Src
entrez
20779
canonical
uniprot
P05480
canonical
ensembl
ENSMUSG00000027646
resolver
ensp
ENSMUSP00000029175
resolver
ensp
ENSMUSP00000090237
resolver
ensp
ENSMUSP00000105155
resolver
ensp
ENSMUSP00000216941
resolver
ensp
ENSMUSP00000216942
resolver
ensp
ENSMUSP00000216943
resolver
ensp
ENSMUSP00000216944
resolver
ensp
ENSMUSP00000216945
resolver
ensp
ENSMUSP00000216946
resolver
ensp
ENSMUSP00000216949
resolver
ensp
ENSMUSP00000328414
resolver
ensp
ENSMUSP00000328423
resolver
genesymbol
Src
resolver
uniprot
F8WI90
resolver
uniprot
Q2M4I4
resolver
uniprot_entry
SRC_MOUSE
resolver
uniprot_sec
F8WI90
resolver
uniprot_sec
Q2M4I4
resolver
activity_regulation
ACTIVITY REGULATION: Phosphorylation by CSK at Tyr-529 inhibits kinase activity. Inhibitory phosphorylation at Tyr-529 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-418 increases kinase activity. {ECO:0000269|PubMed:8910389}.
uniprot
proteins
amino_acid_sequence
MGSNKSKPKDASQRRRSLEPSENVHGAGGAFPASQTPSKPASADGHRGPSAAFVPPAAEPKLFGGFNSSDTVTSPQRAGPLAGGVTTFVALYDYESRTETDLSFKKGERLQIVNNTEGDWWLAHSLSTGQTGYIPSNYVAPSDSIQAEEWYFGKITRRESERLLLNAENPRGTFLVRESETTKGAYCLSVSDFDNAKGLNVKHYKIRKLDSGGFYITSRTQFNSLQQLVAYYSKHADGLCHRLTTVCPTSKPQTQGLAKDAWEIPRESLRLEVKLGQGCFGEVWMGTWNGTTRVAIKTLKPGTMSPEAFLQEAQVMKKLRHEKLVQLYAVVSEEPIYIVTEYMNKGSLLDFLKGETGKYLRLPQLVDMSAQIASGMAYVERMNYVHRDLRAANILVGENLVCKVADFGLARLIEDNEYTARQGAKFPIKWTAPEAALYGRFTIKSDVWSFGILLTELTTKGRVPYPGMVNREVLDQVERGYRMPCPPECPESLHDLMCQCWRKEPEERPTFEYLQAFLEDYFTSTEPQYQPGENL
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. 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) (By similarity). 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 (By similarity). Also plays a role in PDGF-mediated tyrosine phosphorylation of both STAT1 and STAT3, leading to increased DNA binding activity of these transcription factors (PubMed:9344858). Involved in the RAS pathway through phosphorylation of RASA1 and RASGRF1. Plays a role in EGF-mediated calcium-activated chloride channel activation (By similarity). 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 (By similarity). 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:14739300). 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. This leads to DUSP18-mediated SRC dephosphorylation and inactivation, down-regulation of osteoclast differentiation and activity, and consequently suppression of bone resorption (PubMed:38346942). Promotes energy production in osteoclasts by activating mitochondrial cytochrome C oxidase (PubMed:12615910). Phosphorylates DDR2 on tyrosine residues, thereby promoting its subsequent autophosphorylation. Phosphorylates RUNX3 and COX2 on tyrosine residues, TNK2 on 'Tyr-284' and CBL on 'Tyr-738'. Enhances RIGI-elicited antiviral signaling. Phosphorylates PDPK1 at 'Tyr-9', 'Tyr-373' and 'Tyr-376'. Phosphorylates BCAR1 at 'Tyr-226'. Phosphorylates CBLC at multiple tyrosine residues, phosphorylation at 'Tyr-341' activates CBLC E3 activity. Phosphorylates synaptic vesicle protein synaptophysin (SYP) (By similarity). Involved in anchorage-independent cell growth (By similarity). Required for podosome formation (PubMed:21525037). Mediates IL6 signaling by activating YAP1-NOTCH pathway to induce inflammation-induced epithelial regeneration (PubMed:25731159). Phosphorylates OTUB1, promoting deubiquitination of RPTOR (By similarity). Mediates laminin-induced activation of RAC1 signaling through phosphorylation of syntrophin (PubMed:18044967). {ECO:0000250|UniProtKB:P12931, ECO:0000250|UniProtKB:Q9WUD9, ECO:0000269|PubMed:12615910, ECO:0000269|PubMed:14739300, ECO:0000269|PubMed:18044967, ECO:0000269|PubMed:21525037, ECO:0000269|PubMed:25731159, ECO:0000269|PubMed:38346942, ECO:0000269|PubMed:8641341, ECO:0000269|PubMed:9344858, 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-418 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}.
uniprot
proteins
mass_dalton
59891
uniprot
proteins
post_translational_modification
PTM: Myristoylated at Gly-2, and this is essential for targeting to membranes. {ECO:0000250}.; PTM: Dephosphorylated at Tyr-529 by PTPRJ (By similarity). Phosphorylated on Tyr-529 by c-Src kinase (CSK). The phosphorylated form is termed pp60c-src. Dephosphorylated by PTPRJ at Tyr-418. Normally maintained in an inactive conformation with the SH2 domain engaged with Tyr-529, the SH3 domain engaged with the SH2-kinase linker, and Tyr-418 dephosphorylated. Dephosphorylation of Tyr-529 as a result of protein tyrosine phosphatase (PTP) action disrupts the intramolecular interaction between the SH2 domain and Tyr-529, Tyr-418 can then become autophosphorylated, resulting in SRC activation. Phosphorylation of Tyr-529 by CSK allows this interaction to reform, resulting in SRC inactivation. CDK5-mediated phosphorylation at Ser-74 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 (By similarity). Upon activation of IL6ST by IL6, Tyr-418 is phosphorylated and Tyr-529 dephosphorylated (PubMed:25731159). {ECO:0000250, ECO:0000269|PubMed:25731159}.; PTM: [Isoform 1]: Displays reduced levels of autophosphorylation at Tyr-418 compared to isoform 2. {ECO:0000250|UniProtKB:Q9WUD9}.; PTM: [Isoform 2]: Displays enhanced levels of autophosphorylation at Tyr-418 compared to isoform 1. {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-418 and may lead to lysosomal degradation (By similarity). {ECO:0000250}.
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
protein_family
SRC subfamily
uniprot
proteins
protein_family
Tyr protein kinase family
uniprot
proteins
pubmed
11433297
uniprot
proteins
pubmed
11964124
uniprot
proteins
pubmed
12615910
uniprot
proteins
pubmed
12925710
uniprot
proteins
pubmed
14644164
uniprot
proteins
pubmed
14739300
uniprot
proteins
pubmed
16684964
uniprot
proteins
pubmed
17000758
uniprot
proteins
pubmed
18034455
uniprot
proteins
pubmed
18044967
uniprot
proteins
pubmed
19122674
uniprot
proteins
pubmed
19144319
uniprot
proteins
pubmed
19468303
uniprot
proteins
pubmed
20093046
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
21525037
uniprot
proteins
pubmed
22801373
uniprot
proteins
pubmed
2440106
uniprot
proteins
pubmed
25731159
uniprot
proteins
pubmed
28362576
uniprot
proteins
pubmed
31320558
uniprot
proteins
pubmed
38346942
uniprot
proteins
pubmed
39702286
uniprot
proteins
pubmed
7542762
uniprot
proteins
pubmed
7681396
uniprot
proteins
pubmed
8641341
uniprot
proteins
pubmed
8672527
uniprot
proteins
pubmed
8910389
uniprot
proteins
pubmed
9344858
uniprot
proteins
pubmed
9442882
uniprot
proteins
pubmed
9819391
uniprot
proteins
sequence_length
535
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12615910, ECO:0000269|PubMed:21525037}; Lipid-anchor {ECO:0000269|PubMed:22801373}. Mitochondrion inner membrane {ECO:0000269|PubMed:12615910}. Nucleus {ECO:0000269|PubMed:12615910}. Cytoplasm, cytoskeleton {ECO:0000269|PubMed:12615910}. Cytoplasm, perinuclear region {ECO:0000250|UniProtKB:P12931}. Cell junction, focal adhesion {ECO:0000269|PubMed:22801373}. Cell junction {ECO:0000250|UniProtKB:P12931}. Note=Localizes to focal adhesion sites following integrin engagement (PubMed:22801373). Localization to focal adhesion sites requires myristoylation and the SH3 domain. Colocalizes with PDLIM4 at the perinuclear region, but not at focal adhesions. {ECO:0000250|UniProtKB:P12931, ECO:0000269|PubMed:22801373}.
uniprot
proteins