ABL1_HUMAN
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 03-AUG-2022, entry version 275.
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 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 [59]
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 [60]
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 [61]
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 [62]
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 [63]
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 [64]
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 [65]
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 [66]
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 [67]
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 [68]
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 [69]
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 [70]
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 [71]
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 [72]
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 [73]
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 [74]
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 [75]
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 [76]
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 [77]
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. Phosphorylates multiple
CC receptor tyrosine kinases and more particularly promotes endocytosis of
CC EGFR, facilitates the formation of neuromuscular synapses through MUSK,
CC inhibits PDGFRB-mediated chemotaxis and modulates the endocytosis of
CC activated B-cell receptor complexes. Other substrates which are
CC involved in endocytosis regulation are the caveolin (CAV1) and RIN1.
CC Moreover, ABL1 regulates the CBL family of ubiquitin ligases that drive
CC receptor down-regulation and actin remodeling. Phosphorylation of CBL
CC leads to increased EGFR stability. Involved in late-stage autophagy by
CC regulating positively the trafficking and function of lysosomal
CC components. ABL1 targets to mitochondria in response to oxidative
CC stress and thereby mediates mitochondrial dysfunction and cell death.
CC In response to oxidative stress, phosphorylates serine/threonine kinase
CC PRKD2 at 'Tyr-717' (PubMed:28428613). ABL1 is also translocated in the
CC nucleus where it has DNA-binding activity and is involved in DNA-damage
CC response and apoptosis. Many substrates are known mediators of DNA
CC repair: DDB1, DDB2, ERCC3, ERCC6, RAD9A, RAD51, RAD52 or WRN. Activates
CC the proapoptotic pathway when the DNA damage is too severe to be
CC repaired. Phosphorylates TP73, a primary regulator for this type of
CC damage-induced apoptosis. Phosphorylates the caspase CASP9 on 'Tyr-153'
CC and 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 acts also 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. Phosphorylates TBX21 on
CC 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:28428613,
CC ECO:0000269|PubMed:9037071, ECO:0000269|PubMed:9144171,
CC ECO:0000269|PubMed:9461559}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620, 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, inhibits also 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 acts also 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 {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:23006999,
CC ECO:0000269|PubMed:9144171, ECO:0000269|PubMed:9461559}.
CC -!- INTERACTION:
CC P00519; Q8IZP0: ABI1; NbExp=11; IntAct=EBI-375543, EBI-375446;
CC P00519; Q9NYB9: ABI2; NbExp=2; 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=4; IntAct=EBI-375543, EBI-886;
CC P00519; P46109: CRKL; NbExp=3; 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; 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=8; IntAct=EBI-375543, EBI-2804728;
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=4; IntAct=EBI-375543, EBI-366017;
CC P00519; P31947: SFN; NbExp=2; 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; P15498: VAV1; NbExp=5; IntAct=EBI-375543, EBI-625518;
CC P00519; P61981: YWHAG; NbExp=4; IntAct=EBI-375543, EBI-359832;
CC P00519; P63104: YWHAZ; NbExp=3; 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="http://atlasgeneticsoncology.org/Genes/ABLID1.html";
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/abl1/";
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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_005157.5. [P00519-1]
DR RefSeq; NP_009297.2; NM_007313.2. [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 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 AlphaFoldDB; P00519; -.
DR BMRB; P00519; -.
DR SMR; P00519; -.
DR BioGRID; 106543; 211.
DR CORUM; P00519; -.
DR DIP; DIP-1042N; -.
DR IntAct; P00519; 245.
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; DB06616; Bosutinib.
DR DrugBank; DB12267; Brigatinib.
DR DrugBank; DB01254; Dasatinib.
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; DB12323; Radotinib.
DR DrugBank; DB08896; Regorafenib.
DR DrugBank; DB14989; Umbralisib.
DR DrugBank; DB05184; XL228.
DR DrugCentral; P00519; -.
DR GuidetoPHARMACOLOGY; 1923; -.
DR MoonDB; P00519; Predicted.
DR GlyGen; P00519; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P00519; -.
DR PhosphoSitePlus; P00519; -.
DR BioMuta; ABL1; -.
DR DMDM; 85681908; -.
DR CPTAC; CPTAC-1776; -.
DR CPTAC; CPTAC-1788; -.
DR EPD; P00519; -.
DR jPOST; P00519; -.
DR MassIVE; P00519; -.
DR MaxQB; P00519; -.
DR PaxDb; P00519; -.
DR PeptideAtlas; P00519; -.
DR PRIDE; P00519; -.
DR ProteomicsDB; 51259; -. [P00519-1]
DR ProteomicsDB; 51260; -. [P00519-2]
DR Antibodypedia; 3637; 2229 antibodies from 44 providers.
DR DNASU; 25; -.
DR Ensembl; ENST00000318560.6; ENSP00000323315.5; ENSG00000097007.19. [P00519-1]
DR Ensembl; ENST00000372348.7; ENSP00000361423.2; ENSG00000097007.19. [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 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 neXtProt; NX_P00519; -.
DR OpenTargets; ENSG00000097007; -.
DR Orphanet; 585877; B-lymphoblastic leukemia/lymphoma with recurrent genetic abnormality.
DR Orphanet; 521; Chronic myeloid leukemia.
DR Orphanet; 99861; Precursor T-cell acute lymphoblastic leukemia.
DR PharmGKB; PA24413; -.
DR VEuPathDB; HostDB:ENSG00000097007; -.
DR eggNOG; KOG4278; Eukaryota.
DR GeneTree; ENSGT00940000153838; -.
DR HOGENOM; CLU_002795_0_0_1; -.
DR InParanoid; P00519; -.
DR OMA; CPAFLGK; -.
DR PhylomeDB; P00519; -.
DR TreeFam; TF105081; -.
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 SignaLink; P00519; -.
DR SIGNOR; P00519; -.
DR BioGRID-ORCS; 25; 29 hits in 1117 CRISPR screens.
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 194 other tissues.
DR ExpressionAtlas; P00519; baseline and differential.
DR Genevisible; P00519; HS.
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:0005783; C:endoplasmic reticulum; 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:0098794; C:postsynapse; TAS:ARUK-UCL.
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: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:0008022; F:protein C-terminus binding; IPI: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:0043621; F:protein self-association; IPI:BHF-UCL.
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:0017124; F:SH3 domain binding; IPI:UniProtKB.
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:1990051; P:activation of protein kinase C activity; IDA:ParkinsonsUK-UCL.
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:0098609; P:cell-cell adhesion; IEA:Ensembl.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IDA:UniProtKB.
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; TAS:ParkinsonsUK-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:0072359; P:circulatory system development; 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:0006975; P:DNA damage induced protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0006897; P:endocytosis; IEA:UniProtKB-KW.
DR GO; GO:0043542; P:endothelial cell migration; IMP:BHF-UCL.
DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; IEA:Ensembl.
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:0007249; P:I-kappaB kinase/NF-kappaB signaling; IEA:Ensembl.
DR GO; GO:0007229; P:integrin-mediated signaling pathway; IMP:BHF-UCL.
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: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: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:0043124; P:negative regulation of I-kappaB kinase/NF-kappaB signaling; 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:1900275; P:negative regulation of phospholipase C activity; IMP:MGI.
DR GO; GO:0071901; P:negative regulation of protein serine/threonine kinase activity; IDA:BHF-UCL.
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:0070997; P:neuron death; 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:0038083; P:peptidyl-tyrosine autophosphorylation; IMP:UniProtKB.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:UniProtKB.
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:2000251; P:positive regulation of actin cytoskeleton reorganization; IMP:BHF-UCL.
DR GO; GO:1904531; P:positive regulation of actin filament binding; IMP:UniProtKB.
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: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:1901300; P:positive regulation of hydrogen peroxide-mediated programmed cell death; IEA:Ensembl.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IEA:Ensembl.
DR GO; GO:0032729; P:positive regulation of interferon-gamma production; IEA:Ensembl.
DR GO; GO:0032743; P:positive regulation of interleukin-2 production; IEA:Ensembl.
DR GO; GO:1904528; P:positive regulation of microtubule binding; IMP:UniProtKB.
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: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:0001934; P:positive regulation of protein phosphorylation; IMP:UniProtKB.
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: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:0046777; P:protein autophosphorylation; IDA:ParkinsonsUK-UCL.
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:0006468; P:protein phosphorylation; IMP:BHF-UCL.
DR GO; GO:0032956; P:regulation of actin cytoskeleton organization; IMP:UniProtKB.
DR GO; GO:2000249; P:regulation of actin cytoskeleton reorganization; TAS:UniProtKB.
DR GO; GO:0042981; P:regulation of apoptotic process; IBA:GO_Central.
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: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:2001020; P:regulation of response to DNA damage stimulus; IDA:UniProtKB.
DR GO; GO:0045580; P:regulation of T cell differentiation; ISS:UniProtKB.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; TAS:ProtInc.
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 CDD; cd09935; SH2_ABL; 1.
DR Gene3D; 3.30.505.10; -; 1.
DR IDEAL; IID00645; -.
DR InterPro; IPR033221; ABL1.
DR InterPro; IPR035837; ABL_SH2.
DR InterPro; IPR015015; F-actin-binding.
DR InterPro; IPR011009; Kinase-like_dom_sf.
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:SF162; PTHR24418:SF162; 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; SSF50044; SSF50044; 1.
DR SUPFAM; SSF55550; SSF55550; 1.
DR SUPFAM; SSF56112; SSF56112; 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; Proto-oncogene; Reference proteome; SH2 domain; SH3 domain;
KW Transferase; 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 533..549
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 579..601
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 622..638
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 685..703
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 735..753
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 758..772
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 870..894
FT /note="Basic and acidic residues"
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 /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:3EG3"
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
