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Protein

Proto-oncogene tyrosine-protein kinase Src

Gene

src

Organism
Danio rerio (Zebrafish) (Brachydanio rerio)
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 involved in this process. When cells adhere via focal adhesions to the extra-cellular matrix, signals are transmitted by integrins into the cell and result in tyrosine phosphorylation of a number of focal adhesion proteins, including ptk2/fak1 and paxillin (pxn). Also active at the sites of cell-cell contact adherens junctions and at gap junctions. Implicated in the regulation of pre-mRNA-processing. 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 (By similarity).By similarity

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

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Transferase, Tyrosine-protein kinase

Keywords - Biological processi

Cell adhesion, Cell cycle

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-DRE-1227986. Signaling by ERBB2.
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-8853659. RET signaling.
R-DRE-8874081. MET activates PTK2 signaling.

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

GO - Cellular componenti

Complete GO annotation...

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.
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
Contains 1 protein kinase domain.PROSITE-ProRule annotation
Contains 1 SH2 domain.PROSITE-ProRule annotation
Contains 1 SH3 domain.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.
InterProiIPR011009. 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.
[Graphical view]
PfamiPF07714. Pkinase_Tyr. 1 hit.
PF00017. SH2. 1 hit.
PF00018. SH3_1. 1 hit.
[Graphical view]
PRINTSiPR00401. SH2DOMAIN.
PR00452. SH3DOMAIN.
PR00109. TYRKINASE.
SMARTiSM00252. SH2. 1 hit.
SM00326. SH3. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF50044. SSF50044. 1 hit.
SSF55550. SSF55550. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS00107. 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.
[Graphical view]

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.

Cross-referencesi

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.

3D structure databases

ProteinModelPortaliQ1JPZ3.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi7955.ENSDARP00000093618.

Proteomic databases

PaxDbiQ1JPZ3.
PRIDEiQ1JPZ3.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSDART00000102843; ENSDARP00000093618; ENSDARG00000008107.
GeneIDi325084.
KEGGidre:325084.

Organism-specific databases

CTDi6714.
ZFINiZDB-GENE-030131-3809. src.

Phylogenomic databases

eggNOGiKOG0197. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00760000118938.
HOGENOMiHOG000233858.
HOVERGENiHBG008761.
InParanoidiQ1JPZ3.
KOiK05704.
OMAiCQCWRKD.
OrthoDBiEOG091G0D46.
PhylomeDBiQ1JPZ3.
TreeFamiTF351634.

Enzyme and pathway databases

ReactomeiR-DRE-1227986. Signaling by ERBB2.
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-8853659. RET signaling.
R-DRE-8874081. MET activates PTK2 signaling.

Miscellaneous databases

PROiQ1JPZ3.

Gene expression databases

BgeeiENSDARG00000008107.

Family and domain databases

Gene3Di3.30.505.10. 1 hit.
InterProiIPR011009. 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.
[Graphical view]
PfamiPF07714. Pkinase_Tyr. 1 hit.
PF00017. SH2. 1 hit.
PF00018. SH3_1. 1 hit.
[Graphical view]
PRINTSiPR00401. SH2DOMAIN.
PR00452. SH3DOMAIN.
PR00109. TYRKINASE.
SMARTiSM00252. SH2. 1 hit.
SM00326. SH3. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF50044. SSF50044. 1 hit.
SSF55550. SSF55550. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS00107. 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.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiSRC_DANRE
AccessioniPrimary (citable) accession number: Q1JPZ3
Secondary accession number(s): Q6EWH0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 5, 2012
Last sequence update: September 5, 2012
Last modified: November 30, 2016
This is version 92 of the entry and version 2 of the sequence. [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

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.