SRC

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]

SRC Proto-Oncogene, Non-Receptor Tyrosine Kinase

Activation of protein kinase B activityIEA:Ensembl
Adherens junction organizationIEA:Ensembl
Angiotensin-activated signaling pathway involved in heart processISS:BHF-UCL
Bone resorptionISS:UniProtKB
Branching involved in mammary gland duct morphogenesisIEA:Ensembl
Cell adhesionManual Assertion Based On ExperimentIBA:GO_Central
Cell cycleIEA:UniProtKB-KW
Cell differentiationManual Assertion Based On ExperimentIBA:GO_Central
Cell population proliferationIEA:Ensembl
Cell-cell adhesionIEA:Ensembl
Cellular response to fatty acidIEA:Ensembl
Cellular response to fluid shear stressIEA:Ensembl
Cellular response to hydrogen peroxideIEA:Ensembl
Cellular response to hypoxiaIEA:Ensembl
Cellular response to insulin stimulusIEA:Ensembl
Cellular response to lipopolysaccharideIEA:Ensembl
Cellular response to peptide hormone stimulusISS:BHF-UCL
Cellular response to platelet-derived growth factor stimulusIEA:Ensembl
Cellular response to progesterone stimulusISS:BHF-UCL
Entry of bacterium into host cellTAS:Reactome
Ephrin receptor signaling pathwayTAS:Reactome
Epidermal growth factor receptor signaling pathwayManual Assertion Based On ExperimentIBA:GO_Central
ERBB2 signaling pathwayTAS:Reactome
Fc-gamma receptor signaling pathway involved in phagocytosisTAS:Reactome
Focal adhesion assemblyManual Assertion Based On ExperimentIMP:UniProtKB
Forebrain developmentIEA:Ensembl
Innate immune responseManual Assertion Based On ExperimentIBA:GO_Central
Integrin-mediated signaling pathwayManual Assertion Based On ExperimentIMP:UniProtKB
Interleukin-6-mediated signaling pathwayManual Assertion Based On ExperimentIDA:UniProtKB
Intestinal epithelial cell developmentManual Assertion Based On ExperimentIDA:UniProtKB
Intracellular signal transductionManual Assertion Based On ExperimentIDA:ARUK-UCL
Leukocyte migrationTAS:Reactome
MacroautophagyTAS:Reactome
Negative regulation of anoikisManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of apoptotic processManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of cysteine-type endopeptidase activity involved in apoptotic processManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of extrinsic apoptotic signaling pathwayManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of focal adhesion assemblyISS:BHF-UCL
Negative regulation of inflammatory response to antigenic stimulusTAS:Reactome
Negative regulation of intrinsic apoptotic signaling pathwayManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of mitochondrial depolarizationManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of protein-containing complex assemblyManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of telomerase activityManual Assertion Based On ExperimentIMP:BHF-UCL
Negative regulation of telomere maintenance via telomeraseManual Assertion Based On ExperimentIMP:BHF-UCL
Negative regulation of transcription, DNA-templatedIEA:Ensembl
Neurotrophin TRK receptor signaling pathwayIEA:Ensembl
OdontogenesisIEA:Ensembl
OogenesisIEA:Ensembl
Osteoclast developmentManual Assertion Based On ExperimentIBA:GO_Central
Peptidyl-serine phosphorylationIEA:Ensembl
Peptidyl-tyrosine autophosphorylationIEA:Ensembl
Peptidyl-tyrosine phosphorylationManual Assertion Based On ExperimentIDA:UniProtKB
Platelet activationTAS:Reactome
Positive regulation of apoptotic processIEA:Ensembl
Positive regulation of canonical Wnt signaling pathwayIEA:Ensembl
Positive regulation of cyclin-dependent protein serine/threonine kinase activityIEA:Ensembl
Positive regulation of cytokine productionIEA:Ensembl
Positive regulation of dephosphorylationManual Assertion Based On ExperimentIDA:ARUK-UCL
Positive regulation of DNA biosynthetic processIEA:Ensembl
Positive regulation of epithelial cell migrationManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of ERK1 and ERK2 cascadeIEA:Ensembl
Positive regulation of glucose metabolic processIEA:Ensembl
Positive regulation of insulin receptor signaling pathwayIEA:Ensembl
Positive regulation of integrin activationManual Assertion Based On ExperimentTAS:BHF-UCL
Positive regulation of lamellipodium morphogenesisManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of MAP kinase activityIEA:Ensembl
Positive regulation of non-membrane spanning protein tyrosine kinase activity1 PublicationNAS:ARUK-UCL
Positive regulation of Notch signaling pathwayManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of ovarian follicle developmentIEA:Ensembl
Positive regulation of peptidyl-tyrosine phosphorylationManual Assertion Based On ExperimentIMP:ARUK-UCL
Positive regulation of phosphatidylinositol 3-kinase activityIEA:Ensembl
Positive regulation of phosphatidylinositol 3-kinase signalingTAS:Reactome
Positive regulation of platelet-derived growth factor receptor-beta signaling pathwayIEA:Ensembl
Positive regulation of podosome assemblyIEA:Ensembl
Positive regulation of protein autophosphorylationIEA:Ensembl
Positive regulation of protein kinase B signalingManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of protein localization to nucleusIEA:Ensembl
Positive regulation of protein processingIEA:Ensembl
Positive regulation of protein serine/threonine kinase activityManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of protein transportIEA:Ensembl
Positive regulation of small GTPase mediated signal transductionManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Positive regulation of smooth muscle cell migrationIEA:Ensembl
Positive regulation of transcription, DNA-templatedIEA:Ensembl
Primary ovarian follicle growthIEA:Ensembl
Progesterone receptor signaling pathwayISS:BHF-UCL
Protein autophosphorylationManual Assertion Based On ExperimentIDA:UniProtKB
Protein destabilizationIEA:Ensembl
Regulation of bone resorptionManual Assertion Based On ExperimentTAS:BHF-UCL
Regulation of caveolin-mediated endocytosisManual Assertion Based On ExperimentIMP:UniProtKB
Regulation of cell projection assemblyIEA:Ensembl
Regulation of cell-cell adhesionManual Assertion Based On ExperimentIMP:UniProtKB
Regulation of early endosome to late endosome transportManual Assertion Based On ExperimentIMP:UniProtKB
Regulation of epithelial cell migrationManual Assertion Based On ExperimentIMP:UniProtKB
Regulation of intracellular estrogen receptor signaling pathwayIEA:Ensembl
Regulation of postsynaptic neurotransmitter receptor activityIEA:Ensembl
Regulation of protein bindingIEA:Ensembl
Regulation of vascular permeabilityManual Assertion Based On ExperimentTAS:BHF-UCL
Response to acidic pHIEA:Ensembl
Response to electrical stimulusIEA:Ensembl
Response to interleukin-1Manual Assertion Based On ExperimentIMP:BHF-UCL
Response to mechanical stimulusIEA:Ensembl
Response to mineralocorticoidIEA:Ensembl
Response to nutrient levelsIEA:Ensembl
Response to virusIEA:Ensembl
Response to xenobiotic stimulusIEA:Ensembl
Signal complex assemblyManual Assertion Based On ExperimentTAS:ProtInc
Signal transductionManual Assertion Based On ExperimentTAS:ProtInc
Stimulatory C-type lectin receptor signaling pathwayTAS:Reactome
Stress fiber assemblyManual Assertion Based On ExperimentIMP:UniProtKB
Substrate adhesion-dependent cell spreadingIEA:Ensembl
T cell costimulationTAS:Reactome
TranscytosisIEA:Ensembl
Transforming growth factor beta receptor signaling pathwayManual Assertion Based On ExperimentIMP:UniProtKB
Transmembrane receptor protein tyrosine kinase signaling pathwayManual Assertion Based On ExperimentIBA:GO_Central
Uterus developmentIEA:Ensembl
Vascular endothelial growth factor receptor signaling pathwayTAS:Reactome

Cell membrane
Mitochondrion inner membrane
Nucleus
Cytoplasm, cytoskeleton
Cytoplasm, perinuclear region
Cell junction, focal adhesion
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).

Thrombocytopenia 6 (THC6):
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.

Myristoylated at Gly-2, and this is essential for targeting to membranes.
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).
Isoform 1
Displays reduced levels of autophosphorylation at Tyr-419 compared to isoforms 2 and 3.
Isoform 2
Displays enhanced levels of autophosphorylation at Tyr-419 compared to isoform 1.
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).
S-nitrosylation is important for activation of its kinase activity.
Ubiquitinated in response to CDK5-mediated phosphorylation. Ubiquitination mediated by CBLC requires SRC autophosphorylation at Tyr-419 and may lead to lysosomal degradation.