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Protein

Proto-oncogene tyrosine-protein kinase Src

Gene

src

Organism
Danio rerio (Zebrafish) (Brachydanio rerio)
Status
Reviewed-Annotation score: -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 involved in this process (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) (By similarity). Also active at the sites of cell-cell contact adherens junctions and at gap junctions. Implicated in the regulation of pre-mRNA-processing (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. Involved in anchorage-independent cell growth (By similarity).By similarityCurated

Catalytic activityi

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

Enzyme regulationi

Becomes activated when its major tyrosine phosphorylation site is not phosphorylated. It can also be activated by point mutations as well as by truncations at the C-terminal end or by other mutations. Heme regulates its activity by enhancing the phosphorylation on Tyr-528 (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei296ATPPROSITE-ProRule annotation1
Active sitei387Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi274 – 282ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

Keywordsi

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

Enzyme and pathway databases

ReactomeiR-DRE-1227986 Signaling by ERBB2
R-DRE-1257604 PIP3 activates AKT signaling
R-DRE-1295596 Spry regulation of FGF signaling
R-DRE-1433557 Signaling by SCF-KIT
R-DRE-177929 Signaling by EGFR
R-DRE-180292 GAB1 signalosome
R-DRE-186763 Downstream signal transduction
R-DRE-191647 c-src mediated regulation of Cx43 function and closure of gap junctions
R-DRE-2029481 FCGR activation
R-DRE-354192 Integrin alphaIIb beta3 signaling
R-DRE-354194 GRB2:SOS provides linkage to MAPK signaling for Integrins
R-DRE-372708 p130Cas linkage to MAPK signaling for integrins
R-DRE-3928662 EPHB-mediated forward signaling
R-DRE-3928663 EPHA-mediated growth cone collapse
R-DRE-3928664 Ephrin signaling
R-DRE-3928665 EPH-ephrin mediated repulsion of cells
R-DRE-418592 ADP signalling through P2Y purinoceptor 1
R-DRE-418885 DCC mediated attractive signaling
R-DRE-430116 GP1b-IX-V activation signalling
R-DRE-437239 Recycling pathway of L1
R-DRE-4420097 VEGFA-VEGFR2 Pathway
R-DRE-456926 Thrombin signalling through proteinase activated receptors (PARs)
R-DRE-5218921 VEGFR2 mediated cell proliferation
R-DRE-5673000 RAF activation
R-DRE-5674135 MAP2K and MAPK activation
R-DRE-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-DRE-69231 Cyclin D associated events in G1
R-DRE-8853659 RET signaling
R-DRE-8874081 MET activates PTK2 signaling
R-DRE-8934903 Receptor Mediated Mitophagy
R-DRE-8941858 Regulation of RUNX3 expression and activity

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
OrganismiDanio rerio (Zebrafish) (Brachydanio rerio)
Taxonomic identifieri7955 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiActinopterygiiNeopterygiiTeleosteiOstariophysiCypriniformesCyprinidaeDanio
Proteomesi
  • UP000000437 Componenti: Chromosome 23

Organism-specific databases

ZFINiZDB-GENE-030131-3809 src

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

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

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi528Y → F: Lower affinity for AMOTL2-binding compared with wild-type. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00004188802 – 534Proto-oncogene tyrosine-protein kinase SrcAdd BLAST533

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi2N-myristoyl glycineBy similarity1
Modified residuei17PhosphoserineBy similarity1
Modified residuei34PhosphoserineBy similarity1
Modified residuei67PhosphoserineBy similarity1
Modified residuei73PhosphothreonineBy similarity1
Modified residuei74Phosphoserine; by CDK5By similarity1
Modified residuei185PhosphotyrosineBy similarity1
Modified residuei417Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei417Phosphotyrosine; by FAK2By similarity1
Modified residuei437PhosphotyrosineBy similarity1
Modified residuei499S-nitrosocysteineBy similarity1
Modified residuei509PhosphothreonineBy similarity1
Modified residuei520PhosphotyrosineBy similarity1
Modified residuei528Phosphotyrosine; by CSKBy similarity1

Post-translational modificationi

Myristoylated at Gly-2, and this is essential for targeting to membranes.By similarity
Dephosphorylated at Tyr-528 by PTPRJ. Phosphorylated on Tyr-528 by c-Src kinase (CSK). The phosphorylated form is termed pp60c-src. Dephosphorylated by PTPRJ at Tyr-417. Normally maintained in an inactive conformation with the SH2 domain engaged with Tyr-528, the SH3 domain engaged with the SH2-kinase linker, and Tyr-417 dephosphorylated. Dephosphorylation of Tyr-528 as a result of protein tyrosine phosphatase (PTP) action disrupts the intramolecular interaction between the SH2 domain and Tyr-528, Tyr-417 can then become autophosphorylated, resulting in SRC activation. Phosphorylation of Tyr-528 by CSK allows this interaction to reform, resulting in SRC inactivation (By similarity).By similarity
S-nitrosylation is important for activation of kinase activity.By similarity

Keywords - PTMi

Lipoprotein, Myristate, Phosphoprotein, S-nitrosylation

Proteomic databases

PaxDbiQ1JPZ3
PRIDEiQ1JPZ3

Expressioni

Tissue specificityi

Widely expressed.1 Publication

Gene expression databases

BgeeiENSDARG00000008107

Interactioni

Subunit structurei

Interacts with amotl2; this interaction promotes the translocation of phosphorylated src to peripheral cell-matrix adhesion sites.1 Publication

GO - Molecular functioni

Protein-protein interaction databases

STRINGi7955.ENSDARP00000093618

Structurei

3D structure databases

ProteinModelPortaliQ1JPZ3
SMRiQ1JPZ3
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini82 – 143SH3PROSITE-ProRule annotationAdd BLAST62
Domaini149 – 253SH2PROSITE-ProRule annotationAdd BLAST105
Domaini268 – 521Protein 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.By similarity

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
InParanoidiQ1JPZ3
KOiK05704
OMAiCQCWRKD
OrthoDBiEOG091G0D46
PhylomeDBiQ1JPZ3
TreeFamiTF351634

Family and domain databases

Gene3Di3.30.505.10, 1 hit
InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR001245 Ser-Thr/Tyr_kinase_cat_dom
IPR000980 SH2
IPR036860 SH2_dom_sf
IPR036028 SH3-like_dom_sf
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

Sequencei

Sequence statusi: Complete.

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

Q1JPZ3-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGGVKSKPKE LGQRSRSLDD GTGGHHHHTP NPTSFTPNRS PPVEGSRRGT
60 70 80 90 100
QPNIINAEQA LFGGVNSTTN SITSPNRIGI LGGVTTFVAL YDYESRTASD
110 120 130 140 150
LSFRKGERLQ IVNNTEGDWW LARSLTTGES GYIPSNYVAP SDSIQAEEWY
160 170 180 190 200
FGKITRRDSE RLLLNLENRR GTFLVRESET TKGAYCLSVL DYDNVKGLNV
210 220 230 240 250
KHYKIRKLDS GGFYITSRTQ FSTLQQLVNH YRQHADGLCH SLTDVCPVLK
260 270 280 290 300
PPTQGLARDA WEIPRDSLRL DVKLGQGCFG EVWMGTWNGT TRVAIKTLKP
310 320 330 340 350
GTMSPEAFLQ EAQVMKKLRH EKLVQLYAVV SEEPIYIVTE YMGQGSLLDF
360 370 380 390 400
LKGDMGKMLR LPQLVDMASQ IASGMAYVER MNYVHRDLRA ANILVGDNLV
410 420 430 440 450
CKVADFGLAR LIEDNEYTAR QGAKFPIKWT APEAALYGRF TIKSDVWSFG
460 470 480 490 500
ILLTELTTKG RVPYPGMVNR EVLDQVERGY RMPCPAECPD SLHELMLTCW
510 520 530
RKEPEERPTF EYLQGFLEDY FTSTEPQYQP GENL
Length:534
Mass (Da):60,147
Last modified:September 5, 2012 - v2
Checksum:iEC09B5A1BC01A38A
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti4V → A in AAI16545 (Ref. 3) Curated1
Sequence conflicti166L → M in AAI16545 (Ref. 3) Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ620750 mRNA Translation: CAF06181.1
BX548066 Genomic DNA No translation available.
CU302205 Genomic DNA No translation available.
BC116544 mRNA Translation: AAI16545.1
RefSeqiNP_001003837.2, NM_001003837.2
UniGeneiDr.2731

Genome annotation databases

EnsembliENSDART00000102843; ENSDARP00000093618; ENSDARG00000008107
GeneIDi325084
KEGGidre:325084

Similar proteinsi

Entry informationi

Entry nameiSRC_DANRE
AccessioniPrimary (citable) accession number: Q1JPZ3
Secondary accession number(s): Q6EWH0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 5, 2012
Last sequence update: September 5, 2012
Last modified: May 23, 2018
This is version 102 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

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