LipidDB ID

LipidDB-9606-00542

Entry Name

UniProt Accession

P12931; E1P5V4; Q76P87; Q86VB9; Q9H5A8;

Theoretical PI

7.1

Molecular Weight

59834.76

Genbank Protein ID

CAC10573.1; CAC34523.1; EAW76065.1; EAW76064.1; EAW76066.1; EAW76067.1; AAH11566.1; AAH51270.2; AAA60584.1; AAA60584.1; AAA60584.1; AAA60584.1; AAA60584.1; AAA60584.1; AAA60584.1; AAA60584.1; AAA60584.1; AAA60584.1; AAA60584.1; CAA26485.1; CAA26485.1; CAA26485.1; CAA26485.1; CAA26485.1; CAA26485.1; CAA26485.1;

Genbank Nucleotide ID

AL133293; AL133293; CH471077; CH471077; CH471077; CH471077; BC011566; BC051270; K03218; M16237; M16243; M16244; M16245; K03212; K03213; K03214; K03215; K03216; K03217; X02647; X03995; X03996; X03997; X03998; X03999; X04000;

Protein Name

Proto-oncogene tyrosine-protein kinase Src

Protein Synonyms/Alias

2.7.10.2; Proto-oncogene c-Src; pp60c-src; p60-Src;

Gene Name

SRC

Gene Synonyms/Alias

SRC1;

Created Date

01-OCT-1989

Organism

Homo sapiens (Human)

NCBI Taxa ID

9606

Reference

[1] Kaplan KB, Bibbins KB, Swedlow JR, Arnaud M, Morgan DO, Varmus HE. Associationof the amino-terminal half of c-Src with focal adhesions alters their properties and is regulated by phosphorylation of tyrosine 527. EMBO J. 1994 Oct17;13(20):4745-56.[PMID:7525268]

Functional Description

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.

Sequence Annotation

Domain: 84 145 SH3.
Domain: 151 248 SH2.
Domain: 270 523 Protein kinase.
Nucleotide-binding: 276 284 ATP.
Active site: 389 389 Proton acceptor.
Binding site: 298 298 ATP.
Modified residue: 17 17 Phosphoserine.
Modified residue: 35 35 Phosphoserine.
Modified residue: 69 69 Phosphoserine.
Modified residue: 74 74 Phosphothreonine.
Modified residue: 75 75 Phosphoserine; by CDK5.
Modified residue: 187 187 Phosphotyrosine.
Modified residue: 419 419 Phosphotyrosine; by autocatalysis;alternate.
Modified residue: 419 419 Phosphotyrosine; by FAK2; alternate.
Modified residue: 439 439 Phosphotyrosine.
Modified residue: 511 511 Phosphothreonine.
Modified residue: 522 522 Phosphotyrosine.
Modified residue: 530 530 Phosphotyrosine; by CSK.

Protein Length

536 AA.

Protein Sequence
(Canonical)

FASTA
(Canonical)

Gene Ontology

GO:0005901; C:caveola; IDA:BHF-UCL
GO:0005737; C:cytoplasm; IDA:UniProtKB
GO:0005856; C:cytoskeleton; IEA:UniProtKB-KW
GO:0005829; C:cytosol; IDA:UniProtKB
GO:0070062; C:extracellular vesicular exosome; IDA:UniProt
GO:0005770; C:late endosome; IDA:UniProtKB
GO:0005764; C:lysosome; IDA:UniProtKB
GO:0005743; C:mitochondrial inner membrane; IDA:UniProtKB
GO:0005739; C:mitochondrion; IDA:UniProtKB
GO:0005634; C:nucleus; IEA:UniProtKB-KW
GO:0005886; C:plasma membrane; IDA:UniProtKB
GO:0005524; F:ATP binding; IEA:UniProtKB-KW
GO:0019899; F:enzyme binding; IPI:UniProtKB
GO:0046875; F:ephrin receptor binding; IPI:UniProtKB
GO:0070851; F:growth factor receptor binding; IPI:UniProtKB
GO:0020037; F:heme binding; IDA:UniProtKB
GO:0005178; F:integrin binding; TAS:BHF-UCL
GO:0044325; F:ion channel binding; IPI:BHF-UCL
GO:0016301; F:kinase activity; TAS:Reactome
GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; TAS:BHF-UCL
GO:0051219; F:phosphoprotein binding; IPI:UniProtKB
GO:0004672; F:protein kinase activity; IDA:UniProtKB
GO:0004713; F:protein tyrosine kinase activity; IDA:UniProtKB
GO:0005102; F:receptor binding; IPI:UniProtKB
GO:0042169; F:SH2 domain binding; IPI:UniProtKB
GO:0005070; F:SH3/SH2 adaptor activity; TAS:ProtInc
GO:0007411; P:axon guidance; TAS:Reactome
GO:0007596; P:blood coagulation; TAS:Reactome
GO:0045453; P:bone resorption; ISS:UniProtKB
GO:0060444; P:branching involved in mammary gland duct morphogenesis; IEA:Ensembl
GO:0007155; P:cell adhesion; IEA:UniProtKB-KW
GO:0007049; P:cell cycle; IEA:UniProtKB-KW
GO:0071393; P:cellular response to progesterone stimulus; ISS:BHF-UCL
GO:0007173; P:epidermal growth factor receptor signaling pathway; TAS:Reactome
GO:0038096; P:Fc-gamma receptor signaling pathway involved in phagocytosis; TAS:Reactome
GO:0008543; P:fibroblast growth factor receptor signaling pathway; TAS:Reactome
GO:0030900; P:forebrain development; IEA:Ensembl
GO:0045087; P:innate immune response; TAS:Reactome
GO:0007229; P:integrin-mediated signaling pathway; IMP:UniProtKB
GO:0035556; P:intracellular signal transduction; IDA:BHF-UCL
GO:0050900; P:leukocyte migration; TAS:Reactome
GO:0061024; P:membrane organization; TAS:Reactome
GO:2000811; P:negative regulation of anoikis; IMP:UniProtKB
GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB
GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; IMP:UniProtKB
GO:2001237; P:negative regulation of extrinsic apoptotic signaling pathway; IMP:UniProtKB
GO:0051895; P:negative regulation of focal adhesion assembly; ISS:BHF-UCL
GO:2001243; P:negative regulation of intrinsic apoptotic signaling pathway; IMP:UniProtKB
GO:0051902; P:negative regulation of mitochondrial depolarization; IMP:UniProtKB
GO:0032463; P:negative regulation of protein homooligomerization; IMP:UniProtKB
GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome
GO:0048477; P:oogenesis; IEA:Ensembl
GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:MGI
GO:0030168; P:platelet activation; TAS:Reactome
GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IEA:Ensembl
GO:0033625; P:positive regulation of integrin activation; TAS:BHF-UCL
GO:0071803; P:positive regulation of podosome assembly; IEA:Ensembl
GO:0051897; P:positive regulation of protein kinase B signaling; IMP:UniProtKB
GO:0050847; P:progesterone receptor signaling pathway; ISS:BHF-UCL
GO:0046777; P:protein autophosphorylation; IDA:UniProtKB
GO:0007265; P:Ras protein signal transduction; TAS:Reactome
GO:0045124; P:regulation of bone resorption; TAS:BHF-UCL
GO:2001286; P:regulation of caveolin-mediated endocytosis; IMP:UniProtKB
GO:0022407; P:regulation of cell-cell adhesion; IMP:UniProtKB
GO:2000641; P:regulation of early endosome to late endosome transport; IMP:UniProtKB
GO:0010632; P:regulation of epithelial cell migration; IMP:UniProtKB
GO:0033146; P:regulation of intracellular estrogen receptor signaling pathway; IEA:Ensembl
GO:0043393; P:regulation of protein binding; IEA:Ensembl
GO:0043114; P:regulation of vascular permeability; TAS:BHF-UCL
GO:0070555; P:response to interleukin-1; IMP:BHF-UCL
GO:0007172; P:signal complex assembly; TAS:ProtInc
GO:0007165; P:signal transduction; TAS:ProtInc
GO:0043149; P:stress fiber assembly; IMP:UniProtKB
GO:0031295; P:T cell costimulation; TAS:Reactome
GO:0007179; P:transforming growth factor beta receptor signaling pathway; IMP:UniProtKB
GO:0060065; P:uterus development; IEA:Ensembl
GO:0016032; P:viral process; IEA:UniProtKB-KW

Interpro

InterPro; IPR011009; Kinase-like_dom
InterPro; IPR000719; Prot_kinase_dom
InterPro; IPR017441; Protein_kinase_ATP_BS
InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom
InterPro; IPR000980; SH2
InterPro; IPR001452; SH3_domain
InterPro; IPR008266; Tyr_kinase_AS
InterPro; IPR020635; Tyr_kinase_cat_dom

Pfam

Pfam; PF07714; Pkinase_Tyr;
Pfam; PF00017; SH2;
Pfam; PF00018; SH3_1;

SMART

SMART; SM00252; SH2;
SMART; SM00326; SH3;
SMART; SM00219; TyrKc;

PROSITE

PROSITE; PS00107; PROTEIN_KINASE_ATP;
PROSITE; PS50011; PROTEIN_KINASE_DOM;
PROSITE; PS00109; PROTEIN_KINASE_TYR;
PROSITE; PS50001; SH2;
PROSITE; PS50002; SH3;

PRINTS

PRINTS; PR00401; SH2DOMAIN;
PRINTS; PR00452; SH3DOMAIN;
PRINTS; PR00109; TYRKINASE;