ID ABL2_HUMAN Reviewed; 1182 AA. AC P42684; A0M8X0; B7UEF2; B7UEF3; B7UEF4; B7UEF5; Q5T0X6; Q5W0C5; Q6NZY6; AC Q7Z301; DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1995, sequence version 1. DT 27-MAR-2024, entry version 242. DE RecName: Full=Tyrosine-protein kinase ABL2; DE EC=2.7.10.2; DE AltName: Full=Abelson murine leukemia viral oncogene homolog 2; DE AltName: Full=Abelson tyrosine-protein kinase 2; DE AltName: Full=Abelson-related gene protein; DE AltName: Full=Tyrosine-protein kinase ARG; GN Name=ABL2; Synonyms=ABLL, ARG; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND ALTERNATIVE SPLICING (ISOFORM RP 2). RX PubMed=2198571; DOI=10.1073/pnas.87.15.5802; RA Kruh G.D., Perego R., Miki T., Aaronson S.A.; RT "The complete coding sequence of arg defines the Abelson subfamily of RT cytoplasmic tyrosine kinases."; RL Proc. Natl. Acad. Sci. U.S.A. 87:5802-5806(1990). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 4; 5; 6 AND 7), ALTERNATIVE SPLICING RP (ISOFORM 10), AND VARIANT THR-12 (ISOFORM 4). RX PubMed=18810762; DOI=10.1002/jcb.21922; RA Bianchi C., Torsello B., Angeloni V., Bombelli S., Soldi M., Invernizzi L., RA Brambilla P., Perego R.A.; RT "Eight full-length abelson related gene (Arg) isoforms are constitutively RT expressed in caki-1 cell line and cell distribution of two isoforms has RT been analyzed after transfection."; RL J. Cell. Biochem. 105:1219-1227(2008). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 8). RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4). RC TISSUE=Uterine endothelium; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ARG-930; MET-946; ARG-996; RP ASN-1085 AND ALA-1101. RG NIEHS SNPs program; RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [7] 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 [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RC TISSUE=Brain; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [9] RP NUCLEOTIDE SEQUENCE [MRNA] OF 343-469. RX PubMed=3787260; DOI=10.1126/science.3787260; RA Kruh G.D., King C.R., Kraus M.H., Popescu N.C., Amsbaugh S.C., RA McBride W.O., Aaronson S.A.; RT "A novel human gene closely related to the abl proto-oncogene."; RL Science 234:1545-1548(1986). RN [10] RP PHOSPHORYLATION AT TYR-272; TYR-439; TYR-568 AND TYR-683, AND ACTIVITY RP REGULATION. RX PubMed=12748290; DOI=10.1128/mcb.23.11.3884-3896.2003; RA Tanis K.Q., Veach D., Duewel H.S., Bornmann W.G., Koleske A.J.; RT "Two distinct phosphorylation pathways have additive effects on Abl family RT kinase activation."; RL Mol. Cell. Biol. 23:3884-3896(2003). RN [11] RP INTERACTION WITH RIN1, FUNCTION, AND ACTIVITY REGULATION. 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 [12] RP FUNCTION, PHOSPHORYLATION AT TYR-261, AND UBIQUITINATION. RX PubMed=15735735; DOI=10.1038/sj.onc.1208454; RA Cao C., Li Y., Leng Y., Li P., Ma Q., Kufe D.; RT "Ubiquitination and degradation of the Arg tyrosine kinase is regulated by RT oxidative stress."; RL Oncogene 24:2433-2440(2005). RN [13] 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 [14] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=16964243; DOI=10.1038/nbt1240; RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.; RT "A probability-based approach for high-throughput protein phosphorylation RT analysis and site localization."; RL Nat. Biotechnol. 24:1285-1292(2006). RN [15] 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 [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-817, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic kidney; RX PubMed=17525332; DOI=10.1126/science.1140321; RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., RA Gygi S.P., Elledge S.J.; RT "ATM and ATR substrate analysis reveals extensive protein networks RT responsive to DNA damage."; RL Science 316:1160-1166(2007). RN [17] 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 [18] 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 [19] RP REVIEW ON FUNCTION. RX PubMed=14729179; DOI=10.1016/j.tcb.2003.11.003; RA Hernandez S.E., Krishnaswami M., Miller A.L., Koleske A.J.; RT "How do Abl family kinases regulate cell shape and movement?"; RL Trends Cell Biol. 14:36-44(2004). RN [20] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-275 AND SER-915, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the RT kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [21] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-620; SER-631; SER-633; RP SER-655; SER-817; SER-820 AND SER-936, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [22] 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 [23] 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 [24] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-718, PHOSPHORYLATION [LARGE RP SCALE ANALYSIS] AT TYR-668 (ISOFORM 10), PHOSPHORYLATION [LARGE SCALE RP ANALYSIS] AT TYR-647 (ISOFORM 4), PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT RP TYR-683 (ISOFORM 5), PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-662 RP (ISOFORM 7), AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP 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 [25] RP IDENTIFICATION IN A COMPLEX WITH UNC119: ABL1 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 [26] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-820 AND SER-936, 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 [27] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-631 AND SER-936, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [28] 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 [29] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-631, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [30] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-620; SER-631; SER-655; RP SER-671; SER-783; SER-817; SER-820 AND SER-936, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [31] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-620 AND SER-631, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [32] RP STRUCTURE BY NMR OF 163-268. RG RIKEN structural genomics initiative (RSGI); RT "Solution structure of the human ABL2 SH2 domain."; RL Submitted (FEB-2008) to the PDB data bank. RN [33] RP X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 279-546 IN COMPLEXES WITH RP INHIBITORS. RX PubMed=21417343; DOI=10.1021/jm101506n; RA Salah E., Ugochukwu E., Barr A.J., von Delft F., Knapp S., Elkins J.M.; RT "Crystal structures of ABL-related gene (ABL2) in complex with imatinib, RT tozasertib (VX-680), and a type I inhibitor of the triazole carbothioamide RT class."; RL J. Med. Chem. 54:2359-2367(2011). RN [34] RP X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 563-579 IN COMPLEX WITH CTTN, AND RP INTERACTION WITH CTTN. RX PubMed=22297987; DOI=10.1107/s1744309111056132; RA Liu W., MacGrath S.M., Koleske A.J., Boggon T.J.; RT "Lysozyme contamination facilitates crystallization of a heterotrimeric RT cortactin-Arg-lysozyme complex."; RL Acta Crystallogr. F 68:154-158(2012). RN [35] RP VARIANTS [LARGE SCALE ANALYSIS] HIS-78; GLN-99; ILE-519; SER-769; ARG-930 RP AND ARG-996, AND VARIANT [LARGE SCALE ANALYSIS] THR-12 (ISOFORM 4). RX PubMed=17344846; DOI=10.1038/nature05610; RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G., RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., RA Futreal P.A., Stratton M.R.; RT "Patterns of somatic mutation in human cancer genomes."; RL Nature 446:153-158(2007). CC -!- FUNCTION: Non-receptor tyrosine-protein kinase that plays an ABL1- CC overlapping role in key processes linked to cell growth and survival CC such as cytoskeleton remodeling in response to extracellular stimuli, CC cell motility and adhesion and receptor endocytosis. Coordinates actin CC remodeling through tyrosine phosphorylation of proteins controlling CC cytoskeleton dynamics like MYH10 (involved in movement); CTTN (involved CC in signaling); or TUBA1 and TUBB (microtubule subunits). Binds directly CC F-actin and regulates actin cytoskeletal structure through its F-actin- CC bundling activity. Involved in the regulation of cell adhesion and CC motility through phosphorylation of key regulators of these processes CC such as CRK, CRKL, DOK1 or ARHGAP35. Adhesion-dependent phosphorylation CC of ARHGAP35 promotes its association with RASA1, resulting in CC recruitment of ARHGAP35 to the cell periphery where it inhibits RHO. CC Phosphorylates multiple receptor tyrosine kinases like PDGFRB and other CC substrates which are involved in endocytosis regulation such as RIN1. CC In brain, may regulate neurotransmission by phosphorylating proteins at CC the synapse. ABL2 acts also as a regulator of multiple pathological CC signaling cascades during infection. Pathogens can highjack ABL2 kinase CC signaling to reorganize the host actin cytoskeleton for multiple CC purposes, like facilitating intracellular movement and host cell exit. CC Finally, functions as its own regulator through autocatalytic activity CC as well as through phosphorylation of its inhibitor, ABI1. Positively CC regulates chemokine-mediated T-cell migration, polarization, and homing CC to lymph nodes and immune-challenged tissues, potentially via CC activation of NEDD9/HEF1 and RAP1 (By similarity). CC {ECO:0000250|UniProtKB:Q4JIM5, ECO:0000269|PubMed:15735735, CC ECO:0000269|PubMed:15886098, ECO:0000269|PubMed:16678104, CC ECO:0000269|PubMed:17306540, ECO:0000269|PubMed:18945674}. 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 -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; 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. Inhibited by imatinib mesylate (Gleevec) CC which is used for the treatment of chronic myeloid leukemia (CML). CC Phosphatidylinositol 4,5-bisphosphate (PIP2), a highly abundant CC phosphoinositide known to regulate cytoskeletal and membrane proteins, CC inhibits the tyrosine kinase activity (By similarity). {ECO:0000250}. CC -!- SUBUNIT: Interacts with PSMA7. Interacts with CTTN. Found in a complex CC with ABL1, ABL2, CRK and UNC119; leading to the inhibition of CRK CC phosphorylation by ABL kinases. {ECO:0000269|PubMed:15886098, CC ECO:0000269|PubMed:16678104, ECO:0000269|PubMed:19381274, CC ECO:0000269|PubMed:22297987}. CC -!- INTERACTION: CC P42684; Q8IZP0: ABI1; NbExp=2; IntAct=EBI-1102694, EBI-375446; CC P42684; P46108: CRK; NbExp=5; IntAct=EBI-1102694, EBI-886; CC P42684; P00533: EGFR; NbExp=9; IntAct=EBI-1102694, EBI-297353; CC P42684; P04626: ERBB2; NbExp=6; IntAct=EBI-1102694, EBI-641062; CC P42684; P21860: ERBB3; NbExp=10; IntAct=EBI-1102694, EBI-720706; CC P42684; Q15303: ERBB4; NbExp=4; IntAct=EBI-1102694, EBI-80371; CC P42684; P36888: FLT3; NbExp=3; IntAct=EBI-1102694, EBI-3946257; CC P42684; P06241: FYN; NbExp=2; IntAct=EBI-1102694, EBI-515315; CC P42684; P62993: GRB2; NbExp=2; IntAct=EBI-1102694, EBI-401755; CC P42684; P10721: KIT; NbExp=2; IntAct=EBI-1102694, EBI-1379503; CC P42684; P16333: NCK1; NbExp=4; IntAct=EBI-1102694, EBI-389883; CC P42684; P27986: PIK3R1; NbExp=2; IntAct=EBI-1102694, EBI-79464; CC P42684; P19174: PLCG1; NbExp=4; IntAct=EBI-1102694, EBI-79387; CC P42684; Q13671: RIN1; NbExp=5; IntAct=EBI-1102694, EBI-366017; CC P42684; Q15637: SF1; NbExp=3; IntAct=EBI-1102694, EBI-744603; CC P42684; P12931: SRC; NbExp=2; IntAct=EBI-1102694, EBI-621482; CC P42684-3; Q9NYB9-2: ABI2; NbExp=3; IntAct=EBI-10693977, EBI-11096309; CC P42684-3; Q15642-2: TRIP10; NbExp=3; IntAct=EBI-10693977, EBI-6550597; CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton CC {ECO:0000250|UniProtKB:Q4JIM5}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=9; CC Name=1; Synonyms=IB, 1BLCTL; CC IsoId=P42684-1; Sequence=Displayed; CC Name=2; Synonyms=IA, 1ASCTL; CC IsoId=P42684-2; Sequence=VSP_004961; CC Name=3; Synonyms=IC, 1ALCTL; CC IsoId=P42684-3; Sequence=VSP_017112; CC Name=4; Synonyms=1ASCTS; CC IsoId=P42684-4; Sequence=VSP_004961, VSP_021308; CC Name=5; Synonyms=1BLCTS; CC IsoId=P42684-5; Sequence=VSP_021308; CC Name=6; Synonyms=1BSCTL; CC IsoId=P42684-6; Sequence=VSP_041772; CC Name=7; Synonyms=1BSCTS; CC IsoId=P42684-7; Sequence=VSP_041772, VSP_021308; CC Name=10; Synonyms=1ALCTS; CC IsoId=P42684-10; Sequence=VSP_017112, VSP_021308; CC Name=8; CC IsoId=P42684-8; Sequence=VSP_041772, VSP_041773, VSP_041774; CC -!- TISSUE SPECIFICITY: Widely expressed. CC -!- DOMAIN: Contains two distinct classes of F-actin-binding domains. CC Although both can bind F-actin, the 2 are required to bundle actin CC filaments (By similarity). {ECO:0000250}. CC -!- PTM: Phosphorylated at Tyr-261 by ABL1 in response to oxidative stress. CC Phosphorylated by PDGFRB (By similarity). {ECO:0000250}. CC -!- PTM: Polyubiquitinated. Polyubiquitination of ABL2 leads to CC degradation. {ECO:0000269|PubMed:15735735}. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein CC kinase family. ABL subfamily. {ECO:0000255|PROSITE-ProRule:PRU00159}. CC -!- SEQUENCE CAUTION: CC Sequence=CAD98092.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/226/ABL2"; CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/abl2/"; 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; M35296; AAA35553.1; -; mRNA. DR EMBL; FJ542283; ACK76601.1; -; mRNA. DR EMBL; FJ542284; ACK76602.1; -; mRNA. DR EMBL; FJ542285; ACK76603.1; -; mRNA. DR EMBL; FJ542286; ACK76604.1; -; mRNA. DR EMBL; AK311045; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; BX538317; CAD98092.1; ALT_INIT; mRNA. DR EMBL; DQ009672; AAY16984.1; -; Genomic_DNA. DR EMBL; AL139132; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL359179; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL512326; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471067; EAW91040.1; -; Genomic_DNA. DR EMBL; BC065912; AAH65912.1; -; mRNA. DR CCDS; CCDS30947.1; -. [P42684-1] DR CCDS; CCDS41441.2; -. [P42684-3] DR CCDS; CCDS44282.1; -. [P42684-10] DR CCDS; CCDS53435.1; -. [P42684-4] DR CCDS; CCDS53436.1; -. [P42684-6] DR CCDS; CCDS53437.1; -. [P42684-7] DR CCDS; CCDS53438.1; -. [P42684-5] DR PIR; A35962; A35962. DR PIR; B35962; B35962. DR RefSeq; NP_001129472.1; NM_001136000.2. [P42684-10] DR RefSeq; NP_001129473.1; NM_001136001.1. [P42684-8] DR RefSeq; NP_001161708.1; NM_001168236.1. [P42684-6] DR RefSeq; NP_001161709.1; NM_001168237.1. [P42684-5] DR RefSeq; NP_001161710.1; NM_001168238.1. [P42684-7] DR RefSeq; NP_001161711.1; NM_001168239.1. [P42684-4] DR RefSeq; NP_005149.4; NM_005158.4. [P42684-3] DR RefSeq; NP_009298.1; NM_007314.3. [P42684-1] DR RefSeq; XP_005245145.1; XM_005245088.2. [P42684-2] DR PDB; 2ECD; NMR; -; A=163-268. DR PDB; 2KK1; NMR; -; A=1058-1182. DR PDB; 2XYN; X-ray; 2.81 A; A/B/C=279-546. DR PDB; 3GVU; X-ray; 2.05 A; A=279-546. DR PDB; 3HMI; X-ray; 1.65 A; A=279-546. DR PDB; 3ULR; X-ray; 1.65 A; C=563-579. DR PDB; 4EIH; X-ray; 1.20 A; A=165-273. DR PDB; 5NP3; X-ray; 2.00 A; A/B/C/D=110-166. DR PDB; 5NP5; X-ray; 1.40 A; A/B=110-166. DR PDBsum; 2ECD; -. DR PDBsum; 2KK1; -. DR PDBsum; 2XYN; -. DR PDBsum; 3GVU; -. DR PDBsum; 3HMI; -. DR PDBsum; 3ULR; -. DR PDBsum; 4EIH; -. DR PDBsum; 5NP3; -. DR PDBsum; 5NP5; -. DR AlphaFoldDB; P42684; -. DR BMRB; P42684; -. DR EMDB; EMD-41169; -. DR SMR; P42684; -. DR BioGRID; 106545; 104. DR CORUM; P42684; -. DR DIP; DIP-91N; -. DR IntAct; P42684; 75. DR MINT; P42684; -. DR STRING; 9606.ENSP00000427562; -. DR BindingDB; P42684; -. DR ChEMBL; CHEMBL4014; -. DR DrugBank; DB00171; ATP. DR DrugBank; DB01254; Dasatinib. DR DrugBank; DB12010; Fostamatinib. DR DrugBank; DB07664; K-00546. DR DrugBank; DB05184; XL228. DR DrugCentral; P42684; -. DR GuidetoPHARMACOLOGY; 1924; -. DR MoonDB; P42684; Predicted. DR GlyGen; P42684; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P42684; -. DR PhosphoSitePlus; P42684; -. DR BioMuta; ABL2; -. DR DMDM; 1168268; -. DR CPTAC; CPTAC-3138; -. DR CPTAC; CPTAC-3139; -. DR EPD; P42684; -. DR jPOST; P42684; -. DR MassIVE; P42684; -. DR MaxQB; P42684; -. DR PaxDb; 9606-ENSP00000427562; -. DR PeptideAtlas; P42684; -. DR ProteomicsDB; 55528; -. [P42684-1] DR ProteomicsDB; 55529; -. [P42684-10] DR ProteomicsDB; 55530; -. [P42684-2] DR ProteomicsDB; 55531; -. [P42684-3] DR ProteomicsDB; 55532; -. [P42684-4] DR ProteomicsDB; 55533; -. [P42684-5] DR ProteomicsDB; 55534; -. [P42684-6] DR ProteomicsDB; 55535; -. [P42684-7] DR ProteomicsDB; 55536; -. [P42684-8] DR Pumba; P42684; -. DR Antibodypedia; 736; 563 antibodies from 38 providers. DR DNASU; 27; -. DR Ensembl; ENST00000344730.8; ENSP00000339209.3; ENSG00000143322.22. [P42684-10] DR Ensembl; ENST00000367623.8; ENSP00000356595.4; ENSG00000143322.22. [P42684-6] DR Ensembl; ENST00000502732.6; ENSP00000427562.1; ENSG00000143322.22. [P42684-1] DR Ensembl; ENST00000504405.5; ENSP00000426831.1; ENSG00000143322.22. [P42684-4] DR Ensembl; ENST00000507173.5; ENSP00000423413.1; ENSG00000143322.22. [P42684-7] DR Ensembl; ENST00000511413.5; ENSP00000424697.1; ENSG00000143322.22. [P42684-5] DR Ensembl; ENST00000512653.5; ENSP00000423578.1; ENSG00000143322.22. [P42684-3] DR GeneID; 27; -. DR KEGG; hsa:27; -. DR MANE-Select; ENST00000502732.6; ENSP00000427562.1; NM_007314.4; NP_009298.1. DR UCSC; uc001gmg.5; human. [P42684-1] DR AGR; HGNC:77; -. DR CTD; 27; -. DR DisGeNET; 27; -. DR GeneCards; ABL2; -. DR HGNC; HGNC:77; ABL2. DR HPA; ENSG00000143322; Low tissue specificity. DR MIM; 164690; gene. DR neXtProt; NX_P42684; -. DR OpenTargets; ENSG00000143322; -. DR PharmGKB; PA24414; -. DR VEuPathDB; HostDB:ENSG00000143322; -. DR eggNOG; KOG4278; Eukaryota. DR GeneTree; ENSGT00940000153838; -. DR HOGENOM; CLU_002795_0_0_1; -. DR InParanoid; P42684; -. DR OMA; NIFTQHX; -. DR OrthoDB; 1614410at2759; -. DR PhylomeDB; P42684; -. DR TreeFam; TF105081; -. DR BRENDA; 2.7.10.2; 2681. DR PathwayCommons; P42684; -. DR Reactome; R-HSA-428890; Role of ABL in ROBO-SLIT signaling. DR Reactome; R-HSA-9013149; RAC1 GTPase cycle. DR Reactome; R-HSA-9013423; RAC3 GTPase cycle. DR Reactome; R-HSA-9706369; Negative regulation of FLT3. DR SignaLink; P42684; -. DR SIGNOR; P42684; -. DR BioGRID-ORCS; 27; 8 hits in 1191 CRISPR screens. DR ChiTaRS; ABL2; human. DR EvolutionaryTrace; P42684; -. DR GeneWiki; ABL2; -. DR GenomeRNAi; 27; -. DR Pharos; P42684; Tchem. DR PRO; PR:P42684; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; P42684; Protein. DR Bgee; ENSG00000143322; Expressed in tendon of biceps brachii and 175 other cell types or tissues. DR GO; GO:0015629; C:actin cytoskeleton; TAS:UniProtKB. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0051015; F:actin filament binding; TAS:UniProtKB. DR GO; GO:0003785; F:actin monomer binding; TAS:UniProtKB. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB. DR GO; GO:0030145; F:manganese ion binding; IDA:UniProtKB. DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; TAS:UniProtKB. DR GO; GO:0001784; F:phosphotyrosine residue binding; IPI:CAFA. DR GO; GO:0004672; F:protein kinase activity; TAS:ProtInc. DR GO; GO:0004713; F:protein tyrosine kinase activity; IDA:UniProtKB. DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW. DR GO; GO:0071300; P:cellular response to retinoic acid; IMP:BHF-UCL. DR GO; GO:0035640; P:exploration behavior; ISS:ARUK-UCL. DR GO; GO:0035024; P:negative regulation of Rho protein signal transduction; ISS:ARUK-UCL. DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:UniProtKB. DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IMP:MGI. DR GO; GO:1903905; P:positive regulation of establishment of T cell polarity; ISS:UniProtKB. DR GO; GO:0010976; P:positive regulation of neuron projection development; IMP:BHF-UCL. DR GO; GO:0051353; P:positive regulation of oxidoreductase activity; IDA:BHF-UCL. DR GO; GO:0010863; P:positive regulation of phospholipase C activity; IMP:MGI. DR GO; GO:2000406; P:positive regulation of T cell migration; ISS:UniProtKB. DR GO; GO:0036211; P:protein modification process; TAS:ProtInc. DR GO; GO:0032956; P:regulation of actin cytoskeleton organization; 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:0030155; P:regulation of cell adhesion; TAS:UniProtKB. DR GO; GO:2000145; P:regulation of cell motility; TAS:UniProtKB. DR GO; GO:0030100; P:regulation of endocytosis; TAS:UniProtKB. DR GO; GO:0007165; P:signal transduction; TAS:ProtInc. DR CDD; cd05052; PTKc_Abl; 1. DR CDD; cd09935; SH2_ABL; 1. DR CDD; cd11850; SH3_Abl; 1. DR Gene3D; 1.20.120.330; Nucleotidyltransferases domain 2; 1. DR Gene3D; 3.30.505.10; SH2 domain; 1. DR Gene3D; 2.30.30.40; SH3 Domains; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. DR 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; TYROSINE-PROTEIN KINASE; 1. DR PANTHER; PTHR24418:SF87; TYROSINE-PROTEIN KINASE ABL2; 1. DR Pfam; PF08919; F_actin_bind; 1. DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1. DR Pfam; PF00017; SH2; 1. DR Pfam; PF00018; SH3_1; 1. DR PRINTS; PR00401; SH2DOMAIN. DR PRINTS; PR00109; TYRKINASE. DR SMART; SM00808; FABD; 1. DR SMART; SM00252; SH2; 1. DR SMART; SM00326; SH3; 1. DR SMART; SM00219; TyrKc; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR SUPFAM; SSF55550; SH2 domain; 1. DR SUPFAM; SSF50044; SH3-domain; 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1. DR PROSITE; PS50001; SH2; 1. DR PROSITE; PS50002; SH3; 1. DR Genevisible; P42684; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; ATP-binding; KW Cell adhesion; Cytoplasm; Cytoskeleton; Kinase; Lipoprotein; Magnesium; KW Manganese; Metal-binding; Myristate; Nucleotide-binding; Phosphoprotein; KW Reference proteome; SH2 domain; SH3 domain; Transferase; KW Tyrosine-protein kinase; Ubl conjugation. FT INIT_MET 1 FT /note="Removed" FT CHAIN 2..1182 FT /note="Tyrosine-protein kinase ABL2" FT /id="PRO_0000088052" FT DOMAIN 107..167 FT /note="SH3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192" FT DOMAIN 173..263 FT /note="SH2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191" FT DOMAIN 288..539 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT REGION 1..47 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 2..106 FT /note="CAP" FT REGION 60..80 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 611..641 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 654..674 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 694..930 FT /note="F-actin-binding" FT /evidence="ECO:0000250" FT REGION 763..794 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 807..851 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 964..1024 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1020..1182 FT /note="F-actin-binding" FT /evidence="ECO:0000250" FT MOTIF 427..451 FT /note="Kinase activation loop" FT /evidence="ECO:0000250" FT MOTIF 658..660 FT /note="Nuclear localization signal" FT /evidence="ECO:0000255" FT COMPBIAS 774..793 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 807..826 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 828..851 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 966..980 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1000..1021 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 409 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000255|PROSITE-ProRule:PRU10028" FT BINDING 294..302 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 317 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 362..368 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT MOD_RES 97 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P00519" FT MOD_RES 116 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P00519" FT MOD_RES 161 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P00519" FT MOD_RES 174 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P00519" FT MOD_RES 185 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P00519" FT MOD_RES 218 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P00519" FT MOD_RES 231 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P00519" FT MOD_RES 261 FT /note="Phosphotyrosine; by ABL1 and autocatalysis" FT /evidence="ECO:0000269|PubMed:15735735" FT MOD_RES 272 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:12748290" FT MOD_RES 275 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18691976" FT MOD_RES 299 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P00519" FT MOD_RES 303 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P00519" FT MOD_RES 439 FT /note="Phosphotyrosine; by autocatalysis and SRC-type Tyr- FT kinases" FT /evidence="ECO:0000269|PubMed:12748290" FT MOD_RES 459 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P00519" FT MOD_RES 568 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:12748290" FT MOD_RES 620 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569" FT MOD_RES 631 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569" FT MOD_RES 633 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 655 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT MOD_RES 669 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P00519" FT MOD_RES 670 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P00519" FT MOD_RES 671 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 683 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:12748290" FT MOD_RES 718 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:19369195" FT MOD_RES 776 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P00519" FT MOD_RES 783 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 800 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:P00519" FT MOD_RES 817 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17525332, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:23186163" FT MOD_RES 820 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163" FT MOD_RES 915 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18691976" FT MOD_RES 936 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:23186163" FT LIPID 2 FT /note="N-myristoyl glycine" FT /evidence="ECO:0000250" FT VAR_SEQ 1..73 FT /note="MGQQVGRVGEAPGLQQPQPRGIRGSSAARPSGRRRDPAGRTTETGFNIFTQH FT DHFASCVEDGFEGDKTGGSSP -> MVLGTVLLPPNSYGRDQDTSLCCLCTEASESALP FT DLT (in isoform 2 and isoform 4)" FT /evidence="ECO:0000303|PubMed:17974005, FT ECO:0000303|PubMed:18810762" FT /id="VSP_004961" FT VAR_SEQ 1..52 FT /note="MGQQVGRVGEAPGLQQPQPRGIRGSSAARPSGRRRDPAGRTTETGFNIFTQH FT -> MVLGTVLLPPNSYGRDQDTSLCCLCTEASESALPDLT (in isoform 3 and FT isoform 10)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_017112" FT VAR_SEQ 53..73 FT /note="Missing (in isoform 6, isoform 7 and isoform 8)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:18810762" FT /id="VSP_041772" FT VAR_SEQ 550..564 FT /note="EEVAEELGRAASSSS -> EVLLHCANQTCITL (in isoform 8)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_041773" FT VAR_SEQ 565..1182 FT /note="Missing (in isoform 8)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_041774" FT VAR_SEQ 688..790 FT /note="Missing (in isoform 4, isoform 5, isoform 7 and FT isoform 10)" FT /evidence="ECO:0000303|PubMed:17974005, FT ECO:0000303|PubMed:18810762" FT /id="VSP_021308" FT VARIANT 78 FT /note="R -> H (in dbSNP:rs55655202)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_055411" FT VARIANT 99 FT /note="E -> Q (somatic mutation in a breast cancer sample)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_055412" FT VARIANT 519 FT /note="R -> I (somatic mutation in a lung squamous cell FT carcinoma)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_055413" FT VARIANT 769 FT /note="T -> S (in dbSNP:rs55892721)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_055414" FT VARIANT 930 FT /note="K -> R (in dbSNP:rs17277288)" FT /evidence="ECO:0000269|PubMed:17344846, ECO:0000269|Ref.5" FT /id="VAR_029232" FT VARIANT 946 FT /note="V -> M (in dbSNP:rs28913889)" FT /evidence="ECO:0000269|Ref.5" FT /id="VAR_029233" FT VARIANT 996 FT /note="P -> R (in dbSNP:rs28913890)" FT /evidence="ECO:0000269|PubMed:17344846, ECO:0000269|Ref.5" FT /id="VAR_029234" FT VARIANT 1085 FT /note="S -> N (in dbSNP:rs28913891)" FT /evidence="ECO:0000269|Ref.5" FT /id="VAR_029235" FT VARIANT 1101 FT /note="T -> A (in dbSNP:rs28913892)" FT /evidence="ECO:0000269|Ref.5" FT /id="VAR_029236" FT CONFLICT 343..344 FT /note="NL -> TI (in Ref. 9; no nucleotide entry)" FT /evidence="ECO:0000305" FT CONFLICT 435 FT /note="T -> I (in Ref. 3; AK311045)" FT /evidence="ECO:0000305" FT CONFLICT 981 FT /note="K -> R (in Ref. 4; CAD98092)" FT /evidence="ECO:0000305" FT STRAND 111..116 FT /evidence="ECO:0007829|PDB:5NP5" FT STRAND 133..139 FT /evidence="ECO:0007829|PDB:5NP5" FT STRAND 141..150 FT /evidence="ECO:0007829|PDB:5NP5" FT STRAND 153..158 FT /evidence="ECO:0007829|PDB:5NP5" FT HELIX 159..161 FT /evidence="ECO:0007829|PDB:5NP5" FT STRAND 162..164 FT /evidence="ECO:0007829|PDB:5NP5" FT HELIX 168..170 FT /evidence="ECO:0007829|PDB:4EIH" FT STRAND 174..177 FT /evidence="ECO:0007829|PDB:4EIH" FT HELIX 180..187 FT /evidence="ECO:0007829|PDB:4EIH" FT STRAND 194..199 FT /evidence="ECO:0007829|PDB:4EIH" FT STRAND 207..213 FT /evidence="ECO:0007829|PDB:4EIH" FT STRAND 216..221 FT /evidence="ECO:0007829|PDB:4EIH" FT STRAND 226..228 FT /evidence="ECO:0007829|PDB:2ECD" FT STRAND 230..233 FT /evidence="ECO:0007829|PDB:4EIH" FT STRAND 236..240 FT /evidence="ECO:0007829|PDB:4EIH" FT HELIX 241..248 FT /evidence="ECO:0007829|PDB:4EIH" FT STRAND 255..257 FT /evidence="ECO:0007829|PDB:4EIH" FT STRAND 280..282 FT /evidence="ECO:0007829|PDB:3GVU" FT HELIX 285..287 FT /evidence="ECO:0007829|PDB:3HMI" FT STRAND 288..293 FT /evidence="ECO:0007829|PDB:3HMI" FT HELIX 294..297 FT /evidence="ECO:0007829|PDB:3HMI" FT STRAND 300..307 FT /evidence="ECO:0007829|PDB:3HMI" FT HELIX 308..310 FT /evidence="ECO:0007829|PDB:3HMI" FT STRAND 312..318 FT /evidence="ECO:0007829|PDB:3HMI" FT HELIX 326..337 FT /evidence="ECO:0007829|PDB:3HMI" FT STRAND 347..351 FT /evidence="ECO:0007829|PDB:3HMI" FT STRAND 353..356 FT /evidence="ECO:0007829|PDB:3HMI" FT STRAND 358..362 FT /evidence="ECO:0007829|PDB:3HMI" FT HELIX 369..375 FT /evidence="ECO:0007829|PDB:3HMI" FT TURN 378..380 FT /evidence="ECO:0007829|PDB:3HMI" FT HELIX 383..402 FT /evidence="ECO:0007829|PDB:3HMI" FT HELIX 412..414 FT /evidence="ECO:0007829|PDB:3HMI" FT STRAND 415..417 FT /evidence="ECO:0007829|PDB:3HMI" FT HELIX 419..421 FT /evidence="ECO:0007829|PDB:3HMI" FT STRAND 423..425 FT /evidence="ECO:0007829|PDB:3HMI" FT STRAND 435..437 FT /evidence="ECO:0007829|PDB:2XYN" FT STRAND 438..440 FT /evidence="ECO:0007829|PDB:3GVU" FT HELIX 449..451 FT /evidence="ECO:0007829|PDB:3HMI" FT HELIX 454..459 FT /evidence="ECO:0007829|PDB:3HMI" FT HELIX 464..479 FT /evidence="ECO:0007829|PDB:3HMI" FT HELIX 491..493 FT /evidence="ECO:0007829|PDB:3HMI" FT HELIX 494..499 FT /evidence="ECO:0007829|PDB:3HMI" FT HELIX 512..521 FT /evidence="ECO:0007829|PDB:3HMI" FT HELIX 526..528 FT /evidence="ECO:0007829|PDB:3HMI" FT HELIX 532..545 FT /evidence="ECO:0007829|PDB:3HMI" FT HELIX 1069..1071 FT /evidence="ECO:0007829|PDB:2KK1" FT TURN 1076..1078 FT /evidence="ECO:0007829|PDB:2KK1" FT HELIX 1080..1083 FT /evidence="ECO:0007829|PDB:2KK1" FT HELIX 1086..1099 FT /evidence="ECO:0007829|PDB:2KK1" FT HELIX 1106..1123 FT /evidence="ECO:0007829|PDB:2KK1" FT HELIX 1124..1126 FT /evidence="ECO:0007829|PDB:2KK1" FT HELIX 1130..1152 FT /evidence="ECO:0007829|PDB:2KK1" FT STRAND 1155..1158 FT /evidence="ECO:0007829|PDB:2KK1" FT HELIX 1165..1181 FT /evidence="ECO:0007829|PDB:2KK1" FT MOD_RES P42684-4:647 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:19369195" FT VARIANT P42684-4:12 FT /note="S -> T (in dbSNP:rs1318056)" FT /evidence="ECO:0000269|PubMed:18810762, FT ECO:0007744|PubMed:17344846" FT /id="VAR_082895" FT MOD_RES P42684-5:683 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:19369195" FT MOD_RES P42684-7:662 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:19369195" FT MOD_RES P42684-10:668 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:19369195" SQ SEQUENCE 1182 AA; 128343 MW; ED93869BC2B14FAA CRC64; MGQQVGRVGE APGLQQPQPR GIRGSSAARP SGRRRDPAGR TTETGFNIFT QHDHFASCVE DGFEGDKTGG SSPEALHRPY GCDVEPQALN EAIRWSSKEN LLGATESDPN LFVALYDFVA SGDNTLSITK GEKLRVLGYN QNGEWSEVRS KNGQGWVPSN YITPVNSLEK HSWYHGPVSR SAAEYLLSSL INGSFLVRES ESSPGQLSIS LRYEGRVYHY RINTTADGKV YVTAESRFST LAELVHHHST VADGLVTTLH YPAPKCNKPT VYGVSPIHDK WEMERTDITM KHKLGGGQYG EVYVGVWKKY SLTVAVKTLK EDTMEVEEFL KEAAVMKEIK HPNLVQLLGV CTLEPPFYIV TEYMPYGNLL DYLRECNREE VTAVVLLYMA TQISSAMEYL EKKNFIHRDL AARNCLVGEN HVVKVADFGL SRLMTGDTYT AHAGAKFPIK WTAPESLAYN TFSIKSDVWA FGVLLWEIAT YGMSPYPGID LSQVYDLLEK GYRMEQPEGC PPKVYELMRA CWKWSPADRP SFAETHQAFE TMFHDSSISE EVAEELGRAA SSSSVVPYLP RLPILPSKTR TLKKQVENKE NIEGAQDATE NSASSLAPGF IRGAQASSGS PALPRKQRDK SPSSLLEDAK ETCFTRDRKG GFFSSFMKKR NAPTPPKRSS SFREMENQPH KKYELTGNFS SVASLQHADG FSFTPAQQEA NLVPPKCYGG SFAQRNLCND DGGGGGGSGT AGGGWSGITG FFTPRLIKKT LGLRAGKPTA SDDTSKPFPR SNSTSSMSSG LPEQDRMAMT LPRNCQRSKL QLERTVSTSS QPEENVDRAN DMLPKKSEES AAPSRERPKA KLLPRGATAL PLRTPSGDLA ITEKDPPGVG VAGVAAAPKG KEKNGGARLG MAGVPEDGEQ PGWPSPAKAA PVLPTTHNHK VPVLISPTLK HTPADVQLIG TDSQGNKFKL LSEHQVTSSG DKDRPRRVKP KCAPPPPPVM RLLQHPSICS DPTEEPTALT AGQSTSETQE GGKKAALGAV PISGKAGRPV MPPPQVPLPT SSISPAKMAN GTAGTKVALR KTKQAAEKIS ADKISKEALL ECADLLSSAL TEPVPNSQLV DTGHQLLDYC SGYVDCIPQT RNKFAFREAV SKLELSLQEL QVSSAAAGVP GTNPVLNNLL SCVQEISDVV QR //