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Names & Taxonomy

Uniprot ID:: P12931
Entry Name:: SRC_HUMAN
Status:: reviewed
Protein Names:: Proto-oncogene tyrosine-protein kinase Src (EC 2.7.10.2) (Proto-oncogene c-Src) (pp60c-src) (p60-Src)
Gene Names:: SRC SRC1
Gene Names Primary:: SRC
Organism:: Homo sapiens (Human)

Structure

Length:: 536
Sequence:: MGSNKSKPKDASQRRRSLEPAENVHGAGGGAFPASQTPSKPASADGHRGPSAAFAPAAAEPKLFGGFNSSDTVTSPQRAGPLAGGVTTFVALYDYESRTETDLSFKKGERLQIVNNTEGDWWLAHSLSTGQTGYIPSNYVAPSDSIQAEEWYFGKITRRESERLLLNAENPRGTFLVRESETTKGAYCLSVSDFDNAKGLNVKHYKIRKLDSGGFYITSRTQFNSLQQLVAYYSKHADGLCHRLTTVCPTSKPQTQGLAKDAWEIPRESLRLEVKLGQGCFGEVWMGTWNGTTRVAIKTLKPGTMSPEAFLQEAQVMKKLRHEKLVQLYAVVSEEPIYIVTEYMSKGSLLDFLKGETGKYLRLPQLVDMAAQIASGMAYVERMNYVHRDLRAANILVGENLVCKVADFGLARLIEDNEYTARQGAKFPIKWTAPEAALYGRFTIKSDVWSFGILLTELTTKGRVPYPGMVNREVLDQVERGYRMPCPPECPESLHDLMCQCWRKEPEERPTFEYLQAFLEDYFTSTEPQYQPGENL
Proteomes:: UP000005640

Subcellular location

Subcellular Location:: Cell membrane. Mitochondrion inner membrane. Nucleus. Cytoplasm, cytoskeleton. Note=Localizes to focal adhesion sites following integrin engagement. Localization to focal adhesion sites requires myristoylation and the SH3 domain.

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). 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 ADRBK1, 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).
Catalytic Activity:: ATP + a -L-tyrosine = ADP + a -L-tyrosine phosphate.
Enzyme Regulation:: ENZYME 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.
Active Site:: ACT_SITE 389 389 Proton acceptor.
Cross Reference Drug Bank:: DB06616 DB01254 DB09079 DB08901
Gene Ontology Go:: actin filament
caveola
cytoplasm
cytosol
extracellular exosome
extrinsic component of cytoplasmic side of plasma membrane
late endosome
lysosome
mitochondrial inner membrane
mitochondrion
neuron projection
nucleus
perinuclear region of cytoplasm
plasma membrane
postsynaptic density
ruffle membrane
ATP binding
enzyme binding
ephrin receptor binding
growth factor receptor binding
heme binding
hormone receptor binding
integrin binding
ion channel binding
kinase activity
kinase binding
non-membrane spanning protein tyrosine kinase activity
phosphoprotein binding
protein kinase activity
protein tyrosine kinase activity
receptor binding
scaffold protein binding
SH2 domain binding
SH3/SH2 adaptor activity
activation of protein kinase B activity
adherens junction organization
angiotensin-activated signaling pathway involved in heart process
axon guidance
blood coagulation
bone resorption
branching involved in mammary gland duct morphogenesis
cell adhesion
cell cycle
cell proliferation
cellular response to fatty acid
cellular response to fluid shear stress
cellular response to hypoxia
cellular response to insulin stimulus
cellular response to lipopolysaccharide
cellular response to peptide hormone stimulus
cellular response to platelet-derived growth factor stimulus
cellular response to progesterone stimulus
cellular response to reactive oxygen species
ephrin receptor signaling pathway
epidermal growth factor receptor signaling pathway
Fc-gamma receptor signaling pathway involved in phagocytosis
fibroblast growth factor receptor signaling pathway
forebrain development
innate immune response
integrin-mediated signaling pathway
intracellular signal transduction
leukocyte migration
membrane organization
negative regulation of anoikis
negative regulation of apoptotic process
negative regulation of cysteine-type endopeptidase activity involved in apoptotic process
negative regulation of extrinsic apoptotic signaling pathway
negative regulation of focal adhesion assembly
negative regulation of intrinsic apoptotic signaling pathway
negative regulation of mitochondrial depolarization
negative regulation of protein homooligomerization
negative regulation of telomerase activity
negative regulation of telomere maintenance via telomerase
negative regulation of transcription, DNA-templated
neurotrophin TRK receptor signaling pathway
oogenesis
osteoclast development
peptidyl-serine phosphorylation
peptidyl-tyrosine autophosphorylation
peptidyl-tyrosine phosphorylation
platelet activation
positive regulation of apoptotic process
positive regulation of canonical Wnt signaling pathway
positive regulation of cyclin-dependent protein serine/threonine kinase activity
positive regulation of cytokine secretion
positive regulation of DNA biosynthetic process
positive regulation of epithelial cell migration
positive regulation of ERK1 and ERK2 cascade
positive regulation of glucose metabolic process
positive regulation of insulin receptor signaling pathway
positive regulation of integrin activation
positive regulation of lamellipodium morphogenesis
positive regulation of MAP kinase activity
positive regulation of peptidyl-tyrosine phosphorylation
positive regulation of phosphatidylinositol 3-kinase activity
positive regulation of platelet-derived growth factor receptor signaling pathway
positive regulation of podosome assembly
positive regulation of protein autophosphorylation
positive regulation of protein kinase B signaling
positive regulation of protein serine/threonine kinase activity
positive regulation of smooth muscle cell migration
positive regulation of transcription, DNA-templated
progesterone receptor signaling pathway
protein autophosphorylation
protein destabilization
Ras protein signal transduction
regulation of bone resorption
regulation of caveolin-mediated endocytosis
regulation of cell cycle
regulation of cell projection assembly
regulation of cell proliferation
regulation of cell-cell adhesion
regulation of early endosome to late endosome transport
regulation of epithelial cell migration
regulation of intracellular estrogen receptor signaling pathway
regulation of podosome assembly
regulation of protein binding
regulation of vascular permeability
response to acidic pH
response to drug
response to electrical stimulus
response to hydrogen peroxide
response to interleukin-1
response to mechanical stimulus
response to mineralocorticoid
response to nutrient levels
response to virus
signal complex assembly
signal transduction
single organismal cell-cell adhesion
small GTPase mediated signal transduction
stimulatory C-type lectin receptor signaling pathway
stress fiber assembly
substrate adhesion-dependent cell spreading
T cell costimulation
transcytosis
transforming growth factor beta receptor signaling pathway
uterus development
vascular endothelial growth factor receptor signaling pathway
viral process
Gene Ontology Biological Process:: activation of protein kinase B activity
adherens junction organization
angiotensin-activated signaling pathway involved in heart process
axon guidance
blood coagulation
bone resorption
branching involved in mammary gland duct morphogenesis
cell adhesion
cell cycle
cell proliferation
cellular response to fatty acid
cellular response to fluid shear stress
cellular response to hypoxia
cellular response to insulin stimulus
cellular response to lipopolysaccharide
cellular response to peptide hormone stimulus
cellular response to platelet-derived growth factor stimulus
cellular response to progesterone stimulus
cellular response to reactive oxygen species
ephrin receptor signaling pathway
epidermal growth factor receptor signaling pathway
Fc-gamma receptor signaling pathway involved in phagocytosis
fibroblast growth factor receptor signaling pathway
forebrain development
innate immune response
integrin-mediated signaling pathway
intracellular signal transduction
leukocyte migration
membrane organization
negative regulation of anoikis
negative regulation of apoptotic process
negative regulation of cysteine-type endopeptidase activity involved in apoptotic process
negative regulation of extrinsic apoptotic signaling pathway
negative regulation of focal adhesion assembly
negative regulation of intrinsic apoptotic signaling pathway
negative regulation of mitochondrial depolarization
negative regulation of protein homooligomerization
negative regulation of telomerase activity
negative regulation of telomere maintenance via telomerase
negative regulation of transcription, DNA-templated
neurotrophin TRK receptor signaling pathway
oogenesis
osteoclast development
peptidyl-serine phosphorylation
peptidyl-tyrosine autophosphorylation
peptidyl-tyrosine phosphorylation
platelet activation
positive regulation of apoptotic process
positive regulation of canonical Wnt signaling pathway
positive regulation of cyclin-dependent protein serine/threonine kinase activity
positive regulation of cytokine secretion
positive regulation of DNA biosynthetic process
positive regulation of epithelial cell migration
positive regulation of ERK1 and ERK2 cascade
positive regulation of glucose metabolic process
positive regulation of insulin receptor signaling pathway
positive regulation of integrin activation
positive regulation of lamellipodium morphogenesis
positive regulation of MAP kinase activity
positive regulation of peptidyl-tyrosine phosphorylation
positive regulation of phosphatidylinositol 3-kinase activity
positive regulation of platelet-derived growth factor receptor signaling pathway
positive regulation of podosome assembly
positive regulation of protein autophosphorylation
positive regulation of protein kinase B signaling
positive regulation of protein serine/threonine kinase activity
positive regulation of smooth muscle cell migration
positive regulation of transcription, DNA-templated
progesterone receptor signaling pathway
protein autophosphorylation
protein destabilization
Ras protein signal transduction
regulation of bone resorption
regulation of caveolin-mediated endocytosis
regulation of cell-cell adhesion
regulation of cell cycle
regulation of cell projection assembly
regulation of cell proliferation
regulation of early endosome to late endosome transport
regulation of epithelial cell migration
regulation of intracellular estrogen receptor signaling pathway
regulation of podosome assembly
regulation of protein binding
regulation of vascular permeability
response to acidic pH
response to drug
response to electrical stimulus
response to hydrogen peroxide
response to interleukin-1
response to mechanical stimulus
response to mineralocorticoid
response to nutrient levels
response to virus
signal complex assembly
signal transduction
single organismal cell-cell adhesion
small GTPase mediated signal transduction
stimulatory C-type lectin receptor signaling pathway
stress fiber assembly
substrate adhesion-dependent cell spreading
T cell costimulation
transcytosis
transforming growth factor beta receptor signaling pathway
uterus development
vascular endothelial growth factor receptor signaling pathway
viral process
Gene Ontology Molecular Function:: ATP binding
enzyme binding
ephrin receptor binding
growth factor receptor binding
heme binding
hormone receptor binding
integrin binding
ion channel binding
kinase activity
kinase binding
non-membrane spanning protein tyrosine kinase activity
phosphoprotein binding
protein kinase activity
protein tyrosine kinase activity
receptor binding
scaffold protein binding
SH2 domain binding
SH3/SH2 adaptor activity
Gene Ontology Cellular Component:: actin filament
caveola
cytoplasm
cytosol
extracellular exosome
extrinsic component of cytoplasmic side of plasma membrane
late endosome
lysosome
mitochondrial inner membrane
mitochondrion
neuron projection
nucleus
perinuclear region of cytoplasm
plasma membrane
postsynaptic density
ruffle membrane
Keywords:: 3D-structure
ATP-binding
Alternative splicing
Cell adhesion
Cell cycle
Cell membrane
Complete proteome
Cytoplasm
Cytoskeleton
Host-virus interaction
Immunity
Kinase
Lipoprotein
Membrane
Mitochondrion
Mitochondrion inner membrane
Myristate
Nucleotide-binding
Nucleus
Phosphoprotein
Polymorphism
Proto-oncogene
Reference proteome
SH2 domain
SH3 domain
Transferase
Tyrosine-protein kinase
Ubl conjugation
Interacts With:: P00519; P42684; P12814; Q13444; P07550; P10275; Q8R5G7; Q9ULH1; P56945; P22681; P12830; P52800; P00533; P04626; P21860; P03372; P03372-4; P14921-1; P25445; Q8NFZ0; Q13480; P61978; P97288; Q9Y6K9; P35968; Q07666; P10721; Q8TBB1; P07948; Q9H204; P08581; P55196; Q13177; P16284; P27986; Q92569; Q05397; P34152; Q14289; P18031; Q16825; P18433; P18052; Q62884; Q13905; Q01973; P27635; P35326; Q9C0H9; Q68CZ2

Names & Taxonomy

Structure

Subcellular location

Function

Publication