ID SRC_HUMAN Reviewed; 536 AA. AC P12931; E1P5V4; Q76P87; Q86VB9; Q9H5A8; DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 3. DT 09-DEC-2015, entry version 202. DE RecName: Full=Proto-oncogene tyrosine-protein kinase Src; DE EC=2.7.10.2; DE AltName: Full=Proto-oncogene c-Src; DE AltName: Full=pp60c-src; DE Short=p60-Src; GN Name=SRC; Synonyms=SRC1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=11780052; DOI=10.1038/414865a; RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., RA Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., RA Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., RA Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., RA Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., RA Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., RA Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., RA Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., RA Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., RA Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., RA Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., RA Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., RA Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., RA Rogers J.; RT "The DNA sequence and comparative analysis of human chromosome 20."; RL Nature 414:865-871(2001). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Lung, and Skin; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-185 (ISOFORM 1). RX PubMed=3299057; RA Tanaka A., Gibbs C.P., Arthur R.R., Anderson S.K., Kung H.-J., RA Fujita D.J.; RT "DNA sequence encoding the amino-terminal region of the human c-src RT protein: implications of sequence divergence among src-type kinase RT oncogenes."; RL Mol. Cell. Biol. 7:1978-1983(1987). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 186-536 (ISOFORM 1). RX PubMed=2582238; RA Anderson S.K., Gibbs C.P., Tanaka A., Kung H.-J., Fujita D.J.; RT "Human cellular src gene: nucleotide sequence and derived amino acid RT sequence of the region coding for the carboxy-terminal two-thirds of RT pp60c-src."; RL Mol. Cell. Biol. 5:1122-1129(1985). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] OF 98-139 (ISOFORM 2). RX PubMed=2681803; DOI=10.1002/jnr.490240113; RA Pyper J.M., Bolen J.B.; RT "Neuron-specific splicing of C-SRC RNA in human brain."; RL J. Neurosci. Res. 24:89-96(1989). RN [7] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 376-536 (ISOFORM 1). RX PubMed=2581127; RA Parker R.C., Mardon G., Lebo R.V., Varmus H.E., Bishop J.M.; RT "Isolation of duplicated human c-src genes located on chromosomes 1 RT and 20."; RL Mol. Cell. Biol. 5:831-838(1985). RN [8] RP PHOSPHORYLATION AT TYR-419. RX PubMed=6273838; DOI=10.1073/pnas.78.10.6013; RA Smart J.E., Oppermann H., Czernilofsky A.P., Purchio A.F., RA Erikson R.L., Bishop J.M.; RT "Characterization of sites for tyrosine phosphorylation in the RT transforming protein of Rous sarcoma virus (pp60v-src) and its normal RT cellular homologue (pp60c-src)."; RL Proc. Natl. Acad. Sci. U.S.A. 78:6013-6017(1981). RN [9] RP ROLE IN TUMOR TISSUES. RX PubMed=3093483; RA Rosen N., Bolen J.B., Schwartz A.M., Cohen P., DeSeau V., Israel M.A.; RT "Analysis of pp60c-src protein kinase activity in human tumor cell RT lines and tissues."; RL J. Biol. Chem. 261:13754-13759(1986). RN [10] RP ROLE IN COLON CARCINOMA. RX PubMed=2498394; DOI=10.1172/JCI114113; RA Cartwright C.A., Kamps M.P., Meisler A.I., Pipas J.M., Eckhart W.; RT "pp60c-src activation in human colon carcinoma."; RL J. Clin. Invest. 83:2025-2033(1989). RN [11] RP ALTERNATIVE SPLICING. RX PubMed=1691439; RA Pyper J.M., Bolen J.B.; RT "Identification of a novel neuronal C-SRC exon expressed in human RT brain."; RL Mol. Cell. Biol. 10:2035-2040(1990). RN [12] RP SUBCELLULAR LOCATION, PHOSPHORYLATION AT TYR-530, AND MYRISTOYLATION RP AT GLY-2. RX PubMed=7525268; RA Kaplan K.B., Bibbins K.B., Swedlow J.R., Arnaud M., Morgan D.O., RA Varmus H.E.; RT "Association of the amino-terminal half of c-Src with focal adhesions RT alters their properties and is regulated by phosphorylation of RT tyrosine 527."; RL EMBO J. 13:4745-4756(1994). RN [13] RP PHOSPHORYLATION, AND ENZYME REGULATION. RX PubMed=7929427; RA Stover D.R., Liebetanz J., Lydon N.B.; RT "Cdc2-mediated modulation of pp60c-src activity."; RL J. Biol. Chem. 269:26885-26889(1994). RN [14] RP SUBCELLULAR LOCATION, AND FUNCTION. RX PubMed=7853507; RA David-Pfeuty T., Nouvian-Dooghe Y.; RT "Highly specific antibody to Rous sarcoma virus src gene product RT recognizes nuclear and nucleolar antigens in human cells."; RL J. Virol. 69:1699-1713(1995). RN [15] RP INTERACTION WITH FCAMR, ENZYME REGULATION, AND FUNCTION. RX PubMed=8759729; RA Rabinowich H., Manciulea M., Metes D., Sulica A., Herberman R.B., RA Corey S.J., Whiteside T.L.; RT "Physical and functional association of Fc mu receptor on human RT natural killer cells with the zeta- and Fc epsilon RI gamma-chains and RT with src family protein tyrosine kinases."; RL J. Immunol. 157:1485-1491(1996). RN [16] RP FUNCTION IN HGF SIGNALING PATHWAY. RX PubMed=8755529; DOI=10.1073/pnas.93.15.7644; RA Grano M., Galimi F., Zambonin G., Colucci S., Cottone E., RA Zallone A.Z., Comoglio P.M.; RT "Hepatocyte growth factor is a coupling factor for osteoclasts and RT osteoblasts in vitro."; RL Proc. Natl. Acad. Sci. U.S.A. 93:7644-7648(1996). RN [17] RP ENZYME REGULATION. RX PubMed=9571170; DOI=10.1006/bbrc.1998.8452; RA Yang E.B., Zhang K., Cheng L.Y., Mack P.; RT "Butein, a specific protein tyrosine kinase inhibitor."; RL Biochem. Biophys. Res. Commun. 245:435-438(1998). RN [18] RP INTERACTION WITH GNB2L1. RX PubMed=9584165; RA Chang B.Y., Conroy K.B., Machleder E.M., Cartwright C.A.; RT "RACK1, a receptor for activated C kinase and a homolog of the beta RT subunit of G proteins, inhibits activity of src tyrosine kinases and RT growth of NIH 3T3 cells."; RL Mol. Cell. Biol. 18:3245-3256(1998). RN [19] RP INTERACTION WITH ADRB2 AND ARRB1. RX PubMed=9924018; DOI=10.1126/science.283.5402.655; RA Luttrell L.M., Ferguson S.S.G., Daaka Y., Miller W.E., Maudsley S., RA Della Rocca G.J., Lin F.-T., Kawakatsu H., Owada K., Luttrell D.K., RA Caron M.G., Lefkowitz R.J.; RT "Beta-arrestin-dependent formation of beta2 adrenergic receptor-Src RT protein kinase complexes."; RL Science 283:655-661(1999). RN [20] RP INTERACTION WITH ARRB1 AND ARRB2. RX PubMed=10753943; DOI=10.1074/jbc.275.15.11312; RA Miller W.E., Maudsley S., Ahn S., Khan K.D., Luttrell L.M., RA Lefkowitz R.J.; RT "beta-arrestin1 interacts with the catalytic domain of the tyrosine RT kinase c-SRC. Role of beta-arrestin1-dependent targeting of c-SRC in RT receptor endocytosis."; RL J. Biol. Chem. 275:11312-11319(2000). RN [21] RP INTERACTION WITH RALGPS1. RX PubMed=10747847; DOI=10.1074/jbc.C000085200; RA Rebhun J.F., Chen H., Quilliam L.A.; RT "Identification and characterization of a new family of guanine RT nucleotide exchange factors for the ras-related GTPase Ral."; RL J. Biol. Chem. 275:13406-13410(2000). RN [22] RP FUNCTION IN PHOSPHORYLATION OF RASA1 AND RASGRF1. RX PubMed=11389730; DOI=10.1046/j.1432-1327.2001.02230.x; RA Giglione C., Gonfloni S., Parmeggiani A.; RT "Differential actions of p60c-Src and Lck kinases on the Ras RT regulators p120-GAP and GDP/GTP exchange factor CDC25Mm."; RL Eur. J. Biochem. 268:3275-3283(2001). RN [23] RP INTERACTION WITH MUC1. RX PubMed=11152665; DOI=10.1074/jbc.C000754200; RA Li Y., Kuwahara H., Ren J., Wen G., Kufe D.; RT "The c-Src tyrosine kinase regulates signaling of the human DF3/MUC1 RT carcinoma-associated antigen with GSK3 beta and beta-catenin."; RL J. Biol. Chem. 276:6061-6064(2001). RN [24] RP INTERACTION WITH GNB2L1. RX PubMed=11279199; DOI=10.1074/jbc.M101375200; RA Chang B.Y., Chiang M., Cartwright C.A.; RT "The interaction of Src and RACK1 is enhanced by activation of protein RT kinase C and tyrosine phosphorylation of RACK1."; RL J. Biol. Chem. 276:20346-20356(2001). RN [25] RP INTERACTION WITH HEV ORF3 PROTEIN. RX PubMed=11518702; DOI=10.1074/jbc.M101546200; RA Korkaya H., Jameel S., Gupta D., Tyagi S., Kumar R., Zafrullah M., RA Mazumdar M., Lal S.K., Xiaofang L., Sehgal D., Das S.R., Sahal D.; RT "The ORF3 protein of hepatitis E virus binds to Src homology 3 domains RT and activates MAPK."; RL J. Biol. Chem. 276:42389-42400(2001). RN [26] RP INTERACTION WITH CAV2. RX PubMed=12091389; DOI=10.1074/jbc.M204367200; RA Lee H., Park D.S., Wang X.B., Scherer P.E., Schwartz P.E., RA Lisanti M.P.; RT "Src-induced phosphorylation of caveolin-2 on tyrosine 19. Phospho- RT caveolin-2 (Tyr(P)19) is localized near focal adhesions, remains RT associated with lipid rafts/caveolae, but no longer forms a high RT molecular mass hetero-oligomer with caveolin-1."; RL J. Biol. Chem. 277:34556-34567(2002). RN [27] RP INTERACTION WITH PELP1. RX PubMed=12415108; DOI=10.1073/pnas.192569699; RA Wong C.-W., McNally C., Nickbarg E., Komm B.S., Cheskis B.J.; RT "Estrogen receptor-interacting protein that modulates its nongenomic RT activity-crosstalk with Src/Erk phosphorylation cascade."; RL Proc. Natl. Acad. Sci. U.S.A. 99:14783-14788(2002). RN [28] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=12615910; DOI=10.1083/jcb.200209098; RA Miyazaki T., Neff L., Tanaka S., Horne W.C., Baron R.; RT "Regulation of cytochrome c oxidase activity by c-Src in RT osteoclasts."; RL J. Cell Biol. 160:709-718(2003). RN [29] RP INTERACTION WITH EPHB1. RX PubMed=12925710; DOI=10.1083/jcb.200302073; RA Vindis C., Cerretti D.P., Daniel T.O., Huynh-Do U.; RT "EphB1 recruits c-Src and p52Shc to activate MAPK/ERK and promote RT chemotaxis."; RL J. Cell Biol. 162:661-671(2003). RN [30] RP ENZYME REGULATION. RX PubMed=14632929; DOI=10.1046/j.1399-3011.2003.00094.x; RA Kamath J.R., Liu R., Enstrom A.M., Lou Q., Lam K.S.; RT "Development and characterization of potent and specific peptide RT inhibitors of p60c-src protein tyrosine kinase using pseudosubstrate- RT based inhibitor design approach."; RL J. Pept. Res. 62:260-268(2003). RN [31] RP FUNCTION IN PHOSPHORYLATION OF PDPK1, AND INTERACTION WITH PTK2B/PYK2. RX PubMed=14585963; DOI=10.1128/MCB.23.22.8019-8029.2003; RA Taniyama Y., Weber D.S., Rocic P., Hilenski L., Akers M.L., Park J., RA Hemmings B.A., Alexander R.W., Griendling K.K.; RT "Pyk2- and Src-dependent tyrosine phosphorylation of PDK1 regulates RT focal adhesions."; RL Mol. Cell. Biol. 23:8019-8029(2003). RN [32] RP INTERACTION WITH CAV2. RX PubMed=15504032; DOI=10.1021/bi049295+; RA Wang X.B., Lee H., Capozza F., Marmon S., Sotgia F., Brooks J.W., RA Campos-Gonzalez R., Lisanti M.P.; RT "Tyrosine phosphorylation of caveolin-2 at residue 27: differences in RT the spatial and temporal behavior of phospho-Cav-2 (pY19 and pY27)."; RL Biochemistry 43:13694-13706(2004). RN [33] RP INTERACTION WITH CBCLC, PHOSPHORYLATION AT TYR-419, AND MUTAGENESIS OF RP LYS-298. RX PubMed=14661060; DOI=10.1038/sj.onc.1207298; RA Kim M., Tezuka T., Tanaka K., Yamamoto T.; RT "Cbl-c suppresses v-Src-induced transformation through ubiquitin- RT dependent protein degradation."; RL Oncogene 23:1645-1655(2004). RN [34] RP INTERACTION WITH CDCP1. RX PubMed=15851033; DOI=10.1016/j.cell.2005.02.019; RA Benes C.H., Wu N., Elia A.E.H., Dharia T., Cantley L.C., Soltoff S.P.; RT "The C2 domain of PKCdelta is a phosphotyrosine binding domain."; RL Cell 121:271-280(2005). RN [35] RP FUNCTION IN PHOSPHORYLATION OF DDR2. RX PubMed=16186108; DOI=10.1074/jbc.M506921200; RA Yang K., Kim J.H., Kim H.J., Park I.S., Kim I.Y., Yang B.S.; RT "Tyrosine 740 phosphorylation of discoidin domain receptor 2 by Src RT stimulates intramolecular autophosphorylation and Shc signaling RT complex formation."; RL J. Biol. Chem. 280:39058-39066(2005). RN [36] RP INTERACTION WITH TOM1L2. RX PubMed=16479011; DOI=10.1128/MCB.26.5.1932-1947.2006; RA Franco M., Furstoss O., Simon V., Benistant C., Hong W.J., Roche S.; RT "The adaptor protein Tom1L1 is a negative regulator of Src mitogenic RT signaling induced by growth factors."; RL Mol. Cell. Biol. 26:1932-1947(2006). RN [37] RP INTERACTION WITH TGFB1I1. RX PubMed=17202804; DOI=10.1159/000098402; RA Maudsley S., Davidson L., Pawson A.J., Freestone S.H., RA Lopez de Maturana R., Thomson A.A., Millar R.P.; RT "Gonadotropin-releasing hormone functionally antagonizes testosterone RT activation of the human androgen receptor in prostate cells through RT focal adhesion complexes involving Hic-5."; RL Neuroendocrinology 84:285-300(2006). RN [38] RP INTERACTION WITH AMOTL2. RX PubMed=17293535; DOI=10.1242/dev.02782; RA Huang H., Lu F.I., Jia S., Meng S., Cao Y., Wang Y., Ma W., Yin K., RA Wen Z., Peng J., Thisse C., Thisse B., Meng A.; RT "Amotl2 is essential for cell movements in zebrafish embryo and RT regulates c-Src translocation."; RL Development 134:979-988(2007). RN [39] RP INTERACTION WITH SRCIN1. RX PubMed=17525734; DOI=10.1038/sj.emboj.7601724; RA Di Stefano P., Damiano L., Cabodi S., Aramu S., Tordella L., RA Praduroux A., Piva R., Cavallo F., Forni G., Silengo L., Tarone G., RA Turco E., Defilippi P.; RT "p140Cap protein suppresses tumour cell properties, regulating Csk and RT Src kinase activity."; RL EMBO J. 26:2843-2855(2007). RN [40] RP FUNCTION. RX PubMed=18586953; DOI=10.1152/ajplung.90282.2008; RA Jeulin C., Seltzer V., Bailbe D., Andreau K., Marano F.; RT "EGF mediates calcium-activated chloride channel activation in the RT human bronchial epithelial cell line 16HBE14o-: involvement of RT tyrosine kinase p60c-src."; RL Am. J. Physiol. 295:L489-L496(2008). RN [41] RP INTERACTION WITH PDPK1. RX PubMed=18024423; DOI=10.1074/jbc.M706361200; RA Yang K.J., Shin S., Piao L., Shin E., Li Y., Park K.A., Byun H.S., RA Won M., Hong J., Kweon G.R., Hur G.M., Seok J.H., Chun T., RA Brazil D.P., Hemmings B.A., Park J.; RT "Regulation of 3-phosphoinositide-dependent protein kinase-1 (PDK1) by RT Src involves tyrosine phosphorylation of PDK1 and Src homology 2 RT domain binding."; RL J. Biol. Chem. 283:1480-1491(2008). RN [42] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-17, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Platelet; RX PubMed=18088087; DOI=10.1021/pr0704130; RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., RA Schuetz C., Walter U., Gambaryan S., Sickmann A.; RT "Phosphoproteome of resting human platelets."; RL J. Proteome Res. 7:526-534(2008). RN [43] RP INTERACTION WITH PTK2/FAK1; PI3KR1/2 AND ESR1. RX PubMed=18657504; DOI=10.1016/j.molcel.2008.05.025; RA Le Romancer M., Treilleux I., Leconte N., Robin-Lespinasse Y., RA Sentis S., Bouchekioua-Bouzaghou K., Goddard S., Gobert-Gosse S., RA Corbo L.; RT "Regulation of estrogen rapid signaling through arginine methylation RT by PRMT1."; RL Mol. Cell 31:212-221(2008). RN [44] 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 RT the kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [45] RP INTERACTION WITH FASLG. RX PubMed=19807924; DOI=10.1186/1471-2172-10-53; RA Voss M., Lettau M., Janssen O.; RT "Identification of SH3 domain interaction partners of human FasL RT (CD178) by phage display screening."; RL BMC Immunol. 10:53-53(2009). RN [46] RP FUNCTION, AND INTERACTION WITH TRAF3; MAVS; DDX58 AND TBK1. RX PubMed=19419966; DOI=10.1074/jbc.M808233200; RA Johnsen I.B., Nguyen T.T., Bergstroem B., Fitzgerald K.A., RA Anthonsen M.W.; RT "The tyrosine kinase c-Src enhances RIG-I (retinoic acid-inducible RT gene I)-elicited antiviral signaling."; RL J. Biol. Chem. 284:19122-19131(2009). RN [47] RP PHOSPHORYLATION AT TYR-419, AND DEPHOSPHORYLATION AT TYR-419 BY PTPRJ. RX PubMed=18936167; DOI=10.1128/MCB.01374-08; RA Chabot C., Spring K., Gratton J.P., Elchebly M., Royal I.; RT "New role for the protein tyrosine phosphatase DEP-1 in Akt activation RT and endothelial cell survival."; RL Mol. Cell. Biol. 29:241-253(2009). RN [48] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-17 AND TYR-530, AND RP IDENTIFICATION BY 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 [49] 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 [50] RP ENZYME REGULATION. RX PubMed=21036157; DOI=10.1016/j.bbrc.2010.10.101; RA Yao X., Balamurugan P., Arvey A., Leslie C., Zhang L.; RT "Heme controls the regulation of protein tyrosine kinases Jak2 and RT Src."; RL Biochem. Biophys. Res. Commun. 403:30-35(2010). RN [51] RP FUNCTION, AND INTERACTION WITH RUNX3. RX PubMed=20100835; DOI=10.1074/jbc.M109.071381; RA Goh Y.M., Cinghu S., Hong E.T., Lee Y.S., Kim J.H., Jang J.W., RA Li Y.H., Chi X.Z., Lee K.S., Wee H., Ito Y., Oh B.C., Bae S.C.; RT "Src kinase phosphorylates RUNX3 at tyrosine residues and localizes RT the protein in the cytoplasm."; RL J. Biol. Chem. 285:10122-10129(2010). RN [52] RP FUNCTION IN CBLC PHOSPHORYLATION. RX PubMed=20525694; DOI=10.1074/jbc.M109.091157; RA Ryan P.E., Sivadasan-Nair N., Nau M.M., Nicholas S., Lipkowitz S.; RT "The N terminus of Cbl-c regulates ubiquitin ligase activity by RT modulating affinity for the ubiquitin-conjugating enzyme."; RL J. Biol. Chem. 285:23687-23698(2010). RN [53] RP INTERACTION WITH NDFIP1 AND NDFIP2. RX PubMed=20534535; DOI=10.1073/pnas.0911714107; RA Mund T., Pelham H.R.; RT "Regulation of PTEN/Akt and MAP kinase signaling pathways by the RT ubiquitin ligase activators Ndfip1 and Ndfip2."; RL Proc. Natl. Acad. Sci. U.S.A. 107:11429-11434(2010). RN [54] RP FUNCTION, AND INTERACTION WITH TNK2. RX PubMed=21309750; DOI=10.1042/BJ20102156; RA Chan W., Sit S.T., Manser E.; RT "The Cdc42-associated kinase ACK1 is not auto-inhibited but requires RT Src for activation."; RL Biochem. J. 435:355-364(2011). RN [55] RP PHOSPHORYLATION AT SER-75. RX PubMed=21442427; DOI=10.1007/s00018-011-0638-1; RA Pan Q., Qiao F., Gao C., Norman B., Optican L., Zelenka P.S.; RT "Cdk5 targets active Src for ubiquitin-dependent degradation by RT phosphorylating Src(S75)."; RL Cell. Mol. Life Sci. 68:3425-3436(2011). RN [56] RP REVIEW ON FUNCTION. RX PubMed=8672527; DOI=10.1016/0304-419X(96)00003-0; RA Brown M.T., Cooper J.A.; RT "Regulation, substrates and functions of src."; RL Biochim. Biophys. Acta 1287:121-149(1996). RN [57] RP REVIEW ON FUNCTION. RX PubMed=9442882; DOI=10.1146/annurev.cellbio.13.1.513; RA Thomas S.M., Brugge J.S.; RT "Cellular functions regulated by Src family kinases."; RL Annu. Rev. Cell Dev. Biol. 13:513-609(1997). RN [58] RP REVIEW ON FUNCTION. RX PubMed=11964124; DOI=10.1007/s00018-002-8438-2; RA Ma Y.C., Huang X.Y.; RT "Novel regulation and function of Src tyrosine kinase."; RL Cell. Mol. Life Sci. 59:456-462(2002). RN [59] RP FUNCTION IN FOCAL ADHESION DYNAMICS, AND INTERACTION WITH PTK2/FAK1 RP AND DNM2. RX PubMed=21411625; DOI=10.1091/mbc.E10-09-0785; RA Wang Y., Cao H., Chen J., McNiven M.A.; RT "A direct interaction between the large GTPase dynamin-2 and FAK RT regulates focal adhesion dynamics in response to active Src."; RL Mol. Biol. Cell 22:1529-1538(2011). RN [60] RP FUNCTION IN PHOSPHORYLATION OF BCAR1. RX PubMed=22710723; DOI=10.1038/onc.2012.220; RA Zhang P., Guo A., Possemato A., Wang C., Beard L., Carlin C., RA Markowitz S.D., Polakiewicz R.D., Wang Z.; RT "Identification and functional characterization of p130Cas as a RT substrate of protein tyrosine phosphatase nonreceptor 14."; RL Oncogene 32:2087-2095(2013). RN [61] RP INTERACTION WITH TRAP1. RX PubMed=23564345; DOI=10.1073/pnas.1220659110; RA Yoshida S., Tsutsumi S., Muhlebach G., Sourbier C., Lee M.J., Lee S., RA Vartholomaiou E., Tatokoro M., Beebe K., Miyajima N., Mohney R.P., RA Chen Y., Hasumi H., Xu W., Fukushima H., Nakamura K., Koga F., RA Kihara K., Trepel J., Picard D., Neckers L.; RT "Molecular chaperone TRAP1 regulates a metabolic switch between RT mitochondrial respiration and aerobic glycolysis."; RL Proc. Natl. Acad. Sci. U.S.A. 110:E1604-E1612(2013). RN [62] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-17, AND IDENTIFICATION RP 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., RA Wang L., Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human RT liver phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [63] RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 86-536. RX PubMed=9024657; DOI=10.1038/385595a0; RA Xu W., Harrison S.C., Eck M.J.; RT "Three-dimensional structure of the tyrosine kinase c-Src."; RL Nature 385:595-602(1997). RN [64] RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 145-249. RX PubMed=9174343; DOI=10.1021/bi970019n; RA Charifson P.S., Shewchuk L.M., Rocque W., Hummel C.W., Jordan S.R., RA Mohr C., Pacofsky G.J., Peel M.R., Rodriguez M., Sternbach D.D., RA Consler T.G.; RT "Peptide ligands of pp60(c-src) SH2 domains: a thermodynamic and RT structural study."; RL Biochemistry 36:6283-6293(1997). RN [65] RP STRUCTURE BY NMR OF 204-249. RX PubMed=7532003; DOI=10.1021/bi00007a003; RA Xu R.X., Word J.M., Davis D.G., Rink M.J., Willard D.H. Jr., RA Gampe R.T. Jr.; RT "Solution structure of the human pp60c-src SH2 domain complexed with a RT phosphorylated tyrosine pentapeptide."; RL Biochemistry 34:2107-2121(1995). RN [66] RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 412-424 IN COMPLEX WITH RP CBLC, UBIQUITINATION, AND INTERACTION WITH CBLC. RX PubMed=22888118; DOI=10.1093/jb/mvs085; RA Takeshita K., Tezuka T., Isozaki Y., Yamashita E., Suzuki M., Kim M., RA Yamanashi Y., Yamamoto T., Nakagawa A.; RT "Structural flexibility regulates phosphopeptide-binding activity of RT the tyrosine kinase binding domain of Cbl-c."; RL J. Biochem. 152:487-495(2012). RN [67] RP VARIANT [LARGE SCALE ANALYSIS] THR-237. RX PubMed=17344846; DOI=10.1038/nature05610; RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., RA Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., RA O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., RA Bhamra G., Buck G., Choudhury B., Clements J., Cole J., Dicks E., RA Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., RA Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., RA Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., RA West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., RA Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., RA DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., RA Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., RA Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.; RT "Patterns of somatic mutation in human cancer genomes."; RL Nature 446:153-158(2007). CC -!- FUNCTION: Non-receptor protein tyrosine kinase which is activated CC following engagement of many different classes of cellular CC receptors including immune response receptors, integrins and other CC adhesion receptors, receptor protein tyrosine kinases, G protein- CC coupled receptors as well as cytokine receptors. Participates in CC signaling pathways that control a diverse spectrum of biological CC activities including gene transcription, immune response, cell CC adhesion, cell cycle progression, apoptosis, migration, and CC transformation. Due to functional redundancy between members of CC the SRC kinase family, identification of the specific role of each CC SRC kinase is very difficult. SRC appears to be one of the primary CC kinases activated following engagement of receptors and plays a CC role in the activation of other protein tyrosine kinase (PTK) CC families. Receptor clustering or dimerization leads to recruitment CC of SRC to the receptor complexes where it phosphorylates the CC tyrosine residues within the receptor cytoplasmic domains. Plays CC an important role in the regulation of cytoskeletal organization CC through phosphorylation of specific substrates such as AFAP1. CC Phosphorylation of AFAP1 allows the SRC SH2 domain to bind AFAP1 CC and to localize to actin filaments. Cytoskeletal reorganization is CC also controlled through the phosphorylation of cortactin (CTTN). CC When cells adhere via focal adhesions to the extracellular matrix, CC signals are transmitted by integrins into the cell resulting in CC tyrosine phosphorylation of a number of focal adhesion proteins, CC including PTK2/FAK1 and paxillin (PXN). In addition to CC phosphorylating focal adhesion proteins, SRC is also active at the CC sites of cell-cell contact adherens junctions and phosphorylates CC substrates such as beta-catenin (CTNNB1), delta-catenin (CTNND1), CC and plakoglobin (JUP). Another type of cell-cell junction, the gap CC junction, is also a target for SRC, which phosphorylates connexin- CC 43 (GJA1). SRC is implicated in regulation of pre-mRNA-processing CC and phosphorylates RNA-binding proteins such as KHDRBS1. Also CC plays a role in PDGF-mediated tyrosine phosphorylation of both CC STAT1 and STAT3, leading to increased DNA binding activity of CC these transcription factors. Involved in the RAS pathway through CC phosphorylation of RASA1 and RASGRF1. Plays a role in EGF-mediated CC calcium-activated chloride channel activation. Required for CC epidermal growth factor receptor (EGFR) internalization through CC phosphorylation of clathrin heavy chain (CLTC and CLTCL1) at 'Tyr- CC 1477'. Involved in beta-arrestin (ARRB1 and ARRB2) desensitization CC through phosphorylation and activation of ADRBK1, leading to beta- CC arrestin phosphorylation and internalization. Has a critical role CC in the stimulation of the CDK20/MAPK3 mitogen-activated protein CC kinase cascade by epidermal growth factor. Might be involved not CC only in mediating the transduction of mitogenic signals at the CC level of the plasma membrane but also in controlling progression CC through the cell cycle via interaction with regulatory proteins in CC the nucleus. Plays an important role in osteoclastic bone CC resorption in conjunction with PTK2B/PYK2. Both the formation of a CC SRC-PTK2B/PYK2 complex and SRC kinase activity are necessary for CC this function. Recruited to activated integrins by PTK2B/PYK2, CC thereby phosphorylating CBL, which in turn induces the activation CC and recruitment of phosphatidylinositol 3-kinase to the cell CC membrane in a signaling pathway that is critical for osteoclast CC function. Promotes energy production in osteoclasts by activating CC mitochondrial cytochrome C oxidase. Phosphorylates DDR2 on CC tyrosine residues, thereby promoting its subsequent CC autophosphorylation. Phosphorylates RUNX3 and COX2 on tyrosine CC residues, TNK2 on 'Tyr-284' and CBL on 'Tyr-731'. Enhances CC DDX58/RIG-I-elicited antiviral signaling. Phosphorylates PDPK1 at CC 'Tyr-9', 'Tyr-373' and 'Tyr-376'. Phosphorylates BCAR1 at 'Tyr- CC 128'. Phosphorylates CBLC at multiple tyrosine residues, CC phosphorylation at 'Tyr-341' activates CBLC E3 activity. Required CC for podosome formation (By similarity). CC {ECO:0000250|UniProtKB:P05480, ECO:0000269|PubMed:11389730, CC ECO:0000269|PubMed:12615910, ECO:0000269|PubMed:14585963, CC ECO:0000269|PubMed:16186108, ECO:0000269|PubMed:18586953, CC ECO:0000269|PubMed:19419966, ECO:0000269|PubMed:20100835, CC ECO:0000269|PubMed:20525694, ECO:0000269|PubMed:21309750, CC ECO:0000269|PubMed:21411625, ECO:0000269|PubMed:22710723, CC ECO:0000269|PubMed:2498394, ECO:0000269|PubMed:3093483, CC ECO:0000269|PubMed:7853507, ECO:0000269|PubMed:8755529, CC ECO:0000269|PubMed:8759729}. CC -!- CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a CC [protein]-L-tyrosine phosphate. {ECO:0000255|PROSITE- CC ProRule:PRU10028}. CC -!- ENZYME REGULATION: Phosphorylation by CSK at Tyr-530 inhibits CC kinase activity. Inhibitory phosphorylation at Tyr-530 is enhanced CC by heme. Further phosphorylation by CDK1 partially reactivates CC CSK-inactivated SRC and facilitates complete reactivation by CC protein tyrosine phosphatase PTPRC. Integrin engagement stimulates CC kinase activity. Phosphorylation by PTK2/FAK1 enhances kinase CC activity. Butein and pseudosubstrate-based peptide inhibitors like CC CIYKYYF act as inhibitors. Phosphorylation at Tyr-419 increases CC kinase activity. {ECO:0000269|PubMed:14632929, CC ECO:0000269|PubMed:21036157, ECO:0000269|PubMed:7929427, CC ECO:0000269|PubMed:8759729, ECO:0000269|PubMed:9571170}. CC -!- SUBUNIT: Interacts with DDEF1/ASAP1; via the SH3 domain. Interacts CC with CCPG1. Identified in a complex containing FGFR4, NCAM1, CDH2, CC PLCG1, FRS2, SRC, SHC1, GAP43 and CTTN. Interacts with ERBB2, CC STAT1 and PNN. Interacts with DDR1, DDR2 and DAB2. Interacts with CC CDCP1, PELP1, TGFB1I1 and TOM1L2. Interacts with the cytoplasmic CC domain of MUC1, phosphorylates it and increases binding of MUC1 CC with beta-catenin. Interacts with RALGPS1; via the SH3 domain. CC Interacts with HEV ORF3 protein; via the SH3 domain. Interacts CC with CAV2 (tyrosine phosphorylated form). Interacts (via the SH3 CC domain and the protein kinase domain) with ARRB1; the interaction CC is independent of the phosphorylation state of SRC C-terminus. CC Interacts with ARRB1 and ARRB2. Interacts with SRCIN1. Interacts CC with NDFIP2 and more weakly with NDFIP1. Interacts with PIK3CA CC and/or PIK3C2B, PTK2/FAK1 and ESR1 (dimethylated on arginine). CC Interacts with FASLG. Interacts (via SH2 domain) with the 'Tyr- CC 402' phosphorylated form of PTK2B/PYK2. Interacts (via SH2 domain) CC with FLT3 (tyrosine phosphorylated). Interacts with PDGFRA CC (tyrosine phosphorylated). Interacts with CSF1R. Interacts (via CC SH2 and SH3 domain) with TNK2. Interacts (via protein kinase CC domain) with the tyrosine phosphorylated form of RUNX3 (via runt CC domain). Interacts with TRAF3 (via RING-type zinc finger domain). CC Interacts with DDX58, MAVS and TBK1. Interacts (via SH2 domain) CC with GNB2L1/RACK1; the interaction is enhanced by tyrosine CC phosphorylation of GNB2L1 and inhibits SRC activity. Interacts CC with EPHB1; activates the MAPK/ERK cascade to regulate cell CC migration. Interacts with FCAMR. Interacts (via SH2 domain) with CC the 'Tyr-9' phosphorylated form of PDPK1. Interacts with AMOTL2; CC this interaction regulates the translocation of phosphorylated SRC CC to peripheral cell-matrix adhesion sites. Interacts with TRAP1. CC Interacts with CBLC; the interaction is enhanced when SRC is CC phosphorylated at Tyr-419. Interacts with ARHGEF5 (By similarity). CC {ECO:0000250|UniProtKB:P05480, ECO:0000269|PubMed:10747847, CC ECO:0000269|PubMed:10753943, ECO:0000269|PubMed:11152665, CC ECO:0000269|PubMed:11279199, ECO:0000269|PubMed:11518702, CC ECO:0000269|PubMed:12091389, ECO:0000269|PubMed:12415108, CC ECO:0000269|PubMed:12925710, ECO:0000269|PubMed:14585963, CC ECO:0000269|PubMed:14661060, ECO:0000269|PubMed:15504032, CC ECO:0000269|PubMed:15851033, ECO:0000269|PubMed:16479011, CC ECO:0000269|PubMed:17202804, ECO:0000269|PubMed:17293535, CC ECO:0000269|PubMed:17525734, ECO:0000269|PubMed:18024423, CC ECO:0000269|PubMed:18657504, ECO:0000269|PubMed:19419966, CC ECO:0000269|PubMed:19807924, ECO:0000269|PubMed:20100835, CC ECO:0000269|PubMed:20534535, ECO:0000269|PubMed:21309750, CC ECO:0000269|PubMed:21411625, ECO:0000269|PubMed:22888118, CC ECO:0000269|PubMed:23564345, ECO:0000269|PubMed:8759729, CC ECO:0000269|PubMed:9584165, ECO:0000269|PubMed:9924018}. CC -!- INTERACTION: CC P00519:ABL1; NbExp=2; IntAct=EBI-621482, EBI-375543; CC P42684:ABL2; NbExp=2; IntAct=EBI-621482, EBI-1102694; CC P12814:ACTN1; NbExp=2; IntAct=EBI-621482, EBI-351710; CC Q13444:ADAM15; NbExp=3; IntAct=EBI-621482, EBI-77818; CC P07550:ADRB2; NbExp=3; IntAct=EBI-621482, EBI-491169; CC P10275:AR; NbExp=7; IntAct=EBI-621482, EBI-608057; CC Q8R5G7:Arap3 (xeno); NbExp=3; IntAct=EBI-621482, EBI-621463; CC Q9ULH1:ASAP1; NbExp=3; IntAct=EBI-621482, EBI-346622; CC P56945:BCAR1; NbExp=3; IntAct=EBI-621482, EBI-702093; CC P22681:CBL; NbExp=8; IntAct=EBI-621482, EBI-518228; CC P12830:CDH1; NbExp=2; IntAct=EBI-621482, EBI-727477; CC P52800:Efnb2 (xeno); NbExp=2; IntAct=EBI-621482, EBI-1032676; CC P00533:EGFR; NbExp=7; IntAct=EBI-621482, EBI-297353; CC P04626:ERBB2; NbExp=11; IntAct=EBI-621482, EBI-641062; CC P21860:ERBB3; NbExp=2; IntAct=EBI-621482, EBI-720706; CC P03372:ESR1; NbExp=9; IntAct=EBI-621482, EBI-78473; CC P03372-4:ESR1; NbExp=2; IntAct=EBI-621482, EBI-4309277; CC P14921-1:ETS1; NbExp=2; IntAct=EBI-621482, EBI-913224; CC P25445:FAS; NbExp=2; IntAct=EBI-621482, EBI-494743; CC Q8NFZ0:FBXO18; NbExp=4; IntAct=EBI-621482, EBI-724767; CC Q13480:GAB1; NbExp=12; IntAct=EBI-621482, EBI-517684; CC P61978:HNRNPK; NbExp=6; IntAct=EBI-621482, EBI-304185; CC P97288:Htr4 (xeno); NbExp=2; IntAct=EBI-621482, EBI-7149283; CC Q9Y6K9:IKBKG; NbExp=3; IntAct=EBI-621482, EBI-81279; CC P35968:KDR; NbExp=2; IntAct=EBI-621482, EBI-1005487; CC Q07666:KHDRBS1; NbExp=3; IntAct=EBI-621482, EBI-1364; CC P10721:KIT; NbExp=5; IntAct=EBI-621482, EBI-1379503; CC Q8TBB1:LNX1; NbExp=6; IntAct=EBI-621482, EBI-739832; CC Q9H204:MED28; NbExp=3; IntAct=EBI-621482, EBI-514199; CC P08581:MET; NbExp=4; IntAct=EBI-621482, EBI-1039152; CC P55196:MLLT4; NbExp=7; IntAct=EBI-621482, EBI-365875; CC Q13177:PAK2; NbExp=2; IntAct=EBI-621482, EBI-1045887; CC P16284:PECAM1; NbExp=3; IntAct=EBI-621482, EBI-716404; CC P27986:PIK3R1; NbExp=6; IntAct=EBI-621482, EBI-79464; CC Q92569:PIK3R3; NbExp=3; IntAct=EBI-621482, EBI-79893; CC Q05397:PTK2; NbExp=8; IntAct=EBI-621482, EBI-702142; CC P34152:Ptk2 (xeno); NbExp=2; IntAct=EBI-621482, EBI-77070; CC Q14289:PTK2B; NbExp=3; IntAct=EBI-621482, EBI-298640; CC P18031:PTPN1; NbExp=14; IntAct=EBI-621482, EBI-968788; CC Q16825:PTPN21; NbExp=2; IntAct=EBI-621482, EBI-2860264; CC P18433:PTPRA; NbExp=4; IntAct=EBI-621482, EBI-2609645; CC P18052:Ptpra (xeno); NbExp=3; IntAct=EBI-621482, EBI-6597520; CC Q62884:Ptprj (xeno); NbExp=3; IntAct=EBI-621482, EBI-7459400; CC Q13905:RAPGEF1; NbExp=2; IntAct=EBI-621482, EBI-976876; CC Q01973:ROR1; NbExp=9; IntAct=EBI-621482, EBI-6082337; CC P27635:RPL10; NbExp=6; IntAct=EBI-621482, EBI-352398; CC P35326:SPRR2A; NbExp=3; IntAct=EBI-621482, EBI-1047940; CC Q9C0H9:SRCIN1; NbExp=3; IntAct=EBI-621482, EBI-1393949; CC Q68CZ2:TNS3; NbExp=13; IntAct=EBI-621482, EBI-1220488; CC -!- SUBCELLULAR LOCATION: Cell membrane. Mitochondrion inner membrane. CC Nucleus. Cytoplasm, cytoskeleton. Note=Localizes to focal adhesion CC sites following integrin engagement. Localization to focal CC adhesion sites requires myristoylation and the SH3 domain. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P12931-1; Sequence=Displayed; CC Name=2; CC IsoId=P12931-2; Sequence=VSP_012134; CC -!- TISSUE SPECIFICITY: Expressed ubiquitously. Platelets, neurons and CC osteoclasts express 5-fold to 200-fold higher levels than most CC other tissues. CC -!- DOMAIN: The SH2 and SH3 domains are important for the CC intramolecular and intermolecular interactions that regulate CC catalytic activity, localization, and substrate recruitment. CC -!- PTM: Myristoylated at Gly-2, and this is essential for targeting CC to membranes. {ECO:0000269|PubMed:7525268}. CC -!- PTM: Dephosphorylated at Tyr-530 by PTPRJ (By similarity). CC Phosphorylated on Tyr-530 by c-Src kinase (CSK). The CC phosphorylated form is termed pp60c-src. Dephosphorylated by PTPRJ CC at Tyr-419. Normally maintained in an inactive conformation with CC the SH2 domain engaged with Tyr-530, the SH3 domain engaged with CC the SH2-kinase linker, and Tyr-419 dephosphorylated. CC Dephosphorylation of Tyr-530 as a result of protein tyrosine CC phosphatase (PTP) action disrupts the intramolecular interaction CC between the SH2 domain and Tyr-530, Tyr-419 can then become CC autophosphorylated, resulting in SRC activation. Phosphorylation CC of Tyr-530 by CSK allows this interaction to reform, resulting in CC SRC inactivation. CDK5-mediated phosphorylation at Ser-75 targets CC SRC to ubiquitin-dependent degradation and thus leads to CC cytoskeletal reorganization. Phosphorylated by PTK2/FAK1; this CC enhances kinase activity. Phosphorylated by PTK2B/PYK2; this CC enhances kinase activity. {ECO:0000250, CC ECO:0000269|PubMed:14661060, ECO:0000269|PubMed:18936167, CC ECO:0000269|PubMed:21442427, ECO:0000269|PubMed:22888118, CC ECO:0000269|PubMed:6273838, ECO:0000269|PubMed:7525268}. CC -!- PTM: S-nitrosylation is important for activation of its kinase CC activity. {ECO:0000250}. CC -!- PTM: Ubiquitinated in response to CDK5-mediated phosphorylation. CC Ubiquitination mediated by CBLC requires SRC autophosphorylation CC at Tyr-419 and may lead to lysosomal degradation. CC {ECO:0000269|PubMed:14661060, ECO:0000269|PubMed:18936167, CC ECO:0000269|PubMed:22888118, ECO:0000269|PubMed:6273838}. CC -!- DISEASE: Note=SRC kinase activity has been shown to be increased CC in several tumor tissues and tumor cell lines such as colon CC carcinoma cells. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein CC kinase family. SRC subfamily. {ECO:0000255|PROSITE- CC ProRule:PRU00159}. CC -!- SIMILARITY: Contains 1 protein kinase domain. CC {ECO:0000255|PROSITE-ProRule:PRU00159}. CC -!- SIMILARITY: Contains 1 SH2 domain. {ECO:0000255|PROSITE- CC ProRule:PRU00191}. CC -!- SIMILARITY: Contains 1 SH3 domain. {ECO:0000255|PROSITE- CC ProRule:PRU00192}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology CC and Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/SRCID448ch20q11.html"; 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; AL133293; CAC10573.1; -; Genomic_DNA. DR EMBL; AL133293; CAC34523.1; -; Genomic_DNA. DR EMBL; CH471077; EAW76065.1; -; Genomic_DNA. DR EMBL; CH471077; EAW76064.1; -; Genomic_DNA. DR EMBL; CH471077; EAW76066.1; -; Genomic_DNA. DR EMBL; CH471077; EAW76067.1; -; Genomic_DNA. DR EMBL; BC011566; AAH11566.1; -; mRNA. DR EMBL; BC051270; AAH51270.2; -; mRNA. DR EMBL; K03218; AAA60584.1; -; Genomic_DNA. DR EMBL; M16237; AAA60584.1; JOINED; Genomic_DNA. DR EMBL; M16243; AAA60584.1; JOINED; Genomic_DNA. DR EMBL; M16244; AAA60584.1; JOINED; Genomic_DNA. DR EMBL; M16245; AAA60584.1; JOINED; Genomic_DNA. DR EMBL; K03212; AAA60584.1; JOINED; Genomic_DNA. DR EMBL; K03213; AAA60584.1; JOINED; Genomic_DNA. DR EMBL; K03214; AAA60584.1; JOINED; Genomic_DNA. DR EMBL; K03215; AAA60584.1; JOINED; Genomic_DNA. DR EMBL; K03216; AAA60584.1; JOINED; Genomic_DNA. DR EMBL; K03217; AAA60584.1; JOINED; Genomic_DNA. DR EMBL; X02647; CAA26485.1; -; Genomic_DNA. DR EMBL; X03995; CAA26485.1; JOINED; Genomic_DNA. DR EMBL; X03996; CAA26485.1; JOINED; Genomic_DNA. DR EMBL; X03997; CAA26485.1; JOINED; Genomic_DNA. DR EMBL; X03998; CAA26485.1; JOINED; Genomic_DNA. DR EMBL; X03999; CAA26485.1; JOINED; Genomic_DNA. DR EMBL; X04000; CAA26485.1; JOINED; Genomic_DNA. DR CCDS; CCDS13294.1; -. [P12931-1] DR PIR; A26891; TVHUSC. DR RefSeq; NP_005408.1; NM_005417.4. [P12931-1] DR RefSeq; NP_938033.1; NM_198291.2. [P12931-1] DR RefSeq; XP_011527315.1; XM_011529013.1. [P12931-1] DR RefSeq; XP_011527316.1; XM_011529014.1. [P12931-1] DR UniGene; Hs.195659; -. DR PDB; 1A07; X-ray; 2.20 A; A/B=144-249. DR PDB; 1A08; X-ray; 2.20 A; A/B=144-249. DR PDB; 1A09; X-ray; 2.00 A; A/B=144-249. DR PDB; 1A1A; X-ray; 2.00 A; A/B=144-249. DR PDB; 1A1B; X-ray; 2.20 A; A/B=144-249. DR PDB; 1A1C; X-ray; 2.40 A; A/B=144-249. DR PDB; 1A1E; X-ray; 2.20 A; A/B=144-249. DR PDB; 1FMK; X-ray; 1.50 A; A=86-536. DR PDB; 1HCS; NMR; -; B=144-249. DR PDB; 1HCT; NMR; -; B=144-249. DR PDB; 1KSW; X-ray; 2.80 A; A=86-536. DR PDB; 1O41; X-ray; 1.70 A; A=145-252. DR PDB; 1O42; X-ray; 1.70 A; A=145-252. DR PDB; 1O43; X-ray; 1.50 A; A=145-252. DR PDB; 1O44; X-ray; 1.70 A; A=145-252. DR PDB; 1O45; X-ray; 1.80 A; A=145-252. DR PDB; 1O46; X-ray; 2.00 A; A=145-252. DR PDB; 1O47; X-ray; 1.80 A; A=145-252. DR PDB; 1O48; X-ray; 1.55 A; A=145-252. DR PDB; 1O49; X-ray; 1.70 A; A=145-252. DR PDB; 1O4A; X-ray; 1.50 A; A=145-252. DR PDB; 1O4B; X-ray; 1.85 A; A=145-252. DR PDB; 1O4C; X-ray; 1.80 A; A=145-252. DR PDB; 1O4D; X-ray; 1.85 A; A=145-252. DR PDB; 1O4E; X-ray; 2.00 A; A=145-252. DR PDB; 1O4F; X-ray; 2.00 A; A=145-252. DR PDB; 1O4G; X-ray; 1.55 A; A=145-252. DR PDB; 1O4H; X-ray; 2.25 A; A=145-252. DR PDB; 1O4I; X-ray; 1.75 A; A=145-252. DR PDB; 1O4J; X-ray; 1.70 A; A=145-252. DR PDB; 1O4K; X-ray; 1.57 A; A=145-252. DR PDB; 1O4L; X-ray; 1.65 A; A=145-252. DR PDB; 1O4M; X-ray; 1.60 A; A=145-252. DR PDB; 1O4N; X-ray; 1.60 A; A=145-252. DR PDB; 1O4O; X-ray; 1.70 A; A=145-252. DR PDB; 1O4P; X-ray; 1.90 A; A=145-252. DR PDB; 1O4Q; X-ray; 1.70 A; A=145-252. DR PDB; 1O4R; X-ray; 1.50 A; A=145-252. DR PDB; 1SHD; X-ray; 2.00 A; A=144-249. DR PDB; 1Y57; X-ray; 1.91 A; A=86-536. DR PDB; 1YI6; X-ray; 2.00 A; A/B=261-536. DR PDB; 1YOJ; X-ray; 1.95 A; A/B=254-536. DR PDB; 1YOL; X-ray; 2.30 A; A/B=254-536. DR PDB; 1YOM; X-ray; 2.90 A; A/B=254-536. DR PDB; 2BDF; X-ray; 2.10 A; A/B=258-536. DR PDB; 2BDJ; X-ray; 2.50 A; A=258-536. DR PDB; 2H8H; X-ray; 2.20 A; A=2-536. DR PDB; 2SRC; X-ray; 1.50 A; A=86-536. DR PDB; 3VRO; X-ray; 1.80 A; B=412-424. DR PDB; 3ZMP; X-ray; 2.62 A; C/D=527-536. DR PDB; 3ZMQ; X-ray; 3.30 A; C=527-536. DR PDB; 4F59; X-ray; 1.71 A; A=144-252. DR PDB; 4F5A; X-ray; 1.80 A; A=144-252. DR PDB; 4F5B; X-ray; 1.57 A; A=144-252. DR PDB; 4HXJ; X-ray; 2.00 A; A/B=87-144. DR PDB; 4K11; X-ray; 2.30 A; A=87-534. DR PDB; 4MXO; X-ray; 2.10 A; A/B=254-536. DR PDB; 4MXX; X-ray; 2.60 A; A/B=254-536. DR PDB; 4MXY; X-ray; 2.58 A; A/B=254-536. DR PDB; 4MXZ; X-ray; 2.58 A; A/B=254-536. DR PDBsum; 1A07; -. DR PDBsum; 1A08; -. DR PDBsum; 1A09; -. DR PDBsum; 1A1A; -. DR PDBsum; 1A1B; -. DR PDBsum; 1A1C; -. DR PDBsum; 1A1E; -. DR PDBsum; 1FMK; -. DR PDBsum; 1HCS; -. DR PDBsum; 1HCT; -. DR PDBsum; 1KSW; -. DR PDBsum; 1O41; -. DR PDBsum; 1O42; -. DR PDBsum; 1O43; -. DR PDBsum; 1O44; -. DR PDBsum; 1O45; -. DR PDBsum; 1O46; -. DR PDBsum; 1O47; -. DR PDBsum; 1O48; -. DR PDBsum; 1O49; -. DR PDBsum; 1O4A; -. DR PDBsum; 1O4B; -. DR PDBsum; 1O4C; -. DR PDBsum; 1O4D; -. DR PDBsum; 1O4E; -. DR PDBsum; 1O4F; -. DR PDBsum; 1O4G; -. DR PDBsum; 1O4H; -. DR PDBsum; 1O4I; -. DR PDBsum; 1O4J; -. DR PDBsum; 1O4K; -. DR PDBsum; 1O4L; -. DR PDBsum; 1O4M; -. DR PDBsum; 1O4N; -. DR PDBsum; 1O4O; -. DR PDBsum; 1O4P; -. DR PDBsum; 1O4Q; -. DR PDBsum; 1O4R; -. DR PDBsum; 1SHD; -. DR PDBsum; 1Y57; -. DR PDBsum; 1YI6; -. DR PDBsum; 1YOJ; -. DR PDBsum; 1YOL; -. DR PDBsum; 1YOM; -. DR PDBsum; 2BDF; -. DR PDBsum; 2BDJ; -. DR PDBsum; 2H8H; -. DR PDBsum; 2SRC; -. DR PDBsum; 3VRO; -. DR PDBsum; 3ZMP; -. DR PDBsum; 3ZMQ; -. DR PDBsum; 4F59; -. DR PDBsum; 4F5A; -. DR PDBsum; 4F5B; -. DR PDBsum; 4HXJ; -. DR PDBsum; 4K11; -. DR PDBsum; 4MXO; -. DR PDBsum; 4MXX; -. DR PDBsum; 4MXY; -. DR PDBsum; 4MXZ; -. DR ProteinModelPortal; P12931; -. DR SMR; P12931; 86-536. DR BioGrid; 112592; 290. DR DIP; DIP-1059N; -. DR IntAct; P12931; 188. DR MINT; MINT-93621; -. DR STRING; 9606.ENSP00000350941; -. DR BindingDB; P12931; -. DR ChEMBL; CHEMBL2111336; -. DR DrugBank; DB06616; Bosutinib. DR DrugBank; DB01254; Dasatinib. DR DrugBank; DB09079; Nintedanib. DR DrugBank; DB08901; Ponatinib. DR GuidetoPHARMACOLOGY; 2206; -. DR PhosphoSite; P12931; -. DR DMDM; 125711; -. DR OGP; P12931; -. DR MaxQB; P12931; -. DR PaxDb; P12931; -. DR PRIDE; P12931; -. DR DNASU; 6714; -. DR Ensembl; ENST00000358208; ENSP00000350941; ENSG00000197122. [P12931-1] DR Ensembl; ENST00000373558; ENSP00000362659; ENSG00000197122. [P12931-2] DR Ensembl; ENST00000373567; ENSP00000362668; ENSG00000197122. [P12931-1] DR Ensembl; ENST00000373578; ENSP00000362680; ENSG00000197122. [P12931-1] DR GeneID; 6714; -. DR KEGG; hsa:6714; -. DR UCSC; uc002xgx.3; human. [P12931-1] DR CTD; 6714; -. DR GeneCards; SRC; -. DR HGNC; HGNC:11283; SRC. DR HPA; CAB004023; -. DR HPA; HPA030875; -. DR MIM; 190090; gene. DR neXtProt; NX_P12931; -. DR PharmGKB; PA36111; -. DR eggNOG; KOG0197; Eukaryota. DR eggNOG; COG0515; LUCA. DR GeneTree; ENSGT00760000118938; -. DR HOGENOM; HOG000233858; -. DR HOVERGEN; HBG008761; -. DR InParanoid; P12931; -. DR KO; K05704; -. DR OMA; CQCWRKD; -. DR OrthoDB; EOG7GTT2V; -. DR PhylomeDB; P12931; -. DR TreeFam; TF351634; -. DR BioCyc; MetaCyc:HS02256-MONOMER; -. DR BRENDA; 2.7.10.2; 2681. DR Reactome; R-HSA-1227986; Signaling by ERBB2. DR Reactome; R-HSA-1295596; Spry regulation of FGF signaling. DR Reactome; R-HSA-1433557; Signaling by SCF-KIT. DR Reactome; R-HSA-1433559; Regulation of KIT signaling. DR Reactome; R-HSA-171007; p38MAPK events. DR Reactome; R-HSA-177929; Signaling by EGFR. DR Reactome; R-HSA-180292; GAB1 signalosome. DR Reactome; R-HSA-186763; Downstream signal transduction. DR Reactome; R-HSA-191647; c-src mediated regulation of Cx43 function and closure of gap junctions. DR Reactome; R-HSA-2029481; FCGR activation. DR Reactome; R-HSA-210990; PECAM1 interactions. DR Reactome; R-HSA-2682334; EPH-Ephrin signaling. DR Reactome; R-HSA-354192; Integrin alphaIIb beta3 signaling. DR Reactome; R-HSA-354194; GRB2:SOS provides linkage to MAPK signaling for Integrins. DR Reactome; R-HSA-372708; p130Cas linkage to MAPK signaling for integrins. DR Reactome; R-HSA-375165; NCAM signaling for neurite out-growth. DR Reactome; R-HSA-389356; CD28 co-stimulation. DR Reactome; R-HSA-389513; CTLA4 inhibitory signaling. DR Reactome; R-HSA-391160; Signal regulatory protein (SIRP) family interactions. DR Reactome; R-HSA-3928662; EPHB-mediated forward signaling. DR Reactome; R-HSA-3928663; EPHA-mediated growth cone collapse. DR Reactome; R-HSA-3928664; Ephrin signaling. DR Reactome; R-HSA-3928665; EPH-ephrin mediated repulsion of cells. DR Reactome; R-HSA-418592; ADP signalling through P2Y purinoceptor 1. DR Reactome; R-HSA-418885; DCC mediated attractive signaling. DR Reactome; R-HSA-418886; Netrin mediated repulsion signals. DR Reactome; R-HSA-430116; GP1b-IX-V activation signalling. DR Reactome; R-HSA-437239; Recycling pathway of L1. DR Reactome; R-HSA-4420097; VEGFA-VEGFR2 Pathway. DR Reactome; R-HSA-456926; Thrombin signalling through proteinase activated receptors (PARs). DR Reactome; R-HSA-5218921; VEGFR2 mediated cell proliferation. DR Reactome; R-HSA-5607764; CLEC7A (Dectin-1) signaling. DR Reactome; R-HSA-5663220; RHO GTPases Activate Formins. DR Reactome; R-HSA-5673000; RAF activation. DR Reactome; R-HSA-5674135; MAP2K and MAPK activation. DR SignaLink; P12931; -. DR ChiTaRS; SRC; human. DR EvolutionaryTrace; P12931; -. DR GeneWiki; Src_(gene); -. DR GenomeRNAi; 6714; -. DR NextBio; 26186; -. DR PMAP-CutDB; P12931; -. DR PRO; PR:P12931; -. DR Proteomes; UP000005640; Chromosome 20. DR Bgee; P12931; -. DR CleanEx; HS_SRC; -. DR Genevisible; P12931; HS. DR GO; GO:0005884; C:actin filament; IEA:Ensembl. DR GO; GO:0005901; C:caveola; IDA:BHF-UCL. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:UniProtKB. DR GO; GO:0070062; C:extracellular exosome; IDA:UniProtKB. DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; IBA:GO_Central. DR GO; GO:0005770; C:late endosome; IDA:UniProtKB. DR GO; GO:0005764; C:lysosome; IDA:UniProtKB. DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:UniProtKB. DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB. DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0032587; C:ruffle membrane; IEA:Ensembl. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB. DR GO; GO:0046875; F:ephrin receptor binding; IPI:UniProtKB. DR GO; GO:0070851; F:growth factor receptor binding; IPI:UniProtKB. DR GO; GO:0020037; F:heme binding; IDA:UniProtKB. DR GO; GO:0051427; F:hormone receptor binding; IBA:GO_Central. DR GO; GO:0005178; F:integrin binding; TAS:BHF-UCL. DR GO; GO:0044325; F:ion channel binding; IPI:BHF-UCL. DR GO; GO:0016301; F:kinase activity; TAS:Reactome. DR GO; GO:0019900; F:kinase binding; IPI:UniProtKB. DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; TAS:BHF-UCL. DR GO; GO:0051219; F:phosphoprotein binding; IPI:UniProtKB. DR GO; GO:0004672; F:protein kinase activity; IDA:UniProtKB. DR GO; GO:0004713; F:protein tyrosine kinase activity; IDA:UniProtKB. DR GO; GO:0005102; F:receptor binding; IPI:UniProtKB. DR GO; GO:0097110; F:scaffold protein binding; IPI:BHF-UCL. DR GO; GO:0042169; F:SH2 domain binding; IPI:UniProtKB. DR GO; GO:0005070; F:SH3/SH2 adaptor activity; TAS:ProtInc. DR GO; GO:0086098; P:angiotensin-activated signaling pathway involved in heart process; ISS:BHF-UCL. DR GO; GO:0007411; P:axon guidance; TAS:Reactome. DR GO; GO:0007596; P:blood coagulation; TAS:Reactome. DR GO; GO:0045453; P:bone resorption; ISS:UniProtKB. DR GO; GO:0060444; P:branching involved in mammary gland duct morphogenesis; IEA:Ensembl. DR GO; GO:0007155; P:cell adhesion; IBA:GO_Central. DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW. DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central. DR GO; GO:0071498; P:cellular response to fluid shear stress; IEA:Ensembl. DR GO; GO:0071375; P:cellular response to peptide hormone stimulus; ISS:BHF-UCL. DR GO; GO:0036120; P:cellular response to platelet-derived growth factor stimulus; IEA:Ensembl. DR GO; GO:0071393; P:cellular response to progesterone stimulus; ISS:BHF-UCL. DR GO; GO:0034614; P:cellular response to reactive oxygen species; IEA:Ensembl. DR GO; GO:0048013; P:ephrin receptor signaling pathway; TAS:Reactome. DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; IBA:GO_Central. DR GO; GO:0038096; P:Fc-gamma receptor signaling pathway involved in phagocytosis; TAS:Reactome. DR GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; TAS:Reactome. DR GO; GO:0030900; P:forebrain development; IEA:Ensembl. DR GO; GO:0045087; P:innate immune response; IBA:GO_Central. DR GO; GO:0007229; P:integrin-mediated signaling pathway; IMP:UniProtKB. DR GO; GO:0035556; P:intracellular signal transduction; IDA:BHF-UCL. DR GO; GO:0050900; P:leukocyte migration; TAS:Reactome. DR GO; GO:0061024; P:membrane organization; TAS:Reactome. DR GO; GO:2000811; P:negative regulation of anoikis; IMP:UniProtKB. DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB. DR GO; GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; IMP:UniProtKB. DR GO; GO:2001237; P:negative regulation of extrinsic apoptotic signaling pathway; IMP:UniProtKB. DR GO; GO:0051895; P:negative regulation of focal adhesion assembly; ISS:BHF-UCL. DR GO; GO:2001243; P:negative regulation of intrinsic apoptotic signaling pathway; IMP:UniProtKB. DR GO; GO:0051902; P:negative regulation of mitochondrial depolarization; IMP:UniProtKB. DR GO; GO:0032463; P:negative regulation of protein homooligomerization; IMP:UniProtKB. DR GO; GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome. DR GO; GO:0048477; P:oogenesis; IEA:Ensembl. DR GO; GO:0036035; P:osteoclast development; IBA:GO_Central. DR GO; GO:0038083; P:peptidyl-tyrosine autophosphorylation; IBA:GO_Central. DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:MGI. DR GO; GO:0030168; P:platelet activation; TAS:Reactome. DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IEA:Ensembl. DR GO; GO:0010634; P:positive regulation of epithelial cell migration; IMP:UniProtKB. DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IEA:Ensembl. DR GO; GO:0033625; P:positive regulation of integrin activation; TAS:BHF-UCL. DR GO; GO:2000394; P:positive regulation of lamellipodium morphogenesis; IMP:UniProtKB. DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IC:UniProtKB. DR GO; GO:0071803; P:positive regulation of podosome assembly; IEA:Ensembl. DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; IMP:UniProtKB. DR GO; GO:0071902; P:positive regulation of protein serine/threonine kinase activity; IDA:UniProtKB. DR GO; GO:0050847; P:progesterone receptor signaling pathway; ISS:BHF-UCL. DR GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB. DR GO; GO:0031648; P:protein destabilization; IEA:Ensembl. DR GO; GO:0007265; P:Ras protein signal transduction; TAS:Reactome. DR GO; GO:0045124; P:regulation of bone resorption; TAS:BHF-UCL. DR GO; GO:2001286; P:regulation of caveolin-mediated endocytosis; IMP:UniProtKB. DR GO; GO:0051726; P:regulation of cell cycle; IBA:GO_Central. DR GO; GO:0060491; P:regulation of cell projection assembly; IEA:Ensembl. DR GO; GO:0042127; P:regulation of cell proliferation; IBA:GO_Central. DR GO; GO:0022407; P:regulation of cell-cell adhesion; IMP:UniProtKB. DR GO; GO:2000641; P:regulation of early endosome to late endosome transport; IMP:UniProtKB. DR GO; GO:0010632; P:regulation of epithelial cell migration; IMP:UniProtKB. DR GO; GO:0033146; P:regulation of intracellular estrogen receptor signaling pathway; IEA:Ensembl. DR GO; GO:0071801; P:regulation of podosome assembly; IBA:GO_Central. DR GO; GO:0043393; P:regulation of protein binding; IEA:Ensembl. DR GO; GO:0043114; P:regulation of vascular permeability; TAS:BHF-UCL. DR GO; GO:0070555; P:response to interleukin-1; IMP:BHF-UCL. DR GO; GO:0007172; P:signal complex assembly; TAS:ProtInc. DR GO; GO:0007165; P:signal transduction; TAS:ProtInc. DR GO; GO:0007264; P:small GTPase mediated signal transduction; TAS:Reactome. DR GO; GO:0002223; P:stimulatory C-type lectin receptor signaling pathway; TAS:Reactome. DR GO; GO:0043149; P:stress fiber assembly; IMP:UniProtKB. DR GO; GO:0034446; P:substrate adhesion-dependent cell spreading; IEA:Ensembl. DR GO; GO:0031295; P:T cell costimulation; TAS:Reactome. DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; IMP:UniProtKB. DR GO; GO:0060065; P:uterus development; IEA:Ensembl. DR GO; GO:0048010; P:vascular endothelial growth factor receptor signaling pathway; TAS:Reactome. DR GO; GO:0016032; P:viral process; IEA:UniProtKB-KW. DR Gene3D; 3.30.505.10; -; 1. DR InterPro; IPR011009; Kinase-like_dom. 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; IPR001452; SH3_domain. DR InterPro; IPR008266; Tyr_kinase_AS. DR InterPro; IPR020635; Tyr_kinase_cat_dom. DR Pfam; PF07714; Pkinase_Tyr; 1. DR Pfam; PF00017; SH2; 1. DR Pfam; PF00018; SH3_1; 1. DR PRINTS; PR00401; SH2DOMAIN. DR PRINTS; PR00452; SH3DOMAIN. DR PRINTS; PR00109; TYRKINASE. 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; Alternative splicing; ATP-binding; Cell adhesion; KW Cell cycle; Cell membrane; Complete proteome; Cytoplasm; Cytoskeleton; KW Host-virus interaction; Immunity; Kinase; Lipoprotein; Membrane; KW Mitochondrion; Mitochondrion inner membrane; Myristate; KW Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; KW Proto-oncogene; Reference proteome; SH2 domain; SH3 domain; KW Transferase; Tyrosine-protein kinase; Ubl conjugation. FT INIT_MET 1 1 Removed. FT CHAIN 2 536 Proto-oncogene tyrosine-protein kinase FT Src. FT /FTId=PRO_0000088141. FT DOMAIN 84 145 SH3. {ECO:0000255|PROSITE- FT ProRule:PRU00192}. FT DOMAIN 151 248 SH2. {ECO:0000255|PROSITE- FT ProRule:PRU00191}. FT DOMAIN 270 523 Protein kinase. {ECO:0000255|PROSITE- FT ProRule:PRU00159}. FT NP_BIND 276 284 ATP. FT ACT_SITE 389 389 Proton acceptor. FT BINDING 298 298 ATP. FT MOD_RES 17 17 Phosphoserine. FT {ECO:0000244|PubMed:18088087, FT ECO:0000244|PubMed:19369195, FT ECO:0000244|PubMed:24275569}. FT MOD_RES 35 35 Phosphoserine. FT {ECO:0000269|PubMed:7929427}. FT MOD_RES 69 69 Phosphoserine. FT {ECO:0000269|PubMed:7929427}. FT MOD_RES 74 74 Phosphothreonine. FT {ECO:0000269|PubMed:7929427}. FT MOD_RES 75 75 Phosphoserine; by CDK5. FT {ECO:0000269|PubMed:21442427}. FT MOD_RES 187 187 Phosphotyrosine. FT {ECO:0000250|UniProtKB:P05480}. FT MOD_RES 419 419 Phosphotyrosine; by autocatalysis. FT {ECO:0000269|PubMed:14661060, FT ECO:0000269|PubMed:18936167, FT ECO:0000269|PubMed:6273838}. FT MOD_RES 419 419 Phosphotyrosine; by FAK2. {ECO:0000250}. FT MOD_RES 439 439 Phosphotyrosine. FT {ECO:0000269|PubMed:7929427}. FT MOD_RES 511 511 Phosphothreonine. FT {ECO:0000269|PubMed:7929427}. FT MOD_RES 522 522 Phosphotyrosine. FT {ECO:0000269|PubMed:7929427}. FT MOD_RES 530 530 Phosphotyrosine; by CSK. FT {ECO:0000244|PubMed:19369195, FT ECO:0000269|PubMed:7525268}. FT LIPID 2 2 N-myristoyl glycine. FT {ECO:0000269|PubMed:7525268}. FT VAR_SEQ 117 117 T -> TRKVDVR (in isoform 2). FT {ECO:0000303|PubMed:2681803}. FT /FTId=VSP_012134. FT VARIANT 176 176 L -> F (in dbSNP:rs6018260). FT /FTId=VAR_051699. FT VARIANT 237 237 A -> T (in dbSNP:rs34881773). FT {ECO:0000269|PubMed:17344846}. FT /FTId=VAR_041830. FT MUTAGEN 298 298 K->M: Kinase inactive. Abolishes FT ubiquitination promoted by CBLC. FT {ECO:0000269|PubMed:14661060}. FT STRAND 87 93 {ECO:0000244|PDB:1FMK}. FT STRAND 99 102 {ECO:0000244|PDB:1FMK}. FT STRAND 110 114 {ECO:0000244|PDB:1FMK}. FT STRAND 118 126 {ECO:0000244|PDB:1FMK}. FT TURN 127 129 {ECO:0000244|PDB:1FMK}. FT STRAND 132 136 {ECO:0000244|PDB:1FMK}. FT HELIX 137 139 {ECO:0000244|PDB:1FMK}. FT STRAND 140 142 {ECO:0000244|PDB:1FMK}. FT HELIX 146 148 {ECO:0000244|PDB:1FMK}. FT STRAND 152 154 {ECO:0000244|PDB:1FMK}. FT HELIX 158 165 {ECO:0000244|PDB:1FMK}. FT STRAND 167 170 {ECO:0000244|PDB:1SHD}. FT STRAND 174 179 {ECO:0000244|PDB:1FMK}. FT STRAND 181 183 {ECO:0000244|PDB:1FMK}. FT STRAND 187 195 {ECO:0000244|PDB:1FMK}. FT TURN 196 198 {ECO:0000244|PDB:1FMK}. FT STRAND 199 209 {ECO:0000244|PDB:1FMK}. FT STRAND 211 213 {ECO:0000244|PDB:2SRC}. FT STRAND 215 218 {ECO:0000244|PDB:1FMK}. FT STRAND 221 225 {ECO:0000244|PDB:1FMK}. FT HELIX 226 233 {ECO:0000244|PDB:1FMK}. FT STRAND 240 242 {ECO:0000244|PDB:1FMK}. FT STRAND 256 259 {ECO:0000244|PDB:1FMK}. FT HELIX 267 269 {ECO:0000244|PDB:1FMK}. FT STRAND 270 278 {ECO:0000244|PDB:1FMK}. FT STRAND 283 289 {ECO:0000244|PDB:1FMK}. FT TURN 290 292 {ECO:0000244|PDB:1FMK}. FT STRAND 293 299 {ECO:0000244|PDB:1FMK}. FT TURN 302 304 {ECO:0000244|PDB:2BDF}. FT HELIX 307 319 {ECO:0000244|PDB:1FMK}. FT STRAND 328 332 {ECO:0000244|PDB:1FMK}. FT STRAND 334 336 {ECO:0000244|PDB:1FMK}. FT STRAND 338 341 {ECO:0000244|PDB:1FMK}. FT HELIX 349 353 {ECO:0000244|PDB:1FMK}. FT HELIX 355 358 {ECO:0000244|PDB:1FMK}. FT HELIX 363 382 {ECO:0000244|PDB:1FMK}. FT HELIX 392 394 {ECO:0000244|PDB:1FMK}. FT STRAND 395 397 {ECO:0000244|PDB:1FMK}. FT HELIX 399 401 {ECO:0000244|PDB:1FMK}. FT STRAND 403 405 {ECO:0000244|PDB:1FMK}. FT HELIX 410 413 {ECO:0000244|PDB:2SRC}. FT HELIX 417 420 {ECO:0000244|PDB:2SRC}. FT TURN 423 426 {ECO:0000244|PDB:1Y57}. FT HELIX 429 431 {ECO:0000244|PDB:1FMK}. FT HELIX 434 439 {ECO:0000244|PDB:1FMK}. FT HELIX 444 459 {ECO:0000244|PDB:1FMK}. FT TURN 460 462 {ECO:0000244|PDB:1FMK}. FT HELIX 471 479 {ECO:0000244|PDB:1FMK}. FT HELIX 492 501 {ECO:0000244|PDB:1FMK}. FT HELIX 506 508 {ECO:0000244|PDB:1FMK}. FT HELIX 512 520 {ECO:0000244|PDB:1FMK}. FT TURN 521 523 {ECO:0000244|PDB:1FMK}. SQ SEQUENCE 536 AA; 59835 MW; C1908084683E5DE8 CRC64; MGSNKSKPKD ASQRRRSLEP AENVHGAGGG AFPASQTPSK PASADGHRGP SAAFAPAAAE PKLFGGFNSS DTVTSPQRAG PLAGGVTTFV ALYDYESRTE TDLSFKKGER LQIVNNTEGD WWLAHSLSTG QTGYIPSNYV APSDSIQAEE WYFGKITRRE SERLLLNAEN PRGTFLVRES ETTKGAYCLS VSDFDNAKGL NVKHYKIRKL DSGGFYITSR TQFNSLQQLV AYYSKHADGL CHRLTTVCPT SKPQTQGLAK DAWEIPRESL RLEVKLGQGC FGEVWMGTWN GTTRVAIKTL KPGTMSPEAF LQEAQVMKKL RHEKLVQLYA VVSEEPIYIV TEYMSKGSLL DFLKGETGKY LRLPQLVDMA AQIASGMAYV ERMNYVHRDL RAANILVGEN LVCKVADFGL ARLIEDNEYT ARQGAKFPIK WTAPEAALYG RFTIKSDVWS FGILLTELTT KGRVPYPGMV NREVLDQVER GYRMPCPPEC PESLHDLMCQ CWRKEPEERP TFEYLQAFLE DYFTSTEPQY QPGENL //