Proto-oncogene tyrosine-protein kinase Src

NameProto-oncogene tyrosine-protein kinase Src
Synonyms
  • 2.7.10.2
  • p60-Src
  • pp60c-src
  • Proto-oncogene c-Src
  • SRC1
Gene NameSRC
OrganismHuman
Amino acid sequence
>lcl|BSEQ0037090|Proto-oncogene tyrosine-protein kinase Src
MGSNKSKPKDASQRRRSLEPAENVHGAGGGAFPASQTPSKPASADGHRGPSAAFAPAAAE
PKLFGGFNSSDTVTSPQRAGPLAGGVTTFVALYDYESRTETDLSFKKGERLQIVNNTEGD
WWLAHSLSTGQTGYIPSNYVAPSDSIQAEEWYFGKITRRESERLLLNAENPRGTFLVRES
ETTKGAYCLSVSDFDNAKGLNVKHYKIRKLDSGGFYITSRTQFNSLQQLVAYYSKHADGL
CHRLTTVCPTSKPQTQGLAKDAWEIPRESLRLEVKLGQGCFGEVWMGTWNGTTRVAIKTL
KPGTMSPEAFLQEAQVMKKLRHEKLVQLYAVVSEEPIYIVTEYMSKGSLLDFLKGETGKY
LRLPQLVDMAAQIASGMAYVERMNYVHRDLRAANILVGENLVCKVADFGLARLIEDNEYT
ARQGAKFPIKWTAPEAALYGRFTIKSDVWSFGILLTELTTKGRVPYPGMVNREVLDQVER
GYRMPCPPECPESLHDLMCQCWRKEPEERPTFEYLQAFLEDYFTSTEPQYQPGENL
Number of residues536
Molecular Weight59834.295
Theoretical pI7.47
GO Classification
Functions
  • SH3/SH2 adaptor activity
  • kinase binding
  • ATP binding
  • enzyme binding
  • phosphoprotein binding
  • kinase activity
  • integrin binding
  • protein kinase activity
  • ephrin receptor binding
  • growth factor receptor binding
  • protein tyrosine kinase activity
  • receptor binding
  • hormone receptor binding
  • non-membrane spanning protein tyrosine kinase activity
  • ion channel binding
  • heme binding
  • scaffold protein binding
  • SH2 domain binding
Processes
  • regulation of cell proliferation
  • response to interleukin-1
  • platelet activation
  • cellular response to platelet-derived growth factor stimulus
  • signal transduction
  • leukocyte migration
  • negative regulation of focal adhesion assembly
  • negative regulation of telomerase activity
  • positive regulation of ERK1 and ERK2 cascade
  • protein destabilization
  • positive regulation of canonical Wnt signaling pathway
  • progesterone receptor signaling pathway
  • regulation of epithelial cell migration
  • protein autophosphorylation
  • fibroblast growth factor receptor signaling pathway
  • substrate adhesion-dependent cell spreading
  • positive regulation of lamellipodium morphogenesis
  • transforming growth factor beta receptor signaling pathway
  • negative regulation of apoptotic process
  • negative regulation of mitochondrial depolarization
  • negative regulation of extrinsic apoptotic signaling pathway
  • branching involved in mammary gland duct morphogenesis
  • cell adhesion
  • negative regulation of cysteine-type endopeptidase activity involved in apoptotic process
  • negative regulation of telomere maintenance via telomerase
  • osteoclast development
  • blood coagulation
  • neurotrophin TRK receptor signaling pathway
  • cellular response to peptide hormone stimulus
  • angiotensin-activated signaling pathway involved in heart process
  • signal complex assembly
  • negative regulation of anoikis
  • positive regulation of podosome assembly
  • Ras protein signal transduction
  • regulation of vascular permeability
  • cellular response to progesterone stimulus
  • T cell costimulation
  • regulation of podosome assembly
  • stimulatory C-type lectin receptor signaling pathway
  • positive regulation of protein serine/threonine kinase activity
  • positive regulation of integrin activation
  • axon guidance
  • regulation of intracellular estrogen receptor signaling pathway
  • vascular endothelial growth factor receptor signaling pathway
  • regulation of bone resorption
  • regulation of caveolin-mediated endocytosis
  • cell differentiation
  • forebrain development
  • membrane organization
  • bone resorption
  • regulation of cell projection assembly
  • epidermal growth factor receptor signaling pathway
  • ephrin receptor signaling pathway
  • regulation of protein binding
  • regulation of cell cycle
  • integrin-mediated signaling pathway
  • cellular response to fluid shear stress
  • Fc-gamma receptor signaling pathway involved in phagocytosis
  • negative regulation of intrinsic apoptotic signaling pathway
  • cellular response to reactive oxygen species
  • intracellular signal transduction
  • stress fiber assembly
  • innate immune response
  • uterus development
  • oogenesis
  • small GTPase mediated signal transduction
  • regulation of early endosome to late endosome transport
  • peptidyl-tyrosine autophosphorylation
  • peptidyl-tyrosine phosphorylation
  • viral process
  • negative regulation of protein homooligomerization
  • positive regulation of epithelial cell migration
  • positive regulation of peptidyl-tyrosine phosphorylation
  • positive regulation of protein kinase B signaling
  • regulation of cell-cell adhesion
  • cell cycle
Components
  • mitochondrion
  • actin filament
  • cytosol
  • extracellular exosome
  • extrinsic component of cytoplasmic side of plasma membrane
  • perinuclear region of cytoplasm
  • nucleus
  • mitochondrial inner membrane
  • ruffle membrane
  • late endosome
  • plasma membrane
  • lysosome
  • caveola
  • cytoplasm
General FunctionSh3/sh2 adaptor activity
Specific FunctionNon-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).
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein ID10635153
UniProtKB IDP12931
UniProtKB Entry NameSRC_HUMAN
Cellular LocationCell membrane
Gene sequence
>lcl|BSEQ0021959|Proto-oncogene tyrosine-protein kinase Src (SRC)
ATGGGTAGCAACAAGAGCAAGCCCAAGGATGCCAGCCAGCGGCGCCGCAGCCTGGAGCCC
GCCGAGAACGTGCACGGCGCTGGCGGGGGCGCTTTCCCCGCCTCGCAGACCCCCAGCAAG
CCAGCCTCGGCCGACGGCCACCGCGGCCCCAGCGCGGCCTTCGCCCCCGCGGCCGCCGAG
CCCAAGCTGTTCGGAGGCTTCAACTCCTCGGACACCGTCACCTCCCCGCAGAGGGCGGGC
CCGCTGGCCGGTGGAGTGACCACCTTTGTGGCCCTCTATGACTATGAGTCTAGGACGGAG
ACAGACCTGTCCTTCAAGAAAGGCGAGCGGCTCCAGATTGTCAACAACACAGAGGGAGAC
TGGTGGCTGGCCCACTCGCTCAGCACAGGACAGACAGGCTACATCCCCAGCAACTACGTG
GCGCCCTCCGACTCCATCCAGGCTGAGGAGTGGTATTTTGGCAAGATCACCAGACGGGAG
TCAGAGCGGTTACTGCTCAATGCAGAGAACCCGAGAGGGACCTTCCTCGTGCGAGAAAGT
GAGACCACGAAAGGTGCCTACTGCCTCTCAGTGTCTGACTTCGACAACGCCAAGGGCCTC
AACGTGAAGCACTACAAGATCCGCAAGCTGGACAGCGGCGGCTTCTACATCACCTCCCGC
ACCCAGTTCAACAGCCTGCAGCAGCTGGTGGCCTACTACTCCAAACACGCCGATGGCCTG
TGCCACCGCCTCACCACCGTGTGCCCCACGTCCAAGCCGCAGACTCAGGGCCTGGCCAAG
GATGCCTGGGAGATCCCTCGGGAGTCGCTGCGGCTGGAGGTCAAGCTGGGCCAGGGCTGC
TTTGGCGAGGTGTGGATGGGGACCTGGAACGGTACCACCAGGGTGGCCATCAAAACCCTG
AAGCCTGGCACGATGTCTCCAGAGGCCTTCCTGCAGGAGGCCCAGGTCATGAAGAAGCTG
AGGCATGAGAAGCTGGTGCAGTTGTATGCTGTGGTTTCAGAGGAGCCCATTTACATCGTC
ACGGAGTACATGAGCAAGGGGAGTTTGCTGGACTTTCTCAAGGGGGAGACAGGCAAGTAC
CTGCGGCTGCCTCAGCTGGTGGACATGGCTGCTCAGATCGCCTCAGGCATGGCGTACGTG
GAGCGGATGAACTACGTCCACCGGGACCTTCGTGCAGCCAACATCCTGGTGGGAGAGAAC
CTGGTGTGCAAAGTGGCCGACTTTGGGCTGGCTCGGCTCATTGAAGACAATGAGTACACG
GCGCGGCAAGGTGCCAAATTCCCCATCAAGTGGACGGCTCCAGAAGCTGCCCTCTATGGC
CGCTTCACCATCAAGTCGGACGTGTGGTCCTTCGGGATCCTGCTGACTGAGCTCACCACA
AAGGGACGGGTGCCCTACCCTGGGATGGTGAACCGCGAGGTGCTGGACCAGGTGGAGCGG
GGCTACCGGATGCCCTGCCCGCCGGAGTGTCCCGAGTCCCTGCACGACCTCATGTGCCAG
TGCTGGCGGAAGGAGCCTGAGGAGCGGCCCACCTTCGAGTACCTGCAGGCCTTCCTGGAG
GACTACTTCACGTCCACCGAGCCCCAGTACCAGCCCGGGGAGAACCTCTAG
GenBank Gene IDAL133293
GeneCard IDNot Available
GenAtlas IDSRC
HGNC IDHGNC:11283
Chromosome Location20
Locus20q12-q13
References
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