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 26-JUN-2013, entry version 192. DE RecName: Full=Tyrosine-protein kinase ABL1; DE EC=2.7.10.2; 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; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM IA), ALTERNATIVE SPLICING, AND RP 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 RT from 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 RT regions 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; RP SER-900 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., RA Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., RA Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., RA Babbage A.K., Babbage S., Bagguley C.L., Bailey J., Banerjee R., RA Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., RA Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., RA Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., RA Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., RA Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., RA Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., RA Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., RA 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., RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., RA Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., RA McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., RA Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., RA Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., RA Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., RA Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., RA Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., RA Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., RA 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., RA Rogers J., 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., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA 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 RT project: 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., RA Dreazen O., 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 RT viral 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 RT variation of codon 837 of c-abl gene."; RL Leukemia 8:343-344(1994). RN [11] RP MYRISTOYLATION (ISOFORM IB). RX PubMed=2542016; 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 RT cdc2 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., RA Kufe D.; RT "Regulation of DNA damage-induced apoptosis by the c-Abl tyrosine RT 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., RA Herschman H., Witte O., Colicelli J.; RT "Protein binding and signaling properties of RIN1 suggest a unique RT effector 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., RA Kharbanda S., Wang R., Sung P., Shinohara A., Weichselbaum R., RA 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., RA Geromanos S., 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, ENZYME 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., RA Travers A.A., 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 RT domain containing 1 (SORBS1) gene: a protein associated with c-Abl RT during insulin 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 RT by 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- RT 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 RT tyrosine 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 RT region protein (Bcr) to induce neurite extension in a Rac- and Cdc42- RT dependent 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 RT sites 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., RA Ward M., 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 RT epithelial-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 RT apoptotic response to DNA damage."; RL J. Biol. Chem. 280:11147-11151(2005). RN [33] RP INTERACTION WITH YWHAB; YWHAE; YWHAG; YWHAH; SFN AND YWHAZ, RP PHOSPHORYLATION AT THR-735, MASS SPECTROMETRY, SUBCELLULAR LOCATION, RP AND 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 RT c-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 MASS RP SPECTROMETRY. 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., RA Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in RT signaling 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 RT nuclear-cytoplasmic localization."; RL EMBO Rep. 7:727-733(2006). RN [36] RP PHOSPHORYLATION, INTERACTION WITH HCK; LYN AND FYN, AND MASS RP 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., RA Wu J., Hochrein J.M., Engen J.R., Smithgall T.E.; RT "Src family kinases phosphorylate the Bcr-Abl SH3-SH2 region and RT modulate 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 RT factor 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., RA Cao C.; RT "Interaction between c-Abl and Arg tyrosine kinases and proteasome RT subunit 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 RT in 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 RP 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 RT differential binding of ABI2 and CRK."; RL Biochemistry 47:1094-1104(2008). RN [42] RP FUNCTION, AND ENZYME 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 RT by 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 RT function 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 RT regulatory 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 MASS SPECTROMETRY. 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 RT the 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 RP SER-917, AND MASS SPECTROMETRY. 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 RT pathogenesis."; RL Trends Biochem. Sci. 33:80-90(2008). RN [48] 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 [49] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-569, AND MASS RP SPECTROMETRY. 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 [50] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-50 AND SER-569, AND MASS RP SPECTROMETRY. 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 [51] 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 RT ruffling of fibroblasts and axonal morphogenesis."; RL Curr. Biol. 20:783-791(2010). RN [52] 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 RT kinase to regulate endothelial barrier function."; RL Mol. Biol. Cell 21:4042-4056(2010). RN [53] 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 [54] 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., RA Buerckstuemmer T., 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 [55] 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: RT Implications for membrane trafficking in the early secretory RT pathway."; RL Biochim. Biophys. Acta 1823:2109-2119(2012). RN [56] 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 RT c-abl."; RL Cell 70:697-704(1992). RN [57] 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 RT heteronuclear NMR spectroscopy in solution."; RL Proc. Natl. Acad. Sci. U.S.A. 89:11673-11677(1992). RN [58] 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 [59] 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 [60] 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 RT high-affinity peptide ligand: implications for SH3-ligand RT interactions."; RL J. Mol. Biol. 281:513-521(1998). RN [61] 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 RT Crk SH2 domain, and a Crk-derived phosphopeptide."; RL Proc. Natl. Acad. Sci. U.S.A. 99:14053-14058(2002). RN [62] RP X-RAY CRYSTALLOGRAPHY (3.42 ANGSTROMS) OF 27-512, MYRISTOYLATION RP (ISOFORM IB), ENZYME REGULATION, AND 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., RA Bornmann W., 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 [63] RP X-RAY CRYSTALLOGRAPHY (1.91 ANGSTROMS) OF 229-513 OF MUTANT PRO-396 IN RP COMPLEX WITH INHIBITOR VX-680, FUNCTION, AND ENZYME 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., RA Lockhart D.J., 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 [64] RP X-RAY CRYSTALLOGRAPHY (2.27 ANGSTROMS) OF 38-512, MASS SPECTROMETRY, RP MYRISTOYLATION OF N-TERMINUS (ISOFORM IB), PHOSPHORYLATION AT SER-50, RP AUTOINHIBITORY MECHANISM, AND ENZYME 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 RT c-Abl tyrosine kinase."; RL Mol. Cell 21:787-798(2006). RN [65] 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., RA Karplus M., 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 [66] RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 229-500 IN COMPLEXES WITH RP IMATINIB AND WITH THE INHIBITORS NVP-AEG082; NVP-AFN941; NVP-AFG210 RP AND PD180970. RX PubMed=17164530; DOI=10.1107/S0907444906047287; RA Cowan-Jacob S.W., Fendrich G., Floersheimer A., Furet P., RA Liebetanz J., Rummel G., Rheinberger P., Centeleghe M., Fabbro D., RA 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 [67] 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 RT determination of the N114A mutant of the SH3 domain of Abl tyrosine RT kinase complexed with a high-affinity peptide ligand."; RL Acta Crystallogr. D 63:646-652(2007). RN [68] 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., RA Luque I.; RT "Role of interfacial water molecules in proline-rich ligand RT recognition by the Src homology 3 domain of Abl."; RL J. Biol. Chem. 285:2823-2833(2010). RN [69] RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 121-232 IN COMPLEX WITH RP ANTIBODY 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., RA Barkinge J., 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 [70] 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., RA Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., RA O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., RA Bhamra G., Buck G., Choudhury B., Clements J., Cole J., Dicks E., RA Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., RA Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., RA Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., RA West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., RA Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., RA DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., RA Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., RA Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.; RT "Patterns of somatic mutation in human cancer genomes."; RL Nature 446:153-158(2007). CC -!- FUNCTION: Non-receptor tyrosine-protein kinase that plays a role CC in 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 CC tyrosine phosphorylation of proteins controlling cytoskeleton CC dynamics like WASF3 (involved in branch formation); ANXA1 CC (involved in membrane anchoring); DBN1, DBNL, CTTN, RAPH1 and ENAH CC (involved in signaling); or MAPT and PXN (microtubule-binding CC proteins). Phosphorylation of WASF3 is critical for the CC stimulation of lamellipodia formation and cell migration. Involved CC in the regulation of cell adhesion and motility through CC phosphorylation of key regulators of these processes such as CC BCAR1, CRK, CRKL, DOK1, EFS or NEDD9. Phosphorylates multiple CC receptor tyrosine kinases and more particularly promotes CC endocytosis of EGFR, facilitates the formation of neuromuscular CC synapses through MUSK, inhibits PDGFRB-mediated chemotaxis and CC modulates the endocytosis of activated B-cell receptor complexes. CC Other substrates which are involved in endocytosis regulation are CC the caveolin (CAV1) and RIN1. Moreover, ABL1 regulates the CBL CC family of ubiquitin ligases that drive receptor down-regulation CC and actin remodeling. Phosphorylation of CBL leads to increased CC EGFR stability. Involved in late-stage autophagy by regulating CC positively the trafficking and function of lysosomal components. CC ABL1 targets to mitochondria in response to oxidative stress and CC thereby mediates mitochondrial dysfunction and cell death. ABL1 is CC also translocated in the nucleus where it has DNA-binding activity CC and is involved in DNA-damage response and apoptosis. Many CC substrates are known mediators of DNA repair: DDB1, DDB2, ERCC3, CC ERCC6, RAD9A, RAD51, RAD52 or WRN. Activates the proapoptotic CC 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' CC and regulates its processing in the apoptotic response to DNA CC damage. Phosphorylates PSMA7 that leads to an inhibition of CC proteasomal activity and cell cycle transition blocks. ABL1 acts CC also as a regulator of multiple pathological signaling cascades CC during infection. Several known tyrosine-phosphorylated microbial CC proteins have been identified as ABL1 substrates. This is the case CC of A36R of Vaccinia virus, Tir (translocated intimin receptor) of CC pathogenic E.coli and possibly Citrobacter, CagA (cytotoxin- CC associated gene A) of H.pylori, or AnkA (ankyrin repeat-containing CC protein A) of A.phagocytophilum. Pathogens can highjack ABL1 CC kinase signaling to reorganize the host actin cytoskeleton for CC multiple purposes, like facilitating intracellular movement and CC host cell exit. Finally, functions as its own regulator through CC autocatalytic activity as well as through phosphorylation of its CC inhibitor, ABI1. CC -!- CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a CC [protein]-L-tyrosine phosphate. CC -!- COFACTOR: Magnesium or manganese. CC -!- ENZYME REGULATION: Stabilized in the inactive form by an CC association between the SH3 domain and the SH2-TK linker region, CC interactions of the N-terminal cap, and contributions from an N- CC terminal myristoyl group and phospholipids. Activated by CC autophosphorylation as well as by SRC-family kinase-mediated CC phosphorylation. Activated by RIN1 binding to the SH2 and SH3 CC domains. Also stimulated by cell death inducers and DNA-damage. CC Phosphatidylinositol 4,5-bisphosphate (PIP2), a highly abundant CC phosphoinositide known to regulate cytoskeletal and membrane CC proteins, inhibits also the tyrosine kinase activity (By CC similarity). 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 CC chronic myeloid leukemia (CML), and by VX-680, an inhibitor that CC acts also on imatinib-resistant mutants. CC -!- SUBUNIT: Interacts with SORBS1 following insulin stimulation. CC Found in a trimolecular complex containing CDK5 and CABLES1. CC Interacts with CABLES1 and PSTPIP1. Interacts with ZDHHC16, ITGB1 CC and HCK (By similarity). Interacts with STX17; probably CC phosphorylates STX17. Interacts with INPPL1/SHIP2. Interacts with CC the 14-3-3 proteins, YWHAB, YWHAE, YWHAG, YWHAH, SFN AND YWHAZ; CC the interaction with 14-3-3 proteins requires phosphorylation on CC Thr-735 and, sequesters ABL1 into the cytoplasm. Interacts with CC ABI1, ABI2, BCR, CRK, FGR, FYN, HCK, LYN, PSMA7 RAD9A, RAD51, CC RAD52, TP73 and WASF3. A complex made of ABL1, CTTN and MYLK CC regulates cortical actin-based cytoskeletal rearrangement critical CC to sphingosine 1-phosphate (S1P)-mediated endothelial cell (EC) CC 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. CC -!- INTERACTION: CC Q8IZP0:ABI1; NbExp=3; IntAct=EBI-375543, EBI-375446; CC Q14315:FLNC; NbExp=2; IntAct=EBI-375543, EBI-489954; CC Q92918:MAP4K1; NbExp=2; IntAct=EBI-375543, EBI-881; CC P16333:NCK1; NbExp=2; IntAct=EBI-375543, EBI-389883; CC O43900:PRICKLE3; NbExp=2; IntAct=EBI-375543, EBI-1751761; CC Q86UR5:RIMS1; NbExp=2; IntAct=EBI-375543, EBI-1043236; CC Q13671:RIN1; NbExp=4; IntAct=EBI-375543, EBI-366017; CC P31947:SFN; NbExp=2; IntAct=EBI-375543, EBI-476295; CC O75751:SLC22A3; NbExp=2; IntAct=EBI-375543, EBI-1752674; CC Q9BX66:SORBS1; NbExp=2; IntAct=EBI-375543, EBI-433642; CC Q07890:SOS2; NbExp=2; IntAct=EBI-375543, EBI-298181; CC P63104:YWHAZ; NbExp=2; IntAct=EBI-375543, EBI-347088; CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton. Nucleus. CC Mitochondrion (By similarity). Note=Shuttles between the nucleus CC and cytoplasm depending on environmental signals. Sequestered into CC the cytoplasm through interaction with 14-3-3 proteins. Localizes CC to mitochondria in response to oxidative stress (By similarity). 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 Note=Contains a N-myristoyl glycine at position 2; CC -!- TISSUE SPECIFICITY: Widely expressed. CC -!- PTM: Acetylated at Lys-711 by EP300 which promotes the cytoplasmic CC translocation. CC -!- PTM: Phosphorylation at Tyr-70 by members of the SRC family of CC kinases disrupts SH3 domain-based autoinhibitory interactions and CC intermolecular associations, such as that with ABI1, and also CC enhances kinase activity. Phosphorylation at Tyr-226 and Tyr-393 CC correlate with increased activity. DNA damage-induced activation CC of ABL1 requires the function of ATM and Ser-446 phosphorylation CC (By similarity). Phosphorylation at Ser-569 has been attributed to CC a CDC2-associated kinase and is coupled to cell division (By CC similarity). Phosphorylation at Ser-618 and Ser-619 by PAK2 CC increases binding to CRK and reduces binding to ABI1. CC Phosphorylation on Thr-735 is required for binding 14-3-3 proteins CC for cytoplasmic translocation. Phosphorylated by PRKDC (By CC similarity). CC -!- PTM: Polyubiquitinated. Polyubiquitination of ABL1 leads to CC degradation. CC -!- PTM: Isoform IB is myristoylated on Gly-2. CC -!- DISEASE: Note=A chromosomal aberration involving ABL1 is a cause CC of chronic myeloid leukemia. Translocation t(9;22)(q34;q11) with CC BCR. The translocation produces a BCR-ABL found also in acute CC myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein CC kinase family. ABL subfamily. CC -!- SIMILARITY: Contains 1 protein kinase domain. CC -!- SIMILARITY: Contains 1 SH2 domain. CC -!- SIMILARITY: Contains 1 SH3 domain. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology CC and Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/ABL.html"; CC -!- WEB RESOURCE: Name=CGP resequencing studies; CC URL="http://www.sanger.ac.uk/perl/genetics/CGP/cgp_viewer?action=gene&ln=ABL1"; CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/abl1/"; CC -!- WEB RESOURCE: Name=Wikipedia; Note=Abl entry; CC URL="http://en.wikipedia.org/wiki/Abl_gene"; 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; CAM45752.1; -; Genomic_DNA. DR EMBL; AL161733; CAM45752.1; JOINED; Genomic_DNA. DR EMBL; AL161733; CAM45754.1; -; Genomic_DNA. DR EMBL; AL161733; CAM45756.1; -; Genomic_DNA. DR EMBL; AL359092; CAM45756.1; JOINED; Genomic_DNA. DR EMBL; CH471090; EAW87948.1; -; Genomic_DNA. DR EMBL; BC117451; AAI17452.1; -; mRNA. DR EMBL; S69223; AAD14034.1; -; Genomic_DNA. DR IPI; IPI00216969; -. DR IPI; IPI00221171; -. DR PIR; S08519; TVHUA. DR RefSeq; NP_005148.2; NM_005157.4. DR RefSeq; NP_009297.2; NM_007313.2. DR UniGene; Hs.431048; -. DR PDB; 1AB2; NMR; -; A=120-220. DR PDB; 1ABL; Model; -; A=65-121. 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=62-121. 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 PDBsum; 1AB2; -. DR PDBsum; 1ABL; -. 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 ProteinModelPortal; P00519; -. DR DIP; DIP-1042N; -. DR IntAct; P00519; 160. DR MINT; MINT-7236141; -. DR STRING; 9606.ENSP00000361423; -. DR PhosphoSite; P00519; -. DR DMDM; 85681908; -. DR PaxDb; P00519; -. DR PRIDE; P00519; -. DR DNASU; 25; -. DR Ensembl; ENST00000318560; ENSP00000323315; ENSG00000097007. DR Ensembl; ENST00000372348; ENSP00000361423; ENSG00000097007. DR GeneID; 25; -. DR KEGG; hsa:25; -. DR UCSC; uc004bzv.3; human. DR UCSC; uc004bzw.3; human. DR CTD; 25; -. DR GeneCards; GC09P133589; -. DR HGNC; HGNC:76; ABL1. DR HPA; CAB002686; -. DR HPA; HPA027251; -. DR HPA; HPA027280; -. DR HPA; HPA028409; -. DR MIM; 189980; gene. DR MIM; 608232; phenotype. DR neXtProt; NX_P00519; -. DR Orphanet; 521; Chronic myeloid leukemia. DR Orphanet; 99860; Precursor B-cell acute lymphoblastic leukemia. DR Orphanet; 99861; Precursor T-cell acute lymphoblastic leukemia. DR PharmGKB; PA24413; -. DR eggNOG; COG0515; -. DR HOVERGEN; HBG004162; -. DR KO; K06619; -. DR OMA; GAFRESG; -. DR BRENDA; 2.7.10.2; 2681. DR Pathway_Interaction_DB; lis1pathway; Lissencephaly gene (LIS1) in neuronal migration and development. DR Pathway_Interaction_DB; trkrpathway; Neurotrophic factor-mediated Trk receptor signaling. DR Pathway_Interaction_DB; pdgfrbpathway; PDGFR-beta signaling pathway. DR Pathway_Interaction_DB; telomerasepathway; Regulation of Telomerase. DR Reactome; REACT_111045; Developmental Biology. DR Reactome; REACT_604; Hemostasis. DR SignaLink; P00519; -. DR BindingDB; P00519; -. DR ChEMBL; CHEMBL1862; -. DR ChiTaRS; ABL1; human. DR DrugBank; DB00171; Adenosine triphosphate. DR DrugBank; DB01254; Dasatinib. DR DrugBank; DB00619; Imatinib. DR EvolutionaryTrace; P00519; -. DR GenomeRNAi; 25; -. DR NextBio; 79; -. DR PMAP-CutDB; P00519; -. DR ArrayExpress; P00519; -. DR Bgee; P00519; -. DR CleanEx; HS_ABL1; -. DR Genevestigator; P00519; -. DR GermOnline; ENSG00000097007; Homo sapiens. DR GO; GO:0015629; C:actin cytoskeleton; TAS:UniProtKB. DR GO; GO:0031252; C:cell leading edge; IEA:Compara. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell. DR GO; GO:0031965; C:nuclear membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005730; C:nucleolus; IDA:MGI. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB. DR GO; GO:0003785; F:actin monomer binding; TAS:UniProtKB. DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB. DR GO; GO:0003677; F:DNA binding; NAS:UniProtKB. DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB. DR GO; GO:0030145; F:manganese ion binding; IDA:UniProtKB. 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:0070064; F:proline-rich region binding; IDA:UniProtKB. DR GO; GO:0030036; P:actin cytoskeleton organization; ISS:UniProtKB. DR GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW. DR GO; GO:0007411; P:axon guidance; TAS:Reactome. DR GO; GO:0007596; P:blood coagulation; TAS:Reactome. DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW. DR GO; GO:0006975; P:DNA damage induced protein phosphorylation; IDA:UniProtKB. DR GO; GO:0038096; P:Fc-gamma receptor signaling pathway involved in phagocytosis; TAS:Reactome. DR GO; GO:0045087; P:innate immune response; TAS:Reactome. DR GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; TAS:UniProtKB. DR GO; GO:0006298; P:mismatch repair; TAS:ProtInc. DR GO; GO:0042692; P:muscle cell differentiation; TAS:Reactome. DR GO; GO:0071901; P:negative regulation of protein serine/threonine kinase activity; IDA:BHF-UCL. DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:UniProtKB. DR GO; GO:0048008; P:platelet-derived growth factor receptor signaling pathway; IEA:Compara. DR GO; GO:0043065; P:positive regulation of apoptotic process; IDA:UniProtKB. DR GO; GO:0051149; P:positive regulation of muscle cell differentiation; TAS:Reactome. DR GO; GO:0051353; P:positive regulation of oxidoreductase activity; IDA:BHF-UCL. DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IDA:UniProtKB. DR GO; GO:2000249; P:regulation of actin cytoskeleton reorganization; TAS:UniProtKB. DR GO; GO:0010506; P:regulation of autophagy; TAS:UniProtKB. DR GO; GO:0030155; P:regulation of cell adhesion; TAS:UniProtKB. DR GO; GO:0051726; P:regulation of cell cycle; IEA:Compara. DR GO; GO:2000145; P:regulation of cell motility; TAS:UniProtKB. DR GO; GO:0030100; P:regulation of endocytosis; TAS:UniProtKB. DR GO; GO:2001020; P:regulation of response to DNA damage stimulus; IDA:UniProtKB. DR GO; GO:0000115; P:regulation of transcription involved in S phase of mitotic cell cycle; TAS:ProtInc. DR GO; GO:0042770; P:signal transduction in response to DNA damage; IDA:UniProtKB. DR Gene3D; 3.30.505.10; -; 1. DR InterPro; IPR015015; F-actin_binding. DR InterPro; IPR011009; Kinase-like_dom. DR InterPro; IPR000719; Prot_kinase_cat_dom. DR InterPro; IPR017441; Protein_kinase_ATP_BS. DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom. DR InterPro; IPR000980; SH2. DR InterPro; IPR001452; SH3_domain. DR InterPro; IPR008266; Tyr_kinase_AS. DR InterPro; IPR020635; Tyr_kinase_cat_dom. DR Pfam; PF08919; F_actin_bind; 1. DR Pfam; PF07714; Pkinase_Tyr; 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; Kinase_like; 1. DR SUPFAM; SSF50044; SH3; 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; KW ATP-binding; Autophagy; Cell adhesion; Chromosomal rearrangement; KW Complete proteome; Cytoplasm; Cytoskeleton; DNA damage; DNA repair; KW DNA-binding; Endocytosis; Kinase; Lipoprotein; Magnesium; Manganese; KW Membrane; Metal-binding; Mitochondrion; Myristate; Nucleotide-binding; KW Nucleus; Phosphoprotein; Polymorphism; Proto-oncogene; KW Reference proteome; SH2 domain; SH3 domain; Transferase; KW Tyrosine-protein kinase; Ubl conjugation. FT CHAIN 1 1130 Tyrosine-protein kinase ABL1. FT /FTId=PRO_0000088050. FT DOMAIN 61 121 SH3. FT DOMAIN 127 217 SH2. FT DOMAIN 242 493 Protein kinase. FT NP_BIND 248 256 ATP. FT NP_BIND 316 322 ATP. FT REGION 1 60 CAP. FT REGION 869 968 DNA-binding (By similarity). FT REGION 953 1130 F-actin-binding. FT MOTIF 381 405 Kinase activation loop. FT MOTIF 605 609 Nuclear localization signal 1 FT (Potential). FT MOTIF 709 715 Nuclear localization signal 2 FT (Potential). FT MOTIF 762 769 Nuclear localization signal 3 FT (Potential). FT MOTIF 1090 1100 Nuclear export signal (By similarity). FT COMPBIAS 18 22 Poly-Ser. FT COMPBIAS 605 609 Poly-Lys. FT COMPBIAS 782 1019 Pro-rich. FT COMPBIAS 897 903 Poly-Pro. FT ACT_SITE 363 363 Proton acceptor (By similarity). FT BINDING 271 271 ATP. FT SITE 26 27 Breakpoint for translocation to form BCR- FT ABL oncogene. FT MOD_RES 50 50 Phosphoserine. FT MOD_RES 70 70 Phosphotyrosine; by autocatalysis. FT MOD_RES 185 185 Phosphotyrosine. FT MOD_RES 226 226 Phosphotyrosine; by autocatalysis. FT MOD_RES 253 253 Phosphotyrosine. FT MOD_RES 257 257 Phosphotyrosine. FT MOD_RES 264 264 Phosphotyrosine. FT MOD_RES 392 392 Phosphothreonine. FT MOD_RES 393 393 Phosphotyrosine; by autocatalysis and FT SRC-type Tyr-kinases. FT MOD_RES 394 394 Phosphothreonine. FT MOD_RES 446 446 Phosphoserine (By similarity). FT MOD_RES 469 469 Phosphotyrosine. FT MOD_RES 569 569 Phosphoserine. FT MOD_RES 613 613 Phosphothreonine. FT MOD_RES 618 618 Phosphoserine; by PAK2. FT MOD_RES 619 619 Phosphoserine; by PAK2. FT MOD_RES 620 620 Phosphoserine. FT MOD_RES 659 659 Phosphoserine. FT MOD_RES 683 683 Phosphoserine. FT MOD_RES 711 711 N6-acetyllysine; by EP300. FT MOD_RES 718 718 Phosphoserine. FT MOD_RES 735 735 Phosphothreonine. FT MOD_RES 781 781 Phosphothreonine. FT MOD_RES 805 805 Phosphoserine. FT MOD_RES 809 809 Phosphoserine. FT MOD_RES 814 814 Phosphothreonine. FT MOD_RES 844 844 Phosphothreonine. FT MOD_RES 852 852 Phosphothreonine. FT MOD_RES 855 855 Phosphoserine. FT MOD_RES 917 917 Phosphoserine. FT MOD_RES 919 919 Phosphoserine. FT MOD_RES 936 936 Phosphoserine. FT MOD_RES 949 949 Phosphoserine. FT MOD_RES 977 977 Phosphoserine. FT VAR_SEQ 1 26 MLEICLKLVGCKSKKGLSSSSSCYLE -> MGQQPGKVLGD FT QRRPSLPALHFIKGAGKKESSRHGGPHCNVFVEH (in FT isoform IB). FT /FTId=VSP_004957. FT VARIANT 47 47 R -> G (in a lung large cell carcinoma FT sample; somatic mutation). FT /FTId=VAR_032676. FT VARIANT 140 140 L -> P (in dbSNP:rs1064152). FT /FTId=VAR_051692. FT VARIANT 166 166 R -> K (in a melanoma sample; somatic FT mutation). FT /FTId=VAR_032677. FT VARIANT 247 247 K -> R (in dbSNP:rs34549764). FT /FTId=VAR_051693. FT VARIANT 706 706 G -> V (in dbSNP:rs34634745). FT /FTId=VAR_025043. FT VARIANT 810 810 P -> L (in dbSNP:rs2229071). FT /FTId=VAR_032678. FT VARIANT 852 852 T -> P. FT /FTId=VAR_025044. FT VARIANT 900 900 P -> S (in dbSNP:rs35266696). FT /FTId=VAR_025045. FT VARIANT 968 968 S -> P (in dbSNP:rs1064165). FT /FTId=VAR_051694. FT VARIANT 972 972 S -> L (in dbSNP:rs2229067). FT /FTId=VAR_025046. FT MUTAGEN 735 735 T->A: Abolishes phosphorylation. Loss of FT binding YWHAS and YWHAZ. Localizes to the FT nucleus. No effect on kinase activity. FT CONFLICT 159 159 G -> S (in Ref. 1; AAA51561). FT CONFLICT 424 425 AF -> GK (in Ref. 9). FT CONFLICT 445 445 L -> R (in Ref. 1; AAA51561). FT CONFLICT 459 459 E -> K (in Ref. 1; AAA51561). FT CONFLICT 520 520 S -> T (in Ref. 1; AAA51561). FT CONFLICT 719 719 A -> V (in Ref. 1; AAA51561). FT CONFLICT 837 837 G -> E (in Ref. 2; CAA34438). FT CONFLICT 837 837 G -> W (in Ref. 1; AAA51561). FT CONFLICT 863 863 G -> R (in Ref. 1; AAA51561). FT CONFLICT 894 894 R -> K (in Ref. 1; AAA51561). FT CONFLICT 917 919 SPS -> RPG (in Ref. 1; AAA51561). FT CONFLICT 952 952 G -> A (in Ref. 1; AAA51561). FT CONFLICT 967 968 QS -> HP (in Ref. 1; AAA51561). FT CONFLICT 982 982 P -> PL (in Ref. 1; AAA51561). FT CONFLICT 1022 1022 Missing (in Ref. 1; AAA51561). FT CONFLICT 1045 1045 R -> G (in Ref. 1; AAA51561). FT CONFLICT 1103 1103 T -> S (in Ref. 1; AAA51561). FT HELIX 49 53 FT HELIX 58 60 FT STRAND 65 70 FT STRAND 76 79 FT STRAND 87 93 FT STRAND 97 104 FT STRAND 107 112 FT HELIX 113 115 FT STRAND 116 119 FT HELIX 122 124 FT STRAND 128 131 FT HELIX 134 140 FT TURN 141 143 FT STRAND 148 153 FT STRAND 155 157 FT STRAND 161 167 FT STRAND 170 178 FT STRAND 180 182 FT STRAND 184 187 FT STRAND 192 194 FT HELIX 195 204 FT STRAND 209 211 FT STRAND 226 228 FT STRAND 229 231 FT TURN 233 235 FT HELIX 239 241 FT STRAND 242 248 FT HELIX 249 251 FT STRAND 254 261 FT HELIX 262 264 FT STRAND 266 272 FT STRAND 275 278 FT HELIX 280 290 FT STRAND 301 305 FT STRAND 307 310 FT STRAND 312 316 FT STRAND 319 322 FT HELIX 323 329 FT TURN 332 334 FT HELIX 337 356 FT STRAND 359 361 FT HELIX 366 368 FT STRAND 369 371 FT HELIX 373 375 FT STRAND 377 379 FT HELIX 381 383 FT HELIX 384 387 FT HELIX 390 392 FT STRAND 395 401 FT HELIX 403 405 FT HELIX 408 413 FT HELIX 418 433 FT HELIX 445 447 FT HELIX 448 453 FT HELIX 466 475 FT HELIX 480 482 FT HELIX 486 499 FT TURN 510 512 FT HELIX 1029 1045 FT TURN 1046 1048 FT HELIX 1053 1070 FT HELIX 1071 1073 FT HELIX 1080 1097 FT STRAND 1101 1104 FT STRAND 1106 1108 FT HELIX 1115 1128 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 //