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Q1JPZ3

- SRC_DANRE

UniProt

Q1JPZ3 - SRC_DANRE

Protein

Proto-oncogene tyrosine-protein kinase Src

Gene

src

Organism
Danio rerio (Zebrafish) (Brachydanio rerio)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 74 (01 Oct 2014)
      Sequence version 2 (05 Sep 2012)
      Previous versions | rss
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    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)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei296 – 2961ATPPROSITE-ProRule annotation
    Active sitei387 – 3871Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi274 – 2829ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. non-membrane spanning protein tyrosine kinase activity Source: UniProtKB-EC

    GO - Biological processi

    1. cell adhesion Source: UniProtKB-KW
    2. cell cycle Source: UniProtKB-KW
    3. response to yeast Source: ZFIN

    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

    ReactomeiREACT_174907. Regulation of KIT signaling.
    REACT_181648. Signaling by SCF-KIT.
    REACT_182698. Signaling by ERBB2.
    REACT_206122. ADP signalling through P2Y purinoceptor 1.
    REACT_214033. Netrin mediated repulsion signals.
    REACT_221534. FCGR activation.

    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
    ProteomesiUP000000437: Chromosome 23

    Organism-specific databases

    ZFINiZDB-GENE-030131-3809. src.

    Subcellular locationi

    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.By similarity

    GO - Cellular componenti

    1. cytoskeleton Source: UniProtKB-SubCell
    2. mitochondrial inner membrane Source: UniProtKB-SubCell
    3. nucleus Source: UniProtKB-SubCell
    4. plasma membrane Source: UniProtKB-SubCell

    Keywords - Cellular componenti

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

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi528 – 5281Y → F: Lower affinity for AMOTL2-binding compared with wild-type. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11RemovedBy similarity
    Chaini2 – 534533Proto-oncogene tyrosine-protein kinase SrcPRO_0000418880Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Lipidationi2 – 21N-myristoyl glycineBy similarity
    Modified residuei17 – 171PhosphoserineBy similarity
    Modified residuei34 – 341PhosphoserineBy similarity
    Modified residuei67 – 671PhosphoserineBy similarity
    Modified residuei73 – 731PhosphothreonineBy similarity
    Modified residuei74 – 741Phosphoserine; by CDK5By similarity
    Modified residuei185 – 1851PhosphotyrosineBy similarity
    Modified residuei417 – 4171Phosphotyrosine; by autocatalysisBy similarity
    Modified residuei417 – 4171Phosphotyrosine; by FAK2By similarity
    Modified residuei437 – 4371PhosphotyrosineBy similarity
    Modified residuei499 – 4991S-nitrosocysteineBy similarity
    Modified residuei509 – 5091PhosphothreonineBy similarity
    Modified residuei520 – 5201PhosphotyrosineBy similarity
    Modified residuei528 – 5281Phosphotyrosine; by CSKBy similarity

    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

    Expressioni

    Tissue specificityi

    Widely expressed.1 Publication

    Interactioni

    Subunit structurei

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

    Protein-protein interaction databases

    STRINGi7955.ENSDARP00000093618.

    Structurei

    3D structure databases

    ProteinModelPortaliQ1JPZ3.
    SMRiQ1JPZ3. Positions 84-534.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini82 – 14362SH3PROSITE-ProRule annotationAdd
    BLAST
    Domaini149 – 253105SH2PROSITE-ProRule annotationAdd
    BLAST
    Domaini268 – 521254Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    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

    eggNOGiCOG0515.
    GeneTreeiENSGT00620000087702.
    HOGENOMiHOG000233858.
    HOVERGENiHBG008761.
    KOiK05704.
    OMAiCQCWRKD.
    OrthoDBiEOG7GTT2V.
    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

    MGGVKSKPKE LGQRSRSLDD GTGGHHHHTP NPTSFTPNRS PPVEGSRRGT    50
    QPNIINAEQA LFGGVNSTTN SITSPNRIGI LGGVTTFVAL YDYESRTASD 100
    LSFRKGERLQ IVNNTEGDWW LARSLTTGES GYIPSNYVAP SDSIQAEEWY 150
    FGKITRRDSE RLLLNLENRR GTFLVRESET TKGAYCLSVL DYDNVKGLNV 200
    KHYKIRKLDS GGFYITSRTQ FSTLQQLVNH YRQHADGLCH SLTDVCPVLK 250
    PPTQGLARDA WEIPRDSLRL DVKLGQGCFG EVWMGTWNGT TRVAIKTLKP 300
    GTMSPEAFLQ EAQVMKKLRH EKLVQLYAVV SEEPIYIVTE YMGQGSLLDF 350
    LKGDMGKMLR LPQLVDMASQ IASGMAYVER MNYVHRDLRA ANILVGDNLV 400
    CKVADFGLAR LIEDNEYTAR QGAKFPIKWT APEAALYGRF TIKSDVWSFG 450
    ILLTELTTKG RVPYPGMVNR EVLDQVERGY RMPCPAECPD SLHELMLTCW 500
    RKEPEERPTF EYLQGFLEDY FTSTEPQYQP GENL 534
    Length:534
    Mass (Da):60,147
    Last modified:September 5, 2012 - v2
    Checksum:iEC09B5A1BC01A38A
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti4 – 41V → A in AAI16545. 1 PublicationCurated
    Sequence conflicti166 – 1661L → M in AAI16545. 1 PublicationCurated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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.
    ENSDART00000112198; ENSDARP00000097596; ENSDARG00000008107.
    GeneIDi325084.
    KEGGidre:325084.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AJ620750 mRNA. Translation: CAF06181.1 .
    BX548066 Genomic DNA. No translation available.
    CU302205 Genomic DNA. No translation available.
    BC116544 mRNA. Translation: AAI16545.1 .
    RefSeqi NP_001003837.2. NM_001003837.2.
    UniGenei Dr.2731.

    3D structure databases

    ProteinModelPortali Q1JPZ3.
    SMRi Q1JPZ3. Positions 84-534.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    STRINGi 7955.ENSDARP00000093618.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSDART00000102843 ; ENSDARP00000093618 ; ENSDARG00000008107 .
    ENSDART00000112198 ; ENSDARP00000097596 ; ENSDARG00000008107 .
    GeneIDi 325084.
    KEGGi dre:325084.

    Organism-specific databases

    CTDi 6714.
    ZFINi ZDB-GENE-030131-3809. src.

    Phylogenomic databases

    eggNOGi COG0515.
    GeneTreei ENSGT00620000087702.
    HOGENOMi HOG000233858.
    HOVERGENi HBG008761.
    KOi K05704.
    OMAi CQCWRKD.
    OrthoDBi EOG7GTT2V.
    PhylomeDBi Q1JPZ3.
    TreeFami TF351634.

    Enzyme and pathway databases

    Reactomei REACT_174907. Regulation of KIT signaling.
    REACT_181648. Signaling by SCF-KIT.
    REACT_182698. Signaling by ERBB2.
    REACT_206122. ADP signalling through P2Y purinoceptor 1.
    REACT_214033. Netrin mediated repulsion signals.
    REACT_221534. FCGR activation.

    Miscellaneous databases

    NextBioi 20809110.
    PROi Q1JPZ3.

    Family and domain databases

    Gene3Di 3.30.505.10. 1 hit.
    InterProi 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.
    [Graphical view ]
    Pfami PF07714. Pkinase_Tyr. 1 hit.
    PF00017. SH2. 1 hit.
    PF00018. SH3_1. 1 hit.
    [Graphical view ]
    PRINTSi PR00401. SH2DOMAIN.
    PR00452. SH3DOMAIN.
    PR00109. TYRKINASE.
    SMARTi SM00252. SH2. 1 hit.
    SM00326. SH3. 1 hit.
    SM00219. TyrKc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF50044. SSF50044. 1 hit.
    SSF55550. SSF55550. 1 hit.
    SSF56112. SSF56112. 1 hit.
    PROSITEi 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.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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.
      , 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.

    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: October 1, 2014
    This is version 74 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

    External Data

    Dasty 3