SRC_HUMAN
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 03-AUG-2022, entry version 259.
DE RecName: Full=Proto-oncogene tyrosine-protein kinase Src {ECO:0000305};
DE EC=2.7.10.2 {ECO:0000269|PubMed:14632929, ECO:0000269|PubMed:19307596, ECO:0000269|PubMed:21036157, ECO:0000269|PubMed:7929427, ECO:0000269|PubMed:8759729, ECO:0000269|PubMed:9571170};
DE AltName: Full=Proto-oncogene c-Src;
DE AltName: Full=pp60c-src;
DE Short=p60-Src;
GN Name=SRC {ECO:0000312|HGNC:HGNC:11283}; Synonyms=SRC1;
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 [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., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., 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., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., 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., 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 (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 project:
RT 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; DOI=10.1128/mcb.7.5.1978-1983.1987;
RA Tanaka A., Gibbs C.P., Arthur R.R., Anderson S.K., Kung H.-J., 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; DOI=10.1128/mcb.5.5.1122-1129.1985;
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 pp60c-
RT 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; DOI=10.1128/mcb.5.4.831-838.1985;
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 and
RT 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., Erikson R.L.,
RA Bishop J.M.;
RT "Characterization of sites for tyrosine phosphorylation in the transforming
RT protein of Rous sarcoma virus (pp60v-src) and its normal cellular homologue
RT (pp60c-src).";
RL Proc. Natl. Acad. Sci. U.S.A. 78:6013-6017(1981).
RN [9]
RP ROLE IN TUMOR TISSUES.
RX PubMed=3093483; DOI=10.1016/s0021-9258(18)67084-x;
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 lines
RT 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, AND DEVELOPMENTAL STAGE (ISOFORMS 1; 2 AND 3).
RX PubMed=1691439; DOI=10.1128/mcb.10.5.2035-2040.1990;
RA Pyper J.M., Bolen J.B.;
RT "Identification of a novel neuronal C-SRC exon expressed in human brain.";
RL Mol. Cell. Biol. 10:2035-2040(1990).
RN [12]
RP TISSUE SPECIFICITY (ISOFORMS 1; 2 AND 3).
RX PubMed=8319227;
RA Matsunaga T., Shirasawa H., Tanabe M., Ohnuma N., Takahashi H., Simizu B.;
RT "Expression of alternatively spliced src messenger RNAs related to neuronal
RT differentiation in human neuroblastomas.";
RL Cancer Res. 53:3179-3185(1993).
RN [13]
RP SUBCELLULAR LOCATION, PHOSPHORYLATION AT TYR-530, AND MYRISTOYLATION AT
RP GLY-2.
RX PubMed=7525268; DOI=10.1002/j.1460-2075.1994.tb06800.x;
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 tyrosine
RT 527.";
RL EMBO J. 13:4745-4756(1994).
RN [14]
RP CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND PHOSPHORYLATION AT TYR-530.
RX PubMed=7929427; DOI=10.1016/s0021-9258(18)47102-5;
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 [15]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=7853507; DOI=10.1128/jvi.69.3.1699-1713.1995;
RA David-Pfeuty T., Nouvian-Dooghe Y.;
RT "Highly specific antibody to Rous sarcoma virus src gene product recognizes
RT nuclear and nucleolar antigens in human cells.";
RL J. Virol. 69:1699-1713(1995).
RN [16]
RP INTERACTION WITH CEACAM1.
RX PubMed=7478590;
RA Bruemmer J., Neumaier M., Goepfert C., Wagener C.;
RT "Association of pp60c-src with biliary glycoprotein (CD66a), an adhesion
RT molecule of the carcinoembryonic antigen family downregulated in colorectal
RT carcinomas.";
RL Oncogene 11:1649-1655(1995).
RN [17]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND INTERACTION WITH
RP FCAMR.
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 natural
RT killer cells with the zeta- and Fc epsilon RI gamma-chains and with src
RT family protein tyrosine kinases.";
RL J. Immunol. 157:1485-1491(1996).
RN [18]
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., Zallone A.Z.,
RA 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 [19]
RP CATALYTIC ACTIVITY, AND ACTIVITY 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 [20]
RP INTERACTION WITH RACK1.
RX PubMed=9584165; DOI=10.1128/mcb.18.6.3245;
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 subunit
RT of G proteins, inhibits activity of src tyrosine kinases and growth of NIH
RT 3T3 cells.";
RL Mol. Cell. Biol. 18:3245-3256(1998).
RN [21]
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 protein
RT kinase complexes.";
RL Science 283:655-661(1999).
RN [22]
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., Lefkowitz R.J.;
RT "beta-arrestin1 interacts with the catalytic domain of the tyrosine kinase
RT c-SRC. Role of beta-arrestin1-dependent targeting of c-SRC in receptor
RT endocytosis.";
RL J. Biol. Chem. 275:11312-11319(2000).
RN [23]
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 nucleotide
RT exchange factors for the ras-related GTPase Ral.";
RL J. Biol. Chem. 275:13406-13410(2000).
RN [24]
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 regulators
RT p120-GAP and GDP/GTP exchange factor CDC25Mm.";
RL Eur. J. Biochem. 268:3275-3283(2001).
RN [25]
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 [26]
RP INTERACTION WITH RACK1.
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 [27]
RP INTERACTION WITH HEV ORF3 PROTEIN (MICROBIAL INFECTION).
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 and
RT activates MAPK.";
RL J. Biol. Chem. 276:42389-42400(2001).
RN [28]
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., 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 associated
RT with lipid rafts/caveolae, but no longer forms a high molecular mass
RT hetero-oligomer with caveolin-1.";
RL J. Biol. Chem. 277:34556-34567(2002).
RN [29]
RP RETRACTED PAPER.
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 [30]
RP RETRACTION NOTICE OF PUBMED:12415108.
RX PubMed=19666546; DOI=10.1073/pnas.0908685106;
RA Wong C.W., McNally C., Nickbarg E., Komm B.S., Cheskis B.J.;
RL Proc. Natl. Acad. Sci. U.S.A. 106:14180-14180(2009).
RN [31]
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 osteoclasts.";
RL J. Cell Biol. 160:709-718(2003).
RN [32]
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 [33]
RP CATALYTIC ACTIVITY, AND ACTIVITY 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 inhibitors
RT of p60c-src protein tyrosine kinase using pseudosubstrate-based inhibitor
RT design approach.";
RL J. Pept. Res. 62:260-268(2003).
RN [34]
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 focal
RT adhesions.";
RL Mol. Cell. Biol. 23:8019-8029(2003).
RN [35]
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 the
RT spatial and temporal behavior of phospho-Cav-2 (pY19 and pY27).";
RL Biochemistry 43:13694-13706(2004).
RN [36]
RP INTERACTION WITH PELP1.
RX PubMed=14963108; DOI=10.1210/me.2003-0335;
RA Barletta F., Wong C.-W., McNally C., Komm B.S., Katzenellenbogen B.,
RA Cheskis B.J.;
RT "Characterization of the interactions of estrogen receptor and MNAR in the
RT activation of cSrc.";
RL Mol. Endocrinol. 18:1096-1108(2004).
RN [37]
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-dependent
RT protein degradation.";
RL Oncogene 23:1645-1655(2004).
RN [38]
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 [39]
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 complex
RT formation.";
RL J. Biol. Chem. 280:39058-39066(2005).
RN [40]
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 [41]
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 focal
RT adhesion complexes involving Hic-5.";
RL Neuroendocrinology 84:285-300(2006).
RN [42]
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., Wen Z.,
RA Peng J., Thisse C., Thisse B., Meng A.;
RT "Amotl2 is essential for cell movements in zebrafish embryo and regulates
RT c-Src translocation.";
RL Development 134:979-988(2007).
RN [43]
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., Praduroux A.,
RA Piva R., Cavallo F., Forni G., Silengo L., Tarone G., Turco E.,
RA Defilippi P.;
RT "p140Cap protein suppresses tumour cell properties, regulating Csk and Src
RT kinase activity.";
RL EMBO J. 26:2843-2855(2007).
RN [44]
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 human
RT bronchial epithelial cell line 16HBE14o-: involvement of tyrosine kinase
RT p60c-src.";
RL Am. J. Physiol. 295:L489-L496(2008).
RN [45]
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., Won M.,
RA Hong J., Kweon G.R., Hur G.M., Seok J.H., Chun T., Brazil D.P.,
RA Hemmings B.A., Park J.;
RT "Regulation of 3-phosphoinositide-dependent protein kinase-1 (PDK1) by Src
RT involves tyrosine phosphorylation of PDK1 and Src homology 2 domain
RT binding.";
RL J. Biol. Chem. 283:1480-1491(2008).
RN [46]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-17, AND IDENTIFICATION BY
RP 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 [47]
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., Sentis S.,
RA Bouchekioua-Bouzaghou K., Goddard S., Gobert-Gosse S., Corbo L.;
RT "Regulation of estrogen rapid signaling through arginine methylation by
RT PRMT1.";
RL Mol. Cell 31:212-221(2008).
RN [48]
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 [49]
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 (CD178) by
RT phage display screening.";
RL BMC Immunol. 10:53-53(2009).
RN [50]
RP INTERACTION WITH MPP2.
RX PubMed=19665017; DOI=10.1016/j.yexcr.2009.07.028;
RA Baumgartner M., Weiss A., Fritzius T., Heinrich J., Moelling K.;
RT "The PDZ protein MPP2 interacts with c-Src in epithelial cells.";
RL Exp. Cell Res. 315:2888-2898(2009).
RN [51]
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., Anthonsen M.W.;
RT "The tyrosine kinase c-Src enhances RIG-I (retinoic acid-inducible gene I)-
RT elicited antiviral signaling.";
RL J. Biol. Chem. 284:19122-19131(2009).
RN [52]
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH PDLIM4, SUBCELLULAR
RP LOCATION, PHOSPHORYLATION AT TYR-419 AND TYR-530, AND MUTAGENESIS OF
RP PRO-302; PRO-307 AND TYR-419.
RX PubMed=19307596; DOI=10.1083/jcb.200810155;
RA Zhang Y., Tu Y., Zhao J., Chen K., Wu C.;
RT "Reversion-induced LIM interaction with Src reveals a novel Src
RT inactivation cycle.";
RL J. Cell Biol. 184:785-792(2009).
RN [53]
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 and
RT endothelial cell survival.";
RL Mol. Cell. Biol. 29:241-253(2009).
RN [54]
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 [55]
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 [56]
RP CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RX PubMed=21036157; DOI=10.1016/j.bbrc.2010.10.101;
RA Yao X., Balamurugan P., Arvey A., Leslie C., Zhang L.;
RT "Heme controls the regulation of protein tyrosine kinases Jak2 and Src.";
RL Biochem. Biophys. Res. Commun. 403:30-35(2010).
RN [57]
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., Li Y.H.,
RA 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 the
RT protein in the cytoplasm.";
RL J. Biol. Chem. 285:10122-10129(2010).
RN [58]
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 modulating
RT affinity for the ubiquitin-conjugating enzyme.";
RL J. Biol. Chem. 285:23687-23698(2010).
RN [59]
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 ubiquitin
RT ligase activators Ndfip1 and Ndfip2.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:11429-11434(2010).
RN [60]
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 Src
RT for activation.";
RL Biochem. J. 435:355-364(2011).
RN [61]
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 [62]
RP INTERACTION WITH PRR7.
RX PubMed=21460222; DOI=10.1074/jbc.m110.175117;
RA Hrdinka M., Draber P., Stepanek O., Ormsby T., Otahal P., Angelisova P.,
RA Brdicka T., Paces J., Horejsi V., Drbal K.;
RT "PRR7 is a transmembrane adaptor protein expressed in activated T cells
RT involved in regulation of T cell receptor signaling and apoptosis.";
RL J. Biol. Chem. 286:19617-19629(2011).
RN [63]
RP FUNCTION IN FOCAL ADHESION DYNAMICS, AND INTERACTION WITH PTK2/FAK1 AND
RP 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 regulates
RT focal adhesion dynamics in response to active Src.";
RL Mol. Biol. Cell 22:1529-1538(2011).
RN [64]
RP IDENTIFICATION IN A COMPLEX WITH PTPRA; BCAR1 AND BCAR3, AND SUBCELLULAR
RP LOCATION.
RX PubMed=22801373; DOI=10.1128/mcb.00214-12;
RA Sun G., Cheng S.Y., Chen M., Lim C.J., Pallen C.J.;
RT "Protein tyrosine phosphatase alpha phosphotyrosyl-789 binds BCAR3 to
RT position Cas for activation at integrin-mediated focal adhesions.";
RL Mol. Cell. Biol. 32:3776-3789(2012).
RN [65]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-17 AND SER-75, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [66]
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 substrate
RT of protein tyrosine phosphatase nonreceptor 14.";
RL Oncogene 32:2087-2095(2013).
RN [67]
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., Chen Y.,
RA Hasumi H., Xu W., Fukushima H., Nakamura K., Koga F., Kihara K., Trepel J.,
RA 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 [68]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-17, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [69]
RP FUNCTION, PHOSPHORYLATION AT TYR-419, AND INTERACTION WITH IL6ST.
RX PubMed=25731159; DOI=10.1038/nature14228;
RA Taniguchi K., Wu L.W., Grivennikov S.I., de Jong P.R., Lian I., Yu F.X.,
RA Wang K., Ho S.B., Boland B.S., Chang J.T., Sandborn W.J., Hardiman G.,
RA Raz E., Maehara Y., Yoshimura A., Zucman-Rossi J., Guan K.L., Karin M.;
RT "A gp130-Src-YAP module links inflammation to epithelial regeneration.";
RL Nature 519:57-62(2015).
RN [70]
RP PHOSPHORYLATION AT TYR-419 AND TYR-530, INVOLVEMENT IN THC6, VARIANT THC6
RP LYS-527, AND CHARACTERIZATION OF VARIANT THC6 LYS-527.
RX PubMed=26936507; DOI=10.1126/scitranslmed.aad7666;
RG BRIDGE-BPD Consortium;
RA Turro E., Greene D., Wijgaerts A., Thys C., Lentaigne C., Bariana T.K.,
RA Westbury S.K., Kelly A.M., Selleslag D., Stephens J.C., Papadia S.,
RA Simeoni I., Penkett C.J., Ashford S., Attwood A., Austin S., Bakchoul T.,
RA Collins P., Deevi S.V., Favier R., Kostadima M., Lambert M.P., Mathias M.,
RA Millar C.M., Peerlinck K., Perry D.J., Schulman S., Whitehorn D.,
RA Wittevrongel C., De Maeyer M., Rendon A., Gomez K., Erber W.N.,
RA Mumford A.D., Nurden P., Stirrups K., Bradley J.R., Raymond F.L.,
RA Laffan M.A., Van Geet C., Richardson S., Freson K., Ouwehand W.H.;
RT "A dominant gain-of-function mutation in universal tyrosine kinase SRC
RT causes thrombocytopenia, myelofibrosis, bleeding, and bone pathologies.";
RL Sci. Transl. Med. 8:328RA30-328RA30(2016).
RN [71]
RP INTERACTION WITH P85.
RX PubMed=28903391; DOI=10.18632/oncotarget.18973;
RA Lu Y., Zheng X., Hu W., Bian S., Zhang Z., Tao D., Liu Y., Ma Y.;
RT "Cancer/testis antigen PIWIL2 suppresses circadian rhythms by regulating
RT the stability and activity of BMAL1 and CLOCK.";
RL Oncotarget 8:54913-54924(2017).
RN [72]
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 [73]
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 [74]
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 [75]
RP INTERACTION WITH HCV NON-STRUCTURAL PROTEIN 5A (MICROBIAL INFECTION).
RX PubMed=30862675; DOI=10.1074/jbc.ra119.007656;
RA Klinker S., Stindt S., Gremer L., Bode J.G., Gertzen C.G.W., Gohlke H.,
RA Weiergraeber O.H., Hoffmann S., Willbold D.;
RT "Phosphorylated tyrosine 93 of hepatitis C virus nonstructural protein 5A
RT is essential for interaction with host c-Src and efficient viral
RT replication.";
RL J. Biol. Chem. 294:7388-7402(2019).
RN [76]
RP INTERACTION WITH HNRNPA2B1.
RX PubMed=31320558; DOI=10.1126/science.aav0758;
RA Wang L., Wen M., Cao X.;
RT "Nuclear hnRNPA2B1 initiates and amplifies the innate immune response to
RT DNA viruses.";
RL Science 0:0-0(2019).
RN [77]
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 [78]
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 structural
RT study.";
RL Biochemistry 36:6283-6293(1997).
RN [79]
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 [80]
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 412-424 IN COMPLEX WITH CBLC,
RP 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 the
RT tyrosine kinase binding domain of Cbl-c.";
RL J. Biochem. 152:487-495(2012).
RN [81]
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., 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 protein tyrosine kinase which is activated
CC following engagement of many different classes of cellular receptors
CC including immune response receptors, integrins and other adhesion
CC receptors, receptor protein tyrosine kinases, G protein-coupled
CC receptors as well as cytokine receptors. Participates in signaling
CC pathways that control a diverse spectrum of biological activities
CC including gene transcription, immune response, cell adhesion, cell
CC cycle progression, apoptosis, migration, and transformation. Due to
CC functional redundancy between members of the SRC kinase family,
CC identification of the specific role of each SRC kinase is very
CC difficult. SRC appears to be one of the primary kinases activated
CC following engagement of receptors and plays a role in the activation of
CC other protein tyrosine kinase (PTK) families. Receptor clustering or
CC dimerization leads to recruitment of SRC to the receptor complexes
CC where it phosphorylates the tyrosine residues within the receptor
CC cytoplasmic domains. Plays an important role in the regulation of
CC cytoskeletal organization through phosphorylation of specific
CC substrates such as AFAP1. Phosphorylation of AFAP1 allows the SRC SH2
CC domain to bind AFAP1 and to localize to actin filaments. Cytoskeletal
CC reorganization is also controlled through the phosphorylation of
CC cortactin (CTTN) (Probable). When cells adhere via focal adhesions to
CC the extracellular matrix, signals are transmitted by integrins into the
CC cell resulting in tyrosine phosphorylation of a number of focal
CC adhesion proteins, including PTK2/FAK1 and paxillin (PXN)
CC (PubMed:21411625). In addition to phosphorylating focal adhesion
CC proteins, SRC is also active at the sites of cell-cell contact adherens
CC junctions and phosphorylates substrates such as beta-catenin (CTNNB1),
CC delta-catenin (CTNND1), and plakoglobin (JUP). Another type of cell-
CC cell junction, the gap junction, is also a target for SRC, which
CC phosphorylates connexin-43 (GJA1). SRC is implicated in regulation of
CC pre-mRNA-processing and phosphorylates RNA-binding proteins such as
CC KHDRBS1 (Probable). Also plays a role in PDGF-mediated tyrosine
CC phosphorylation of both STAT1 and STAT3, leading to increased DNA
CC binding activity of these transcription factors (By similarity).
CC Involved in the RAS pathway through phosphorylation of RASA1 and
CC RASGRF1 (PubMed:11389730). Plays a role in EGF-mediated calcium-
CC activated chloride channel activation (PubMed:18586953). 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 GRK2, leading to beta-
CC arrestin phosphorylation and internalization. Has a critical role in
CC the stimulation of the CDK20/MAPK3 mitogen-activated protein kinase
CC cascade by epidermal growth factor (Probable). Might be involved not
CC only in mediating the transduction of mitogenic signals at the level of
CC the plasma membrane but also in controlling progression through the
CC cell cycle via interaction with regulatory proteins in the nucleus
CC (PubMed:7853507). Plays an important role in osteoclastic bone
CC resorption in conjunction with PTK2B/PYK2. Both the formation of a SRC-
CC PTK2B/PYK2 complex and SRC kinase activity are necessary for this
CC function. Recruited to activated integrins by PTK2B/PYK2, thereby
CC phosphorylating CBL, which in turn induces the activation and
CC recruitment of phosphatidylinositol 3-kinase to the cell membrane in a
CC signaling pathway that is critical for osteoclast function
CC (PubMed:8755529, PubMed:14585963). Promotes energy production in
CC osteoclasts by activating mitochondrial cytochrome C oxidase
CC (PubMed:12615910). Phosphorylates DDR2 on tyrosine residues, thereby
CC promoting its subsequent autophosphorylation (PubMed:16186108).
CC Phosphorylates RUNX3 and COX2 on tyrosine residues, TNK2 on 'Tyr-284'
CC and CBL on 'Tyr-731' (PubMed:20100835, PubMed:21309750). Enhances
CC DDX58/RIG-I-elicited antiviral signaling (PubMed:19419966).
CC Phosphorylates PDPK1 at 'Tyr-9', 'Tyr-373' and 'Tyr-376'
CC (PubMed:14585963). Phosphorylates BCAR1 at 'Tyr-128' (PubMed:22710723).
CC Phosphorylates CBLC at multiple tyrosine residues, phosphorylation at
CC 'Tyr-341' activates CBLC E3 activity (PubMed:20525694). Phosphorylates
CC synaptic vesicle protein synaptophysin (SYP) (By similarity). Involved
CC in anchorage-independent cell growth (PubMed:19307596). Required for
CC podosome formation (By similarity). Mediates IL6 signaling by
CC activating YAP1-NOTCH pathway to induce inflammation-induced epithelial
CC regeneration (PubMed:25731159). {ECO:0000250|UniProtKB:P05480,
CC ECO:0000250|UniProtKB:Q9WUD9, 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:19307596, ECO:0000269|PubMed:19419966,
CC ECO:0000269|PubMed:20100835, ECO:0000269|PubMed:20525694,
CC ECO:0000269|PubMed:21309750, ECO:0000269|PubMed:21411625,
CC ECO:0000269|PubMed:22710723, ECO:0000269|PubMed:25731159,
CC ECO:0000269|PubMed:7853507, ECO:0000269|PubMed:8755529,
CC ECO:0000269|PubMed:8759729, ECO:0000305|PubMed:11964124,
CC ECO:0000305|PubMed:8672527, ECO:0000305|PubMed:9442882}.
CC -!- FUNCTION: [Isoform 1]: Non-receptor protein tyrosine kinase which
CC phosphorylates synaptophysin with high affinity.
CC {ECO:0000250|UniProtKB:Q9WUD9}.
CC -!- FUNCTION: [Isoform 2]: Non-receptor protein tyrosine kinase which shows
CC higher basal kinase activity than isoform 1, possibly due to weakened
CC intramolecular interactions which enhance autophosphorylation of Tyr-
CC 419 and subsequent activation (By similarity). The SH3 domain shows
CC reduced affinity with the linker sequence between the SH2 and kinase
CC domains which may account for the increased basal activity (By
CC similarity). Displays altered substrate specificity compared to isoform
CC 1, showing weak affinity for synaptophysin and for peptide substrates
CC containing class I or class II SH3 domain-binding motifs (By
CC similarity). Plays a role in L1CAM-mediated neurite elongation,
CC possibly by acting downstream of L1CAM to drive cytoskeletal
CC rearrangements involved in neurite outgrowth (By similarity).
CC {ECO:0000250|UniProtKB:Q9WUD9}.
CC -!- FUNCTION: [Isoform 3]: Non-receptor protein tyrosine kinase which shows
CC higher basal kinase activity than isoform 1, possibly due to weakened
CC intramolecular interactions which enhance autophosphorylation of Tyr-
CC 419 and subsequent activation (By similarity). The SH3 domain shows
CC reduced affinity with the linker sequence between the SH2 and kinase
CC domains which may account for the increased basal activity (By
CC similarity). Displays altered substrate specificity compared to isoform
CC 1, showing weak affinity for synaptophysin and for peptide substrates
CC containing class I or class II SH3 domain-binding motifs (By
CC similarity). Plays a role in neurite elongation (By similarity).
CC {ECO:0000250|UniProtKB:Q9WUD9}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.2;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10028,
CC ECO:0000269|PubMed:14632929, ECO:0000269|PubMed:19307596,
CC ECO:0000269|PubMed:21036157, ECO:0000269|PubMed:7929427,
CC ECO:0000269|PubMed:8759729, ECO:0000269|PubMed:9571170};
CC -!- CATALYTIC ACTIVITY: [Isoform 1]:
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:0000250|UniProtKB:Q9WUD9};
CC -!- CATALYTIC ACTIVITY: [Isoform 2]:
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:0000250|UniProtKB:Q9WUD9};
CC -!- CATALYTIC ACTIVITY: [Isoform 3]:
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:0000250|UniProtKB:Q9WUD9};
CC -!- ACTIVITY REGULATION: Phosphorylation by CSK at Tyr-530 inhibits kinase
CC activity. Inhibitory phosphorylation at Tyr-530 is enhanced by heme.
CC Further phosphorylation by CDK1 partially reactivates CSK-inactivated
CC SRC and facilitates complete reactivation by protein tyrosine
CC phosphatase PTPRC. Integrin engagement stimulates kinase activity.
CC Phosphorylation by PTK2/FAK1 enhances kinase activity. Butein and
CC pseudosubstrate-based peptide inhibitors like CIYKYYF act as
CC inhibitors. Phosphorylation at Tyr-419 increases kinase activity.
CC {ECO:0000269|PubMed:14632929, ECO:0000269|PubMed:21036157,
CC ECO:0000269|PubMed:7929427, ECO:0000269|PubMed:8759729,
CC ECO:0000269|PubMed:9571170}.
CC -!- SUBUNIT: Part of a complex comprised of PTPRA, BCAR1, BCAR3 (via SH2
CC domain) and SRC; the formation of the complex is dependent on integrin
CC mediated-tyrosine phosphorylation of PTPRA (PubMed:22801373). Interacts
CC with DDEF1/ASAP1; via the SH3 domain (By similarity). Interacts with
CC CCPG1 (By similarity). Identified in a complex containing FGFR4, NCAM1,
CC CDH2, PLCG1, FRS2, SRC, SHC1, GAP43 and CTTN (By similarity). Interacts
CC with ERBB2, STAT1 and PNN (By similarity). Interacts with DDR1, DDR2
CC and DAB2 (By similarity). Interacts with CDCP1, TGFB1I1 and TOM1L2
CC (PubMed:15851033, PubMed:16479011, PubMed:17202804). Interacts with the
CC cytoplasmic domain of MUC1, phosphorylates it and increases binding of
CC MUC1 with beta-catenin (PubMed:11152665). Interacts with RALGPS1; via
CC the SH3 domain (PubMed:10747847). Interacts with CAV2 (tyrosine
CC phosphorylated form) (PubMed:12091389, PubMed:15504032). Interacts (via
CC the SH3 domain and the protein kinase domain) with ARRB1; the
CC interaction is independent of the phosphorylation state of SRC C-
CC terminus (By similarity). Interacts with ARRB1 and ARRB2
CC (PubMed:10753943, PubMed:9924018). Interacts with SRCIN1
CC (PubMed:17525734). Interacts with NDFIP2 and more weakly with NDFIP1
CC (PubMed:20534535). Interacts with PIK3CA and/or PIK3C2B, PTK2/FAK1 and
CC ESR1 (dimethylated on arginine) (PubMed:18657504, PubMed:21411625).
CC Interacts with FASLG (PubMed:19807924). Interacts (via SH2 domain) with
CC the 'Tyr-402' phosphorylated form of PTK2B/PYK2 (PubMed:14585963).
CC Interacts (via SH2 domain) with FLT3 (tyrosine phosphorylated) (By
CC similarity). Interacts with PDGFRA (tyrosine phosphorylated) (By
CC similarity). Interacts with CSF1R (By similarity). Interacts (via SH2
CC and SH3 domain) with TNK2 (PubMed:21309750). Interacts (via protein
CC kinase domain) with the tyrosine phosphorylated form of RUNX3 (via runt
CC domain) (PubMed:20100835). Interacts with TRAF3 (via RING-type zinc
CC finger domain) (PubMed:19419966). Interacts with DDX58, MAVS and TBK1
CC (PubMed:19419966). Interacts (via SH2 domain) with RACK1; the
CC interaction is enhanced by tyrosine phosphorylation of RACK1 and
CC inhibits SRC activity (PubMed:9584165, PubMed:11279199). Interacts with
CC EPHB1; activates the MAPK/ERK cascade to regulate cell migration
CC (PubMed:12925710). Interacts with FCAMR (PubMed:8759729). Interacts
CC (via SH2 domain) with the 'Tyr-9' phosphorylated form of PDPK1
CC (PubMed:18024423). Interacts with AMOTL2; this interaction regulates
CC the translocation of phosphorylated SRC to peripheral cell-matrix
CC adhesion sites (PubMed:17293535). Interacts with TRAP1
CC (PubMed:23564345). Interacts with CBLC; the interaction is enhanced
CC when SRC is phosphorylated at Tyr-419 (PubMed:14661060,
CC PubMed:22888118). Interacts with ARHGEF5 (By similarity). Interacts
CC (via cytoplasmic domain) with CEACAM1 (via SH2 domain); this
CC interaction is regulated by trans-homophilic cell adhesion
CC (PubMed:7478590). Interacts with MPP2 (PubMed:19665017). Interacts with
CC PRR7 (PubMed:21460222). Interacts (via kinase domain and to a lesser
CC extent the SH2 domain) directly with PDLIM4; this interaction results
CC in PTPN13-mediated dephosphorylation of this protein leading to its
CC inactivation (PubMed:19307596). Interacts with P85 (PIK3R1 or PIK3R2)
CC (PubMed:28903391). Interacts with HNRNPA2B1 (PubMed:31320558).
CC Interacts with IL6ST/gp130 (PubMed:25731159). Interacts (via SH3
CC domain) with PELP1 in the presence of 17-beta-estradiol. Interacts with
CC AMBRA1 (By similarity). {ECO:0000250|UniProtKB:P05480,
CC ECO:0000250|UniProtKB:Q9WUD9, ECO:0000269|PubMed:10747847,
CC ECO:0000269|PubMed:10753943, ECO:0000269|PubMed:11152665,
CC ECO:0000269|PubMed:11279199, ECO:0000269|PubMed:12091389,
CC ECO:0000269|PubMed:12925710, ECO:0000269|PubMed:14585963,
CC ECO:0000269|PubMed:14661060, ECO:0000269|PubMed:14963108,
CC ECO:0000269|PubMed:15504032, ECO:0000269|PubMed:15851033,
CC ECO:0000269|PubMed:16479011, ECO:0000269|PubMed:17202804,
CC ECO:0000269|PubMed:17293535, ECO:0000269|PubMed:17525734,
CC ECO:0000269|PubMed:18024423, ECO:0000269|PubMed:18657504,
CC ECO:0000269|PubMed:19307596, ECO:0000269|PubMed:19419966,
CC ECO:0000269|PubMed:19665017, ECO:0000269|PubMed:19807924,
CC ECO:0000269|PubMed:20100835, ECO:0000269|PubMed:20534535,
CC ECO:0000269|PubMed:21309750, ECO:0000269|PubMed:21411625,
CC ECO:0000269|PubMed:22801373, ECO:0000269|PubMed:22888118,
CC ECO:0000269|PubMed:23564345, ECO:0000269|PubMed:25731159,
CC ECO:0000269|PubMed:28903391, ECO:0000269|PubMed:31320558,
CC ECO:0000269|PubMed:7478590, ECO:0000269|PubMed:8759729,
CC ECO:0000269|PubMed:9584165, ECO:0000269|PubMed:9924018}.
CC -!- SUBUNIT: (Microbial infection) Interacts with HEV ORF3 protein; via the
CC SH3 domain. {ECO:0000269|PubMed:11518702}.
CC -!- SUBUNIT: (Microbial infection) Interacts (via SH2 domain) with HCV non-
CC structural protein 5A (via N-terminus). {ECO:0000269|PubMed:30862675}.
CC -!- INTERACTION:
CC P12931; P00519: ABL1; NbExp=2; IntAct=EBI-621482, EBI-375543;
CC P12931; P42684: ABL2; NbExp=2; IntAct=EBI-621482, EBI-1102694;
CC P12931; P12814: ACTN1; NbExp=2; IntAct=EBI-621482, EBI-351710;
CC P12931; O14672: ADAM10; NbExp=3; IntAct=EBI-621482, EBI-1536151;
CC P12931; O43184: ADAM12; NbExp=2; IntAct=EBI-621482, EBI-2625825;
CC P12931; Q13444: ADAM15; NbExp=4; IntAct=EBI-621482, EBI-77818;
CC P12931; P07550: ADRB2; NbExp=3; IntAct=EBI-621482, EBI-491169;
CC P12931; P55196: AFDN; NbExp=7; IntAct=EBI-621482, EBI-365875;
CC P12931; P10275: AR; NbExp=7; IntAct=EBI-621482, EBI-608057;
CC P12931; P49407: ARRB1; NbExp=3; IntAct=EBI-621482, EBI-743313;
CC P12931; P32121: ARRB2; NbExp=2; IntAct=EBI-621482, EBI-714559;
CC P12931; Q9ULH1: ASAP1; NbExp=3; IntAct=EBI-621482, EBI-346622;
CC P12931; Q6XD76: ASCL4; NbExp=3; IntAct=EBI-621482, EBI-10254793;
CC P12931; P56945: BCAR1; NbExp=3; IntAct=EBI-621482, EBI-702093;
CC P12931; Q14457: BECN1; NbExp=3; IntAct=EBI-621482, EBI-949378;
CC P12931; P22681: CBL; NbExp=8; IntAct=EBI-621482, EBI-518228;
CC P12931; Q16543: CDC37; NbExp=5; IntAct=EBI-621482, EBI-295634;
CC P12931; Q9H5V8: CDCP1; NbExp=3; IntAct=EBI-621482, EBI-1019736;
CC P12931; P12830: CDH1; NbExp=2; IntAct=EBI-621482, EBI-727477;
CC P12931; P68400: CSNK2A1; NbExp=2; IntAct=EBI-621482, EBI-347804;
CC P12931; P35222: CTNNB1; NbExp=2; IntAct=EBI-621482, EBI-491549;
CC P12931; P00533: EGFR; NbExp=9; IntAct=EBI-621482, EBI-297353;
CC P12931; P04626: ERBB2; NbExp=11; IntAct=EBI-621482, EBI-641062;
CC P12931; P21860: ERBB3; NbExp=2; IntAct=EBI-621482, EBI-720706;
CC P12931; P03372: ESR1; NbExp=12; IntAct=EBI-621482, EBI-78473;
CC P12931; P03372-4: ESR1; NbExp=2; IntAct=EBI-621482, EBI-4309277;
CC P12931; P14921-1: ETS1; NbExp=2; IntAct=EBI-621482, EBI-913224;
CC P12931; P25445: FAS; NbExp=2; IntAct=EBI-621482, EBI-494743;
CC P12931; Q8NFZ0: FBH1; NbExp=4; IntAct=EBI-621482, EBI-724767;
CC P12931; P06241: FYN; NbExp=3; IntAct=EBI-621482, EBI-515315;
CC P12931; Q13480: GAB1; NbExp=12; IntAct=EBI-621482, EBI-517684;
CC P12931; Q13322-4: GRB10; NbExp=3; IntAct=EBI-621482, EBI-12353035;
CC P12931; P19367: HK1; NbExp=2; IntAct=EBI-621482, EBI-713162;
CC P12931; P61978: HNRNPK; NbExp=6; IntAct=EBI-621482, EBI-304185;
CC P12931; P07900: HSP90AA1; NbExp=3; IntAct=EBI-621482, EBI-296047;
CC P12931; Q9Y6K9: IKBKG; NbExp=3; IntAct=EBI-621482, EBI-81279;
CC P12931; P35968: KDR; NbExp=6; IntAct=EBI-621482, EBI-1005487;
CC P12931; Q07666: KHDRBS1; NbExp=3; IntAct=EBI-621482, EBI-1364;
CC P12931; P10721: KIT; NbExp=5; IntAct=EBI-621482, EBI-1379503;
CC P12931; Q9UIH9: KLF15; NbExp=3; IntAct=EBI-621482, EBI-2796400;
CC P12931; Q8TBB1: LNX1; NbExp=6; IntAct=EBI-621482, EBI-739832;
CC P12931; Q14693: LPIN1; NbExp=3; IntAct=EBI-621482, EBI-5278370;
CC P12931; P07948: LYN; NbExp=4; IntAct=EBI-621482, EBI-79452;
CC P12931; Q9H204: MED28; NbExp=3; IntAct=EBI-621482, EBI-514199;
CC P12931; P08581: MET; NbExp=4; IntAct=EBI-621482, EBI-1039152;
CC P12931; Q13177: PAK2; NbExp=2; IntAct=EBI-621482, EBI-1045887;
CC P12931; P16284: PECAM1; NbExp=3; IntAct=EBI-621482, EBI-716404;
CC P12931; P27986: PIK3R1; NbExp=7; IntAct=EBI-621482, EBI-79464;
CC P12931; P27986-2: PIK3R1; NbExp=3; IntAct=EBI-621482, EBI-9090282;
CC P12931; Q92569: PIK3R3; NbExp=3; IntAct=EBI-621482, EBI-79893;
CC P12931; Q05397: PTK2; NbExp=9; IntAct=EBI-621482, EBI-702142;
CC P12931; Q14289: PTK2B; NbExp=3; IntAct=EBI-621482, EBI-298640;
CC P12931; P18031: PTPN1; NbExp=14; IntAct=EBI-621482, EBI-968788;
CC P12931; Q16825: PTPN21; NbExp=2; IntAct=EBI-621482, EBI-2860264;
CC P12931; P18433: PTPRA; NbExp=4; IntAct=EBI-621482, EBI-2609645;
CC P12931; Q15907: RAB11B; NbExp=3; IntAct=EBI-621482, EBI-722234;
CC P12931; Q13905: RAPGEF1; NbExp=2; IntAct=EBI-621482, EBI-976876;
CC P12931; Q01973: ROR1; NbExp=9; IntAct=EBI-621482, EBI-6082337;
CC P12931; P27635: RPL10; NbExp=6; IntAct=EBI-621482, EBI-352398;
CC P12931; O00560: SDCBP; NbExp=2; IntAct=EBI-621482, EBI-727004;
CC P12931; O60880: SH2D1A; NbExp=3; IntAct=EBI-621482, EBI-6983382;
CC P12931; O14796: SH2D1B; NbExp=3; IntAct=EBI-621482, EBI-3923013;
CC P12931; P35326: SPRR2A; NbExp=3; IntAct=EBI-621482, EBI-1047940;
CC P12931; Q9C0H9: SRCIN1; NbExp=3; IntAct=EBI-621482, EBI-1393949;
CC P12931; Q13829: TNFAIP1; NbExp=3; IntAct=EBI-621482, EBI-2505861;
CC P12931; Q68CZ2: TNS3; NbExp=13; IntAct=EBI-621482, EBI-1220488;
CC P12931; Q9UNY5: ZNF232; NbExp=3; IntAct=EBI-621482, EBI-749023;
CC P12931; Q8R5G7: Arap3; Xeno; NbExp=3; IntAct=EBI-621482, EBI-621463;
CC P12931; P52800: Efnb2; Xeno; NbExp=2; IntAct=EBI-621482, EBI-1032676;
CC P12931; P97288: Htr4; Xeno; NbExp=2; IntAct=EBI-621482, EBI-7149283;
CC P12931; P34152: Ptk2; Xeno; NbExp=2; IntAct=EBI-621482, EBI-77070;
CC P12931; P18052: Ptpra; Xeno; NbExp=3; IntAct=EBI-621482, EBI-6597520;
CC P12931; Q62884; Xeno; NbExp=3; IntAct=EBI-621482, EBI-7459400;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:7525268};
CC Lipid-anchor {ECO:0000269|PubMed:22801373}. Mitochondrion inner
CC membrane {ECO:0000269|PubMed:12615910}. Nucleus
CC {ECO:0000269|PubMed:7853507}. Cytoplasm, cytoskeleton
CC {ECO:0000269|PubMed:7525268}. Cytoplasm, perinuclear region
CC {ECO:0000269|PubMed:19307596}. Cell junction, focal adhesion
CC {ECO:0000269|PubMed:22801373}. Note=Localizes to focal adhesion sites
CC following integrin engagement (PubMed:22801373). Localization to focal
CC adhesion sites requires myristoylation and the SH3 domain
CC (PubMed:7525268). Colocalizes with PDLIM4 at the perinuclear region,
CC but not at focal adhesions (PubMed:19307596).
CC {ECO:0000269|PubMed:19307596, ECO:0000269|PubMed:22801373,
CC ECO:0000269|PubMed:7525268}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=c-src {ECO:0000303|PubMed:8319227};
CC IsoId=P12931-1; Sequence=Displayed;
CC Name=2; Synonyms=c-srcN1 {ECO:0000303|PubMed:8319227}, N1-Src
CC {ECO:0000250|UniProtKB:Q9WUD9};
CC IsoId=P12931-2; Sequence=VSP_012134;
CC Name=3; Synonyms=c-srcN2 {ECO:0000303|PubMed:8319227}, N2-Src
CC {ECO:0000250|UniProtKB:Q9WUD9};
CC IsoId=P12931-3; Sequence=VSP_061494;
CC -!- TISSUE SPECIFICITY: Expressed ubiquitously. Platelets, neurons and
CC osteoclasts express 5-fold to 200-fold higher levels than most other
CC tissues.
CC -!- TISSUE SPECIFICITY: [Isoform 1]: Expressed in spleen and liver.
CC {ECO:0000269|PubMed:8319227}.
CC -!- TISSUE SPECIFICITY: [Isoform 2]: Expressed in brain.
CC {ECO:0000269|PubMed:8319227}.
CC -!- TISSUE SPECIFICITY: [Isoform 3]: Expressed in brain.
CC {ECO:0000269|PubMed:8319227}.
CC -!- DEVELOPMENTAL STAGE: [Isoform 1]: Expressed at higher levels in fetal
CC liver than in adult liver. {ECO:0000269|PubMed:1691439}.
CC -!- DEVELOPMENTAL STAGE: [Isoform 2]: Expressed at higher levels in fetal
CC brain than in adult brain. {ECO:0000269|PubMed:1691439}.
CC -!- DEVELOPMENTAL STAGE: [Isoform 3]: Expressed at similar levels in adult
CC and fetal brain. {ECO:0000269|PubMed:1691439}.
CC -!- DOMAIN: The SH2 and SH3 domains are important for the intramolecular
CC and intermolecular interactions that regulate catalytic activity,
CC localization, and substrate recruitment.
CC -!- PTM: Myristoylated at Gly-2, and this is essential for targeting to
CC 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 phosphorylated
CC form is termed pp60c-src. Dephosphorylated by PTPRJ at Tyr-419.
CC Normally maintained in an inactive conformation with the SH2 domain
CC engaged with Tyr-530, the SH3 domain engaged with the SH2-kinase
CC linker, and Tyr-419 dephosphorylated. Dephosphorylation of Tyr-530 as a
CC result of protein tyrosine phosphatase (PTP) action disrupts the
CC intramolecular interaction between the SH2 domain and Tyr-530, Tyr-419
CC can then become autophosphorylated, resulting in SRC activation.
CC Phosphorylation of Tyr-530 by CSK allows this interaction to reform,
CC resulting in SRC inactivation. CDK5-mediated phosphorylation at Ser-75
CC targets SRC to ubiquitin-dependent degradation and thus leads to
CC cytoskeletal reorganization. Phosphorylated by PTK2/FAK1; this enhances
CC kinase activity. Phosphorylated by PTK2B/PYK2; this enhances kinase
CC activity. Upon activation of IL6ST by IL6, Tyr-419 is phosphorylated
CC and Tyr-530 dephosphorylated (PubMed:25731159). {ECO:0000250,
CC ECO:0000269|PubMed:14661060, ECO:0000269|PubMed:18936167,
CC ECO:0000269|PubMed:21442427, ECO:0000269|PubMed:22888118,
CC ECO:0000269|PubMed:25731159, ECO:0000269|PubMed:6273838,
CC ECO:0000269|PubMed:7525268}.
CC -!- PTM: [Isoform 1]: Displays reduced levels of autophosphorylation at
CC Tyr-419 compared to isoforms 2 and 3. {ECO:0000250|UniProtKB:Q9WUD9}.
CC -!- PTM: [Isoform 2]: Displays enhanced levels of autophosphorylation at
CC Tyr-419 compared to isoform 1. {ECO:0000250|UniProtKB:Q9WUD9}.
CC -!- PTM: [Isoform 3]: Displays enhanced levels of autophosphorylation at
CC Tyr-419 compared to isoform 1 (By similarity). Shows reduced
CC phosphorylation at Tyr-527 compared to isoforms 1 and 2 (By
CC similarity). {ECO:0000250|UniProtKB:Q9WUD9}.
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 at
CC 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 in
CC several tumor tissues and tumor cell lines such as colon carcinoma
CC cells. {ECO:0000269|PubMed:2498394, ECO:0000269|PubMed:3093483}.
CC -!- DISEASE: Thrombocytopenia 6 (THC6) [MIM:616937]: A form of
CC thrombocytopenia, a hematologic disorder defined by a decrease in the
CC number of platelets in circulating blood, resulting in the potential
CC for increased bleeding and decreased ability for clotting. THC6 is an
CC autosomal dominant form. Affected individuals may also have bone
CC abnormalities and an increased risk for myelofibrosis.
CC {ECO:0000269|PubMed:26936507}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. SRC subfamily. {ECO:0000255|PROSITE-ProRule:PRU00159}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/SRCID448ch20q11.html";
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DR EMBL; AL133293; -; NOT_ANNOTATED_CDS; 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_011529013.2. [P12931-1]
DR RefSeq; XP_016883513.1; XM_017028024.1. [P12931-2]
DR RefSeq; XP_016883514.1; XM_017028025.1. [P12931-2]
DR RefSeq; XP_016883515.1; XM_017028026.1. [P12931-2]
DR RefSeq; XP_016883516.1; XM_017028027.1. [P12931-2]
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 PDB; 6ATE; X-ray; 2.40 A; A=254-536.
DR PDB; 6C4S; X-ray; 1.50 A; A/B=87-144.
DR PDB; 6E6E; X-ray; 2.15 A; A/B/C/D/E/F/G/H=261-536.
DR PDB; 6EHJ; X-ray; 2.10 A; D/F=2-9.
DR PDB; 7NG7; X-ray; 1.50 A; A=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 PDBsum; 6ATE; -.
DR PDBsum; 6C4S; -.
DR PDBsum; 6E6E; -.
DR PDBsum; 6EHJ; -.
DR PDBsum; 7NG7; -.
DR AlphaFoldDB; P12931; -.
DR BMRB; P12931; -.
DR SASBDB; P12931; -.
DR SMR; P12931; -.
DR BioGRID; 112592; 546.
DR CORUM; P12931; -.
DR DIP; DIP-1059N; -.
DR ELM; P12931; -.
DR IntAct; P12931; 388.
DR MINT; P12931; -.
DR STRING; 9606.ENSP00000362680; -.
DR BindingDB; P12931; -.
DR ChEMBL; CHEMBL267; -.
DR DrugBank; DB08564; (2E)-N-{4-[(3-bromophenyl)amino]quinazolin-6-yl}-4-(dimethylamino)but-2-enamide.
DR DrugBank; DB08054; 1-(1-methylethyl)-3-quinolin-6-yl-1H-pyrazolo[3,4-d]pyrimidin-4-amine.
DR DrugBank; DB06882; 1-[1-(3-aminophenyl)-3-tert-butyl-1H-pyrazol-5-yl]-3-naphthalen-1-ylurea.
DR DrugBank; DB06883; 1-[1-(3-aminophenyl)-3-tert-butyl-1H-pyrazol-5-yl]-3-phenylurea.
DR DrugBank; DB08053; 1-cyclobutyl-3-(3,4-dimethoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine.
DR DrugBank; DB03023; 1-Tert-Butyl-3-(4-Chloro-Phenyl)-1h-Pyrazolo[3,4-D]Pyrimidin-4-Ylamine.
DR DrugBank; DB08192; 2-(4-CARCOXY-5-ISOPROPYLTHIAZOLYL)BENZOPIPERIDINE.
DR DrugBank; DB03104; 2-[4-[(Z)-2-Acetamido-3-oxo-3-[[(3S)-2-oxo-1-[(4-phenylphenyl)methyl]azepan-3-yl]amino]prop-1-enyl]-2-formylphenyl]acetic acid.
DR DrugBank; DB07335; 3-[4-AMINO-1-(1-METHYLETHYL)-1H-PYRAZOLO[3,4-D]PYRIMIDIN-3-YL]PHENOL.
DR DrugBank; DB04739; 4-[(4-METHYL-1-PIPERAZINYL)METHYL]-N-[3-[[4-(3-PYRIDINYL)-2-PYRIMIDINYL]AMINO]PHENYL]-BENZAMIDE.
DR DrugBank; DB07966; [4-({4-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]quinazolin-2-yl}amino)phenyl]acetonitrile.
DR DrugBank; DB06616; Bosutinib.
DR DrugBank; DB04272; Citric acid.
DR DrugBank; DB01254; Dasatinib.
DR DrugBank; DB03217; DPI59.
DR DrugBank; DB12010; Fostamatinib.
DR DrugBank; DB03628; ISO24.
DR DrugBank; DB02175; Malonic acid.
DR DrugBank; DB08462; N-(4-PHENYLAMINO-QUINAZOLIN-6-YL)-ACRYLAMIDE.
DR DrugBank; DB01893; N6-Benzyl Adenosine-5'-Diphosphate.
DR DrugBank; DB09079; Nintedanib.
DR DrugBank; DB03902; Oxalic Acid.
DR DrugBank; DB04495; Paratoulene phosphate.
DR DrugBank; DB03114; PAS219.
DR DrugBank; DB03078; PASBN.
DR DrugBank; DB07662; PD-168393.
DR DrugBank; DB03298; Phenylphosphate.
DR DrugBank; DB01962; Phosphonotyrosine.
DR DrugBank; DB08901; Ponatinib.
DR DrugBank; DB08052; PP-121.
DR DrugBank; DB04751; Purvalanol A.
DR DrugBank; DB04080; RU78191.
DR DrugBank; DB01947; RU78262.
DR DrugBank; DB03828; RU78299.
DR DrugBank; DB03306; RU78300.
DR DrugBank; DB02908; RU78783.
DR DrugBank; DB02762; RU79072.
DR DrugBank; DB03525; RU79073.
DR DrugBank; DB01866; RU79256.
DR DrugBank; DB03268; RU82197.
DR DrugBank; DB03591; RU82209.
DR DrugBank; DB02336; RU83876.
DR DrugBank; DB01678; RU84687.
DR DrugBank; DB03712; RU85053.
DR DrugBank; DB01908; RU85493.
DR DrugBank; DB02432; RU90395.
DR DrugBank; DB06137; Tirbanibulin.
DR DrugBank; DB05184; XL228.
DR DrugCentral; P12931; -.
DR GuidetoPHARMACOLOGY; 2206; -.
DR MoonDB; P12931; Predicted.
DR TCDB; 8.A.23.1.12; the basigin (basigin) family.
DR GlyGen; P12931; 2 sites, 1 O-linked glycan (1 site).
DR iPTMnet; P12931; -.
DR PhosphoSitePlus; P12931; -.
DR SwissPalm; P12931; -.
DR BioMuta; SRC; -.
DR DMDM; 125711; -.
DR OGP; P12931; -.
DR CPTAC; CPTAC-905; -.
DR EPD; P12931; -.
DR jPOST; P12931; -.
DR MassIVE; P12931; -.
DR MaxQB; P12931; -.
DR PaxDb; P12931; -.
DR PeptideAtlas; P12931; -.
DR PRIDE; P12931; -.
DR ProteomicsDB; 52884; -. [P12931-1]
DR ProteomicsDB; 52885; -. [P12931-2]
DR ABCD; P12931; 8 sequenced antibodies.
DR Antibodypedia; 3409; 1997 antibodies from 47 providers.
DR DNASU; 6714; -.
DR Ensembl; ENST00000358208.9; ENSP00000350941.5; ENSG00000197122.13. [P12931-3]
DR Ensembl; ENST00000373558.2; ENSP00000362659.2; ENSG00000197122.13. [P12931-2]
DR Ensembl; ENST00000373567.6; ENSP00000362668.2; ENSG00000197122.13. [P12931-1]
DR Ensembl; ENST00000373578.7; ENSP00000362680.2; ENSG00000197122.13. [P12931-1]
DR Ensembl; ENST00000692112.1; ENSP00000508666.1; ENSG00000197122.13. [P12931-1]
DR Ensembl; ENST00000692423.1; ENSP00000509325.1; ENSG00000197122.13. [P12931-1]
DR GeneID; 6714; -.
DR KEGG; hsa:6714; -.
DR MANE-Select; ENST00000373578.7; ENSP00000362680.2; NM_198291.3; NP_938033.1.
DR UCSC; uc002xgy.5; human. [P12931-1]
DR CTD; 6714; -.
DR DisGeNET; 6714; -.
DR GeneCards; SRC; -.
DR HGNC; HGNC:11283; SRC.
DR HPA; ENSG00000197122; Low tissue specificity.
DR MalaCards; SRC; -.
DR MIM; 190090; gene.
DR MIM; 616937; phenotype.
DR neXtProt; NX_P12931; -.
DR OpenTargets; ENSG00000197122; -.
DR Orphanet; 480851; Hereditary thrombocytopenia with early-onset myelofibrosis.
DR PharmGKB; PA36111; -.
DR VEuPathDB; HostDB:ENSG00000197122; -.
DR eggNOG; KOG0197; Eukaryota.
DR GeneTree; ENSGT00940000158250; -.
DR HOGENOM; CLU_000288_7_2_1; -.
DR InParanoid; P12931; -.
DR OMA; GMMNMEV; -.
DR OrthoDB; 1155741at2759; -.
DR PhylomeDB; P12931; -.
DR TreeFam; TF351634; -.
DR BioCyc; MetaCyc:HS02256-MON; -.
DR BRENDA; 2.7.10.2; 2681.
DR PathwayCommons; P12931; -.
DR Reactome; R-HSA-1227986; Signaling by ERBB2.
DR Reactome; R-HSA-1251985; Nuclear signaling by ERBB4.
DR Reactome; R-HSA-1253288; Downregulation of ERBB4 signaling.
DR Reactome; R-HSA-1257604; PIP3 activates AKT signaling.
DR Reactome; R-HSA-1295596; Spry regulation of FGF signaling. [P12931-1]
DR Reactome; R-HSA-1433557; Signaling by SCF-KIT. [P12931-1]
DR Reactome; R-HSA-1433559; Regulation of KIT signaling. [P12931-1]
DR Reactome; R-HSA-171007; p38MAPK events. [P12931-1]
DR Reactome; R-HSA-177929; Signaling by EGFR. [P12931-1]
DR Reactome; R-HSA-180292; GAB1 signalosome.
DR Reactome; R-HSA-186763; Downstream signal transduction.
DR Reactome; R-HSA-191650; Regulation of gap junction activity. [P12931-2]
DR Reactome; R-HSA-201556; Signaling by ALK. [P12931-1]
DR Reactome; R-HSA-2029481; FCGR activation. [P12931-1]
DR Reactome; R-HSA-210990; PECAM1 interactions. [P12931-1]
DR Reactome; R-HSA-2219530; Constitutive Signaling by Aberrant PI3K in Cancer.
DR Reactome; R-HSA-2682334; EPH-Ephrin signaling. [P12931-1]
DR Reactome; R-HSA-354192; Integrin 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. [P12931-1]
DR Reactome; R-HSA-389356; CD28 co-stimulation. [P12931-1]
DR Reactome; R-HSA-389513; CTLA4 inhibitory signaling. [P12931-1]
DR Reactome; R-HSA-391160; Signal regulatory protein family interactions. [P12931-1]
DR Reactome; R-HSA-3928662; EPHB-mediated forward signaling. [P12931-1]
DR Reactome; R-HSA-3928663; EPHA-mediated growth cone collapse. [P12931-1]
DR Reactome; R-HSA-3928664; Ephrin signaling. [P12931-1]
DR Reactome; R-HSA-3928665; EPH-ephrin mediated repulsion of cells. [P12931-1]
DR Reactome; R-HSA-418555; G alpha (s) signalling events.
DR Reactome; R-HSA-418592; ADP signalling through P2Y purinoceptor 1. [P12931-1]
DR Reactome; R-HSA-418594; G alpha (i) signalling events.
DR Reactome; R-HSA-418885; DCC mediated attractive signaling.
DR Reactome; R-HSA-418886; Netrin mediated repulsion signals.
DR Reactome; R-HSA-428542; Regulation of commissural axon pathfinding by SLIT and ROBO.
DR Reactome; R-HSA-430116; GP1b-IX-V activation signalling. [P12931-1]
DR Reactome; R-HSA-437239; Recycling pathway of L1. [P12931-1]
DR Reactome; R-HSA-4420097; VEGFA-VEGFR2 Pathway. [P12931-1]
DR Reactome; R-HSA-456926; Thrombin signalling through proteinase activated receptors (PARs). [P12931-1]
DR Reactome; R-HSA-5218921; VEGFR2 mediated cell proliferation. [P12931-1]
DR Reactome; R-HSA-5607764; CLEC7A (Dectin-1) signaling. [P12931-1]
DR Reactome; R-HSA-5663220; RHO GTPases Activate Formins. [P12931-1]
DR Reactome; R-HSA-5673000; RAF activation.
DR Reactome; R-HSA-5674135; MAP2K and MAPK activation.
DR Reactome; R-HSA-6802946; Signaling by moderate kinase activity BRAF mutants.
DR Reactome; R-HSA-6802948; Signaling by high-kinase activity BRAF mutants.
DR Reactome; R-HSA-6802952; Signaling by BRAF and RAF1 fusions.
DR Reactome; R-HSA-6802955; Paradoxical activation of RAF signaling by kinase inactive BRAF.
DR Reactome; R-HSA-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR Reactome; R-HSA-69231; Cyclin D associated events in G1. [P12931-1]
DR Reactome; R-HSA-8853659; RET signaling. [P12931-1]
DR Reactome; R-HSA-8874081; MET activates PTK2 signaling.
DR Reactome; R-HSA-8876493; InlA-mediated entry of Listeria monocytogenes into host cells.
DR Reactome; R-HSA-8934593; Regulation of RUNX1 Expression and Activity.
DR Reactome; R-HSA-8934903; Receptor Mediated Mitophagy. [P12931-1]
DR Reactome; R-HSA-8940973; RUNX2 regulates osteoblast differentiation.
DR Reactome; R-HSA-8941858; Regulation of RUNX3 expression and activity.
DR Reactome; R-HSA-9009391; Extra-nuclear estrogen signaling.
DR Reactome; R-HSA-9013420; RHOU GTPase cycle.
DR Reactome; R-HSA-9032500; Activated NTRK2 signals through FYN.
DR Reactome; R-HSA-9603381; Activated NTRK3 signals through PI3K.
DR Reactome; R-HSA-9620244; Long-term potentiation.
DR Reactome; R-HSA-9634597; GPER1 signaling.
DR Reactome; R-HSA-9649948; Signaling downstream of RAS mutants.
DR Reactome; R-HSA-9656223; Signaling by RAF1 mutants.
DR Reactome; R-HSA-9664323; FCGR3A-mediated IL10 synthesis. [P12931-1]
DR Reactome; R-HSA-9664422; FCGR3A-mediated phagocytosis. [P12931-1]
DR Reactome; R-HSA-9670439; Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants. [P12931-1]
DR SignaLink; P12931; -.
DR SIGNOR; P12931; -.
DR BioGRID-ORCS; 6714; 31 hits in 1121 CRISPR screens.
DR ChiTaRS; SRC; human.
DR EvolutionaryTrace; P12931; -.
DR GeneWiki; Src_(gene); -.
DR GenomeRNAi; 6714; -.
DR Pharos; P12931; Tclin.
DR PRO; PR:P12931; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; P12931; protein.
DR Bgee; ENSG00000197122; Expressed in body of stomach and 161 other tissues.
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:0030054; C:cell junction; IDA:HPA.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:1902737; C:dendritic filopodium; IEA:Ensembl.
DR GO; GO:0044294; C:dendritic growth cone; IEA:Ensembl.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; IBA:GO_Central.
DR GO; GO:0005925; C:focal adhesion; ISS:UniProtKB.
DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR GO; GO:0005770; C:late endosome; IDA:UniProtKB.
DR GO; GO:0005764; C:lysosome; IDA:UniProtKB.
DR GO; GO:0045121; C:membrane raft; ISS:ARUK-UCL.
DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0002102; C:podosome; IEA:Ensembl.
DR GO; GO:0014069; C:postsynaptic density; IEA:Ensembl.
DR GO; GO:0099091; C:postsynaptic specialization, intracellular component; IEA:Ensembl.
DR GO; GO:0032587; C:ruffle membrane; IEA:Ensembl.
DR GO; GO:0097060; C:synaptic membrane; IEA:Ensembl.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0051117; F:ATPase binding; ISS:ARUK-UCL.
DR GO; GO:0070700; F:BMP receptor binding; IPI:ARUK-UCL.
DR GO; GO:0045296; F:cadherin binding; HDA:BHF-UCL.
DR GO; GO:0071253; F:connexin binding; IEA:Ensembl.
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:0005158; F:insulin receptor binding; IEA:Ensembl.
DR GO; GO:0005178; F:integrin binding; IPI:UniProtKB.
DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IDA:ARUK-UCL.
DR GO; GO:0030331; F:nuclear estrogen receptor binding; IEA:Ensembl.
DR GO; GO:0016004; F:phospholipase activator activity; IDA:ARUK-UCL.
DR GO; GO:0043274; F:phospholipase binding; IPI:ARUK-UCL.
DR GO; GO:0051219; F:phosphoprotein binding; IPI:UniProtKB.
DR GO; GO:0008022; F:protein C-terminus binding; IPI:CAFA.
DR GO; GO:0004672; F:protein kinase activity; IDA:UniProtKB.
DR GO; GO:0005080; F:protein kinase C binding; IEA:Ensembl.
DR GO; GO:0004713; F:protein tyrosine kinase activity; IDA: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:0005102; F:signaling receptor binding; IPI:UniProtKB.
DR GO; GO:0044325; F:transmembrane transporter binding; IPI:BHF-UCL.
DR GO; GO:0032148; P:activation of protein kinase B activity; IEA:Ensembl.
DR GO; GO:0034332; P:adherens junction organization; IEA:Ensembl.
DR GO; GO:0086098; P:angiotensin-activated signaling pathway involved in heart process; ISS:BHF-UCL.
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:0008283; P:cell population proliferation; IEA:Ensembl.
DR GO; GO:0098609; P:cell-cell adhesion; IEA:Ensembl.
DR GO; GO:0071398; P:cellular response to fatty acid; IEA:Ensembl.
DR GO; GO:0071498; P:cellular response to fluid shear stress; IEA:Ensembl.
DR GO; GO:0070301; P:cellular response to hydrogen peroxide; IEA:Ensembl.
DR GO; GO:0071456; P:cellular response to hypoxia; IEA:Ensembl.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IEA:Ensembl.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; 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:1990646; P:cellular response to prolactin; IEA:Ensembl.
DR GO; GO:0071897; P:DNA biosynthetic process; IEA:Ensembl.
DR GO; GO:0035635; P:entry of bacterium into host cell; TAS:Reactome.
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:0038128; P:ERBB2 signaling pathway; TAS:Reactome.
DR GO; GO:0038096; P:Fc-gamma receptor signaling pathway involved in phagocytosis; TAS:Reactome.
DR GO; GO:0048041; P:focal adhesion assembly; IMP:UniProtKB.
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:0070102; P:interleukin-6-mediated signaling pathway; IDA:UniProtKB.
DR GO; GO:0060576; P:intestinal epithelial cell development; IDA:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; IDA:ARUK-UCL.
DR GO; GO:0007611; P:learning or memory; IEA:Ensembl.
DR GO; GO:0050900; P:leukocyte migration; TAS:Reactome.
DR GO; GO:0016236; P:macroautophagy; 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:0002862; P:negative regulation of inflammatory response to antigenic stimulus; TAS:Reactome.
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:0031333; P:negative regulation of protein-containing complex assembly; IMP:UniProtKB.
DR GO; GO:0051974; P:negative regulation of telomerase activity; IMP:BHF-UCL.
DR GO; GO:0032211; P:negative regulation of telomere maintenance via telomerase; IMP:BHF-UCL.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IEA:Ensembl.
DR GO; GO:0048011; P:neurotrophin TRK receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0042476; P:odontogenesis; IEA:Ensembl.
DR GO; GO:0048477; P:oogenesis; IEA:Ensembl.
DR GO; GO:0036035; P:osteoclast development; IBA:GO_Central.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IEA:Ensembl.
DR GO; GO:0038083; P:peptidyl-tyrosine autophosphorylation; IEA:Ensembl.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:UniProtKB.
DR GO; GO:0030168; P:platelet activation; TAS:Reactome.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IEA:Ensembl.
DR GO; GO:0045780; P:positive regulation of bone resorption; IEA:Ensembl.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IEA:Ensembl.
DR GO; GO:0045737; P:positive regulation of cyclin-dependent protein serine/threonine kinase activity; IEA:Ensembl.
DR GO; GO:0001819; P:positive regulation of cytokine production; IEA:Ensembl.
DR GO; GO:0035306; P:positive regulation of dephosphorylation; IDA:ARUK-UCL.
DR GO; GO:2000573; P:positive regulation of DNA biosynthetic process; 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:0010907; P:positive regulation of glucose metabolic process; IEA:Ensembl.
DR GO; GO:0035332; P:positive regulation of hippo signaling; IMP:FlyBase.
DR GO; GO:0046628; P:positive regulation of insulin receptor signaling pathway; 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:2000256; P:positive regulation of male germ cell proliferation; IEA:Ensembl.
DR GO; GO:0043406; P:positive regulation of MAP kinase activity; IEA:Ensembl.
DR GO; GO:1903997; P:positive regulation of non-membrane spanning protein tyrosine kinase activity; NAS:ARUK-UCL.
DR GO; GO:0045747; P:positive regulation of Notch signaling pathway; IDA:UniProtKB.
DR GO; GO:2000386; P:positive regulation of ovarian follicle development; IEA:Ensembl.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IMP:ARUK-UCL.
DR GO; GO:0043552; P:positive regulation of phosphatidylinositol 3-kinase activity; IEA:Ensembl.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; TAS:Reactome.
DR GO; GO:2000588; P:positive regulation of platelet-derived growth factor receptor-beta signaling pathway; IEA:Ensembl.
DR GO; GO:0071803; P:positive regulation of podosome assembly; IEA:Ensembl.
DR GO; GO:0031954; P:positive regulation of protein autophosphorylation; IEA:Ensembl.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; IMP:UniProtKB.
DR GO; GO:1900182; P:positive regulation of protein localization to nucleus; IEA:Ensembl.
DR GO; GO:0010954; P:positive regulation of protein processing; IEA:Ensembl.
DR GO; GO:0071902; P:positive regulation of protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0051222; P:positive regulation of protein transport; IEA:Ensembl.
DR GO; GO:0046579; P:positive regulation of Ras protein signal transduction; IEA:Ensembl.
DR GO; GO:0051057; P:positive regulation of small GTPase mediated signal transduction; IMP:ParkinsonsUK-UCL.
DR GO; GO:0014911; P:positive regulation of smooth muscle cell migration; IEA:Ensembl.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IEA:Ensembl.
DR GO; GO:1904707; P:positive regulation of vascular associated smooth muscle cell proliferation; IEA:Ensembl.
DR GO; GO:0001545; P:primary ovarian follicle growth; IEA:Ensembl.
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:0045124; P:regulation of bone resorption; TAS:BHF-UCL.
DR GO; GO:2001286; P:regulation of caveolin-mediated endocytosis; IMP:UniProtKB.
DR GO; GO:0060491; P:regulation of cell projection assembly; IEA:Ensembl.
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:0098962; P:regulation of postsynaptic neurotransmitter receptor activity; IEA:Ensembl.
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:0010447; P:response to acidic pH; IEA:Ensembl.
DR GO; GO:0051602; P:response to electrical stimulus; IEA:Ensembl.
DR GO; GO:0070555; P:response to interleukin-1; IMP:BHF-UCL.
DR GO; GO:0009612; P:response to mechanical stimulus; IEA:Ensembl.
DR GO; GO:0051385; P:response to mineralocorticoid; IEA:Ensembl.
DR GO; GO:0031667; P:response to nutrient levels; IEA:Ensembl.
DR GO; GO:0009615; P:response to virus; IEA:Ensembl.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0007172; P:signal complex assembly; TAS:ProtInc.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR GO; GO:0007283; P:spermatogenesis; IEA:Ensembl.
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:0045056; P:transcytosis; IEA:Ensembl.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR GO; GO:0060065; P:uterus development; IEA:Ensembl.
DR GO; GO:0048010; P:vascular endothelial growth factor receptor signaling pathway; TAS:Reactome.
DR DisProt; DP01570; -.
DR Gene3D; 3.30.505.10; -; 1.
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 Pfam; PF07714; PK_Tyr_Ser-Thr; 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; Cell cycle;
KW Cell junction; Cell membrane; Cytoplasm; Cytoskeleton; Disease variant;
KW Host-virus interaction; Immunity; Kinase; Lipoprotein; Membrane;
KW Mitochondrion; Mitochondrion inner membrane; Myristate; Nucleotide-binding;
KW Nucleus; Phosphoprotein; Proto-oncogene; Reference proteome; SH2 domain;
KW SH3 domain; Transferase; Tyrosine-protein kinase; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT CHAIN 2..536
FT /note="Proto-oncogene tyrosine-protein kinase Src"
FT /id="PRO_0000088141"
FT DOMAIN 84..145
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 151..248
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 270..523
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..53
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 389
FT /note="Proton acceptor"
FT BINDING 276..284
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 298
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT MOD_RES 17
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18088087,
FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 75
FT /note="Phosphoserine; by CDK5"
FT /evidence="ECO:0000269|PubMed:21442427,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 187
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P05480"
FT MOD_RES 419
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:14661060,
FT ECO:0000269|PubMed:18936167, ECO:0000269|PubMed:19307596,
FT ECO:0000269|PubMed:25731159, ECO:0000269|PubMed:26936507,
FT ECO:0000269|PubMed:6273838"
FT MOD_RES 419
FT /note="Phosphotyrosine; by FAK2"
FT /evidence="ECO:0000250"
FT MOD_RES 530
FT /note="Phosphotyrosine; by CSK"
FT /evidence="ECO:0000269|PubMed:19307596,
FT ECO:0000269|PubMed:26936507, ECO:0000269|PubMed:7525268,
FT ECO:0000269|PubMed:7929427, ECO:0007744|PubMed:19369195"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000269|PubMed:7525268"
FT VAR_SEQ 117
FT /note="T -> TRKVDVR (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:2681803"
FT /id="VSP_012134"
FT VAR_SEQ 117
FT /note="T -> TRKVDVSQTWFTFRWLQR (in isoform 3)"
FT /id="VSP_061494"
FT VARIANT 176
FT /note="L -> F (in dbSNP:rs6018260)"
FT /id="VAR_051699"
FT VARIANT 237
FT /note="A -> T (in dbSNP:rs34881773)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041830"
FT VARIANT 527
FT /note="E -> K (in THC6; increased protein tyrosine kinase
FT activity; increased autophosphorylation at Y-419; causes
FT defective megakaryopoiesis associated with increased
FT overall tyrosine phosphorylation in megakaryocytes;
FT dbSNP:rs879255268)"
FT /evidence="ECO:0000269|PubMed:26936507"
FT /id="VAR_076919"
FT MUTAGEN 298
FT /note="K->M: Kinase inactive. Abolishes ubiquitination
FT promoted by CBLC."
FT /evidence="ECO:0000269|PubMed:14661060"
FT MUTAGEN 302
FT /note="P->E: Kinase active. Interacts with PDLIM4; when
FT associated with E-307 and F-419."
FT /evidence="ECO:0000269|PubMed:19307596"
FT MUTAGEN 307
FT /note="P->E: Kinase active. Interacts with PDLIM4; when
FT associated with E-302 and F-419."
FT /evidence="ECO:0000269|PubMed:19307596"
FT MUTAGEN 419
FT /note="Y->F: Loss of kinase activity. Loss of interaction
FT with PDLIM4."
FT /evidence="ECO:0000269|PubMed:19307596"
FT STRAND 87..93
FT /evidence="ECO:0007829|PDB:1FMK"
FT STRAND 99..102
FT /evidence="ECO:0007829|PDB:1FMK"
FT STRAND 110..114
FT /evidence="ECO:0007829|PDB:1FMK"
FT STRAND 118..126
FT /evidence="ECO:0007829|PDB:1FMK"
FT TURN 127..129
FT /evidence="ECO:0007829|PDB:1FMK"
FT STRAND 132..136
FT /evidence="ECO:0007829|PDB:1FMK"
FT HELIX 137..139
FT /evidence="ECO:0007829|PDB:1FMK"
FT STRAND 140..142
FT /evidence="ECO:0007829|PDB:1FMK"
FT HELIX 146..148
FT /evidence="ECO:0007829|PDB:1FMK"
FT STRAND 152..154
FT /evidence="ECO:0007829|PDB:1FMK"
FT HELIX 158..165
FT /evidence="ECO:0007829|PDB:1FMK"
FT STRAND 167..170
FT /evidence="ECO:0007829|PDB:1SHD"
FT STRAND 174..179
FT /evidence="ECO:0007829|PDB:1FMK"
FT STRAND 181..183
FT /evidence="ECO:0007829|PDB:1FMK"
FT STRAND 187..195
FT /evidence="ECO:0007829|PDB:1FMK"
FT TURN 196..198
FT /evidence="ECO:0007829|PDB:1FMK"
FT STRAND 199..209
FT /evidence="ECO:0007829|PDB:1FMK"
FT STRAND 211..213
FT /evidence="ECO:0007829|PDB:2SRC"
FT STRAND 215..218
FT /evidence="ECO:0007829|PDB:1FMK"
FT STRAND 221..225
FT /evidence="ECO:0007829|PDB:1FMK"
FT HELIX 226..233
FT /evidence="ECO:0007829|PDB:1FMK"
FT STRAND 240..242
FT /evidence="ECO:0007829|PDB:1FMK"
FT STRAND 256..259
FT /evidence="ECO:0007829|PDB:1FMK"
FT HELIX 267..269
FT /evidence="ECO:0007829|PDB:1FMK"
FT STRAND 270..278
FT /evidence="ECO:0007829|PDB:1FMK"
FT STRAND 280..282
FT /evidence="ECO:0007829|PDB:6ATE"
FT STRAND 283..289
FT /evidence="ECO:0007829|PDB:1FMK"
FT TURN 290..292
FT /evidence="ECO:0007829|PDB:1FMK"
FT STRAND 293..299
FT /evidence="ECO:0007829|PDB:1FMK"
FT TURN 302..304
FT /evidence="ECO:0007829|PDB:2BDF"
FT HELIX 307..319
FT /evidence="ECO:0007829|PDB:1FMK"
FT STRAND 328..332
FT /evidence="ECO:0007829|PDB:1FMK"
FT STRAND 334..336
FT /evidence="ECO:0007829|PDB:1FMK"
FT STRAND 338..341
FT /evidence="ECO:0007829|PDB:1FMK"
FT STRAND 345..348
FT /evidence="ECO:0007829|PDB:6ATE"
FT HELIX 349..353
FT /evidence="ECO:0007829|PDB:1FMK"
FT HELIX 355..358
FT /evidence="ECO:0007829|PDB:1FMK"
FT HELIX 363..382
FT /evidence="ECO:0007829|PDB:1FMK"
FT HELIX 392..394
FT /evidence="ECO:0007829|PDB:1FMK"
FT STRAND 395..397
FT /evidence="ECO:0007829|PDB:1FMK"
FT HELIX 399..401
FT /evidence="ECO:0007829|PDB:1FMK"
FT STRAND 403..405
FT /evidence="ECO:0007829|PDB:1FMK"
FT HELIX 410..413
FT /evidence="ECO:0007829|PDB:2SRC"
FT HELIX 417..420
FT /evidence="ECO:0007829|PDB:2SRC"
FT TURN 423..426
FT /evidence="ECO:0007829|PDB:1Y57"
FT HELIX 429..431
FT /evidence="ECO:0007829|PDB:1FMK"
FT HELIX 434..439
FT /evidence="ECO:0007829|PDB:1FMK"
FT HELIX 444..459
FT /evidence="ECO:0007829|PDB:1FMK"
FT TURN 460..462
FT /evidence="ECO:0007829|PDB:1FMK"
FT HELIX 471..479
FT /evidence="ECO:0007829|PDB:1FMK"
FT HELIX 492..501
FT /evidence="ECO:0007829|PDB:1FMK"
FT HELIX 506..508
FT /evidence="ECO:0007829|PDB:1FMK"
FT HELIX 512..520
FT /evidence="ECO:0007829|PDB:1FMK"
FT TURN 521..523
FT /evidence="ECO:0007829|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
