SRC | Proto-oncogene tyrosine-protein kinase Src
 
              DARK BACKGROUND
Sequence Viewer
Gene
SRC
Synonyms
SRC1
Protein Name
Proto-oncogene tyrosine-protein kinase Src
UniProt ID
P12931 [go to UniProt ] [go to PDBe-KB ]
Ensembl Gene ID
ENSP00000350941
NCBI Gene ID
6714
Molecular Weight
59835
Protein Length
536.0
Protein Domain
InterPro | Pfam
3D Structure
(PDB ID : 1a07)
PDBe | PDBj | RCSB PDB
DrugPort | ModBase | SwissModel
Target by Small Molecules
chEMBL
Protein-protein Interaction Database
STRING | IntAct | MINT
Gene Expression
Gene Expression Atlas | The Human Protein Atlas
Drugs and Diseases
Open Targets | OMIM
Enzyme Class
2.7.10.2; (BRENDA)
Catalytic Site
Catalytic Site Atlas
Catalytic Activity
ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-[protein]
Localization
Cell membrane,Mitochondrion inner membrane,Nucleus,Cytoplasm,Cytoskeleton,Cytoplasm,Perinuclear region,Cell junction,Focal adhesion;
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 ki...nases, 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). (+)

Gene Ontology

ID Name
GO:0032148 activation of protein kinase B activity
GO:0034332 adherens junction organization
GO:0086098 angiotensin-activated signaling pathway involved in heart process
GO:0007411 axon guidance
GO:0045453 bone resorption
GO:0060444 branching involved in mammary gland duct morphogenesis
GO:0007155 cell adhesion
GO:0007049 cell cycle
GO:0030154 cell differentiation
GO:0008283 cell population proliferation
GO:0098609 cell-cell adhesion
GO:0071398 cellular response to fatty acid
GO:0071498 cellular response to fluid shear stress
GO:0070301 cellular response to hydrogen peroxide
GO:0071456 cellular response to hypoxia
GO:0032869 cellular response to insulin stimulus
GO:0071222 cellular response to lipopolysaccharide
GO:0071375 cellular response to peptide hormone stimulus
GO:0036120 cellular response to platelet-derived growth factor stimulus
GO:0071393 cellular response to progesterone stimulus
GO:0035635 entry of bacterium into host cell
GO:0048013 ephrin receptor signaling pathway
GO:0007173 epidermal growth factor receptor signaling pathway
GO:0038128 ERBB2 signaling pathway
GO:0038096 Fc-gamma receptor signaling pathway involved in phagocytosis
GO:0048041 focal adhesion assembly
GO:0030900 forebrain development
GO:0007186 G protein-coupled receptor signaling pathway
GO:0045087 innate immune response
GO:0007229 integrin-mediated signaling pathway
GO:0070102 interleukin-6-mediated signaling pathway
GO:0060576 intestinal epithelial cell development
GO:0035556 intracellular signal transduction
GO:0050900 leukocyte migration
GO:0016236 macroautophagy
GO:2000811 negative regulation of anoikis
GO:0043066 negative regulation of apoptotic process
GO:0043154 negative regulation of cysteine-type endopeptidase activity involved in apoptotic process
GO:2001237 negative regulation of extrinsic apoptotic signaling pathway
GO:0051895 negative regulation of focal adhesion assembly
GO:2001243 negative regulation of intrinsic apoptotic signaling pathway
GO:0051902 negative regulation of mitochondrial depolarization
GO:0031333 negative regulation of protein-containing complex assembly
GO:0051974 negative regulation of telomerase activity
GO:0032211 negative regulation of telomere maintenance via telomerase
GO:0045892 negative regulation of transcription, DNA-templated
GO:0048011 neurotrophin TRK receptor signaling pathway
GO:0042476 odontogenesis
GO:0048477 oogenesis
GO:0036035 osteoclast development
GO:0018105 peptidyl-serine phosphorylation
GO:0038083 peptidyl-tyrosine autophosphorylation
GO:0018108 peptidyl-tyrosine phosphorylation
GO:0030168 platelet activation
GO:0043065 positive regulation of apoptotic process
GO:0090263 positive regulation of canonical Wnt signaling pathway
GO:0045737 positive regulation of cyclin-dependent protein serine/threonine kinase activity
GO:0035306 positive regulation of dephosphorylation
GO:2000573 positive regulation of DNA biosynthetic process
GO:0010634 positive regulation of epithelial cell migration
GO:0070374 positive regulation of ERK1 and ERK2 cascade
GO:0010907 positive regulation of glucose metabolic process
GO:0046628 positive regulation of insulin receptor signaling pathway
GO:0033625 positive regulation of integrin activation
GO:2000394 positive regulation of lamellipodium morphogenesis
GO:0043406 positive regulation of MAP kinase activity
GO:1903997 positive regulation of non-membrane spanning protein tyrosine kinase activity
GO:0045747 positive regulation of Notch signaling pathway
GO:2000386 positive regulation of ovarian follicle development
GO:0050731 positive regulation of peptidyl-tyrosine phosphorylation
GO:0043552 positive regulation of phosphatidylinositol 3-kinase activity
GO:0014068 positive regulation of phosphatidylinositol 3-kinase signaling
GO:2000588 positive regulation of platelet-derived growth factor receptor-beta signaling pathway
GO:0071803 positive regulation of podosome assembly
GO:0031954 positive regulation of protein autophosphorylation
GO:0051897 positive regulation of protein kinase B signaling
GO:1900182 positive regulation of protein localization to nucleus
GO:0010954 positive regulation of protein processing
GO:0071902 positive regulation of protein serine/threonine kinase activity
GO:0051222 positive regulation of protein transport
GO:0051057 positive regulation of small GTPase mediated signal transduction
GO:0014911 positive regulation of smooth muscle cell migration
GO:0045893 positive regulation of transcription, DNA-templated
GO:0001545 primary ovarian follicle growth
GO:0050847 progesterone receptor signaling pathway
GO:0046777 protein autophosphorylation
GO:0031648 protein destabilization
GO:0045124 regulation of bone resorption
GO:2001286 regulation of caveolin-mediated endocytosis
GO:0042127 regulation of cell population proliferation
GO:0060491 regulation of cell projection assembly
GO:0022407 regulation of cell-cell adhesion
GO:2000641 regulation of early endosome to late endosome transport
GO:0010632 regulation of epithelial cell migration
GO:0033146 regulation of intracellular estrogen receptor signaling pathway
GO:0098962 regulation of postsynaptic neurotransmitter receptor activity
GO:0043393 regulation of protein binding
GO:0043114 regulation of vascular permeability
GO:0010447 response to acidic pH
GO:0042493 response to drug
GO:0051602 response to electrical stimulus
GO:0070555 response to interleukin-1
GO:0009612 response to mechanical stimulus
GO:0051385 response to mineralocorticoid
GO:0031667 response to nutrient levels
GO:0009615 response to virus
GO:0007172 signal complex assembly
GO:0007165 signal transduction
GO:0002223 stimulatory C-type lectin receptor signaling pathway
GO:0043149 stress fiber assembly
GO:0034446 substrate adhesion-dependent cell spreading
GO:0031295 T cell costimulation
GO:0045056 transcytosis
GO:0007179 transforming growth factor beta receptor signaling pathway
GO:0007169 transmembrane receptor protein tyrosine kinase signaling pathway
GO:0060065 uterus development
GO:0048010 vascular endothelial growth factor receptor signaling pathway
GO:0016032 viral process
ID Name
GO:0005884 actin filament
GO:0005901 caveola
GO:0030054 cell junction
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0070062 extracellular exosome
GO:0031234 extrinsic component of cytoplasmic side of plasma membrane
GO:0005925 focal adhesion
GO:0098978 glutamatergic synapse
GO:0005770 late endosome
GO:0005764 lysosome
GO:0045121 membrane raft
GO:0005743 mitochondrial inner membrane
GO:0005739 mitochondrion
GO:0043005 neuron projection
GO:0005634 nucleus
GO:0048471 perinuclear region of cytoplasm
GO:0005886 plasma membrane
GO:0002102 podosome
GO:0014069 postsynaptic density
GO:0099091 postsynaptic specialization, intracellular component
GO:0032587 ruffle membrane
ID Name
GO:0005524 ATP binding
GO:0051117 ATPase binding
GO:0070700 BMP receptor binding
GO:0045296 cadherin binding
GO:0071253 connexin binding
GO:0019899 enzyme binding
GO:0046875 ephrin receptor binding
GO:0030331 estrogen receptor binding
GO:0070851 growth factor receptor binding
GO:0020037 heme binding
GO:0005158 insulin receptor binding
GO:0005178 integrin binding
GO:0044325 ion channel binding
GO:0016301 kinase activity
GO:0019900 kinase binding
GO:0004715 non-membrane spanning protein tyrosine kinase activity
GO:0051219 phosphoprotein binding
GO:0008022 protein C-terminus binding
GO:0004672 protein kinase activity
GO:0005080 protein kinase C binding
GO:0004713 protein tyrosine kinase activity
GO:0097110 scaffold protein binding
GO:0042169 SH2 domain binding
GO:0005102 signaling receptor binding
GO:0031625 ubiquitin protein ligase binding


 
Gene Ontology (maximum 10 per group shown, click on any section to view sub-classification)