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 BCR_HUMAN Reviewed; 1271 AA. AC P11274; P78501; Q12842; Q4LE80; Q6NZI3; DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot. DT 03-APR-2007, sequence version 2. DT 28-JAN-2026, entry version 260. DE RecName: Full=Breakpoint cluster region protein {ECO:0000305}; DE EC=2.7.11.1 {ECO:0000269|PubMed:1657398}; DE AltName: Full=Renal carcinoma antigen NY-REN-26; GN Name=BCR {ECO:0000312|HGNC:HGNC:1014}; Synonyms=BCR1, D22S11; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND VARIANT SER-796. RX PubMed=3285291; RA Lifshitz B., Fainstein E., Marcelle C., Shtivelman E., Amson R., Gale R.P., RA Canaani E.; RT "bcr genes and transcripts."; RL Oncogene 2:113-117(1988). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND CHROMOSOMAL TRANSLOCATION. RX PubMed=7665185; DOI=10.1006/geno.1995.1008; RA Chissoe S.L., Bodenteich A., Wang Y.-F., Wang Y.-P., Burian D., RA Clifton S.W., Crabtree J., Freeman A., Iyer K., Jian L., Ma Y., RA McLaury H.-J., Pan H.-Q., Sarhan O.H., Toth S., Wang Z., Zhang G., RA Heisterkamp N., Groffen J., Roe B.A.; RT "Sequence and analysis of the human ABL gene, the BCR gene, and regions RT involved in the Philadelphia chromosomal translocation."; RL Genomics 27:67-82(1995). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT SER-796. RC TISSUE=Brain; RA Nakajima D., Saito K., Yamakawa H., Kikuno R.F., Nakayama M., Ohara R., RA Okazaki N., Koga H., Nagase T., Ohara O.; RT "Preparation of a set of expression-ready clones of mammalian long cDNAs RT encoding large proteins by the ORF trap cloning method."; RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-872, CHROMOSOMAL TRANSLOCATION, INVOLVEMENT RP IN CML, AND VARIANT SER-796. RX PubMed=3107980; DOI=10.1002/j.1460-2075.1987.tb04727.x; RA Hariharan I.K., Adams J.M.; RT "cDNA sequence for human bcr, the gene that translocates to the abl RT oncogene in chronic myeloid leukaemia."; RL EMBO J. 6:115-119(1987). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-693, AND INVOLVEMENT IN CML. RX PubMed=3540951; DOI=10.1073/pnas.83.24.9768; RA Mes-Masson A.-M., McLaughlin J., Daley G.Q., Paskind M., Witte O.N.; RT "Overlapping cDNA clones define the complete coding region for the P210c- RT abl gene product associated with chronic myelogenous leukemia cells RT containing the Philadelphia chromosome."; RL Proc. Natl. Acad. Sci. U.S.A. 83:9768-9772(1986). RN [6] RP ERRATUM OF PUBMED:3540951, AND SEQUENCE REVISION. RA Mes-Masson A.M., McLaughlin J., Daley G.Q., Paskind M., Witte O.N.; RL Proc. Natl. Acad. Sci. U.S.A. 84:2507-2507(1987). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] OF 683-1271 (ISOFORM 1). RX PubMed=2989703; DOI=10.1038/315758a0; RA Heisterkamp N., Stam K., Groffen J., de Klein A., Grosveld G.; RT "Structural organization of the bcr gene and its role in the Ph' RT translocation."; RL Nature 315:758-761(1985). RN [8] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-46 AND 275-426. RX PubMed=2263470; DOI=10.1093/nar/18.23.7119; RA Zhu Q.S., Heisterkamp N., Groffen J.; RT "Unique organization of the human BCR gene promoter."; RL Nucleic Acids Res. 18:7119-7125(1990). RN [9] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 56-426. RX PubMed=2825022; DOI=10.1038/330386a0; RA Fainstein E., Marcelle C., Rosner A., Canaani E., Gale R.P., Dreazen O., RA Smith S.D., Croce C.M.; RT "A new fused transcript in Philadelphia chromosome positive acute RT lymphocytic leukaemia."; RL Nature 330:386-388(1987). RN [10] RP NUCLEOTIDE SEQUENCE [MRNA] OF 362-438, AND ALTERNATIVE SPLICING. RX PubMed=2915904; RA Romero P., Beran M., Shtalrid M., Andersson B., Talpaz M., Blick M.; RT "Alternative 5' end of the bcr-abl transcript in chronic myelogenous RT leukemia."; RL Oncogene 4:93-98(1989). RN [11] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 670-842, INVOLVEMENT IN CML, AND RP VARIANT SER-796. RX PubMed=2407300; RA Selleri L., von Lindern M., Hermans A., Meijer D., Torelli G., Grosveld G.; RT "Chronic myeloid leukemia may be associated with several bcr-abl RT transcripts including the acute lymphoid leukemia-type 7 kb transcript."; RL Blood 75:1146-1153(1990). RN [12] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-4. RX PubMed=1900918; DOI=10.1128/mcb.11.4.1854-1860.1991; RA Shah N.P., Witte O.N., Denny C.T.; RT "Characterization of the BCR promoter in Philadelphia chromosome-positive RT and -negative cell lines."; RL Mol. Cell. Biol. 11:1854-1860(1991). RN [13] RP FUNCTION. RX PubMed=1903516; DOI=10.1038/351400a0; RA Diekmann D., Brill S., Garrett M.D., Totty N., Hsuan J., Monfries C., RA Hall C., Lim L., Hall A.; RT "Bcr encodes a GTPase-activating protein for p21rac."; RL Nature 351:400-402(1991). RN [14] RP INTERACTION WITH ABL1 SH2-DOMAIN. RX PubMed=1712671; DOI=10.1016/0092-8674(91)90148-r; RA Pendergast A.M., Muller A.J., Havlik M.H., Maru Y., Witte O.N.; RT "BCR sequences essential for transformation by the BCR-ABL oncogene bind to RT the ABL SH2 regulatory domain in a non-phosphotyrosine-dependent manner."; RL Cell 66:161-171(1991). RN [15] RP FUNCTION AS PROTEIN KINASE, AND CATALYTIC ACTIVITY. RX PubMed=1657398; DOI=10.1016/0092-8674(91)90521-y; RA Maru Y., Witte O.N.; RT "The BCR gene encodes a novel serine/threonine kinase activity within a RT single exon."; RL Cell 67:459-468(1991). RN [16] RP FUNCTION, AND DOMAIN. RX PubMed=7479768; DOI=10.1073/pnas.92.22.10282; RA Chuang T.H., Xu X., Kaartinen V., Heisterkamp N., Groffen J., Bokoch G.M.; RT "Abr and Bcr are multifunctional regulators of the Rho GTP-binding protein RT family."; RL Proc. Natl. Acad. Sci. U.S.A. 92:10282-10286(1995). RN [17] RP PHOSPHORYLATION AT TYR-177 BY HCK, MUTAGENESIS OF TYR-177, AND INTERACTION RP WITH HCK AND GRB2. RX PubMed=9407116; DOI=10.1074/jbc.272.52.33260; RA Warmuth M., Bergmann M., Priess A., Hauslmann K., Emmerich B., Hallek M.; RT "The Src family kinase Hck interacts with Bcr-Abl by a kinase-independent RT mechanism and phosphorylates the Grb2-binding site of Bcr."; RL J. Biol. Chem. 272:33260-33270(1997). RN [18] RP IDENTIFICATION AS A RENAL CANCER ANTIGEN. RC TISSUE=Renal cell carcinoma; RX PubMed=10508479; RX DOI=10.1002/(sici)1097-0215(19991112)83:4<456::aid-ijc4>3.0.co;2-5; RA Scanlan M.J., Gordan J.D., Williamson B., Stockert E., Bander N.H., RA Jongeneel C.V., Gure A.O., Jaeger D., Jaeger E., Knuth A., Chen Y.-T., RA Old L.J.; RT "Antigens recognized by autologous antibody in patients with renal-cell RT carcinoma."; RL Int. J. Cancer 83:456-464(1999). RN [19] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1264, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=15144186; DOI=10.1021/ac035352d; RA Brill L.M., Salomon A.R., Ficarro S.B., Mukherji M., Stettler-Gill M., RA Peters E.C.; RT "Robust phosphoproteomic profiling of tyrosine phosphorylation sites from RT human T cells using immobilized metal affinity chromatography and tandem RT mass spectrometry."; RL Anal. Chem. 76:2763-2772(2004). RN [20] RP INTERACTION WITH FES/FPS; ABL1; PIK3R1 AND GRB2, MUTAGENESIS OF TYR-177, RP PHOSPHORYLATION AT TYR-246, AND FUNCTION. RX PubMed=15302586; DOI=10.1016/j.yexcr.2004.05.010; RA Laurent C.E., Smithgall T.E.; RT "The c-Fes tyrosine kinase cooperates with the breakpoint cluster region RT protein (Bcr) to induce neurite extension in a Rac- and Cdc42-dependent RT manner."; RL Exp. Cell Res. 299:188-198(2004). RN [21] RP INTERACTION WITH PDZK1, AND MUTAGENESIS OF 1269-THR--GLU-1271 AND VAL-1271. RX PubMed=15494376; DOI=10.1242/jcs.01472; RA Malmberg E.K., Andersson C.X., Gentzsch M., Chen J.H., Mengos A., Cui L., RA Hansson G.C., Riordan J.R.; RT "Bcr (breakpoint cluster region) protein binds to PDZ-domains of scaffold RT protein PDZK1 and vesicle coat protein Mint3."; RL J. Cell Sci. 117:5535-5541(2004). RN [22] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling RT networks."; RL Cell 127:635-648(2006). RN [23] RP FUNCTION, AND MUTAGENESIS OF ARG-1090 AND ASN-1202. RX PubMed=17116687; DOI=10.1128/mcb.00756-06; RA Cho Y.J., Cunnick J.M., Yi S.J., Kaartinen V., Groffen J., Heisterkamp N.; RT "Abr and Bcr, two homologous Rac GTPase-activating proteins, control RT multiple cellular functions of murine macrophages."; RL Mol. Cell. Biol. 27:899-911(2007). RN [24] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Platelet; RX PubMed=18088087; DOI=10.1021/pr0704130; RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., RA Schuetz C., Walter U., Gambaryan S., Sickmann A.; RT "Phosphoproteome of resting human platelets."; RL J. Proteome Res. 7:526-534(2008). RN [25] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-459, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [26] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-177; SER-459 AND SER-1264, RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [27] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [28] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-122; SER-215 AND SER-459, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [29] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22223895; DOI=10.1074/mcp.m111.015131; RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., RA Giglione C.; RT "Comparative large-scale characterisation of plant vs. mammal proteins RT reveals similar and idiosyncratic N-alpha acetylation features."; RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012). RN [30] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-122; SER-139; SER-202; RP SER-215; SER-222; SER-356; SER-377; SER-459; SER-463; SER-473; SER-488; RP TYR-554; THR-641; TYR-644; THR-693 AND SER-894, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [31] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-459, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [32] RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 3-72, AND HOMOTETRAMERIZATION. RX PubMed=11780146; DOI=10.1038/nsb747; RA Zhao X., Ghaffari S., Lodish H., Malashkevich V.N., Kim P.S.; RT "Structure of the Bcr-Abl oncoprotein oligomerization domain."; RL Nat. Struct. Biol. 9:117-120(2002). RN [33] RP FUNCTION, INTERACTION WITH DLG4, AND MUTAGENESIS OF VAL-1271. RX PubMed=20962234; DOI=10.1523/jneurosci.1711-10.2010; RA Oh D., Han S., Seo J., Lee J.R., Choi J., Groffen J., Kim K., Cho Y.S., RA Choi H.S., Shin H., Woo J., Won H., Park S.K., Kim S.Y., Jo J., RA Whitcomb D.J., Cho K., Kim H., Bae Y.C., Heisterkamp N., Choi S.Y., Kim E.; RT "Regulation of synaptic Rac1 activity, long-term potentiation maintenance, RT and learning and memory by BCR and ABR Rac GTPase-activating proteins."; RL J. Neurosci. 30:14134-14144(2010). RN [34] RP FUNCTION, AND MUTAGENESIS OF 689-ASN-GLU-690. RX PubMed=23940119; DOI=10.1083/jcb.201304133; RA Dubash A.D., Koetsier J.L., Amargo E.V., Najor N.A., Harmon R.M., RA Green K.J.; RT "The GEF Bcr activates RhoA/MAL signaling to promote keratinocyte RT differentiation via desmoglein-1."; RL J. Cell Biol. 202:653-666(2013). RN [35] RP INTERACTION WITH SH2D5. RX PubMed=25331951; DOI=10.1074/jbc.m114.615112; RA Gray E.J., Petsalaki E., James D.A., Bagshaw R.D., Stacey M.M., Rocks O., RA Gingras A.C., Pawson T.; RT "src homology 2 domain containing protein 5 (sh2d5) binds the breakpoint RT cluster region protein, BCR, and regulates levels of Rac1-GTP."; RL J. Biol. Chem. 289:35397-35408(2014). RN [36] RP VARIANTS [LARGE SCALE ANALYSIS] PRO-400; MET-413; GLU-752; SER-796; RP CYS-910; ILE-949; LYS-1037; MET-1091; ALA-1096; GLY-1104; ASN-1106; RP THR-1149; LYS-1161; GLU-1187; MET-1189; GLY-1204 AND ARG-1235. RX PubMed=17344846; DOI=10.1038/nature05610; RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G., RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., RA Futreal P.A., Stratton M.R.; RT "Patterns of somatic mutation in human cancer genomes."; RL Nature 446:153-158(2007). CC -!- FUNCTION: Protein with a unique structure having two opposing CC regulatory activities toward small GTP-binding proteins. The C-terminus CC is a GTPase-activating protein (GAP) domain which stimulates GTP CC hydrolysis by RAC1, RAC2 and CDC42. Accelerates the intrinsic rate of CC GTP hydrolysis of RAC1 or CDC42, leading to down-regulation of the CC active GTP-bound form (PubMed:17116687, PubMed:1903516, CC PubMed:7479768). The central Dbl homology (DH) domain functions as CC guanine nucleotide exchange factor (GEF) that modulates the GTPases CC CDC42, RHOA and RAC1. Promotes the conversion of CDC42, RHOA and RAC1 CC from the GDP-bound to the GTP-bound form (PubMed:23940119, CC PubMed:7479768). The amino terminus contains an intrinsic kinase CC activity (PubMed:1657398). Functions as an important negative regulator CC of neuronal RAC1 activity (By similarity). Regulates macrophage CC functions such as CSF1-directed motility and phagocytosis through the CC modulation of RAC1 activity (PubMed:17116687). Plays a major role as a CC RHOA GEF in keratinocytes being involved in focal adhesion formation CC and keratinocyte differentiation (PubMed:23940119). CC {ECO:0000250|UniProtKB:Q6PAJ1, ECO:0000269|PubMed:1657398, CC ECO:0000269|PubMed:17116687, ECO:0000269|PubMed:1903516, CC ECO:0000269|PubMed:23940119, ECO:0000269|PubMed:7479768}. CC -!- CATALYTIC ACTIVITY: CC Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + CC H(+); Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA- CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1; CC Evidence={ECO:0000269|PubMed:1657398}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17990; CC Evidence={ECO:0000269|PubMed:1657398}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + CC ADP + H(+); Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA- CC COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.1; CC Evidence={ECO:0000269|PubMed:1657398}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46609; CC Evidence={ECO:0000269|PubMed:1657398}; CC -!- SUBUNIT: Homotetramer. Interacts with PDZK1 (PubMed:15494376). May CC interact with CCPG1 (By similarity). Interacts with FES/FPS, ABL1, CC PIK3R1 and GRB2 (PubMed:15302586, PubMed:1712671, PubMed:9407116). CC Interacts with HCK (PubMed:9407116). Interacts with SH2D5 CC (PubMed:25331951). Interacts with DLG4 (PubMed:20962234). CC {ECO:0000250|UniProtKB:Q6PAJ1, ECO:0000269|PubMed:15302586, CC ECO:0000269|PubMed:15494376, ECO:0000269|PubMed:1712671, CC ECO:0000269|PubMed:20962234, ECO:0000269|PubMed:25331951, CC ECO:0000269|PubMed:9407116}. CC -!- INTERACTION: CC P11274; O96018: APBA3; NbExp=5; IntAct=EBI-712838, EBI-6115839; CC P11274; Q12959: DLG1; NbExp=3; IntAct=EBI-712838, EBI-357481; CC P11274; Q15700: DLG2; NbExp=2; IntAct=EBI-712838, EBI-80426; CC P11274; Q92796: DLG3; NbExp=2; IntAct=EBI-712838, EBI-80440; CC P11274; P78352: DLG4; NbExp=2; IntAct=EBI-712838, EBI-80389; CC P11274; P62993: GRB2; NbExp=13; IntAct=EBI-712838, EBI-401755; CC P11274; Q86UL8: MAGI2; NbExp=3; IntAct=EBI-712838, EBI-311035; CC P11274; Q8NI35: PATJ; NbExp=5; IntAct=EBI-712838, EBI-724390; CC P11274; Q5T2W1: PDZK1; NbExp=8; IntAct=EBI-712838, EBI-349819; CC P11274; Q14160: SCRIB; NbExp=3; IntAct=EBI-712838, EBI-357345; CC P11274; Q6ZV89-1: SH2D5; NbExp=2; IntAct=EBI-712838, EBI-15101685; CC P11274; Q9H2K2: TNKS2; NbExp=3; IntAct=EBI-712838, EBI-4398527; CC P11274; A2AM67: Sh2d5; Xeno; NbExp=7; IntAct=EBI-712838, EBI-15101945; CC P11274; Q8JZW5: Sh2d5; Xeno; NbExp=2; IntAct=EBI-712838, EBI-15101675; CC P11274-1; P18031: PTPN1; NbExp=3; IntAct=EBI-8658094, EBI-968788; CC -!- SUBCELLULAR LOCATION: Postsynaptic density CC {ECO:0000250|UniProtKB:Q6PAJ1}. Cell projection, dendritic spine CC {ECO:0000250|UniProtKB:Q6PAJ1}. Cell projection, axon CC {ECO:0000250|UniProtKB:Q6PAJ1}. Synapse {ECO:0000250|UniProtKB:F1LXF1}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P11274-1; Sequence=Displayed; CC Name=2; CC IsoId=P11274-2; Sequence=VSP_024352; CC -!- DOMAIN: The region involved in binding to ABL1 SH2-domain is rich in CC serine residues and needs to be Ser/Thr phosphorylated prior to SH2 CC binding. This region is essential for the activation of the ABL1 CC tyrosine kinase and transforming potential of the chimeric BCR-ABL CC oncogene. CC -!- DOMAIN: The DH domain is involved in interaction with CCPG1. CC {ECO:0000250|UniProtKB:Q6PAJ1}. CC -!- DOMAIN: The amino terminus contains an intrinsic kinase activity. The CC central Dbl homology (DH) domain functions as a guanine nucleotide CC exchange factor (GEF) that modulates the GTPases CDC42, RHOA and RAC1. CC Promotes the conversion of CDC42, RHOA and RAC1 from the GDP-bound to CC the GTP-bound form. The C-terminus is a Rho-GAP domain which stimulates CC GTP hydrolysis by RAC1, RAC2 and CDC42. The protein has a unique CC structure having two opposing regulatory activities toward small GTP- CC binding proteins. {ECO:0000305|PubMed:7479768}. CC -!- PTM: Autophosphorylated. Phosphorylated by FES/FPS on tyrosine CC residues, leading to down-regulation of the BCR kinase activity. CC Phosphorylation at Tyr-177 by HCK is important for interaction with CC GRB2. {ECO:0000269|PubMed:15302586, ECO:0000269|PubMed:9407116}. CC -!- DISEASE: Leukemia, chronic myeloid (CML) [MIM:608232]: A clonal CC myeloproliferative disorder of a pluripotent stem cell with a specific CC cytogenetic abnormality, the Philadelphia chromosome (Ph), involving CC myeloid, erythroid, megakaryocytic, B-lymphoid, and sometimes T- CC lymphoid cells, but not marrow fibroblasts. CC {ECO:0000269|PubMed:2407300, ECO:0000269|PubMed:3107980, CC ECO:0000269|PubMed:3540951}. Note=The gene represented in this entry is CC involved in disease pathogenesis. CC -!- DISEASE: Note=A chromosomal aberration involving BCR has been found in CC patients with chronic myeloid leukemia. Translocation t(9;22)(q34;q11) CC with ABL1. The translocation produces a BCR-ABL found also in acute CC myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). CC {ECO:0000269|PubMed:3107980, ECO:0000269|PubMed:7665185}. CC -!- SEQUENCE CAUTION: CC Sequence=BAE06073.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/55/BCR"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; Y00661; CAA68676.1; -; mRNA. DR EMBL; U07000; AAB60388.1; -; Genomic_DNA. DR EMBL; AB209991; BAE06073.1; ALT_INIT; mRNA. DR EMBL; X02596; CAA26441.1; -; mRNA. DR EMBL; M15025; AAA35594.1; -; Genomic_DNA. DR EMBL; X52828; CAA37010.1; -; Genomic_DNA. DR EMBL; X52829; CAA37011.1; -; Genomic_DNA. DR EMBL; X14676; CAA32806.1; -; mRNA. DR EMBL; M64437; -; NOT_ANNOTATED_CDS; mRNA. DR CCDS; CCDS13806.1; -. [P11274-1] DR CCDS; CCDS13807.1; -. [P11274-2] DR PIR; A26664; TVHUA2. DR PIR; A91064; TVHUBR. DR RefSeq; NP_004318.3; NM_004327.3. [P11274-1] DR RefSeq; NP_067585.2; NM_021574.3. [P11274-2] DR PDB; 1K1F; X-ray; 2.20 A; A/B/C/D/E/F/G/H=1-72. DR PDB; 2AIN; NMR; -; B=1266-1271. DR PDB; 5N6R; NMR; -; A=487-702. DR PDB; 5N7E; X-ray; 1.65 A; B=487-702. DR PDB; 5OC7; X-ray; 1.65 A; A/D=704-893. DR PDBsum; 1K1F; -. DR PDBsum; 2AIN; -. DR PDBsum; 5N6R; -. DR PDBsum; 5N7E; -. DR PDBsum; 5OC7; -. DR AlphaFoldDB; P11274; -. DR SASBDB; P11274; -. DR SMR; P11274; -. DR BioGRID; 107083; 230. DR CORUM; P11274; -. DR ELM; P11274; -. DR FunCoup; P11274; 1481. DR IntAct; P11274; 222. DR MINT; P11274; -. DR STRING; 9606.ENSP00000303507; -. DR BindingDB; P11274; -. DR ChEMBL; CHEMBL5146; -. DR DrugBank; DB01254; Dasatinib. DR DrugBank; DB00619; Imatinib. DR DrugBank; DB08901; Ponatinib. DR DrugCentral; P11274; -. DR GlyCosmos; P11274; 1 site, 1 glycan. DR GlyGen; P11274; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P11274; -. DR MetOSite; P11274; -. DR PhosphoSitePlus; P11274; -. DR BioMuta; BCR; -. DR DMDM; 143811366; -. DR jPOST; P11274; -. DR MassIVE; P11274; -. DR PaxDb; 9606-ENSP00000303507; -. DR PeptideAtlas; P11274; -. DR ProteomicsDB; 52729; -. [P11274-1] DR ProteomicsDB; 52730; -. [P11274-2] DR Pumba; P11274; -. DR ABCD; P11274; 2 sequenced antibodies. DR Antibodypedia; 9277; 677 antibodies from 41 providers. DR DNASU; 613; -. DR Ensembl; ENST00000305877.13; ENSP00000303507.8; ENSG00000186716.22. [P11274-1] DR Ensembl; ENST00000359540.7; ENSP00000352535.3; ENSG00000186716.22. [P11274-2] DR GeneID; 613; -. DR KEGG; hsa:613; -. DR MANE-Select; ENST00000305877.13; ENSP00000303507.8; NM_004327.4; NP_004318.3. DR UCSC; uc002zww.4; human. [P11274-1] DR AGR; HGNC:1014; -. DR ClinPGx; PA25321; -. DR CTD; 613; -. DR DisGeNET; 613; -. DR GeneCards; BCR; -. DR HGNC; HGNC:1014; BCR. DR HPA; ENSG00000186716; Low tissue specificity. DR MalaCards; BCR; -. DR MIM; 151410; gene. DR MIM; 608232; phenotype. DR OpenTargets; ENSG00000186716; -. DR Orphanet; 585909; B-lymphoblastic leukemia/lymphoma with t(9;22)(q34.1;q11.2). DR Orphanet; 521; Chronic myeloid leukemia. DR Orphanet; 261330; Distal 22q11.2 microdeletion syndrome. DR Orphanet; 99861; Precursor T-cell acute lymphoblastic leukemia. DR VEuPathDB; HostDB:ENSG00000186716; -. DR eggNOG; KOG4269; Eukaryota. DR GeneTree; ENSGT00940000153491; -. DR HOGENOM; CLU_004164_0_0_1; -. DR InParanoid; P11274; -. DR OMA; HDLMPFI; -. DR OrthoDB; 2155291at2759; -. DR PAN-GO; P11274; 1 GO annotation based on evolutionary models. DR PhylomeDB; P11274; -. DR PathwayCommons; P11274; -. DR Reactome; R-HSA-1839117; Signaling by cytosolic FGFR1 fusion mutants. DR Reactome; R-HSA-5655302; Signaling by FGFR1 in disease. DR Reactome; R-HSA-8980692; RHOA GTPase cycle. DR Reactome; R-HSA-9013026; RHOB GTPase cycle. DR Reactome; R-HSA-9013106; RHOC GTPase cycle. DR Reactome; R-HSA-9013148; CDC42 GTPase cycle. DR Reactome; R-HSA-9013149; RAC1 GTPase cycle. DR Reactome; R-HSA-9013404; RAC2 GTPase cycle. DR Reactome; R-HSA-9013423; RAC3 GTPase cycle. DR SignaLink; P11274; -. DR SIGNOR; P11274; -. DR Agora; ENSG00000186716; -. DR BioGRID-ORCS; 613; 37 hits in 1202 CRISPR screens. DR CD-CODE; FB4E32DD; Presynaptic clusters and postsynaptic densities. DR ChiTaRS; BCR; human. DR EvolutionaryTrace; P11274; -. DR GeneWiki; BCR_(gene); -. DR GenomeRNAi; 613; -. DR Pharos; P11274; Tclin. DR PRO; PR:P11274; -. DR Proteomes; UP000005640; Chromosome 22. DR RNAct; P11274; protein. DR Bgee; ENSG00000186716; Expressed in nucleus accumbens and 182 other cell types or tissues. DR ExpressionAtlas; P11274; baseline and differential. DR GO; GO:0030424; C:axon; IEA:UniProtKB-SubCell. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0043197; C:dendritic spine; IEA:UniProtKB-SubCell. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0098978; C:glutamatergic synapse; ISS:UniProtKB. DR GO; GO:0016020; C:membrane; HDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IEA:Ensembl. DR GO; GO:0014069; C:postsynaptic density; IEA:UniProtKB-SubCell. DR GO; GO:0032991; C:protein-containing complex; IDA:MGI. DR GO; GO:0098685; C:Schaffer collateral - CA1 synapse; ISS:UniProtKB. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0005096; F:GTPase activator activity; IDA:UniProtKB. DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IDA:UniProtKB. DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA. DR GO; GO:0004674; F:protein serine/threonine kinase activity; TAS:ProtInc. DR GO; GO:0004713; F:protein tyrosine kinase activity; TAS:Reactome. DR GO; GO:0030036; P:actin cytoskeleton organization; IEA:Ensembl. DR GO; GO:0090630; P:activation of GTPase activity; IDA:UniProtKB. DR GO; GO:0007420; P:brain development; IEA:Ensembl. DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IEA:Ensembl. DR GO; GO:0060216; P:definitive hemopoiesis; IEA:Ensembl. DR GO; GO:0048041; P:focal adhesion assembly; IMP:UniProtKB. DR GO; GO:0048872; P:homeostasis of number of cells; IEA:Ensembl. DR GO; GO:0042472; P:inner ear morphogenesis; IEA:Ensembl. DR GO; GO:0065002; P:intracellular protein transmembrane transport; IEA:Ensembl. DR GO; GO:0030216; P:keratinocyte differentiation; IMP:UniProtKB. DR GO; GO:1905517; P:macrophage migration; IEA:Ensembl. DR GO; GO:0050804; P:modulation of chemical synaptic transmission; ISS:UniProtKB. DR GO; GO:0060313; P:negative regulation of blood vessel remodeling; IEA:Ensembl. DR GO; GO:0002692; P:negative regulation of cellular extravasation; IEA:Ensembl. DR GO; GO:0050728; P:negative regulation of inflammatory response; IEA:Ensembl. DR GO; GO:1905522; P:negative regulation of macrophage migration; IEA:Ensembl. DR GO; GO:0043314; P:negative regulation of neutrophil degranulation; IEA:Ensembl. DR GO; GO:2000378; P:negative regulation of reactive oxygen species metabolic process; IEA:Ensembl. DR GO; GO:0060268; P:negative regulation of respiratory burst; IEA:Ensembl. DR GO; GO:0050885; P:neuromuscular process controlling balance; IEA:Ensembl. DR GO; GO:0043312; P:neutrophil degranulation; IEA:Ensembl. DR GO; GO:0006909; P:phagocytosis; IEA:Ensembl. DR GO; GO:0050766; P:positive regulation of phagocytosis; IEA:Ensembl. DR GO; GO:0006468; P:protein phosphorylation; TAS:ProtInc. DR GO; GO:0051726; P:regulation of cell cycle; IEA:Ensembl. DR GO; GO:0035023; P:regulation of Rho protein signal transduction; IMP:UniProtKB. DR GO; GO:0051056; P:regulation of small GTPase mediated signal transduction; TAS:Reactome. DR GO; GO:0043114; P:regulation of vascular permeability; IEA:Ensembl. DR GO; GO:0003014; P:renal system process; IEA:Ensembl. DR GO; GO:0007165; P:signal transduction; TAS:ProtInc. DR GO; GO:0007264; P:small GTPase-mediated signal transduction; IMP:UniProtKB. DR CDD; cd08686; C2_ABR; 1. DR CDD; cd13367; PH_BCR_vertebrate; 1. DR CDD; cd04387; RhoGAP_Bcr; 1. DR CDD; cd00160; RhoGEF; 1. DR DisProt; DP03016; -. DR FunFam; 2.60.40.150:FF:000057; active breakpoint cluster region-related protein isoform X1; 1. DR FunFam; 1.20.900.10:FF:000014; active breakpoint cluster region-related protein isoform X2; 1. DR FunFam; 1.10.555.10:FF:000004; active breakpoint cluster region-related protein-like; 1. DR Gene3D; 4.10.280.30; Bcr-Abl oncoprotein oligomerisation domain; 1. DR Gene3D; 2.60.40.150; C2 domain; 1. DR Gene3D; 1.20.900.10; Dbl homology (DH) domain; 1. DR Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 1. DR Gene3D; 1.10.555.10; Rho GTPase activation protein; 1. DR InterPro; IPR037769; Abr/Bcr. DR InterPro; IPR015123; Bcr-Abl_oncoprot_oligo. DR InterPro; IPR036481; Bcr-Abl_oncoprot_oligo_sf. DR InterPro; IPR000008; C2_dom. DR InterPro; IPR035892; C2_domain_sf. DR InterPro; IPR035899; DBL_dom_sf. DR InterPro; IPR000219; DH_dom. DR InterPro; IPR001331; GDS_CDC24_CS. DR InterPro; IPR011993; PH-like_dom_sf. DR InterPro; IPR001849; PH_domain. DR InterPro; IPR008936; Rho_GTPase_activation_prot. DR InterPro; IPR000198; RhoGAP_dom. DR PANTHER; PTHR23182:SF3; BREAKPOINT CLUSTER REGION PROTEIN; 1. DR PANTHER; PTHR23182; BREAKPOINT CLUSTER REGION PROTEIN BCR; 1. DR Pfam; PF09036; Bcr-Abl_Oligo; 1. DR Pfam; PF00168; C2; 1. DR Pfam; PF19057; PH_19; 1. DR Pfam; PF00620; RhoGAP; 1. DR Pfam; PF00621; RhoGEF; 1. DR SMART; SM00239; C2; 1. DR SMART; SM00233; PH; 1. DR SMART; SM00324; RhoGAP; 1. DR SMART; SM00325; RhoGEF; 1. DR SUPFAM; SSF69036; Bcr-Abl oncoprotein oligomerization domain; 1. DR SUPFAM; SSF49562; C2 domain (Calcium/lipid-binding domain, CaLB); 1. DR SUPFAM; SSF48065; DBL homology domain (DH-domain); 1. DR SUPFAM; SSF48350; GTPase activation domain, GAP; 1. DR SUPFAM; SSF50729; PH domain-like; 1. DR PROSITE; PS50004; C2; 1. DR PROSITE; PS00741; DH_1; 1. DR PROSITE; PS50010; DH_2; 1. DR PROSITE; PS50003; PH_DOMAIN; 1. DR PROSITE; PS50238; RHOGAP; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; ATP-binding; KW Cell projection; Chromosomal rearrangement; Coiled coil; GTPase activation; KW Guanine-nucleotide releasing factor; Kinase; Methylation; KW Nucleotide-binding; Phosphoprotein; Proteomics identification; KW Proto-oncogene; Reference proteome; Serine/threonine-protein kinase; KW Synapse; Transferase. FT CHAIN 1..1271 FT /note="Breakpoint cluster region protein" FT /id="PRO_0000080933" FT DOMAIN 498..691 FT /note="DH" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00062" FT DOMAIN 708..866 FT /note="PH" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145" FT DOMAIN 893..1020 FT /note="C2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041" FT DOMAIN 1054..1248 FT /note="Rho-GAP" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00172" FT REGION 1..426 FT /note="Kinase" FT REGION 67..173 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 185..247 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 197..385 FT /note="Binding to ABL SH2-domain" FT REGION 286..392 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 416..476 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COILED 28..55 FT /evidence="ECO:0000255" FT COMPBIAS 87..105 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 123..138 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 185..198 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 199..208 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 346..356 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 369..382 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 441..451 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT SITE 426..427 FT /note="Breakpoint for translocation to form BCR-ABL FT oncogene" FT SITE 1090 FT /note="Arginine finger; crucial for GTP hydrolysis by FT stabilizing the transition state" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00172" FT MOD_RES 1 FT /note="N-acetylmethionine" FT /evidence="ECO:0007744|PubMed:22223895" FT MOD_RES 122 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163" FT MOD_RES 139 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 177 FT /note="Phosphotyrosine; by HCK" FT /evidence="ECO:0000269|PubMed:9407116, FT ECO:0007744|PubMed:19690332" FT MOD_RES 202 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 215 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163" FT MOD_RES 222 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 236 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q6PAJ1" FT MOD_RES 246 FT /note="Phosphotyrosine; by FES" FT /evidence="ECO:0000269|PubMed:15302586" FT MOD_RES 356 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 377 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 382 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q6PAJ1" FT MOD_RES 385 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q6PAJ1" FT MOD_RES 459 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569" FT MOD_RES 463 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 471 FT /note="Omega-N-methylarginine" FT /evidence="ECO:0000250|UniProtKB:Q6PAJ1" FT MOD_RES 473 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 488 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 554 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 641 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 644 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 693 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 894 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 1264 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:15144186, FT ECO:0007744|PubMed:19690332" FT VAR_SEQ 961..1004 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:3285291" FT /id="VSP_024352" FT VARIANT 400 FT /note="S -> P (in a bladder transitional cell carcinoma FT sample; somatic mutation)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041883" FT VARIANT 413 FT /note="I -> M (in dbSNP:rs56321828)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041884" FT VARIANT 558 FT /note="K -> T (in dbSNP:rs4437065)" FT /id="VAR_051983" FT VARIANT 752 FT /note="D -> E (in dbSNP:rs12484731)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041885" FT VARIANT 796 FT /note="N -> S (in dbSNP:rs140504)" FT /evidence="ECO:0000269|PubMed:17344846, FT ECO:0000269|PubMed:2407300, ECO:0000269|PubMed:3107980, FT ECO:0000269|PubMed:3285291, ECO:0000269|Ref.3" FT /id="VAR_031552" FT VARIANT 910 FT /note="Y -> C (in dbSNP:rs35537221)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041886" FT VARIANT 949 FT /note="V -> I (in dbSNP:rs2229038)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041887" FT VARIANT 1037 FT /note="E -> K (in dbSNP:rs776552570)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_031553" FT VARIANT 1091 FT /note="V -> M (in dbSNP:rs778229520)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041888" FT VARIANT 1096 FT /note="T -> A (in dbSNP:rs745459086)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041889" FT VARIANT 1104 FT /note="A -> G (in dbSNP:rs11558696)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041890" FT VARIANT 1106 FT /note="D -> N (in dbSNP:rs879255379)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041891" FT VARIANT 1127 FT /note="T -> M (in dbSNP:rs35812689)" FT /id="VAR_031554" FT VARIANT 1149 FT /note="A -> T (in dbSNP:rs200099830)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041892" FT VARIANT 1161 FT /note="E -> K (in dbSNP:rs2074037194)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041893" FT VARIANT 1187 FT /note="K -> E (in dbSNP:rs1195127922)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041894" FT VARIANT 1189 FT /note="V -> M (in dbSNP:rs55816482)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041895" FT VARIANT 1204 FT /note="A -> G (in dbSNP:rs56265970)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041896" FT VARIANT 1235 FT /note="W -> R (in dbSNP:rs55719322)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041897" FT MUTAGEN 177 FT /note="Y->F: Abolishes interaction with FES and GRB2." FT /evidence="ECO:0000269|PubMed:15302586, FT ECO:0000269|PubMed:9407116" FT MUTAGEN 689..690 FT /note="NE->AA: Loss of RHOA GEF activity." FT /evidence="ECO:0000269|PubMed:23940119" FT MUTAGEN 1090 FT /note="R->A: Loss of GAP activity. Loss of GAP activity; FT when associated with A-1202." FT /evidence="ECO:0000269|PubMed:17116687" FT MUTAGEN 1202 FT /note="N->A: Loss of GAP activity; when associated with A- FT 1090." FT /evidence="ECO:0000269|PubMed:17116687" FT MUTAGEN 1269..1271 FT /note="Missing: Abolishes interaction with PDZK1." FT /evidence="ECO:0000269|PubMed:15494376" FT MUTAGEN 1271 FT /note="V->A: Reduces interaction with PDZK1. Abolishes FT interaction with DLG4. No effect on synaptic localization." FT /evidence="ECO:0000269|PubMed:15494376, FT ECO:0000269|PubMed:20962234" FT CONFLICT 287 FT /note="M -> I (in Ref. 1; CAA68676)" FT /evidence="ECO:0000305" FT CONFLICT 418 FT /note="G -> D (in Ref. 1; CAA68676)" FT /evidence="ECO:0000305" FT CONFLICT 483 FT /note="E -> K (in Ref. 1; CAA68676)" FT /evidence="ECO:0000305" FT CONFLICT 560 FT /note="F -> S (in Ref. 1; CAA68676)" FT /evidence="ECO:0000305" FT CONFLICT 690 FT /note="E -> D (in Ref. 11)" FT /evidence="ECO:0000305" FT CONFLICT 733 FT /note="D -> E (in Ref. 4; CAA26441)" FT /evidence="ECO:0000305" FT HELIX 4..14 FT /evidence="ECO:0007829|PDB:1K1F" FT HELIX 28..64 FT /evidence="ECO:0007829|PDB:1K1F" FT HELIX 492..521 FT /evidence="ECO:0007829|PDB:5N7E" FT HELIX 524..531 FT /evidence="ECO:0007829|PDB:5N7E" FT STRAND 533..535 FT /evidence="ECO:0007829|PDB:5N7E" FT HELIX 540..546 FT /evidence="ECO:0007829|PDB:5N7E" FT TURN 547..549 FT /evidence="ECO:0007829|PDB:5N7E" FT HELIX 550..569 FT /evidence="ECO:0007829|PDB:5N7E" FT HELIX 578..586 FT /evidence="ECO:0007829|PDB:5N7E" FT HELIX 588..611 FT /evidence="ECO:0007829|PDB:5N7E" FT HELIX 613..618 FT /evidence="ECO:0007829|PDB:5N7E" FT STRAND 630..634 FT /evidence="ECO:0007829|PDB:5N6R" FT HELIX 639..651 FT /evidence="ECO:0007829|PDB:5N7E" FT HELIX 653..661 FT /evidence="ECO:0007829|PDB:5N7E" FT HELIX 670..687 FT /evidence="ECO:0007829|PDB:5N7E" FT STRAND 694..697 FT /evidence="ECO:0007829|PDB:5N6R" FT STRAND 709..719 FT /evidence="ECO:0007829|PDB:5OC7" FT STRAND 722..740 FT /evidence="ECO:0007829|PDB:5OC7" FT STRAND 751..758 FT /evidence="ECO:0007829|PDB:5OC7" FT HELIX 759..761 FT /evidence="ECO:0007829|PDB:5OC7" FT STRAND 762..767 FT /evidence="ECO:0007829|PDB:5OC7" FT STRAND 830..838 FT /evidence="ECO:0007829|PDB:5OC7" FT STRAND 843..847 FT /evidence="ECO:0007829|PDB:5OC7" FT HELIX 851..865 FT /evidence="ECO:0007829|PDB:5OC7" FT HELIX 876..885 FT /evidence="ECO:0007829|PDB:5OC7" FT STRAND 1268..1271 FT /evidence="ECO:0007829|PDB:2AIN" SQ SEQUENCE 1271 AA; 142819 MW; 4BF66FA1E9D205FE CRC64; MVDPVGFAEA WKAQFPDSEP PRMELRSVGD IEQELERCKA SIRRLEQEVN QERFRMIYLQ TLLAKEKKSY DRQRWGFRRA AQAPDGASEP RASASRPQPA PADGADPPPA EEPEARPDGE GSPGKARPGT ARRPGAAASG ERDDRGPPAS VAALRSNFER IRKGHGQPGA DAEKPFYVNV EFHHERGLVK VNDKEVSDRI SSLGSQAMQM ERKKSQHGAG SSVGDASRPP YRGRSSESSC GVDGDYEDAE LNPRFLKDNL IDANGGSRPP WPPLEYQPYQ SIYVGGMMEG EGKGPLLRSQ STSEQEKRLT WPRRSYSPRS FEDCGGGYTP DCSSNENLTS SEEDFSSGQS SRVSPSPTTY RMFRDKSRSP SQNSQQSFDS SSPPTPQCHK RHRHCPVVVS EATIVGVRKT GQIWPNDGEG AFHGDADGSF GTPPGYGCAA DRAEEQRRHQ DGLPYIDDSP SSSPHLSSKG RGSRDALVSG ALESTKASEL DLEKGLEMRK WVLSGILASE ETYLSHLEAL LLPMKPLKAA ATTSQPVLTS QQIETIFFKV PELYEIHKEF YDGLFPRVQQ WSHQQRVGDL FQKLASQLGV YRAFVDNYGV AMEMAEKCCQ ANAQFAEISE NLRARSNKDA KDPTTKNSLE TLLYKPVDRV TRSTLVLHDL LKHTPASHPD HPLLQDALRI SQNFLSSINE EITPRRQSMT VKKGEHRQLL KDSFMVELVE GARKLRHVFL FTDLLLCTKL KKQSGGKTQQ YDCKWYIPLT DLSFQMVDEL EAVPNIPLVP DEELDALKIK ISQIKNDIQR EKRANKGSKA TERLKKKLSE QESLLLLMSP SMAFRVHSRN GKSYTFLISS DYERAEWREN IREQQKKCFR SFSLTSVELQ MLTNSCVKLQ TVHSIPLTIN KEDDESPGLY GFLNVIVHSA TGFKQSSNLY CTLEVDSFGY FVNKAKTRVY RDTAEPNWNE EFEIELEGSQ TLRILCYEKC YNKTKIPKED GESTDRLMGK GQVQLDPQAL QDRDWQRTVI AMNGIEVKLS VKFNSREFSL KRMPSRKQTG VFGVKIAVVT KRERSKVPYI VRQCVEEIER RGMEEVGIYR VSGVATDIQA LKAAFDVNNK DVSVMMSEMD VNAIAGTLKL YFRELPEPLF TDEFYPNFAE GIALSDPVAK ESCMLNLLLS LPEANLLTFL FLLDHLKRVA EKEAVNKMSL HNLATVFGPT LLRPSEKESK LPANPSQPIT MTDSWSLEVM SQVQVLLYFL QLEAIPAPDS KRQSILFSTE V // ID JAK2_HUMAN Reviewed; 1132 AA. AC O60674; O14636; O75297; DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot. DT 24-JAN-2001, sequence version 2. DT 28-JAN-2026, entry version 249. DE RecName: Full=Tyrosine-protein kinase JAK2 {ECO:0000305}; DE EC=2.7.10.2 {ECO:0000269|PubMed:15690087, ECO:0000269|PubMed:16174768, ECO:0000269|PubMed:7615558, ECO:0000269|PubMed:9618263, ECO:0000269|PubMed:9657743}; DE AltName: Full=Janus kinase 2; DE Short=JAK-2; GN Name=JAK2 {ECO:0000312|HGNC:HGNC:6192}; 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], FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=9618263; DOI=10.1006/bbrc.1998.8685; RA Saltzman A., Stone M., Franks C., Searfoss G., Munro R., Jaye M., RA Ivashchenko Y.; RT "Cloning and characterization of human Jak-2 kinase: high mRNA expression RT in immune cells and muscle tissue."; RL Biochem. Biophys. Res. Commun. 246:627-633(1998). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=9446644; RA Dalal I., Arpaia E., Dadi H., Kulkarni S., Squire J., Roifman C.M.; RT "Cloning and characterization of the human homolog of mouse Jak2."; RL Blood 91:844-851(1998). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA], AND CHROMOSOMAL TRANSLOCATION WITH ETV6. RX PubMed=9326218; RA Peeters P., Raynaud S.D., Cools J., Wlodarska I., Grosgeorge J., Philip P., RA Monpoux F., Van Rompaey L., Baens M., Van Den Berghe H., Marynen P.; RT "Fusion of TEL, the ETS-variant gene 6 (ETV6), to the receptor-associated RT kinase JAK2 as a result of t(9;12) in a lymphoid and t(9;15;12) in a RT myeloid leukemia."; RL Blood 90:2535-2540(1997). RN [4] 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 [5] RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, INTERACTION WITH IFNGR2, AND RP PHOSPHORYLATION. RX PubMed=7615558; DOI=10.1074/jbc.270.29.17528; RA Sakatsume M., Igarashi K., Winestock K.D., Garotta G., Larner A.C., RA Finbloom D.S.; RT "The Jak kinases differentially associate with the alpha and beta RT (accessory factor) chains of the interferon gamma receptor to form a RT functional receptor unit capable of activating STAT transcription RT factors."; RL J. Biol. Chem. 270:17528-17534(1995). RN [6] RP INTERACTION WITH IFNGR2, AND PHOSPHORYLATION. RX PubMed=7673114; DOI=10.1074/jbc.270.36.20915; RA Kotenko S.V., Izotova L.S., Pollack B.P., Mariano T.M., Donnelly R.J., RA Muthukumaran G., Cook J.R., Garotta G., Silvennoinen O., Ihle J.N.; RT "Interaction between the components of the interferon gamma receptor RT complex."; RL J. Biol. Chem. 270:20915-20921(1995). RN [7] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=9657743; RA Oda A., Sawada K., Druker B.J., Ozaki K., Takano H., Koizumi K., Fukada Y., RA Handa M., Koike T., Ikeda Y.; RT "Erythropoietin induces tyrosine phosphorylation of Jak2, STAT5A, and RT STAT5B in primary cultured human erythroid precursors."; RL Blood 92:443-451(1998). RN [8] RP INTERACTION WITH SKB1. RX PubMed=10531356; DOI=10.1074/jbc.274.44.31531; RA Pollack B.P., Kotenko S.V., He W., Izotova L.S., Barnoski B.L., Pestka S.; RT "The human homologue of the yeast proteins Skb1 and Hsl7p interacts with RT Jak kinases and contains protein methyltransferase activity."; RL J. Biol. Chem. 274:31531-31542(1999). RN [9] RP INTERACTION WITH STAM2. RC TISSUE=Fetal brain; RX PubMed=10899310; DOI=10.1016/s0014-5793(00)01760-9; RA Endo K., Takeshita T., Kasai H., Sasaki Y., Tanaka N., Asao H., Kikuchi K., RA Yamada M., Chenb M., O'Shea J.J., Sugamura K.; RT "STAM2, a new member of the STAM family, binding to the Janus kinases."; RL FEBS Lett. 477:55-61(2000). RN [10] RP FUNCTION, AND INTERACTION WITH IL23R. RX PubMed=12023369; DOI=10.4049/jimmunol.168.11.5699; RA Parham C., Chirica M., Timans J., Vaisberg E., Travis M., Cheung J., RA Pflanz S., Zhang R., Singh K.P., Vega F., To W., Wagner J., RA O'Farrell A.-M., McClanahan T.K., Zurawski S., Hannum C., Gorman D., RA Rennick D.M., Kastelein R.A., de Waal Malefyt R., Moore K.W.; RT "A receptor for the heterodimeric cytokine IL-23 is composed of IL-12Rbeta1 RT and a novel cytokine receptor subunit, IL-23R."; RL J. Immunol. 168:5699-5708(2002). RN [11] RP CHROMOSOMAL TRANSLOCATION WITH PCM1. RX PubMed=15805263; DOI=10.1158/0008-5472.can-04-4263; RA Reiter A., Walz C., Watmore A., Schoch C., Blau I., Schlegelberger B., RA Berger U., Telford N., Aruliah S., Yin J.A., Vanstraelen D., Barker H.F., RA Taylor P.C., O'Driscoll A., Benedetti F., Rudolph C., Kolb H.-J., RA Hochhaus A., Hehlmann R., Chase A., Cross N.C.P.; RT "The t(8;9)(p22;p24) is a recurrent abnormality in chronic and acute RT leukemia that fuses PCM1 to JAK2."; RL Cancer Res. 65:2662-2667(2005). RN [12] RP CHROMOSOMAL TRANSLOCATION WITH PCM1. RX PubMed=16034466; DOI=10.1038/sj.leu.2403879; RA Murati A., Gelsi-Boyer V., Adelaide J., Perot C., Talmant P., Giraudier S., RA Lode L., Letessier A., Delaval B., Brunel V., Imbert M., Garand R., RA Xerri L., Birnbaum D., Mozziconacci M.-J., Chaffanet M.; RT "PCM1-JAK2 fusion in myeloproliferative disorders and acute erythroid RT leukemia with t(8;9) translocation."; RL Leukemia 19:1692-1696(2005). RN [13] RP CHROMOSOMAL TRANSLOCATION WITH PCM1. RX PubMed=16091753; DOI=10.1038/sj.onc.1208850; RA Bousquet M., Quelen C., De Mas V., Duchayne E., Roquefeuil B., Delsol G., RA Laurent G., Dastugue N., Brousset P.; RT "The t(8;9)(p22;p24) translocation in atypical chronic myeloid leukaemia RT yields a new PCM1-JAK2 fusion gene."; RL Oncogene 24:7248-7252(2005). RN [14] RP CHROMOSOMAL TRANSLOCATION WITH PCM1. RX PubMed=16769584; RA Bacher U., Reiter A., Haferlach T., Mueller L., Schnittger S., Kern W., RA Schoch C.; RT "A combination of cytomorphology, cytogenetic analysis, fluorescence in RT situ hybridization and reverse transcriptase polymerase chain reaction for RT establishing clonality in cases of persisting hypereosinophilia."; RL Haematologica 91:817-820(2006). RN [15] RP FUNCTION, AND INTERACTION WITH MPL/TPOR. RX PubMed=15899890; DOI=10.1074/jbc.m501376200; RA Royer Y., Staerk J., Costuleanu M., Courtoy P.J., Constantinescu S.N.; RT "Janus kinases affect thrombopoietin receptor cell surface localization and RT stability."; RL J. Biol. Chem. 280:27251-27261(2005). RN [16] RP TISSUE SPECIFICITY, AND CHROMOSOMAL TRANSLOCATION WITH PCM1. RX PubMed=16424865; DOI=10.1038/sj.leu.2404104; RA Adelaide J., Perot C., Gelsi-Boyer V., Pautas C., Murati A., RA Copie-Bergman C., Imbert M., Chaffanet M., Birnbaum D., Mozziconacci M.-J.; RT "A t(8;9) translocation with PCM1-JAK2 fusion in a patient with T-cell RT lymphoma."; RL Leukemia 20:536-537(2006). RN [17] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=19783980; DOI=10.1038/nature08448; RA Dawson M.A., Bannister A.J., Gottgens B., Foster S.D., Bartke T., RA Green A.R., Kouzarides T.; RT "JAK2 phosphorylates histone H3Y41 and excludes HP1alpha from chromatin."; RL Nature 461:819-822(2009). RN [18] RP ACTIVITY REGULATION. RX PubMed=21036157; DOI=10.1016/j.bbrc.2010.10.101; RA Yao X., Balamurugan P., Arvey A., Leslie C., Zhang L.; RT "Heme controls the regulation of protein tyrosine kinases Jak2 and Src."; RL Biochem. Biophys. Res. Commun. 403:30-35(2010). RN [19] RP INTERACTION WITH HSP90AB1. RX PubMed=20353823; DOI=10.1016/j.cellsig.2010.03.012; RA Cheng M.B., Zhang Y., Zhong X., Sutter B., Cao C.Y., Chen X.S., Cheng X.K., RA Zhang Y., Xiao L., Shen Y.F.; RT "Stat1 mediates an auto-regulation of hsp90beta gene in heat shock RT response."; RL Cell. Signal. 22:1206-1213(2010). RN [20] RP FUNCTION. RX PubMed=20098430; DOI=10.1038/nm.2079; RA Guilluy C., Bregeon J., Toumaniantz G., Rolli-Derkinderen M., RA Retailleau K., Loufrani L., Henrion D., Scalbert E., Bril A., Torres R.M., RA Offermanns S., Pacaud P., Loirand G.; RT "The Rho exchange factor Arhgef1 mediates the effects of angiotensin II on RT vascular tone and blood pressure."; RL Nat. Med. 16:183-190(2010). RN [21] RP FUNCTION IN PHOSPHORYLATION OF CDKN1B. RX PubMed=21423214; DOI=10.1038/onc.2011.68; RA Jakel H., Weinl C., Hengst L.; RT "Phosphorylation of p27Kip1 by JAK2 directly links cytokine receptor RT signaling to cell cycle control."; RL Oncogene 30:3502-3512(2011). RN [22] RP FUNCTION, INTERACTION WITH STRA6, AND PHOSPHORYLATION. RX PubMed=21368206; DOI=10.1073/pnas.1011115108; RA Berry D.C., Jin H., Majumdar A., Noy N.; RT "Signaling by vitamin A and retinol-binding protein regulates gene RT expression to inhibit insulin responses."; RL Proc. Natl. Acad. Sci. U.S.A. 108:4340-4345(2011). RN [23] RP REVIEW ON FUNCTION. RX PubMed=16456223; DOI=10.1385/cbb:44:2:213; RA Wallace T.A., Sayeski P.P.; RT "Jak2 tyrosine kinase: a mediator of both housekeeping and ligand-dependent RT gene expression?"; RL Cell Biochem. Biophys. 44:213-222(2006). RN [24] RP REVIEW ON FUNCTION. RX PubMed=19290934; DOI=10.1111/j.1600-065x.2008.00754.x; RA Ghoreschi K., Laurence A., O'Shea J.J.; RT "Janus kinases in immune cell signaling."; RL Immunol. Rev. 228:273-287(2009). RN [25] RP INTERACTION WITH ASB2, AND PROTEASOMAL DEGRADATION. RX PubMed=21119685; DOI=10.1038/cr.2010.165; RA Nie L., Zhao Y., Wu W., Yang Y.Z., Wang H.C., Sun X.H.; RT "Notch-induced Asb2 expression promotes protein ubiquitination by forming RT non-canonical E3 ligase complexes."; RL Cell Res. 21:754-769(2011). RN [26] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-570, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [27] RP INTERACTION WITH RHEX. RX PubMed=25092874; DOI=10.1084/jem.20130624; RA Verma R., Su S., McCrann D.J., Green J.M., Leu K., Young P.R., Schatz P.J., RA Silva J.C., Stokes M.P., Wojchowski D.M.; RT "RHEX, a novel regulator of human erythroid progenitor cell expansion and RT erythroblast development."; RL J. Exp. Med. 211:1715-1722(2014). RN [28] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=15690087; DOI=10.1172/jci22710; RA Greenhalgh C.J., Rico-Bautista E., Lorentzon M., Thaus A.L., Morgan P.O., RA Willson T.A., Zervoudakis P., Metcalf D., Street I., Nicola N.A., RA Nash A.D., Fabri L.J., Norstedt G., Ohlsson C., Flores-Morales A., RA Alexander W.S., Hilton D.J.; RT "SOCS2 negatively regulates growth hormone action in vitro and in vivo."; RL J. Clin. Invest. 115:397-406(2005). RN [29] RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 840-1132 IN COMPLEX WITH SYNTHETIC RP INHIBITOR, CATALYTIC ACTIVITY, IDENTIFICATION BY MASS SPECTROMETRY, AND RP PHOSPHORYLATION AT TYR-1007 AND TYR-1008. RX PubMed=16174768; DOI=10.1182/blood-2005-06-2413; RA Lucet I.S., Fantino E., Styles M., Bamert R., Patel O., Broughton S.E., RA Walter M., Burns C.J., Treutlein H., Wilks A.F., Rossjohn J.; RT "The structural basis of Janus kinase 2 inhibition by a potent and specific RT pan-Janus kinase inhibitor."; RL Blood 107:176-183(2006). RN [30] RP VARIANT PV PHE-617. RX PubMed=15781101; DOI=10.1016/s0140-6736(05)71142-9; RG The cancer genome project; RA Baxter E.J., Scott L.M., Campbell P.J., East C., Fourouclas N., Swanton S., RA Vassiliou G.S., Bench A.J., Boyd E.M., Curtin N., Scott M.A., Erber W.N., RA Green A.R.; RT "Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative RT disorders."; RL Lancet 365:1054-1061(2005). RN [31] RP ERRATUM OF PUBMED:15781101. RG The cancer genome project; RA Baxter E.J., Scott L.M., Campbell P.J., East C., Fourouclas N., Swanton S., RA Vassiliou G.S., Bench A.J., Boyd E.M., Curtin N., Scott M.A., Erber W.N., RA Green A.R.; RL Lancet 366:122-122(2005). RN [32] RP VARIANT THCYT3 PHE-617. RX PubMed=16325696; DOI=10.1016/s0140-6736(05)67785-9; RG The United Kingdom myeloproliferative disorders study group; RG The medical research council adult leukaemia working party; RG The Australasian leukaemia and lymphoma group; RA Campbell P.J., Scott L.M., Buck G., Wheatley K., East C.L., Marsden J.T., RA Duffy A., Boyd E.M., Bench A.J., Scott M.A., Vassiliou G.S., Milligan D.W., RA Smith S.R., Erber W.N., Bareford D., Wilkins B.S., Reilly J.T., RA Harrison C.N., Green A.R.; RT "Definition of subtypes of essential thrombocythaemia and relation to RT polycythaemia vera based on JAK2 V617F mutation status: a prospective RT study."; RL Lancet 366:1945-1953(2005). RN [33] RP VARIANT PV PHE-617, AND CHARACTERIZATION OF VARIANT PV PHE-617. RX PubMed=15793561; DOI=10.1038/nature03546; RA James C., Ugo V., Le Couedic J.-P., Staerk J., Delhommeau F., Lacout C., RA Garcon L., Raslova H., Berger R., Bennaceur-Griscelli A., Villeval J.L., RA Constantinescu S.N., Casadevall N., Vainchenker W.; RT "A unique clonal JAK2 mutation leading to constitutive signalling causes RT polycythaemia vera."; RL Nature 434:1144-1148(2005). RN [34] RP VARIANT PV PHE-617. RX PubMed=15858187; DOI=10.1056/nejmoa051113; RA Kralovics R., Passamonti F., Buser A.S., Teo S.-S., Tiedt R., Passweg J.R., RA Tichelli A., Cazzola M., Skoda R.C.; RT "A gain-of-function mutation of JAK2 in myeloproliferative disorders."; RL N. Engl. J. Med. 352:1779-1790(2005). RN [35] RP ASSOCIATION OF VARIANT PHE-617 WITH SUSCEPTIBILITY BUDD-CHIARI SYNDROME. RX PubMed=16707754; DOI=10.1056/nejmcpc069006; RA Chung R.T., Iafrate A.J., Amrein P.C., Sahani D.V., Misdraji J.; RT "Case records of the Massachusetts General Hospital. Case 15-2006: a 46- RT year-old woman with sudden onset of abdominal distention."; RL N. Engl. J. Med. 354:2166-2175(2006). RN [36] RP VARIANTS AML ASN-607 AND PHE-617. RX PubMed=16247455; DOI=10.1038/sj.onc.1209163; RA Lee J.W., Kim Y.G., Soung Y.H., Han K.J., Kim S.Y., Rhim H.S., Min W.S., RA Nam S.W., Park W.S., Lee J.Y., Yoo N.J., Lee S.H.; RT "The JAK2 V617F mutation in de novo acute myelogenous leukemias."; RL Oncogene 25:1434-1436(2006). RN [37] RP VARIANT PV PHE-617. RX PubMed=16603627; DOI=10.1073/pnas.0601462103; RA Jamieson C.H.M., Gotlib J., Durocher J.A., Chao M.P., Mariappan M.R., RA Lay M., Jones C., Zehnder J.L., Lilleberg S.L., Weissman I.L.; RT "The JAK2 V617F mutation occurs in hematopoietic stem cells in polycythemia RT vera and predisposes toward erythroid differentiation."; RL Proc. Natl. Acad. Sci. U.S.A. 103:6224-6229(2006). RN [38] RP VARIANTS MYELOPROLIFERATIVE DISORDER WITH ERYTHROCYTOSIS 537-PHE--LYS-539 RP DELINS LEU; 538-HIS-LYS-539 DELINS GLN-LEU AND LEU-539. RX PubMed=17267906; DOI=10.1056/nejmoa065202; RA Scott L.M., Tong W., Levine R.L., Scott M.A., Beer P.A., Stratton M.R., RA Futreal P.A., Erber W.N., McMullin M.F., Harrison C.N., Warren A.J., RA Gilliland D.G., Lodish H.F., Green A.R.; RT "JAK2 exon 12 mutations in polycythemia vera and idiopathic RT erythrocytosis."; RL N. Engl. J. Med. 356:459-468(2007). RN [39] RP VARIANTS [LARGE SCALE ANALYSIS] ASP-127; GLN-191; ARG-346; GLU-377; VAL-393 RP AND HIS-1063. 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 [40] RP VARIANT THCYT3 ILE-617. RX PubMed=22397670; DOI=10.1056/nejmc1200349; RA Mead A.J., Rugless M.J., Jacobsen S.E., Schuh A.; RT "Germline JAK2 mutation in a family with hereditary thrombocytosis."; RL N. Engl. J. Med. 366:967-969(2012). RN [41] RP CHARACTERIZATION OF VARIANT PV PHE-617, FUNCTION, AND MUTAGENESIS OF RP LYS-882. RX PubMed=25644777; DOI=10.1007/s00232-015-9772-2; RA Hosseinzadeh Z., Warsi J., Elvira B., Almilaji A., Shumilina E., Lang F.; RT "Up-regulation of Kv1.3 channels by janus kinase 2."; RL J. Membr. Biol. 248:309-317(2015). CC -!- FUNCTION: Non-receptor tyrosine kinase involved in various processes CC such as cell growth, development, differentiation or histone CC modifications. Mediates essential signaling events in both innate and CC adaptive immunity. In the cytoplasm, plays a pivotal role in signal CC transduction via its association with type I receptors such as growth CC hormone (GHR), prolactin (PRLR), leptin (LEPR), erythropoietin (EPOR), CC thrombopoietin receptor (MPL/TPOR); or type II receptors including IFN- CC alpha, IFN-beta, IFN-gamma and multiple interleukins (PubMed:15690087, CC PubMed:7615558, PubMed:9657743, PubMed:15899890). Following ligand- CC binding to cell surface receptors, phosphorylates specific tyrosine CC residues on the cytoplasmic tails of the receptor, creating docking CC sites for STATs proteins (PubMed:15690087, PubMed:9618263). CC Subsequently, phosphorylates the STATs proteins once they are recruited CC to the receptor. Phosphorylated STATs then form homodimer or CC heterodimers and translocate to the nucleus to activate gene CC transcription. For example, cell stimulation with erythropoietin (EPO) CC during erythropoiesis leads to JAK2 autophosphorylation, activation, CC and its association with erythropoietin receptor (EPOR) that becomes CC phosphorylated in its cytoplasmic domain (PubMed:9657743). Then, STAT5 CC (STAT5A or STAT5B) is recruited, phosphorylated and activated by JAK2. CC Once activated, dimerized STAT5 translocates into the nucleus and CC promotes the transcription of several essential genes involved in the CC modulation of erythropoiesis. Part of a signaling cascade that is CC activated by increased cellular retinol and that leads to the CC activation of STAT5 (STAT5A or STAT5B) (PubMed:21368206). In addition, CC JAK2 mediates angiotensin-2-induced ARHGEF1 phosphorylation CC (PubMed:20098430). Plays a role in cell cycle by phosphorylating CDKN1B CC (PubMed:21423214). Cooperates with TEC through reciprocal CC phosphorylation to mediate cytokine-driven activation of FOS CC transcription. In the nucleus, plays a key role in chromatin by CC specifically mediating phosphorylation of 'Tyr-41' of histone H3 CC (H3Y41ph), a specific tag that promotes exclusion of CBX5 (HP1 alpha) CC from chromatin (PubMed:19783980). Up-regulates the potassium voltage- CC gated channel activity of KCNA3 (PubMed:25644777). CC {ECO:0000269|PubMed:12023369, ECO:0000269|PubMed:15690087, CC ECO:0000269|PubMed:19783980, ECO:0000269|PubMed:20098430, CC ECO:0000269|PubMed:21368206, ECO:0000269|PubMed:21423214, CC ECO:0000269|PubMed:25644777, ECO:0000269|PubMed:7615558, CC ECO:0000269|PubMed:9618263, ECO:0000269|PubMed:9657743}. 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:15690087, ECO:0000269|PubMed:16174768, CC ECO:0000269|PubMed:7615558, ECO:0000269|PubMed:9618263}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000305}; CC Note=Mn(2+) was used in the in vitro kinase assay but Mg(2+) is likely CC to be the in vivo cofactor. {ECO:0000305|PubMed:7615558}; CC -!- ACTIVITY REGULATION: Regulated by autophosphorylation, can both CC activate or decrease activity (By similarity). Heme regulates its CC activity by enhancing the phosphorylation on Tyr-1007 and Tyr-1008 CC (PubMed:21036157). {ECO:0000250|UniProtKB:Q62120, CC ECO:0000269|PubMed:21036157}. CC -!- SUBUNIT: Interacts with EPOR, LYN, SIRPA, SH2B1 and TEC (By CC similarity). Interacts with IL23R (PubMed:12023369). Interacts with CC SKB1 (PubMed:10531356). Interacts with STAM2 (PubMed:10899310). CC Interacts with IFNGR2 (via intracellular domain) (PubMed:7615558, CC PubMed:7673114). Interacts with LEPR (Isoform B) (By similarity). CC Interacts with HSP90AB1; promotes functional activation in a heat CC shock-dependent manner (PubMed:20353823). Interacts with STRA6 CC (PubMed:21368206). Interacts with RHEX; this interaction occurs in a CC erythropoietin (EPO)-dependent manner (PubMed:25092874). Interacts with CC ASB2; the interaction targets JAK2 for Notch-induced proteasomal CC degradation (PubMed:21119685). Interacts with MPL/TPOR CC (PubMed:15899890). {ECO:0000250|UniProtKB:Q62120, CC ECO:0000269|PubMed:10531356, ECO:0000269|PubMed:10899310, CC ECO:0000269|PubMed:12023369, ECO:0000269|PubMed:15899890, CC ECO:0000269|PubMed:16174768, ECO:0000269|PubMed:20353823, CC ECO:0000269|PubMed:21119685, ECO:0000269|PubMed:21368206, CC ECO:0000269|PubMed:25092874, ECO:0000269|PubMed:7615558, CC ECO:0000269|PubMed:7673114}. CC -!- INTERACTION: CC O60674; P32927: CSF2RB; NbExp=4; IntAct=EBI-518647, EBI-1809771; CC O60674; Q01344: IL5RA; NbExp=2; IntAct=EBI-518647, EBI-1759442; CC O60674; P23458: JAK1; NbExp=4; IntAct=EBI-518647, EBI-1383438; CC O60674; O60674: JAK2; NbExp=7; IntAct=EBI-518647, EBI-518647; CC O60674; P40238: MPL; NbExp=6; IntAct=EBI-518647, EBI-6511486; CC O60674; P16333: NCK1; NbExp=2; IntAct=EBI-518647, EBI-389883; CC O60674; P18031: PTPN1; NbExp=5; IntAct=EBI-518647, EBI-968788; CC O60674; O75116: ROCK2; NbExp=2; IntAct=EBI-518647, EBI-366288; CC O60674; P29597: TYK2; NbExp=2; IntAct=EBI-518647, EBI-1383454; CC O60674; Q9JHI9: Slc40a1; Xeno; NbExp=3; IntAct=EBI-518647, EBI-2931424; CC -!- SUBCELLULAR LOCATION: Endomembrane system {ECO:0000250}; Peripheral CC membrane protein {ECO:0000250}. Cytoplasm CC {ECO:0000269|PubMed:19783980}. Nucleus {ECO:0000269|PubMed:19783980}. CC -!- TISSUE SPECIFICITY: Ubiquitously expressed throughout most tissues. CC {ECO:0000269|PubMed:16424865}. CC -!- DOMAIN: Possesses 2 protein kinase domains. The second one probably CC contains the catalytic domain, while the presence of slight differences CC suggest a different role for protein kinase 1 (By similarity). CC {ECO:0000250}. CC -!- PTM: Autophosphorylated, leading to regulate its activity. Leptin CC promotes phosphorylation on tyrosine residues, including CC phosphorylation on Tyr-813 (By similarity). Autophosphorylation on Tyr- CC 119 in response to EPO down-regulates its kinase activity (By CC similarity). Autophosphorylation on Tyr-868, Tyr-966 and Tyr-972 in CC response to growth hormone (GH) are required for maximal kinase CC activity (By similarity). Also phosphorylated by TEC (By similarity). CC Phosphorylated on tyrosine residues in response to interferon gamma CC signaling (PubMed:7615558, PubMed:7673114). Phosphorylated on tyrosine CC residues in response to a signaling cascade that is activated by CC increased cellular retinol (PubMed:21368206). CC {ECO:0000250|UniProtKB:Q62120, ECO:0000269|PubMed:21368206, CC ECO:0000269|PubMed:7615558, ECO:0000269|PubMed:7673114}. CC -!- PTM: Undergoes Notch-induced ubiquitination and subsequent proteasomal CC degradation which is mediated by ASB1 or ASB2, the substrate- CC recognition components of probable ECS E3 ubiquitin-protein ligase CC complexes. {ECO:0000269|PubMed:21119685}. CC -!- DISEASE: Note=Chromosomal aberrations involving JAK2 are found in both CC chronic and acute forms of eosinophilic, lymphoblastic and myeloid CC leukemia. Translocation t(8;9)(p22;p24) with PCM1 links the protein CC kinase domain of JAK2 to the major portion of PCM1. Translocation CC t(9;12)(p24;p13) with ETV6. CC -!- DISEASE: Budd-Chiari syndrome (BDCHS) [MIM:600880]: A syndrome caused CC by obstruction of hepatic venous outflow involving either the hepatic CC veins or the terminal segment of the inferior vena cava. Obstructions CC are generally caused by thrombosis and lead to hepatic congestion and CC ischemic necrosis. Clinical manifestations observed in the majority of CC patients include hepatomegaly, right upper quadrant pain and abdominal CC ascites. Budd-Chiari syndrome is associated with a combination of CC disease states including primary myeloproliferative syndromes and CC thrombophilia due to factor V Leiden, protein C deficiency and CC antithrombin III deficiency. Budd-Chiari syndrome is a rare but typical CC complication in patients with polycythemia vera. CC {ECO:0000269|PubMed:16707754}. Note=Disease susceptibility is CC associated with variants affecting the gene represented in this entry. CC -!- DISEASE: Polycythemia vera (PV) [MIM:263300]: A myeloproliferative CC disorder characterized by abnormal proliferation of all hematopoietic CC bone marrow elements, erythroid hyperplasia, an absolute increase in CC total blood volume, but also by myeloid leukocytosis, thrombocytosis CC and splenomegaly. {ECO:0000269|PubMed:15781101, CC ECO:0000269|PubMed:15793561, ECO:0000269|PubMed:15858187, CC ECO:0000269|PubMed:16603627, ECO:0000269|PubMed:25644777}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Thrombocythemia 3 (THCYT3) [MIM:614521]: A myeloproliferative CC disorder characterized by excessive platelet production, resulting in CC increased numbers of circulating platelets. It can be associated with CC spontaneous hemorrhages and thrombotic episodes. CC {ECO:0000269|PubMed:16325696, ECO:0000269|PubMed:22397670}. Note=The CC disease may be caused by variants affecting the gene represented in CC this entry. CC -!- DISEASE: Myelofibrosis (MYELOF) [MIM:254450]: A disorder characterized CC by replacement of the bone marrow by fibrous tissue, occurring in CC association with a myeloproliferative disorder. Clinical manifestations CC may include anemia, pallor, splenomegaly, hypermetabolic state, CC petechiae, ecchymosis, bleeding, lymphadenopathy, hepatomegaly, portal CC hypertension. Note=The disease is caused by variants affecting the gene CC represented in this entry. CC -!- DISEASE: Leukemia, acute myelogenous (AML) [MIM:601626]: A subtype of CC acute leukemia, a cancer of the white blood cells. AML is a malignant CC disease of bone marrow characterized by maturational arrest of CC hematopoietic precursors at an early stage of development. Clonal CC expansion of myeloid blasts occurs in bone marrow, blood, and other CC tissue. Myelogenous leukemias develop from changes in cells that CC normally produce neutrophils, basophils, eosinophils and monocytes. CC {ECO:0000269|PubMed:16247455}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein CC kinase family. JAK 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/98/JAK"; 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; AF058925; AAC23982.1; -; mRNA. DR EMBL; AF001362; AAC23653.1; -; mRNA. DR EMBL; AF005216; AAB82092.1; -; mRNA. DR EMBL; AL161450; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR CCDS; CCDS6457.1; -. DR PIR; JW0091; JW0091. DR RefSeq; NP_001309123.1; NM_001322194.2. DR RefSeq; NP_001309124.1; NM_001322195.2. DR RefSeq; NP_001309125.1; NM_001322196.2. DR RefSeq; NP_001309133.1; NM_001322204.1. DR RefSeq; NP_004963.1; NM_004972.4. DR PDB; 2B7A; X-ray; 2.00 A; A/B=840-1132. DR PDB; 2W1I; X-ray; 2.60 A; A/B=835-1132. DR PDB; 2XA4; X-ray; 2.04 A; A/B=835-1132. DR PDB; 3E62; X-ray; 1.92 A; A=839-1131. DR PDB; 3E63; X-ray; 1.90 A; A=839-1131. DR PDB; 3E64; X-ray; 1.80 A; A=839-1131. DR PDB; 3FUP; X-ray; 2.40 A; A/B=840-1132. DR PDB; 3IO7; X-ray; 2.60 A; A=842-1132. DR PDB; 3IOK; X-ray; 2.10 A; A=842-1132. DR PDB; 3JY9; X-ray; 2.10 A; A=842-1130. DR PDB; 3KCK; X-ray; 2.20 A; A=842-1132. DR PDB; 3KRR; X-ray; 1.80 A; A=840-1132. DR PDB; 3LPB; X-ray; 2.00 A; A/B=840-1132. DR PDB; 3Q32; X-ray; 2.50 A; A/B=839-1132. DR PDB; 3RVG; X-ray; 2.50 A; A=835-1132. DR PDB; 3TJC; X-ray; 2.40 A; A/B=837-1132. DR PDB; 3TJD; X-ray; 2.90 A; A/B=837-1132. DR PDB; 3UGC; X-ray; 1.34 A; A=840-1132. DR PDB; 3ZMM; X-ray; 2.51 A; A/B=835-1132. DR PDB; 4AQC; X-ray; 1.90 A; A/B=835-1132. DR PDB; 4BBE; X-ray; 1.90 A; A/B/C/D=839-1132. DR PDB; 4BBF; X-ray; 2.00 A; A/B/C/D=839-1132. DR PDB; 4C61; X-ray; 2.45 A; A/B=835-1132. DR PDB; 4C62; X-ray; 2.75 A; A/B=835-1132. DR PDB; 4D0W; X-ray; 1.77 A; A=835-1132. DR PDB; 4D0X; X-ray; 1.82 A; A=835-1132. DR PDB; 4D1S; X-ray; 1.66 A; A=835-1132. DR PDB; 4E4M; X-ray; 2.25 A; A/B/D/E=833-1132. DR PDB; 4E6D; X-ray; 2.22 A; A/B=835-1132. DR PDB; 4E6Q; X-ray; 1.95 A; A/B=835-1132. DR PDB; 4F08; X-ray; 2.82 A; A/B=833-1132. DR PDB; 4F09; X-ray; 2.40 A; A=833-1132. DR PDB; 4FVP; X-ray; 2.01 A; A=536-812. DR PDB; 4FVQ; X-ray; 1.75 A; A=536-812. DR PDB; 4FVR; X-ray; 2.00 A; A=536-812. DR PDB; 4GFM; X-ray; 2.30 A; A=833-1132. DR PDB; 4GMY; X-ray; 2.40 A; A=833-1132. DR PDB; 4HGE; X-ray; 2.30 A; A/B=833-1132. DR PDB; 4IVA; X-ray; 1.50 A; A=833-1132. DR PDB; 4JI9; X-ray; 2.40 A; A/B=833-1132. DR PDB; 4JIA; X-ray; 1.85 A; A=833-1132. DR PDB; 4P7E; X-ray; 2.40 A; A/B=840-1132. DR PDB; 4YTC; X-ray; 2.16 A; A=842-1132. DR PDB; 4YTF; X-ray; 1.78 A; A=842-1132. DR PDB; 4YTH; X-ray; 2.04 A; A=842-1132. DR PDB; 4YTI; X-ray; 2.52 A; A=842-1132. DR PDB; 4Z32; X-ray; 3.04 A; A/B/C/D/E/F/G/H=31-516. DR PDB; 4ZIM; X-ray; 2.65 A; A/B=839-1132. DR PDB; 5AEP; X-ray; 1.95 A; A=835-1132. DR PDB; 5CF4; X-ray; 2.38 A; A/B=839-1132. DR PDB; 5CF5; X-ray; 2.45 A; A/B=839-1132. DR PDB; 5CF6; X-ray; 2.50 A; A/B=839-1132. DR PDB; 5CF8; X-ray; 1.80 A; A/B=839-1132. DR PDB; 5HEZ; X-ray; 2.66 A; A/B/C/D=833-1132. DR PDB; 5I4N; X-ray; 1.54 A; A=535-812. DR PDB; 5L3A; X-ray; 1.98 A; A=840-1132. DR PDB; 5TQ3; X-ray; 2.69 A; A/B=837-1132. DR PDB; 5TQ4; X-ray; 2.30 A; A=837-1132. DR PDB; 5TQ5; X-ray; 2.30 A; A=837-1132. DR PDB; 5TQ6; X-ray; 2.06 A; A/B=837-1132. DR PDB; 5TQ7; X-ray; 2.10 A; A/B=837-1132. DR PDB; 5TQ8; X-ray; 1.59 A; A=837-1132. DR PDB; 5USY; X-ray; 2.00 A; A/B=840-1132. DR PDB; 5USZ; X-ray; 2.10 A; A=536-812. DR PDB; 5UT0; X-ray; 2.10 A; A=536-812. DR PDB; 5UT1; X-ray; 1.95 A; A=536-812. DR PDB; 5UT2; X-ray; 1.75 A; A=536-812. DR PDB; 5UT3; X-ray; 1.50 A; A=536-812. DR PDB; 5UT4; X-ray; 2.00 A; A=536-812. DR PDB; 5UT5; X-ray; 1.90 A; A=536-812. DR PDB; 5UT6; X-ray; 1.65 A; A=536-812. DR PDB; 5WEV; X-ray; 1.85 A; A=833-1132. DR PDB; 5WIJ; X-ray; 2.04 A; A=536-812. DR PDB; 5WIK; X-ray; 2.60 A; B=536-812. DR PDB; 5WIL; X-ray; 2.20 A; A=536-812. DR PDB; 5WIM; X-ray; 2.55 A; A=536-812. DR PDB; 5WIN; X-ray; 2.38 A; A=536-812. DR PDB; 6AAJ; X-ray; 2.37 A; A/B=834-1132. DR PDB; 6BBV; X-ray; 1.80 A; A=837-1132. DR PDB; 6BRW; X-ray; 2.03 A; A=536-812. DR PDB; 6BS0; X-ray; 1.54 A; A=536-812. DR PDB; 6BSS; X-ray; 2.10 A; A=536-812. DR PDB; 6D2I; X-ray; 3.19 A; A/B=536-808. DR PDB; 6DRW; X-ray; 2.30 A; A=840-1132. DR PDB; 6E2P; X-ray; 2.83 A; A/B=36-514. DR PDB; 6E2Q; X-ray; 2.65 A; A/B/C/D=36-514. DR PDB; 6G3C; X-ray; 1.60 A; A/B=537-808. DR PDB; 6M9H; X-ray; 1.79 A; A=536-812. DR PDB; 6OAV; X-ray; 1.94 A; A=536-812. DR PDB; 6OBB; X-ray; 1.90 A; A=536-812. DR PDB; 6OBF; X-ray; 1.71 A; A=536-812. DR PDB; 6OBL; X-ray; 2.06 A; A=536-812. DR PDB; 6OCC; X-ray; 2.03 A; A=536-812. DR PDB; 6TPD; X-ray; 1.99 A; A=842-1130. DR PDB; 6VGL; X-ray; 1.90 A; A/B/C/D=840-1132. DR PDB; 6VN8; X-ray; 1.90 A; A/B=840-1132. DR PDB; 6VNB; X-ray; 2.19 A; A/B=840-1132. DR PDB; 6VNC; X-ray; 2.30 A; A/B=840-1132. DR PDB; 6VNE; X-ray; 2.32 A; A/B=840-1132. DR PDB; 6VNF; X-ray; 2.06 A; A/B=840-1132. DR PDB; 6VNG; X-ray; 2.50 A; A/B=840-1132. DR PDB; 6VNH; X-ray; 2.40 A; A/B=840-1132. DR PDB; 6VNI; X-ray; 2.10 A; A/B=840-1132. DR PDB; 6VNJ; X-ray; 1.90 A; A/B=840-1132. DR PDB; 6VNK; X-ray; 2.00 A; A/B/C/D=840-1132. DR PDB; 6VNL; X-ray; 2.40 A; A/B/C/D=840-1132. DR PDB; 6VNM; X-ray; 2.20 A; A/B=840-1132. DR PDB; 6VS3; X-ray; 2.00 A; A/B=840-1132. DR PDB; 6VSN; X-ray; 2.50 A; A/B/C/D=840-1132. DR PDB; 6WTN; X-ray; 1.83 A; A=835-1132. DR PDB; 6WTO; X-ray; 1.74 A; A=835-1132. DR PDB; 6WTP; X-ray; 2.50 A; A=835-1132. DR PDB; 6WTQ; X-ray; 1.80 A; A=835-1132. DR PDB; 6X8E; X-ray; 1.75 A; A/B=837-1132. DR PDB; 6XJK; X-ray; 2.02 A; A=536-812. DR PDB; 7F7W; X-ray; 1.83 A; A/B=536-810. DR PDB; 7JYO; X-ray; 2.16 A; A=536-812. DR PDB; 7JYQ; X-ray; 1.86 A; A=536-812. DR PDB; 7LL4; X-ray; 1.31 A; A=839-1132. DR PDB; 7LL5; X-ray; 1.50 A; A=840-1132. DR PDB; 7Q7I; X-ray; 1.78 A; A=839-1132. DR PDB; 7Q7K; X-ray; 1.61 A; A=839-1132. DR PDB; 7Q7L; X-ray; 1.97 A; A=839-1132. DR PDB; 7Q7W; X-ray; 1.85 A; A=839-1132. DR PDB; 7REE; X-ray; 1.38 A; A=839-1132. DR PDB; 7RN6; X-ray; 1.50 A; A=839-1132. DR PDB; 7SZW; X-ray; 1.91 A; A=536-812. DR PDB; 7T0P; X-ray; 2.04 A; A/B=536-812. DR PDB; 7T1T; X-ray; 2.08 A; A=536-812. DR PDB; 7TEU; X-ray; 1.45 A; A=837-1132. DR PDB; 7UYW; X-ray; 2.51 A; A=842-1132. DR PDB; 8B8N; X-ray; 2.00 A; A=536-812. DR PDB; 8B8U; X-ray; 1.50 A; A/B=536-812. DR PDB; 8B99; X-ray; 1.60 A; A=536-812. DR PDB; 8B9E; X-ray; 1.50 A; A=536-812. DR PDB; 8B9H; X-ray; 1.50 A; A=536-812. DR PDB; 8BA2; X-ray; 1.50 A; A=536-812. DR PDB; 8BA3; X-ray; 1.40 A; A=536-812. DR PDB; 8BA4; X-ray; 2.10 A; A/B=536-812. DR PDB; 8BAB; X-ray; 1.55 A; A=536-812. DR PDB; 8BAK; X-ray; 1.65 A; A=536-812. DR PDB; 8BM2; X-ray; 1.50 A; A/B=840-1132. DR PDB; 8BPV; X-ray; 1.70 A; A=840-1132. DR PDB; 8BPW; X-ray; 1.80 A; A/B=840-1132. DR PDB; 8BX6; X-ray; 1.50 A; A=840-1132. DR PDB; 8BX9; X-ray; 1.40 A; A/B=840-1132. DR PDB; 8BXC; X-ray; 1.90 A; A/B=840-1132. DR PDB; 8BXH; X-ray; 1.30 A; A=840-1132. DR PDB; 8C08; X-ray; 2.20 A; A/B=536-812. DR PDB; 8C09; X-ray; 1.90 A; A=536-812. DR PDB; 8C0A; X-ray; 1.70 A; A/B=536-812. DR PDB; 8CZ9; X-ray; 1.65 A; C=811-818. DR PDB; 8EX0; X-ray; 1.85 A; A=536-812. DR PDB; 8EX1; X-ray; 1.50 A; A=536-812. DR PDB; 8EX2; X-ray; 1.90 A; A=536-812. DR PDB; 8EXK; X-ray; 2.10 A; B=1000-1015. DR PDB; 8EYA; X-ray; 2.10 A; D/E=1000-1015. DR PDB; 8EYB; X-ray; 2.35 A; D/E=1000-1015. DR PDB; 8F88; X-ray; 3.10 A; E/F/G=1000-1015. DR PDB; 8G6Z; X-ray; 2.45 A; A/B=837-1132. DR PDB; 8G8O; X-ray; 2.20 A; A/B=837-1132. DR PDB; 8G8X; X-ray; 1.97 A; A/B=837-1132. DR PDBsum; 2B7A; -. DR PDBsum; 2W1I; -. DR PDBsum; 2XA4; -. DR PDBsum; 3E62; -. DR PDBsum; 3E63; -. DR PDBsum; 3E64; -. DR PDBsum; 3FUP; -. DR PDBsum; 3IO7; -. DR PDBsum; 3IOK; -. DR PDBsum; 3JY9; -. DR PDBsum; 3KCK; -. DR PDBsum; 3KRR; -. DR PDBsum; 3LPB; -. DR PDBsum; 3Q32; -. DR PDBsum; 3RVG; -. DR PDBsum; 3TJC; -. DR PDBsum; 3TJD; -. DR PDBsum; 3UGC; -. DR PDBsum; 3ZMM; -. DR PDBsum; 4AQC; -. DR PDBsum; 4BBE; -. DR PDBsum; 4BBF; -. DR PDBsum; 4C61; -. DR PDBsum; 4C62; -. DR PDBsum; 4D0W; -. DR PDBsum; 4D0X; -. DR PDBsum; 4D1S; -. DR PDBsum; 4E4M; -. DR PDBsum; 4E6D; -. DR PDBsum; 4E6Q; -. DR PDBsum; 4F08; -. DR PDBsum; 4F09; -. DR PDBsum; 4FVP; -. DR PDBsum; 4FVQ; -. DR PDBsum; 4FVR; -. DR PDBsum; 4GFM; -. DR PDBsum; 4GMY; -. DR PDBsum; 4HGE; -. DR PDBsum; 4IVA; -. DR PDBsum; 4JI9; -. DR PDBsum; 4JIA; -. DR PDBsum; 4P7E; -. DR PDBsum; 4YTC; -. DR PDBsum; 4YTF; -. DR PDBsum; 4YTH; -. DR PDBsum; 4YTI; -. DR PDBsum; 4Z32; -. DR PDBsum; 4ZIM; -. DR PDBsum; 5AEP; -. DR PDBsum; 5CF4; -. DR PDBsum; 5CF5; -. DR PDBsum; 5CF6; -. DR PDBsum; 5CF8; -. DR PDBsum; 5HEZ; -. DR PDBsum; 5I4N; -. DR PDBsum; 5L3A; -. DR PDBsum; 5TQ3; -. DR PDBsum; 5TQ4; -. DR PDBsum; 5TQ5; -. DR PDBsum; 5TQ6; -. DR PDBsum; 5TQ7; -. DR PDBsum; 5TQ8; -. DR PDBsum; 5USY; -. DR PDBsum; 5USZ; -. DR PDBsum; 5UT0; -. DR PDBsum; 5UT1; -. DR PDBsum; 5UT2; -. DR PDBsum; 5UT3; -. DR PDBsum; 5UT4; -. DR PDBsum; 5UT5; -. DR PDBsum; 5UT6; -. DR PDBsum; 5WEV; -. DR PDBsum; 5WIJ; -. DR PDBsum; 5WIK; -. DR PDBsum; 5WIL; -. DR PDBsum; 5WIM; -. DR PDBsum; 5WIN; -. DR PDBsum; 6AAJ; -. DR PDBsum; 6BBV; -. DR PDBsum; 6BRW; -. DR PDBsum; 6BS0; -. DR PDBsum; 6BSS; -. DR PDBsum; 6D2I; -. DR PDBsum; 6DRW; -. DR PDBsum; 6E2P; -. DR PDBsum; 6E2Q; -. DR PDBsum; 6G3C; -. DR PDBsum; 6M9H; -. DR PDBsum; 6OAV; -. DR PDBsum; 6OBB; -. DR PDBsum; 6OBF; -. DR PDBsum; 6OBL; -. DR PDBsum; 6OCC; -. DR PDBsum; 6TPD; -. DR PDBsum; 6VGL; -. DR PDBsum; 6VN8; -. DR PDBsum; 6VNB; -. DR PDBsum; 6VNC; -. DR PDBsum; 6VNE; -. DR PDBsum; 6VNF; -. DR PDBsum; 6VNG; -. DR PDBsum; 6VNH; -. DR PDBsum; 6VNI; -. DR PDBsum; 6VNJ; -. DR PDBsum; 6VNK; -. DR PDBsum; 6VNL; -. DR PDBsum; 6VNM; -. DR PDBsum; 6VS3; -. DR PDBsum; 6VSN; -. DR PDBsum; 6WTN; -. DR PDBsum; 6WTO; -. DR PDBsum; 6WTP; -. DR PDBsum; 6WTQ; -. DR PDBsum; 6X8E; -. DR PDBsum; 6XJK; -. DR PDBsum; 7F7W; -. DR PDBsum; 7JYO; -. DR PDBsum; 7JYQ; -. DR PDBsum; 7LL4; -. DR PDBsum; 7LL5; -. DR PDBsum; 7Q7I; -. DR PDBsum; 7Q7K; -. DR PDBsum; 7Q7L; -. DR PDBsum; 7Q7W; -. DR PDBsum; 7REE; -. DR PDBsum; 7RN6; -. DR PDBsum; 7SZW; -. DR PDBsum; 7T0P; -. DR PDBsum; 7T1T; -. DR PDBsum; 7TEU; -. DR PDBsum; 7UYW; -. DR PDBsum; 8B8N; -. DR PDBsum; 8B8U; -. DR PDBsum; 8B99; -. DR PDBsum; 8B9E; -. DR PDBsum; 8B9H; -. DR PDBsum; 8BA2; -. DR PDBsum; 8BA3; -. DR PDBsum; 8BA4; -. DR PDBsum; 8BAB; -. DR PDBsum; 8BAK; -. DR PDBsum; 8BM2; -. DR PDBsum; 8BPV; -. DR PDBsum; 8BPW; -. DR PDBsum; 8BX6; -. DR PDBsum; 8BX9; -. DR PDBsum; 8BXC; -. DR PDBsum; 8BXH; -. DR PDBsum; 8C08; -. DR PDBsum; 8C09; -. DR PDBsum; 8C0A; -. DR PDBsum; 8CZ9; -. DR PDBsum; 8EX0; -. DR PDBsum; 8EX1; -. DR PDBsum; 8EX2; -. DR PDBsum; 8EXK; -. DR PDBsum; 8EYA; -. DR PDBsum; 8EYB; -. DR PDBsum; 8F88; -. DR PDBsum; 8G6Z; -. DR PDBsum; 8G8O; -. DR PDBsum; 8G8X; -. DR AlphaFoldDB; O60674; -. DR SMR; O60674; -. DR BioGRID; 109920; 164. DR ComplexPortal; CPX-506; Interleukin-5 receptor-ligand complex. DR ComplexPortal; CPX-512; Granulocyte-macrophage colony-stimulating factor-receptor complex. DR CORUM; O60674; -. DR DIP; DIP-33880N; -. DR FunCoup; O60674; 2183. DR IntAct; O60674; 66. DR MINT; O60674; -. DR STRING; 9606.ENSP00000371067; -. DR BindingDB; O60674; -. DR ChEMBL; CHEMBL2971; -. DR DrugBank; DB04716; 2-tert-butyl-9-fluoro-1,6-dihydrobenzo[h]imidazo[4,5-f]isoquinolin-7-one. DR DrugBank; DB07162; 4-(3-amino-1H-indazol-5-yl)-N-tert-butylbenzenesulfonamide. DR DrugBank; DB08067; 4-[(2-{4-[(CYCLOPROPYLCARBAMOYL)AMINO]-1H-PYRAZOL-3-YL}-1H-BENZIMIDAZOL-6-YL)METHYL]MORPHOLIN-4-IUM. DR DrugBank; DB07161; 5-phenyl-1H-indazol-3-amine. DR DrugBank; DB14973; Abrocitinib. DR DrugBank; DB12535; AC-430. DR DrugBank; DB12588; AZD-1480. DR DrugBank; DB11817; Baricitinib. DR DrugBank; DB12591; BMS-911543. DR DrugBank; DB15499; Cerdulatinib. DR DrugBank; DB16133; Delgocitinib. DR DrugBank; DB18847; Deuruxolitinib. DR DrugBank; DB11986; Entrectinib. DR DrugBank; DB12500; Fedratinib. DR DrugBank; DB12010; Fostamatinib. DR DrugBank; DB13040; Gandotinib. DR DrugBank; DB12645; Givinostat. DR DrugBank; DB12784; Ilginatinib. DR DrugBank; DB12154; Itacitinib. DR DrugBank; DB11763; Momelotinib. DR DrugBank; DB11697; Pacritinib. DR DrugBank; DB15822; Pralsetinib. DR DrugBank; DB08877; Ruxolitinib. DR DrugBank; DB15294; SB-1578. DR DrugBank; DB13245; Thiram. DR DrugBank; DB08895; Tofacitinib. DR DrugBank; DB05243; XL019. DR DrugBank; DB15035; Zanubrutinib. DR DrugCentral; O60674; -. DR GuidetoPHARMACOLOGY; 2048; -. DR GlyGen; O60674; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; O60674; -. DR PhosphoSitePlus; O60674; -. DR BioMuta; JAK2; -. DR CPTAC; CPTAC-1252; -. DR CPTAC; CPTAC-3095; -. DR CPTAC; CPTAC-3096; -. DR jPOST; O60674; -. DR MassIVE; O60674; -. DR PaxDb; 9606-ENSP00000371067; -. DR PeptideAtlas; O60674; -. DR ProteomicsDB; 49519; -. DR Pumba; O60674; -. DR Antibodypedia; 24086; 1263 antibodies from 47 providers. DR CPTC; O60674; 1 antibody. DR DNASU; 3717; -. DR Ensembl; ENST00000381652.4; ENSP00000371067.4; ENSG00000096968.15. DR GeneID; 3717; -. DR KEGG; hsa:3717; -. DR MANE-Select; ENST00000381652.4; ENSP00000371067.4; NM_004972.4; NP_004963.1. DR UCSC; uc003ziw.3; human. DR AGR; HGNC:6192; -. DR CIViC; 3717; 12 evidence items across 10 molecular profiles. DR ClinPGx; PA29989; -. DR CTD; 3717; -. DR DisGeNET; 3717; -. DR GeneCards; JAK2; -. DR HGNC; HGNC:6192; JAK2. DR HPA; ENSG00000096968; Low tissue specificity. DR MalaCards; JAK2; -. DR MIM; 147796; gene. DR MIM; 254450; phenotype. DR MIM; 263300; phenotype. DR MIM; 600880; phenotype. DR MIM; 601626; phenotype. DR MIM; 614521; phenotype. DR OpenTargets; ENSG00000096968; -. DR Orphanet; 667662; Breast implant-associated anaplastic large cell lymphoma. DR Orphanet; 131; Budd-Chiari syndrome. DR Orphanet; 3318; Essential thrombocythemia. DR Orphanet; 71493; Familial thrombocytosis. DR Orphanet; 729; Polycythemia vera. DR Orphanet; 824; Primary myelofibrosis. DR VEuPathDB; HostDB:ENSG00000096968; -. DR eggNOG; KOG0197; Eukaryota. DR GeneTree; ENSGT00940000155640; -. DR HOGENOM; CLU_008155_1_0_1; -. DR InParanoid; O60674; -. DR OMA; RCHNILV; -. DR OrthoDB; 1915767at2759; -. DR PAN-GO; O60674; 10 GO annotations based on evolutionary models. DR PhylomeDB; O60674; -. DR BRENDA; 2.7.10.2; 2681. DR PathwayCommons; O60674; -. DR Reactome; R-HSA-1059683; Interleukin-6 signaling. DR Reactome; R-HSA-110056; MAPK3 (ERK1) activation. DR Reactome; R-HSA-112411; MAPK1 (ERK2) activation. DR Reactome; R-HSA-1170546; Prolactin receptor signaling. DR Reactome; R-HSA-1433557; Signaling by SCF-KIT. DR Reactome; R-HSA-2586552; Signaling by Leptin. DR Reactome; R-HSA-3214858; RMTs methylate histone arginines. DR Reactome; R-HSA-512988; Interleukin-3, Interleukin-5 and GM-CSF signaling. DR Reactome; R-HSA-5673000; RAF activation. DR Reactome; R-HSA-5673001; RAF/MAP kinase cascade. DR Reactome; R-HSA-6785807; Interleukin-4 and Interleukin-13 signaling. DR Reactome; R-HSA-6788467; IL-6-type cytokine receptor ligand interactions. DR Reactome; R-HSA-6802946; Signaling by moderate kinase activity BRAF mutants. DR Reactome; R-HSA-6802952; Signaling by BRAF and RAF1 fusions. DR Reactome; R-HSA-6802955; Paradoxical activation of RAF signaling by kinase inactive BRAF. DR Reactome; R-HSA-69231; Cyclin D associated events in G1. DR Reactome; R-HSA-877300; Interferon gamma signaling. DR Reactome; R-HSA-877312; Regulation of IFNG signaling. DR Reactome; R-HSA-8854691; Interleukin-20 family signaling. DR Reactome; R-HSA-8984722; Interleukin-35 Signalling. DR Reactome; R-HSA-9006335; Signaling by Erythropoietin. DR Reactome; R-HSA-9020591; Interleukin-12 signaling. DR Reactome; R-HSA-9020933; Interleukin-23 signaling. DR Reactome; R-HSA-9020956; Interleukin-27 signaling. DR Reactome; R-HSA-9027276; Erythropoietin activates Phosphoinositide-3-kinase (PI3K). DR Reactome; R-HSA-9027277; Erythropoietin activates Phospholipase C gamma (PLCG). DR Reactome; R-HSA-9027283; Erythropoietin activates STAT5. DR Reactome; R-HSA-9027284; Erythropoietin activates RAS. DR Reactome; R-HSA-912526; Interleukin receptor SHC signaling. DR Reactome; R-HSA-9649948; Signaling downstream of RAS mutants. DR Reactome; R-HSA-9656223; Signaling by RAF1 mutants. DR Reactome; R-HSA-9670439; Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants. DR Reactome; R-HSA-9674555; Signaling by CSF3 (G-CSF). DR Reactome; R-HSA-9679191; Potential therapeutics for SARS. DR Reactome; R-HSA-9705462; Inactivation of CSF3 (G-CSF) signaling. DR Reactome; R-HSA-9732724; IFNG signaling activates MAPKs. DR Reactome; R-HSA-982772; Growth hormone receptor signaling. DR Reactome; R-HSA-983231; Factors involved in megakaryocyte development and platelet production. DR SignaLink; O60674; -. DR SIGNOR; O60674; -. DR Agora; ENSG00000096968; -. DR BioGRID-ORCS; 3717; 30 hits in 1210 CRISPR screens. DR ChiTaRS; JAK2; human. DR EvolutionaryTrace; O60674; -. DR GeneWiki; Janus_kinase_2; -. DR GenomeRNAi; 3717; -. DR Pharos; O60674; Tclin. DR PRO; PR:O60674; -. DR Proteomes; UP000005640; Chromosome 9. DR RNAct; O60674; protein. DR Bgee; ENSG00000096968; Expressed in calcaneal tendon and 184 other cell types or tissues. DR ExpressionAtlas; O60674; baseline and differential. DR GO; GO:0005901; C:caveola; ISS:BHF-UCL. DR GO; GO:0000785; C:chromatin; IDA:UniProt. DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL. DR GO; GO:0009898; C:cytoplasmic side of plasma membrane; IDA:UniProt. DR GO; GO:0005829; C:cytosol; IBA:GO_Central. DR GO; GO:0031904; C:endosome lumen; TAS:Reactome. DR GO; GO:0000791; C:euchromatin; IEA:Ensembl. DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; IDA:UniProt. DR GO; GO:0019897; C:extrinsic component of plasma membrane; IDA:UniProt. DR GO; GO:0005925; C:focal adhesion; IDA:HPA. DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl. DR GO; GO:0030526; C:granulocyte macrophage colony-stimulating factor receptor complex; IDA:ComplexPortal. DR GO; GO:0042022; C:interleukin-12 receptor complex; IPI:ComplexPortal. DR GO; GO:0072536; C:interleukin-23 receptor complex; IPI:ComplexPortal. DR GO; GO:0045121; C:membrane raft; ISS:BHF-UCL. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0098794; C:postsynapse; IEA:Ensembl. DR GO; GO:0033130; F:acetylcholine receptor binding; IEA:Ensembl. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0005131; F:growth hormone receptor binding; ISS:BHF-UCL. DR GO; GO:0020037; F:heme binding; IDA:UniProtKB. DR GO; GO:0042393; F:histone binding; IEA:InterPro. DR GO; GO:0035401; F:histone H3Y41 kinase activity; IDA:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0043560; F:insulin receptor substrate binding; IEA:Ensembl. DR GO; GO:0005143; F:interleukin-12 receptor binding; ISS:BHF-UCL. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IDA:UniProt. DR GO; GO:0051428; F:peptide hormone receptor binding; IEA:Ensembl. DR GO; GO:0043548; F:phosphatidylinositol 3-kinase binding; IEA:Ensembl. DR GO; GO:0004672; F:protein kinase activity; NAS:ProtInc. DR GO; GO:0019901; F:protein kinase binding; IDA:BHF-UCL. DR GO; GO:0004713; F:protein tyrosine kinase activity; IDA:UniProtKB. DR GO; GO:0042169; F:SH2 domain binding; IPI:UniProtKB. DR GO; GO:0030546; F:signaling receptor activator activity; ISS:ARUK-UCL. DR GO; GO:0005102; F:signaling receptor binding; IPI:UniProtKB. DR GO; GO:0031702; F:type 1 angiotensin receptor binding; IEA:Ensembl. DR GO; GO:0030041; P:actin filament polymerization; NAS:BHF-UCL. DR GO; GO:0042976; P:activation of Janus kinase activity; ISS:UniProtKB. DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW. DR GO; GO:0006915; P:apoptotic process; ISS:BHF-UCL. DR GO; GO:0031103; P:axon regeneration; IEA:Ensembl. DR GO; GO:0007155; P:cell adhesion; IDA:UniProt. DR GO; GO:0030154; P:cell differentiation; ISS:BHF-UCL. DR GO; GO:0007259; P:cell surface receptor signaling pathway via JAK-STAT; IDA:ARUK-UCL. DR GO; GO:0071549; P:cellular response to dexamethasone stimulus; IEA:Ensembl. DR GO; GO:0036016; P:cellular response to interleukin-3; IEA:Ensembl. DR GO; GO:0098586; P:cellular response to virus; NAS:ComplexPortal. DR GO; GO:0038065; P:collagen-activated signaling pathway; IMP:ARUK-UCL. DR GO; GO:0019221; P:cytokine-mediated signaling pathway; IDA:BHF-UCL. DR GO; GO:0007167; P:enzyme-linked receptor protein signaling pathway; ISS:BHF-UCL. DR GO; GO:0030218; P:erythrocyte differentiation; ISS:UniProtKB. DR GO; GO:0038162; P:erythropoietin-mediated signaling pathway; IDA:UniProt. DR GO; GO:0097191; P:extrinsic apoptotic signaling pathway; ISS:BHF-UCL. DR GO; GO:0038157; P:granulocyte-macrophage colony-stimulating factor signaling pathway; IDA:ComplexPortal. DR GO; GO:0060396; P:growth hormone receptor signaling pathway; IDA:BHF-UCL. DR GO; GO:0060397; P:growth hormone receptor signaling pathway via JAK-STAT; IDA:UniProtKB. DR GO; GO:0006955; P:immune response; NAS:ComplexPortal. DR GO; GO:0035722; P:interleukin-12-mediated signaling pathway; IDA:BHF-UCL. DR GO; GO:0038155; P:interleukin-23-mediated signaling pathway; IDA:UniProt. DR GO; GO:0038156; P:interleukin-3-mediated signaling pathway; IDA:UniProt. DR GO; GO:0070757; P:interleukin-35-mediated signaling pathway; TAS:Reactome. DR GO; GO:0038043; P:interleukin-5-mediated signaling pathway; IDA:UniProt. DR GO; GO:0070102; P:interleukin-6-mediated signaling pathway; TAS:Reactome. DR GO; GO:0035556; P:intracellular signal transduction; ISS:BHF-UCL. DR GO; GO:0008631; P:intrinsic apoptotic signaling pathway in response to oxidative stress; IEA:Ensembl. DR GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; ISS:BHF-UCL. DR GO; GO:0061180; P:mammary gland epithelium development; ISS:BHF-UCL. DR GO; GO:0007498; P:mesoderm development; TAS:ProtInc. DR GO; GO:0001774; P:microglial cell activation; ISS:ARUK-UCL. DR GO; GO:0050804; P:modulation of chemical synaptic transmission; IEA:Ensembl. DR GO; GO:0010667; P:negative regulation of cardiac muscle cell apoptotic process; IEA:Ensembl. DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISS:BHF-UCL. DR GO; GO:0022408; P:negative regulation of cell-cell adhesion; IEA:Ensembl. DR GO; GO:1900016; P:negative regulation of cytokine production involved in inflammatory response; ISS:UniProt. DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IEA:Ensembl. DR GO; GO:0120186; P:negative regulation of protein localization to chromatin; IDA:UniProt. DR GO; GO:0031959; P:nuclear receptor-mediated mineralocorticoid signaling pathway; IEA:Ensembl. DR GO; GO:0048008; P:platelet-derived growth factor receptor signaling pathway; IEA:Ensembl. DR GO; GO:2001235; P:positive regulation of apoptotic signaling pathway; IEA:Ensembl. DR GO; GO:0045597; P:positive regulation of cell differentiation; IEA:Ensembl. DR GO; GO:0030335; P:positive regulation of cell migration; IEA:Ensembl. DR GO; GO:0010811; P:positive regulation of cell-substrate adhesion; IDA:BHF-UCL. DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; ISS:YuBioLab. DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IEA:Ensembl. DR GO; GO:1904037; P:positive regulation of epithelial cell apoptotic process; IEA:Ensembl. DR GO; GO:1902728; P:positive regulation of growth factor dependent skeletal muscle satellite cell proliferation; IEA:Ensembl. DR GO; GO:0060399; P:positive regulation of growth hormone receptor signaling pathway; ISS:BHF-UCL. DR GO; GO:0032024; P:positive regulation of insulin secretion; IEA:Ensembl. DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; ISS:ARUK-UCL. DR GO; GO:0032740; P:positive regulation of interleukin-17 production; NAS:ComplexPortal. DR GO; GO:0070665; P:positive regulation of leukocyte proliferation; IDA:ComplexPortal. DR GO; GO:0043410; P:positive regulation of MAPK cascade; IEA:Ensembl. DR GO; GO:0045348; P:positive regulation of MHC class II biosynthetic process; ISS:ARUK-UCL. DR GO; GO:0032819; P:positive regulation of natural killer cell proliferation; IDA:ComplexPortal. DR GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; IEA:Ensembl. DR GO; GO:0051142; P:positive regulation of NK T cell proliferation; IDA:ComplexPortal. DR GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; ISS:BHF-UCL. DR GO; GO:0010572; P:positive regulation of platelet activation; IDA:ARUK-UCL. DR GO; GO:1901731; P:positive regulation of platelet aggregation; IDA:ARUK-UCL. DR GO; GO:0042307; P:positive regulation of protein import into nucleus; IEA:Ensembl. DR GO; GO:0046427; P:positive regulation of receptor signaling pathway via JAK-STAT; IDA:ComplexPortal. DR GO; GO:0060391; P:positive regulation of SMAD protein signal transduction; IGI:MGI. DR GO; GO:0042102; P:positive regulation of T cell proliferation; IDA:ComplexPortal. DR GO; GO:2000318; P:positive regulation of T-helper 17 type immune response; NAS:ComplexPortal. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:ARUK-UCL. DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; ISS:ARUK-UCL. DR GO; GO:0032729; P:positive regulation of type II interferon production; IDA:ComplexPortal. DR GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; ISS:UniProtKB. DR GO; GO:1904707; P:positive regulation of vascular associated smooth muscle cell proliferation; IEA:Ensembl. DR GO; GO:0035166; P:post-embryonic hemopoiesis; IEA:Ensembl. DR GO; GO:0043687; P:post-translational protein modification; IDA:UniProtKB. DR GO; GO:0046777; P:protein autophosphorylation; ISS:UniProtKB. DR GO; GO:0042981; P:regulation of apoptotic process; IBA:GO_Central. DR GO; GO:0050727; P:regulation of inflammatory response; IDA:BHF-UCL. DR GO; GO:0045428; P:regulation of nitric oxide biosynthetic process; ISS:ARUK-UCL. DR GO; GO:1905539; P:regulation of postsynapse to nucleus signaling pathway; IEA:Ensembl. DR GO; GO:0046425; P:regulation of receptor signaling pathway via JAK-STAT; ISS:BHF-UCL. DR GO; GO:0046677; P:response to antibiotic; IDA:MGI. DR GO; GO:0033194; P:response to hydroperoxide; IEA:Ensembl. DR GO; GO:0070671; P:response to interleukin-12; IDA:BHF-UCL. DR GO; GO:0034612; P:response to tumor necrosis factor; IDA:BHF-UCL. DR GO; GO:0007165; P:signal transduction; ISS:UniProtKB. DR GO; GO:0034050; P:symbiont-induced defense-related programmed cell death; IEA:Ensembl. DR GO; GO:0038163; P:thrombopoietin-mediated signaling pathway; IDA:UniProt. DR GO; GO:0006366; P:transcription by RNA polymerase II; IEA:Ensembl. DR GO; GO:0033209; P:tumor necrosis factor-mediated signaling pathway; IDA:BHF-UCL. DR GO; GO:0060333; P:type II interferon-mediated signaling pathway; TAS:Reactome. DR CDD; cd14473; FERM_B-lobe; 1. DR CDD; cd13333; FERM_C_JAK2; 1. DR CDD; cd05078; PTK_Jak2_rpt1; 1. DR CDD; cd14205; PTKc_Jak2_rpt2; 1. DR CDD; cd10379; SH2_Jak2; 1. DR FunFam; 1.10.510.10:FF:000110; Tyrosine-protein kinase; 1. DR FunFam; 2.30.29.30:FF:000177; Tyrosine-protein kinase; 1. DR FunFam; 3.30.200.20:FF:000084; Tyrosine-protein kinase; 1. DR FunFam; 3.30.200.20:FF:000135; Tyrosine-protein kinase; 1. DR FunFam; 3.30.505.10:FF:000037; Tyrosine-protein kinase; 1. DR FunFam; 1.10.510.10:FF:000114; Tyrosine-protein kinase JAK2; 1. DR Gene3D; 3.30.200.20; Phosphorylase Kinase, domain 1; 2. DR Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 1. DR Gene3D; 3.30.505.10; SH2 domain; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 2. DR InterPro; IPR019749; Band_41_domain. DR InterPro; IPR035963; FERM_2. DR InterPro; IPR019748; FERM_central. DR InterPro; IPR000299; FERM_domain. DR InterPro; IPR041155; FERM_F1. DR InterPro; IPR041046; FERM_F2. DR InterPro; IPR051286; JAK. DR InterPro; IPR041381; JAK1-3/TYK2_PHL_dom. DR InterPro; IPR037838; JAK2_FERM_C-lobe. DR InterPro; IPR035860; JAK2_SH2. DR InterPro; IPR011009; Kinase-like_dom_sf. DR InterPro; IPR011993; PH-like_dom_sf. DR InterPro; IPR000719; Prot_kinase_dom. DR InterPro; IPR017441; Protein_kinase_ATP_BS. DR InterPro; IPR035588; PTK_Jak2_rpt1. DR InterPro; IPR035589; PTKc_Jak2_rpt2. DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom. DR InterPro; IPR000980; SH2. DR InterPro; IPR036860; SH2_dom_sf. DR InterPro; IPR008266; Tyr_kinase_AS. DR InterPro; IPR020635; Tyr_kinase_cat_dom. DR InterPro; IPR016251; Tyr_kinase_non-rcpt_Jak/Tyk2. DR InterPro; IPR020693; Tyr_kinase_non-rcpt_Jak2. DR PANTHER; PTHR45807; TYROSINE-PROTEIN KINASE HOPSCOTCH; 1. DR PANTHER; PTHR45807:SF1; TYROSINE-PROTEIN KINASE JAK2; 1. DR Pfam; PF18379; FERM_F1; 1. DR Pfam; PF18377; FERM_F2; 1. DR Pfam; PF17887; Jak1_Phl; 1. DR Pfam; PF07714; PK_Tyr_Ser-Thr; 2. DR Pfam; PF21990; SH2_1; 1. DR PIRSF; PIRSF000636; TyrPK_Jak; 1. DR PRINTS; PR01823; JANUSKINASE. DR PRINTS; PR01825; JANUSKINASE2. DR PRINTS; PR00109; TYRKINASE. DR SMART; SM00295; B41; 1. DR SMART; SM00252; SH2; 1. DR SMART; SM00219; TyrKc; 2. DR SUPFAM; SSF50729; PH domain-like; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 2. DR SUPFAM; SSF47031; Second domain of FERM; 1. DR SUPFAM; SSF55550; SH2 domain; 1. DR PROSITE; PS50057; FERM_3; 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 2. DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1. DR PROSITE; PS50001; SH2; 1. PE 1: Evidence at protein level; KW 3D-structure; Adaptive immunity; ATP-binding; Chromatin regulator; KW Chromosomal rearrangement; Cytoplasm; Disease variant; Immunity; KW Innate immunity; Kinase; Magnesium; Membrane; Metal-binding; KW Nucleotide-binding; Nucleus; Phosphoprotein; Proteomics identification; KW Proto-oncogene; Reference proteome; Repeat; SH2 domain; Transferase; KW Tyrosine-protein kinase; Ubl conjugation. FT CHAIN 1..1132 FT /note="Tyrosine-protein kinase JAK2" FT /id="PRO_0000088112" FT DOMAIN 37..380 FT /note="FERM" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00084" FT DOMAIN 401..482 FT /note="SH2; atypical" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191" FT DOMAIN 545..809 FT /note="Protein kinase 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT DOMAIN 849..1124 FT /note="Protein kinase 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT REGION 1..239 FT /note="Interaction with cytokine/interferon/growth hormone FT receptors" FT /evidence="ECO:0000250" FT ACT_SITE 976 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000255|PROSITE-ProRule:PRU10028" FT BINDING 855..863 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 882 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT SITE 352..353 FT /note="Breakpoint for translocation to form PCM1-JAK2 FT fusion protein" FT SITE 442..443 FT /note="Breakpoint for translocation to form PCM1-JAK2 FT fusion protein" FT SITE 450..451 FT /note="Breakpoint for translocation to form PCM1-JAK2 FT fusion protein" FT SITE 504..505 FT /note="Breakpoint for translocation to form PCM1-JAK2 FT fusion protein" FT SITE 710..711 FT /note="Breakpoint for translocation to form PCM1-JAK2 FT fusion protein" FT MOD_RES 119 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000250|UniProtKB:Q62120" FT MOD_RES 372 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:Q62120" FT MOD_RES 373 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:Q62120" FT MOD_RES 523 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q62120" FT MOD_RES 570 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 813 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:Q62120" FT MOD_RES 868 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000250|UniProtKB:Q62120" FT MOD_RES 966 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000250|UniProtKB:Q62120" FT MOD_RES 972 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000250|UniProtKB:Q62120" FT MOD_RES 1007 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:16174768" FT MOD_RES 1008 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000305|PubMed:16174768" FT VARIANT 127 FT /note="G -> D (in dbSNP:rs56118985)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041716" FT VARIANT 191 FT /note="K -> Q (in an ovarian serous carcinoma sample; FT somatic mutation)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041717" FT VARIANT 346 FT /note="K -> R (in dbSNP:rs55667734)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041718" FT VARIANT 377 FT /note="A -> E (in dbSNP:rs55953208)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041719" FT VARIANT 393 FT /note="L -> V (in dbSNP:rs2230723)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041720" FT VARIANT 537..539 FT /note="FHK -> L (in myeloproliferative disorder with FT erythrocytosis)" FT /evidence="ECO:0000269|PubMed:17267906" FT /id="VAR_032693" FT VARIANT 538..539 FT /note="HK -> QL (in myeloproliferative disorder with FT erythrocytosis)" FT /evidence="ECO:0000269|PubMed:17267906" FT /id="VAR_032694" FT VARIANT 539 FT /note="K -> L (in myeloproliferative disorder with FT erythrocytosis; requires 2 nucleotide substitutions; FT dbSNP:rs121912473)" FT /evidence="ECO:0000269|PubMed:17267906" FT /id="VAR_032695" FT VARIANT 584 FT /note="D -> E (in dbSNP:rs17490221)" FT /id="VAR_043129" FT VARIANT 607 FT /note="K -> N (in AML; dbSNP:rs121912472)" FT /evidence="ECO:0000269|PubMed:16247455" FT /id="VAR_032696" FT VARIANT 617 FT /note="V -> F (in PV, THCYT3 and AML; risk factor for Budd- FT Chiari syndrome; somatic mutation in a high percentage of FT patients with essential thrombocythemia or myelofibrosis; FT leads to constitutive tyrosine phosphorylation activity FT that promotes cytokine hypersensitivity; no effect on its FT ability to up-regulate potassium voltage-gated channel FT activity of KCNA3; dbSNP:rs77375493)" FT /evidence="ECO:0000269|PubMed:15781101, FT ECO:0000269|PubMed:15793561, ECO:0000269|PubMed:15858187, FT ECO:0000269|PubMed:16247455, ECO:0000269|PubMed:16325696, FT ECO:0000269|PubMed:16603627, ECO:0000269|PubMed:25644777" FT /id="VAR_032697" FT VARIANT 617 FT /note="V -> I (in THCYT3; dbSNP:rs77375493)" FT /evidence="ECO:0000269|PubMed:22397670" FT /id="VAR_067534" FT VARIANT 1063 FT /note="R -> H (in dbSNP:rs41316003)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041721" FT MUTAGEN 882 FT /note="K->E: Loss of ability to up-regulate potassium FT voltage-gated channel activity of KCNA3." FT /evidence="ECO:0000269|PubMed:25644777" FT CONFLICT 321 FT /note="P -> S (in Ref. 1; AAC23982)" FT /evidence="ECO:0000305" FT CONFLICT 1126 FT /note="I -> V (in Ref. 2; AAC23653)" FT /evidence="ECO:0000305" FT STRAND 38..45 FT /evidence="ECO:0007829|PDB:6E2Q" FT TURN 47..49 FT /evidence="ECO:0007829|PDB:6E2Q" FT STRAND 50..55 FT /evidence="ECO:0007829|PDB:6E2Q" FT STRAND 59..63 FT /evidence="ECO:0007829|PDB:6E2Q" FT HELIX 64..75 FT /evidence="ECO:0007829|PDB:6E2Q" FT TURN 79..81 FT /evidence="ECO:0007829|PDB:6E2Q" FT HELIX 82..84 FT /evidence="ECO:0007829|PDB:6E2Q" FT STRAND 85..89 FT /evidence="ECO:0007829|PDB:6E2Q" FT TURN 90..92 FT /evidence="ECO:0007829|PDB:6E2Q" FT STRAND 101..104 FT /evidence="ECO:0007829|PDB:6E2Q" FT STRAND 109..116 FT /evidence="ECO:0007829|PDB:6E2Q" FT STRAND 123..125 FT /evidence="ECO:0007829|PDB:6E2Q" FT STRAND 127..129 FT /evidence="ECO:0007829|PDB:6E2Q" FT STRAND 131..134 FT /evidence="ECO:0007829|PDB:6E2Q" FT TURN 136..139 FT /evidence="ECO:0007829|PDB:4Z32" FT HELIX 147..162 FT /evidence="ECO:0007829|PDB:6E2Q" FT HELIX 172..193 FT /evidence="ECO:0007829|PDB:6E2Q" FT HELIX 197..203 FT /evidence="ECO:0007829|PDB:6E2Q" FT HELIX 206..209 FT /evidence="ECO:0007829|PDB:6E2Q" FT HELIX 212..219 FT /evidence="ECO:0007829|PDB:6E2Q" FT HELIX 223..240 FT /evidence="ECO:0007829|PDB:6E2Q" FT HELIX 247..261 FT /evidence="ECO:0007829|PDB:6E2Q" FT HELIX 263..266 FT /evidence="ECO:0007829|PDB:6E2Q" FT STRAND 268..273 FT /evidence="ECO:0007829|PDB:6E2Q" FT STRAND 285..291 FT /evidence="ECO:0007829|PDB:6E2Q" FT TURN 292..294 FT /evidence="ECO:0007829|PDB:6E2Q" FT STRAND 295..301 FT /evidence="ECO:0007829|PDB:6E2Q" FT HELIX 311..313 FT /evidence="ECO:0007829|PDB:6E2Q" FT STRAND 315..318 FT /evidence="ECO:0007829|PDB:6E2Q" FT HELIX 320..322 FT /evidence="ECO:0007829|PDB:6E2Q" FT STRAND 323..330 FT /evidence="ECO:0007829|PDB:6E2Q" FT STRAND 340..349 FT /evidence="ECO:0007829|PDB:6E2Q" FT STRAND 352..358 FT /evidence="ECO:0007829|PDB:6E2Q" FT HELIX 359..376 FT /evidence="ECO:0007829|PDB:6E2Q" FT HELIX 385..387 FT /evidence="ECO:0007829|PDB:6E2Q" FT HELIX 390..398 FT /evidence="ECO:0007829|PDB:6E2Q" FT HELIX 406..415 FT /evidence="ECO:0007829|PDB:6E2Q" FT STRAND 422..427 FT /evidence="ECO:0007829|PDB:6E2Q" FT STRAND 434..443 FT /evidence="ECO:0007829|PDB:6E2Q" FT STRAND 446..456 FT /evidence="ECO:0007829|PDB:6E2Q" FT STRAND 462..464 FT /evidence="ECO:0007829|PDB:6E2Q" FT STRAND 471..473 FT /evidence="ECO:0007829|PDB:6E2Q" FT HELIX 474..481 FT /evidence="ECO:0007829|PDB:6E2Q" FT STRAND 485..488 FT /evidence="ECO:0007829|PDB:6E2Q" FT STRAND 491..494 FT /evidence="ECO:0007829|PDB:6E2Q" FT STRAND 510..513 FT /evidence="ECO:0007829|PDB:6E2Q" FT STRAND 539..541 FT /evidence="ECO:0007829|PDB:8C0A" FT HELIX 542..544 FT /evidence="ECO:0007829|PDB:8BA3" FT STRAND 545..554 FT /evidence="ECO:0007829|PDB:8BA3" FT STRAND 557..567 FT /evidence="ECO:0007829|PDB:8BA3" FT HELIX 569..571 FT /evidence="ECO:0007829|PDB:8BA3" FT STRAND 573..583 FT /evidence="ECO:0007829|PDB:8BA3" FT HELIX 585..590 FT /evidence="ECO:0007829|PDB:8BA3" FT HELIX 591..603 FT /evidence="ECO:0007829|PDB:8BA3" FT STRAND 612..616 FT /evidence="ECO:0007829|PDB:8BA3" FT HELIX 618..620 FT /evidence="ECO:0007829|PDB:6G3C" FT STRAND 623..627 FT /evidence="ECO:0007829|PDB:8BA3" FT HELIX 634..640 FT /evidence="ECO:0007829|PDB:8BA3" FT TURN 641..644 FT /evidence="ECO:0007829|PDB:8BA3" FT HELIX 647..666 FT /evidence="ECO:0007829|PDB:8BA3" FT HELIX 676..678 FT /evidence="ECO:0007829|PDB:8BA3" FT STRAND 679..683 FT /evidence="ECO:0007829|PDB:8BA3" FT TURN 687..689 FT /evidence="ECO:0007829|PDB:8BA3" FT STRAND 694..697 FT /evidence="ECO:0007829|PDB:8BA3" FT HELIX 704..706 FT /evidence="ECO:0007829|PDB:8BA3" FT HELIX 709..714 FT /evidence="ECO:0007829|PDB:8BA3" FT TURN 715..718 FT /evidence="ECO:0007829|PDB:8BA3" FT HELIX 721..723 FT /evidence="ECO:0007829|PDB:8BA3" FT HELIX 727..729 FT /evidence="ECO:0007829|PDB:8BA3" FT HELIX 732..747 FT /evidence="ECO:0007829|PDB:8BA3" FT TURN 748..750 FT /evidence="ECO:0007829|PDB:8BA3" FT TURN 753..756 FT /evidence="ECO:0007829|PDB:8BA3" FT HELIX 759..767 FT /evidence="ECO:0007829|PDB:8BA3" FT HELIX 778..787 FT /evidence="ECO:0007829|PDB:8BA3" FT HELIX 792..794 FT /evidence="ECO:0007829|PDB:8BA3" FT HELIX 798..808 FT /evidence="ECO:0007829|PDB:8BA3" FT STRAND 836..838 FT /evidence="ECO:0007829|PDB:4E4M" FT TURN 841..843 FT /evidence="ECO:0007829|PDB:6DRW" FT HELIX 846..848 FT /evidence="ECO:0007829|PDB:8BXH" FT STRAND 849..857 FT /evidence="ECO:0007829|PDB:8BXH" FT STRAND 859..868 FT /evidence="ECO:0007829|PDB:8BXH" FT STRAND 872..874 FT /evidence="ECO:0007829|PDB:7LL4" FT STRAND 876..886 FT /evidence="ECO:0007829|PDB:8BXH" FT HELIX 889..903 FT /evidence="ECO:0007829|PDB:8BXH" FT STRAND 913..917 FT /evidence="ECO:0007829|PDB:8BXH" FT HELIX 919..922 FT /evidence="ECO:0007829|PDB:8BXH" FT STRAND 926..930 FT /evidence="ECO:0007829|PDB:8BXH" FT HELIX 937..943 FT /evidence="ECO:0007829|PDB:8BXH" FT HELIX 945..947 FT /evidence="ECO:0007829|PDB:8BXH" FT HELIX 950..969 FT /evidence="ECO:0007829|PDB:8BXH" FT HELIX 979..981 FT /evidence="ECO:0007829|PDB:8BXH" FT STRAND 982..986 FT /evidence="ECO:0007829|PDB:8BXH" FT STRAND 989..992 FT /evidence="ECO:0007829|PDB:8BXH" FT HELIX 995..997 FT /evidence="ECO:0007829|PDB:7Q7K" FT STRAND 1006..1009 FT /evidence="ECO:0007829|PDB:8BX9" FT HELIX 1018..1020 FT /evidence="ECO:0007829|PDB:8BXH" FT HELIX 1023..1028 FT /evidence="ECO:0007829|PDB:8BXH" FT STRAND 1030..1032 FT /evidence="ECO:0007829|PDB:4IVA" FT HELIX 1033..1049 FT /evidence="ECO:0007829|PDB:8BXH" FT HELIX 1053..1055 FT /evidence="ECO:0007829|PDB:4IVA" FT HELIX 1057..1065 FT /evidence="ECO:0007829|PDB:8BXH" FT STRAND 1069..1071 FT /evidence="ECO:0007829|PDB:5HEZ" FT HELIX 1072..1083 FT /evidence="ECO:0007829|PDB:8BXH" FT TURN 1084..1086 FT /evidence="ECO:0007829|PDB:5HEZ" FT HELIX 1096..1105 FT /evidence="ECO:0007829|PDB:8BXH" FT HELIX 1110..1112 FT /evidence="ECO:0007829|PDB:8BXH" FT HELIX 1116..1129 FT /evidence="ECO:0007829|PDB:8BXH" SQ SEQUENCE 1132 AA; 130674 MW; C30669EF1A7DA80C CRC64; MGMACLTMTE MEGTSTSSIY QNGDISGNAN SMKQIDPVLQ VYLYHSLGKS EADYLTFPSG EYVAEEICIA ASKACGITPV YHNMFALMSE TERIWYPPNH VFHIDESTRH NVLYRIRFYF PRWYCSGSNR AYRHGISRGA EAPLLDDFVM SYLFAQWRHD FVHGWIKVPV THETQEECLG MAVLDMMRIA KENDQTPLAI YNSISYKTFL PKCIRAKIQD YHILTRKRIR YRFRRFIQQF SQCKATARNL KLKYLINLET LQSAFYTEKF EVKEPGSGPS GEEIFATIII TGNGGIQWSR GKHKESETLT EQDLQLYCDF PNIIDVSIKQ ANQEGSNESR VVTIHKQDGK NLEIELSSLR EALSFVSLID GYYRLTADAH HYLCKEVAPP AVLENIQSNC HGPISMDFAI SKLKKAGNQT GLYVLRCSPK DFNKYFLTFA VERENVIEYK HCLITKNENE EYNLSGTKKN FSSLKDLLNC YQMETVRSDN IIFQFTKCCP PKPKDKSNLL VFRTNGVSDV PTSPTLQRPT HMNQMVFHKI RNEDLIFNES LGQGTFTKIF KGVRREVGDY GQLHETEVLL KVLDKAHRNY SESFFEAASM MSKLSHKHLV LNYGVCVCGD ENILVQEFVK FGSLDTYLKK NKNCINILWK LEVAKQLAWA MHFLEENTLI HGNVCAKNIL LIREEDRKTG NPPFIKLSDP GISITVLPKD ILQERIPWVP PECIENPKNL NLATDKWSFG TTLWEICSGG DKPLSALDSQ RKLQFYEDRH QLPAPKWAEL ANLINNCMDY EPDFRPSFRA IIRDLNSLFT PDYELLTEND MLPNMRIGAL GFSGAFEDRD PTQFEERHLK FLQQLGKGNF GSVEMCRYDP LQDNTGEVVA VKKLQHSTEE HLRDFEREIE ILKSLQHDNI VKYKGVCYSA GRRNLKLIME YLPYGSLRDY LQKHKERIDH IKLLQYTSQI CKGMEYLGTK RYIHRDLATR NILVENENRV KIGDFGLTKV LPQDKEYYKV KEPGESPIFW YAPESLTESK FSVASDVWSF GVVLYELFTY IEKSKSPPAE FMRMIGNDKQ GQMIVFHLIE LLKNNGRLPR PDGCPDEIYM IMTECWNNNV NQRPSFRDLA LRVDQIRDNM AG // ID KIT_HUMAN Reviewed; 976 AA. AC P10721; B5A956; D5LXN2; D5M931; F5H8F8; Q6IQ28; Q99662; Q9UM99; DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot. DT 01-JUL-1989, sequence version 1. DT 28-JAN-2026, entry version 265. DE RecName: Full=Mast/stem cell growth factor receptor Kit; DE Short=SCFR; DE EC=2.7.10.1; DE AltName: Full=Piebald trait protein; DE Short=PBT; DE AltName: Full=Proto-oncogene c-Kit; DE AltName: Full=Tyrosine-protein kinase Kit; DE AltName: Full=p145 c-kit; DE AltName: Full=v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog; DE AltName: CD_antigen=CD117; DE Flags: Precursor; GN Name=KIT; Synonyms=SCFR; 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), CATALYTIC ACTIVITY, RP AUTOPHOSPHORYLATION, AND SUBCELLULAR LOCATION. RC TISSUE=Fetal brain, and Term placenta; RX PubMed=2448137; DOI=10.1002/j.1460-2075.1987.tb02655.x; RA Yarden Y., Kuang W.-J., Yang-Feng T., Coussens L., Munemitsu S., Dull T.J., RA Chen E., Schlessinger J., Francke U., Ullrich A.; RT "Human proto-oncogene c-kit: a new cell surface receptor tyrosine kinase RT for an unidentified ligand."; RL EMBO J. 6:3341-3351(1987). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND ALTERNATIVE SPLICING (ISOFORMS 1 AND RP 2). RX PubMed=1279499; RA Giebel L.B., Strunk K.M., Holmes S.A., Spritz R.A.; RT "Organization and nucleotide sequence of the human KIT (mast/stem cell RT growth factor receptor) proto-oncogene."; RL Oncogene 7:2207-2217(1992). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3). RC TISSUE=Colon carcinoma; RX PubMed=7505199; RA Toyota M., Hinoda Y., Itoh F., Takaoka A., Imai K., Yachi A.; RT "Complementary DNA cloning and characterization of truncated form of c-kit RT in human colon carcinoma cells."; RL Cancer Res. 54:272-275(1994). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=9027509; DOI=10.1006/geno.1996.4482; RA Andre C., Hampe A., Lachaume P., Martin E., Wang X.P., Manus V., Hu W.X., RA Galibert F.; RT "Sequence analysis of two genomic regions containing the KIT and the FMS RT receptor tyrosine kinase genes."; RL Genomics 39:216-226(1997). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3). RC TISSUE=Prostate cancer; RX PubMed=15039213; DOI=10.1016/s0002-9440(10)63212-9; RA Paronetto M.P., Farini D., Sammarco I., Maturo G., Vespasiani G., RA Geremia R., Rossi P., Sette C.; RT "Expression of a truncated form of the c-Kit tyrosine kinase receptor and RT activation of Src kinase in human prostatic cancer."; RL Am. J. Pathol. 164:1243-1251(2004). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), SUBCELLULAR LOCATION, AND RP INDUCTION. RX PubMed=20658618; DOI=10.1002/pbc.22603; RA Neumann I., Foell J.L., Bremer M., Volkmer I., Korholz D., Burdach S., RA Staege M.S.; RT "Retinoic acid enhances sensitivity of neuroblastoma cells for imatinib RT mesylate."; RL Pediatr. Blood Cancer 55:464-470(2010). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RA Staege M.S., Neumann I., Volkmer I.; RT "Sequence of KIT mRNA from all-trans retinoic acid treated neuroblastoma RT cell lines."; RL Submitted (MAR-2010) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Trachea; 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 [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 4."; RL Nature 434:724-731(2005). RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). 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 [MRNA] OF 1-411 (ISOFORMS 1/2). RX PubMed=18593464; DOI=10.1186/ar2447; RA Jin P., Zhang J., Sumariwalla P.F., Ni I., Jorgensen B., Crawford D., RA Phillips S., Feldmann M., Shepard H.M., Paleolog E.M.; RT "Novel splice variants derived from the receptor tyrosine kinase RT superfamily are potential therapeutics for rheumatoid arthritis."; RL Arthritis Res. Ther. 10:R73-R73(2008). RN [12] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-22. RX PubMed=7506248; DOI=10.1111/j.1349-7006.1993.tb02813.x; RA Yamamoto K., Tojo A., Aoki N., Shibuya M.; RT "Characterization of the promoter region of the human c-kit proto- RT oncogene."; RL Jpn. J. Cancer Res. 84:1136-1144(1993). RN [13] RP FUNCTION IN PHOSPHORYLATION OF PIK3R1; RAF1 AND MAPK1, INTERACTION WITH RP GRB2; PIK3R1 AND PIK3 CATALYTIC SUBUNIT, ACTIVITY REGULATION, AND RP PHOSPHORYLATION. RX PubMed=7520444; DOI=10.1016/s0021-9258(17)31874-4; RA Blume-Jensen P., Ronnstrand L., Gout I., Waterfield M.D., Heldin C.H.; RT "Modulation of Kit/stem cell factor receptor-induced signaling by protein RT kinase C."; RL J. Biol. Chem. 269:21793-21802(1994). RN [14] RP PHOSPHORYLATION AT SER-741; SER-746; SER-821 AND SER-959, ACTIVITY RP REGULATION, PARTIAL PROTEIN SEQUENCE, AND MUTAGENESIS OF SER-741 AND RP SER-746. RX PubMed=7539802; DOI=10.1074/jbc.270.23.14192; RA Blume-Jensen P., Wernstedt C., Heldin C.H., Ronnstrand L.; RT "Identification of the major phosphorylation sites for protein kinase C in RT kit/stem cell factor receptor in vitro and in intact cells."; RL J. Biol. Chem. 270:14192-14200(1995). RN [15] RP INTERACTION WITH PIK3R1; MATK/CHK; FYN AND SHC1, AND PHOSPHORYLATION AT RP TYR-568; TYR-570 AND TYR-721. RX PubMed=9038210; DOI=10.1074/jbc.272.9.5915; RA Price D.J., Rivnay B., Fu Y., Jiang S., Avraham S., Avraham H.; RT "Direct association of Csk homologous kinase (CHK) with the RT diphosphorylated site Tyr568/570 of the activated c-KIT in RT megakaryocytes."; RL J. Biol. Chem. 272:5915-5920(1997). RN [16] RP INTERACTION WITH LYN. RX PubMed=9341198; DOI=10.1074/jbc.272.43.27450; RA Linnekin D., DeBerry C.S., Mou S.; RT "Lyn associates with the juxtamembrane region of c-Kit and is activated by RT stem cell factor in hematopoietic cell lines and normal progenitor cells."; RL J. Biol. Chem. 272:27450-27455(1997). RN [17] RP INTERACTION WITH PTPN6, AUTOPHOSPHORYLATION, AND FUNCTION IN RP PHOSPHORYLATION OF PTPN6. RX PubMed=9528781; DOI=10.1128/mcb.18.4.2089; RA Kozlowski M., Larose L., Lee F., Le D.M., Rottapel R., Siminovitch K.A.; RT "SHP-1 binds and negatively modulates the c-Kit receptor by interaction RT with tyrosine 569 in the c-Kit juxtamembrane domain."; RL Mol. Cell. Biol. 18:2089-2099(1998). RN [18] RP INTERACTION WITH GRB2 AND GRB7, PARTIAL PROTEIN SEQUENCE, RP AUTOPHOSPHORYLATION, AND PHOSPHORYLATION AT TYR-703 AND TYR-936. RX PubMed=10377264; DOI=10.1042/bj3410211; RA Thommes K., Lennartsson J., Carlberg M., Ronnstrand L.; RT "Identification of Tyr-703 and Tyr-936 as the primary association sites for RT Grb2 and Grb7 in the c-Kit/stem cell factor receptor."; RL Biochem. J. 341:211-216(1999). RN [19] RP INTERACTION WITH PTPRU, AND FUNCTION IN PHOSPHORYLATION OF PTPRU. RX PubMed=10397721; RA Taniguchi Y., London R., Schinkmann K., Jiang S., Avraham H.; RT "The receptor protein tyrosine phosphatase, PTP-RO, is upregulated during RT megakaryocyte differentiation and is associated with the c-Kit receptor."; RL Blood 94:539-549(1999). RN [20] RP INTERACTION WITH MPDZ, CHARACTERIZATION OF VARIANT VAL-816, AND MUTAGENESIS RP OF LYS-623. RX PubMed=11018522; DOI=10.1016/s0014-5793(00)02036-6; RA Mancini A., Koch A., Stefan M., Niemann H., Tamura T.; RT "The direct association of the multiple PDZ domain containing proteins RT (MUPP-1) with the human c-Kit C-terminus is regulated by tyrosine kinase RT activity."; RL FEBS Lett. 482:54-58(2000). RN [21] RP INTERACTION WITH LYN; TEC AND DOK1. RX PubMed=11825908; DOI=10.1074/jbc.m200277200; RA Liang X., Wisniewski D., Strife A., Shivakrupa R., Clarkson B., Resh M.D.; RT "Phosphatidylinositol 3-kinase and Src family kinases are required for RT phosphorylation and membrane recruitment of Dok-1 in c-Kit signaling."; RL J. Biol. Chem. 277:13732-13738(2002). RN [22] RP INTERACTION WITH SH2B2/APS, FUNCTION IN PHOSPHORYLATION OF SH2B2/APS, AND RP MUTAGENESIS OF ILE-571 AND LEU-939. RX PubMed=12444928; DOI=10.1042/bj20020716; RA Wollberg P., Lennartsson J., Gottfridsson E., Yoshimura A., Ronnstrand L.; RT "The adapter protein APS associates with the multifunctional docking sites RT Tyr-568 and Tyr-936 in c-Kit."; RL Biochem. J. 370:1033-1038(2003). RN [23] RP PHOSPHORYLATION AT SER-891 AND TYR-900, PARTIAL PROTEIN SEQUENCE, RP INTERACTION WITH CRK AND PIK3R1, FUNCTION IN PHOSPHORYLATION OF CRK; AKT1 RP AND MAP KINASES, AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=12878163; DOI=10.1016/s0014-4827(03)00206-4; RA Lennartsson J., Wernstedt C., Engstrom U., Hellman U., Ronnstrand L.; RT "Identification of Tyr900 in the kinase domain of c-Kit as a Src-dependent RT phosphorylation site mediating interaction with c-Crk."; RL Exp. Cell Res. 288:110-118(2003). RN [24] RP FUNCTION, AND ALTERNATIVE SPLICING. RX PubMed=12511554; DOI=10.1074/jbc.m211726200; RA Voytyuk O., Lennartsson J., Mogi A., Caruana G., Courtneidge S., RA Ashman L.K., Ronnstrand L.; RT "Src family kinases are involved in the differential signaling from two RT splice forms of c-Kit."; RL J. Biol. Chem. 278:9159-9166(2003). RN [25] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-130. RC TISSUE=Plasma; RX PubMed=16335952; DOI=10.1021/pr0502065; RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., RA Smith R.D.; RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction, RT hydrazide chemistry, and mass spectrometry."; RL J. Proteome Res. 4:2070-2080(2005). RN [26] RP INTERACTION WITH FES/FPS, AND CHARACTERIZATION OF VARIANT VAL-816. RX PubMed=17595334; DOI=10.1182/blood-2007-02-076471; RA Voisset E., Lopez S., Dubreuil P., De Sepulveda P.; RT "The tyrosine kinase FES is an essential effector of KITD816V proliferation RT signal."; RL Blood 110:2593-2599(2007). RN [27] RP INTERACTION WITH GRB2 AND CBL, UBIQUITINATION, AND FUNCTION IN RP PHOSPHORYLATION OF CBL. RX PubMed=17904548; DOI=10.1016/j.yexcr.2007.08.021; RA Sun J., Pedersen M., Bengtsson S., Ronnstrand L.; RT "Grb2 mediates negative regulation of stem cell factor receptor/c-Kit RT signaling by recruitment of Cbl."; RL Exp. Cell Res. 313:3935-3942(2007). RN [28] RP FUNCTION IN ACTIVATION OF SIGNALING PATHWAYS AND CELL SURVIVAL, FUNCTION IN RP PHOSPHORYLATION OF CBL, PHOSPHORYLATION AT TYR-568; TYR-703; TYR-721 AND RP TYR-936, UBIQUITINATION, SUBCELLULAR LOCATION, AND CHARACTERIZATION OF RP VARIANT VAL-816. RX PubMed=19265199; DOI=10.1074/jbc.m808058200; RA Sun J., Pedersen M., Ronnstrand L.; RT "The D816V mutation of c-Kit circumvents a requirement for Src family RT kinases in c-Kit signal transduction."; RL J. Biol. Chem. 284:11039-11047(2009). RN [29] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-959, 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 [30] RP SUBCELLULAR LOCATION, ALTERNATIVE SPLICING, AND TISSUE SPECIFICITY. RX PubMed=20601678; DOI=10.1093/humrep/deq168; RA Muciaccia B., Sette C., Paronetto M.P., Barchi M., Pensini S., RA D'Agostino A., Gandini L., Geremia R., Stefanini M., Rossi P.; RT "Expression of a truncated form of KIT tyrosine kinase in human spermatozoa RT correlates with sperm DNA integrity."; RL Hum. Reprod. 25:2188-2202(2010). RN [31] RP PHOSPHORYLATION AT TYR-547; TYR-553; TYR-703; TYR-721; TYR-730; TYR-823 AND RP TYR-900, IDENTIFICATION BY MASS SPECTROMETRY, MUTAGENESIS OF TYR-823, AND RP CHARACTERIZATION OF VARIANT HIS-816. RX PubMed=20147452; DOI=10.1093/jb/mvq015; RA DiNitto J.P., Deshmukh G.D., Zhang Y., Jacques S.L., Coli R., Worrall J.W., RA Diehl W., English J.M., Wu J.C.; RT "Function of activation loop tyrosine phosphorylation in the mechanism of RT c-Kit auto-activation and its implication in sunitinib resistance."; RL J. Biochem. 147:601-609(2010). RN [32] RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AUTOPHOSPHORYLATION, RP SUBUNIT, AND CHARACTERIZATION OF VARIANT VAL-816. RX PubMed=21640708; DOI=10.1016/j.bbrc.2011.05.111; RA Kim S.Y., Kang J.J., Lee H.H., Kang J.J., Kim B., Kim C.G., Park T.K., RA Kang H.; RT "Mechanism of activation of human c-KIT kinase by internal tandem RT duplications of the juxtamembrane domain and point mutations at aspartic RT acid 816."; RL Biochem. Biophys. Res. Commun. 410:224-228(2011). RN [33] RP FUNCTION IN ACTIVATION AND PHOSPHORYLATION OF STAT1; STAT3; STAT5A AND RP STAT5B. RX PubMed=21135090; DOI=10.1074/jbc.m110.182642; RA Chaix A., Lopez S., Voisset E., Gros L., Dubreuil P., De Sepulveda P.; RT "Mechanisms of STAT protein activation by oncogenic KIT mutants in RT neoplastic mast cells."; RL J. Biol. Chem. 286:5956-5966(2011). RN [34] RP REVIEW. RX PubMed=15526160; DOI=10.1007/s00018-004-4189-6; RA Ronnstrand L.; RT "Signal transduction via the stem cell factor receptor/c-Kit."; RL Cell. Mol. Life Sci. 61:2535-2548(2004). RN [35] RP REVIEW ON KIT SIGNALING. RX PubMed=16129412; DOI=10.1016/j.bbrc.2005.08.055; RA Roskoski R. Jr.; RT "Signaling by Kit protein-tyrosine kinase--the stem cell factor receptor."; RL Biochem. Biophys. Res. Commun. 337:1-13(2005). RN [36] RP REVIEW. RX PubMed=15625120; DOI=10.1634/stemcells.2004-0117; RA Lennartsson J., Jelacic T., Linnekin D., Shivakrupa R.; RT "Normal and oncogenic forms of the receptor tyrosine kinase kit."; RL Stem Cells 23:16-43(2005). RN [37] RP REVIEW. RX PubMed=18381929; DOI=10.1158/1078-0432.ccr-07-5134; RA Kent D., Copley M., Benz C., Dykstra B., Bowie M., Eaves C.; RT "Regulation of hematopoietic stem cells by the steel factor/KIT signaling RT pathway."; RL Clin. Cancer Res. 14:1926-1930(2008). RN [38] RP REVIEW. RX PubMed=21057534; DOI=10.1038/onc.2010.494; RA Pittoni P., Piconese S., Tripodo C., Colombo M.P.; RT "Tumor-intrinsic and -extrinsic roles of c-Kit: mast cells as the primary RT off-target of tyrosine kinase inhibitors."; RL Oncogene 30:757-769(2011). RN [39] RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 549-931 IN COMPLEX WITH ADP AND RP MAGNESIUM IONS, SUBUNIT, PHOSPHORYLATION AT TYR-568 AND TYR-570, AND RP IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=12824176; DOI=10.1074/jbc.c300186200; RA Mol C.D., Lim K.B., Sridhar V., Zou H., Chien E.Y., Sang B.C., RA Nowakowski J., Kassel D.B., Cronin C.N., McRee D.E.; RT "Structure of a c-kit product complex reveals the basis for kinase RT transactivation."; RL J. Biol. Chem. 278:31461-31464(2003). RN [40] RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 565-935 IN COMPLEXES WITH RP INHIBITOR IMATINIB AND PHOSPHATE, AND ACTIVITY REGULATION. RX PubMed=15123710; DOI=10.1074/jbc.m403319200; RA Mol C.D., Dougan D.R., Schneider T.R., Skene R.J., Kraus M.L., RA Scheibe D.N., Snell G.P., Zou H., Sang B.C., Wilson K.P.; RT "Structural basis for the autoinhibition and STI-571 inhibition of c-Kit RT tyrosine kinase."; RL J. Biol. Chem. 279:31655-31663(2004). RN [41] RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 1-519 IN COMPLEX WITH KITLG/SCF, RP INTERACTION WITH KITLG/SCF, SUBUNIT, DISULFIDE BONDS, CATALYTIC ACTIVITY, RP AUTOPHOSPHORYLATION, MUTAGENESIS OF ARG-381 AND GLU-386, AND GLYCOSYLATION RP AT ASN-130; ASN-283; ASN-293; ASN-300; ASN-320; ASN-352 AND ASN-367. RX PubMed=17662946; DOI=10.1016/j.cell.2007.05.055; RA Yuzawa S., Opatowsky Y., Zhang Z., Mandiyan V., Lax I., Schlessinger J.; RT "Structural basis for activation of the receptor tyrosine kinase KIT by RT stem cell factor."; RL Cell 130:323-334(2007). RN [42] RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 544-935 IN COMPLEX WITH SUNITINIB, RP CATALYTIC ACTIVITY, AUTOPHOSPHORYLATION, CHARACTERIZATION OF VARIANTS RP HIS-816 AND VAL-816, AND ACTIVITY REGULATION. RX PubMed=19164557; DOI=10.1073/pnas.0812413106; RA Gajiwala K.S., Wu J.C., Christensen J., Deshmukh G.D., Diehl W., RA DiNitto J.P., English J.M., Greig M.J., He Y.A., Jacques S.L., Lunney E.A., RA McTigue M., Molina D., Quenzer T., Wells P.A., Yu X., Zhang Y., Zou A., RA Emmett M.R., Marshall A.G., Zhang H.M., Demetri G.D.; RT "KIT kinase mutants show unique mechanisms of drug resistance to imatinib RT and sunitinib in gastrointestinal stromal tumor patients."; RL Proc. Natl. Acad. Sci. U.S.A. 106:1542-1547(2009). RN [43] RP X-RAY CRYSTALLOGRAPHY (1.45 ANGSTROMS) OF 564-574 IN COMPLEX WITH SOCS6, RP AND PHOSPHORYLATION AT TYR-568. RX PubMed=21030588; DOI=10.1074/jbc.m110.173526; RA Zadjali F., Pike A.C., Vesterlund M., Sun J., Wu C., Li S.S., RA Ronnstrand L., Knapp S., Bullock A.N., Flores-Morales A.; RT "Structural basis for c-KIT inhibition by the suppressor of cytokine RT signaling 6 (SOCS6) ubiquitin ligase."; RL J. Biol. Chem. 286:480-490(2011). RN [44] RP VARIANT PBT LYS-583. RX PubMed=1376329; DOI=10.1172/jci115772; RA Fleischman R.A.; RT "Human piebald trait resulting from a dominant negative mutant allele of RT the c-kit membrane receptor gene."; RL J. Clin. Invest. 89:1713-1717(1992). RN [45] RP VARIANT PBT LEU-584. RX PubMed=1370874; RA Spritz R.A., Giebel L.B., Holmes S.A.; RT "Dominant negative and loss of function mutations of the c-kit (mast/stem RT cell growth factor receptor) proto-oncogene in human piebaldism."; RL Am. J. Hum. Genet. 50:261-269(1992). RN [46] RP VARIANT PBT ARG-664. RX PubMed=1717985; DOI=10.1073/pnas.88.19.8696; RA Giebel L.B., Spritz R.A.; RT "Mutation of the KIT (mast/stem cell growth factor receptor) protooncogene RT in human piebaldism."; RL Proc. Natl. Acad. Sci. U.S.A. 88:8696-8699(1991). RN [47] RP VARIANT MAST CELL LEUKEMIA VAL-816. RX PubMed=7691885; DOI=10.1172/jci116761; RA Furitsu T., Tsujimura T., Tono T., Ikeda H., Kitayama H., Koshimizu U., RA Sugahara H., Butterfield J.H., Ashman L.K., Kanayama Y., Matsuzawa Y., RA Kitamura Y., Kanakura Y.; RT "Identification of mutations in the coding sequence of the proto-oncogene RT c-kit in a human mast cell leukemia cell line causing ligand-independent RT activation of c-kit product."; RL J. Clin. Invest. 92:1736-1744(1993). RN [48] RP VARIANTS PBT GLY-791 AND VAL-812. RX PubMed=7687267; DOI=10.1111/1523-1747.ep12358440; RA Spritz R.A., Holmes S.A., Itin P., Kuester W.; RT "Novel mutations of the KIT (mast/stem cell growth factor receptor) proto- RT oncogene in human piebaldism."; RL J. Invest. Dermatol. 101:22-25(1993). RN [49] RP VARIANT PBT 893-GLU--PRO-896 DEL. RX PubMed=8680409; DOI=10.1002/humu.1380060409; RA Riva P., Milani N., Gandolfi P., Larizza L.; RT "A 12-bp deletion (7818del12) in the c-kit protooncogene in a large Italian RT kindred with piebaldism."; RL Hum. Mutat. 6:343-345(1995). RN [50] RP VARIANT MAST CELL DISEASE GLY-820. RX PubMed=9029028; DOI=10.1046/j.1365-2141.1997.d01-2042.x; RA Pignon J.-M., Giraudier S., Duquesnoy P., Jouault H., Imbert M., RA Vainchenker W., Vernant J.-P., Tulliez M.; RT "A new c-kit mutation in a case of aggressive mast cell disease."; RL Br. J. Haematol. 96:374-376(1997). RN [51] RP VARIANT PBT GLY-796. RX PubMed=9450866; RX DOI=10.1002/(sici)1096-8628(19980106)75:1<101::aid-ajmg20>3.0.co;2-p; RA Spritz R.A., Beighton P.; RT "Piebaldism with deafness: molecular evidence for an expanded syndrome."; RL Am. J. Med. Genet. 75:101-103(1998). RN [52] RP VARIANT ACUTE MYELOID LEUKEMIA TYR-816. RX PubMed=9657776; RA Beghini A., Larizza L., Cairoli R., Morra E.; RT "c-kit activating mutations and mast cell proliferation in human RT leukemia."; RL Blood 92:701-702(1998). RN [53] RP VARIANT PBT PRO-847. RX PubMed=9699740; DOI=10.1046/j.1523-1747.1998.00269.x; RA Nomura K., Hatayama I., Narita T., Kaneko T., Shiraishi M.; RT "A novel KIT gene missense mutation in a Japanese family with piebaldism."; RL J. Invest. Dermatol. 111:337-338(1998). RN [54] RP VARIANT GIST VAL-559 DEL. RX PubMed=9697690; DOI=10.1038/1209; RA Nishida T., Hirota S., Taniguchi M., Hashimoto K., Isozaki K., Nakamura H., RA Kanakura Y., Tanaka T., Takabayashi A., Matsuda H., Kitamura Y.; RT "Familial gastrointestinal stromal tumours with germline mutation of the RT KIT gene."; RL Nat. Genet. 19:323-324(1998). RN [55] RP VARIANTS GIST ILE-550; 550-LYS--LYS-558 DEL; 551-PRO--VAL-555 DEL; ASP-559 RP AND 559-VAL-VAL-560 DEL. RX PubMed=9438854; DOI=10.1126/science.279.5350.577; RA Hirota S., Isozaki K., Moriyama Y., Hashimoto K., Nishida T., Ishiguro S., RA Kawano K., Hanada M., Kurata A., Takeda M., Muhammad Tunio G., RA Matsuzawa Y., Kanakura Y., Shinomura Y., Kitamura Y.; RT "Gain-of-function mutations of c-kit in human gastrointestinal stromal RT tumors."; RL Science 279:577-580(1998). RN [56] RP VARIANT HIS-816, AND CHARACTERIZATION OF VARIANT HIS-816. RX PubMed=10362788; DOI=10.1016/s0002-9440(10)65419-3; RA Tian Q., Frierson H.F. Jr., Krystal G.W., Moskaluk C.A.; RT "Activating c-kit gene mutations in human germ cell tumors."; RL Am. J. Pathol. 154:1643-1647(1999). RN [57] RP VARIANTS MASTSYS VAL-816 AND TYR-816, VARIANTS MASTC PHE-816 AND LYS-839, RP CHARACTERIZATION OF VARIANTS MASTSYS VAL-816 AND TYR-816, CHARACTERIZATION RP OF VARIANTS MASTC PHE-816 AND LYS-839, AND INVOLVEMENT IN MASTSYS AND RP MASTC. RX PubMed=9990072; DOI=10.1073/pnas.96.4.1609; RA Longley B.J. Jr., Metcalfe D.D., Tharp M., Wang X., Tyrrell L., Lu S.-Z., RA Heitjan D., Ma Y.; RT "Activating and dominant inactivating c-KIT catalytic domain mutations in RT distinct clinical forms of human mastocytosis."; RL Proc. Natl. Acad. Sci. U.S.A. 96:1609-1614(1999). RN [58] RP VARIANTS PBT CYS-584; ARG-601 AND PRO-656. RX PubMed=11074500; RX DOI=10.1002/1096-8628(20001106)95:1<79::aid-ajmg16>3.0.co;2-4; RA Syrris P., Malik N.M., Murday V.A., Patton M.A., Carter N.D., Hughes H.E., RA Metcalfe K.; RT "Three novel mutations of the proto-oncogene KIT cause human piebaldism."; RL Am. J. Med. Genet. 95:79-81(2000). RN [59] RP VARIANT GIST ALA-559. RX PubMed=11505412; RX DOI=10.1002/1097-0142(20010801)92:3<657::aid-cncr1367>3.0.co;2-d; RA Beghini A., Tibiletti M.G., Roversi G., Chiaravalli A.M., Serio G., RA Capella C., Larizza L.; RT "Germline mutation in the juxtamembrane domain of the kit gene in a family RT with gastrointestinal stromal tumors and urticaria pigmentosa."; RL Cancer 92:657-662(2001). RN [60] RP VARIANT MASTC ASP-533, AND INVOLVEMENT IN MASTC. RX PubMed=15173254; DOI=10.1136/jmg.2003.015156; RA Tang X., Boxer M., Drummond A., Ogston P., Hodgins M., Burden A.D.; RT "A germline mutation in KIT in familial diffuse cutaneous mastocytosis."; RL J. Med. Genet. 41:E88-E88(2004). RN [61] RP VARIANT GIST 550-LYS--LYS-558 DEL. RX PubMed=15824741; DOI=10.1038/sj.onc.1208587; RA Chen L.L., Sabripour M., Wu E.F., Prieto V.G., Fuller G.N., Frazier M.L.; RT "A mutation-created novel intra-exonic pre-mRNA splice site causes RT constitutive activation of KIT in human gastrointestinal stromal tumors."; RL Oncogene 24:4271-4280(2005). RN [62] RP VARIANTS TYR-816; LYS-822 AND PRO-829. RX PubMed=16175573; DOI=10.1002/gcc.20265; RA Bignell G., Smith R., Hunter C., Stephens P., Davies H., Greenman C., RA Teague J., Butler A., Edkins S., Stevens C., O'meara S., Parker A., RA Avis T., Barthorpe S., Brackenbury L., Buck G., Clements J., Cole J., RA Dicks E., Edwards K., Forbes S., Gorton M., Gray K., Halliday K., RA Harrison R., Hills K., Hinton J., Jones D., Kosmidou V., Laman R., Lugg R., RA Menzies A., Perry J., Petty R., Raine K., Shepherd R., Small A., RA Solomon H., Stephens Y., Tofts C., Varian J., Webb A., West S., Widaa S., RA Yates A., Gillis A.J.M., Stoop H.J., van Gurp R.J.H.L.M., Oosterhuis J.W., RA Looijenga L.H.J., Futreal P.A., Wooster R., Stratton M.R.; RT "Sequence analysis of the protein kinase gene family in human testicular RT germ-cell tumors of adolescents and adults."; RL Genes Chromosomes Cancer 45:42-46(2006). RN [63] RP VARIANTS [LARGE SCALE ANALYSIS] ILE-532; LEU-541; SER-691; ASN-715; RP ASN-737; TRP-804; TYR-816; LYS-822 AND PRO-829. 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 [64] RP VARIANT LEU-541, VARIANTS MASTC ILE-816; TYR-816 AND VAL-816, AND RP CHARACTERIZATION OF VARIANTS MASTC ILE-816; TYR-816 AND VAL-816. RX PubMed=19865100; DOI=10.1038/jid.2009.281; RA Bodemer C., Hermine O., Palmerini F., Yang Y., Grandpeix-Guyodo C., RA Leventhal P.S., Hadj-Rabia S., Nasca L., Georgin-Lavialle S., RA Cohen-Akenine A., Launay J.M., Barete S., Feger F., Arock M., Catteau B., RA Sans B., Stalder J.F., Skowron F., Thomas L., Lorette G., Plantin P., RA Bordigoni P., Lortholary O., de Prost Y., Moussy A., Sobol H., Dubreuil P.; RT "Pediatric mastocytosis is a clonal disease associated with D816V and other RT activating c-KIT mutations."; RL J. Invest. Dermatol. 130:804-815(2010). RN [65] RP VARIANT MASTC ILE-822, CHARACTERIZATION OF VARIANT MASTC ILE-822, AND RP INVOLVEMENT IN MASTC. RX PubMed=21689725; DOI=10.1016/j.exphem.2011.05.009; RA Wasag B., Niedoszytko M., Piskorz A., Lange M., Renke J., Jassem E., RA Biernat W., Debiec-Rychter M., Limon J.; RT "Novel, activating KIT-N822I mutation in familial cutaneous mastocytosis."; RL Exp. Hematol. 39:859-865(2011). RN [66] RP VARIANT MASTC CYS-451, AND INVOLVEMENT IN MASTC. RX PubMed=24289326; DOI=10.1111/ced.12225; RA Wang H.J., Lin Z.M., Zhang J., Yin J.H., Yang Y.; RT "A new germline mutation in KIT associated with diffuse cutaneous RT mastocytosis in a Chinese family."; RL Clin. Exp. Dermatol. 39:146-149(2014). CC -!- FUNCTION: Tyrosine-protein kinase that acts as a cell-surface receptor CC for the cytokine KITLG/SCF and plays an essential role in the CC regulation of cell survival and proliferation, hematopoiesis, stem cell CC maintenance, gametogenesis, mast cell development, migration and CC function, and in melanogenesis. In response to KITLG/SCF binding, KIT CC can activate several signaling pathways. Phosphorylates PIK3R1, PLCG1, CC SH2B2/APS and CBL. Activates the AKT1 signaling pathway by CC phosphorylation of PIK3R1, the regulatory subunit of CC phosphatidylinositol 3-kinase. Activated KIT also transmits signals via CC GRB2 and activation of RAS, RAF1 and the MAP kinases MAPK1/ERK2 and/or CC MAPK3/ERK1. Promotes activation of STAT family members STAT1, STAT3, CC STAT5A and STAT5B. Activation of PLCG1 leads to the production of the CC cellular signaling molecules diacylglycerol and inositol 1,4,5- CC trisphosphate. KIT signaling is modulated by protein phosphatases, and CC by rapid internalization and degradation of the receptor. Activated KIT CC promotes phosphorylation of the protein phosphatases PTPN6/SHP-1 and CC PTPRU, and of the transcription factors STAT1, STAT3, STAT5A and CC STAT5B. Promotes phosphorylation of PIK3R1, CBL, CRK (isoform Crk-II), CC LYN, MAPK1/ERK2 and/or MAPK3/ERK1, PLCG1, SRC and SHC1. CC {ECO:0000269|PubMed:10397721, ECO:0000269|PubMed:12444928, CC ECO:0000269|PubMed:12511554, ECO:0000269|PubMed:12878163, CC ECO:0000269|PubMed:17904548, ECO:0000269|PubMed:19265199, CC ECO:0000269|PubMed:21135090, ECO:0000269|PubMed:21640708, CC ECO:0000269|PubMed:7520444, ECO:0000269|PubMed:9528781}. 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=2.7.10.1; CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10028, CC ECO:0000269|PubMed:17662946, ECO:0000269|PubMed:19164557, CC ECO:0000269|PubMed:21640708, ECO:0000269|PubMed:2448137}; CC -!- ACTIVITY REGULATION: Present in an inactive conformation in the absence CC of bound ligand. KITLG/SCF binding leads to dimerization and activation CC by autophosphorylation on tyrosine residues. Activity is down-regulated CC by PRKCA-mediated phosphorylation on serine residues. Inhibited by CC imatinib/STI-571 (Gleevec) and sunitinib; these compounds maintain the CC kinase in an inactive conformation. {ECO:0000269|PubMed:15123710, CC ECO:0000269|PubMed:19164557, ECO:0000269|PubMed:21640708, CC ECO:0000269|PubMed:7520444, ECO:0000269|PubMed:7539802}. CC -!- SUBUNIT: Monomer in the absence of bound KITLG/SCF. Homodimer in the CC presence of bound KITLG/SCF, forming a heterotetramer with two CC KITLG/SCF molecules. Interacts (via phosphorylated tyrosine residues) CC with the adapter proteins GRB2 and GRB7 (via SH2 domain), and CC SH2B2/APS. Interacts (via C-terminus) with MPDZ (via the tenth PDZ CC domain). Interacts (via phosphorylated tyrosine residues) with PIK3R1 CC and PIK3 catalytic subunit. Interacts (via phosphorylated tyrosine) CC with CRK (isoform Crk-II), FYN, SHC1 and MATK/CHK (via SH2 domain). CC Interacts with LYN and FES/FPS. Interacts (via phosphorylated tyrosine CC residues) with the protein phosphatases PTPN6/SHP-1 (via SH2 domain), CC PTPN11/SHP-2 (via SH2 domain) and PTPRU. Interacts with PLCG1. CC Interacts with DOK1 and TEC. Interacts (KITLG/SCF-bound) with IL1RL1. CC Interacts with IL1RAP (independent of stimulation with KITLG/SCF). A CC mast cell-specific KITLG/SCF-induced interleukin-33 signaling complex CC contains IL1RL1, IL1RAP, KIT and MYD88. {ECO:0000250|UniProtKB:P05532, CC ECO:0000269|PubMed:10377264, ECO:0000269|PubMed:10397721, CC ECO:0000269|PubMed:11018522, ECO:0000269|PubMed:11825908, CC ECO:0000269|PubMed:12444928, ECO:0000269|PubMed:12824176, CC ECO:0000269|PubMed:12878163, ECO:0000269|PubMed:17595334, CC ECO:0000269|PubMed:17662946, ECO:0000269|PubMed:17904548, CC ECO:0000269|PubMed:19164557, ECO:0000269|PubMed:21030588, CC ECO:0000269|PubMed:21640708, ECO:0000269|PubMed:7520444, CC ECO:0000269|PubMed:9038210, ECO:0000269|PubMed:9341198, CC ECO:0000269|PubMed:9528781}. CC -!- INTERACTION: CC P10721; P00519: ABL1; NbExp=2; IntAct=EBI-1379503, EBI-375543; CC P10721; P42684: ABL2; NbExp=2; IntAct=EBI-1379503, EBI-1102694; CC P10721; O75815: BCAR3; NbExp=3; IntAct=EBI-1379503, EBI-702336; CC P10721; P51451: BLK; NbExp=5; IntAct=EBI-1379503, EBI-2105445; CC P10721; Q8WV28: BLNK; NbExp=2; IntAct=EBI-1379503, EBI-2623522; CC P10721; P46108: CRK; NbExp=4; IntAct=EBI-1379503, EBI-886; CC P10721; P07332: FES; NbExp=2; IntAct=EBI-1379503, EBI-1055635; CC P10721; P09769: FGR; NbExp=2; IntAct=EBI-1379503, EBI-1383732; CC P10721; O75791: GRAP2; NbExp=2; IntAct=EBI-1379503, EBI-740418; CC P10721; P62993: GRB2; NbExp=6; IntAct=EBI-1379503, EBI-401755; CC P10721; Q14451: GRB7; NbExp=4; IntAct=EBI-1379503, EBI-970191; CC P10721; P08631: HCK; NbExp=2; IntAct=EBI-1379503, EBI-346340; CC P10721; Q96JZ2: HSH2D; NbExp=5; IntAct=EBI-1379503, EBI-3919324; CC P10721; P21583: KITLG; NbExp=2; IntAct=EBI-1379503, EBI-1379527; CC P10721; P06239: LCK; NbExp=8; IntAct=EBI-1379503, EBI-1348; CC P10721; P07948: LYN; NbExp=7; IntAct=EBI-1379503, EBI-79452; CC P10721; P16333: NCK1; NbExp=3; IntAct=EBI-1379503, EBI-389883; CC P10721; O43639: NCK2; NbExp=2; IntAct=EBI-1379503, EBI-713635; CC P10721; P27986: PIK3R1; NbExp=19; IntAct=EBI-1379503, EBI-79464; CC P10721; O00459: PIK3R2; NbExp=19; IntAct=EBI-1379503, EBI-346930; CC P10721; Q92569: PIK3R3; NbExp=31; IntAct=EBI-1379503, EBI-79893; CC P10721; P19174: PLCG1; NbExp=31; IntAct=EBI-1379503, EBI-79387; CC P10721; P16885: PLCG2; NbExp=8; IntAct=EBI-1379503, EBI-617403; CC P10721; Q13882: PTK6; NbExp=4; IntAct=EBI-1379503, EBI-1383632; CC P10721; Q06124: PTPN11; NbExp=29; IntAct=EBI-1379503, EBI-297779; CC P10721; Q92729: PTPRU; NbExp=2; IntAct=EBI-1379503, EBI-7052301; CC P10721; P20936: RASA1; NbExp=16; IntAct=EBI-1379503, EBI-1026476; CC P10721; Q9UQQ2: SH2B3; NbExp=2; IntAct=EBI-1379503, EBI-7879749; CC P10721; O14796: SH2D1B; NbExp=8; IntAct=EBI-1379503, EBI-3923013; CC P10721; Q9NP31: SH2D2A; NbExp=10; IntAct=EBI-1379503, EBI-490630; CC P10721; Q8N5H7: SH2D3C; NbExp=4; IntAct=EBI-1379503, EBI-745980; CC P10721; P78314: SH3BP2; NbExp=3; IntAct=EBI-1379503, EBI-727062; CC P10721; Q15464: SHB; NbExp=2; IntAct=EBI-1379503, EBI-4402156; CC P10721; P29353: SHC1; NbExp=8; IntAct=EBI-1379503, EBI-78835; CC P10721; P98077: SHC2; NbExp=5; IntAct=EBI-1379503, EBI-7256023; CC P10721; Q92529: SHC3; NbExp=3; IntAct=EBI-1379503, EBI-79084; CC P10721; Q9H6Q3: SLA2; NbExp=2; IntAct=EBI-1379503, EBI-1222854; CC P10721; O14508: SOCS2; NbExp=4; IntAct=EBI-1379503, EBI-617737; CC P10721; O14543: SOCS3; NbExp=3; IntAct=EBI-1379503, EBI-714146; CC P10721; O14544: SOCS6; NbExp=12; IntAct=EBI-1379503, EBI-3929549; CC P10721; P12931: SRC; NbExp=5; IntAct=EBI-1379503, EBI-621482; CC P10721; Q9ULZ2: STAP1; NbExp=3; IntAct=EBI-1379503, EBI-6083058; CC P10721; Q9HBL0: TNS1; NbExp=2; IntAct=EBI-1379503, EBI-3389814; CC P10721; Q63HR2: TNS2; NbExp=2; IntAct=EBI-1379503, EBI-949753; CC P10721; Q68CZ2: TNS3; NbExp=5; IntAct=EBI-1379503, EBI-1220488; CC P10721; P42681: TXK; NbExp=3; IntAct=EBI-1379503, EBI-7877438; CC P10721; P07947: YES1; NbExp=7; IntAct=EBI-1379503, EBI-515331; CC P10721; P43403: ZAP70; NbExp=2; IntAct=EBI-1379503, EBI-1211276; CC P10721; Q8VBX6: Mpdz; Xeno; NbExp=4; IntAct=EBI-1379503, EBI-8026435; CC P10721; P35235: Ptpn11; Xeno; NbExp=2; IntAct=EBI-1379503, EBI-397236; CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane; Single-pass type I CC membrane protein. CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cell membrane; Single-pass type I CC membrane protein. CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Cytoplasm CC {ECO:0000269|PubMed:20601678}. Note=Detected in the cytoplasm of CC spermatozoa, especially in the equatorial and subacrosomal region of CC the sperm head. {ECO:0000269|PubMed:20601678}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; Synonyms=GNNK(+), KitA(+); CC IsoId=P10721-1; Sequence=Displayed; CC Name=2; Synonyms=GNNK(-), Kit(+); CC IsoId=P10721-2; Sequence=VSP_038385; CC Name=3; Synonyms=TR-KIT {ECO:0000303|PubMed:20601678}; CC IsoId=P10721-4; Sequence=VSP_060976; CC -!- TISSUE SPECIFICITY: [Isoform 3]: In testis, detected in spermatogonia CC in the basal layer and in interstitial Leydig cells but not in Sertoli CC cells or spermatocytes inside the seminiferous tubules (at protein CC level) (PubMed:20601678). Expression is maintained in ejaculated CC spermatozoa (at protein level) (PubMed:20601678). CC {ECO:0000269|PubMed:20601678}. CC -!- INDUCTION: Up-regulated by cis-retinoic acid in neuroblastoma cell CC lines. {ECO:0000269|PubMed:20658618}. CC -!- PTM: Ubiquitinated by SOCS6. KIT is rapidly ubiquitinated after CC autophosphorylation induced by KITLG/SCF binding, leading to CC internalization and degradation. {ECO:0000269|PubMed:17904548, CC ECO:0000269|PubMed:19265199}. CC -!- PTM: Autophosphorylated on tyrosine residues. KITLG/SCF binding CC enhances autophosphorylation. Isoform 1 shows low levels of tyrosine CC phosphorylation in the absence of added KITLG/SCF (in vitro). Kinase CC activity is down-regulated by phosphorylation on serine residues by CC protein kinase C family members. Phosphorylation at Tyr-568 is required CC for interaction with PTPN11/SHP-2, CRK (isoform Crk-II) and members of CC the SRC tyrosine-protein kinase family. Phosphorylation at Tyr-570 is CC required for interaction with PTPN6/SHP-1. Phosphorylation at Tyr-703, CC Tyr-823 and Tyr-936 is important for interaction with GRB2. CC Phosphorylation at Tyr-721 is important for interaction with PIK3R1. CC Phosphorylation at Tyr-823 and Tyr-936 is important for interaction CC with GRB7. {ECO:0000269|PubMed:10377264, ECO:0000269|PubMed:12824176, CC ECO:0000269|PubMed:19265199, ECO:0000269|PubMed:20147452, CC ECO:0000269|PubMed:21030588, ECO:0000269|PubMed:9038210}. CC -!- DISEASE: Piebald trait (PBT) [MIM:172800]: Autosomal dominant genetic CC developmental abnormality of pigmentation characterized by congenital CC patches of white skin and hair that lack melanocytes. CC {ECO:0000269|PubMed:11074500, ECO:0000269|PubMed:1370874, CC ECO:0000269|PubMed:1376329, ECO:0000269|PubMed:1717985, CC ECO:0000269|PubMed:7687267, ECO:0000269|PubMed:8680409, CC ECO:0000269|PubMed:9450866, ECO:0000269|PubMed:9699740}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Gastrointestinal stromal tumor (GIST) [MIM:606764]: Common CC mesenchymal neoplasms arising in the gastrointestinal tract, most often CC in the stomach. They are histologically, immunohistochemically, and CC genetically different from typical leiomyomas, leiomyosarcomas, and CC schwannomas. Most GISTs are composed of a fairly uniform population of CC spindle-shaped cells. Some tumors are dominated by epithelioid cells or CC contain a mixture of spindle and epithelioid morphologies. Primary CC GISTs in the gastrointestinal tract commonly metastasize in the omentum CC and mesenteries, often as multiple nodules. However, primary tumors may CC also occur outside of the gastrointestinal tract, in other intra- CC abdominal locations, especially in the omentum and mesentery. CC {ECO:0000269|PubMed:11505412, ECO:0000269|PubMed:15824741, CC ECO:0000269|PubMed:9438854, ECO:0000269|PubMed:9697690}. Note=The gene CC represented in this entry is involved in disease pathogenesis. CC -!- DISEASE: Testicular germ cell tumor (TGCT) [MIM:273300]: A common CC malignancy in males representing 95% of all testicular neoplasms. TGCTs CC have various pathologic subtypes including: unclassified intratubular CC germ cell neoplasia, seminoma (including cases with CC syncytiotrophoblastic cells), spermatocytic seminoma, embryonal CC carcinoma, yolk sac tumor, choriocarcinoma, and teratoma. Note=The gene CC represented in this entry may be involved in disease pathogenesis. CC -!- DISEASE: Leukemia, acute myelogenous (AML) [MIM:601626]: A subtype of CC acute leukemia, a cancer of the white blood cells. AML is a malignant CC disease of bone marrow characterized by maturational arrest of CC hematopoietic precursors at an early stage of development. Clonal CC expansion of myeloid blasts occurs in bone marrow, blood, and other CC tissue. Myelogenous leukemias develop from changes in cells that CC normally produce neutrophils, basophils, eosinophils and monocytes. CC Note=The gene represented in this entry is involved in disease CC pathogenesis. Somatic mutations that lead to constitutive activation of CC KIT are detected in AML patients. These mutations fall into two CC classes, the most common being in-frame internal tandem duplications of CC variable length in the juxtamembrane region that disrupt the normal CC regulation of the kinase activity. Likewise, point mutations in the CC kinase domain can result in a constitutively activated kinase. CC -!- DISEASE: Mastocytosis, cutaneous (MASTC) [MIM:154800]: A form of CC mastocytosis, a heterogeneous group of disorders associated with CC abnormal proliferation and accumulation of mast cells in various CC tissues, especially in the skin and hematopoietic organs. MASTC is an CC autosomal dominant form characterized by macules, papules, nodules, or CC diffuse infiltration of the skin, often associated with localized CC hyperpigmentation. Gentle rubbing of the lesions induces histamine CC release from mechanically activated mast cells, causing local wheals, CC erythema, and often pruritus, a phenomenon termed Darier sign. CC {ECO:0000269|PubMed:15173254, ECO:0000269|PubMed:19865100, CC ECO:0000269|PubMed:21689725, ECO:0000269|PubMed:24289326, CC ECO:0000269|PubMed:9990072}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Mastocytosis, systemic (MASTSYS) [MIM:154800]: A severe form CC of mastocytosis characterized by abnormal proliferation and CC accumulation of mast cells in several organs, resulting in a systemic CC disease that may affect bone, gastrointestinal tract, lymphatics, CC spleen, and liver. In some cases, it is associated with a clonal CC hematologic non-mast-cell lineage disease, such as a myelodysplastic or CC myeloproliferative disorder. It can also lead to mast cell leukemia, CC which carries a high risk of mortality. {ECO:0000269|PubMed:9990072}. CC Note=The disease is caused by variants affecting the gene represented CC in this entry. CC -!- MISCELLANEOUS: Numerous proteins are phosphorylated in response to KIT CC signaling, but it is not evident to determine which are directly CC phosphorylated by KIT under in vivo conditions. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein CC kinase family. CSF-1/PDGF receptor subfamily. {ECO:0000255|PROSITE- CC ProRule:PRU00159}. CC -!- SEQUENCE CAUTION: CC Sequence=ACF47630.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/127/KIT"; CC -!- WEB RESOURCE: Name=Wikipedia; Note=CD117 entry; CC URL="https://en.wikipedia.org/wiki/CD117"; CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=two's company - Issue 163 of CC August 2014; CC URL="https://www.proteinspotlight.org/back_issues/163/"; 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; X06182; CAA29548.1; -; mRNA. DR EMBL; X69301; CAA49159.1; -; Genomic_DNA. DR EMBL; X69302; CAA49159.1; JOINED; Genomic_DNA. DR EMBL; X69303; CAA49159.1; JOINED; Genomic_DNA. DR EMBL; X69304; CAA49159.1; JOINED; Genomic_DNA. DR EMBL; X69305; CAA49159.1; JOINED; Genomic_DNA. DR EMBL; X69306; CAA49159.1; JOINED; Genomic_DNA. DR EMBL; X69307; CAA49159.1; JOINED; Genomic_DNA. DR EMBL; X69308; CAA49159.1; JOINED; Genomic_DNA. DR EMBL; X69309; CAA49159.1; JOINED; Genomic_DNA. DR EMBL; X69310; CAA49159.1; JOINED; Genomic_DNA. DR EMBL; X69311; CAA49159.1; JOINED; Genomic_DNA. DR EMBL; X69312; CAA49159.1; JOINED; Genomic_DNA. DR EMBL; X69313; CAA49159.1; JOINED; Genomic_DNA. DR EMBL; X69314; CAA49159.1; JOINED; Genomic_DNA. DR EMBL; X69315; CAA49159.1; JOINED; Genomic_DNA. DR EMBL; X69316; CAA49159.1; JOINED; Genomic_DNA. DR EMBL; U63834; AAC50968.1; -; Genomic_DNA. DR EMBL; U63834; AAC50969.1; -; Genomic_DNA. DR EMBL; GU983671; ADF36702.1; -; mRNA. DR EMBL; HM015525; ADF50068.1; -; mRNA. DR EMBL; HM015526; ADF50069.1; -; mRNA. DR EMBL; AK304031; BAG64945.1; -; mRNA. DR EMBL; AC006552; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC092545; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC071593; AAH71593.1; -; mRNA. DR EMBL; EU826594; ACF47630.1; ALT_SEQ; mRNA. DR EMBL; S67773; AAB29529.1; -; Genomic_DNA. DR CCDS; CCDS3496.1; -. [P10721-1] DR CCDS; CCDS47058.1; -. [P10721-2] DR PIR; S01426; TVHUKT. DR RefSeq; NP_000213.1; NM_000222.3. [P10721-1] DR RefSeq; NP_001087241.1; NM_001093772.2. [P10721-2] DR PDB; 1PKG; X-ray; 2.90 A; A/B=549-935. DR PDB; 1T45; X-ray; 1.90 A; A=547-693, A=754-935. DR PDB; 1T46; X-ray; 1.60 A; A=565-693, A=754-935. DR PDB; 2E9W; X-ray; 3.50 A; A/B=26-514. DR PDB; 2EC8; X-ray; 3.00 A; A=1-519. DR PDB; 2IUH; X-ray; 2.00 A; B=718-728. DR PDB; 2VIF; X-ray; 1.45 A; P=564-574. DR PDB; 3G0E; X-ray; 1.60 A; A=544-693, A=754-935. DR PDB; 3G0F; X-ray; 2.60 A; A/B=544-693, A/B=754-935. DR PDB; 4HVS; X-ray; 1.90 A; A=551-934. DR PDB; 4K94; X-ray; 2.40 A; C=308-518. DR PDB; 4K9E; X-ray; 2.70 A; C=308-518. DR PDB; 4PGZ; X-ray; 2.40 A; A/B/C=308-518. DR PDB; 4U0I; X-ray; 2.00 A; A=563-693, A=754-935. DR PDB; 6GQJ; X-ray; 2.33 A; A/B=551-933. DR PDB; 6GQK; X-ray; 2.31 A; A/B=551-687, A/B=771-934. DR PDB; 6GQL; X-ray; 2.01 A; A/B=551-934. DR PDB; 6GQM; X-ray; 2.00 A; A/B=551-934. DR PDB; 6HH1; X-ray; 2.25 A; A=565-702, A=802-929. DR PDB; 6ITT; X-ray; 2.10 A; A/B=547-693, A/B=754-935. DR PDB; 6ITV; X-ray; 1.88 A; A=547-693, A=754-935. DR PDB; 6KLA; X-ray; 2.11 A; A=547-693, A=754-935. DR PDB; 6MOB; X-ray; 1.80 A; A=566-693, A=754-935. DR PDB; 6XV9; X-ray; 3.38 A; A/B=551-687, A/B=766-934. DR PDB; 6XVA; X-ray; 2.30 A; A/B=551-687, A/B=766-934. DR PDB; 6XVB; X-ray; 2.15 A; A/B=551-687, A/B=766-934. DR PDB; 7KHG; X-ray; 2.15 A; A=545-934. DR PDB; 7KHJ; X-ray; 2.80 A; A/B=545-934. DR PDB; 7KHK; X-ray; 2.34 A; A/B=545-934. DR PDB; 7ZW8; X-ray; 2.12 A; A=551-935. DR PDB; 7ZY6; X-ray; 3.09 A; A=551-935. DR PDB; 8DFM; EM; 3.45 A; A/B=32-976. DR PDB; 8DFP; EM; 3.17 A; A/B=32-976. DR PDB; 8DFQ; EM; 3.96 A; A/B=32-976. DR PDB; 8PQ9; X-ray; 1.70 A; A/C=551-687, A/C=766-934. DR PDB; 8PQA; X-ray; 1.65 A; A/C=551-687, A/C=766-934. DR PDB; 8PQB; X-ray; 1.87 A; A=551-687, A=766-934. DR PDB; 8PQC; X-ray; 1.77 A; A/B=551-687, A/B=766-934. DR PDB; 8PQD; X-ray; 1.50 A; A/B=551-687, A/B=766-934. DR PDB; 8PQE; X-ray; 2.00 A; A/B=551-687, A/B=766-934. DR PDB; 8PQF; X-ray; 1.90 A; A/C=551-687, A/C=766-934. DR PDB; 8PQG; X-ray; 2.40 A; A/C=551-687, A/C=766-934. DR PDB; 8S13; X-ray; 2.00 A; A=551-687, A=766-934. DR PDB; 8S14; X-ray; 1.50 A; A=551-687, A=766-934. DR PDB; 8S15; X-ray; 2.40 A; A=551-687, A=766-934. DR PDB; 8S16; X-ray; 1.85 A; A/B=551-687, A/B=766-934. DR PDB; 8S17; X-ray; 2.20 A; A/B=551-687, A/B=766-934. DR PDB; 8S18; X-ray; 2.10 A; A/B=551-687, A/B=766-934. DR PDB; 8S19; X-ray; 2.30 A; A/B=551-687, A/B=766-934. DR PDB; 8S1A; X-ray; 1.85 A; A/B=551-687, A/B=766-934. DR PDB; 8S1B; X-ray; 2.00 A; A/B=551-687, A/B=766-934. DR PDBsum; 1PKG; -. DR PDBsum; 1T45; -. DR PDBsum; 1T46; -. DR PDBsum; 2E9W; -. DR PDBsum; 2EC8; -. DR PDBsum; 2IUH; -. DR PDBsum; 2VIF; -. DR PDBsum; 3G0E; -. DR PDBsum; 3G0F; -. DR PDBsum; 4HVS; -. DR PDBsum; 4K94; -. DR PDBsum; 4K9E; -. DR PDBsum; 4PGZ; -. DR PDBsum; 4U0I; -. DR PDBsum; 6GQJ; -. DR PDBsum; 6GQK; -. DR PDBsum; 6GQL; -. DR PDBsum; 6GQM; -. DR PDBsum; 6HH1; -. DR PDBsum; 6ITT; -. DR PDBsum; 6ITV; -. DR PDBsum; 6KLA; -. DR PDBsum; 6MOB; -. DR PDBsum; 6XV9; -. DR PDBsum; 6XVA; -. DR PDBsum; 6XVB; -. DR PDBsum; 7KHG; -. DR PDBsum; 7KHJ; -. DR PDBsum; 7KHK; -. DR PDBsum; 7ZW8; -. DR PDBsum; 7ZY6; -. DR PDBsum; 8DFM; -. DR PDBsum; 8DFP; -. DR PDBsum; 8DFQ; -. DR PDBsum; 8PQ9; -. DR PDBsum; 8PQA; -. DR PDBsum; 8PQB; -. DR PDBsum; 8PQC; -. DR PDBsum; 8PQD; -. DR PDBsum; 8PQE; -. DR PDBsum; 8PQF; -. DR PDBsum; 8PQG; -. DR PDBsum; 8S13; -. DR PDBsum; 8S14; -. DR PDBsum; 8S15; -. DR PDBsum; 8S16; -. DR PDBsum; 8S17; -. DR PDBsum; 8S18; -. DR PDBsum; 8S19; -. DR PDBsum; 8S1A; -. DR PDBsum; 8S1B; -. DR AlphaFoldDB; P10721; -. DR EMDB; EMD-27408; -. DR EMDB; EMD-27410; -. DR EMDB; EMD-27411; -. DR SMR; P10721; -. DR BioGRID; 110015; 108. DR CORUM; P10721; -. DR DIP; DIP-1055N; -. DR FunCoup; P10721; 1086. DR IntAct; P10721; 106. DR MINT; P10721; -. DR STRING; 9606.ENSP00000288135; -. DR BindingDB; P10721; -. DR ChEMBL; CHEMBL1936; -. DR DrugBank; DB12742; Amuvatinib. DR DrugBank; DB09103; Ancestim. DR DrugBank; DB15233; Avapritinib. DR DrugBank; DB18041; Bezuclastinib. DR DrugBank; DB01254; Dasatinib. DR DrugBank; DB12147; Erdafitinib. DR DrugBank; DB11741; Famitinib. DR DrugBank; DB12010; Fostamatinib. DR DrugBank; DB00619; Imatinib. DR DrugBank; DB17140; JNJ-28312141. DR DrugBank; DB09078; Lenvatinib. DR DrugBank; DB06080; Linifanib. DR DrugBank; DB06595; Midostaurin. DR DrugBank; DB05575; Motesanib. DR DrugBank; DB04868; Nilotinib. DR DrugBank; DB05913; OSI-930. DR DrugBank; DB06589; Pazopanib. DR DrugBank; DB08339; PD-166326. DR DrugBank; DB12978; Pexidartinib. DR DrugBank; DB01962; Phosphonotyrosine. DR DrugBank; DB08901; Ponatinib. DR DrugBank; DB08896; Regorafenib. DR DrugBank; DB14840; Ripretinib. DR DrugBank; DB06436; Semaxanib. DR DrugBank; DB00398; Sorafenib. DR DrugBank; DB01268; Sunitinib. DR DrugBank; DB11800; Tivozanib. DR DrugBank; DB05146; XL820. DR DrugCentral; P10721; -. DR GuidetoPHARMACOLOGY; 1805; -. DR CarbonylDB; P10721; -. DR GlyConnect; 1492; 3 N-Linked glycans (2 sites). DR GlyCosmos; P10721; 10 sites, 4 glycans. DR GlyGen; P10721; 12 sites, 26 N-linked glycans (6 sites). DR iPTMnet; P10721; -. DR PhosphoSitePlus; P10721; -. DR BioMuta; KIT; -. DR DMDM; 125472; -. DR CPTAC; CPTAC-3066; -. DR CPTAC; CPTAC-3067; -. DR jPOST; P10721; -. DR MassIVE; P10721; -. DR PaxDb; 9606-ENSP00000288135; -. DR PeptideAtlas; P10721; -. DR ProteomicsDB; 52640; -. [P10721-1] DR ProteomicsDB; 52641; -. [P10721-2] DR Pumba; P10721; -. DR ABCD; P10721; 2 sequenced antibodies. DR Antibodypedia; 1392; 5560 antibodies from 59 providers. DR DNASU; 3815; -. DR Ensembl; ENST00000288135.6; ENSP00000288135.6; ENSG00000157404.18. [P10721-1] DR Ensembl; ENST00000687295.1; ENSP00000509450.1; ENSG00000157404.18. [P10721-2] DR GeneID; 3815; -. DR KEGG; hsa:3815; -. DR MANE-Select; ENST00000288135.6; ENSP00000288135.6; NM_000222.3; NP_000213.1. DR UCSC; uc010igr.4; human. [P10721-1] DR AGR; HGNC:6342; -. DR CIViC; 3815; 1 clinical assertion and 310 evidence items across 136 molecular profiles. DR ClinPGx; PA30128; -. DR CTD; 3815; -. DR DisGeNET; 3815; -. DR GeneCards; KIT; -. DR HGNC; HGNC:6342; KIT. DR HPA; ENSG00000157404; Tissue enhanced (breast). DR MalaCards; KIT; -. DR MIM; 154800; phenotype. DR MIM; 164920; gene. DR MIM; 172800; phenotype. DR MIM; 273300; phenotype. DR MIM; 601626; phenotype. DR MIM; 606764; phenotype. DR OpenTargets; ENSG00000157404; -. DR Orphanet; 566393; Acute mast cell leukemia. DR Orphanet; 98834; Acute myeloblastic leukemia with maturation. DR Orphanet; 98829; Acute myeloid leukemia with abnormal bone marrow eosinophils inv(16)(p13q22) or t(16;16)(p13;q22). DR Orphanet; 102724; Acute myeloid leukemia with t(8;21)(q22;q22) translocation. DR Orphanet; 280785; Bullous diffuse cutaneous mastocytosis. DR Orphanet; 566396; Chronic mast cell leukemia. DR Orphanet; 79455; Cutaneous mastocytoma. DR Orphanet; 44890; Gastrointestinal stromal tumor. DR Orphanet; 158778; Isolated bone marrow mastocytosis. DR Orphanet; 158772; Nodular urticaria pigmentosa. DR Orphanet; 2884; Piebaldism. DR Orphanet; 158769; Plaque-form urticaria pigmentosa. DR Orphanet; 280794; Pseudoxanthomatous diffuse cutaneous mastocytosis. DR Orphanet; 158775; Smoldering systemic mastocytosis. DR Orphanet; 98849; Systemic mastocytosis with associated hematologic neoplasm. DR Orphanet; 90389; Telangiectasia macularis eruptiva perstans. DR Orphanet; 842; Testicular seminomatous germ cell tumor. DR Orphanet; 158766; Typical urticaria pigmentosa. DR VEuPathDB; HostDB:ENSG00000157404; -. DR eggNOG; KOG0200; Eukaryota. DR GeneTree; ENSGT00940000155626; -. DR HOGENOM; CLU_000288_49_0_1; -. DR InParanoid; P10721; -. DR OMA; ANEECEW; -. DR OrthoDB; 6077854at2759; -. DR PAN-GO; P10721; 10 GO annotations based on evolutionary models. DR PhylomeDB; P10721; -. DR BRENDA; 2.7.10.1; 2681. DR PathwayCommons; P10721; -. DR Reactome; R-HSA-1257604; PIP3 activates AKT signaling. DR Reactome; R-HSA-1433557; Signaling by SCF-KIT. DR Reactome; R-HSA-1433559; Regulation of KIT signaling. DR Reactome; R-HSA-2219530; Constitutive Signaling by Aberrant PI3K in Cancer. DR Reactome; R-HSA-5673001; RAF/MAP kinase cascade. DR Reactome; R-HSA-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling. DR Reactome; R-HSA-8866910; TFAP2 (AP-2) family regulates transcription of growth factors and their receptors. DR Reactome; R-HSA-9669914; Dasatinib-resistant KIT mutants. DR Reactome; R-HSA-9669917; Imatinib-resistant KIT mutants. DR Reactome; R-HSA-9669921; KIT mutants bind TKIs. DR Reactome; R-HSA-9669924; Masitinib-resistant KIT mutants. DR Reactome; R-HSA-9669926; Nilotinib-resistant KIT mutants. DR Reactome; R-HSA-9669929; Regorafenib-resistant KIT mutants. DR Reactome; R-HSA-9669933; Signaling by kinase domain mutants of KIT. DR Reactome; R-HSA-9669934; Sunitinib-resistant KIT mutants. DR Reactome; R-HSA-9669935; Signaling by juxtamembrane domain KIT mutants. DR Reactome; R-HSA-9669936; Sorafenib-resistant KIT mutants. DR Reactome; R-HSA-9670439; Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants. DR Reactome; R-HSA-9680187; Signaling by extracellular domain mutants of KIT. DR Reactome; R-HSA-9856649; Transcriptional and post-translational regulation of MITF-M expression and activity. DR SignaLink; P10721; -. DR SIGNOR; P10721; -. DR Agora; ENSG00000157404; -. DR BioGRID-ORCS; 3815; 9 hits in 1192 CRISPR screens. DR CD-CODE; 91857CE7; Nucleolus. DR ChiTaRS; KIT; human. DR EvolutionaryTrace; P10721; -. DR GeneWiki; CD117; -. DR GenomeRNAi; 3815; -. DR Pharos; P10721; Tclin. DR PRO; PR:P10721; -. DR Proteomes; UP000005640; Chromosome 4. DR RNAct; P10721; protein. DR Bgee; ENSG00000157404; Expressed in lateral nuclear group of thalamus and 193 other cell types or tissues. DR GO; GO:0001669; C:acrosomal vesicle; IEA:Ensembl. DR GO; GO:0005911; C:cell-cell junction; IEA:Ensembl. DR GO; GO:0009898; C:cytoplasmic side of plasma membrane; IEA:Ensembl. DR GO; GO:0009897; C:external side of plasma membrane; IEA:Ensembl. DR GO; GO:0005615; C:extracellular space; IDA:BHF-UCL. DR GO; GO:0001650; C:fibrillar center; IDA:HPA. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0043235; C:receptor complex; IBA:GO_Central. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0019955; F:cytokine binding; IDA:UniProtKB. DR GO; GO:0019838; F:growth factor binding; IBA:GO_Central. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0002020; F:protease binding; IEA:Ensembl. DR GO; GO:0042803; F:protein homodimerization activity; IPI:UniProtKB. DR GO; GO:0004713; F:protein tyrosine kinase activity; TAS:Reactome. DR GO; GO:0042169; F:SH2 domain binding; IEA:Ensembl. DR GO; GO:0005020; F:stem cell factor receptor activity; IEA:Ensembl. DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IDA:UniProtKB. DR GO; GO:0030036; P:actin cytoskeleton organization; IDA:UniProtKB. DR GO; GO:0030183; P:B cell differentiation; IBA:GO_Central. DR GO; GO:0060326; P:cell chemotaxis; IDA:UniProtKB. DR GO; GO:0016477; P:cell migration; IBA:GO_Central. DR GO; GO:0019221; P:cytokine-mediated signaling pathway; IDA:UniProtKB. DR GO; GO:0050910; P:detection of mechanical stimulus involved in sensory perception of sound; ISS:UniProtKB. DR GO; GO:0048565; P:digestive tract development; ISS:UniProtKB. DR GO; GO:0035234; P:ectopic germ cell programmed cell death; IEA:Ensembl. DR GO; GO:0035162; P:embryonic hemopoiesis; ISS:UniProtKB. DR GO; GO:0050673; P:epithelial cell proliferation; IEA:Ensembl. DR GO; GO:0030218; P:erythrocyte differentiation; ISS:UniProtKB. DR GO; GO:0038162; P:erythropoietin-mediated signaling pathway; ISS:UniProtKB. DR GO; GO:0038093; P:Fc receptor signaling pathway; IDA:UniProtKB. DR GO; GO:0008354; P:germ cell migration; IEA:Ensembl. DR GO; GO:0006687; P:glycosphingolipid metabolic process; IEA:Ensembl. DR GO; GO:0002244; P:hematopoietic progenitor cell differentiation; IBA:GO_Central. DR GO; GO:0035701; P:hematopoietic stem cell migration; IEA:Ensembl. DR GO; GO:0030097; P:hemopoiesis; TAS:UniProtKB. DR GO; GO:0002327; P:immature B cell differentiation; ISS:UniProtKB. DR GO; GO:0006954; P:inflammatory response; ISS:UniProtKB. DR GO; GO:0035556; P:intracellular signal transduction; IEA:Ensembl. DR GO; GO:0038109; P:Kit signaling pathway; IDA:UniProtKB. DR GO; GO:0030032; P:lamellipodium assembly; ISS:UniProtKB. DR GO; GO:0002320; P:lymphoid progenitor cell differentiation; IEA:Ensembl. DR GO; GO:0008584; P:male gonad development; IEP:UniProtKB. DR GO; GO:0002551; P:mast cell chemotaxis; IDA:UniProtKB. DR GO; GO:0043303; P:mast cell degranulation; IMP:UniProtKB. DR GO; GO:0060374; P:mast cell differentiation; ISS:UniProtKB. DR GO; GO:0070662; P:mast cell proliferation; TAS:UniProtKB. DR GO; GO:0035855; P:megakaryocyte development; ISS:UniProtKB. DR GO; GO:0097326; P:melanocyte adhesion; ISS:UniProtKB. DR GO; GO:0030318; P:melanocyte differentiation; ISS:UniProtKB. DR GO; GO:0097324; P:melanocyte migration; ISS:UniProtKB. DR GO; GO:0002318; P:myeloid progenitor cell differentiation; IEA:Ensembl. DR GO; GO:0051093; P:negative regulation of developmental process; IEA:Ensembl. DR GO; GO:0043069; P:negative regulation of programmed cell death; IEA:Ensembl. DR GO; GO:2000242; P:negative regulation of reproductive process; IEA:Ensembl. DR GO; GO:0001541; P:ovarian follicle development; ISS:UniProtKB. DR GO; GO:0043473; P:pigmentation; ISS:UniProtKB. DR GO; GO:0030335; P:positive regulation of cell migration; IBA:GO_Central. DR GO; GO:0008284; P:positive regulation of cell population proliferation; IBA:GO_Central. DR GO; GO:1904343; P:positive regulation of colon smooth muscle contraction; IEA:Ensembl. DR GO; GO:0002732; P:positive regulation of dendritic cell cytokine production; ISS:UniProtKB. DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; IMP:UniProtKB. DR GO; GO:0048170; P:positive regulation of long-term neuronal synaptic plasticity; IEA:Ensembl. DR GO; GO:0043410; P:positive regulation of MAPK cascade; IMP:UniProtKB. DR GO; GO:0032765; P:positive regulation of mast cell cytokine production; IDA:UniProtKB. DR GO; GO:0070668; P:positive regulation of mast cell proliferation; IEA:Ensembl. DR GO; GO:0045747; P:positive regulation of Notch signaling pathway; IEA:Ensembl. DR GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; TAS:UniProtKB. DR GO; GO:0031274; P:positive regulation of pseudopodium assembly; IEA:Ensembl. DR GO; GO:0120072; P:positive regulation of pyloric antrum smooth muscle contraction; IEA:Ensembl. DR GO; GO:0046427; P:positive regulation of receptor signaling pathway via JAK-STAT; IMP:UniProtKB. DR GO; GO:1904349; P:positive regulation of small intestine smooth muscle contraction; IEA:Ensembl. DR GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; IMP:UniProtKB. DR GO; GO:1905065; P:positive regulation of vascular associated smooth muscle cell differentiation; IDA:BHF-UCL. DR GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB. DR GO; GO:1904251; P:regulation of bile acid metabolic process; IEA:Ensembl. DR GO; GO:0042127; P:regulation of cell population proliferation; TAS:UniProtKB. DR GO; GO:0008360; P:regulation of cell shape; ISS:UniProtKB. DR GO; GO:0046686; P:response to cadmium ion; IEA:Ensembl. DR GO; GO:0007165; P:signal transduction; TAS:ProtInc. DR GO; GO:0035019; P:somatic stem cell population maintenance; IEA:Ensembl. DR GO; GO:0007286; P:spermatid development; IEA:Ensembl. DR GO; GO:0007283; P:spermatogenesis; ISS:UniProtKB. DR GO; GO:0048863; P:stem cell differentiation; ISS:UniProtKB. DR GO; GO:0019827; P:stem cell population maintenance; TAS:UniProtKB. DR GO; GO:0030217; P:T cell differentiation; ISS:UniProtKB. DR GO; GO:0043586; P:tongue development; IEA:Ensembl. DR GO; GO:0008542; P:visual learning; IEA:Ensembl. DR CDD; cd00096; Ig; 2. DR CDD; cd05860; IgI_4_SCFR; 1. DR CDD; cd05104; PTKc_Kit; 1. DR DisProt; DP02247; -. DR FunFam; 1.10.510.10:FF:000177; Mast/stem cell growth factor receptor; 1. DR FunFam; 2.60.40.10:FF:000422; Mast/stem cell growth factor receptor; 1. DR FunFam; 2.60.40.10:FF:000429; Mast/stem cell growth factor receptor; 1. DR FunFam; 2.60.40.10:FF:000469; Mast/stem cell growth factor receptor; 1. DR FunFam; 2.60.40.10:FF:000544; Mast/stem cell growth factor receptor; 1. DR FunFam; 2.60.40.10:FF:000815; Mast/stem cell growth factor receptor; 1. DR FunFam; 3.30.200.20:FF:000025; Platelet-derived growth factor receptor alpha; 1. DR Gene3D; 2.60.40.10; Immunoglobulins; 5. DR Gene3D; 3.30.200.20; Phosphorylase Kinase, domain 1; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. DR InterPro; IPR007110; Ig-like_dom. DR InterPro; IPR036179; Ig-like_dom_sf. DR InterPro; IPR013783; Ig-like_fold. DR InterPro; IPR003599; Ig_sub. DR InterPro; IPR003598; Ig_sub2. DR InterPro; IPR013151; Immunoglobulin_dom. DR InterPro; IPR011009; Kinase-like_dom_sf. DR InterPro; IPR000719; Prot_kinase_dom. DR InterPro; IPR017441; Protein_kinase_ATP_BS. DR InterPro; IPR050122; RTK. DR InterPro; IPR027263; SCGF_receptor. DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom. DR InterPro; IPR008266; Tyr_kinase_AS. DR InterPro; IPR020635; Tyr_kinase_cat_dom. DR InterPro; IPR001824; Tyr_kinase_rcpt_3_CS. DR PANTHER; PTHR24416:SF46; MAST_STEM CELL GROWTH FACTOR RECEPTOR KIT; 1. DR PANTHER; PTHR24416; TYROSINE-PROTEIN KINASE RECEPTOR; 1. DR Pfam; PF00047; ig; 1. DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1. DR PIRSF; PIRSF500951; SCGF_recepter; 1. DR PIRSF; PIRSF000615; TyrPK_CSF1-R; 1. DR SMART; SM00409; IG; 3. DR SMART; SM00408; IGc2; 1. DR SMART; SM00219; TyrKc; 1. DR SUPFAM; SSF48726; Immunoglobulin; 3. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR PROSITE; PS50835; IG_LIKE; 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1. DR PROSITE; PS00240; RECEPTOR_TYR_KIN_III; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; ATP-binding; Cell membrane; Cytoplasm; KW Direct protein sequencing; Disease variant; Disulfide bond; Glycoprotein; KW Immunoglobulin domain; Kinase; Magnesium; Membrane; Metal-binding; KW Nucleotide-binding; Phosphoprotein; Proteomics identification; KW Proto-oncogene; Receptor; Reference proteome; Repeat; Signal; Transferase; KW Transmembrane; Transmembrane helix; Tyrosine-protein kinase; KW Ubl conjugation. FT SIGNAL 1..25 FT /evidence="ECO:0000255" FT CHAIN 26..976 FT /note="Mast/stem cell growth factor receptor Kit" FT /id="PRO_0000016754" FT TOPO_DOM 26..524 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 525..545 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 546..976 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 27..112 FT /note="Ig-like C2-type 1" FT DOMAIN 121..205 FT /note="Ig-like C2-type 2" FT DOMAIN 212..308 FT /note="Ig-like C2-type 3" FT DOMAIN 317..410 FT /note="Ig-like C2-type 4" FT DOMAIN 413..507 FT /note="Ig-like C2-type 5" FT DOMAIN 589..937 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT REGION 568..570 FT /note="Important for interaction with phosphotyrosine- FT binding proteins" FT ACT_SITE 792 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000255|PROSITE-ProRule:PRU10028" FT BINDING 568 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT BINDING 596..603 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT BINDING 623 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT BINDING 671..677 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT BINDING 796 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT BINDING 797 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT BINDING 810 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT SITE 936 FT /note="Important for interaction with phosphotyrosine- FT binding proteins" FT MOD_RES 547 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000305|PubMed:20147452" FT MOD_RES 553 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000305|PubMed:20147452" FT MOD_RES 568 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:12824176, FT ECO:0000269|PubMed:19265199, ECO:0000269|PubMed:21030588, FT ECO:0000269|PubMed:9038210" FT MOD_RES 570 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:12824176, FT ECO:0000269|PubMed:9038210" FT MOD_RES 703 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:10377264, FT ECO:0000269|PubMed:19265199, ECO:0000269|PubMed:20147452" FT MOD_RES 721 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:19265199, FT ECO:0000269|PubMed:20147452, ECO:0000269|PubMed:9038210" FT MOD_RES 730 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000305|PubMed:20147452" FT MOD_RES 741 FT /note="Phosphoserine; by PKC/PRKCA" FT /evidence="ECO:0000269|PubMed:7539802" FT MOD_RES 746 FT /note="Phosphoserine; by PKC/PRKCA" FT /evidence="ECO:0000269|PubMed:7539802" FT MOD_RES 821 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:7539802" FT MOD_RES 823 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:20147452" FT MOD_RES 891 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:12878163" FT MOD_RES 900 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:12878163, FT ECO:0000269|PubMed:20147452" FT MOD_RES 936 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:10377264, FT ECO:0000269|PubMed:19265199" FT MOD_RES 959 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:7539802, FT ECO:0007744|PubMed:19369195" FT CARBOHYD 130 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:16335952, FT ECO:0000269|PubMed:17662946" FT CARBOHYD 145 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 283 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:17662946" FT CARBOHYD 293 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:17662946" FT CARBOHYD 300 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:17662946" FT CARBOHYD 320 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:17662946" FT CARBOHYD 352 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:17662946" FT CARBOHYD 367 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:17662946" FT CARBOHYD 463 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 486 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 58..97 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114, FT ECO:0000269|PubMed:17662946" FT DISULFID 136..186 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114, FT ECO:0000269|PubMed:17662946" FT DISULFID 151..183 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114, FT ECO:0000269|PubMed:17662946" FT DISULFID 233..290 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114, FT ECO:0000269|PubMed:17662946" FT DISULFID 428..491 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114, FT ECO:0000269|PubMed:17662946" FT VAR_SEQ 1..744 FT /note="MRGARGAWDFLCVLLLLLRVQTGSSQPSVSPGEPSPPSIHPGKSDLIVRVGD FT EIRLLCTDPGFVKWTFEILDETNENKQNEWITEKAEATNTGKYTCTNKHGLSNSIYVFV FT RDPAKLFLVDRSLYGKEDNDTLVRCPLTDPEVTNYSLKGCQGKPLPKDLRFIPDPKAGI FT MIKSVKRAYHRLCLHCSVDQEGKSVLSEKFILKVRPAFKAVPVVSVSKASYLLREGEEF FT TVTCTIKDVSSSVYSTWKRENSQTKLQEKYNSWHHGDFNYERQATLTISSARVNDSGVF FT MCYANNTFGSANVTTTLEVVDKGFINIFPMINTTVFVNDGENVDLIVEYEAFPKPEHQQ FT WIYMNRTFTDKWEDYPKSENESNIRYVSELHLTRLKGTEGGTYTFLVSNSDVNAAIAFN FT VYVNTKPEILTYDRLVNGMLQCVAAGFPEPTIDWYFCPGTEQRCSASVLPVDVQTLNSS FT GPPFGKLVVQSSIDSSAFKHNGTVECKAYNDVGKTSAYFNFAFKGNNKEQIHPHTLFTP FT LLIGFVIVAGMMCIIVMILTYKYLQKPMYEVQWKVVEEINGNNYVYIDPTQLPYDHKWE FT FPRNRLSFGKTLGAGAFGKVVEATAYGLIKSDAAMTVAVKMLKPSAHLTEREALMSELK FT VLSYLGNHMNIVNLLGACTIGGPTLVITEYCCYGDLLNFLRRKRDSFICSKQEDHAEAA FT LYKNLLHSKESSCSDSTNEYMDMKPGVSYVVPTKADKRRSVRI -> MSLPLSFPFLTF FT MVVIAKKNPLFLT (in isoform 3)" FT /id="VSP_060976" FT VAR_SEQ 510..513 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:20658618, ECO:0000303|Ref.7" FT /id="VSP_038385" FT VARIANT 451 FT /note="S -> C (in MASTC; uncertain significance; FT dbSNP:rs1060502556)" FT /evidence="ECO:0000269|PubMed:24289326" FT /id="VAR_081062" FT VARIANT 532 FT /note="V -> I (in dbSNP:rs55792975)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_042021" FT VARIANT 533 FT /note="A -> D (in MASTC; uncertain significance; FT dbSNP:rs753212327)" FT /evidence="ECO:0000269|PubMed:15173254" FT /id="VAR_081063" FT VARIANT 541 FT /note="M -> L (in dbSNP:rs3822214)" FT /evidence="ECO:0000269|PubMed:17344846, FT ECO:0000269|PubMed:19865100" FT /id="VAR_042022" FT VARIANT 541 FT /note="M -> V (in dbSNP:rs3822214)" FT /id="VAR_061289" FT VARIANT 550..558 FT /note="Missing (in GIST; somatic mutation)" FT /evidence="ECO:0000269|PubMed:15824741, FT ECO:0000269|PubMed:9438854" FT /id="VAR_033124" FT VARIANT 550 FT /note="K -> I (in GIST; somatic mutation; FT dbSNP:rs2109775477)" FT /evidence="ECO:0000269|PubMed:9438854" FT /id="VAR_033123" FT VARIANT 551..555 FT /note="Missing (in GIST; somatic mutation; FT dbSNP:rs2109775521)" FT /evidence="ECO:0000269|PubMed:9438854" FT /id="VAR_033125" FT VARIANT 559..560 FT /note="Missing (in GIST; somatic mutation; FT dbSNP:rs121913685)" FT /evidence="ECO:0000269|PubMed:9438854" FT /id="VAR_033128" FT VARIANT 559 FT /note="V -> A (in GIST; dbSNP:rs121913517)" FT /evidence="ECO:0000269|PubMed:11505412" FT /id="VAR_033126" FT VARIANT 559 FT /note="V -> D (in GIST; somatic mutation; FT dbSNP:rs121913517)" FT /evidence="ECO:0000269|PubMed:9438854" FT /id="VAR_033127" FT VARIANT 559 FT /note="Missing (in GIST; dbSNP:rs121913685)" FT /evidence="ECO:0000269|PubMed:9697690" FT /id="VAR_007965" FT VARIANT 583 FT /note="E -> K (in PBT; dbSNP:rs121913680)" FT /evidence="ECO:0000269|PubMed:1376329" FT /id="VAR_004104" FT VARIANT 584 FT /note="F -> C (in PBT; dbSNP:rs28933371)" FT /evidence="ECO:0000269|PubMed:11074500" FT /id="VAR_033129" FT VARIANT 584 FT /note="F -> L (in PBT; dbSNP:rs794726671)" FT /evidence="ECO:0000269|PubMed:1370874" FT /id="VAR_004105" FT VARIANT 601 FT /note="G -> R (in PBT; dbSNP:rs2109779521)" FT /evidence="ECO:0000269|PubMed:11074500" FT /id="VAR_033130" FT VARIANT 656 FT /note="L -> P (in PBT)" FT /evidence="ECO:0000269|PubMed:11074500" FT /id="VAR_033131" FT VARIANT 664 FT /note="G -> R (in PBT; dbSNP:rs121913679)" FT /evidence="ECO:0000269|PubMed:1717985" FT /id="VAR_004106" FT VARIANT 691 FT /note="C -> S (in dbSNP:rs35200131)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_042023" FT VARIANT 715 FT /note="S -> N (in dbSNP:rs56094246)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_042024" FT VARIANT 737 FT /note="D -> N (in a colorectal adenocarcinoma sample; FT somatic mutation; dbSNP:rs751005114)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_042025" FT VARIANT 791 FT /note="R -> G (in PBT; dbSNP:rs1722708855)" FT /evidence="ECO:0000269|PubMed:7687267" FT /id="VAR_004107" FT VARIANT 796 FT /note="R -> G (in PBT; with sensorineural deafness; FT dbSNP:rs121913684)" FT /evidence="ECO:0000269|PubMed:9450866" FT /id="VAR_033132" FT VARIANT 804 FT /note="R -> W (in a colorectal adenocarcinoma sample; FT somatic mutation; dbSNP:rs145602440)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_042026" FT VARIANT 812 FT /note="G -> V (in PBT; dbSNP:rs2109801595)" FT /evidence="ECO:0000269|PubMed:7687267" FT /id="VAR_004108" FT VARIANT 816 FT /note="D -> F (in MASTC; sporadic case; somatic mutation; FT constitutively activated and is much more rapidly FT autophosphorylated than wild type; requires 2 nucleotide FT substitutions; dbSNP:rs1057519709)" FT /evidence="ECO:0000269|PubMed:9990072" FT /id="VAR_033133" FT VARIANT 816 FT /note="D -> H (in a testicular tumor; seminoma; somatic FT mutation; constitutively activated; dbSNP:rs121913506)" FT /evidence="ECO:0000269|PubMed:10362788, FT ECO:0000269|PubMed:19164557, ECO:0000269|PubMed:20147452" FT /id="VAR_033134" FT VARIANT 816 FT /note="D -> I (in MASTC; somatic mutation; constitutively FT activated; requires 2 nucleotide substitutions; FT dbSNP:rs1057519709)" FT /evidence="ECO:0000269|PubMed:19865100" FT /id="VAR_081064" FT VARIANT 816 FT /note="D -> V (in MASTSYS, MASTC and mast cell leukemia; FT somatic mutation; constitutively activated; loss of FT interaction with MPDZ; dbSNP:rs121913507)" FT /evidence="ECO:0000269|PubMed:11018522, FT ECO:0000269|PubMed:17595334, ECO:0000269|PubMed:19164557, FT ECO:0000269|PubMed:19265199, ECO:0000269|PubMed:19865100, FT ECO:0000269|PubMed:21640708, ECO:0000269|PubMed:7691885, FT ECO:0000269|PubMed:9990072" FT /id="VAR_004109" FT VARIANT 816 FT /note="D -> Y (in MASTSYS and MASTC; also found in acute FT myeloid leukemia and a germ cell tumor of the testis; FT somatic mutation; constitutively activated; FT dbSNP:rs121913506)" FT /evidence="ECO:0000269|PubMed:16175573, FT ECO:0000269|PubMed:17344846, ECO:0000269|PubMed:19865100, FT ECO:0000269|PubMed:9657776, ECO:0000269|PubMed:9990072" FT /id="VAR_023828" FT VARIANT 820 FT /note="D -> G (in mast cell disease; systemic; FT dbSNP:rs121913682)" FT /evidence="ECO:0000269|PubMed:9029028" FT /id="VAR_033135" FT VARIANT 822 FT /note="N -> I (in MASTC; constitutively activated; FT dbSNP:rs993022333)" FT /evidence="ECO:0000269|PubMed:21689725" FT /id="VAR_081065" FT VARIANT 822 FT /note="N -> K (in a germ cell tumor of the testis; somatic FT mutation; dbSNP:rs121913514)" FT /evidence="ECO:0000269|PubMed:16175573, FT ECO:0000269|PubMed:17344846" FT /id="VAR_023829" FT VARIANT 829 FT /note="A -> P (in a germ cell tumor of the testis; somatic FT mutation; dbSNP:rs1057519713)" FT /evidence="ECO:0000269|PubMed:16175573, FT ECO:0000269|PubMed:17344846" FT /id="VAR_023830" FT VARIANT 839 FT /note="E -> K (in MASTC; sporadic case; somatic mutation; FT dominant negative mutation; loss of autophosphorylation; FT dbSNP:rs121913509)" FT /evidence="ECO:0000269|PubMed:9990072" FT /id="VAR_033136" FT VARIANT 847 FT /note="T -> P (in PBT; dbSNP:rs121913687)" FT /evidence="ECO:0000269|PubMed:9699740" FT /id="VAR_033137" FT VARIANT 893..896 FT /note="Missing (in PBT; severe)" FT /evidence="ECO:0000269|PubMed:8680409" FT /id="VAR_004110" FT MUTAGEN 381 FT /note="R->A: Reduces autophosphorylation in response to FT KITLG/SCF." FT /evidence="ECO:0000269|PubMed:17662946" FT MUTAGEN 386 FT /note="E->A: Reduces autophosphorylation in response to FT KITLG/SCF." FT /evidence="ECO:0000269|PubMed:17662946" FT MUTAGEN 571 FT /note="I->A: Reduction in SH2B2/APS binding. Abolishes FT SH2B2/APS binding; when associated with A-939." FT /evidence="ECO:0000269|PubMed:12444928" FT MUTAGEN 623 FT /note="K->M: Stronger interaction with MPDZ." FT /evidence="ECO:0000269|PubMed:11018522" FT MUTAGEN 741 FT /note="S->A: Abolishes down-regulation of kinase activity FT by PKC/PRKCA-mediated phosphorylation; when associated with FT A-746." FT /evidence="ECO:0000269|PubMed:7539802" FT MUTAGEN 746 FT /note="S->A: Abolishes down-regulation of kinase activity FT by PKC/PRKCA-mediated phosphorylation; when associated with FT A-741." FT /evidence="ECO:0000269|PubMed:7539802" FT MUTAGEN 823 FT /note="Y->F: No decrease in activity. Leads to FT autophosphorylation at Tyr-900." FT /evidence="ECO:0000269|PubMed:20147452" FT MUTAGEN 939 FT /note="L->A: Reduction in SH2B2/APS binding. Abolishes FT SH2B2/APS binding; when associated with A-571." FT /evidence="ECO:0000269|PubMed:12444928" FT CONFLICT 764 FT /note="L -> I (in Ref. 10; AAH71593)" FT /evidence="ECO:0000305" FT CONFLICT 838 FT /note="P -> H (in Ref. 10; AAH71593)" FT /evidence="ECO:0000305" FT STRAND 38..41 FT /evidence="ECO:0007829|PDB:2EC8" FT STRAND 44..47 FT /evidence="ECO:0007829|PDB:2EC8" FT STRAND 54..59 FT /evidence="ECO:0007829|PDB:2EC8" FT STRAND 63..72 FT /evidence="ECO:0007829|PDB:2EC8" FT STRAND 75..77 FT /evidence="ECO:0007829|PDB:2EC8" FT STRAND 79..86 FT /evidence="ECO:0007829|PDB:2EC8" FT HELIX 89..91 FT /evidence="ECO:0007829|PDB:8DFP" FT STRAND 93..99 FT /evidence="ECO:0007829|PDB:2EC8" FT STRAND 104..110 FT /evidence="ECO:0007829|PDB:2EC8" FT STRAND 125..127 FT /evidence="ECO:0007829|PDB:8DFP" FT STRAND 132..134 FT /evidence="ECO:0007829|PDB:2EC8" FT STRAND 146..149 FT /evidence="ECO:0007829|PDB:2EC8" FT STRAND 151..153 FT /evidence="ECO:0007829|PDB:2EC8" FT STRAND 161..165 FT /evidence="ECO:0007829|PDB:2EC8" FT TURN 166..168 FT /evidence="ECO:0007829|PDB:2EC8" FT STRAND 169..174 FT /evidence="ECO:0007829|PDB:2EC8" FT HELIX 177..179 FT /evidence="ECO:0007829|PDB:2EC8" FT STRAND 183..188 FT /evidence="ECO:0007829|PDB:2EC8" FT STRAND 194..196 FT /evidence="ECO:0007829|PDB:8DFP" FT STRAND 200..205 FT /evidence="ECO:0007829|PDB:8DFP" FT STRAND 213..215 FT /evidence="ECO:0007829|PDB:2EC8" FT STRAND 219..224 FT /evidence="ECO:0007829|PDB:2EC8" FT STRAND 229..239 FT /evidence="ECO:0007829|PDB:2EC8" FT STRAND 243..248 FT /evidence="ECO:0007829|PDB:2EC8" FT STRAND 258..263 FT /evidence="ECO:0007829|PDB:2EC8" FT STRAND 265..267 FT /evidence="ECO:0007829|PDB:2EC8" FT STRAND 269..279 FT /evidence="ECO:0007829|PDB:2EC8" FT TURN 282..284 FT /evidence="ECO:0007829|PDB:2EC8" FT STRAND 286..293 FT /evidence="ECO:0007829|PDB:2EC8" FT STRAND 298..310 FT /evidence="ECO:0007829|PDB:2EC8" FT STRAND 312..319 FT /evidence="ECO:0007829|PDB:4K94" FT STRAND 321..325 FT /evidence="ECO:0007829|PDB:4K94" FT STRAND 331..341 FT /evidence="ECO:0007829|PDB:4K94" FT STRAND 344..350 FT /evidence="ECO:0007829|PDB:4K94" FT STRAND 356..364 FT /evidence="ECO:0007829|PDB:4K94" FT STRAND 367..369 FT /evidence="ECO:0007829|PDB:2EC8" FT STRAND 372..379 FT /evidence="ECO:0007829|PDB:4K94" FT HELIX 384..386 FT /evidence="ECO:0007829|PDB:4K94" FT STRAND 388..395 FT /evidence="ECO:0007829|PDB:4K94" FT STRAND 400..409 FT /evidence="ECO:0007829|PDB:4K94" FT STRAND 411..420 FT /evidence="ECO:0007829|PDB:4K94" FT HELIX 422..424 FT /evidence="ECO:0007829|PDB:4K94" FT STRAND 425..434 FT /evidence="ECO:0007829|PDB:4K94" FT STRAND 437..444 FT /evidence="ECO:0007829|PDB:4K94" FT STRAND 445..449 FT /evidence="ECO:0007829|PDB:4PGZ" FT STRAND 452..454 FT /evidence="ECO:0007829|PDB:4PGZ" FT STRAND 458..462 FT /evidence="ECO:0007829|PDB:4K94" FT STRAND 465..468 FT /evidence="ECO:0007829|PDB:4PGZ" FT STRAND 472..479 FT /evidence="ECO:0007829|PDB:4K94" FT HELIX 481..483 FT /evidence="ECO:0007829|PDB:4PGZ" FT STRAND 485..494 FT /evidence="ECO:0007829|PDB:4K94" FT STRAND 499..506 FT /evidence="ECO:0007829|PDB:4K94" FT HELIX 550..552 FT /evidence="ECO:0007829|PDB:7KHG" FT STRAND 558..564 FT /evidence="ECO:0007829|PDB:3G0E" FT STRAND 567..570 FT /evidence="ECO:0007829|PDB:3G0E" FT HELIX 573..575 FT /evidence="ECO:0007829|PDB:8PQD" FT HELIX 580..582 FT /evidence="ECO:0007829|PDB:8PQD" FT HELIX 586..588 FT /evidence="ECO:0007829|PDB:8PQD" FT STRAND 589..597 FT /evidence="ECO:0007829|PDB:8PQD" FT STRAND 599..609 FT /evidence="ECO:0007829|PDB:8PQD" FT STRAND 611..613 FT /evidence="ECO:0007829|PDB:8PQD" FT STRAND 617..625 FT /evidence="ECO:0007829|PDB:8PQD" FT HELIX 627..629 FT /evidence="ECO:0007829|PDB:6HH1" FT HELIX 631..647 FT /evidence="ECO:0007829|PDB:8PQD" FT STRAND 656..660 FT /evidence="ECO:0007829|PDB:8PQD" FT STRAND 662..664 FT /evidence="ECO:0007829|PDB:8PQD" FT STRAND 667..671 FT /evidence="ECO:0007829|PDB:8PQD" FT STRAND 674..677 FT /evidence="ECO:0007829|PDB:7KHK" FT HELIX 678..685 FT /evidence="ECO:0007829|PDB:8PQD" FT HELIX 686..689 FT /evidence="ECO:0007829|PDB:3G0E" FT STRAND 719..721 FT /evidence="ECO:0007829|PDB:2IUH" FT HELIX 754..756 FT /evidence="ECO:0007829|PDB:4HVS" FT STRAND 757..759 FT /evidence="ECO:0007829|PDB:4HVS" FT HELIX 760..762 FT /evidence="ECO:0007829|PDB:4HVS" FT HELIX 766..785 FT /evidence="ECO:0007829|PDB:8PQD" FT STRAND 788..790 FT /evidence="ECO:0007829|PDB:3G0F" FT HELIX 795..797 FT /evidence="ECO:0007829|PDB:8PQD" FT STRAND 798..801 FT /evidence="ECO:0007829|PDB:8PQD" FT HELIX 802..804 FT /evidence="ECO:0007829|PDB:8PQD" FT STRAND 805..808 FT /evidence="ECO:0007829|PDB:8PQD" FT HELIX 812..814 FT /evidence="ECO:0007829|PDB:1T46" FT TURN 818..820 FT /evidence="ECO:0007829|PDB:8PQD" FT STRAND 821..824 FT /evidence="ECO:0007829|PDB:8PQD" FT STRAND 827..831 FT /evidence="ECO:0007829|PDB:1T46" FT HELIX 833..835 FT /evidence="ECO:0007829|PDB:8PQD" FT HELIX 838..843 FT /evidence="ECO:0007829|PDB:8PQD" FT HELIX 848..863 FT /evidence="ECO:0007829|PDB:8PQD" FT TURN 864..866 FT /evidence="ECO:0007829|PDB:1T46" FT STRAND 869..872 FT /evidence="ECO:0007829|PDB:6ITT" FT HELIX 877..885 FT /evidence="ECO:0007829|PDB:8PQD" FT HELIX 897..906 FT /evidence="ECO:0007829|PDB:8PQD" FT HELIX 911..913 FT /evidence="ECO:0007829|PDB:8PQD" FT HELIX 917..930 FT /evidence="ECO:0007829|PDB:8PQD" FT TURN 931..933 FT /evidence="ECO:0007829|PDB:1T45" SQ SEQUENCE 976 AA; 109865 MW; 81B0CD76817F3454 CRC64; MRGARGAWDF LCVLLLLLRV QTGSSQPSVS PGEPSPPSIH PGKSDLIVRV GDEIRLLCTD PGFVKWTFEI LDETNENKQN EWITEKAEAT NTGKYTCTNK HGLSNSIYVF VRDPAKLFLV DRSLYGKEDN DTLVRCPLTD PEVTNYSLKG CQGKPLPKDL RFIPDPKAGI MIKSVKRAYH RLCLHCSVDQ EGKSVLSEKF ILKVRPAFKA VPVVSVSKAS YLLREGEEFT VTCTIKDVSS SVYSTWKREN SQTKLQEKYN SWHHGDFNYE RQATLTISSA RVNDSGVFMC YANNTFGSAN VTTTLEVVDK GFINIFPMIN TTVFVNDGEN VDLIVEYEAF PKPEHQQWIY MNRTFTDKWE DYPKSENESN IRYVSELHLT RLKGTEGGTY TFLVSNSDVN AAIAFNVYVN TKPEILTYDR LVNGMLQCVA AGFPEPTIDW YFCPGTEQRC SASVLPVDVQ TLNSSGPPFG KLVVQSSIDS SAFKHNGTVE CKAYNDVGKT SAYFNFAFKG NNKEQIHPHT LFTPLLIGFV IVAGMMCIIV MILTYKYLQK PMYEVQWKVV EEINGNNYVY IDPTQLPYDH KWEFPRNRLS FGKTLGAGAF GKVVEATAYG LIKSDAAMTV AVKMLKPSAH LTEREALMSE LKVLSYLGNH MNIVNLLGAC TIGGPTLVIT EYCCYGDLLN FLRRKRDSFI CSKQEDHAEA ALYKNLLHSK ESSCSDSTNE YMDMKPGVSY VVPTKADKRR SVRIGSYIER DVTPAIMEDD ELALDLEDLL SFSYQVAKGM AFLASKNCIH RDLAARNILL THGRITKICD FGLARDIKND SNYVVKGNAR LPVKWMAPES IFNCVYTFES DVWSYGIFLW ELFSLGSSPY PGMPVDSKFY KMIKEGFRML SPEHAPAEMY DIMKTCWDAD PLKRPTFKQI VQLIEKQISE STNHIYSNLA NCSPNRQKPV VDHSVRINSV GSTASSSQPL LVHDDV //