SRC_RAT
ID SRC_RAT Reviewed; 536 AA.
AC Q9WUD9; G3V776; Q45QJ2; Q9JJ10;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 13-NOV-2013, sequence version 4.
DT 03-AUG-2022, entry version 202.
DE RecName: Full=Proto-oncogene tyrosine-protein kinase Src;
DE EC=2.7.10.2 {ECO:0000269|PubMed:26026271, ECO:0000269|PubMed:28220894, ECO:0000269|PubMed:8849729};
DE AltName: Full=Proto-oncogene c-Src;
DE AltName: Full=pp60c-src;
DE Short=p60-Src;
GN Name=Src;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC STRAIN=Sprague-Dawley; TISSUE=Testis;
RA Stockand J.D., Al-Khalili O., Spier B.J., Eaton D.C.;
RT "Rattus norvegicus proto-oncogene encoding tyrosine-protein kinase pp60-c-
RT src.";
RL Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY, AND INDUCTION.
RC STRAIN=Wistar; TISSUE=Temporal cortex;
RX PubMed=11249956; DOI=10.1016/s0028-3908(00)00185-4;
RA Linden A., Storvik M., Lakso M., Haapasalo A., Lee D., Witkin J.M., Sei Y.,
RA Castren E., Wong G.;
RT "Increased expression of neuronal Src and tyrosine phosphorylation of NMDA
RT receptors in rat brain after systemic treatment with MK-801.";
RL Neuropharmacology 40:469-481(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 7-529 (ISOFORM 1).
RC STRAIN=SHR, and Wistar Kyoto;
RA Jackson E.K., Zhu C.;
RT "Genetic similarity between spontaneously hypertensive rats and Wistar-
RT Kyoto rats in the coding regions of signal transduction proteins.";
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP CATALYTIC ACTIVITY, ACTIVITY REGULATION, INTERACTION WITH PTK2B/PYK2, AND
RP PHOSPHORYLATION AT TYR-419.
RX PubMed=8849729; DOI=10.1038/383547a0;
RA Dikic I., Tokiwa G., Lev S., Courtneidge S.A., Schlessinger J.;
RT "A role for Pyk2 and Src in linking G-protein-coupled receptors with MAP
RT kinase activation.";
RL Nature 383:547-550(1996).
RN [7]
RP INTERACTION WITH ARRB1.
RX PubMed=10995467; DOI=10.1073/pnas.190276697;
RA DeFea K.A., Vaughn Z.D., O'Bryan E.M., Nishijima D., Dery O., Bunnett N.W.;
RT "The proliferative and antiapoptotic effects of substance P are facilitated
RT by formation of a beta -arrestin-dependent scaffolding complex.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:11086-11091(2000).
RN [8]
RP INTERACTION WITH DDR2.
RX PubMed=11884411; DOI=10.1074/jbc.m201078200;
RA Ikeda K., Wang L.H., Torres R., Zhao H., Olaso E., Eng F.J., Labrador P.,
RA Klein R., Lovett D., Yancopoulos G.D., Friedman S.L., Lin H.C.;
RT "Discoidin domain receptor 2 interacts with Src and Shc following its
RT activation by type I collagen.";
RL J. Biol. Chem. 277:19206-19212(2002).
RN [9]
RP INTERACTION WITH DAB2.
RX PubMed=12473651; DOI=10.1074/jbc.m210628200;
RA Zhou J., Scholes J., Hsieh J.T.;
RT "Characterization of a novel negative regulator (DOC-2/DAB2) of c-Src in
RT normal prostatic epithelium and cancer.";
RL J. Biol. Chem. 278:6936-6941(2003).
RN [10]
RP FUNCTION, AND INTERACTION WITH 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 [11]
RP INTERACTION WITH CEACAM1.
RX PubMed=19948503; DOI=10.1083/jcb.200904150;
RA Mueller M.M., Klaile E., Vorontsova O., Singer B.B., Obrink B.;
RT "Homophilic adhesion and CEACAM1-S regulate dimerization of CEACAM1-L and
RT recruitment of SHP-2 and c-Src.";
RL J. Cell Biol. 187:569-581(2009).
RN [12]
RP PHOSPHORYLATION AT TYR-530, AND DEPHOSPHORYLATION AT TYR-530 BY PTPRJ.
RX PubMed=15735685; DOI=10.1038/sj.onc.1208510;
RA Pera I.L., Iuliano R., Florio T., Susini C., Trapasso F., Santoro M.,
RA Chiariotti L., Schettini G., Viglietto G., Fusco A.;
RT "The rat tyrosine phosphatase eta increases cell adhesion by activating c-
RT Src through dephosphorylation of its inhibitory phosphotyrosine residue.";
RL Oncogene 24:3187-3195(2005).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-17, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [14]
RP FUNCTION (ISOFORMS 1; 2 AND 3), CATALYTIC ACTIVITY (ISOFORMS 1; 2 AND 3),
RP ALTERNATIVE SPLICING, AND PHOSPHORYLATION AT TYR-419 AND TYR-530.
RX PubMed=26026271; DOI=10.1016/j.febslet.2015.05.033;
RA Keenan S., Lewis P.A., Wetherill S.J., Dunning C.J., Evans G.J.;
RT "The N2-Src neuronal splice variant of C-Src has altered SH3 domain ligand
RT specificity and a higher constitutive activity than N1-Src.";
RL FEBS Lett. 589:1995-2000(2015).
RN [15]
RP FUNCTION (ISOFORMS 2 AND 3), AND CATALYTIC ACTIVITY.
RX PubMed=28220894; DOI=10.1038/srep43106;
RA Keenan S., Wetherill S.J., Ugbode C.I., Chawla S., Brackenbury W.J.,
RA Evans G.J.;
RT "Inhibition of N1-Src kinase by a specific SH3 peptide ligand reveals a
RT role for N1-Src in neurite elongation by L1-CAM.";
RL Sci. Rep. 7:43106-43106(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 (By similarity).
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. Plays an important
CC role in osteoclastic bone resorption in conjunction with PTK2B/PYK2.
CC Both the formation of a SRC-PTK2B/PYK2 complex and SRC kinase activity
CC are necessary for this function. Recruited to activated integrins by
CC PTK2B/PYK2, thereby phosphorylating CBL, which in turn induces the
CC activation and recruitment of phosphatidylinositol 3-kinase to the cell
CC membrane in a signaling pathway that is critical for osteoclast
CC function. Promotes energy production in osteoclasts by activating
CC mitochondrial cytochrome C oxidase (By similarity). Phosphorylates DDR2
CC on tyrosine residues, thereby promoting its subsequent
CC autophosphorylation (PubMed:16186108). Phosphorylates RUNX3 and COX2 on
CC tyrosine residues, TNK2 on 'Tyr-284' and CBL on 'Tyr-738'. Enhances
CC DDX58/RIG-I-elicited antiviral signaling. Phosphorylates PDPK1 at 'Tyr-
CC 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) (PubMed:26026271). Involved in anchorage-
CC independent cell growth (By similarity). Required for podosome
CC formation (By similarity). Mediates IL6 signaling by activating YAP1-
CC NOTCH pathway to induce inflammation-induced epithelial regeneration
CC (By similarity). {ECO:0000250|UniProtKB:P05480,
CC ECO:0000250|UniProtKB:P12931, ECO:0000269|PubMed:16186108,
CC ECO:0000269|PubMed:26026271, ECO:0000305}.
CC -!- FUNCTION: [Isoform 1]: Non-receptor protein tyrosine kinase which
CC phosphorylates synaptophysin with high affinity.
CC {ECO:0000269|PubMed:26026271}.
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 (PubMed:26026271). 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
CC (PubMed:26026271). Displays altered substrate specificity compared to
CC isoform 1, showing weak affinity for synaptophysin and for peptide
CC substrates containing class I or class II SH3 domain-binding motifs
CC (PubMed:26026271). Plays a role in L1CAM-mediated neurite elongation,
CC possibly by acting downstream of L1CAM to drive cytoskeletal
CC rearrangements involved in neurite outgrowth (PubMed:28220894).
CC {ECO:0000269|PubMed:26026271, ECO:0000269|PubMed:28220894}.
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 (PubMed:26026271). 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
CC (PubMed:26026271). Displays altered substrate specificity compared to
CC isoform 1, showing weak affinity for synaptophysin and for peptide
CC substrates containing class I or class II SH3 domain-binding motifs
CC (PubMed:26026271). Plays a role in neurite elongation
CC (PubMed:28220894). {ECO:0000269|PubMed:26026271,
CC ECO:0000269|PubMed:28220894}.
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:8849729};
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:0000269|PubMed:26026271, ECO:0000269|PubMed:28220894};
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:0000269|PubMed:26026271, ECO:0000269|PubMed:28220894};
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:0000269|PubMed:26026271};
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 inhibitors
CC (By similarity). Phosphorylation at Tyr-419 increases kinase activity.
CC {ECO:0000250, ECO:0000269|PubMed:8849729}.
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 (By similarity). 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 CDCP1,
CC TGFB1I1 and TOM1L2 (By similarity). Interacts with the cytoplasmic
CC domain of MUC1, phosphorylates it and increases binding of MUC1 with
CC beta-catenin (By similarity). Interacts with RALGPS1; via the SH3
CC domain (By similarity). Interacts with CAV2 (tyrosine phosphorylated
CC form) (By similarity). Interacts (via the SH3 domain and the protein
CC kinase domain) with ARRB1; the interaction is independent of the
CC phosphorylation state of SRC C-terminus (PubMed:10995467). Interacts
CC with ARRB1 and ARRB2 (PubMed:10995467) (By similarity). Interacts with
CC SRCIN1 (By similarity). Interacts with NDFIP2 and more weakly with
CC NDFIP1 (By similarity). Interacts with PIK3CA and/or PIK3C2B, PTK2/FAK1
CC and ESR1 (dimethylated on arginine) (PubMed:8849729). Interacts with
CC FASLG (By similarity). Interacts (via SH2 domain) with the 'Tyr-402'
CC phosphorylated form of PTK2B/PYK2 (PubMed:8849729). Interacts (via SH2
CC domain) with FLT3 (tyrosine phosphorylated) (By similarity). Interacts
CC (via SH2 and SH3 domain) with TNK2 (By similarity). Interacts (via
CC protein kinase domain) with the tyrosine phosphorylated form of RUNX3
CC (via runt domain) (By similarity). Interacts with TRAF3 (via RING-type
CC zinc finger domain) (By similarity). Interacts with DDX58, MAVS and
CC TBK1 (By similarity). Interacts (via SH2 domain) with RACK1; the
CC interaction is enhanced by tyrosine phosphorylation of RACK1 and
CC inhibits SRC activity (By similarity). Interacts with EPHB1; activates
CC the MAPK/ERK cascade to regulate cell migration (By similarity).
CC Interacts with FCAMR (By similarity). Interacts with PDGFRA (tyrosine
CC phosphorylated) (By similarity). Interacts with CSF1R (By similarity).
CC Interacts with DDR1 (By similarity). Interacts (via SH2 domain) with
CC the 'Tyr-9' phosphorylated form of PDPK1 (By similarity). Interacts
CC with AMOTL2; this interaction promotes the translocation of
CC phosphorylated SRC to peripheral cell-matrix adhesion sites (By
CC similarity). Interacts with DDR2 and DAB2 (PubMed:11884411,
CC PubMed:12473651, PubMed:16186108). Interacts with TRAP1 (By
CC similarity). Interacts with CBLC; the interaction is enhanced when SRC
CC is phosphorylated at Tyr-419 (By similarity). Interacts with ARHGEF5
CC (By similarity). Interacts (via cytoplasmic domain) with CEACAM1 (via
CC SH2 domain); this interaction is regulated by trans-homophilic cell
CC adhesion (PubMed:19948503). 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 (By
CC similarity). Interacts with IL6ST/gp130 (By similarity). Interacts (via
CC SH3 domain) with PELP1 in the presence of 17-beta-estradiol (By
CC similarity). Interacts with AMBRA1 (By similarity).
CC {ECO:0000250|UniProtKB:P05480, ECO:0000250|UniProtKB:P12931,
CC ECO:0000269|PubMed:10995467, ECO:0000269|PubMed:11884411,
CC ECO:0000269|PubMed:12473651, ECO:0000269|PubMed:16186108,
CC ECO:0000269|PubMed:19948503, ECO:0000269|PubMed:8849729}.
CC -!- INTERACTION:
CC Q9WUD9; P22002: Cacna1c; NbExp=4; IntAct=EBI-7784541, EBI-1185084;
CC Q9WUD9; P28648: Cd63; NbExp=2; IntAct=EBI-7784541, EBI-7784314;
CC Q9WUD9; O08617: Ptprr; NbExp=2; IntAct=EBI-7784541, EBI-8584374;
CC Q9WUD9; P18031: PTPN1; Xeno; NbExp=2; IntAct=EBI-7784541, EBI-968788;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P05480};
CC Lipid-anchor {ECO:0000250|UniProtKB:P05480}. Mitochondrion inner
CC membrane {ECO:0000250|UniProtKB:P05480}. Nucleus
CC {ECO:0000250|UniProtKB:P05480}. Cytoplasm, cytoskeleton
CC {ECO:0000250|UniProtKB:P05480}. Cytoplasm, perinuclear region
CC {ECO:0000250|UniProtKB:P12931}. Cell junction, focal adhesion
CC {ECO:0000250|UniProtKB:P05480}. Note=Localizes to focal adhesion sites
CC following integrin engagement. Localization to focal adhesion sites
CC requires myristoylation and the SH3 domain (By similarity). Colocalizes
CC with PDLIM4 at the perinuclear region, but not at focal adhesions.
CC {ECO:0000250|UniProtKB:P05480, ECO:0000250|UniProtKB:P12931}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=c-Src {ECO:0000303|PubMed:26026271};
CC IsoId=Q9WUD9-1; Sequence=Displayed;
CC Name=2; Synonyms=Neuronal Src, N1-Src {ECO:0000303|PubMed:26026271};
CC IsoId=Q9WUD9-2; Sequence=VSP_053395;
CC Name=3; Synonyms=N2-Src {ECO:0000303|PubMed:26026271};
CC IsoId=Q9WUD9-3; Sequence=VSP_061495;
CC -!- TISSUE SPECIFICITY: [Isoform 1]: Expressed at very low levels in the
CC forebrain. {ECO:0000269|PubMed:11249956}.
CC -!- TISSUE SPECIFICITY: [Isoform 2]: Expressed in the brain with highest
CC expression in the pyramidal layers of the hippocampus and the granular
CC layer of the dentate gyrus and moderate expression in cortical regions,
CC with higher levels in the superficial layers than in the deep layers.
CC May be neuron-specific. {ECO:0000269|PubMed:11249956}.
CC -!- INDUCTION: [Isoform 2]: Up-regulated by MK-801, an uncompetitive N-
CC methyl-d-aspartate (NMDA) receptor antagonist, mostly in the
CC superficial layers of the parietal, temporal, occipital and frontal
CC cortices. {ECO:0000269|PubMed:11249956}.
CC -!- PTM: Myristoylated at Gly-2, and this is essential for targeting to
CC membranes. {ECO:0000250}.
CC -!- PTM: Dephosphorylated at Tyr-530 by PTPRJ. Phosphorylated on Tyr-530 by
CC c-Src kinase (CSK). The phosphorylated form is termed pp60c-src (By
CC similarity). Dephosphorylated by PTPRJ at Tyr-419. Normally maintained
CC in an inactive conformation with the SH2 domain engaged with Tyr-530,
CC the SH3 domain engaged with the SH2-kinase linker, and Tyr-419
CC dephosphorylated. Dephosphorylation of Tyr-530 as a result of protein
CC tyrosine phosphatase (PTP) action disrupts the intramolecular
CC interaction between the SH2 domain and Tyr-530, Tyr-419 can then become
CC autophosphorylated, resulting in SRX activation. Phosphorylation of
CC Tyr-530 by CSK allows this interaction to reform, resulting in SRC
CC inactivation. CDK5-mediated phosphorylation at Ser-75 targets SRC to
CC ubiquitin-dependent degradation and thus leads to cytoskeletal
CC reorganization. Phosphorylated by PTK2/FAK1; this enhances kinase
CC activity (By similarity). Phosphorylated by PTK2B/PYK2; this enhances
CC kinase activity. Upon activation of IL6ST by IL6, Tyr-419 is
CC phosphorylated and Tyr-530 dephosphorylated (By similarity).
CC {ECO:0000250, ECO:0000250|UniProtKB:P12931,
CC ECO:0000269|PubMed:15735685, ECO:0000269|PubMed:8849729}.
CC -!- PTM: [Isoform 1]: Displays reduced levels of autophosphorylation at
CC Tyr-419 compared to isoforms 2 and 3. {ECO:0000269|PubMed:26026271}.
CC -!- PTM: [Isoform 2]: Displays enhanced levels of autophosphorylation at
CC Tyr-419 compared to isoform 1. {ECO:0000269|PubMed:26026271}.
CC -!- PTM: [Isoform 3]: Displays enhanced levels of autophosphorylation at
CC Tyr-419 compared to isoform 1 (PubMed:26026271). Shows reduced
CC phosphorylation at Tyr-527 compared to isoforms 1 and 2
CC (PubMed:26026271). {ECO:0000269|PubMed:26026271}.
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 (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; AF130457; AAD24180.1; -; mRNA.
DR EMBL; AF157016; AAF80335.1; -; mRNA.
DR EMBL; AABR06027223; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH474005; EDL96675.1; -; Genomic_DNA.
DR EMBL; CH474005; EDL96676.1; -; Genomic_DNA.
DR EMBL; CH474005; EDL96677.1; -; Genomic_DNA.
DR EMBL; CH474005; EDL96678.1; -; Genomic_DNA.
DR EMBL; CH474005; EDL96679.1; -; Genomic_DNA.
DR EMBL; DQ120509; AAZ23848.1; -; mRNA.
DR EMBL; DQ120510; AAZ23849.1; -; mRNA.
DR RefSeq; NP_114183.1; NM_031977.1. [Q9WUD9-2]
DR RefSeq; XP_008760609.1; XM_008762387.2. [Q9WUD9-2]
DR RefSeq; XP_008760610.1; XM_008762388.2. [Q9WUD9-2]
DR RefSeq; XP_017447554.1; XM_017592065.1. [Q9WUD9-2]
DR RefSeq; XP_017447555.1; XM_017592066.1. [Q9WUD9-2]
DR RefSeq; XP_017447556.1; XM_017592067.1. [Q9WUD9-2]
DR RefSeq; XP_017447557.1; XM_017592068.1. [Q9WUD9-2]
DR RefSeq; XP_017447558.1; XM_017592069.1. [Q9WUD9-2]
DR RefSeq; XP_017447559.1; XM_017592070.1. [Q9WUD9-2]
DR RefSeq; XP_017447560.1; XM_017592071.1. [Q9WUD9-2]
DR RefSeq; XP_017447561.1; XM_017592072.1. [Q9WUD9-1]
DR AlphaFoldDB; Q9WUD9; -.
DR SMR; Q9WUD9; -.
DR BioGRID; 249840; 18.
DR CORUM; Q9WUD9; -.
DR DIP; DIP-42731N; -.
DR ELM; Q9WUD9; -.
DR IntAct; Q9WUD9; 33.
DR MINT; Q9WUD9; -.
DR STRING; 10116.ENSRNOP00000012739; -.
DR BindingDB; Q9WUD9; -.
DR ChEMBL; CHEMBL3014; -.
DR iPTMnet; Q9WUD9; -.
DR PhosphoSitePlus; Q9WUD9; -.
DR jPOST; Q9WUD9; -.
DR PaxDb; Q9WUD9; -.
DR PeptideAtlas; Q9WUD9; -.
DR PRIDE; Q9WUD9; -.
DR Ensembl; ENSRNOT00000012739; ENSRNOP00000012739; ENSRNOG00000009495. [Q9WUD9-2]
DR Ensembl; ENSRNOT00000080516; ENSRNOP00000071837; ENSRNOG00000009495. [Q9WUD9-1]
DR GeneID; 83805; -.
DR KEGG; rno:83805; -.
DR UCSC; RGD:620795; rat. [Q9WUD9-1]
DR CTD; 6714; -.
DR RGD; 620795; Src.
DR eggNOG; KOG0197; Eukaryota.
DR GeneTree; ENSGT00940000158250; -.
DR HOGENOM; CLU_000288_7_2_1; -.
DR InParanoid; Q9WUD9; -.
DR OMA; GMMNMEV; -.
DR OrthoDB; 539311at2759; -.
DR TreeFam; TF351634; -.
DR BRENDA; 2.7.10.2; 5301.
DR Reactome; R-RNO-1227986; Signaling by ERBB2.
DR Reactome; R-RNO-1251985; Nuclear signaling by ERBB4.
DR Reactome; R-RNO-1253288; Downregulation of ERBB4 signaling.
DR Reactome; R-RNO-1257604; PIP3 activates AKT signaling.
DR Reactome; R-RNO-1295596; Spry regulation of FGF signaling.
DR Reactome; R-RNO-1433557; Signaling by SCF-KIT.
DR Reactome; R-RNO-1433559; Regulation of KIT signaling.
DR Reactome; R-RNO-177929; Signaling by EGFR.
DR Reactome; R-RNO-180292; GAB1 signalosome.
DR Reactome; R-RNO-186763; Downstream signal transduction.
DR Reactome; R-RNO-191650; Regulation of gap junction activity.
DR Reactome; R-RNO-2029481; FCGR activation.
DR Reactome; R-RNO-210990; PECAM1 interactions.
DR Reactome; R-RNO-354192; Integrin signaling.
DR Reactome; R-RNO-354194; GRB2:SOS provides linkage to MAPK signaling for Integrins.
DR Reactome; R-RNO-372708; p130Cas linkage to MAPK signaling for integrins.
DR Reactome; R-RNO-389356; CD28 co-stimulation.
DR Reactome; R-RNO-389513; CTLA4 inhibitory signaling.
DR Reactome; R-RNO-3928662; EPHB-mediated forward signaling.
DR Reactome; R-RNO-3928663; EPHA-mediated growth cone collapse.
DR Reactome; R-RNO-3928664; Ephrin signaling.
DR Reactome; R-RNO-3928665; EPH-ephrin mediated repulsion of cells.
DR Reactome; R-RNO-418592; ADP signalling through P2Y purinoceptor 1.
DR Reactome; R-RNO-418594; G alpha (i) signalling events.
DR Reactome; R-RNO-418885; DCC mediated attractive signaling.
DR Reactome; R-RNO-430116; GP1b-IX-V activation signalling.
DR Reactome; R-RNO-437239; Recycling pathway of L1.
DR Reactome; R-RNO-4420097; VEGFA-VEGFR2 Pathway.
DR Reactome; R-RNO-456926; Thrombin signalling through proteinase activated receptors (PARs).
DR Reactome; R-RNO-5218921; VEGFR2 mediated cell proliferation.
DR Reactome; R-RNO-5607764; CLEC7A (Dectin-1) signaling.
DR Reactome; R-RNO-5673000; RAF activation.
DR Reactome; R-RNO-5674135; MAP2K and MAPK activation.
DR Reactome; R-RNO-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR Reactome; R-RNO-69231; Cyclin D associated events in G1.
DR Reactome; R-RNO-8853659; RET signaling.
DR Reactome; R-RNO-8874081; MET activates PTK2 signaling.
DR Reactome; R-RNO-8934903; Receptor Mediated Mitophagy.
DR Reactome; R-RNO-8941858; Regulation of RUNX3 expression and activity.
DR Reactome; R-RNO-9009391; Extra-nuclear estrogen signaling.
DR Reactome; R-RNO-9603381; Activated NTRK3 signals through PI3K.
DR PRO; PR:Q9WUD9; -.
DR Proteomes; UP000002494; Chromosome 3.
DR Proteomes; UP000234681; Chromosome 3.
DR Bgee; ENSRNOG00000009495; Expressed in frontal cortex and 19 other tissues.
DR Genevisible; Q9WUD9; RN.
DR GO; GO:0005884; C:actin filament; ISO:RGD.
DR GO; GO:0005901; C:caveola; IDA:RGD.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005856; C:cytoskeleton; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:1902737; C:dendritic filopodium; IDA:RGD.
DR GO; GO:0044294; C:dendritic growth cone; IDA:RGD.
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; IDA:SynGO.
DR GO; GO:0005770; C:late endosome; ISO:RGD.
DR GO; GO:0005764; C:lysosome; ISO:RGD.
DR GO; GO:0016020; C:membrane; ISO:RGD.
DR GO; GO:0005743; C:mitochondrial inner membrane; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR GO; GO:0043005; C:neuron projection; IDA:RGD.
DR GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
DR GO; GO:0002102; C:podosome; ISO:RGD.
DR GO; GO:0014069; C:postsynaptic density; IDA:RGD.
DR GO; GO:0099091; C:postsynaptic specialization, intracellular component; IDA:SynGO.
DR GO; GO:0032587; C:ruffle membrane; ISO:RGD.
DR GO; GO:0097060; C:synaptic membrane; IDA:RGD.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0070700; F:BMP receptor binding; ISO:RGD.
DR GO; GO:0050839; F:cell adhesion molecule binding; IPI:RGD.
DR GO; GO:0071253; F:connexin binding; ISO:RGD.
DR GO; GO:0019899; F:enzyme binding; IPI:RGD.
DR GO; GO:0046875; F:ephrin receptor binding; ISO:RGD.
DR GO; GO:0070851; F:growth factor receptor binding; ISO:RGD.
DR GO; GO:0020037; F:heme binding; ISS:UniProtKB.
DR GO; GO:0005158; F:insulin receptor binding; IPI:RGD.
DR GO; GO:0005178; F:integrin binding; ISO:RGD.
DR GO; GO:0016301; F:kinase activity; ISO:RGD.
DR GO; GO:0019900; F:kinase binding; ISO:RGD.
DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; ISO:RGD.
DR GO; GO:0030331; F:nuclear estrogen receptor binding; IPI:RGD.
DR GO; GO:0016004; F:phospholipase activator activity; ISO:RGD.
DR GO; GO:0043274; F:phospholipase binding; ISO:RGD.
DR GO; GO:0051219; F:phosphoprotein binding; ISO:RGD.
DR GO; GO:0008022; F:protein C-terminus binding; IPI:RGD.
DR GO; GO:0019904; F:protein domain specific binding; ISO:RGD.
DR GO; GO:0004672; F:protein kinase activity; ISO:RGD.
DR GO; GO:0019901; F:protein kinase binding; IPI:RGD.
DR GO; GO:0005080; F:protein kinase C binding; IPI:RGD.
DR GO; GO:0004713; F:protein tyrosine kinase activity; IDA:UniProtKB.
DR GO; GO:0044877; F:protein-containing complex binding; IPI:RGD.
DR GO; GO:0097110; F:scaffold protein binding; ISO:RGD.
DR GO; GO:0042169; F:SH2 domain binding; ISO:RGD.
DR GO; GO:0005102; F:signaling receptor binding; IPI:RGD.
DR GO; GO:0044325; F:transmembrane transporter binding; IPI:RGD.
DR GO; GO:0032148; P:activation of protein kinase B activity; IMP:UniProtKB.
DR GO; GO:0034332; P:adherens junction organization; IEP:RGD.
DR GO; GO:0086098; P:angiotensin-activated signaling pathway involved in heart process; ISO:RGD.
DR GO; GO:0045453; P:bone resorption; ISS:UniProtKB.
DR GO; GO:0007420; P:brain development; IEP:RGD.
DR GO; GO:0060444; P:branching involved in mammary gland duct morphogenesis; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0008283; P:cell population proliferation; IDA:RGD.
DR GO; GO:0098609; P:cell-cell adhesion; IEP:RGD.
DR GO; GO:1904385; P:cellular response to angiotensin; IEP:RGD.
DR GO; GO:0071398; P:cellular response to fatty acid; IEP:RGD.
DR GO; GO:0071498; P:cellular response to fluid shear stress; ISO:RGD.
DR GO; GO:0070301; P:cellular response to hydrogen peroxide; IEP:RGD.
DR GO; GO:0071456; P:cellular response to hypoxia; IEP:RGD.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IEP:RGD.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IEP:RGD.
DR GO; GO:0071375; P:cellular response to peptide hormone stimulus; ISO:RGD.
DR GO; GO:0036120; P:cellular response to platelet-derived growth factor stimulus; IEP:RGD.
DR GO; GO:0071393; P:cellular response to progesterone stimulus; IMP:BHF-UCL.
DR GO; GO:1990646; P:cellular response to prolactin; IEP:RGD.
DR GO; GO:0034614; P:cellular response to reactive oxygen species; ISO:RGD.
DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; ISO:RGD.
DR GO; GO:0071897; P:DNA biosynthetic process; IMP:RGD.
DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; IEP:RGD.
DR GO; GO:0048041; P:focal adhesion assembly; ISO:RGD.
DR GO; GO:0030900; P:forebrain development; ISO:RGD.
DR GO; GO:0045087; P:innate immune response; IBA:GO_Central.
DR GO; GO:0007229; P:integrin-mediated signaling pathway; ISO:RGD.
DR GO; GO:0070102; P:interleukin-6-mediated signaling pathway; ISO:RGD.
DR GO; GO:0060576; P:intestinal epithelial cell development; ISO:RGD.
DR GO; GO:0035556; P:intracellular signal transduction; ISO:RGD.
DR GO; GO:0007611; P:learning or memory; IEP:RGD.
DR GO; GO:2000811; P:negative regulation of anoikis; ISO:RGD.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:RGD.
DR GO; GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; ISO:RGD.
DR GO; GO:2001237; P:negative regulation of extrinsic apoptotic signaling pathway; ISO:RGD.
DR GO; GO:0051895; P:negative regulation of focal adhesion assembly; IMP:BHF-UCL.
DR GO; GO:2001243; P:negative regulation of intrinsic apoptotic signaling pathway; ISO:RGD.
DR GO; GO:0051902; P:negative regulation of mitochondrial depolarization; ISO:RGD.
DR GO; GO:0031333; P:negative regulation of protein-containing complex assembly; ISO:RGD.
DR GO; GO:0051974; P:negative regulation of telomerase activity; ISO:RGD.
DR GO; GO:0032211; P:negative regulation of telomere maintenance via telomerase; ISO:RGD.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IMP:UniProtKB.
DR GO; GO:0048011; P:neurotrophin TRK receptor signaling pathway; IDA:RGD.
DR GO; GO:0042476; P:odontogenesis; ISO:RGD.
DR GO; GO:0048477; P:oogenesis; ISO:RGD.
DR GO; GO:0036035; P:osteoclast development; ISO:RGD.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IMP:UniProtKB.
DR GO; GO:0038083; P:peptidyl-tyrosine autophosphorylation; IMP:CACAO.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; ISO:RGD.
DR GO; GO:0016310; P:phosphorylation; ISO:RGD.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IDA:RGD.
DR GO; GO:0045780; P:positive regulation of bone resorption; IMP:RGD.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; ISO:RGD.
DR GO; GO:0045785; P:positive regulation of cell adhesion; IDA:RGD.
DR GO; GO:0045737; P:positive regulation of cyclin-dependent protein serine/threonine kinase activity; IMP:UniProtKB.
DR GO; GO:0001819; P:positive regulation of cytokine production; IMP:RGD.
DR GO; GO:0035306; P:positive regulation of dephosphorylation; ISO:RGD.
DR GO; GO:2000573; P:positive regulation of DNA biosynthetic process; IMP:UniProtKB.
DR GO; GO:0010634; P:positive regulation of epithelial cell migration; ISO:RGD.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IMP:UniProtKB.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:RGD.
DR GO; GO:0010907; P:positive regulation of glucose metabolic process; IMP:RGD.
DR GO; GO:0035332; P:positive regulation of hippo signaling; IEA:Ensembl.
DR GO; GO:0046628; P:positive regulation of insulin receptor signaling pathway; IDA:RGD.
DR GO; GO:1902533; P:positive regulation of intracellular signal transduction; IMP:RGD.
DR GO; GO:2000394; P:positive regulation of lamellipodium morphogenesis; ISO:RGD.
DR GO; GO:2000256; P:positive regulation of male germ cell proliferation; IMP:RGD.
DR GO; GO:0043406; P:positive regulation of MAP kinase activity; IMP:UniProtKB.
DR GO; GO:0045747; P:positive regulation of Notch signaling pathway; ISO:RGD.
DR GO; GO:2000386; P:positive regulation of ovarian follicle development; IMP:RGD.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IMP:RGD.
DR GO; GO:0043552; P:positive regulation of phosphatidylinositol 3-kinase activity; IMP:UniProtKB.
DR GO; GO:0010641; P:positive regulation of platelet-derived growth factor receptor signaling pathway; IEP:UniProtKB.
DR GO; GO:2000588; P:positive regulation of platelet-derived growth factor receptor-beta signaling pathway; ISO:RGD.
DR GO; GO:0071803; P:positive regulation of podosome assembly; ISO:RGD.
DR GO; GO:0031954; P:positive regulation of protein autophosphorylation; IMP:UniProtKB.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; ISO:RGD.
DR GO; GO:1900182; P:positive regulation of protein localization to nucleus; ISO:RGD.
DR GO; GO:0010954; P:positive regulation of protein processing; ISO:RGD.
DR GO; GO:0071902; P:positive regulation of protein serine/threonine kinase activity; ISO:RGD.
DR GO; GO:0051222; P:positive regulation of protein transport; IMP:RGD.
DR GO; GO:0046579; P:positive regulation of Ras protein signal transduction; IMP:RGD.
DR GO; GO:0051057; P:positive regulation of small GTPase mediated signal transduction; ISO:RGD.
DR GO; GO:0014911; P:positive regulation of smooth muscle cell migration; IMP:RGD.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IMP:UniProtKB.
DR GO; GO:1904707; P:positive regulation of vascular associated smooth muscle cell proliferation; IMP:RGD.
DR GO; GO:0001545; P:primary ovarian follicle growth; IMP:RGD.
DR GO; GO:0050847; P:progesterone receptor signaling pathway; IMP:BHF-UCL.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
DR GO; GO:0031648; P:protein destabilization; ISO:RGD.
DR GO; GO:0006468; P:protein phosphorylation; ISO:RGD.
DR GO; GO:2001286; P:regulation of caveolin-mediated endocytosis; ISO:RGD.
DR GO; GO:0060491; P:regulation of cell projection assembly; ISO:RGD.
DR GO; GO:0022407; P:regulation of cell-cell adhesion; ISO:RGD.
DR GO; GO:2000641; P:regulation of early endosome to late endosome transport; ISO:RGD.
DR GO; GO:0010632; P:regulation of epithelial cell migration; ISO:RGD.
DR GO; GO:0033146; P:regulation of intracellular estrogen receptor signaling pathway; ISO:RGD.
DR GO; GO:0098962; P:regulation of postsynaptic neurotransmitter receptor activity; IDA:SynGO.
DR GO; GO:0043393; P:regulation of protein binding; ISO:RGD.
DR GO; GO:0010447; P:response to acidic pH; IEP:RGD.
DR GO; GO:0051602; P:response to electrical stimulus; IEP:RGD.
DR GO; GO:0070542; P:response to fatty acid; IEP:RGD.
DR GO; GO:0042542; P:response to hydrogen peroxide; IEP:RGD.
DR GO; GO:0070555; P:response to interleukin-1; ISO:RGD.
DR GO; GO:0009612; P:response to mechanical stimulus; IEP:RGD.
DR GO; GO:0051385; P:response to mineralocorticoid; IEP:RGD.
DR GO; GO:0031667; P:response to nutrient levels; IEP:RGD.
DR GO; GO:0009615; P:response to virus; IEP:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0007283; P:spermatogenesis; IEP:RGD.
DR GO; GO:0043149; P:stress fiber assembly; ISO:RGD.
DR GO; GO:0034446; P:substrate adhesion-dependent cell spreading; ISO:RGD.
DR GO; GO:0045056; P:transcytosis; IDA:RGD.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; ISO:RGD.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR GO; GO:0060065; P:uterus development; ISO:RGD.
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 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..536
FT /note="Proto-oncogene tyrosine-protein kinase Src"
FT /id="PRO_0000088143"
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..49
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 389
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 276..284
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 298
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:22673903"
FT MOD_RES 75
FT /note="Phosphoserine; by CDK5"
FT /evidence="ECO:0000250|UniProtKB:P12931"
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:26026271"
FT MOD_RES 419
FT /note="Phosphotyrosine; by FAK2"
FT /evidence="ECO:0000269|PubMed:8849729"
FT MOD_RES 530
FT /note="Phosphotyrosine; by CSK"
FT /evidence="ECO:0000269|PubMed:26026271"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000250"
FT VAR_SEQ 117
FT /note="T -> TRKVDVR (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11249956"
FT /id="VSP_053395"
FT VAR_SEQ 117
FT /note="T -> TRKVDVSQTWFTFRWLQR (in isoform 3)"
FT /id="VSP_061495"
FT CONFLICT 143
FT /note="S -> F (in Ref. 1; AAD24180 and 5; AAZ23849/
FT AAZ23848)"
FT /evidence="ECO:0000305"
FT CONFLICT 381
FT /note="E -> D (in Ref. 1; AAD24180 and 5; AAZ23849/
FT AAZ23848)"
FT /evidence="ECO:0000305"
FT CONFLICT 528
FT /note="P -> R (in Ref. 1; AAD24180 and 5; AAZ23849/
FT AAZ23848)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 536 AA; 59973 MW; 453D1E904EC660A3 CRC64;
MGSNKSKPKD ASQRRRSLEP AENVHGAGGA FPASQTPSKP ASADGHRGPN AAFVPPAAAE
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 TEYMNKGSLL DFLKGETGKY
LRLPQLVDMS AQIASGMAYV ERMNYVHRDL RAANILVGEN LVCKVADFGL ARLIEDNEYT
ARQGAKFPIK WTAPEAALYG RFTIKSDVWS FGILLTELTT KGRVPYPGMV NREVLDQVER
GYRMPCPPEC PESLHDLMCQ CWRKEPEERP TFEYLQAFLE DYFTSTEPQY QPGENL
