| 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). 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). 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. Also plays a role in PDGF-mediated tyrosine phosphorylation of both STAT1 and STAT3, leading to increased DNA binding activity of these transcription factors. Involved in the RAS pathway through phosphorylation of RASA1 and RASGRF1. Plays a role in EGF-mediated calcium-activated chloride channel activation. 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. 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. 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. Promotes energy production in osteoclasts by activating mitochondrial cytochrome C oxidase. 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-731'. Enhances DDX58/RIG-I-elicited antiviral signaling. Phosphorylates PDPK1 at 'Tyr-9', 'Tyr-373' and 'Tyr-376'. Phosphorylates BCAR1 at 'Tyr-128'. Phosphorylates CBLC at multiple tyrosine residues, phosphorylation at 'Tyr-341' activates CBLC E3 activity. Required for podosome formation (By similarity). |
| Tissue Specificity: |
Expressed ubiquitously. Platelets, neurons and osteoclasts express 5-fold to 200-fold higher levels than most other tissues. |
| Involvement in Disease: |
Thrombocytopenia 6: 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. |
| Sequence Similarities: |
Belongs to the protein kinase superfamily. Tyr protein kinase family. SRC subfamily. |
| Post-Translational Modification: |
Myristoylated at Gly-2, and this is essential for targeting to membranes. |
| Cellular Location: |
Cell membrane. Mitochondrion inner membrane. Nucleus. Cytoplasm > Cytoskeleton.
Localizes to focal adhesion sites following integrin engagement. Localization to focal adhesion sites requires myristoylation and the SH3 domain. |
| Database Links: |
Entrez Gene: 6714?HumanEntrez Gene: 20779?MouseEntrez Gene: 83805?RatOmim: 190090?HumanSwissProt: P12931?HumanSwissProt: P05480?MouseSwissProt: Q9WUD9?RatUnigene: 195659?HumanUnigene: 22845?MouseUnigene: 112600?Rat |
| Synonyms: |
ASV AntibodyAvian sarcoma virus Antibodyc SRC AntibodyCDNA FLJ14219 fis clone NT2RP3003800 highly similar to Rattus norvegicus tyrosine protein kinase pp60 c src mRNA AntibodycSrc AntibodyEC 2.7.10.2 AntibodyNeuronal CSRC tyrosine specific protein kinase AntibodyNeuronal SRC AntibodyOncogene SRC AntibodyOTTHUMP00000174476 AntibodyOTTHUMP00000174477 Antibodyp60 Src Antibodyp60-Src Antibodyp60Src Antibodypp60c src Antibodypp60c-src Antibodypp60csrc AntibodyProto oncogene tyrosine protein kinase Src AntibodyProto-oncogene c-Src AntibodyProto-oncogene tyrosine-protein kinase Src AntibodyProtooncogene SRC AntibodyProtooncogene SRC Rous sarcoma AntibodySrc AntibodySRC Oncogene AntibodySRC proto oncogene non receptor tyrosine kinase AntibodySRC1 AntibodySRC_HUMAN AntibodyTyrosine kinase pp60c src AntibodyTyrosine protein kinase SRC 1 AntibodyTyrosine protein kinase SRC1 Antibodyv src avian sarcoma (Schmidt Ruppin A2) viral oncogene homolog AntibodyV src sarcoma (Schmidt Ruppin A 2) viral oncogene homolog (avian) Antibodyv src sarcoma (Schmidt Ruppin A 2) viral oncogene homolog avian Antibody |
| Information: |
Target information shown above is from the UniProt Consortium. |
