SRC_MOUSE
ID SRC_MOUSE Reviewed; 535 AA.
AC P05480; F8WI90; Q2M4I4;
DT 01-NOV-1988, integrated into UniProtKB/Swiss-Prot.
DT 10-FEB-2021, sequence version 5.
DT 03-AUG-2022, entry version 230.
DE RecName: Full=Proto-oncogene tyrosine-protein kinase Src {ECO:0000305};
DE EC=2.7.10.2 {ECO:0000269|PubMed:8910389};
DE AltName: Full=Proto-oncogene c-Src;
DE AltName: Full=pp60c-src;
DE Short=p60-Src;
GN Name=Src {ECO:0000312|MGI:MGI:98397};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC STRAIN=BALB/cJ;
RX PubMed=2440106; DOI=10.1126/science.2440106;
RA Martinez R., Mathey-Prevot B., Bernards A., Baltimore D.;
RT "Neuronal pp60c-src contains a six-amino acid insertion relative to its
RT non-neuronal counterpart.";
RL Science 237:411-415(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 2).
RC STRAIN=CAST/EiJ; TISSUE=Brain;
RA Farber C.R., Corva P.M., Medrano J.F.;
RT "Characterization of quantitative trait loci influencing growth and
RT adiposity using congenic mouse strains.";
RL Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP INTERACTION WITH CSF1R.
RX PubMed=7681396; DOI=10.1002/j.1460-2075.1993.tb05735.x;
RA Courtneidge S.A., Dhand R., Pilat D., Twamley G.M., Waterfield M.D.,
RA Roussel M.F.;
RT "Activation of Src family kinases by colony stimulating factor-1, and their
RT association with its receptor.";
RL EMBO J. 12:943-950(1993).
RN [6]
RP INTERACTION WITH ERBB2.
RX PubMed=7542762;
RA Muthuswamy S.K., Muller W.J.;
RT "Direct and specific interaction of c-Src with Neu is involved in signaling
RT by the epidermal growth factor receptor.";
RL Oncogene 11:271-279(1995).
RN [7]
RP FUNCTION IN IL11-SIGNALING.
RX PubMed=8641341;
RA Fuhrer D.K., Yang Y.C.;
RT "Activation of Src-family protein tyrosine kinases and phosphatidylinositol
RT 3-kinase in 3T3-L1 mouse preadipocytes by interleukin-11.";
RL Exp. Hematol. 24:195-203(1996).
RN [8]
RP CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RX PubMed=8910389; DOI=10.1074/jbc.271.44.27895;
RA Rodriguez-Fernandez J.L., Rozengurt E.;
RT "Bombesin, bradykinin, vasopressin, and phorbol esters rapidly and
RT transiently activate Src family tyrosine kinases in Swiss 3T3 cells.
RT Dissociation from tyrosine phosphorylation of p125 focal adhesion kinase.";
RL J. Biol. Chem. 271:27895-27901(1996).
RN [9]
RP FUNCTION, AND INTERACTION WITH STAT1.
RX PubMed=9344858; DOI=10.1006/bbrc.1997.7493;
RA Cirri P., Chiarugi P., Marra F., Raugei G., Camici G., Manao G.,
RA Ramponi G.;
RT "c-Src activates both STAT1 and STAT3 in PDGF-stimulated NIH3T3 cells.";
RL Biochem. Biophys. Res. Commun. 239:493-497(1997).
RN [10]
RP INTERACTION WITH DDEF1/ASAP1.
RX PubMed=9819391; DOI=10.1128/mcb.18.12.7038;
RA Brown M.T., Andrade J., Radhakrishna H., Donaldson J.G., Cooper J.A.,
RA Randazzo P.A.;
RT "ASAP1, a phospholipid-dependent arf GTPase-activating protein that
RT associates with and is phosphorylated by Src.";
RL Mol. Cell. Biol. 18:7038-7051(1998).
RN [11]
RP IDENTIFICATION IN A COMPLEX WITH NCAM1; CDH2; PLCG1; FRS2; FGFR4; SHC1;
RP GAP43 AND CTTN.
RX PubMed=11433297; DOI=10.1038/35083041;
RA Cavallaro U., Niedermeyer J., Fuxa M., Christofori G.;
RT "N-CAM modulates tumour-cell adhesion to matrix by inducing FGF-receptor
RT signalling.";
RL Nat. Cell Biol. 3:650-657(2001).
RN [12]
RP INTERACTION WITH PDGFRA.
RX PubMed=14644164; DOI=10.1016/j.yexcr.2003.08.001;
RA Avrov K., Kazlauskas A.;
RT "The role of c-Src in platelet-derived growth factor alpha receptor
RT internalization.";
RL Exp. Cell Res. 291:426-434(2003).
RN [13]
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 [14]
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 [15]
RP FUNCTION, AND INTERACTION WITH PTK2B/PYK2.
RX PubMed=14739300; DOI=10.1074/jbc.m311032200;
RA Miyazaki T., Sanjay A., Neff L., Tanaka S., Horne W.C., Baron R.;
RT "Src kinase activity is essential for osteoclast function.";
RL J. Biol. Chem. 279:17660-17666(2004).
RN [16]
RP INTERACTION WITH FLT3.
RX PubMed=16684964; DOI=10.1182/blood-2005-07-008896;
RA Heiss E., Masson K., Sundberg C., Pedersen M., Sun J., Bengtsson S.,
RA Ronnstrand L.;
RT "Identification of Y589 and Y599 in the juxtamembrane domain of Flt3 as
RT ligand-induced autophosphorylation sites involved in binding of Src family
RT kinases and the protein tyrosine phosphatase SHP2.";
RL Blood 108:1542-1550(2006).
RN [17]
RP INTERACTION WITH CCPG1.
RX PubMed=17000758; DOI=10.1128/mcb.00670-06;
RA Kostenko E.V., Olabisi O.O., Sahay S., Rodriguez P.L., Whitehead I.P.;
RT "Ccpg1, a novel scaffold protein that regulates the activity of the Rho
RT guanine nucleotide exchange factor Dbs.";
RL Mol. Cell. Biol. 26:8964-8975(2006).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-186, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=18034455; DOI=10.1021/pr0701254;
RA Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P.;
RT "Large-scale identification and evolution indexing of tyrosine
RT phosphorylation sites from murine brain.";
RL J. Proteome Res. 7:311-318(2008).
RN [19]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [20]
RP INTERACTION WITH ARRB2.
RX PubMed=19122674; DOI=10.1038/nature07617;
RA Luan B., Zhao J., Wu H., Duan B., Shu G., Wang X., Li D., Jia W., Kang J.,
RA Pei G.;
RT "Deficiency of a beta-arrestin-2 signal complex contributes to insulin
RT resistance.";
RL Nature 457:1146-1149(2009).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-17; SER-21 AND SER-74, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Heart, Kidney, Lung, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [22]
RP INTERACTION WITH DDR1.
RX PubMed=20093046; DOI=10.1016/j.carpath.2009.12.006;
RA Lu K.K., Trcka D., Bendeck M.P.;
RT "Collagen stimulates discoidin domain receptor 1-mediated migration of
RT smooth muscle cells through Src.";
RL Cardiovasc. Pathol. 20:71-76(2011).
RN [23]
RP FUNCTION, INTERACTION WITH ARHGEF5, AND SUBCELLULAR LOCATION.
RX PubMed=21525037; DOI=10.1242/jcs.080291;
RA Kuroiwa M., Oneyama C., Nada S., Okada M.;
RT "The guanine nucleotide exchange factor Arhgef5 plays crucial roles in Src-
RT induced podosome formation.";
RL J. Cell Sci. 124:1726-1738(2011).
RN [24]
RP IDENTIFICATION IN A COMPLEX WITH PTPRA; BCAR1 AND BCAR3, SUBCELLULAR
RP LOCATION, AND PHOSPHORYLATION AT TYR-418 AND TYR-529.
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 [25]
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 [26]
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 [27]
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 [28]
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 [29]
RP FUNCTION, AND PHOSPHORYLATION AT TYR-418 AND TYR-529.
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 [30]
RP INTERACTION WITH AMBRA1.
RX PubMed=28362576; DOI=10.7554/elife.23172;
RA Schoenherr C., Byron A., Sandilands E., Paliashvili K., Baillie G.S.,
RA Garcia-Munoz A., Valacca C., Cecconi F., Serrels B., Frame M.C.;
RT "Ambra1 spatially regulates Src activity and Src/FAK-mediated cancer cell
RT invasion via trafficking networks.";
RL Elife 6:0-0(2017).
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) (By
CC similarity). In addition to phosphorylating focal adhesion proteins,
CC SRC is also active at the sites of cell-cell contact adherens junctions
CC and phosphorylates substrates such as beta-catenin (CTNNB1), delta-
CC catenin (CTNND1), and plakoglobin (JUP). Another type of cell-cell
CC 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 (PubMed:9344858).
CC Involved in the RAS pathway through phosphorylation of RASA1 and
CC RASGRF1. Plays a role in EGF-mediated calcium-activated chloride
CC channel activation (By similarity). Required for epidermal growth
CC factor receptor (EGFR) internalization through phosphorylation of
CC clathrin heavy chain (CLTC and CLTCL1) at 'Tyr-1477'. Involved in beta-
CC arrestin (ARRB1 and ARRB2) desensitization through phosphorylation and
CC activation of GRK2, leading to beta-arrestin phosphorylation and
CC internalization. Has a critical role in the stimulation of the
CC CDK20/MAPK3 mitogen-activated protein kinase cascade by epidermal
CC growth factor (Probable). Might be involved not only in mediating the
CC transduction of mitogenic signals at the level of the plasma membrane
CC but also in controlling progression through the cell cycle via
CC interaction with regulatory proteins in the nucleus (By similarity).
CC Plays an important role in osteoclastic bone resorption in conjunction
CC with PTK2B/PYK2. Both the formation of a SRC-PTK2B/PYK2 complex and SRC
CC kinase activity are necessary for this function. Recruited to activated
CC integrins by PTK2B/PYK2, thereby phosphorylating CBL, which in turn
CC induces the activation and recruitment of phosphatidylinositol 3-kinase
CC to the cell membrane in a signaling pathway that is critical for
CC osteoclast function (PubMed:14739300). 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. Phosphorylates RUNX3 and
CC COX2 on tyrosine residues, TNK2 on 'Tyr-284' and CBL on 'Tyr-738'.
CC Enhances DDX58/RIG-I-elicited antiviral signaling. Phosphorylates PDPK1
CC at 'Tyr-9', 'Tyr-373' and 'Tyr-376'. Phosphorylates BCAR1 at 'Tyr-226'.
CC Phosphorylates CBLC at multiple tyrosine residues, phosphorylation at
CC 'Tyr-341' activates CBLC E3 activity. Phosphorylates synaptic vesicle
CC protein synaptophysin (SYP) (By similarity). Involved in anchorage-
CC independent cell growth (By similarity). Required for podosome
CC formation (PubMed:21525037). Mediates IL6 signaling by activating YAP1-
CC NOTCH pathway to induce inflammation-induced epithelial regeneration
CC (PubMed:25731159). {ECO:0000250|UniProtKB:P12931,
CC ECO:0000250|UniProtKB:Q9WUD9, ECO:0000269|PubMed:12615910,
CC ECO:0000269|PubMed:14739300, ECO:0000269|PubMed:21525037,
CC ECO:0000269|PubMed:25731159, ECO:0000269|PubMed:8641341,
CC ECO:0000269|PubMed:9344858, 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 418 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 -!- 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:8910389};
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 -!- ACTIVITY REGULATION: Phosphorylation by CSK at Tyr-529 inhibits kinase
CC activity. Inhibitory phosphorylation at Tyr-529 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-418 increases kinase activity.
CC {ECO:0000269|PubMed:8910389}.
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 CDCP1, TGFB1I1 and TOM1L2 (By similarity). Interacts with
CC DDEF1/ASAP1 via its SH3 domain (PubMed:9819391). Interacts with CCPG1
CC (PubMed:17000758). Interacts with the cytoplasmic domain of MUC1,
CC phosphorylates it and increases binding of MUC1 with beta-catenin (By
CC similarity). Interacts with RALGPS1 via its SH3 domain (By similarity).
CC Interacts with CAV2 (tyrosine phosphorylated form) (By similarity).
CC Interacts (via the SH3 domain and the protein kinase domain) with
CC ARRB1; the interaction is independent of the phosphorylation state of
CC SRC C-terminus (By similarity). Interacts with FCAMR and PXN (By
CC similarity). Interacts with ARRB2 (PubMed:19122674). Interacts with
CC ARRB1 (By similarity). Interacts with SRCIN1 (By similarity). Interacts
CC with NDFIP2 and more weakly with NDFIP1 (By similarity). Interacts with
CC PIK3CA and/or PIK3C2B, PTK2/FAK1, ESR1 (dimethylated on arginine) and
CC FAK (PubMed:14739300). Interacts (via SH2 and SH3 domain) with TNK2 (By
CC similarity). Interacts (via protein kinase domain) with the tyrosine
CC phosphorylated form of RUNX3 (via runt domain) (By similarity).
CC Interacts with TRAF3 (via RING-type zinc finger domain) (By
CC similarity). Interacts with DDX58, MAVS and TBK1 (By similarity).
CC Interacts (via SH2 domain) with RACK1; the interaction is enhanced by
CC tyrosine phosphorylation of RACK1 and inhibits SRC activity (By
CC similarity). Interacts (via SH2 domain) with the 'Tyr-402'
CC phosphorylated form of PTK2B/PYK2 (PubMed:14739300). Interacts (via SH2
CC domain) with FLT3 (tyrosine phosphorylated) (PubMed:16684964).
CC Identified in a complex containing FGFR4, NCAM1, CDH2, PLCG1, FRS2,
CC SRC, SHC1, GAP43 and CTTN (PubMed:11433297). Interacts with EPHB1;
CC activates the MAPK/ERK cascade to regulate cell migration
CC (PubMed:12925710). Interacts with ERBB2 and STAT1 (PubMed:7542762,
CC PubMed:9344858). Interacts with PDGFRA (tyrosine phosphorylated)
CC (PubMed:14644164). Interacts with CSF1R (PubMed:7681396). Interacts
CC (via SH2 domain) with the 'Tyr-9' phosphorylated form of PDPK1 (By
CC similarity). Interacts with DDR2 (By similarity). Interacts with
CC AMOTL2; this interaction regulates the translocation of phosphorylated
CC SRC to peripheral cell-matrix adhesion sites (By similarity). Interacts
CC with DDR1 and DAB2 (PubMed:20093046). Interacts with TRAP1 (By
CC similarity). Interacts with CBLC; the interaction is enhanced when SRC
CC is phosphorylated at 'Tyr-424' (By similarity). Interacts with ARHGEF5
CC (PubMed:21525037). Interacts (via cytoplasmic domain) with CEACAM1 (via
CC SH2 domain); this interaction is regulated by trans-homophilic cell
CC adhesion (By similarity). Interacts with MPP2 (By similarity).
CC Interacts with PRR7 (By similarity). Interacts (via kinase domain and
CC to a lesser extent the SH2 domain) directly with PDLIM4; this
CC interaction results in PTPN13-mediated dephosphorylation of this
CC protein leading to its inactivation (By similarity). Interacts with P85
CC (PIK3R1 or PIK3R2) (By similarity). Interacts with HNRNPA2B1
CC (PubMed:31320558). Interacts with IL6ST/gp130 (By similarity).
CC Interacts (via SH3 domain) with PELP1 in the presence of 17-beta-
CC estradiol (By similarity). Interacts with AMBRA1 (PubMed:28362576).
CC {ECO:0000250|UniProtKB:P00523, ECO:0000250|UniProtKB:P12931,
CC ECO:0000250|UniProtKB:Q9WUD9, ECO:0000269|PubMed:11433297,
CC ECO:0000269|PubMed:12925710, ECO:0000269|PubMed:14644164,
CC ECO:0000269|PubMed:14739300, ECO:0000269|PubMed:16684964,
CC ECO:0000269|PubMed:17000758, ECO:0000269|PubMed:19122674,
CC ECO:0000269|PubMed:20093046, ECO:0000269|PubMed:21525037,
CC ECO:0000269|PubMed:22801373, ECO:0000269|PubMed:28362576,
CC ECO:0000269|PubMed:31320558, ECO:0000269|PubMed:7542762,
CC ECO:0000269|PubMed:7681396, ECO:0000269|PubMed:9344858,
CC ECO:0000269|PubMed:9819391}.
CC -!- INTERACTION:
CC P05480; P31750: Akt1; NbExp=3; IntAct=EBI-298680, EBI-298707;
CC P05480; P07141: Csf1; NbExp=2; IntAct=EBI-298680, EBI-777188;
CC P05480; P54763: Ephb2; NbExp=3; IntAct=EBI-298680, EBI-537711;
CC P05480; P23242: Gja1; NbExp=3; IntAct=EBI-298680, EBI-298630;
CC P05480; P18052: Ptpra; NbExp=2; IntAct=EBI-298680, EBI-6597520;
CC P05480; P70315: Was; NbExp=2; IntAct=EBI-298680, EBI-644195;
CC P05480; P31016: Dlg4; Xeno; NbExp=9; IntAct=EBI-298680, EBI-375655;
CC P05480; Q8T4F7: ena; Xeno; NbExp=2; IntAct=EBI-298680, EBI-466810;
CC P05480; Q00959: Grin2a; Xeno; NbExp=4; IntAct=EBI-298680, EBI-630970;
CC P05480; P19367: HK1; Xeno; NbExp=8; IntAct=EBI-298680, EBI-713162;
CC P05480; P52789: HK2; Xeno; NbExp=4; IntAct=EBI-298680, EBI-741469;
CC P05480; Q05397: PTK2; Xeno; NbExp=5; IntAct=EBI-298680, EBI-702142;
CC P05480; Q01973: ROR1; Xeno; NbExp=2; IntAct=EBI-298680, EBI-6082337;
CC P05480; Q13507-3: TRPC3; Xeno; NbExp=4; IntAct=EBI-298680, EBI-15563545;
CC P05480-2; P05106: ITGB3; Xeno; NbExp=4; IntAct=EBI-26656723, EBI-702847;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12615910,
CC ECO:0000269|PubMed:21525037}; Lipid-anchor
CC {ECO:0000269|PubMed:22801373}. Mitochondrion inner membrane
CC {ECO:0000269|PubMed:12615910}. Nucleus {ECO:0000269|PubMed:12615910}.
CC Cytoplasm, cytoskeleton {ECO:0000269|PubMed:12615910}. Cytoplasm,
CC perinuclear region {ECO:0000250|UniProtKB:P12931}. Cell junction, focal
CC adhesion {ECO:0000269|PubMed:22801373}. Note=Localizes to focal
CC adhesion sites following integrin engagement (PubMed:22801373).
CC Localization to focal adhesion sites requires myristoylation and the
CC SH3 domain. Colocalizes with PDLIM4 at the perinuclear region, but not
CC at focal adhesions. {ECO:0000250|UniProtKB:P12931,
CC ECO:0000269|PubMed:22801373}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=c-Src {ECO:0000250|UniProtKB:Q9WUD9};
CC IsoId=P05480-2; Sequence=Displayed;
CC Name=2; Synonyms=N1-Src {ECO:0000250|UniProtKB:Q9WUD9};
CC IsoId=P05480-1; Sequence=VSP_060883;
CC -!- PTM: Myristoylated at Gly-2, and this is essential for targeting to
CC membranes. {ECO:0000250}.
CC -!- PTM: Dephosphorylated at Tyr-529 by PTPRJ (By similarity).
CC Phosphorylated on Tyr-529 by c-Src kinase (CSK). The phosphorylated
CC form is termed pp60c-src. Dephosphorylated by PTPRJ at Tyr-418.
CC Normally maintained in an inactive conformation with the SH2 domain
CC engaged with Tyr-529, the SH3 domain engaged with the SH2-kinase
CC linker, and Tyr-418 dephosphorylated. Dephosphorylation of Tyr-529 as a
CC result of protein tyrosine phosphatase (PTP) action disrupts the
CC intramolecular interaction between the SH2 domain and Tyr-529, Tyr-418
CC can then become autophosphorylated, resulting in SRC activation.
CC Phosphorylation of Tyr-529 by CSK allows this interaction to reform,
CC resulting in SRC inactivation. CDK5-mediated phosphorylation at Ser-74
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 (By similarity). Upon activation of IL6ST by IL6, Tyr-418 is
CC phosphorylated and Tyr-529 dephosphorylated (PubMed:25731159).
CC {ECO:0000250, ECO:0000269|PubMed:25731159}.
CC -!- PTM: [Isoform 1]: Displays reduced levels of autophosphorylation at
CC Tyr-418 compared to isoform 2. {ECO:0000250|UniProtKB:Q9WUD9}.
CC -!- PTM: [Isoform 2]: Displays enhanced levels of autophosphorylation at
CC Tyr-418 compared to isoform 1. {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-418 and may lead to lysosomal degradation (By similarity).
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. SRC subfamily. {ECO:0000255|PROSITE-ProRule:PRU00159}.
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DR EMBL; M17031; AAA40135.1; -; mRNA.
DR EMBL; AY902331; AAX90616.1; -; Genomic_DNA.
DR EMBL; AL672259; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466551; EDL06234.1; -; Genomic_DNA.
DR CCDS; CCDS16978.1; -. [P05480-2]
DR CCDS; CCDS38305.1; -. [P05480-1]
DR PIR; A43610; A43610.
DR RefSeq; NP_001020566.1; NM_001025395.2. [P05480-2]
DR RefSeq; NP_033297.2; NM_009271.3. [P05480-1]
DR PDB; 6F3F; X-ray; 2.42 A; A=85-535.
DR PDBsum; 6F3F; -.
DR AlphaFoldDB; P05480; -.
DR BMRB; P05480; -.
DR SMR; P05480; -.
DR BioGRID; 203491; 87.
DR CORUM; P05480; -.
DR DIP; DIP-31071N; -.
DR IntAct; P05480; 41.
DR MINT; P05480; -.
DR STRING; 10090.ENSMUSP00000029175; -.
DR BindingDB; P05480; -.
DR ChEMBL; CHEMBL3074; -.
DR iPTMnet; P05480; -.
DR PhosphoSitePlus; P05480; -.
DR SwissPalm; P05480; -.
DR jPOST; P05480; -.
DR MaxQB; P05480; -.
DR PaxDb; P05480; -.
DR PeptideAtlas; P05480; -.
DR PRIDE; P05480; -.
DR ProteomicsDB; 263340; -. [P05480-2]
DR ProteomicsDB; 343377; -.
DR Antibodypedia; 3409; 1997 antibodies from 47 providers.
DR DNASU; 20779; -.
DR Ensembl; ENSMUST00000029175; ENSMUSP00000029175; ENSMUSG00000027646. [P05480-2]
DR Ensembl; ENSMUST00000092576; ENSMUSP00000090237; ENSMUSG00000027646. [P05480-1]
DR Ensembl; ENSMUST00000109529; ENSMUSP00000105155; ENSMUSG00000027646. [P05480-1]
DR Ensembl; ENSMUST00000109531; ENSMUSP00000105157; ENSMUSG00000027646. [P05480-2]
DR Ensembl; ENSMUST00000109533; ENSMUSP00000105159; ENSMUSG00000027646. [P05480-2]
DR GeneID; 20779; -.
DR KEGG; mmu:20779; -.
DR UCSC; uc008npa.1; mouse. [P05480-2]
DR CTD; 6714; -.
DR MGI; MGI:98397; Src.
DR VEuPathDB; HostDB:ENSMUSG00000027646; -.
DR eggNOG; KOG0197; Eukaryota.
DR GeneTree; ENSGT00940000158250; -.
DR InParanoid; P05480; -.
DR OMA; GMMNMEV; -.
DR OrthoDB; 539311at2759; -.
DR PhylomeDB; P05480; -.
DR BRENDA; 2.7.10.2; 3474.
DR Reactome; R-MMU-1227986; Signaling by ERBB2.
DR Reactome; R-MMU-1251985; Nuclear signaling by ERBB4.
DR Reactome; R-MMU-1253288; Downregulation of ERBB4 signaling.
DR Reactome; R-MMU-1257604; PIP3 activates AKT signaling.
DR Reactome; R-MMU-1295596; Spry regulation of FGF signaling.
DR Reactome; R-MMU-1433557; Signaling by SCF-KIT.
DR Reactome; R-MMU-1433559; Regulation of KIT signaling.
DR Reactome; R-MMU-177929; Signaling by EGFR.
DR Reactome; R-MMU-180292; GAB1 signalosome.
DR Reactome; R-MMU-186763; Downstream signal transduction.
DR Reactome; R-MMU-191650; Regulation of gap junction activity.
DR Reactome; R-MMU-2029481; FCGR activation.
DR Reactome; R-MMU-210990; PECAM1 interactions.
DR Reactome; R-MMU-354192; Integrin signaling.
DR Reactome; R-MMU-354194; GRB2:SOS provides linkage to MAPK signaling for Integrins.
DR Reactome; R-MMU-372708; p130Cas linkage to MAPK signaling for integrins.
DR Reactome; R-MMU-389356; CD28 co-stimulation.
DR Reactome; R-MMU-389513; CTLA4 inhibitory signaling.
DR Reactome; R-MMU-3928662; EPHB-mediated forward signaling.
DR Reactome; R-MMU-3928663; EPHA-mediated growth cone collapse.
DR Reactome; R-MMU-3928664; Ephrin signaling.
DR Reactome; R-MMU-3928665; EPH-ephrin mediated repulsion of cells.
DR Reactome; R-MMU-418592; ADP signalling through P2Y purinoceptor 1.
DR Reactome; R-MMU-418594; G alpha (i) signalling events.
DR Reactome; R-MMU-418885; DCC mediated attractive signaling.
DR Reactome; R-MMU-430116; GP1b-IX-V activation signalling.
DR Reactome; R-MMU-437239; Recycling pathway of L1.
DR Reactome; R-MMU-4420097; VEGFA-VEGFR2 Pathway.
DR Reactome; R-MMU-456926; Thrombin signalling through proteinase activated receptors (PARs).
DR Reactome; R-MMU-5218921; VEGFR2 mediated cell proliferation.
DR Reactome; R-MMU-5607764; CLEC7A (Dectin-1) signaling.
DR Reactome; R-MMU-5663220; RHO GTPases Activate Formins.
DR Reactome; R-MMU-5673000; RAF activation.
DR Reactome; R-MMU-5674135; MAP2K and MAPK activation.
DR Reactome; R-MMU-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR Reactome; R-MMU-69231; Cyclin D associated events in G1.
DR Reactome; R-MMU-8853659; RET signaling.
DR Reactome; R-MMU-8874081; MET activates PTK2 signaling.
DR Reactome; R-MMU-8934903; Receptor Mediated Mitophagy.
DR Reactome; R-MMU-8941858; Regulation of RUNX3 expression and activity.
DR Reactome; R-MMU-9009391; Extra-nuclear estrogen signaling.
DR Reactome; R-MMU-9603381; Activated NTRK3 signals through PI3K.
DR BioGRID-ORCS; 20779; 1 hit in 73 CRISPR screens.
DR ChiTaRS; Src; mouse.
DR PRO; PR:P05480; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; P05480; protein.
DR Bgee; ENSMUSG00000027646; Expressed in dentate gyrus of hippocampal formation granule cell and 210 other tissues.
DR ExpressionAtlas; P05480; baseline and differential.
DR Genevisible; P05480; MM.
DR GO; GO:0005884; C:actin filament; IDA:MGI.
DR GO; GO:0005901; C:caveola; IDA:BHF-UCL.
DR GO; GO:0030054; C:cell junction; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:CAFA.
DR GO; GO:0005856; C:cytoskeleton; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:1902737; C:dendritic filopodium; ISO:MGI.
DR GO; GO:0044294; C:dendritic growth cone; ISO:MGI.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; IBA:GO_Central.
DR GO; GO:0005925; C:focal adhesion; IMP:UniProtKB.
DR GO; GO:0098978; C:glutamatergic synapse; ISO:MGI.
DR GO; GO:0005770; C:late endosome; ISO:MGI.
DR GO; GO:0005764; C:lysosome; ISO:MGI.
DR GO; GO:0016020; C:membrane; IMP:UniProtKB.
DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0043005; C:neuron projection; ISO:MGI.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:MGI.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0002102; C:podosome; IDA:MGI.
DR GO; GO:0014069; C:postsynaptic density; ISO:MGI.
DR GO; GO:0099091; C:postsynaptic specialization, intracellular component; ISO:MGI.
DR GO; GO:0032587; C:ruffle membrane; IDA:MGI.
DR GO; GO:0097060; C:synaptic membrane; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0070700; F:BMP receptor binding; ISO:MGI.
DR GO; GO:0050839; F:cell adhesion molecule binding; ISO:MGI.
DR GO; GO:0071253; F:connexin binding; IPI:CAFA.
DR GO; GO:0019899; F:enzyme binding; ISO:MGI.
DR GO; GO:0046875; F:ephrin receptor binding; IPI:UniProtKB.
DR GO; GO:0070851; F:growth factor receptor binding; ISO:MGI.
DR GO; GO:0020037; F:heme binding; ISS:UniProtKB.
DR GO; GO:0005158; F:insulin receptor binding; ISO:MGI.
DR GO; GO:0005178; F:integrin binding; ISO:MGI.
DR GO; GO:0016301; F:kinase activity; IMP:MGI.
DR GO; GO:0019900; F:kinase binding; ISO:MGI.
DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; ISO:MGI.
DR GO; GO:0030331; F:nuclear estrogen receptor binding; ISO:MGI.
DR GO; GO:0016004; F:phospholipase activator activity; ISO:MGI.
DR GO; GO:0043274; F:phospholipase binding; ISO:MGI.
DR GO; GO:0051219; F:phosphoprotein binding; ISO:MGI.
DR GO; GO:0008022; F:protein C-terminus binding; ISO:MGI.
DR GO; GO:0019904; F:protein domain specific binding; IPI:MGI.
DR GO; GO:0004672; F:protein kinase activity; IDA:MGI.
DR GO; GO:0019901; F:protein kinase binding; ISO:MGI.
DR GO; GO:0005080; F:protein kinase C binding; ISO:MGI.
DR GO; GO:0004713; F:protein tyrosine kinase activity; IDA:UniProtKB.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0097110; F:scaffold protein binding; IPI:BHF-UCL.
DR GO; GO:0042169; F:SH2 domain binding; ISO:MGI.
DR GO; GO:0005102; F:signaling receptor binding; ISO:MGI.
DR GO; GO:0044325; F:transmembrane transporter binding; ISO:MGI.
DR GO; GO:0032148; P:activation of protein kinase B activity; ISO:MGI.
DR GO; GO:0034332; P:adherens junction organization; IEA:Ensembl.
DR GO; GO:0086098; P:angiotensin-activated signaling pathway involved in heart process; IGI:BHF-UCL.
DR GO; GO:0045453; P:bone resorption; IMP:UniProtKB.
DR GO; GO:0060444; P:branching involved in mammary gland duct morphogenesis; IMP:MGI.
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:0016477; P:cell migration; IMP:MGI.
DR GO; GO:0008283; P:cell population proliferation; ISO:MGI.
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; IMP:MGI.
DR GO; GO:0070301; P:cellular response to hydrogen peroxide; IMP:MGI.
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; IGI:BHF-UCL.
DR GO; GO:0036120; P:cellular response to platelet-derived growth factor stimulus; IDA:MGI.
DR GO; GO:0071393; P:cellular response to progesterone stimulus; ISO:MGI.
DR GO; GO:1990646; P:cellular response to prolactin; IEA:Ensembl.
DR GO; GO:0034614; P:cellular response to reactive oxygen species; IDA:MGI.
DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; IGI:MGI.
DR GO; GO:0071897; P:DNA biosynthetic process; ISO:MGI.
DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0048041; P:focal adhesion assembly; ISO:MGI.
DR GO; GO:0030900; P:forebrain development; IGI:MGI.
DR GO; GO:0045087; P:innate immune response; IBA:GO_Central.
DR GO; GO:0007229; P:integrin-mediated signaling pathway; ISO:MGI.
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; IGI:MGI.
DR GO; GO:0007611; P:learning or memory; IEA:Ensembl.
DR GO; GO:2000811; P:negative regulation of anoikis; ISO:MGI.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:MGI.
DR GO; GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; ISO:MGI.
DR GO; GO:2001237; P:negative regulation of extrinsic apoptotic signaling pathway; ISO:MGI.
DR GO; GO:0051895; P:negative regulation of focal adhesion assembly; ISO:MGI.
DR GO; GO:2001243; P:negative regulation of intrinsic apoptotic signaling pathway; ISO:MGI.
DR GO; GO:0051902; P:negative regulation of mitochondrial depolarization; ISO:MGI.
DR GO; GO:0031333; P:negative regulation of protein-containing complex assembly; ISO:MGI.
DR GO; GO:0051974; P:negative regulation of telomerase activity; ISO:MGI.
DR GO; GO:0032211; P:negative regulation of telomere maintenance via telomerase; ISO:MGI.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISO:MGI.
DR GO; GO:0048011; P:neurotrophin TRK receptor signaling pathway; ISO:MGI.
DR GO; GO:0042476; P:odontogenesis; IMP:MGI.
DR GO; GO:0048477; P:oogenesis; IMP:MGI.
DR GO; GO:0036035; P:osteoclast development; IGI:MGI.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; ISO:MGI.
DR GO; GO:0038083; P:peptidyl-tyrosine autophosphorylation; ISO:MGI.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:MGI.
DR GO; GO:0016310; P:phosphorylation; IMP:BHF-UCL.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:MGI.
DR GO; GO:0045780; P:positive regulation of bone resorption; ISO:MGI.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IGI:MGI.
DR GO; GO:0045785; P:positive regulation of cell adhesion; ISO:MGI.
DR GO; GO:0045737; P:positive regulation of cyclin-dependent protein serine/threonine kinase activity; ISO:MGI.
DR GO; GO:0001819; P:positive regulation of cytokine production; ISO:MGI.
DR GO; GO:0035306; P:positive regulation of dephosphorylation; ISO:MGI.
DR GO; GO:2000573; P:positive regulation of DNA biosynthetic process; ISO:MGI.
DR GO; GO:0010634; P:positive regulation of epithelial cell migration; ISO:MGI.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IMP:BHF-UCL.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:MGI.
DR GO; GO:0010907; P:positive regulation of glucose metabolic process; ISO:MGI.
DR GO; GO:0035332; P:positive regulation of hippo signaling; IEA:Ensembl.
DR GO; GO:0046628; P:positive regulation of insulin receptor signaling pathway; ISO:MGI.
DR GO; GO:1902533; P:positive regulation of intracellular signal transduction; ISO:MGI.
DR GO; GO:2000394; P:positive regulation of lamellipodium morphogenesis; ISO:MGI.
DR GO; GO:2000256; P:positive regulation of male germ cell proliferation; ISO:MGI.
DR GO; GO:0043406; P:positive regulation of MAP kinase activity; ISO:MGI.
DR GO; GO:0045747; P:positive regulation of Notch signaling pathway; IDA:UniProtKB.
DR GO; GO:2000386; P:positive regulation of ovarian follicle development; ISO:MGI.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IGI:MGI.
DR GO; GO:0043552; P:positive regulation of phosphatidylinositol 3-kinase activity; ISO:MGI.
DR GO; GO:2000588; P:positive regulation of platelet-derived growth factor receptor-beta signaling pathway; IMP:MGI.
DR GO; GO:0071803; P:positive regulation of podosome assembly; IDA:MGI.
DR GO; GO:0031954; P:positive regulation of protein autophosphorylation; ISO:MGI.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; ISO:MGI.
DR GO; GO:1900182; P:positive regulation of protein localization to nucleus; IGI:MGI.
DR GO; GO:0010954; P:positive regulation of protein processing; IGI:MGI.
DR GO; GO:0071902; P:positive regulation of protein serine/threonine kinase activity; ISO:MGI.
DR GO; GO:0051222; P:positive regulation of protein transport; ISO:MGI.
DR GO; GO:0046579; P:positive regulation of Ras protein signal transduction; ISO:MGI.
DR GO; GO:0051057; P:positive regulation of small GTPase mediated signal transduction; ISO:MGI.
DR GO; GO:0014911; P:positive regulation of smooth muscle cell migration; ISO:MGI.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISO:MGI.
DR GO; GO:1904707; P:positive regulation of vascular associated smooth muscle cell proliferation; ISO:MGI.
DR GO; GO:0001545; P:primary ovarian follicle growth; ISO:MGI.
DR GO; GO:0050847; P:progesterone receptor signaling pathway; ISO:MGI.
DR GO; GO:0046777; P:protein autophosphorylation; ISO:MGI.
DR GO; GO:0031648; P:protein destabilization; IMP:CACAO.
DR GO; GO:0006468; P:protein phosphorylation; IDA:MGI.
DR GO; GO:2001286; P:regulation of caveolin-mediated endocytosis; ISO:MGI.
DR GO; GO:0060491; P:regulation of cell projection assembly; IGI:MGI.
DR GO; GO:0022407; P:regulation of cell-cell adhesion; ISO:MGI.
DR GO; GO:2000641; P:regulation of early endosome to late endosome transport; ISO:MGI.
DR GO; GO:0010632; P:regulation of epithelial cell migration; ISO:MGI.
DR GO; GO:0033146; P:regulation of intracellular estrogen receptor signaling pathway; IMP:MGI.
DR GO; GO:0098962; P:regulation of postsynaptic neurotransmitter receptor activity; ISO:MGI.
DR GO; GO:0043393; P:regulation of protein binding; IDA:MGI.
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; ISO:MGI.
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:0007283; P:spermatogenesis; IEA:Ensembl.
DR GO; GO:0043149; P:stress fiber assembly; ISO:MGI.
DR GO; GO:0034446; P:substrate adhesion-dependent cell spreading; IDA:MGI.
DR GO; GO:0045056; P:transcytosis; ISO:MGI.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; ISO:MGI.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR GO; GO:0060065; P:uterus development; IMP:MGI.
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; Immunity; Kinase;
KW Lipoprotein; Membrane; Mitochondrion; Mitochondrion inner membrane;
KW Myristate; Nucleotide-binding; Nucleus; Phosphoprotein; Proto-oncogene;
KW Reference proteome; SH2 domain; SH3 domain; Transferase;
KW Tyrosine-protein kinase; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P12931"
FT CHAIN 2..535
FT /note="Proto-oncogene tyrosine-protein kinase Src"
FT /id="PRO_0000088142"
FT DOMAIN 83..144
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 150..247
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 269..522
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..56
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 388
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 275..283
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 297
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 17
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 21
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 74
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 186
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:18034455"
FT MOD_RES 418
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:22801373,
FT ECO:0000269|PubMed:25731159"
FT MOD_RES 418
FT /note="Phosphotyrosine; by FAK2"
FT /evidence="ECO:0000269|PubMed:22801373"
FT MOD_RES 529
FT /note="Phosphotyrosine; by CSK"
FT /evidence="ECO:0000269|PubMed:22801373,
FT ECO:0000269|PubMed:25731159"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000250"
FT VAR_SEQ 116
FT /note="T -> TRKVDVR (in isoform 2)"
FT /id="VSP_060883"
FT CONFLICT 80
FT /note="P -> A (in Ref. 1; AAA40135)"
FT /evidence="ECO:0000305"
FT STRAND 85..92
FT /evidence="ECO:0007829|PDB:6F3F"
FT STRAND 98..101
FT /evidence="ECO:0007829|PDB:6F3F"
FT STRAND 109..113
FT /evidence="ECO:0007829|PDB:6F3F"
FT STRAND 118..125
FT /evidence="ECO:0007829|PDB:6F3F"
FT TURN 126..128
FT /evidence="ECO:0007829|PDB:6F3F"
FT STRAND 131..135
FT /evidence="ECO:0007829|PDB:6F3F"
FT HELIX 136..138
FT /evidence="ECO:0007829|PDB:6F3F"
FT STRAND 139..144
FT /evidence="ECO:0007829|PDB:6F3F"
FT HELIX 145..147
FT /evidence="ECO:0007829|PDB:6F3F"
FT HELIX 157..164
FT /evidence="ECO:0007829|PDB:6F3F"
FT STRAND 174..178
FT /evidence="ECO:0007829|PDB:6F3F"
FT STRAND 180..182
FT /evidence="ECO:0007829|PDB:6F3F"
FT STRAND 186..194
FT /evidence="ECO:0007829|PDB:6F3F"
FT TURN 195..197
FT /evidence="ECO:0007829|PDB:6F3F"
FT STRAND 198..208
FT /evidence="ECO:0007829|PDB:6F3F"
FT STRAND 214..217
FT /evidence="ECO:0007829|PDB:6F3F"
FT STRAND 220..224
FT /evidence="ECO:0007829|PDB:6F3F"
FT HELIX 225..232
FT /evidence="ECO:0007829|PDB:6F3F"
FT STRAND 239..241
FT /evidence="ECO:0007829|PDB:6F3F"
FT STRAND 255..258
FT /evidence="ECO:0007829|PDB:6F3F"
FT HELIX 266..268
FT /evidence="ECO:0007829|PDB:6F3F"
FT STRAND 269..277
FT /evidence="ECO:0007829|PDB:6F3F"
FT STRAND 279..288
FT /evidence="ECO:0007829|PDB:6F3F"
FT TURN 289..291
FT /evidence="ECO:0007829|PDB:6F3F"
FT STRAND 292..299
FT /evidence="ECO:0007829|PDB:6F3F"
FT HELIX 306..316
FT /evidence="ECO:0007829|PDB:6F3F"
FT STRAND 327..331
FT /evidence="ECO:0007829|PDB:6F3F"
FT STRAND 333..335
FT /evidence="ECO:0007829|PDB:6F3F"
FT STRAND 337..340
FT /evidence="ECO:0007829|PDB:6F3F"
FT HELIX 348..352
FT /evidence="ECO:0007829|PDB:6F3F"
FT HELIX 354..358
FT /evidence="ECO:0007829|PDB:6F3F"
FT HELIX 362..381
FT /evidence="ECO:0007829|PDB:6F3F"
FT HELIX 391..393
FT /evidence="ECO:0007829|PDB:6F3F"
FT STRAND 394..396
FT /evidence="ECO:0007829|PDB:6F3F"
FT HELIX 398..400
FT /evidence="ECO:0007829|PDB:6F3F"
FT STRAND 402..404
FT /evidence="ECO:0007829|PDB:6F3F"
FT HELIX 409..412
FT /evidence="ECO:0007829|PDB:6F3F"
FT HELIX 416..419
FT /evidence="ECO:0007829|PDB:6F3F"
FT HELIX 428..430
FT /evidence="ECO:0007829|PDB:6F3F"
FT HELIX 433..438
FT /evidence="ECO:0007829|PDB:6F3F"
FT HELIX 443..458
FT /evidence="ECO:0007829|PDB:6F3F"
FT HELIX 470..478
FT /evidence="ECO:0007829|PDB:6F3F"
FT HELIX 491..500
FT /evidence="ECO:0007829|PDB:6F3F"
FT HELIX 505..507
FT /evidence="ECO:0007829|PDB:6F3F"
FT HELIX 511..519
FT /evidence="ECO:0007829|PDB:6F3F"
FT TURN 520..522
FT /evidence="ECO:0007829|PDB:6F3F"
SQ SEQUENCE 535 AA; 59891 MW; 22CB5C6BE7A061C0 CRC64;
MGSNKSKPKD ASQRRRSLEP SENVHGAGGA FPASQTPSKP ASADGHRGPS AAFVPPAAEP
KLFGGFNSSD TVTSPQRAGP LAGGVTTFVA LYDYESRTET DLSFKKGERL QIVNNTEGDW
WLAHSLSTGQ TGYIPSNYVA PSDSIQAEEW YFGKITRRES ERLLLNAENP RGTFLVRESE
TTKGAYCLSV SDFDNAKGLN VKHYKIRKLD SGGFYITSRT QFNSLQQLVA YYSKHADGLC
HRLTTVCPTS KPQTQGLAKD AWEIPRESLR LEVKLGQGCF GEVWMGTWNG TTRVAIKTLK
PGTMSPEAFL QEAQVMKKLR HEKLVQLYAV VSEEPIYIVT EYMNKGSLLD FLKGETGKYL
RLPQLVDMSA QIASGMAYVE RMNYVHRDLR AANILVGENL VCKVADFGLA RLIEDNEYTA
RQGAKFPIKW TAPEAALYGR FTIKSDVWSF GILLTELTTK GRVPYPGMVN REVLDQVERG
YRMPCPPECP ESLHDLMCQC WRKEPEERPT FEYLQAFLED YFTSTEPQYQ PGENL
