Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q1JPZ3 (SRC_DANRE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 72. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:src
OrganismDanio rerio (Zebrafish) (Brachydanio rerio) [Reference proteome]
Taxonomic identifier7955 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiActinopterygiiNeopterygiiTeleosteiOstariophysiCypriniformesCyprinidaeDanio

Protein attributes

Sequence length534 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Catalytic activity

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

Enzyme regulation

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.

Subunit structure

Interacts with amotl2; this interaction promotes the translocation of phosphorylated src to peripheral cell-matrix adhesion sites. Ref.4

Subcellular location

Cell membrane By similarity. Mitochondrion inner membrane By similarity. Nucleus By similarity. Cytoplasmcytoskeleton By similarity. Note: Localizes to focal adhesion sites following integrin engagement. Localization to focal adhesion sites requires myristoylation and the SH3 domain By similarity.

Tissue specificity

Widely expressed. Ref.1

Domain

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

Post-translational modification

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.

S-nitrosylation is important for activation of kinase activity By similarity.

Sequence similarities

Belongs to the protein kinase superfamily. Tyr protein kinase family. SRC subfamily.

Contains 1 protein kinase domain.

Contains 1 SH2 domain.

Contains 1 SH3 domain.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 534533Proto-oncogene tyrosine-protein kinase Src
PRO_0000418880

Regions

Domain82 – 14362SH3
Domain149 – 253105SH2
Domain268 – 521254Protein kinase
Nucleotide binding274 – 2829ATP By similarity

Sites

Active site3871Proton acceptor By similarity
Binding site2961ATP By similarity

Amino acid modifications

Modified residue171Phosphoserine By similarity
Modified residue341Phosphoserine By similarity
Modified residue671Phosphoserine By similarity
Modified residue731Phosphothreonine By similarity
Modified residue741Phosphoserine; by CDK5 By similarity
Modified residue1851Phosphotyrosine By similarity
Modified residue4171Phosphotyrosine; by autocatalysis By similarity
Modified residue4171Phosphotyrosine; by FAK2 By similarity
Modified residue4371Phosphotyrosine By similarity
Modified residue4991S-nitrosocysteine By similarity
Modified residue5091Phosphothreonine By similarity
Modified residue5201Phosphotyrosine By similarity
Modified residue5281Phosphotyrosine; by CSK By similarity
Lipidation21N-myristoyl glycine By similarity

Experimental info

Mutagenesis5281Y → F: Lower affinity for AMOTL2-binding compared with wild-type. Ref.4
Sequence conflict41V → A in AAI16545. Ref.3
Sequence conflict1661L → M in AAI16545. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Q1JPZ3 [UniParc].

Last modified September 5, 2012. Version 2.
Checksum: EC09B5A1BC01A38A

FASTA53460,147
        10         20         30         40         50         60 
MGGVKSKPKE LGQRSRSLDD GTGGHHHHTP NPTSFTPNRS PPVEGSRRGT QPNIINAEQA 

        70         80         90        100        110        120 
LFGGVNSTTN SITSPNRIGI LGGVTTFVAL YDYESRTASD LSFRKGERLQ IVNNTEGDWW 

       130        140        150        160        170        180 
LARSLTTGES GYIPSNYVAP SDSIQAEEWY FGKITRRDSE RLLLNLENRR GTFLVRESET 

       190        200        210        220        230        240 
TKGAYCLSVL DYDNVKGLNV KHYKIRKLDS GGFYITSRTQ FSTLQQLVNH YRQHADGLCH 

       250        260        270        280        290        300 
SLTDVCPVLK PPTQGLARDA WEIPRDSLRL DVKLGQGCFG EVWMGTWNGT TRVAIKTLKP 

       310        320        330        340        350        360 
GTMSPEAFLQ EAQVMKKLRH EKLVQLYAVV SEEPIYIVTE YMGQGSLLDF LKGDMGKMLR 

       370        380        390        400        410        420 
LPQLVDMASQ IASGMAYVER MNYVHRDLRA ANILVGDNLV CKVADFGLAR LIEDNEYTAR 

       430        440        450        460        470        480 
QGAKFPIKWT APEAALYGRF TIKSDVWSFG ILLTELTTKG RVPYPGMVNR EVLDQVERGY 

       490        500        510        520        530 
RMPCPAECPD SLHELMLTCW RKEPEERPTF EYLQGFLEDY FTSTEPQYQP GENL 

« Hide

References

« Hide 'large scale' references
[1]"Fyn/Yes and non-canonical Wnt signalling converge on RhoA in vertebrate gastrulation cell movements."
Jopling C., den Hertog J.
EMBO Rep. 6:426-431(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
[2]"The zebrafish reference genome sequence and its relationship to the human genome."
Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M., Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I., Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J. expand/collapse author list , White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y., Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B., Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S., Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M., Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J., Clee C., Oliver K., Clark R., Riddle C., Eliott D., Threadgold G., Harden G., Ware D., Mortimer B., Kerry G., Heath P., Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S., Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J., Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J., Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D., McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S., Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E., Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A., Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P., Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J., Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E., Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C., Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C., Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M., Oberlander M., Rudolph-Geiger S., Teucke M., Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M., Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M., de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C., Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.
Nature 496:498-503(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: Tuebingen.
[3]NIH - Zebrafish Gene Collection (ZGC) project
Submitted (MAY-2006) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Ovary.
[4]"Amotl2 is essential for cell movements in zebrafish embryo and regulates c-Src translocation."
Huang H., Lu F.I., Jia S., Meng S., Cao Y., Wang Y., Ma W., Yin K., Wen Z., Peng J., Thisse C., Thisse B., Meng A.
Development 134:979-988(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH AMOTL2, MUTAGENESIS OF TYR-528.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AJ620750 mRNA. Translation: CAF06181.1.
BX548066 Genomic DNA. No translation available.
CU302205 Genomic DNA. No translation available.
BC116544 mRNA. Translation: AAI16545.1.
RefSeqNP_001003837.2. NM_001003837.2.
UniGeneDr.2731.

3D structure databases

ProteinModelPortalQ1JPZ3.
SMRQ1JPZ3. Positions 84-534.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING7955.ENSDARP00000093618.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSDART00000102843; ENSDARP00000093618; ENSDARG00000008107.
ENSDART00000112198; ENSDARP00000097596; ENSDARG00000008107.
GeneID325084.
KEGGdre:325084.

Organism-specific databases

CTD6714.
ZFINZDB-GENE-030131-3809. src.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00620000087702.
HOGENOMHOG000233858.
HOVERGENHBG008761.
KOK05704.
OMACQCWRKD.
OrthoDBEOG7GTT2V.
PhylomeDBQ1JPZ3.
TreeFamTF351634.

Family and domain databases

Gene3D3.30.505.10. 1 hit.
InterProIPR011009. 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]
PfamPF07714. Pkinase_Tyr. 1 hit.
PF00017. SH2. 1 hit.
PF00018. SH3_1. 1 hit.
[Graphical view]
PRINTSPR00401. SH2DOMAIN.
PR00452. SH3DOMAIN.
PR00109. TYRKINASE.
SMARTSM00252. SH2. 1 hit.
SM00326. SH3. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMSSF50044. SSF50044. 1 hit.
SSF55550. SSF55550. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEPS00107. 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]
ProtoNetSearch...

Other

NextBio20809110.
PROQ1JPZ3.

Entry information

Entry nameSRC_DANRE
AccessionPrimary (citable) accession number: Q1JPZ3
Secondary accession number(s): Q6EWH0
Entry history
Integrated into UniProtKB/Swiss-Prot: September 5, 2012
Last sequence update: September 5, 2012
Last modified: April 16, 2014
This is version 72 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families