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UniProtKB - P12931 (SRC_HUMAN)

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Protein

Proto-oncogene tyrosine-protein kinase Src

Gene

SRC

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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).By similarity16 Publications

Catalytic activityi

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotation

Enzyme regulationi

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.5 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei298ATP1
Active sitei389Proton acceptor1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi276 – 284ATP9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • cadherin binding Source: BHF-UCL
  • connexin binding Source: Ensembl
  • enzyme binding Source: UniProtKB
  • ephrin receptor binding Source: UniProtKB
  • estrogen receptor binding Source: Ensembl
  • growth factor receptor binding Source: UniProtKB
  • heme binding Source: UniProtKB
  • hormone receptor binding Source: GO_Central
  • insulin receptor binding Source: Ensembl
  • integrin binding Source: BHF-UCL
  • ion channel binding Source: BHF-UCL
  • kinase activity Source: Reactome
  • kinase binding Source: UniProtKB
  • non-membrane spanning protein tyrosine kinase activity Source: BHF-UCL
  • phosphoprotein binding Source: UniProtKB
  • protein C-terminus binding Source: CAFA
  • protein kinase activity Source: UniProtKB
  • protein kinase C binding Source: Ensembl
  • protein tyrosine kinase activity Source: UniProtKB
  • receptor binding Source: UniProtKB
  • scaffold protein binding Source: BHF-UCL
  • SH2 domain binding Source: UniProtKB
  • SH3/SH2 adaptor activity Source: ProtInc
  • ubiquitin protein ligase binding Source: Ensembl
Complete GO annotation...

GO - Biological processi

Complete GO annotation...

Keywordsi

Molecular functionKinase, Transferase, Tyrosine-protein kinase
Biological processCell adhesion, Cell cycle, Host-virus interaction, Immunity
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciMetaCyc:HS02256-MONOMER.
BRENDAi2.7.10.2. 2681.
ReactomeiR-HSA-1227986. Signaling by ERBB2.
R-HSA-1295596. Spry regulation of FGF signaling.
R-HSA-1433557. Signaling by SCF-KIT.
R-HSA-1433559. Regulation of KIT signaling.
R-HSA-171007. p38MAPK events.
R-HSA-177929. Signaling by EGFR.
R-HSA-180292. GAB1 signalosome.
R-HSA-186763. Downstream signal transduction.
R-HSA-191647. c-src mediated regulation of Cx43 function and closure of gap junctions.
R-HSA-2029481. FCGR activation.
R-HSA-210990. PECAM1 interactions.
R-HSA-2682334. EPH-Ephrin signaling.
R-HSA-354192. Integrin alphaIIb beta3 signaling.
R-HSA-354194. GRB2:SOS provides linkage to MAPK signaling for Integrins.
R-HSA-372708. p130Cas linkage to MAPK signaling for integrins.
R-HSA-375165. NCAM signaling for neurite out-growth.
R-HSA-389356. CD28 co-stimulation.
R-HSA-389513. CTLA4 inhibitory signaling.
R-HSA-391160. Signal regulatory protein (SIRP) family interactions.
R-HSA-3928662. EPHB-mediated forward signaling.
R-HSA-3928663. EPHA-mediated growth cone collapse.
R-HSA-3928664. Ephrin signaling.
R-HSA-3928665. EPH-ephrin mediated repulsion of cells.
R-HSA-418592. ADP signalling through P2Y purinoceptor 1.
R-HSA-418885. DCC mediated attractive signaling.
R-HSA-418886. Netrin mediated repulsion signals.
R-HSA-430116. GP1b-IX-V activation signalling.
R-HSA-437239. Recycling pathway of L1.
R-HSA-4420097. VEGFA-VEGFR2 Pathway.
R-HSA-456926. Thrombin signalling through proteinase activated receptors (PARs).
R-HSA-5218921. VEGFR2 mediated cell proliferation.
R-HSA-5607764. CLEC7A (Dectin-1) signaling.
R-HSA-5663220. RHO GTPases Activate Formins.
R-HSA-5673000. RAF activation.
R-HSA-5674135. MAP2K and MAPK activation.
R-HSA-6802946. Signaling by moderate kinase activity BRAF mutants.
R-HSA-6802948. Signaling by high-kinase activity BRAF mutants.
R-HSA-6802949. Signaling by RAS mutants.
R-HSA-6802952. Signaling by BRAF and RAF fusions.
R-HSA-6802955. Paradoxical activation of RAF signaling by kinase inactive BRAF.
R-HSA-6811558. PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
R-HSA-69231. Cyclin D associated events in G1.
R-HSA-8853659. RET signaling.
R-HSA-8874081. MET activates PTK2 signaling.
R-HSA-8876493. InlA-mediated entry of Listeria monocytogenes into host cells.
R-HSA-8934903. Receptor Mediated Mitophagy.
R-HSA-8941858. Regulation of RUNX3 expression and activity.
SignaLinkiP12931.
SIGNORiP12931.

Names & Taxonomyi

Protein namesi
Recommended name:
Proto-oncogene tyrosine-protein kinase Src (EC:2.7.10.2)
Alternative name(s):
Proto-oncogene c-Src
pp60c-src
Short name:
p60-Src
Gene namesi
Name:SRC
Synonyms:SRC1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 20

Organism-specific databases

HGNCiHGNC:11283. SRC.

Subcellular locationi

GO - Cellular componenti

  • actin filament Source: Ensembl
  • caveola Source: BHF-UCL
  • cytoplasm Source: UniProtKB
  • cytosol Source: UniProtKB
  • extracellular exosome Source: UniProtKB
  • extrinsic component of cytoplasmic side of plasma membrane Source: GO_Central
  • late endosome Source: UniProtKB
  • lysosome Source: UniProtKB
  • mitochondrial inner membrane Source: UniProtKB
  • mitochondrion Source: UniProtKB
  • neuron projection Source: Ensembl
  • nucleus Source: UniProtKB-SubCell
  • perinuclear region of cytoplasm Source: Ensembl
  • plasma membrane Source: UniProtKB
  • podosome Source: Ensembl
  • postsynaptic density Source: Ensembl
  • ruffle membrane Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Cytoskeleton, Membrane, Mitochondrion, Mitochondrion inner membrane, Nucleus

Pathology & Biotechi

Involvement in diseasei

SRC kinase activity has been shown to be increased in several tumor tissues and tumor cell lines such as colon carcinoma cells.
Thrombocytopenia 6 (THC6)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:616937
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_076919527E → K in THC6; increased protein tyrosine kinase activity; increased autophosphorylation at Y-419; causes defective megakaryopoiesis associated with increased overall tyrosine phosphorylation in megakaryocytes. 1 PublicationCorresponds to variant dbSNP:rs879255268Ensembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi298K → M: Kinase inactive. Abolishes ubiquitination promoted by CBLC. 1 Publication1

Keywords - Diseasei

Disease mutation, Proto-oncogene

Organism-specific databases

DisGeNETi6714.
MalaCardsiSRC.
MIMi616937. phenotype.
OpenTargetsiENSG00000197122.
PharmGKBiPA36111.

Chemistry databases

ChEMBLiCHEMBL267.
DrugBankiDB08564. (2E)-N-{4-[(3-bromophenyl)amino]quinazolin-6-yl}-4-(dimethylamino)but-2-enamide.
DB06882. 1-[1-(3-aminophenyl)-3-tert-butyl-1H-pyrazol-5-yl]-3-naphthalen-1-ylurea.
DB06883. 1-[1-(3-aminophenyl)-3-tert-butyl-1H-pyrazol-5-yl]-3-phenylurea.
DB08192. 2-(4-CARCOXY-5-ISOPROPYLTHIAZOLYL)BENZOPIPERIDINE.
DB04739. 4-[(4-METHYL-1-PIPERAZINYL)METHYL]-N-[3-[[4-(3-PYRIDINYL)-2-PYRIMIDINYL]AMINO]PHENYL]-BENZAMIDE.
DB07966. [4-({4-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]quinazolin-2-yl}amino)phenyl]acetonitrile.
DB06616. Bosutinib.
DB04272. Citric Acid.
DB01254. Dasatinib.
DB03217. DPI59.
DB03628. ISO24.
DB02175. Malonic acid.
DB08462. N-(4-PHENYLAMINO-QUINAZOLIN-6-YL)-ACRYLAMIDE.
DB07662. N-[4-(3-BROMO-PHENYLAMINO)-QUINAZOLIN-6-YL]-ACRYLAMIDE.
DB01893. N6-Benzyl Adenosine-5'-Diphosphate.
DB09079. Nintedanib.
DB03902. Oxalic Acid.
DB03114. PAS219.
DB03078. PASBN.
DB03298. Phenylphosphate.
DB01962. Phosphonotyrosine.
DB08901. Ponatinib.
DB04751. Purvalanol A.
DB04080. RU78191.
DB01947. RU78262.
DB03828. RU78299.
DB03306. RU78300.
DB02908. RU78783.
DB02762. RU79072.
DB03525. RU79073.
DB01866. RU79256.
DB04495. RU81843.
DB03104. RU82129.
DB03268. RU82197.
DB03591. RU82209.
DB02336. RU83876.
DB01678. RU84687.
DB03712. RU85053.
DB01908. RU85493.
DB02432. RU90395.
DB05184. XL228.
GuidetoPHARMACOLOGYi2206.

Polymorphism and mutation databases

DMDMi125711.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved
ChainiPRO_00000881412 – 536Proto-oncogene tyrosine-protein kinase SrcAdd BLAST535

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi2N-myristoyl glycine1 Publication1
Modified residuei17PhosphoserineCombined sources1
Modified residuei35Phosphoserine1 Publication1
Modified residuei69Phosphoserine1 Publication1
Modified residuei74Phosphothreonine1 Publication1
Modified residuei75Phosphoserine; by CDK5Combined sources1 Publication1
Modified residuei187PhosphotyrosineBy similarity1
Modified residuei419Phosphotyrosine; by autocatalysis4 Publications1
Modified residuei419Phosphotyrosine; by FAK2By similarity1
Modified residuei439Phosphotyrosine1 Publication1
Modified residuei511Phosphothreonine1 Publication1
Modified residuei522Phosphotyrosine1 Publication1
Modified residuei530Phosphotyrosine; by CSKCombined sources2 Publications1

Post-translational modificationi

Myristoylated at Gly-2, and this is essential for targeting to membranes.1 Publication
Dephosphorylated at Tyr-530 by PTPRJ (By similarity). Phosphorylated on Tyr-530 by c-Src kinase (CSK). The phosphorylated form is termed pp60c-src. Dephosphorylated by PTPRJ at Tyr-419. Normally maintained in an inactive conformation with the SH2 domain engaged with Tyr-530, the SH3 domain engaged with the SH2-kinase linker, and Tyr-419 dephosphorylated. Dephosphorylation of Tyr-530 as a result of protein tyrosine phosphatase (PTP) action disrupts the intramolecular interaction between the SH2 domain and Tyr-530, Tyr-419 can then become autophosphorylated, resulting in SRC activation. Phosphorylation of Tyr-530 by CSK allows this interaction to reform, resulting in SRC inactivation. CDK5-mediated phosphorylation at Ser-75 targets SRC to ubiquitin-dependent degradation and thus leads to cytoskeletal reorganization. Phosphorylated by PTK2/FAK1; this enhances kinase activity. Phosphorylated by PTK2B/PYK2; this enhances kinase activity.By similarity6 Publications
S-nitrosylation is important for activation of its kinase activity.By similarity
Ubiquitinated in response to CDK5-mediated phosphorylation. Ubiquitination mediated by CBLC requires SRC autophosphorylation at Tyr-419 and may lead to lysosomal degradation.4 Publications

Keywords - PTMi

Lipoprotein, Myristate, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP12931.
MaxQBiP12931.
PaxDbiP12931.
PeptideAtlasiP12931.
PRIDEiP12931.

2D gel databases

OGPiP12931.

PTM databases

iPTMnetiP12931.
PhosphoSitePlusiP12931.
SwissPalmiP12931.

Miscellaneous databases

PMAP-CutDBiP12931.

Expressioni

Tissue specificityi

Expressed ubiquitously. Platelets, neurons and osteoclasts express 5-fold to 200-fold higher levels than most other tissues.

Gene expression databases

BgeeiENSG00000197122.
CleanExiHS_SRC.
GenevisibleiP12931. HS.

Organism-specific databases

HPAiCAB004023.
HPA030875.

Interactioni

Subunit structurei

Interacts with DDEF1/ASAP1; via the SH3 domain. Interacts with CCPG1. Identified in a complex containing FGFR4, NCAM1, CDH2, PLCG1, FRS2, SRC, SHC1, GAP43 and CTTN. Interacts with ERBB2, STAT1 and PNN. Interacts with DDR1, DDR2 and DAB2. Interacts with CDCP1, PELP1, TGFB1I1 and TOM1L2. Interacts with the cytoplasmic domain of MUC1, phosphorylates it and increases binding of MUC1 with beta-catenin. Interacts with RALGPS1; via the SH3 domain. Interacts with HEV ORF3 protein; via the SH3 domain. Interacts with CAV2 (tyrosine phosphorylated form). Interacts (via the SH3 domain and the protein kinase domain) with ARRB1; the interaction is independent of the phosphorylation state of SRC C-terminus. Interacts with ARRB1 and ARRB2. Interacts with SRCIN1. Interacts with NDFIP2 and more weakly with NDFIP1. Interacts with PIK3CA and/or PIK3C2B, PTK2/FAK1 and ESR1 (dimethylated on arginine). Interacts with FASLG. Interacts (via SH2 domain) with the 'Tyr-402' phosphorylated form of PTK2B/PYK2. Interacts (via SH2 domain) with FLT3 (tyrosine phosphorylated). Interacts with PDGFRA (tyrosine phosphorylated). Interacts with CSF1R. Interacts (via SH2 and SH3 domain) with TNK2. Interacts (via protein kinase domain) with the tyrosine phosphorylated form of RUNX3 (via runt domain). Interacts with TRAF3 (via RING-type zinc finger domain). Interacts with DDX58, MAVS and TBK1. Interacts (via SH2 domain) with RACK1; the interaction is enhanced by tyrosine phosphorylation of RACK1 and inhibits SRC activity. Interacts with EPHB1; activates the MAPK/ERK cascade to regulate cell migration. Interacts with FCAMR. Interacts (via SH2 domain) with the 'Tyr-9' phosphorylated form of PDPK1. Interacts with AMOTL2; this interaction regulates the translocation of phosphorylated SRC to peripheral cell-matrix adhesion sites. Interacts with TRAP1. Interacts with CBLC; the interaction is enhanced when SRC is phosphorylated at Tyr-419. Interacts with ARHGEF5 (By similarity). Interacts (via cytoplasmic domain) with CEACAM1 (via SH2 domain); this interaction is regulated by trans-homophilic cell adhesion (By similarity) (PubMed:7478590). Interacts with MPP2 (PubMed:19665017).By similarity31 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • cadherin binding Source: BHF-UCL
  • connexin binding Source: Ensembl
  • enzyme binding Source: UniProtKB
  • ephrin receptor binding Source: UniProtKB
  • estrogen receptor binding Source: Ensembl
  • growth factor receptor binding Source: UniProtKB
  • hormone receptor binding Source: GO_Central
  • insulin receptor binding Source: Ensembl
  • integrin binding Source: BHF-UCL
  • ion channel binding Source: BHF-UCL
  • kinase binding Source: UniProtKB
  • phosphoprotein binding Source: UniProtKB
  • protein C-terminus binding Source: CAFA
  • protein kinase C binding Source: Ensembl
  • receptor binding Source: UniProtKB
  • scaffold protein binding Source: BHF-UCL
  • SH2 domain binding Source: UniProtKB
  • SH3/SH2 adaptor activity Source: ProtInc
  • ubiquitin protein ligase binding Source: Ensembl
Complete GO annotation...

Protein-protein interaction databases

BioGridi112592. 269 interactors.
DIPiDIP-1059N.
IntActiP12931. 191 interactors.
MINTiMINT-93621.
STRINGi9606.ENSP00000350941.

Chemistry databases

BindingDBiP12931.

Structurei

Secondary structure

1536
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi87 – 93Combined sources7
Beta strandi99 – 102Combined sources4
Beta strandi110 – 114Combined sources5
Beta strandi118 – 126Combined sources9
Turni127 – 129Combined sources3
Beta strandi132 – 136Combined sources5
Helixi137 – 139Combined sources3
Beta strandi140 – 142Combined sources3
Helixi146 – 148Combined sources3
Beta strandi152 – 154Combined sources3
Helixi158 – 165Combined sources8
Beta strandi167 – 170Combined sources4
Beta strandi174 – 179Combined sources6
Beta strandi181 – 183Combined sources3
Beta strandi187 – 195Combined sources9
Turni196 – 198Combined sources3
Beta strandi199 – 209Combined sources11
Beta strandi211 – 213Combined sources3
Beta strandi215 – 218Combined sources4
Beta strandi221 – 225Combined sources5
Helixi226 – 233Combined sources8
Beta strandi240 – 242Combined sources3
Beta strandi256 – 259Combined sources4
Helixi267 – 269Combined sources3
Beta strandi270 – 278Combined sources9
Beta strandi283 – 289Combined sources7
Turni290 – 292Combined sources3
Beta strandi293 – 299Combined sources7
Turni302 – 304Combined sources3
Helixi307 – 319Combined sources13
Beta strandi328 – 332Combined sources5
Beta strandi334 – 336Combined sources3
Beta strandi338 – 341Combined sources4
Helixi349 – 353Combined sources5
Helixi355 – 358Combined sources4
Helixi363 – 382Combined sources20
Helixi392 – 394Combined sources3
Beta strandi395 – 397Combined sources3
Helixi399 – 401Combined sources3
Beta strandi403 – 405Combined sources3
Helixi410 – 413Combined sources4
Helixi417 – 420Combined sources4
Turni423 – 426Combined sources4
Helixi429 – 431Combined sources3
Helixi434 – 439Combined sources6
Helixi444 – 459Combined sources16
Turni460 – 462Combined sources3
Helixi471 – 479Combined sources9
Helixi492 – 501Combined sources10
Helixi506 – 508Combined sources3
Helixi512 – 520Combined sources9
Turni521 – 523Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1A07X-ray2.20A/B144-249[»]
1A08X-ray2.20A/B144-249[»]
1A09X-ray2.00A/B144-249[»]
1A1AX-ray2.00A/B144-249[»]
1A1BX-ray2.20A/B144-249[»]
1A1CX-ray2.40A/B144-249[»]
1A1EX-ray2.20A/B144-249[»]
1FMKX-ray1.50A86-536[»]
1HCSNMR-B144-249[»]
1HCTNMR-B144-249[»]
1KSWX-ray2.80A86-536[»]
1O41X-ray1.70A145-252[»]
1O42X-ray1.70A145-252[»]
1O43X-ray1.50A145-252[»]
1O44X-ray1.70A145-252[»]
1O45X-ray1.80A145-252[»]
1O46X-ray2.00A145-252[»]
1O47X-ray1.80A145-252[»]
1O48X-ray1.55A145-252[»]
1O49X-ray1.70A145-252[»]
1O4AX-ray1.50A145-252[»]
1O4BX-ray1.85A145-252[»]
1O4CX-ray1.80A145-252[»]
1O4DX-ray1.85A145-252[»]
1O4EX-ray2.00A145-252[»]
1O4FX-ray2.00A145-252[»]
1O4GX-ray1.55A145-252[»]
1O4HX-ray2.25A145-252[»]
1O4IX-ray1.75A145-252[»]
1O4JX-ray1.70A145-252[»]
1O4KX-ray1.57A145-252[»]
1O4LX-ray1.65A145-252[»]
1O4MX-ray1.60A145-252[»]
1O4NX-ray1.60A145-252[»]
1O4OX-ray1.70A145-252[»]
1O4PX-ray1.90A145-252[»]
1O4QX-ray1.70A145-252[»]
1O4RX-ray1.50A145-252[»]
1SHDX-ray2.00A144-249[»]
1Y57X-ray1.91A86-536[»]
1YI6X-ray2.00A/B261-536[»]
1YOJX-ray1.95A/B254-536[»]
1YOLX-ray2.30A/B254-536[»]
1YOMX-ray2.90A/B254-536[»]
2BDFX-ray2.10A/B258-536[»]
2BDJX-ray2.50A258-536[»]
2H8HX-ray2.20A2-536[»]
2SRCX-ray1.50A86-536[»]
3VROX-ray1.80B412-424[»]
3ZMPX-ray2.62C/D527-536[»]
3ZMQX-ray3.30C527-536[»]
4F59X-ray1.71A144-252[»]
4F5AX-ray1.80A144-252[»]
4F5BX-ray1.57A144-252[»]
4HXJX-ray2.00A/B87-144[»]
4K11X-ray2.30A87-534[»]
4MXOX-ray2.10A/B254-536[»]
4MXXX-ray2.60A/B254-536[»]
4MXYX-ray2.58A/B254-536[»]
4MXZX-ray2.58A/B254-536[»]
ProteinModelPortaliP12931.
SMRiP12931.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP12931.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini84 – 145SH3PROSITE-ProRule annotationAdd BLAST62
Domaini151 – 248SH2PROSITE-ProRule annotationAdd BLAST98
Domaini270 – 523Protein kinasePROSITE-ProRule annotationAdd BLAST254

Domaini

The SH2 and SH3 domains are important for the intramolecular and intermolecular interactions that regulate catalytic activity, localization, and substrate recruitment.

Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family. SRC subfamily.PROSITE-ProRule annotation

Keywords - Domaini

SH2 domain, SH3 domain

Phylogenomic databases

eggNOGiKOG0197. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00760000118938.
HOGENOMiHOG000233858.
HOVERGENiHBG008761.
InParanoidiP12931.
KOiK05704.
OMAiCQCWRKD.
OrthoDBiEOG091G0D46.
PhylomeDBiP12931.
TreeFamiTF351634.

Family and domain databases

Gene3Di3.30.505.10. 1 hit.
InterProiView protein in InterPro
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR000980. SH2.
IPR001452. SH3_domain.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
PfamiView protein in Pfam
PF07714. Pkinase_Tyr. 1 hit.
PF00017. SH2. 1 hit.
PF00018. SH3_1. 1 hit.
PRINTSiPR00401. SH2DOMAIN.
PR00452. SH3DOMAIN.
PR00109. TYRKINASE.
SMARTiView protein in SMART
SM00252. SH2. 1 hit.
SM00326. SH3. 1 hit.
SM00219. TyrKc. 1 hit.
SUPFAMiSSF50044. SSF50044. 1 hit.
SSF55550. SSF55550. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiView protein in PROSITE
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
PS50001. SH2. 1 hit.
PS50002. SH3. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P12931-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MGSNKSKPKD ASQRRRSLEP AENVHGAGGG AFPASQTPSK PASADGHRGP 
        60         70         80         90        100
SAAFAPAAAE PKLFGGFNSS DTVTSPQRAG PLAGGVTTFV ALYDYESRTE 
       110        120        130        140        150
TDLSFKKGER LQIVNNTEGD WWLAHSLSTG QTGYIPSNYV APSDSIQAEE 
       160        170        180        190        200
WYFGKITRRE SERLLLNAEN PRGTFLVRES ETTKGAYCLS VSDFDNAKGL 
       210        220        230        240        250
NVKHYKIRKL DSGGFYITSR TQFNSLQQLV AYYSKHADGL CHRLTTVCPT 
       260        270        280        290        300
SKPQTQGLAK DAWEIPRESL RLEVKLGQGC FGEVWMGTWN GTTRVAIKTL 
       310        320        330        340        350
KPGTMSPEAF LQEAQVMKKL RHEKLVQLYA VVSEEPIYIV TEYMSKGSLL 
       360        370        380        390        400
DFLKGETGKY LRLPQLVDMA AQIASGMAYV ERMNYVHRDL RAANILVGEN 
       410        420        430        440        450
LVCKVADFGL ARLIEDNEYT ARQGAKFPIK WTAPEAALYG RFTIKSDVWS 
       460        470        480        490        500
FGILLTELTT KGRVPYPGMV NREVLDQVER GYRMPCPPEC PESLHDLMCQ 
       510        520        530 
CWRKEPEERP TFEYLQAFLE DYFTSTEPQY QPGENL
Length:536
Mass (Da):59,835
Last modified:January 23, 2007 - v3
Checksum:iC1908084683E5DE8
GO
Isoform 2 (identifier: P12931-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     117-117: T → TRKVDVR

Show »
Length:542
Mass (Da):60,589
Checksum:iC12D30F8BCD5FF6B
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_051699176L → F. Corresponds to variant dbSNP:rs6018260Ensembl.1
Natural variantiVAR_041830237A → T1 PublicationCorresponds to variant dbSNP:rs34881773Ensembl.1
Natural variantiVAR_076919527E → K in THC6; increased protein tyrosine kinase activity; increased autophosphorylation at Y-419; causes defective megakaryopoiesis associated with increased overall tyrosine phosphorylation in megakaryocytes. 1 PublicationCorresponds to variant dbSNP:rs879255268Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_012134117T → TRKVDVR in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL133293 Genomic DNA. Translation: CAC10573.1.
AL133293 Genomic DNA. Translation: CAC34523.1.
CH471077 Genomic DNA. Translation: EAW76065.1.
CH471077 Genomic DNA. Translation: EAW76064.1.
CH471077 Genomic DNA. Translation: EAW76066.1.
CH471077 Genomic DNA. Translation: EAW76067.1.
BC011566 mRNA. Translation: AAH11566.1.
BC051270 mRNA. Translation: AAH51270.2.
K03218
, M16237, M16243, M16244, M16245, K03212, K03213, K03214, K03215, K03216, K03217 Genomic DNA. Translation: AAA60584.1.
X02647
, X03995, X03996, X03997, X03998, X03999, X04000 Genomic DNA. Translation: CAA26485.1.
CCDSiCCDS13294.1. [P12931-1]
PIRiA26891. TVHUSC.
RefSeqiNP_005408.1. NM_005417.4. [P12931-1]
NP_938033.1. NM_198291.2. [P12931-1]
XP_011527315.1. XM_011529013.2. [P12931-1]
XP_016883513.1. XM_017028024.1. [P12931-2]
XP_016883514.1. XM_017028025.1. [P12931-2]
XP_016883515.1. XM_017028026.1. [P12931-2]
XP_016883516.1. XM_017028027.1. [P12931-2]
UniGeneiHs.195659.

Genome annotation databases

EnsembliENST00000358208; ENSP00000350941; ENSG00000197122. [P12931-1]
ENST00000373558; ENSP00000362659; ENSG00000197122. [P12931-2]
ENST00000373567; ENSP00000362668; ENSG00000197122. [P12931-1]
ENST00000373578; ENSP00000362680; ENSG00000197122. [P12931-1]
GeneIDi6714.
KEGGihsa:6714.
UCSCiuc002xgy.5. human. [P12931-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.

Entry informationi

Entry nameiSRC_HUMAN
AccessioniPrimary (citable) accession number: P12931
Secondary accession number(s): E1P5V4
, Q76P87, Q86VB9, Q9H5A8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1989
Last sequence update: January 23, 2007
Last modified: July 5, 2017
This is version 220 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 20
    Human chromosome 20: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. SIMILARITY comments
    Index of protein domains and families