SRC
entrez
6714
canonical
uniprot
P12931
canonical
ensembl
ENSG00000197122
resolver
ensembl
ENSG00000291971
resolver
ensp
ENSP00000362659
resolver
ensp
ENSP00000362680
resolver
ensp
ENSP00000508666
resolver
ensp
ENSP00000509325
resolver
ensp
ENSP00000546285
resolver
ensp
ENSP00000546286
resolver
ensp
ENSP00000546289
resolver
ensp
ENSP00000546292
resolver
ensp
ENSP00000546295
resolver
ensp
ENSP00000591742
resolver
genesymbol
SRC
resolver
genesymbol_syn
SRC1
resolver
hgnc
HGNC:11283
resolver
uniprot
E1P5V4
resolver
uniprot
Q76P87
resolver
uniprot
Q86VB9
resolver
uniprot
Q9H5A8
resolver
uniprot_entry
SRC_HUMAN
resolver
uniprot_sec
E1P5V4
resolver
uniprot_sec
Q76P87
resolver
uniprot_sec
Q86VB9
resolver
uniprot_sec
Q9H5A8
resolver
activity_regulation
ACTIVITY REGULATION: Phosphorylation by CSK at Tyr-530 inhibits kinase activity. Inhibitory phosphorylation at Tyr-530 is enhanced by heme. Further phosphorylation by CDK1 partially reactivates CSK-inactivated SRC and facilitates complete reactivation by protein tyrosine phosphatase PTPRC. Integrin engagement stimulates kinase activity. Phosphorylation by PTK2/FAK1 enhances kinase activity. Butein and pseudosubstrate-based peptide inhibitors like CIYKYYF act as inhibitors. Phosphorylation at Tyr-419 increases kinase activity. {ECO:0000269|PubMed:14632929, ECO:0000269|PubMed:21036157, ECO:0000269|PubMed:7929427, ECO:0000269|PubMed:8759729, ECO:0000269|PubMed:9571170}.
uniprot
proteins
amino_acid_sequence
MGSNKSKPKDASQRRRSLEPAENVHGAGGGAFPASQTPSKPASADGHRGPSAAFAPAAAEPKLFGGFNSSDTVTSPQRAGPLAGGVTTFVALYDYESRTETDLSFKKGERLQIVNNTEGDWWLAHSLSTGQTGYIPSNYVAPSDSIQAEEWYFGKITRRESERLLLNAENPRGTFLVRESETTKGAYCLSVSDFDNAKGLNVKHYKIRKLDSGGFYITSRTQFNSLQQLVAYYSKHADGLCHRLTTVCPTSKPQTQGLAKDAWEIPRESLRLEVKLGQGCFGEVWMGTWNGTTRVAIKTLKPGTMSPEAFLQEAQVMKKLRHEKLVQLYAVVSEEPIYIVTEYMSKGSLLDFLKGETGKYLRLPQLVDMAAQIASGMAYVERMNYVHRDLRAANILVGENLVCKVADFGLARLIEDNEYTARQGAKFPIKWTAPEAALYGRFTIKSDVWSFGILLTELTTKGRVPYPGMVNREVLDQVERGYRMPCPPECPESLHDLMCQCWRKEPEERPTFEYLQAFLEDYFTSTEPQYQPGENL
uniprot
proteins
disease_involvement
DISEASE: Note=SRC kinase activity has been shown to be increased in several tumor tissues and tumor cell lines such as colon carcinoma cells. {ECO:0000269|PubMed:2498394, ECO:0000269|PubMed:3093483}.; DISEASE: Thrombocytopenia 6 (THC6) [MIM:616937]: A form of thrombocytopenia, a hematologic disorder defined by a decrease in the number of platelets in circulating blood, resulting in the potential for increased bleeding and decreased ability for clotting. THC6 is an autosomal dominant form. Affected individuals may also have bone abnormalities and an increased risk for myelofibrosis. {ECO:0000269|PubMed:26936507}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
2.7.10.2
uniprot
proteins
function
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 (PubMed:34234773). 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). Phosphorylates PKP3 at 'Tyr-195' in response to reactive oxygen species, which may cause the release of PKP3 from desmosome cell junctions into the cytoplasm (PubMed:25501895). 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:14585963, PubMed:8755529). Upon activation of the G(q)-dependent KISS1/KISS1R signaling pathway, active SRC is recruited, together with the phosphatase DUSP18, to the KISS1R C-terminus (PubMed:38346942). This leads to DUSP18-mediated SRC dephosphorylation and inactivation, down-regulation of osteoclast differentiation and activity, and consequently suppression of bone resorption (By similarity). 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 RIGI-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). Phosphorylates synaptic vesicle protein synaptophysin (SYP) (By similarity). 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). Phosphorylates OTUB1, promoting deubiquitination of RPTOR (PubMed:35927303). Phosphorylates caspase CASP8 at 'Tyr-380' which negatively regulates CASP8 processing and activation, down-regulating CASP8 proapoptotic function (PubMed:16619028). Mediates laminin-induced activation of RAC1 signaling through phosphorylation of syntrophin (By similarity). {ECO:0000250|UniProtKB:P05480, ECO:0000250|UniProtKB:Q9WUD9, ECO:0000269|PubMed:11389730, ECO:0000269|PubMed:12615910, ECO:0000269|PubMed:14585963, ECO:0000269|PubMed:16186108, ECO:0000269|PubMed:16619028, ECO:0000269|PubMed:18586953, ECO:0000269|PubMed:19307596, ECO:0000269|PubMed:19419966, ECO:0000269|PubMed:20100835, ECO:0000269|PubMed:20525694, ECO:0000269|PubMed:21309750, ECO:0000269|PubMed:21411625, ECO:0000269|PubMed:22710723, ECO:0000269|PubMed:25501895, ECO:0000269|PubMed:25731159, ECO:0000269|PubMed:34234773, ECO:0000269|PubMed:35927303, ECO:0000269|PubMed:38346942, ECO:0000269|PubMed:7853507, ECO:0000269|PubMed:8755529, ECO:0000269|PubMed:8759729, ECO:0000305|PubMed:11964124, ECO:0000305|PubMed:8672527, ECO:0000305|PubMed:9442882}.; FUNCTION: [Isoform 1]: Non-receptor protein tyrosine kinase which phosphorylates synaptophysin with high affinity. {ECO:0000250|UniProtKB:Q9WUD9}.; FUNCTION: [Isoform 2]: Non-receptor protein tyrosine kinase which shows higher basal kinase activity than isoform 1, possibly due to weakened intramolecular interactions which enhance autophosphorylation of Tyr-419 and subsequent activation (By similarity). The SH3 domain shows reduced affinity with the linker sequence between the SH2 and kinase domains which may account for the increased basal activity (By similarity). Displays altered substrate specificity compared to isoform 1, showing weak affinity for synaptophysin and for peptide substrates containing class I or class II SH3 domain-binding motifs (By similarity). Plays a role in L1CAM-mediated neurite elongation, possibly by acting downstream of L1CAM to drive cytoskeletal rearrangements involved in neurite outgrowth (By similarity). {ECO:0000250|UniProtKB:Q9WUD9}.; FUNCTION: [Isoform 3]: Non-receptor protein tyrosine kinase which shows higher basal kinase activity than isoform 1, possibly due to weakened intramolecular interactions which enhance autophosphorylation of Tyr-419 and subsequent activation (By similarity). The SH3 domain shows reduced affinity with the linker sequence between the SH2 and kinase domains which may account for the increased basal activity (By similarity). Displays altered substrate specificity compared to isoform 1, showing weak affinity for synaptophysin and for peptide substrates containing class I or class II SH3 domain-binding motifs (By similarity). Plays a role in neurite elongation (By similarity). {ECO:0000250|UniProtKB:Q9WUD9}.
uniprot
proteins
mass_dalton
59835
uniprot
proteins
mutagenesis
MUTAGEN 298; /note="K->M: Kinase inactive. Abolishes ubiquitination promoted by CBLC."; /evidence="ECO:0000269|PubMed:14661060"; MUTAGEN 302; /note="P->E: Kinase active. Interacts with PDLIM4; when associated with E-307 and F-419."; /evidence="ECO:0000269|PubMed:19307596"; MUTAGEN 307; /note="P->E: Kinase active. Interacts with PDLIM4; when associated with E-302 and F-419."; /evidence="ECO:0000269|PubMed:19307596"; MUTAGEN 419; /note="Y->F: Loss of kinase activity. Loss of interaction with PDLIM4."; /evidence="ECO:0000269|PubMed:19307596
uniprot
proteins
post_translational_modification
PTM: Myristoylated at Gly-2, and this is essential for targeting to membranes. {ECO:0000269|PubMed:7525268}.; PTM: Dephosphorylated at Tyr-530 by PTPRJ (By similarity). Phosphorylated on Tyr-530 by c-Src kinase (CSK). The phosphorylated form is termed pp60c-src. Dephosphorylated by PTPRJ at Tyr-419. Normally maintained in an inactive conformation with the SH2 domain engaged with Tyr-530, the SH3 domain engaged with the SH2-kinase linker, and Tyr-419 dephosphorylated. Dephosphorylation of Tyr-530 as a result of protein tyrosine phosphatase (PTP) action disrupts the intramolecular interaction between the SH2 domain and Tyr-530, Tyr-419 can then become autophosphorylated, resulting in SRC activation. Phosphorylation of Tyr-530 by CSK allows this interaction to reform, resulting in SRC inactivation. CDK5-mediated phosphorylation at Ser-75 targets SRC to ubiquitin-dependent degradation and thus leads to cytoskeletal reorganization. Phosphorylated by PTK2/FAK1; this enhances kinase activity. Phosphorylated by PTK2B/PYK2; this enhances kinase activity. Upon activation of IL6ST by IL6, Tyr-419 is phosphorylated and Tyr-530 dephosphorylated (PubMed:25731159). {ECO:0000250, ECO:0000269|PubMed:14661060, ECO:0000269|PubMed:18936167, ECO:0000269|PubMed:21442427, ECO:0000269|PubMed:22888118, ECO:0000269|PubMed:25731159, ECO:0000269|PubMed:6273838, ECO:0000269|PubMed:7525268}.; PTM: [Isoform 1]: Displays reduced levels of autophosphorylation at Tyr-419 compared to isoforms 2 and 3. {ECO:0000250|UniProtKB:Q9WUD9}.; PTM: [Isoform 2]: Displays enhanced levels of autophosphorylation at Tyr-419 compared to isoform 1. {ECO:0000250|UniProtKB:Q9WUD9}.; PTM: [Isoform 3]: Displays enhanced levels of autophosphorylation at Tyr-419 compared to isoform 1 (By similarity). Shows reduced phosphorylation at Tyr-527 compared to isoforms 1 and 2 (By similarity). {ECO:0000250|UniProtKB:Q9WUD9}.; PTM: S-nitrosylation is important for activation of its kinase activity. {ECO:0000250}.; PTM: Ubiquitinated in response to CDK5-mediated phosphorylation. Ubiquitination mediated by CBLC requires SRC autophosphorylation at Tyr-419 and may lead to lysosomal degradation. {ECO:0000269|PubMed:14661060, ECO:0000269|PubMed:18936167, ECO:0000269|PubMed:22888118, ECO:0000269|PubMed:6273838}.
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
protein_family
SRC subfamily
uniprot
proteins
protein_family
Tyr protein kinase family
uniprot
proteins
pubmed
10747847
uniprot
proteins
pubmed
10753943
uniprot
proteins
pubmed
11152665
uniprot
proteins
pubmed
11279199
uniprot
proteins
pubmed
11389730
uniprot
proteins
pubmed
11518702
uniprot
proteins
pubmed
11780052
uniprot
proteins
pubmed
11964124
uniprot
proteins
pubmed
12091389
uniprot
proteins
pubmed
12415108
uniprot
proteins
pubmed
12615910
uniprot
proteins
pubmed
12925710
uniprot
proteins
pubmed
14585963
uniprot
proteins
pubmed
14632929
uniprot
proteins
pubmed
14661060
uniprot
proteins
pubmed
14963108
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15504032
uniprot
proteins
pubmed
15851033
uniprot
proteins
pubmed
16186108
uniprot
proteins
pubmed
16479011
uniprot
proteins
pubmed
16619028
uniprot
proteins
pubmed
1691439
uniprot
proteins
pubmed
17202804
uniprot
proteins
pubmed
17293535
uniprot
proteins
pubmed
17344846
uniprot
proteins
pubmed
17525734
uniprot
proteins
pubmed
18024423
uniprot
proteins
pubmed
18088087
uniprot
proteins
pubmed
18586953
uniprot
proteins
pubmed
18657504
uniprot
proteins
pubmed
18691976
uniprot
proteins
pubmed
18936167
uniprot
proteins
pubmed
19307596
uniprot
proteins
pubmed
19369195
uniprot
proteins
pubmed
19419966
uniprot
proteins
pubmed
19665017
uniprot
proteins
pubmed
19666546
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
19807924
uniprot
proteins
pubmed
20100835
uniprot
proteins
pubmed
20525694
uniprot
proteins
pubmed
20534535
uniprot
proteins
pubmed
21036157
uniprot
proteins
pubmed
21309750
uniprot
proteins
pubmed
21411625
uniprot
proteins
pubmed
21442427
uniprot
proteins
pubmed
21460222
uniprot
proteins
pubmed
22294297
uniprot
proteins
pubmed
22710723
uniprot
proteins
pubmed
22801373
uniprot
proteins
pubmed
22888118
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23564345
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
2498394
uniprot
proteins
pubmed
25501895
uniprot
proteins
pubmed
25731159
uniprot
proteins
pubmed
2581127
uniprot
proteins
pubmed
2582238
uniprot
proteins
pubmed
2681803
uniprot
proteins
pubmed
26936507
uniprot
proteins
pubmed
28903391
uniprot
proteins
pubmed
30862675
uniprot
proteins
pubmed
3093483
uniprot
proteins
pubmed
31320558
uniprot
proteins
pubmed
3299057
uniprot
proteins
pubmed
34234773
uniprot
proteins
pubmed
35927303
uniprot
proteins
pubmed
38346942
uniprot
proteins
pubmed
39702286
uniprot
proteins
pubmed
6273838
uniprot
proteins
pubmed
7478590
uniprot
proteins
pubmed
7525268
uniprot
proteins
pubmed
7532003
uniprot
proteins
pubmed
7853507
uniprot
proteins
pubmed
7929427
uniprot
proteins
pubmed
8319227
uniprot
proteins
pubmed
8672527
uniprot
proteins
pubmed
8755529
uniprot
proteins
pubmed
8759729
uniprot
proteins
pubmed
9024657
uniprot
proteins
pubmed
9174343
uniprot
proteins
pubmed
9442882
uniprot
proteins
pubmed
9571170
uniprot
proteins
pubmed
9584165
uniprot
proteins
pubmed
9924018
uniprot
proteins
sequence_length
536
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:7525268}; Lipid-anchor {ECO:0000269|PubMed:22801373}. Mitochondrion inner membrane {ECO:0000269|PubMed:12615910}. Nucleus {ECO:0000269|PubMed:7853507}. Cytoplasm, cytoskeleton {ECO:0000269|PubMed:7525268}. Cytoplasm, perinuclear region {ECO:0000269|PubMed:19307596}. Cell junction, focal adhesion {ECO:0000269|PubMed:22801373}. Cell junction {ECO:0000269|PubMed:22294297}. Note=Localizes to focal adhesion sites following integrin engagement (PubMed:22801373). Localization to focal adhesion sites requires myristoylation and the SH3 domain (PubMed:7525268). Colocalizes with PDLIM4 at the perinuclear region, but not at focal adhesions (PubMed:19307596). {ECO:0000269|PubMed:19307596, ECO:0000269|PubMed:22801373, ECO:0000269|PubMed:7525268}.
uniprot
proteins