FT /evidence="ECO:0007829|PDB:8OXQ" FT TURN 2565..2567 FT /evidence="ECO:0007829|PDB:8OXQ" FT HELIX 2568..2572 FT /evidence="ECO:0007829|PDB:8OXQ" FT HELIX 2593..2612 FT /evidence="ECO:0007829|PDB:8OXQ" FT HELIX 2614..2632 FT /evidence="ECO:0007829|PDB:8OXQ" FT HELIX 2637..2640 FT /evidence="ECO:0007829|PDB:8OXQ" FT TURN 2652..2655 FT /evidence="ECO:0007829|PDB:8OXQ" FT STRAND 2659..2663 FT /evidence="ECO:0007829|PDB:8OXQ" FT STRAND 2665..2667 FT /evidence="ECO:0007829|PDB:8OXQ" FT STRAND 2673..2675 FT /evidence="ECO:0007829|PDB:8OXQ" FT STRAND 2682..2686 FT /evidence="ECO:0007829|PDB:8OXQ" FT STRAND 2688..2692 FT /evidence="ECO:0007829|PDB:8OXQ" FT STRAND 2695..2697 FT /evidence="ECO:0007829|PDB:8OXQ" FT STRAND 2700..2706 FT /evidence="ECO:0007829|PDB:8OXQ" FT STRAND 2707..2709 FT /evidence="ECO:0007829|PDB:7NI4" FT STRAND 2711..2717 FT /evidence="ECO:0007829|PDB:8OXQ" FT HELIX 2723..2740 FT /evidence="ECO:0007829|PDB:8OXQ" FT HELIX 2743..2748 FT /evidence="ECO:0007829|PDB:8OXQ" FT STRAND 2757..2759 FT /evidence="ECO:0007829|PDB:8OXQ" FT STRAND 2761..2763 FT /evidence="ECO:0007829|PDB:8OXQ" FT STRAND 2765..2768 FT /evidence="ECO:0007829|PDB:8OXQ" FT STRAND 2773..2775 FT /evidence="ECO:0007829|PDB:8OXQ" FT HELIX 2776..2780 FT /evidence="ECO:0007829|PDB:8OXQ" FT TURN 2783..2785 FT /evidence="ECO:0007829|PDB:8OXQ" FT HELIX 2787..2791 FT /evidence="ECO:0007829|PDB:8OXQ" FT HELIX 2798..2807 FT /evidence="ECO:0007829|PDB:8OXQ" FT HELIX 2808..2810 FT /evidence="ECO:0007829|PDB:8OXQ" FT HELIX 2813..2825 FT /evidence="ECO:0007829|PDB:8OXQ" FT HELIX 2833..2838 FT /evidence="ECO:0007829|PDB:8OXQ" FT HELIX 2842..2866 FT /evidence="ECO:0007829|PDB:8OXQ" FT HELIX 2873..2875 FT /evidence="ECO:0007829|PDB:8OXQ" FT STRAND 2876..2879 FT /evidence="ECO:0007829|PDB:8OXQ" FT TURN 2880..2882 FT /evidence="ECO:0007829|PDB:8OXQ" FT STRAND 2885..2887 FT /evidence="ECO:0007829|PDB:8OXQ" FT TURN 2894..2899 FT /evidence="ECO:0007829|PDB:8OXQ" FT STRAND 2900..2902 FT /evidence="ECO:0007829|PDB:8OXQ" FT STRAND 2906..2908 FT /evidence="ECO:0007829|PDB:8OXP" FT HELIX 2912..2916 FT /evidence="ECO:0007829|PDB:8OXQ" FT TURN 2920..2925 FT /evidence="ECO:0007829|PDB:8OXQ" FT HELIX 2926..2940 FT /evidence="ECO:0007829|PDB:8OXQ" FT HELIX 2942..2953 FT /evidence="ECO:0007829|PDB:8OXQ" FT HELIX 2964..2970 FT /evidence="ECO:0007829|PDB:8OXQ" FT HELIX 3002..3017 FT /evidence="ECO:0007829|PDB:8OXQ" FT STRAND 3020..3025 FT /evidence="ECO:0007829|PDB:8OXQ" FT HELIX 3028..3040 FT /evidence="ECO:0007829|PDB:8OXQ" FT HELIX 3042..3047 FT /evidence="ECO:0007829|PDB:8OXQ" FT HELIX 3050..3052 FT /evidence="ECO:0007829|PDB:8OXQ" SQ SEQUENCE 3056 AA; 350687 MW; C0B4866E1E3199E2 CRC64; MSLVLNDLLI CCRQLEHDRA TERKKEVEKF KRLIRDPETI KHLDRHSDSK QGKYLNWDAV FRFLQKYIQK ETECLRIAKP NVSASTQASR QKKMQEISSL VKYFIKCANR RAPRLKCQEL LNYIMDTVKD SSNGAIYGAD CSNILLKDIL SVRKYWCEIS QQQWLELFSV YFRLYLKPSQ DVHRVLVARI IHAVTKGCCS QTDGLNSKFL DFFSKAIQCA RQEKSSSGLN HILAALTIFL KTLAVNFRIR VCELGDEILP TLLYIWTQHR LNDSLKEVII ELFQLQIYIH HPKGAKTQEK GAYESTKWRS ILYNLYDLLV NEISHIGSRG KYSSGFRNIA VKENLIELMA DICHQVFNED TRSLEISQSY TTTQRESSDY SVPCKRKKIE LGWEVIKDHL QKSQNDFDLV PWLQIATQLI SKYPASLPNC ELSPLLMILS QLLPQQRHGE RTPYVLRCLT EVALCQDKRS NLESSQKSDL LKLWNKIWCI TFRGISSEQI QAENFGLLGA IIQGSLVEVD REFWKLFTGS ACRPSCPAVC CLTLALTTSI VPGTVKMGIE QNMCEVNRSF SLKESIMKWL LFYQLEGDLE NSTEVPPILH SNFPHLVLEK ILVSLTMKNC KAAMNFFQSV PECEHHQKDK EELSFSEVEE LFLQTTFDKM DFLTIVRECG IEKHQSSIGF SVHQNLKESL DRCLLGLSEQ LLNNYSSEIT NSETLVRCSR LLVGVLGCYC YMGVIAEEEA YKSELFQKAK SLMQCAGESI TLFKNKTNEE FRIGSLRNMM QLCTRCLSNC TKKSPNKIAS GFFLRLLTSK LMNDIADICK SLASFIKKPF DRGEVESMED DTNGNLMEVE DQSSMNLFND YPDSSVSDAN EPGESQSTIG AINPLAEEYL SKQDLLFLDM LKFLCLCVTT AQTNTVSFRA ADIRRKLLML IDSSTLEPTK SLHLHMYLML LKELPGEEYP LPMEDVLELL KPLSNVCSLY RRDQDVCKTI LNHVLHVVKN LGQSNMDSEN TRDAQGQFLT VIGAFWHLTK ERKYIFSVRM ALVNCLKTLL EADPYSKWAI LNVMGKDFPV NEVFTQFLAD NHHQVRMLAA ESINRLFQDT KGDSSRLLKA LPLKLQQTAF ENAYLKAQEG MREMSHSAEN PETLDEIYNR KSVLLTLIAV VLSCSPICEK QALFALCKSV KENGLEPHLV KKVLEKVSET FGYRRLEDFM ASHLDYLVLE WLNLQDTEYN LSSFPFILLN YTNIEDFYRS CYKVLIPHLV IRSHFDEVKS IANQIQEDWK SLLTDCFPKI LVNILPYFAY EGTRDSGMAQ QRETATKVYD MLKSENLLGK QIDHLFISNL PEIVVELLMT LHEPANSSAS QSTDLCDFSG DLDPAPNPPH FPSHVIKATF AYISNCHKTK LKSILEILSK SPDSYQKILL AICEQAAETN NVYKKHRILK IYHLFVSLLL KDIKSGLGGA WAFVLRDVIY TLIHYINQRP SCIMDVSLRS FSLCCDLLSQ VCQTAVTYCK DALENHLHVI VGTLIPLVYE QVEVQKQVLD LLKYLVIDNK DNENLYITIK LLDPFPDHVV FKDLRITQQK IKYSRGPFSL LEEINHFLSV SVYDALPLTR LEGLKDLRRQ LELHKDQMVD IMRASQDNPQ DGIMVKLVVN LLQLSKMAIN HTGEKEVLEA VGSCLGEVGP IDFSTIAIQH SKDASYTKAL KLFEDKELQW TFIMLTYLNN TLVEDCVKVR SAAVTCLKNI LATKTGHSFW EIYKMTTDPM LAYLQPFRTS RKKFLEVPRF DKENPFEGLD DINLWIPLSE NHDIWIKTLT CAFLDSGGTK CEILQLLKPM CEVKTDFCQT VLPYLIHDIL LQDTNESWRN LLSTHVQGFF TSCLRHFSQT SRSTTPANLD SESEHFFRCC LDKKSQRTML AVVDYMRRQK RPSSGTIFND AFWLDLNYLE VAKVAQSCAA HFTALLYAEI YADKKSMDDQ EKRSLAFEEG SQSTTISSLS EKSKEETGIS LQDLLLEIYR SIGEPDSLYG CGGGKMLQPI TRLRTYEHEA MWGKALVTYD LETAIPSSTR QAGIIQALQN LGLCHILSVY LKGLDYENKD WCPELEELHY QAAWRNMQWD HCTSVSKEVE GTSYHESLYN ALQSLRDREF STFYESLKYA RVKEVEEMCK RSLESVYSLY PTLSRLQAIG ELESIGELFS RSVTHRQLSE VYIKWQKHSQ LLKDSDFSFQ EPIMALRTVI LEILMEKEMD NSQRECIKDI LTKHLVELSI LARTFKNTQL PERAIFQIKQ YNSVSCGVSE WQLEEAQVFW AKKEQSLALS ILKQMIKKLD ASCAANNPSL KLTYTECLRV CGNWLAETCL ENPAVIMQTY LEKAVEVAGN YDGESSDELR NGKMKAFLSL ARFSDTQYQR IENYMKSSEF ENKQALLKRA KEEVGLLREH KIQTNRYTVK VQRELELDEL ALRALKEDRK RFLCKAVENY INCLLSGEEH DMWVFRLCSL WLENSGVSEV NGMMKRDGMK IPTYKFLPLM YQLAARMGTK MMGGLGFHEV LNNLISRISM DHPHHTLFII LALANANRDE FLTKPEVARR SRITKNVPKQ SSQLDEDRTE AANRIICTIR SRRPQMVRSV EALCDAYIIL ANLDATQWKT QRKGINIPAD QPITKLKNLE DVVVPTMEIK VDHTGEYGNL VTIQSFKAEF RLAGGVNLPK IIDCVGSDGK ERRQLVKGRD DLRQDAVMQQ VFQMCNTLLQ RNTETRKRKL TICTYKVVPL SQRSGVLEWC TGTVPIGEFL VNNEDGAHKR YRPNDFSAFQ CQKKMMEVQK KSFEEKYEVF MDVCQNFQPV FRYFCMEKFL DPAIWFEKRL AYTRSVATSS IVGYILGLGD RHVQNILINE QSAELVHIDL GVAFEQGKIL PTPETVPFRL TRDIVDGMGI TGVEGVFRRC CEKTMEVMRN SQETLLTIVE VLLYDPLFDW TMNPLKALYL QQRPEDETEL HPTLNADDQE CKRNLSDIDQ SFNKVAERVL MRLQEKLKGV EEGTVLSVGG QVNLLIQQAI DPKNLSRLFP GWKAWV // ID NPM_HUMAN Reviewed; 294 AA. AC P06748; A8K3N7; B5BU00; D3DQL6; P08693; Q12826; Q13440; Q13441; Q14115; AC Q5EU94; Q5EU95; Q5EU96; Q5EU97; Q5EU98; Q5EU99; Q6V962; Q8WTW5; Q96AT6; AC Q96DC4; Q96EA5; Q9BYG9; Q9UDJ7; DT 01-JAN-1988, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1990, sequence version 2. DT 28-JAN-2026, entry version 271. DE RecName: Full=Nucleophosmin; DE Short=NPM; DE AltName: Full=Nucleolar phosphoprotein B23; DE AltName: Full=Nucleolar protein NO38; DE AltName: Full=Numatrin; GN Name=NPM1 {ECO:0000312|HGNC:HGNC:7910}; Synonyms=NPM; 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). RC TISSUE=Placenta; RX PubMed=2713355; DOI=10.1021/bi00429a017; RA Chan W.-Y., Liu Q.R., Borjigin J., Busch H., Rennert O.M., Tease L.A., RA Chan P.-K.; RT "Characterization of the cDNA encoding human nucleophosmin and studies of RT its role in normal and abnormal growth."; RL Biochemistry 28:1033-1039(1989). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=B-cell lymphoma; RX PubMed=2775293; DOI=10.1016/0006-291x(89)92100-1; RA Li X., McNeilage L.J., Whittingham S.; RT "The nucleotide sequence of a human cDNA encoding the highly conserved RT nucleolar phosphoprotein B23."; RL Biochem. Biophys. Res. Commun. 163:72-78(1989). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Amnion; RX PubMed=2478125; DOI=10.1016/0006-291x(89)91699-9; RA Zhang X.T., Thomis D.C., Samuel C.E.; RT "Isolation and characterization of a molecular cDNA clone of a human mRNA RT from interferon-treated cells encoding nucleolar protein B23, numatrin."; RL Biochem. Biophys. Res. Commun. 164:176-184(1989). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1). RX PubMed=9092633; DOI=10.1093/nar/25.6.1225; RA Chan P.-K., Chan F.Y., Morris S.W., Xie Z.; RT "Isolation and characterization of the human nucleophosmin/B23 (NPM) gene: RT identification of the YY1 binding site at the 5' enhancer region."; RL Nucleic Acids Res. 25:1225-1232(1997). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3). RA Okuwaki M., Nagata K.; RT "Human homologue of Rat B23.2."; RL Submitted (APR-2000) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, AND RP INVOLVEMENT IN ACUTE MYELOGENOUS LEUKEMIA. RC TISSUE=Bone marrow; RX PubMed=15659725; DOI=10.1056/nejmoa041974; RA Falini B., Mecucci C., Tiacci E., Alcalay M., Rosati R., Pasqualucci L., RA La Starza R., Diverio D., Colombo E., Santucci A., Bigerna B., Pacini R., RA Pucciarini A., Liso A., Vignetti M., Fazi P., Meani N., Pettirossi V., RA Saglio G., Mandelli F., Lo-Coco F., Pelicci P.-G., Martelli M.F.; RT "Cytoplasmic nucleophosmin in acute myelogenous leukemia with a normal RT karyotype."; RL N. Engl. J. Med. 352:254-266(2005). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=16574551; DOI=10.1016/s1470-2045(06)70661-1; RA Bolli N., Galimberti S., Martelli M.P., Tabarrini A., Roti G., Mecucci C., RA Martelli M.F., Petrini M., Falini B.; RT "Cytoplasmic nucleophosmin in myeloid sarcoma occurring 20 years after RT diagnosis of acute myeloid leukaemia."; RL Lancet Oncol. 7:350-352(2006). RN [8] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Testis; RA Lu L., Huang X.Y., Yin L.L., Xu M., Li J.M., Zhou Z.M., Sha J.H.; RT "Cloning of a new transcript of nucleophosmin in testis."; RL Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases. RN [9] 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 [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Embryo; 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 [11] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RX PubMed=19054851; DOI=10.1038/nmeth.1273; RA Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R., RA Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y., RA Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B., RA Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H., Maruyama Y., RA Matsuo K., Minami K., Mitsubori M., Mori M., Morishita R., Murase A., RA Nishikawa A., Nishikawa S., Okamoto T., Sakagami N., Sakamoto Y., RA Sasaki Y., Seki T., Sono S., Sugiyama A., Sumiya T., Takayama T., RA Takayama Y., Takeda H., Togashi T., Yahata K., Yamada H., Yanagisawa Y., RA Endo Y., Imamoto F., Kisu Y., Tanaka S., Isogai T., Imai J., Watanabe S., RA Nomura N.; RT "Human protein factory for converting the transcriptome into an in vitro- RT expressed proteome."; RL Nat. Methods 5:1011-1017(2008). RN [12] 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 [13] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3). RC TISSUE=Bone marrow, Brain, Kidney, Lung, Prostate, Testis, and RC Urinary bladder; 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 [14] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-133, AND CHROMOSOMAL TRANSLOCATION WITH RP RARA. RC TISSUE=Bone marrow; RX PubMed=8562957; RA Redner R.L., Rush E.A., Faas S., Rudert W.A., Corey S.J.; RT "The t(5;17) variant of acute promyelocytic leukemia expresses a RT nucleophosmin-retinoic acid receptor fusion."; RL Blood 87:882-886(1996). RN [15] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-117, AND CHROMOSOMAL TRANSLOCATION WITH RP ALK. RC TISSUE=T-cell lymphoma; RX PubMed=8122112; DOI=10.1126/science.8122112; RA Morris S.W., Kirstein M.N., Valentine M.B., Dittmer K.G., Shapiro D.N., RA Saltman D.L., Look A.T.; RT "Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non- RT Hodgkin's lymphoma."; RL Science 263:1281-1284(1994). RN [16] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-117, AND CHROMOSOMAL TRANSLOCATION WITH RP ALK. RC TISSUE=Lymphoma; RX PubMed=8633037; DOI=10.1073/pnas.93.9.4181; RA Fujimoto J., Shiota M., Iwahara T., Seki N., Satoh H., Mori S., RA Yamamoto T.; RT "Characterization of the transforming activity of p80, a RT hyperphosphorylated protein in a Ki-1 lymphoma cell line with chromosomal RT translocation t(2;5)."; RL Proc. Natl. Acad. Sci. U.S.A. 93:4181-4186(1996). RN [17] RP PROTEIN SEQUENCE OF 1-24; 33-101; 104-141; 240-248 AND 278-291, ACETYLATION RP AT MET-1, PHOSPHORYLATION AT SER-125, AND IDENTIFICATION BY MASS RP SPECTROMETRY. RC TISSUE=Cervix carcinoma; RA Bienvenut W.V., Waridel P., Quadroni M.; RL Submitted (MAR-2009) to UniProtKB. RN [18] RP NUCLEOTIDE SEQUENCE [MRNA] OF 15-294 (ISOFORM 1). RC TISSUE=Placenta; RX PubMed=2602120; RA Hale T.K., Mansfield B.C.; RT "Nucleotide sequence of a cDNA clone representing a third allele of human RT protein B23."; RL Nucleic Acids Res. 17:10112-10112(1989). RN [19] RP PROTEIN SEQUENCE OF 33-54. RC TISSUE=Colon carcinoma; RX PubMed=9150948; DOI=10.1002/elps.1150180344; RA Ji H., Reid G.E., Moritz R.L., Eddes J.S., Burgess A.W., Simpson R.J.; RT "A two-dimensional gel database of human colon carcinoma proteins."; RL Electrophoresis 18:605-613(1997). RN [20] RP PROTEIN SEQUENCE OF 34-42; 50-67; 137-151; 218-227; 252-266 AND 277-286 RP (ISOFORM 1), AND INTERACTION WITH HTLV1 REX PROTEIN (MICROBIAL INFECTION). RX PubMed=8314759; DOI=10.1016/s0021-9258(19)85191-8; RA Adachi Y., Copeland T.D., Hatanaka M., Oroszlan S.; RT "Nucleolar targeting signal of Rex protein of human T-cell leukemia virus RT type I specifically binds to nucleolar shuttle protein B-23."; RL J. Biol. Chem. 268:13930-13934(1993). RN [21] RP PROTEIN SEQUENCE OF 33-42; 213-221; 251-257 AND 268-274, FUNCTION, RP INTERACTION WITH EIF2AK2, AND PHOSPHORYLATION. RX PubMed=12882984; DOI=10.1074/jbc.m301392200; RA Pang Q., Christianson T.A., Koretsky T., Carlson H., David L., Keeble W., RA Faulkner G.R., Speckhart A., Bagby G.C.; RT "Nucleophosmin interacts with and inhibits the catalytic function of RT eukaryotic initiation factor 2 kinase PKR."; RL J. Biol. Chem. 278:41709-41717(2003). RN [22] RP PROTEIN SEQUENCE OF 115-134. RX PubMed=3944116; DOI=10.1016/s0021-9258(17)36022-2; RA Chan P.-K., Aldrich M.B., Cook R.G., Busch H.; RT "Amino acid sequence of protein B23 phosphorylation site."; RL J. Biol. Chem. 261:1868-1872(1986). RN [23] RP NUCLEOTIDE SEQUENCE [MRNA] OF 213-294 (ISOFORM 1), AND PROTEIN SEQUENCE OF RP 227-294. RX PubMed=2429957; DOI=10.1016/s0021-9258(18)67023-1; RA Chan P.-K., Chan W.-Y., Yung B.Y.M., Cook R.G., Aldrich M.B., Ku D., RA Goldknopf I.L., Busch H.; RT "Amino acid sequence of a specific antigenic peptide of protein B23."; RL J. Biol. Chem. 261:14335-14341(1986). RN [24] RP INTERACTION WITH NOP2. RX PubMed=8089149; DOI=10.1016/s0021-9258(17)31583-1; RA Valdez B.C., Perlaky L., Henning D., Saijo Y., Chan P.K., Busch H.; RT "Identification of the nuclear and nucleolar localization signals of the RT protein p120. Interaction with translocation protein B23."; RL J. Biol. Chem. 269:23776-23783(1994). RN [25] RP ADP-RIBOSYLATION. RX PubMed=7631008; DOI=10.2307/3579152; RA Ramsamooj P., Notario V., Dritschilo A.; RT "Modification of nucleolar protein B23 after exposure to ionizing RT radiation."; RL Radiat. Res. 143:158-164(1995). RN [26] RP CHROMOSOMAL TRANSLOCATION WITH MLF1. RX PubMed=8570204; RA Yoneda-Kato N., Look A.T., Kirstein M.N., Valentine M.B., Raimondi S.C., RA Cohen K.J., Carroll A.J., Morris S.W.; RT "The t(3;5)(q25.1;q34) of myelodysplastic syndrome and acute myeloid RT leukemia produces a novel fusion gene, NPM-MLF1."; RL Oncogene 12:265-275(1996). RN [27] RP PHOSPHORYLATION BY CDK2. RX PubMed=11051553; DOI=10.1016/s0092-8674(00)00093-3; RA Okuda M., Horn H.F., Tarapore P., Tokuyama Y., Smulian A.G., Chan P.K., RA Knudsen E.S., Hofmann I.A., Snyder J.D., Bove K.E., Fukasawa K.; RT "Nucleophosmin/B23 is a target of CDK2/cyclin E in centrosome RT duplication."; RL Cell 103:127-140(2000). RN [28] RP INTERACTION WITH HEPATITIS DELTA VIRUS S-HDAG (MICROBIAL INFECTION). RX PubMed=11309377; DOI=10.1074/jbc.m010087200; RA Huang W.H., Yung B.Y., Syu W.J., Lee Y.H.; RT "The nucleolar phosphoprotein B23 interacts with hepatitis delta antigens RT and modulates the hepatitis delta virus RNA replication."; RL J. Biol. Chem. 276:25166-25175(2001). RN [29] RP PHOSPHORYLATION AT THR-199; THR-219 AND THR-237, AND MUTAGENESIS OF RP THR-199; THR-219; THR-234 AND THR-237. RX PubMed=12058066; DOI=10.1091/mbc.02-03-0036; RA Okuwaki M., Tsujimoto M., Nagata K.; RT "The RNA binding activity of a ribosome biogenesis factor, RT nucleophosmin/B23, is modulated by phosphorylation with a cell cycle- RT dependent kinase and by association with its subtype."; RL Mol. Biol. Cell 13:2016-2030(2002). RN [30] RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=12429849; DOI=10.1091/mbc.e02-05-0271; RA Scherl A., Coute Y., Deon C., Calle A., Kindbeiter K., Sanchez J.-C., RA Greco A., Hochstrasser D.F., Diaz J.-J.; RT "Functional proteomic analysis of human nucleolus."; RL Mol. Biol. Cell 13:4100-4109(2002). RN [31] RP REVIEW. RX PubMed=12214246; DOI=10.1038/sj.onc.1205708; RA Okuda M.; RT "The role of nucleophosmin in centrosome duplication."; RL Oncogene 21:6170-6174(2002). RN [32] RP IDENTIFICATION BY MASS SPECTROMETRY, AND SUBCELLULAR LOCATION [LARGE SCALE RP ANALYSIS]. RC TISSUE=Lymphoblast; RX PubMed=14654843; DOI=10.1038/nature02166; RA Andersen J.S., Wilkinson C.J., Mayor T., Mortensen P., Nigg E.A., Mann M.; RT "Proteomic characterization of the human centrosome by protein correlation RT profiling."; RL Nature 426:570-574(2003). RN [33] RP SUBCELLULAR LOCATION, PHOSPHORYLATION, AND INTERACTION WITH NEK2. RX PubMed=15388344; DOI=10.1016/j.febslet.2004.08.047; RA Yao J., Fu C., Ding X., Guo Z., Zenreski A., Chen Y., Ahmed K., Liao J., RA Dou Z., Yao X.; RT "Nek2A kinase regulates the localization of numatrin to centrosome in RT mitosis."; RL FEBS Lett. 575:112-118(2004). RN [34] RP PHOSPHORYLATION AT SER-4 BY PLK1. RX PubMed=15190079; DOI=10.1074/jbc.m403264200; RA Zhang H., Shi X., Paddon H., Hampong M., Dai W., Pelech S.; RT "B23/nucleophosmin serine 4 phosphorylation mediates mitotic functions of RT polo-like kinase 1."; RL J. Biol. Chem. 279:35726-35734(2004). RN [35] RP INTERACTION WITH RPGR. RX PubMed=15772089; DOI=10.1093/hmg/ddi129; RA Shu X., Fry A.M., Tulloch B., Manson F.D., Crabb J.W., Khanna H., RA Faragher A.J., Lennon A., He S., Trojan P., Giessl A., Wolfrum U., RA Vervoort R., Swaroop A., Wright A.F.; RT "RPGR ORF15 isoform co-localizes with RPGRIP1 at centrioles and basal RT bodies and interacts with nucleophosmin."; RL Hum. Mol. Genet. 14:1183-1197(2005). RN [36] RP ACETYLATION AT LYS-212; LYS-229; LYS-230; LYS-250; LYS-257 AND LYS-292, AND RP FUNCTION AS A CHAPERONE. RX PubMed=16107701; DOI=10.1128/mcb.25.17.7534-7545.2005; RA Swaminathan V., Kishore A.H., Febitha K.K., Kundu T.K.; RT "Human histone chaperone nucleophosmin enhances acetylation-dependent RT chromatin transcription."; RL Mol. Cell. Biol. 25:7534-7545(2005). RN [37] RP SUMOYLATION AT LYS-230 AND LYS-263. RX PubMed=15897463; DOI=10.1073/pnas.0502978102; RA Tago K., Chiocca S., Sherr C.J.; RT "Sumoylation induced by the Arf tumor suppressor: a p53-independent RT function."; RL Proc. Natl. Acad. Sci. U.S.A. 102:7689-7694(2005). RN [38] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-70 AND THR-95, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling RT networks."; RL Cell 127:635-648(2006). RN [39] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-150; LYS-154 AND LYS-212, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=16916647; DOI=10.1016/j.molcel.2006.06.026; RA Kim S.C., Sprung R., Chen Y., Xu Y., Ball H., Pei J., Cheng T., Kho Y., RA Xiao H., Xiao L., Grishin N.V., White M., Yang X.-J., Zhao Y.; RT "Substrate and functional diversity of lysine acetylation revealed by a RT proteomics survey."; RL Mol. Cell 23:607-618(2006). RN [40] RP FUNCTION, AND INTERACTION WITH ROCK2. RX PubMed=17015463; DOI=10.1128/mcb.01383-06; RA Ma Z., Kanai M., Kawamura K., Kaibuchi K., Ye K., Fukasawa K.; RT "Interaction between ROCK II and nucleophosmin/B23 in the regulation of RT centrosome duplication."; RL Mol. Cell. Biol. 26:9016-9034(2006). RN [41] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-70; THR-199 AND SER-254, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17924679; DOI=10.1021/pr070152u; RA Yu L.R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D.; RT "Improved titanium dioxide enrichment of phosphopeptides from HeLa cells RT and high confident phosphopeptide identification by cross-validation of RT MS/MS and MS/MS/MS spectra."; RL J. Proteome Res. 6:4150-4162(2007). RN [42] RP INTERACTION WITH NSUN2. RX PubMed=17215513; DOI=10.1091/mbc.e06-11-1021; RA Sakita-Suto S., Kanda A., Suzuki F., Sato S., Takata T., Tatsuka M.; RT "Aurora-B regulates RNA methyltransferase NSUN2."; RL Mol. Biol. Cell 18:1107-1117(2007). RN [43] RP INTERACTION WITH SENP3, AND MUTAGENESIS OF LYS-263. RX PubMed=18259216; DOI=10.1038/embor.2008.3; RA Haindl M., Harasim T., Eick D., Muller S.; RT "The nucleolar SUMO-specific protease SENP3 reverses SUMO modification of RT nucleophosmin and is required for rRNA processing."; RL EMBO Rep. 9:273-279(2008). RN [44] RP INTERACTION WITH SENP3, AND SUBCELLULAR LOCATION. RX PubMed=19015314; DOI=10.1083/jcb.200807185; RA Yun C., Wang Y., Mukhopadhyay D., Backlund P., Kolli N., Yergey A., RA Wilkinson K.D., Dasso M.; RT "Nucleolar protein B23/nucleophosmin regulates the vertebrate SUMO pathway RT through SENP3 and SENP5 proteases."; RL J. Cell Biol. 183:589-595(2008). RN [45] RP REVIEW. RX PubMed=18024471; DOI=10.1093/jb/mvm222; RA Okuwaki M.; RT "The structure and functions of NPM1/Nucleophosmin/B23, a multifunctional RT nucleolar acidic protein."; RL J. Biochem. 143:441-448(2008). RN [46] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-70; SER-125 AND THR-279, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18220336; DOI=10.1021/pr0705441; RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III; RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient RT phosphoproteomic analysis."; RL J. Proteome Res. 7:1346-1351(2008). RN [47] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-70 AND SER-125, AND RP IDENTIFICATION BY MASS SPECTROMETRY [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 [48] RP FUNCTION. RX PubMed=18809582; DOI=10.1128/mcb.01548-07; RA Maggi L.B. Jr., Kuchenruether M., Dadey D.Y., Schwope R.M., Grisendi S., RA Townsend R.R., Pandolfi P.P., Weber J.D.; RT "Nucleophosmin serves as a rate-limiting nuclear export chaperone for the RT Mammalian ribosome."; RL Mol. Cell. Biol. 28:7050-7065(2008). RN [49] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-70; THR-75; THR-95; SER-125; RP SER-139; THR-234; THR-237 AND SER-243, AND IDENTIFICATION BY MASS RP 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 [50] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-125, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=18318008; DOI=10.1002/pmic.200700884; RA Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D., RA Zou H., Gu J.; RT "Large-scale phosphoproteome analysis of human liver tissue by enrichment RT and fractionation of phosphopeptides with strong anion exchange RT chromatography."; RL Proteomics 8:1346-1361(2008). RN [51] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS RP 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 [52] RP INTERACTION WITH RRP1B. RX PubMed=19710015; DOI=10.1074/jbc.m109.023457; RA Crawford N.P., Yang H., Mattaini K.R., Hunter K.W.; RT "The metastasis efficiency modifier ribosomal RNA processing 1 homolog B RT (RRP1B) is a chromatin-associated factor."; RL J. Biol. Chem. 284:28660-28673(2009). RN [53] RP SUBCELLULAR LOCATION, UBIQUITINATION, AND DEUBIQUITINATION BY USP36. RX PubMed=19208757; DOI=10.1242/jcs.044461; RA Endo A., Matsumoto M., Inada T., Yamamoto A., Nakayama K.I., Kitamura N., RA Komada M.; RT "Nucleolar structure and function are regulated by the deubiquitylating RT enzyme USP36."; RL J. Cell Sci. 122:678-686(2009). RN [54] RP FUNCTION, INTERACTION WITH APEX1, IDENTIFICATION BY MASS SPECTROMETRY, AND RP SUBCELLULAR LOCATION. RX PubMed=19188445; DOI=10.1128/mcb.01337-08; RA Vascotto C., Fantini D., Romanello M., Cesaratto L., Deganuto M., RA Leonardi A., Radicella J.P., Kelley M.R., D'Ambrosio C., Scaloni A., RA Quadrifoglio F., Tell G.; RT "APE1/Ref-1 interacts with NPM1 within nucleoli and plays a role in the RT rRNA quality control process."; RL Mol. Cell. Biol. 29:1834-1854(2009). RN [55] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-125, 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 [56] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-70 AND SER-125, 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 [57] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-32; LYS-150; LYS-257; LYS-267 AND RP LYS-273, ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-257 (ISOFORM 3), AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., RA Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [58] RP INTERACTION WITH CEBPA. RX PubMed=20075868; DOI=10.1038/emboj.2009.404; RA Muller C., Bremer A., Schreiber S., Eichwald S., Calkhoven C.F.; RT "Nucleolar retention of a translational C/EBPalpha isoform stimulates rDNA RT transcription and cell size."; RL EMBO J. 29:897-909(2010). RN [59] RP SUBCELLULAR LOCATION, AND INTERACTION WITH RPS10. RX PubMed=20159986; DOI=10.1074/jbc.m110.103911; RA Ren J., Wang Y., Liang Y., Zhang Y., Bao S., Xu Z.; RT "Methylation of ribosomal protein S10 by protein-arginine methyltransferase RT 5 regulates ribosome biogenesis."; RL J. Biol. Chem. 285:12695-12705(2010). RN [60] RP INTERACTION WITH RRP1B. RX PubMed=20926688; DOI=10.1091/mbc.e10-04-0287; RA Chamousset D., De Wever V., Moorhead G.B., Chen Y., Boisvert F.M., RA Lamond A.I., Trinkle-Mulcahy L.; RT "RRP1B targets PP1 to mammalian cell nucleoli and is associated with pre- RT 60S ribosomal subunits."; RL Mol. Biol. Cell 21:4212-4226(2010). RN [61] RP FUNCTION, PHOSPHORYLATION AT SER-4 BY PLK2, AND MUTAGENESIS OF SER-4; RP THR-95; SER-125 AND THR-199. RX PubMed=20352051; DOI=10.1371/journal.pone.0009849; RA Krause A., Hoffmann I.; RT "Polo-like kinase 2-dependent phosphorylation of NPM/B23 on serine 4 RT triggers centriole duplication."; RL PLoS ONE 5:E9849-E9849(2010). RN [62] RP PHOSPHORYLATION AT THR-199 BY CDK6. RX PubMed=20333249; DOI=10.1371/journal.ppat.1000818; RA Sarek G., Jaerviluoma A., Moore H.M., Tojkander S., Vartia S., RA Biberfeld P., Laiho M., Ojala P.M.; RT "Nucleophosmin phosphorylation by v-cyclin-CDK6 controls KSHV latency."; RL PLoS Pathog. 6:E1000818-E1000818(2010). RN [63] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, PHOSPHORYLATION [LARGE SCALE RP ANALYSIS] AT SER-4; SER-10; SER-70; THR-95; SER-125; SER-137; SER-139; RP THR-199; SER-242; SER-243; SER-260 AND THR-279, PHOSPHORYLATION [LARGE RP SCALE ANALYSIS] AT SER-254 (ISOFORM 3), AND IDENTIFICATION BY MASS RP 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 [64] 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 [65] RP FUNCTION, AND INTERACTION WITH BRCA2. RX PubMed=21084279; DOI=10.1158/0008-5472.can-10-0030; RA Wang H.F., Takenaka K., Nakanishi A., Miki Y.; RT "BRCA2 and nucleophosmin coregulate centrosome amplification and form a RT complex with the Rho effector kinase ROCK2."; RL Cancer Res. 71:68-77(2011). RN [66] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH CENPW. RX PubMed=22002061; DOI=10.1074/jbc.m111.228411; RA Chun Y., Park B., Koh W., Lee S., Cheon Y., Kim R., Che L., Lee S.; RT "New centromeric component CENP-W is an RNA-associated nuclear matrix RT protein that interacts with nucleophosmin/B23 protein."; RL J. Biol. Chem. 286:42758-42769(2011). RN [67] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, PHOSPHORYLATION [LARGE SCALE RP ANALYSIS] AT SER-4; SER-70; SER-125; SER-227; SER-243 AND SER-254, 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 [68] RP FUNCTION, INTERACTION WITH ATF5, AND SUBCELLULAR LOCATION. RX PubMed=22528486; DOI=10.1074/jbc.m112.363622; RA Liu X., Liu D., Qian D., Dai J., An Y., Jiang S., Stanley B., Yang J., RA Wang B., Liu X., Liu D.X.; RT "Nucleophosmin (NPM1/B23) interacts with activating transcription factor 5 RT (ATF5) protein and promotes proteasome- and caspase-dependent ATF5 RT degradation in hepatocellular carcinoma cells."; RL J. Biol. Chem. 287:19599-19609(2012). RN [69] RP INTERACTION WITH DDX31. RX PubMed=23019224; DOI=10.1158/0008-5472.can-12-1645; RA Fukawa T., Ono M., Matsuo T., Uehara H., Miki T., Nakamura Y., RA Kanayama H.O., Katagiri T.; RT "DDX31 regulates the p53-HDM2 pathway and rRNA gene transcription through RT its interaction with NPM1 in renal cell carcinomas."; RL Cancer Res. 72:5867-5877(2012). RN [70] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22223895; DOI=10.1074/mcp.m111.015131; RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., RA Giglione C.; RT "Comparative large-scale characterisation of plant vs. mammal proteins RT reveals similar and idiosyncratic N-alpha acetylation features."; RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012). RN [71] RP INTERACTION WITH NPM3. RX PubMed=22362753; DOI=10.1093/nar/gks162; RA Okuwaki M., Sumi A., Hisaoka M., Saotome-Nakamura A., Akashi S., RA Nishimura Y., Nagata K.; RT "Function of homo- and hetero-oligomers of human RT nucleoplasmin/nucleophosmin family proteins NPM1, NPM2 and NPM3 during RT sperm chromatin remodeling."; RL Nucleic Acids Res. 40:4861-4878(2012). RN [72] RP INTERACTION WITH ALKBH2. RX PubMed=23972994; DOI=10.1016/j.celrep.2013.07.027; RA Li P., Gao S., Wang L., Yu F., Li J., Wang C., Li J., Wong J.; RT "ABH2 couples regulation of ribosomal DNA transcription with DNA alkylation RT repair."; RL Cell Rep. 4:817-829(2013). RN [73] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-4; SER-10; SER-43; SER-70; RP THR-95; SER-125; SER-139; THR-234; THR-237; SER-242; SER-243; SER-254 AND RP SER-260, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [74] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-70 AND SER-243, AND RP IDENTIFICATION BY 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 [75] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-27; LYS-32; LYS-248 AND LYS-250, RP AND 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 [76] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-32; LYS-248; LYS-257 AND LYS-267, RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25114211; DOI=10.1073/pnas.1413825111; RA Impens F., Radoshevich L., Cossart P., Ribet D.; RT "Mapping of SUMO sites and analysis of SUMOylation changes induced by RT external stimuli."; RL Proc. Natl. Acad. Sci. U.S.A. 111:12432-12437(2014). RN [77] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH MYC AND NOP53. RX PubMed=25956029; DOI=10.1016/j.ajpath.2015.03.016; RA Kim J.Y., Cho Y.E., Park J.H.; RT "The nucleolar protein GLTSCR2 is an upstream negative regulator of the RT oncogenic Nucleophosmin-MYC axis."; RL Am. J. Pathol. 185:2061-2068(2015). RN [78] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-32 AND LYS-215, 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 [79] RP SUBUNIT, SUBCELLULAR LOCATION, AND UBIQUITINATION. RX PubMed=25818168; DOI=10.1111/jcmm.12474; RA Kim J.Y., Cho Y.E., An Y.M., Kim S.H., Lee Y.G., Park J.H., Lee S.; RT "GLTSCR2 is an upstream negative regulator of nucleophosmin in cervical RT cancer."; RL J. Cell. Mol. Med. 19:1245-1252(2015). RN [80] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-32, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE 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 [81] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [82] RP ADP-RIBOSYLATION AT SER-207. RX PubMed=28190768; DOI=10.1016/j.molcel.2017.01.003; RA Bonfiglio J.J., Fontana P., Zhang Q., Colby T., Gibbs-Seymour I., RA Atanassov I., Bartlett E., Zaja R., Ahel I., Matic I.; RT "Serine ADP-ribosylation depends on HPF1."; RL Mol. Cell 0:0-0(2017). RN [83] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-32; LYS-141; LYS-150; LYS-215; RP LYS-248; LYS-250; LYS-257; LYS-263; LYS-267 AND LYS-273, AND IDENTIFICATION RP 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 [84] RP INTERACTION WITH ARID3C, AND SUBCELLULAR LOCATION. RX PubMed=38231884; DOI=10.1021/acs.jproteome.3c00509; RA Kim H.S., Kim Y.I., Cho J.Y.; RT "ARID3C Acts as a Regulator of Monocyte-to-Macrophage Differentiation RT Interacting with NPM1."; RL J. Proteome Res. 0:0-0(2024). RN [85] RP X-RAY CRYSTALLOGRAPHY (2.75 ANGSTROMS) OF 9-124. RX PubMed=17879352; DOI=10.1002/prot.21504; RA Lee H.H., Kim H.S., Kang J.Y., Lee B.I., Ha J.Y., Yoon H.J., Lim S.O., RA Jung G., Suh S.W.; RT "Crystal structure of human nucleophosmin-core reveals plasticity of the RT pentamer-pentamer interface."; RL Proteins 69:672-678(2007). RN [86] RP STRUCTURE BY NMR OF 243-294, AND MUTAGENESIS OF LYS-248; LYS-250; LYS-267; RP PHE-268; PHE-276; TRP-288 AND TRP-290. RX PubMed=18511415; DOI=10.1074/jbc.m801706200; RA Grummitt C.G., Townsley F.M., Johnson C.M., Warren A.J., Bycroft M.; RT "Structural consequences of nucleophosmin mutations in acute myeloid RT leukemia."; RL J. Biol. Chem. 283:23326-23332(2008). CC -!- FUNCTION: Involved in diverse cellular processes such as ribosome CC biogenesis, centrosome duplication, protein chaperoning, histone CC assembly, cell proliferation, and regulation of tumor suppressors CC p53/TP53 and ARF. Binds ribosome presumably to drive ribosome nuclear CC export. Associated with nucleolar ribonucleoprotein structures and bind CC single-stranded nucleic acids. Acts as a chaperonin for the core CC histones H3, H2B and H4. Stimulates APEX1 endonuclease activity on CC apurinic/apyrimidinic (AP) double-stranded DNA but inhibits APEX1 CC endonuclease activity on AP single-stranded RNA. May exert a control of CC APEX1 endonuclease activity within nucleoli devoted to repair AP on CC rDNA and the removal of oxidized rRNA molecules. In concert with BRCA2, CC regulates centrosome duplication. Regulates centriole duplication: CC phosphorylation by PLK2 is able to trigger centriole replication. CC Negatively regulates the activation of EIF2AK2/PKR and suppresses CC apoptosis through inhibition of EIF2AK2/PKR autophosphorylation. CC Antagonizes the inhibitory effect of ATF5 on cell proliferation and CC relieves ATF5-induced G2/M blockade (PubMed:22528486). In complex with CC MYC enhances the transcription of MYC target genes (PubMed:25956029). CC May act as chaperonin or cotransporter in the nucleolar localization of CC transcription termination factor TTF1 (By similarity). CC {ECO:0000250|UniProtKB:Q61937, ECO:0000269|PubMed:12882984, CC ECO:0000269|PubMed:16107701, ECO:0000269|PubMed:17015463, CC ECO:0000269|PubMed:18809582, ECO:0000269|PubMed:19188445, CC ECO:0000269|PubMed:20352051, ECO:0000269|PubMed:21084279, CC ECO:0000269|PubMed:22002061, ECO:0000269|PubMed:22528486, CC ECO:0000269|PubMed:25956029}. CC -!- SUBUNIT: Decamer formed by two pentameric rings associated in a head- CC to-head fashion (By similarity). Disulfide-linked dimers under certain CC conditions (PubMed:25818168). The SWAP complex consists of NPM1, NCL, CC PARP1 and SWAP70 (By similarity). Interacts with NSUN2 and SENP3. CC Interacts with the methylated form of RPS10. Interacts (via N-terminal CC domain) with APEX1; the interaction is RNA-dependent and decreases in CC hydrogen peroxide-damaged cells. Interacts with isoform 1 of NEK2. CC Interacts with ROCK2 and BRCA2. Interacts with RPGR. Interacts with CC CENPW. Interacts with EIF2AK2/PKR. Interacts with CEBPA (isoform 4) CC (PubMed:20075868). Interacts with DDX31; this interaction prevents CC interaction between NPM1 and HDM2 (PubMed:23019224). Interacts with CC MYC; competitive with NOP53 (PubMed:25956029). Interacts with NOP53; CC the interaction is direct and competitive with MYC (PubMed:25956029). CC Interacts with LRRC34 (By similarity). Interacts with RRP1B CC (PubMed:19710015, PubMed:20926688). Interacts with NPM3 CC (PubMed:22362753). Interacts with ALKBH2 (PubMed:23972994). Interacts CC with TTF1 (via C-terminal region) (By similarity). Interacts with NOP2 CC (PubMed:8089149). Interacts with ARID3C (via REKLES DOMAIN); the CC interaction mediates ARID3C nuclear shuttling (PubMed:38231884). CC {ECO:0000250|UniProtKB:Q61937, ECO:0000269|PubMed:12882984, CC ECO:0000269|PubMed:15388344, ECO:0000269|PubMed:15772089, CC ECO:0000269|PubMed:17015463, ECO:0000269|PubMed:17215513, CC ECO:0000269|PubMed:18259216, ECO:0000269|PubMed:19015314, CC ECO:0000269|PubMed:19188445, ECO:0000269|PubMed:19710015, CC ECO:0000269|PubMed:20075868, ECO:0000269|PubMed:20159986, CC ECO:0000269|PubMed:20926688, ECO:0000269|PubMed:21084279, CC ECO:0000269|PubMed:22002061, ECO:0000269|PubMed:22362753, CC ECO:0000269|PubMed:22528486, ECO:0000269|PubMed:23019224, CC ECO:0000269|PubMed:23972994, ECO:0000269|PubMed:25818168, CC ECO:0000269|PubMed:25956029, ECO:0000269|PubMed:38231884, CC ECO:0000269|PubMed:8089149}. CC -!- SUBUNIT: (Microbial infection) Interacts with hepatitis delta virus S- CC HDAg. {ECO:0000269|PubMed:11309377}. CC -!- SUBUNIT: (Microbial infection) Interacts with HTLV1 Rex protein (via N- CC terminal nuclear localization signal). {ECO:0000269|PubMed:8314759}. CC -!- INTERACTION: CC P06748; O14965: AURKA; NbExp=3; IntAct=EBI-78579, EBI-448680; CC P06748; Q96GD4: AURKB; NbExp=6; IntAct=EBI-78579, EBI-624291; CC P06748; Q96CT7: CCDC124; NbExp=8; IntAct=EBI-78579, EBI-5461329; CC P06748; Q8N726: CDKN2A; NbExp=2; IntAct=EBI-78579, EBI-625922; CC P06748; Q96MT8: CEP63; NbExp=2; IntAct=EBI-78579, EBI-741977; CC P06748; P10176: COX8A; NbExp=3; IntAct=EBI-78579, EBI-3904738; CC P06748; Q10570: CPSF1; NbExp=2; IntAct=EBI-78579, EBI-347859; CC P06748; P19525: EIF2AK2; NbExp=4; IntAct=EBI-78579, EBI-640775; CC P06748; P60228: EIF3E; NbExp=3; IntAct=EBI-78579, EBI-347740; CC P06748; Q13547: HDAC1; NbExp=2; IntAct=EBI-78579, EBI-301834; CC P06748; Q92769: HDAC2; NbExp=2; IntAct=EBI-78579, EBI-301821; CC P06748; Q9BXL5: HEMGN; NbExp=7; IntAct=EBI-78579, EBI-3916399; CC P06748; Q92876: KLK6; NbExp=3; IntAct=EBI-78579, EBI-2432309; CC P06748; O00505: KPNA3; NbExp=2; IntAct=EBI-78579, EBI-358297; CC P06748; O00629: KPNA4; NbExp=2; IntAct=EBI-78579, EBI-396343; CC P06748; Q71RC2: LARP4; NbExp=3; IntAct=EBI-78579, EBI-2878091; CC P06748; Q9NX58: LYAR; NbExp=2; IntAct=EBI-78579, EBI-713507; CC P06748; Q00987: MDM2; NbExp=5; IntAct=EBI-78579, EBI-389668; CC P06748; Q9BZQ8: NIBAN1; NbExp=7; IntAct=EBI-78579, EBI-6916466; CC P06748; Q86SE8: NPM2; NbExp=8; IntAct=EBI-78579, EBI-6658150; CC P06748; Q86SE8-2: NPM2; NbExp=5; IntAct=EBI-78579, EBI-12193061; CC P06748; Q8IZL8: PELP1; NbExp=4; IntAct=EBI-78579, EBI-716449; CC P06748; Q96BK5: PINX1; NbExp=13; IntAct=EBI-78579, EBI-721782; CC P06748; P49207: RPL34; NbExp=2; IntAct=EBI-78579, EBI-1051893; CC P06748; P62753: RPS6; NbExp=3; IntAct=EBI-78579, EBI-356625; CC P06748; Q9H4L4: SENP3; NbExp=7; IntAct=EBI-78579, EBI-2880236; CC P06748; O14746: TERT; NbExp=5; IntAct=EBI-78579, EBI-1772203; CC P06748; P05549: TFAP2A; NbExp=6; IntAct=EBI-78579, EBI-347351; CC P06748; P04637: TP53; NbExp=6; IntAct=EBI-78579, EBI-366083; CC P06748; P63104: YWHAZ; NbExp=2; IntAct=EBI-78579, EBI-347088; CC P06748; Q64364: Cdkn2a; Xeno; NbExp=2; IntAct=EBI-78579, EBI-1202287; CC P06748; P24938: L2; Xeno; NbExp=4; IntAct=EBI-78579, EBI-7481199; CC P06748; P68951: L2; Xeno; NbExp=5; IntAct=EBI-78579, EBI-7481182; CC P06748; P0DOE7: M; Xeno; NbExp=3; IntAct=EBI-78579, EBI-10042882; CC P06748; Q6UPD4: NP; Xeno; NbExp=4; IntAct=EBI-78579, EBI-25616456; CC P06748; P03427: PB2; Xeno; NbExp=3; IntAct=EBI-78579, EBI-8430745; CC P06748; B1Q2W9: pre-C/C; Xeno; NbExp=8; IntAct=EBI-78579, EBI-9081051; CC P06748; Q98147; Xeno; NbExp=2; IntAct=EBI-78579, EBI-626601; CC P06748-1; P49450-1: CENPA; NbExp=3; IntAct=EBI-354150, EBI-15826012; CC P06748-1; P63165: SUMO1; NbExp=3; IntAct=EBI-354150, EBI-80140; CC P06748-1; P04637: TP53; NbExp=3; IntAct=EBI-354150, EBI-366083; CC P06748-1; Q14669: TRIP12; NbExp=2; IntAct=EBI-354150, EBI-308443; CC P06748-2; Q86SE8-2: NPM2; NbExp=4; IntAct=EBI-354154, EBI-12193061; CC -!- SUBCELLULAR LOCATION: Nucleus, nucleolus {ECO:0000269|PubMed:19208757, CC ECO:0000269|PubMed:22528486, ECO:0000269|PubMed:25818168, CC ECO:0000269|PubMed:25956029}. Nucleus, nucleoplasm CC {ECO:0000269|PubMed:25818168}. Cytoplasm, cytoskeleton, microtubule CC organizing center, centrosome {ECO:0000269|PubMed:14654843}. CC Note=Generally nucleolar, but is translocated to the nucleoplasm in CC case of serum starvation or treatment with anticancer drugs. Has been CC found in the cytoplasm in patients with primary acute myelogenous CC leukemia (AML), but not with secondary AML. Co-localizes with the CC methylated form of RPS10 in the granular component (GC) region of the CC nucleolus. Colocalized with nucleolin and APEX1 in nucleoli. Isoform 1 CC of NEK2 is required for its localization to the centrosome during CC mitosis. Can shuttle between cytoplasm and nucleus (PubMed:38231884). CC {ECO:0000269|PubMed:38231884}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=P06748-1; Sequence=Displayed; CC Name=2; CC IsoId=P06748-2; Sequence=VSP_003616; CC Name=3; CC IsoId=P06748-3; Sequence=VSP_043599; CC -!- PTM: Acetylated at C-terminal lysine residues, thereby increasing CC affinity to histones. {ECO:0000269|PubMed:16107701, CC ECO:0000269|Ref.17}. CC -!- PTM: ADP-ribosylated. CC -!- PTM: Phosphorylated at Ser-4 by PLK1 and PLK2. Phosphorylation at Ser-4 CC by PLK2 in S phase is required for centriole duplication and is CC sufficient to trigger centriole replication. Phosphorylation at Ser-4 CC by PLK1 takes place during mitosis. Phosphorylated by CDK2 at Ser-125 CC and Thr-199. Phosphorylation at Thr-199 may trigger initiation of CC centrosome duplication. Phosphorylated by CDK1 at Thr-199, Thr-219, CC Thr-234 and Thr-237 during cell mitosis. When these four sites are CC phosphorylated, RNA-binding activity seem to be abolished. May be CC phosphorylated at Ser-70 by NEK2. The Thr-199 phosphorylated form has CC higher affinity for ROCK2. CDK6 triggers Thr-199 phosphorylation when CC complexed to Kaposi's sarcoma herpesvirus (KSHV) V-cyclin, leading to CC viral reactivation by reducing viral LANA levels. CC {ECO:0000269|PubMed:11051553, ECO:0000269|PubMed:12058066, CC ECO:0000269|PubMed:12882984, ECO:0000269|PubMed:15190079, CC ECO:0000269|PubMed:15388344, ECO:0000269|PubMed:20333249, CC ECO:0000269|PubMed:20352051, ECO:0000269|Ref.17}. CC -!- PTM: Sumoylated by ARF. {ECO:0000269|PubMed:15897463}. CC -!- PTM: Ubiquitinated. Ubiquitination leads to proteasomal degradation. CC Deubiquitinated by USP36 (PubMed:19208757). CC {ECO:0000269|PubMed:19208757, ECO:0000269|PubMed:25818168}. CC -!- DISEASE: Note=A chromosomal aberration involving NPM1 is found in a CC form of non-Hodgkin lymphoma. Translocation t(2;5)(p23;q35) with ALK. CC The resulting chimeric NPM1-ALK protein homodimerize and the kinase CC becomes constitutively activated. {ECO:0000269|PubMed:8122112, CC ECO:0000269|PubMed:8633037}. CC -!- DISEASE: Note=A chromosomal aberration involving NPM1 is found in a CC form of acute promyelocytic leukemia. Translocation t(5;17)(q32;q11) CC with RARA. {ECO:0000269|PubMed:8562957}. CC -!- DISEASE: Note=A chromosomal aberration involving NPM1 is a cause of CC myelodysplastic syndrome (MDS). Translocation t(3;5)(q25.1;q34) with CC MLF1. {ECO:0000269|PubMed:8570204}. CC -!- DISEASE: Note=Defects in NPM1 are associated with acute myelogenous CC leukemia (AML). Mutations in exon 12 affecting the C-terminus of the CC protein are associated with an aberrant cytoplasmic location. CC {ECO:0000269|PubMed:15659725}. CC -!- SIMILARITY: Belongs to the nucleoplasmin family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/22/NPM1"; 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; M23613; AAA36380.1; -; mRNA. DR EMBL; M28699; AAA58386.1; -; mRNA. DR EMBL; M26697; AAA36385.1; -; mRNA. DR EMBL; U89321; AAB94739.1; -; Genomic_DNA. DR EMBL; U89309; AAB94739.1; JOINED; Genomic_DNA. DR EMBL; U89310; AAB94739.1; JOINED; Genomic_DNA. DR EMBL; U89311; AAB94739.1; JOINED; Genomic_DNA. DR EMBL; U89313; AAB94739.1; JOINED; Genomic_DNA. DR EMBL; U89314; AAB94739.1; JOINED; Genomic_DNA. DR EMBL; U89317; AAB94739.1; JOINED; Genomic_DNA. DR EMBL; U89319; AAB94739.1; JOINED; Genomic_DNA. DR EMBL; AB042278; BAB40600.1; -; mRNA. DR EMBL; AY740634; AAW67752.1; -; mRNA. DR EMBL; AY740635; AAW67753.1; -; mRNA. DR EMBL; AY740636; AAW67754.1; -; mRNA. DR EMBL; AY740637; AAW67755.1; -; mRNA. DR EMBL; AY740638; AAW67756.1; -; mRNA. DR EMBL; AY740639; AAW67757.1; -; mRNA. DR EMBL; AY740640; AAW67758.1; -; mRNA. DR EMBL; DQ303464; ABC40399.1; -; mRNA. DR EMBL; AY347529; AAQ24860.1; -; mRNA. DR EMBL; BT007011; AAP35657.1; -; mRNA. DR EMBL; AK290652; BAF83341.1; -; mRNA. DR EMBL; AB451236; BAG70050.1; -; mRNA. DR EMBL; AB451361; BAG70175.1; -; mRNA. DR EMBL; CH471062; EAW61443.1; -; Genomic_DNA. DR EMBL; CH471062; EAW61446.1; -; Genomic_DNA. DR EMBL; BC002398; AAH02398.1; -; mRNA. DR EMBL; BC008495; AAH08495.1; -; mRNA. DR EMBL; BC009623; AAH09623.1; -; mRNA. DR EMBL; BC012566; AAH12566.1; -; mRNA. DR EMBL; BC014349; AAH14349.1; -; mRNA. DR EMBL; BC016716; AAH16716.1; -; mRNA. DR EMBL; BC016768; AAH16768.1; -; mRNA. DR EMBL; BC016824; AAH16824.1; -; mRNA. DR EMBL; BC021668; AAH21668.1; -; mRNA. DR EMBL; BC021983; AAH21983.1; -; mRNA. DR EMBL; BC050628; AAH50628.1; -; mRNA. DR EMBL; BC107754; AAI07755.1; -; mRNA. DR EMBL; U41742; AAB00112.1; ALT_TERM; mRNA. DR EMBL; U41743; AAB00113.1; ALT_TERM; mRNA. DR EMBL; U04946; AAA58698.1; ALT_TERM; mRNA. DR EMBL; D45915; BAA08343.1; ALT_TERM; mRNA. DR EMBL; X16934; CAA34809.1; -; mRNA. DR EMBL; J02590; AAA36473.1; -; mRNA. DR EMBL; M31004; AAA36474.1; -; mRNA. DR CCDS; CCDS43399.1; -. [P06748-3] DR CCDS; CCDS4376.1; -. [P06748-1] DR CCDS; CCDS4377.1; -. [P06748-2] DR PIR; A33423; A32915. DR PIR; I38491; I38491. DR RefSeq; NP_001032827.1; NM_001037738.3. [P06748-3] DR RefSeq; NP_001341935.1; NM_001355006.2. [P06748-1] DR RefSeq; NP_002511.1; NM_002520.7. [P06748-1] DR RefSeq; NP_954654.1; NM_199185.4. [P06748-2] DR PDB; 2LLH; NMR; -; A=225-294. DR PDB; 2P1B; X-ray; 2.75 A; A/B/C/D/E/F/G/H/I/J=9-122. DR PDB; 2VXD; NMR; -; A=243-294. DR PDB; 5EHD; X-ray; 2.55 A; A/B/C/D/E/F/G/H/I/J/a/b/c/d/e/f/g/h/i/j=9-124. DR PDB; 7OBG; X-ray; 1.80 A; B=284-294. DR PDB; 7OBH; X-ray; 2.00 A; B=284-294. DR PDB; 8AH2; X-ray; 2.90 A; A/C=44-55. DR PDB; 8AS5; EM; 2.50 A; A/B/C/D/E=1-294. DR PDBsum; 2LLH; -. DR PDBsum; 2P1B; -. DR PDBsum; 2VXD; -. DR PDBsum; 5EHD; -. DR PDBsum; 7OBG; -. DR PDBsum; 7OBH; -. DR PDBsum; 8AH2; -. DR PDBsum; 8AS5; -. DR AlphaFoldDB; P06748; -. DR BMRB; P06748; -. DR EMDB; EMD-15606; -. DR SMR; P06748; -. DR BioGRID; 110929; 1283. DR CORUM; P06748; -. DR DIP; DIP-30932N; -. DR FunCoup; P06748; 1923. DR IntAct; P06748; 1134. DR MINT; P06748; -. DR STRING; 9606.ENSP00000296930; -. DR BindingDB; P06748; -. DR ChEMBL; CHEMBL5178; -. DR DrugBank; DB11638; Artenimol. DR DrugCentral; P06748; -. DR GlyCosmos; P06748; 4 sites, 1 glycan. DR GlyGen; P06748; 8 sites, 1 O-linked glycan (8 sites). DR iPTMnet; P06748; -. DR MetOSite; P06748; -. DR PhosphoSitePlus; P06748; -. DR SwissPalm; P06748; -. DR BioMuta; NPM1; -. DR DMDM; 114762; -. DR REPRODUCTION-2DPAGE; IPI00549248; -. DR jPOST; P06748; -. DR MassIVE; P06748; -. DR PaxDb; 9606-ENSP00000296930; -. DR PeptideAtlas; P06748; -. DR PRIDE; P06748; -. DR ProteomicsDB; 51927; -. [P06748-1] DR ProteomicsDB; 51928; -. [P06748-2] DR ProteomicsDB; 51929; -. [P06748-3] DR Pumba; P06748; -. DR TopDownProteomics; P06748-1; -. [P06748-1] DR TopDownProteomics; P06748-2; -. [P06748-2] DR TopDownProteomics; P06748-3; -. [P06748-3] DR Antibodypedia; 1828; 1350 antibodies from 48 providers. DR DNASU; 4869; -. DR Ensembl; ENST00000296930.10; ENSP00000296930.5; ENSG00000181163.15. [P06748-1] DR Ensembl; ENST00000351986.10; ENSP00000341168.6; ENSG00000181163.15. [P06748-2] DR Ensembl; ENST00000393820.2; ENSP00000377408.2; ENSG00000181163.15. [P06748-3] DR Ensembl; ENST00000517671.5; ENSP00000428755.1; ENSG00000181163.15. [P06748-1] DR Ensembl; ENST00000678280.1; ENSP00000503235.1; ENSG00000181163.15. [P06748-3] DR GeneID; 4869; -. DR KEGG; hsa:4869; -. DR MANE-Select; ENST00000296930.10; ENSP00000296930.5; NM_002520.7; NP_002511.1. DR UCSC; uc003mbh.4; human. [P06748-1] DR AGR; HGNC:7910; -. DR CIViC; 4869; 1 clinical assertion and 37 evidence items across 4 molecular profiles. DR ClinPGx; PA31712; -. DR CTD; 4869; -. DR DisGeNET; 4869; -. DR GeneCards; NPM1; -. DR HGNC; HGNC:7910; NPM1. DR HPA; ENSG00000181163; Low tissue specificity. DR MalaCards; NPM1; -. DR MIM; 164040; gene. DR OpenTargets; ENSG00000181163; -. DR Orphanet; 98834; Acute myeloblastic leukemia with maturation. DR Orphanet; 98833; Acute myeloblastic leukemia without maturation. DR Orphanet; 402026; Acute myeloid leukemia with NPM1 somatic mutations. DR Orphanet; 520; Acute promyelocytic leukemia. DR Orphanet; 1775; Dyskeratosis congenita. DR Orphanet; 98842; Lymphomatoid papulosis. DR Orphanet; 300865; Primary cutaneous anaplastic large cell lymphoma. DR VEuPathDB; HostDB:ENSG00000181163; -. DR eggNOG; KOG0488; Eukaryota. DR GeneTree; ENSGT00940000153052; -. DR HOGENOM; CLU_058838_0_0_1; -. DR InParanoid; P06748; -. DR OMA; MEKGMNL; -. DR OrthoDB; 9946910at2759; -. DR PAN-GO; P06748; 16 GO annotations based on evolutionary models. DR PhylomeDB; P06748; -. DR PathwayCommons; P06748; -. DR Reactome; R-HSA-180746; Nuclear import of Rev protein. DR Reactome; R-HSA-3899300; SUMOylation of transcription cofactors. DR Reactome; R-HSA-606279; Deposition of new CENPA-containing nucleosomes at the centromere. DR Reactome; R-HSA-6804115; TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain. DR Reactome; R-HSA-8869496; TFAP2A acts as a transcriptional repressor during retinoic acid induced cell differentiation. DR Reactome; R-HSA-9692914; SARS-CoV-1-host interactions. DR Reactome; R-HSA-9700645; ALK mutants bind TKIs. DR Reactome; R-HSA-9725370; Signaling by ALK fusions and activated point mutants. DR Reactome; R-HSA-9725371; Nuclear events stimulated by ALK signaling in cancer. DR Reactome; R-HSA-9833482; PKR-mediated signaling. DR SignaLink; P06748; -. DR SIGNOR; P06748; -. DR Agora; ENSG00000181163; -. DR BioGRID-ORCS; 4869; 540 hits in 1103 CRISPR screens. DR CD-CODE; 6AB35885; Synthetic Condensate 000052. DR CD-CODE; 71F78BB1; Synthetic Condensate 000049. DR CD-CODE; 80B4651A; Granular component. DR CD-CODE; 8C2F96ED; Centrosome. DR CD-CODE; 91857CE7; Nucleolus. DR CD-CODE; 9E412E21; Synthetic Condensate 000044. DR CD-CODE; A3AA02E8; Synthetic Condensate 000061. DR CD-CODE; CBF57B02; Synthetic Condensate 000043. DR CD-CODE; D551D4B1; Synthetic Condensate 000051. DR CD-CODE; DEE660B4; Stress granule. DR ChiTaRS; NPM1; human. DR EvolutionaryTrace; P06748; -. DR GeneWiki; NPM1; -. DR GenomeRNAi; 4869; -. DR Pharos; P06748; Tbio. DR PRO; PR:P06748; -. DR Proteomes; UP000005640; Chromosome 5. DR RNAct; P06748; protein. DR Bgee; ENSG00000181163; Expressed in calcaneal tendon and 191 other cell types or tissues. DR ExpressionAtlas; P06748; baseline and differential. DR GO; GO:0005813; C:centrosome; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005925; C:focal adhesion; HDA:UniProtKB. DR GO; GO:0001652; C:granular component; TAS:Reactome. DR GO; GO:0015934; C:large ribosomal subunit; IEA:Ensembl. DR GO; GO:0016020; C:membrane; HDA:UniProtKB. DR GO; GO:0016607; C:nuclear speck; IEA:Ensembl. DR GO; GO:0005730; C:nucleolus; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0032991; C:protein-containing complex; IDA:CAFA. DR GO; GO:0032993; C:protein-DNA complex; IDA:CAFA. DR GO; GO:1990904; C:ribonucleoprotein complex; IDA:MGI. DR GO; GO:0015935; C:small ribosomal subunit; IEA:Ensembl. DR GO; GO:0031616; C:spindle pole centrosome; IDA:UniProtKB. DR GO; GO:0003682; F:chromatin binding; IBA:GO_Central. DR GO; GO:0001046; F:core promoter sequence-specific DNA binding; IDA:CAFA. DR GO; GO:0140297; F:DNA-binding transcription factor binding; IPI:CAFA. DR GO; GO:0042393; F:histone binding; IDA:UniProtKB. DR GO; GO:0060090; F:molecular adaptor activity; IDA:UniProt. DR GO; GO:0051059; F:NF-kappaB binding; IDA:UniProtKB. DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB. DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB. DR GO; GO:0004860; F:protein kinase inhibitor activity; IDA:UniProtKB. DR GO; GO:0043023; F:ribosomal large subunit binding; IDA:MGI. DR GO; GO:0043024; F:ribosomal small subunit binding; IDA:MGI. DR GO; GO:0003723; F:RNA binding; IDA:UniProtKB. DR GO; GO:0019843; F:rRNA binding; IPI:DisProt. DR GO; GO:0030957; F:Tat protein binding; IDA:UniProtKB. DR GO; GO:0003713; F:transcription coactivator activity; IDA:UniProtKB. DR GO; GO:0051082; F:unfolded protein binding; IDA:UniProtKB. DR GO; GO:0006884; P:cell volume homeostasis; IEA:Ensembl. DR GO; GO:0034644; P:cellular response to UV; IDA:CAFA. DR GO; GO:0090398; P:cellular senescence; IMP:GO_Central. DR GO; GO:0007098; P:centrosome cycle; IMP:UniProtKB. DR GO; GO:0006338; P:chromatin remodeling; IBA:GO_Central. DR GO; GO:0006281; P:DNA repair; IDA:UniProtKB. DR GO; GO:0008104; P:intracellular protein localization; IDA:UniProtKB. DR GO; GO:0006886; P:intracellular protein transport; TAS:UniProtKB. DR GO; GO:0030225; P:macrophage differentiation; IDA:UniProt. DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB. DR GO; GO:0008285; P:negative regulation of cell population proliferation; IMP:UniProtKB. DR GO; GO:0010826; P:negative regulation of centrosome duplication; IMP:UniProtKB. DR GO; GO:0048025; P:negative regulation of mRNA splicing, via spliceosome; IEA:Ensembl. DR GO; GO:0044387; P:negative regulation of protein kinase activity by regulation of protein phosphorylation; IDA:UniProtKB. DR GO; GO:0006913; P:nucleocytoplasmic transport; IDA:UniProtKB. DR GO; GO:0006334; P:nucleosome assembly; IDA:UniProtKB. DR GO; GO:1902751; P:positive regulation of cell cycle G2/M phase transition; IDA:UniProtKB. DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:UniProtKB. DR GO; GO:0010825; P:positive regulation of centrosome duplication; IEA:Ensembl. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IMP:UniProtKB. DR GO; GO:1904751; P:positive regulation of protein localization to nucleolus; IEA:Ensembl. DR GO; GO:0031398; P:positive regulation of protein ubiquitination; IEA:Ensembl. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:CAFA. DR GO; GO:0045727; P:positive regulation of translation; IDA:UniProtKB. DR GO; GO:0006606; P:protein import into nucleus; IDA:UniProt. DR GO; GO:0050821; P:protein stabilization; IEA:Ensembl. DR GO; GO:0001558; P:regulation of cell growth; IEA:Ensembl. DR GO; GO:0046599; P:regulation of centriole replication; IMP:UniProtKB. DR GO; GO:0010824; P:regulation of centrosome duplication; IBA:GO_Central. DR GO; GO:0043516; P:regulation of DNA damage response, signal transduction by p53 class mediator; IEA:Ensembl. DR GO; GO:0060735; P:regulation of eIF2 alpha phosphorylation by dsRNA; IDA:UniProtKB. DR GO; GO:1902629; P:regulation of mRNA stability involved in cellular response to UV; IMP:UniProtKB. DR GO; GO:0042273; P:ribosomal large subunit biogenesis; IBA:GO_Central. DR GO; GO:0000055; P:ribosomal large subunit export from nucleus; IBA:GO_Central. DR GO; GO:0042274; P:ribosomal small subunit biogenesis; IBA:GO_Central. DR GO; GO:0000056; P:ribosomal small subunit export from nucleus; IBA:GO_Central. DR GO; GO:0042255; P:ribosome assembly; TAS:UniProtKB. DR GO; GO:0007165; P:signal transduction; NAS:UniProtKB. DR DisProt; DP01474; -. DR FunFam; 1.10.10.2100:FF:000001; Nucleophosmin 1; 1. DR FunFam; 2.60.120.340:FF:000001; Nucleophosmin 1; 1. DR Gene3D; 1.10.10.2100; -; 1. DR Gene3D; 2.60.120.340; Nucleoplasmin core domain; 1. DR IDEAL; IID00295; -. DR InterPro; IPR032569; NPM1_C. DR InterPro; IPR004301; Nucleoplasmin. DR InterPro; IPR024057; Nucleoplasmin_core_dom. DR InterPro; IPR036824; Nucleoplasmin_core_dom_sf. DR PANTHER; PTHR22747:SF28; NUCLEOPHOSMIN; 1. DR PANTHER; PTHR22747; NUCLEOPLASMIN; 1. DR Pfam; PF16276; NPM1-C; 1. DR Pfam; PF03066; Nucleoplasmin; 1. DR SUPFAM; SSF69203; Nucleoplasmin-like core domain; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; ADP-ribosylation; Alternative splicing; KW Chaperone; Chromosomal rearrangement; Cytoplasm; Cytoskeleton; KW Direct protein sequencing; Disulfide bond; Host-virus interaction; KW Isopeptide bond; Nucleus; Phosphoprotein; Proteomics identification; KW Proto-oncogene; Reference proteome; RNA-binding; Ubl conjugation. FT CHAIN 1..294 FT /note="Nucleophosmin" FT /id="PRO_0000219481" FT REGION 1..186 FT /note="Required for interaction with SENP3" FT REGION 1..117 FT /note="Necessary for interaction with APEX1" FT /evidence="ECO:0000269|PubMed:19188445" FT REGION 120..247 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 187..215 FT /note="Interaction with NOP2" FT /evidence="ECO:0000269|PubMed:8089149" FT REGION 243..294 FT /note="Required for nucleolar localization" FT MOTIF 152..157 FT /note="Nuclear localization signal" FT /evidence="ECO:0000255" FT MOTIF 191..197 FT /note="Nuclear localization signal" FT /evidence="ECO:0000255" FT COMPBIAS 120..132 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 161..187 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 188..200 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 202..222 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 223..235 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT SITE 55 FT /note="Interaction between pentamers" FT /evidence="ECO:0000250" FT SITE 80 FT /note="Interaction between pentamers" FT /evidence="ECO:0000250" FT SITE 175..176 FT /note="Breakpoint for translocation to form NPM1-MLF1" FT /evidence="ECO:0000269|PubMed:8570204" FT MOD_RES 1 FT /note="N-acetylmethionine" FT /evidence="ECO:0000269|Ref.17, ECO:0007744|PubMed:19413330, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:22223895" FT MOD_RES 4 FT /note="Phosphoserine; by PLK1 and PLK2" FT /evidence="ECO:0000269|PubMed:15190079, FT ECO:0000269|PubMed:20352051, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163" FT MOD_RES 10 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:23186163" FT MOD_RES 32 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 43 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 67 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:Q61937" FT MOD_RES 70 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17081983, FT ECO:0007744|PubMed:17924679, ECO:0007744|PubMed:18220336, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:18691976, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163, FT ECO:0007744|PubMed:24275569" FT MOD_RES 75 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 95 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:17081983, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:23186163" FT MOD_RES 125 FT /note="Phosphoserine; by CDK2" FT /evidence="ECO:0000269|Ref.17, ECO:0007744|PubMed:18220336, FT ECO:0007744|PubMed:18318008, ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:19369195, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163" FT MOD_RES 137 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231" FT MOD_RES 139 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163" FT MOD_RES 150 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0007744|PubMed:16916647, FT ECO:0007744|PubMed:19608861" FT MOD_RES 154 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:16916647" FT MOD_RES 199 FT /note="Phosphothreonine; by CDK1, CDK2 and CDK6" FT /evidence="ECO:0000269|PubMed:12058066, FT ECO:0000269|PubMed:20333249, ECO:0007744|PubMed:17924679, FT ECO:0007744|PubMed:20068231" FT MOD_RES 207 FT /note="ADP-ribosylserine" FT /evidence="ECO:0000269|PubMed:28190768" FT MOD_RES 212 FT /note="N6-acetyllysine" FT /evidence="ECO:0000269|PubMed:16107701, FT ECO:0007744|PubMed:16916647" FT MOD_RES 219 FT /note="Phosphothreonine; by CDK1" FT /evidence="ECO:0000305|PubMed:12058066" FT MOD_RES 227 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692" FT MOD_RES 229 FT /note="N6-acetyllysine" FT /evidence="ECO:0000269|PubMed:16107701" FT MOD_RES 230 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000269|PubMed:16107701" FT MOD_RES 234 FT /note="Phosphothreonine; by CDK1" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT MOD_RES 237 FT /note="Phosphothreonine; by CDK1" FT /evidence="ECO:0000269|PubMed:12058066, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:23186163" FT MOD_RES 242 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:23186163" FT MOD_RES 243 FT /note="Phosphoserine" FT /evidence="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 250 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000269|PubMed:16107701" FT MOD_RES 254 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17924679, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163" FT MOD_RES 257 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000269|PubMed:16107701, FT ECO:0007744|PubMed:19608861" FT MOD_RES 260 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:23186163" FT MOD_RES 267 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 267 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q61937" FT MOD_RES 273 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 279 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:18220336, FT ECO:0007744|PubMed:20068231" FT MOD_RES 292 FT /note="N6-acetyllysine" FT /evidence="ECO:0000269|PubMed:16107701" FT CROSSLNK 27 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:25218447" FT CROSSLNK 32 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO1); alternate" FT /evidence="ECO:0007744|PubMed:25114211" FT CROSSLNK 32 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0007744|PubMed:25114211, FT ECO:0007744|PubMed:25218447, ECO:0007744|PubMed:25755297, FT ECO:0007744|PubMed:25772364, ECO:0007744|PubMed:28112733" FT CROSSLNK 141 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 150 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 215 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:25772364, FT ECO:0007744|PubMed:28112733" FT CROSSLNK 230 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO); alternate" FT CROSSLNK 248 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO1); alternate" FT /evidence="ECO:0007744|PubMed:25114211" FT CROSSLNK 248 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0007744|PubMed:25114211, FT ECO:0007744|PubMed:25218447, ECO:0007744|PubMed:28112733" FT CROSSLNK 250 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0007744|PubMed:25218447, FT ECO:0007744|PubMed:28112733" FT CROSSLNK 257 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO1); alternate" FT /evidence="ECO:0007744|PubMed:25114211" FT CROSSLNK 257 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0007744|PubMed:25114211, FT ECO:0007744|PubMed:28112733" FT CROSSLNK 263 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO); alternate" FT /evidence="ECO:0000269|PubMed:15897463" FT CROSSLNK 263 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 267 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO1); alternate" FT /evidence="ECO:0007744|PubMed:25114211" FT CROSSLNK 267 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 273 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0007744|PubMed:28112733" FT VAR_SEQ 195..223 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_003616" FT VAR_SEQ 258..294 FT /note="GGSLPKVEAKFINYVKNCFRMTDQEAIQDLWQWRKSL -> AH (in FT isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334, ECO:0000303|Ref.5" FT /id="VSP_043599" FT MUTAGEN 4 FT /note="S->A: Abolishes phosphorylation by PLK2 and impairs FT centriole duplication." FT /evidence="ECO:0000269|PubMed:20352051" FT MUTAGEN 4 FT /note="S->D,E: Mimicks phosphorylation state, inducing FT accumulation of centrioles." FT /evidence="ECO:0000269|PubMed:20352051" FT MUTAGEN 95 FT /note="T->A: Does not affect phosphorylation by PLK2." FT /evidence="ECO:0000269|PubMed:20352051" FT MUTAGEN 125 FT /note="S->A: Does not affect phosphorylation by PLK2." FT /evidence="ECO:0000269|PubMed:20352051" FT MUTAGEN 199 FT /note="T->A: Partial loss of phosphorylation. Does not FT affect phosphorylation by PLK2." FT /evidence="ECO:0000269|PubMed:12058066, FT ECO:0000269|PubMed:20352051" FT MUTAGEN 219 FT /note="T->A: Partial loss of phosphorylation." FT /evidence="ECO:0000269|PubMed:12058066" FT MUTAGEN 234 FT /note="T->A: Partial loss of phosphorylation; when FT associated with A-237." FT /evidence="ECO:0000269|PubMed:12058066" FT MUTAGEN 237 FT /note="T->A: Partial loss of phosphorylation." FT /evidence="ECO:0000269|PubMed:12058066" FT MUTAGEN 248 FT /note="K->A: Partial destabilization of the structure." FT /evidence="ECO:0000269|PubMed:18511415" FT MUTAGEN 250 FT /note="K->A: Increase in the stabilization of the FT structure." FT /evidence="ECO:0000269|PubMed:18511415" FT MUTAGEN 263 FT /note="K->A: Increase in the stabilization of the structure FT and partial delocalization to the nucleoplasm. Complete FT delocalization to the nucleoplasm; when associated with A- FT 267." FT /evidence="ECO:0000269|PubMed:18259216" FT MUTAGEN 263 FT /note="K->R: No change in the sumoylation level." FT /evidence="ECO:0000269|PubMed:18259216" FT MUTAGEN 267 FT /note="K->A: Increase in the stabilization of the structure FT and complete delocalization to the nucleoplasm. Complete FT delocalization to the nucleoplasm; when associated with A- FT 263." FT /evidence="ECO:0000269|PubMed:18511415" FT MUTAGEN 268 FT /note="F->A: Complete destabilization of the structure and FT loss of nucleolus localization; when associated with A- FT 276." FT /evidence="ECO:0000269|PubMed:18511415" FT MUTAGEN 276 FT /note="F->A: Complete destabilization of the structure and FT loss of nucleolus localization; when associated with A- FT 268." FT /evidence="ECO:0000269|PubMed:18511415" FT MUTAGEN 288 FT /note="W->A: Complete destabilization of the structure; FT when associated with A-290." FT /evidence="ECO:0000269|PubMed:18511415" FT MUTAGEN 290 FT /note="W->A: Partial destabilization of the structure. FT Complete destabilization of the structure; when associated FT with A-288." FT /evidence="ECO:0000269|PubMed:18511415" FT CONFLICT 80 FT /note="K -> E (in Ref. 13; AAH21983)" FT /evidence="ECO:0000305" FT CONFLICT 129 FT /note="E -> D (in Ref. 22; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 168 FT /note="Missing (in Ref. 6; AAW67758)" FT /evidence="ECO:0000305" FT CONFLICT 178 FT /note="D -> G (in Ref. 13; AAH16768)" FT /evidence="ECO:0000305" FT CONFLICT 183 FT /note="D -> N (in Ref. 11; BAG70175/BAG70050)" FT /evidence="ECO:0000305" FT CONFLICT 213 FT /note="D -> P (in Ref. 23; AAA36473/AAA36474)" FT /evidence="ECO:0000305" FT CONFLICT 214 FT /note="S -> L (in Ref. 21; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 216 FT /note="P -> S (in Ref. 23; AAA36473)" FT /evidence="ECO:0000305" FT CONFLICT 219..221 FT /note="TPR -> SSS (in Ref. 23; AAA36473)" FT /evidence="ECO:0000305" FT CONFLICT 231 FT /note="Q -> R (in Ref. 8; AAQ24860)" FT /evidence="ECO:0000305" FT CONFLICT 271 FT /note="Y -> C (in Ref. 13; AAH16768)" FT /evidence="ECO:0000305" FT CONFLICT 287 FT /note="L -> F (in Ref. 13; AAH12566)" FT /evidence="ECO:0000305" FT CONFLICT 288..294 FT /note="WQWRKSL -> CLAVEEVSLRK (in Ref. 6; AAW67752/ FT AAW67755)" FT /evidence="ECO:0000305" FT CONFLICT 288..294 FT /note="WQWRKSL -> CMAVEEVSLRK (in Ref. 6; AAW67753 and 7; FT ABC40399)" FT /evidence="ECO:0000305" FT CONFLICT 288..294 FT /note="WQWRKSL -> CVAVEEVSLRK (in Ref. 6; AAW67754)" FT /evidence="ECO:0000305" FT CONFLICT 290..294 FT /note="WRKSL -> SLAQVSLRK (in Ref. 6; AAW67756)" FT /evidence="ECO:0000305" FT CONFLICT 290..294 FT /note="WRKSL -> SLEKVSLRK (in Ref. 6; AAW67757)" FT /evidence="ECO:0000305" FT STRAND 15..24 FT /evidence="ECO:0007829|PDB:5EHD" FT STRAND 29..31 FT /evidence="ECO:0007829|PDB:5EHD" FT STRAND 40..49 FT /evidence="ECO:0007829|PDB:5EHD" FT STRAND 58..65 FT /evidence="ECO:0007829|PDB:5EHD" FT STRAND 71..80 FT /evidence="ECO:0007829|PDB:5EHD" FT TURN 81..83 FT /evidence="ECO:0007829|PDB:5EHD" FT STRAND 84..94 FT /evidence="ECO:0007829|PDB:5EHD" FT STRAND 96..104 FT /evidence="ECO:0007829|PDB:5EHD" FT STRAND 109..117 FT /evidence="ECO:0007829|PDB:5EHD" FT HELIX 244..257 FT /evidence="ECO:0007829|PDB:2LLH" FT HELIX 265..275 FT /evidence="ECO:0007829|PDB:2LLH" FT HELIX 281..292 FT /evidence="ECO:0007829|PDB:2LLH" FT MOD_RES P06748-3:254 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231" FT MOD_RES P06748-3:257 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" SQ SEQUENCE 294 AA; 32575 MW; 620BC7BA2E4A0054 CRC64; MEDSMDMDMS PLRPQNYLFG CELKADKDYH FKVDNDENEH QLSLRTVSLG AGAKDELHIV EAEAMNYEGS PIKVTLATLK MSVQPTVSLG GFEITPPVVL RLKCGSGPVH ISGQHLVAVE EDAESEDEEE EDVKLLSISG KRSAPGGGSK VPQKKVKLAA DEDDDDDDEE DDDEDDDDDD FDDEEAEEKA PVKKSIRDTP AKNAQKSNQN GKDSKPSSTP RSKGQESFKK QEKTPKTPKG PSSVEDIKAK MQASIEKGGS LPKVEAKFIN YVKNCFRMTD QEAIQDLWQW RKSL //