SRC (SRC proto-oncogene, non-receptor tyrosine kinase)

Gene

• Entrez ID: 6714
• Gene name: SRC proto-oncogene, non-receptor tyrosine kinase
• Gene symbol: SRC
• Synonyms: ASV, SRC1, THC6, c-SRC, p60-Src
• Chromosome: 20
• Chromosome location: 20q11.23
• Summary: This gene is highly similar to the v-src gene of Rous sarcoma virus. This proto-oncogene may play a role in the regulation of embryonic development and cell growth. The protein encoded by this gene is a tyrosine-protein kinase whose activity can be inhibited by phosphorylation by c-SRC kinase. Mutations in this gene could be involved in the malignant progression of colon cancer. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs121913314	C>T	Likely-pathogenic, pathogenic	Stop gained, coding sequence variant
rs879255268	G>A	Likely-pathogenic, pathogenic	Missense variant, coding sequence variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT007051	hsa-miR-23b-3p	Luciferase reporter assay	23074286
MIRT007357	hsa-miR-33a-5p	Immunofluorescence, Luciferase reporter assay, Western blot	23547260
MIRT024971	hsa-miR-205-5p	Reporter assay	21330408
MIRT053284	hsa-miR-203a-3p	Immunoprecipitaion, qRT-PCR, Western blot	23462723
MIRT053284	hsa-miR-203a-3p	Microarray	23807165
MIRT053284	hsa-miR-203a-3p	Luciferase reporter assay, qRT-PCR, Western blot	23790975
MIRT053592	hsa-miR-34a-5p	Luciferase reporter assay, qRT-PCR, Western blot	23790975
MIRT053592	hsa-miR-34a-5p	Immunoblot, Immunoprecipitaion, Luciferase reporter assay, qRT-PCR	23533633
MIRT053592	hsa-miR-34a-5p	Luciferase reporter assay, qRT-PCR, Western blot	26676753
MIRT053750	hsa-miR-31-5p	Immunoblot, Immunohistochemistry, Luciferase reporter assay, qRT-PCR	22948084
MIRT054922	hsa-miR-33b-5p	Luciferase reporter assay, qRT-PCR	23716591
MIRT733469	hsa-miR-135a-5p	Immunoblot, Microarray	26364608

Transcription factors

Transcription factor	Regulation	Reference
SP1	Unknown	19112177
TAF1	Unknown	14993269

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001545	Process	Primary ovarian follicle growth	IEA
GO:0002102	Component	Podosome	IEA
GO:0002223	Process	Stimulatory C-type lectin receptor signaling pathway	TAS
GO:0004672	Function	Protein kinase activity	IDA	18616680
GO:0004672	Function	Protein kinase activity	TAS
GO:0004713	Function	Protein tyrosine kinase activity	EXP	1381360, 9799234, 11448999, 12923167, 15735019, 18697750, 20100835
GO:0004713	Function	Protein tyrosine kinase activity	IBA	21873635
GO:0004713	Function	Protein tyrosine kinase activity	IDA	16441665, 19059439, 19307596
GO:0004713	Function	Protein tyrosine kinase activity	IMP	20624904, 25425738
GO:0004713	Function	Protein tyrosine kinase activity	NAS	28386764
GO:0004713	Function	Protein tyrosine kinase activity	TAS
GO:0004715	Function	Non-membrane spanning protein tyrosine kinase activity	IBA	21873635
GO:0004715	Function	Non-membrane spanning protein tyrosine kinase activity	NAS	20018849
GO:0004715	Function	Non-membrane spanning protein tyrosine kinase activity	TAS	19267251
GO:0005080	Function	Protein kinase C binding	IEA
GO:0005102	Function	Signaling receptor binding	IBA	21873635
GO:0005102	Function	Signaling receptor binding	IPI	19332538
GO:0005158	Function	Insulin receptor binding	IEA
GO:0005178	Function	Integrin binding	IPI	19141530
GO:0005178	Function	Integrin binding	TAS	19267251
GO:0005515	Function	Protein binding	IPI	7478590, 7537265, 8070403, 8681387, 8849729, 9148935, 9162084, 9600099, 9763511, 10521452, 10542110, 10698938, 10801826, 11007774, 11149930, 11741929, 11923305, 11940572, 12509223, 12857726, 14963108, 15143158, 15546919, 15735685, 15749833, 15866871, 16115959, 16169070, 16273093, 162
GO:0005524	Function	ATP binding	IEA
GO:0005654	Component	Nucleoplasm	IDA
GO:0005737	Component	Cytoplasm	IDA	16441665
GO:0005739	Component	Mitochondrion	IDA	19767770
GO:0005743	Component	Mitochondrial inner membrane	IDA	12615910
GO:0005764	Component	Lysosome	IDA	20605918
GO:0005770	Component	Late endosome	IDA	20605918
GO:0005829	Component	Cytosol	IDA	19767770
GO:0005829	Component	Cytosol	TAS
GO:0005884	Component	Actin filament	IEA
GO:0005886	Component	Plasma membrane	IDA	20605918
GO:0005886	Component	Plasma membrane	TAS
GO:0005901	Component	Caveola	IDA	17848177
GO:0005925	Component	Focal adhesion	ISS
GO:0007049	Process	Cell cycle	IEA
GO:0007155	Process	Cell adhesion	IBA	21873635
GO:0007165	Process	Signal transduction	TAS	9020193, 10734107
GO:0007169	Process	Transmembrane receptor protein tyrosine kinase signaling pathway	IBA	21873635
GO:0007172	Process	Signal complex assembly	TAS	9924018
GO:0007173	Process	Epidermal growth factor receptor signaling pathway	IBA	21873635
GO:0007173	Process	Epidermal growth factor receptor signaling pathway	TAS
GO:0007179	Process	Transforming growth factor beta receptor signaling pathway	IMP	24036928
GO:0007186	Process	G protein-coupled receptor signaling pathway	TAS
GO:0007229	Process	Integrin-mediated signaling pathway	IMP	24036928
GO:0007411	Process	Axon guidance	TAS
GO:0008022	Function	Protein C-terminus binding	IPI	25425738
GO:0008283	Process	Cell population proliferation	IEA
GO:0009612	Process	Response to mechanical stimulus	IEA
GO:0009615	Process	Response to virus	IEA
GO:0010447	Process	Response to acidic pH	IEA
GO:0010632	Process	Regulation of epithelial cell migration	IMP	21724833
GO:0010634	Process	Positive regulation of epithelial cell migration	IMP	18054784
GO:0010907	Process	Positive regulation of glucose metabolic process	IEA
GO:0010954	Process	Positive regulation of protein processing	IEA
GO:0014068	Process	Positive regulation of phosphatidylinositol 3-kinase signaling	TAS
GO:0014069	Component	Postsynaptic density	IEA
GO:0014911	Process	Positive regulation of smooth muscle cell migration	IEA
GO:0016032	Process	Viral process	IEA
GO:0016236	Process	Macroautophagy	TAS
GO:0016301	Function	Kinase activity	TAS
GO:0018105	Process	Peptidyl-serine phosphorylation	IEA
GO:0018108	Process	Peptidyl-tyrosine phosphorylation	IDA	12051764, 22732588
GO:0018108	Process	Peptidyl-tyrosine phosphorylation	IMP	20624904, 25425738
GO:0018108	Process	Peptidyl-tyrosine phosphorylation	NAS	20018849
GO:0019899	Function	Enzyme binding	IPI	21724833
GO:0019900	Function	Kinase binding	IPI	19059439
GO:0020037	Function	Heme binding	IDA	21036157
GO:0022407	Process	Regulation of cell-cell adhesion	IMP	21724833
GO:0030054	Component	Cell junction	IDA
GO:0030154	Process	Cell differentiation	IBA	21873635
GO:0030168	Process	Platelet activation	TAS
GO:0030331	Function	Estrogen receptor binding	IEA
GO:0030900	Process	Forebrain development	IEA
GO:0031234	Component	Extrinsic component of cytoplasmic side of plasma membrane	IBA	21873635
GO:0031295	Process	T cell costimulation	TAS
GO:0031333	Process	Negative regulation of protein-containing complex assembly	IMP	19767770
GO:0031625	Function	Ubiquitin protein ligase binding	IEA
GO:0031648	Process	Protein destabilization	IEA
GO:0031667	Process	Response to nutrient levels	IEA
GO:0031954	Process	Positive regulation of protein autophosphorylation	IEA
GO:0032148	Process	Activation of protein kinase B activity	IEA
GO:0032211	Process	Negative regulation of telomere maintenance via telomerase	IMP	21531765
GO:0032587	Component	Ruffle membrane	IEA
GO:0032869	Process	Cellular response to insulin stimulus	IEA
GO:0033146	Process	Regulation of intracellular estrogen receptor signaling pathway	IEA
GO:0033625	Process	Positive regulation of integrin activation	TAS	19267251
GO:0034332	Process	Adherens junction organization	IEA
GO:0034446	Process	Substrate adhesion-dependent cell spreading	IEA
GO:0035306	Process	Positive regulation of dephosphorylation	IDA	23159740
GO:0035556	Process	Intracellular signal transduction	IDA	15248232
GO:0035635	Process	Entry of bacterium into host cell	TAS
GO:0036035	Process	Osteoclast development	IBA	21873635
GO:0036120	Process	Cellular response to platelet-derived growth factor stimulus	IEA
GO:0038096	Process	Fc-gamma receptor signaling pathway involved in phagocytosis	TAS
GO:0038128	Process	ERBB2 signaling pathway	TAS
GO:0042169	Function	SH2 domain binding	IPI	8070403
GO:0042476	Process	Odontogenesis	IEA
GO:0042493	Process	Response to drug	IEA
GO:0043005	Component	Neuron projection	IEA
GO:0043065	Process	Positive regulation of apoptotic process	IEA
GO:0043066	Process	Negative regulation of apoptotic process	IMP	19767770
GO:0043114	Process	Regulation of vascular permeability	TAS	19267251
GO:0043149	Process	Stress fiber assembly	IMP	24036928
GO:0043154	Process	Negative regulation of cysteine-type endopeptidase activity involved in apoptotic process	IMP	19767770
GO:0043393	Process	Regulation of protein binding	IEA
GO:0043406	Process	Positive regulation of MAP kinase activity	IEA
GO:0043552	Process	Positive regulation of phosphatidylinositol 3-kinase activity	IEA
GO:0044325	Function	Ion channel binding	IPI	8953041, 12538589
GO:0045056	Process	Transcytosis	IEA
GO:0045087	Process	Innate immune response	IBA	21873635
GO:0045121	Component	Membrane raft	ISS
GO:0045124	Process	Regulation of bone resorption	TAS	19267251
GO:0045296	Function	Cadherin binding	HDA	25468996
GO:0045453	Process	Bone resorption	IBA	21873635
GO:0045453	Process	Bone resorption	ISS
GO:0045737	Process	Positive regulation of cyclin-dependent protein serine/threonine kinase activity	IEA
GO:0045747	Process	Positive regulation of Notch signaling pathway	IDA	25731159
GO:0045892	Process	Negative regulation of transcription, DNA-templated	IEA
GO:0045893	Process	Positive regulation of transcription, DNA-templated	IEA
GO:0046628	Process	Positive regulation of insulin receptor signaling pathway	IEA
GO:0046777	Process	Protein autophosphorylation	IDA	16441665
GO:0046875	Function	Ephrin receptor binding	IPI	12925710
GO:0048010	Process	Vascular endothelial growth factor receptor signaling pathway	TAS
GO:0048011	Process	Neurotrophin TRK receptor signaling pathway	IEA
GO:0048013	Process	Ephrin receptor signaling pathway	TAS
GO:0048041	Process	Focal adhesion assembly	IMP	21411625
GO:0048471	Component	Perinuclear region of cytoplasm	IDA	19307596
GO:0048477	Process	Oogenesis	IEA
GO:0050731	Process	Positive regulation of peptidyl-tyrosine phosphorylation	IC	18054784
GO:0050731	Process	Positive regulation of peptidyl-tyrosine phosphorylation	IMP	26598555, 26706435
GO:0050847	Process	Progesterone receptor signaling pathway	IBA	21873635
GO:0050847	Process	Progesterone receptor signaling pathway	ISS
GO:0050900	Process	Leukocyte migration	TAS
GO:0051057	Process	Positive regulation of small GTPase mediated signal transduction	IMP	18541665
GO:0051117	Function	ATPase binding	ISS
GO:0051219	Function	Phosphoprotein binding	IPI	16441665
GO:0051222	Process	Positive regulation of protein transport	IEA
GO:0051385	Process	Response to mineralocorticoid	IEA
GO:0051602	Process	Response to electrical stimulus	IEA
GO:0051895	Process	Negative regulation of focal adhesion assembly	ISS
GO:0051897	Process	Positive regulation of protein kinase B signaling	IMP	19767770
GO:0051897	Process	Positive regulation of protein kinase B signaling	TAS
GO:0051902	Process	Negative regulation of mitochondrial depolarization	IMP	19767770
GO:0051974	Process	Negative regulation of telomerase activity	IMP	21531765
GO:0060065	Process	Uterus development	IEA
GO:0060444	Process	Branching involved in mammary gland duct morphogenesis	IEA
GO:0060491	Process	Regulation of cell projection assembly	IEA
GO:0060576	Process	Intestinal epithelial cell development	IDA	25731159
GO:0070062	Component	Extracellular exosome	HDA	19056867, 20458337
GO:0070102	Process	Interleukin-6-mediated signaling pathway	IDA	25731159
GO:0070301	Process	Cellular response to hydrogen peroxide	IEA
GO:0070374	Process	Positive regulation of ERK1 and ERK2 cascade	IEA
GO:0070555	Process	Response to interleukin-1	IMP	19281832
GO:0070700	Function	BMP receptor binding	IPI	26598555
GO:0070851	Function	Growth factor receptor binding	IBA	21873635
GO:0070851	Function	Growth factor receptor binding	IPI	16479011
GO:0071222	Process	Cellular response to lipopolysaccharide	IEA
GO:0071253	Function	Connexin binding	IEA
GO:0071375	Process	Cellular response to peptide hormone stimulus	ISS
GO:0071393	Process	Cellular response to progesterone stimulus	ISS
GO:0071398	Process	Cellular response to fatty acid	IEA
GO:0071456	Process	Cellular response to hypoxia	IEA
GO:0071498	Process	Cellular response to fluid shear stress	IEA
GO:0071803	Process	Positive regulation of podosome assembly	IEA
GO:0071902	Process	Positive regulation of protein serine/threonine kinase activity	IDA	19059439
GO:0086098	Process	Angiotensin-activated signaling pathway involved in heart process	ISS
GO:0090263	Process	Positive regulation of canonical Wnt signaling pathway	IEA
GO:0097110	Function	Scaffold protein binding	IPI	25006397
GO:0098609	Process	Cell-cell adhesion	IEA
GO:0098962	Process	Regulation of postsynaptic neurotransmitter receptor activity	IEA
GO:0098978	Component	Glutamatergic synapse	IEA
GO:0099091	Component	Postsynaptic specialization, intracellular component	IEA
GO:1900182	Process	Positive regulation of protein localization to nucleus	IEA
GO:1903997	Process	Positive regulation of non-membrane spanning protein tyrosine kinase activity	NAS	20018849
GO:2000386	Process	Positive regulation of ovarian follicle development	IEA
GO:2000394	Process	Positive regulation of lamellipodium morphogenesis	IMP	18054784
GO:2000573	Process	Positive regulation of DNA biosynthetic process	IEA
GO:2000588	Process	Positive regulation of platelet-derived growth factor receptor-beta signaling pathway	IEA
GO:2000641	Process	Regulation of early endosome to late endosome transport	IMP	21724833
GO:2000811	Process	Negative regulation of anoikis	IMP	22402981
GO:2001237	Process	Negative regulation of extrinsic apoptotic signaling pathway	IBA	21873635
GO:2001237	Process	Negative regulation of extrinsic apoptotic signaling pathway	IMP	19767770
GO:2001243	Process	Negative regulation of intrinsic apoptotic signaling pathway	IBA	21873635
GO:2001243	Process	Negative regulation of intrinsic apoptotic signaling pathway	IMP	19767770
GO:2001286	Process	Regulation of caveolin-mediated endocytosis	IMP	21724833

Other IDs

• MIM: 190090
• HGNC: 11283
• e!Ensembl: ENSG00000197122

Protein

• UniProt ID: P12931
• Protein name: Proto-oncogene tyrosine-protein kinase Src (EC 2.7.10.2) (Proto-oncogene c-Src) (pp60c-src) (p60-Src)
• Protein function: Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors, receptor protein tyrosine kinases, G protein-coupled receptors as well as cytokine receptors. Participates in signaling pathways that control a diverse spectrum of biological activities including gene transcription, immune response, cell adhesion, cell cycle progression, apoptosis, migration, and transformation. Due to functional redundancy between members of the SRC kinase family, identification of the specific role of each SRC kinase is very difficult. SRC appears to be one of the primary kinases activated following engagement of receptors and plays a role in the activation of other protein tyrosine kinase (PTK) families. Receptor clustering or dimerization leads to recruitment of SRC to the receptor complexes where it phosphorylates the tyrosine residues within the receptor cytoplasmic domains. Plays an important role in the regulation of cytoskeletal organization through phosphorylation of specific substrates such as AFAP1. Phosphorylation of AFAP1 allows the SRC SH2 domain to bind AFAP1 and to localize to actin filaments. Cytoskeletal reorganization is also controlled through the phosphorylation of cortactin (CTTN) (Probable). When cells adhere via focal adhesions to the extracellular matrix, signals are transmitted by integrins into the cell resulting in tyrosine phosphorylation of a number of focal adhesion proteins, including PTK2/FAK1 and paxillin (PXN) (PubMed:21411625). In addition to phosphorylating focal adhesion proteins, SRC is also active at the sites of cell-cell contact adherens junctions and phosphorylates substrates such as beta-catenin (CTNNB1), delta-catenin (CTNND1), and plakoglobin (JUP). Another type of cell-cell junction, the gap junction, is also a target for SRC, which phosphorylates connexin-43 (GJA1). SRC is implicated in regulation of pre-mRNA-processing and phosphorylates RNA-binding proteins such as KHDRBS1 (Probable). Also plays a role in PDGF-mediated tyrosine phosphorylation of both STAT1 and STAT3, leading to increased DNA binding activity of these transcription factors (By similarity). Involved in the RAS pathway through phosphorylation of RASA1 and RASGRF1 (PubMed:11389730). Plays a role in EGF-mediated calcium-activated chloride channel activation (PubMed:18586953). Required for epidermal growth factor receptor (EGFR) internalization through phosphorylation of clathrin heavy chain (CLTC and CLTCL1) at 'Tyr-1477'. Involved in beta-arrestin (ARRB1 and ARRB2) desensitization through phosphorylation and activation of GRK2, leading to beta-arrestin phosphorylation and internalization. Has a critical role in the stimulation of the CDK20/MAPK3 mitogen-activated protein kinase cascade by epidermal growth factor (Probable). Might be involved not only in mediating the transduction of mitogenic signals at the level of the plasma membrane but also in controlling progression through the cell cycle via interaction with regulatory proteins in the nucleus (PubMed:7853507). Plays an important role in osteoclastic bone resorption in conjunction with PTK2B/PYK2. Both the formation of a SRC-PTK2B/PYK2 complex and SRC kinase activity are necessary for this function. Recruited to activated integrins by PTK2B/PYK2, thereby phosphorylating CBL, which in turn induces the activation and recruitment of phosphatidylinositol 3-kinase to the cell membrane in a signaling pathway that is critical for osteoclast function (PubMed:8755529, PubMed:14585963). Promotes energy production in osteoclasts by activating mitochondrial cytochrome C oxidase (PubMed:12615910). Phosphorylates DDR2 on tyrosine residues, thereby promoting its subsequent autophosphorylation (PubMed:16186108). Phosphorylates RUNX3 and COX2 on tyrosine residues, TNK2 on 'Tyr-284' and CBL on 'Tyr-731' (PubMed:20100835, PubMed:21309750). Enhances DDX58/RIG-I-elicited antiviral signaling (PubMed:19419966). Phosphorylates PDPK1 at 'Tyr-9', 'Tyr-373' and 'Tyr-376' (PubMed:14585963). Phosphorylates BCAR1 at 'Tyr-128' (PubMed:22710723). Phosphorylates CBLC at multiple tyrosine residues, phosphorylation at 'Tyr-341' activates CBLC E3 activity (PubMed:20525694). Involved in anchorage-independent cell growth (PubMed:19307596). Required for podosome formation (By similarity). Mediates IL6 signaling by activating YAP1-NOTCH pathway to induce inflammation-induced epithelial regeneration (PubMed:25731159).
• PDB: 1A07, 1A08, 1A09, 1A1A, 1A1B, 1A1C, 1A1E, 1FMK, 1HCS, 1HCT, 1KSW, 1O41, 1O42, 1O43, 1O44, 1O45, 1O46, 1O47, 1O48, 1O49, 1O4A, 1O4B, 1O4C, 1O4D, 1O4E, 1O4F, 1O4G, 1O4H, 1O4I, 1O4J, 1O4K, 1O4L, 1O4M, 1O4N, 1O4O, 1O4P, 1O4Q, 1O4R, 1SHD, 1Y57, 1YI6, 1YOJ, 1YOL, 1YOM, 2BDF, 2BDJ, 2H8H, 2SRC, 3VRO, 3ZMP, 3ZMQ
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00018	SH3_1	90 → 137	SH3 domain	Domain
  PF00017	SH2	151 → 233	SH2 domain	Domain
  PF07714	PK_Tyr_Ser-Thr	270 → 519	Protein tyrosine and serine/threonine kinase	Domain

• Sequence:

  MGSNKSKPKDASQRRRSLEPAENVHGAGGGAFPASQTPSKPASADGHRGPSAAFAPAAAE
  PKLFGGFNSSDTVTSPQRAGPLAGGVTTFVALYDYESRTETDLSFKKGERLQIVNNTEGD
  WWLAHSLSTGQTGYIPSNYVAPSDSIQAEEWYFGKITRRESERLLLNAENPRGTFLVRES
  ETTKGAYCLSVSDFDNAKGLNVKHYKIRKLDSGGFYITSRTQFNSLQQLVAYYSKHADGL
  CHRLTTVCPTSKPQTQGLAKDAWEIPRESLRLEVKLGQGCFGEVWMGTWNGTTRVAIKTL
  KPGTMSPEAFLQEAQVMKKLRHEKLVQLYAVVSEEPIYIVTEYMSKGSLLDFLKGETGKY
  LRLPQLVDMAAQIASGMAYVERMNYVHRDLRAANILVGENLVCKVADFGLARLIEDNEYT
  ARQGAKFPIKWTAPEAALYGRFTIKSDVWSFGILLTELTTKGRVPYPGMVNREVLDQVER
  GYRMPCPPECPESLHDLMCQCWRKEPEERPTFEYLQAFLEDYFTSTEPQYQPGENL

• Sequence length: 536