Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Basket 0
(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

P32577

- CSK_RAT

UniProt

P32577 - CSK_RAT

Protein

Tyrosine-protein kinase CSK

Gene

Csk

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
    • BLAST
    • Align
    • Format
    • Add to basket
    • History
      Entry version 143 (01 Oct 2014)
      Sequence version 1 (01 Oct 1993)
      Previous versions | rss
    • Help video
    • Feedback
    • Comment

    Functioni

    Non-receptor tyrosine-protein kinase that plays an important role in the regulation of cell growth, differentiation, migration and immune response. Phosphorylates tyrosine residues located in the C-terminal tails of Src-family kinases (SFKs) including LCK, SRC, HCK, FYN, LYN or YES1. Upon tail phosphorylation, Src-family members engage in intramolecular interactions between the phosphotyrosine tail and the SH2 domain that result in an inactive conformation. To inhibit SFKs, CSK is recruited to the plasma membrane via binding to transmembrane proteins or adapter proteins located near the plasma membrane. Suppresses signaling by various surface receptors, including T-cell receptor (TCR) and B-cell receptor (BCR) by phosphorylating and maintaining inactive several positive effectors such as FYN or LCK By similarity.By similarity

    Catalytic activityi

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

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei222 – 2221ATPPROSITE-ProRule annotation
    Active sitei314 – 3141Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi201 – 2099ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. non-membrane spanning protein tyrosine kinase activity Source: UniProtKB-EC
    3. proline-rich region binding Source: BHF-UCL
    4. protein phosphatase binding Source: BHF-UCL
    5. protein tyrosine kinase activity Source: RGD

    GO - Biological processi

    1. adherens junction organization Source: RGD
    2. brain development Source: RGD
    3. cellular response to peptide hormone stimulus Source: RGD
    4. immune system process Source: UniProtKB-KW
    5. negative regulation of bone resorption Source: RGD
    6. negative regulation of cell proliferation Source: RGD
    7. negative regulation of ERK1 and ERK2 cascade Source: RGD
    8. negative regulation of Golgi to plasma membrane protein transport Source: Ensembl
    9. negative regulation of interleukin-6 production Source: RGD
    10. negative regulation of kinase activity Source: RGD
    11. negative regulation of low-density lipoprotein particle clearance Source: RGD
    12. negative regulation of phagocytosis Source: RGD
    13. oligodendrocyte differentiation Source: RGD
    14. peptidyl-tyrosine phosphorylation Source: GOC
    15. positive regulation of MAP kinase activity Source: RGD
    16. protein autophosphorylation Source: RGD
    17. protein phosphorylation Source: RGD
    18. regulation of Fc receptor mediated stimulatory signaling pathway Source: RGD

    Keywords - Molecular functioni

    Kinase, Transferase, Tyrosine-protein kinase

    Keywords - Biological processi

    Adaptive immunity, Immunity

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    BRENDAi2.7.10.2. 5301.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Tyrosine-protein kinase CSK (EC:2.7.10.2)
    Alternative name(s):
    C-Src kinase
    Gene namesi
    Name:Csk
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    ProteomesiUP000002494: Chromosome 8

    Organism-specific databases

    RGDi1308800. Csk.

    Subcellular locationi

    Cytoplasm By similarity. Cell membrane By similarity
    Note: Mainly cytoplasmic, also present in lipid rafts.By similarity

    GO - Cellular componenti

    1. cell-cell junction Source: Ensembl
    2. centrosome Source: Ensembl
    3. cytoplasm Source: RGD
    4. Golgi apparatus Source: Ensembl
    5. membrane raft Source: RGD
    6. plasma membrane Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cell membrane, Cytoplasm, Membrane

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11RemovedBy similarity
    Chaini2 – 450449Tyrosine-protein kinase CSKPRO_0000088072Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei2 – 21N-acetylserineBy similarity
    Modified residuei184 – 1841PhosphotyrosineBy similarity
    Modified residuei304 – 3041PhosphotyrosineBy similarity
    Modified residuei364 – 3641Phosphoserine; by PKABy similarity
    Modified residuei416 – 4161Phosphotyrosine

    Post-translational modificationi

    Phosphorylated at Ser-364 by PKA, leading to increased activity. Autophosphorylated By similarity.By similarity

    Keywords - PTMi

    Acetylation, Phosphoprotein

    Proteomic databases

    PaxDbiP32577.
    PRIDEiP32577.

    PTM databases

    PhosphoSiteiP32577.

    Expressioni

    Tissue specificityi

    Enriched in lymphoid tissues.

    Gene expression databases

    GenevestigatoriP32577.

    Interactioni

    Subunit structurei

    Homodimer (via SH3-domain). Interacts with PTPN8. Interacts with phosphorylated SIT1, PAG1, LIME1 and TGFB1I1; these interactions serve to recruit CSK to the membrane where it can phosphorylate and inhibit Src-family kinases. Interacts with SRCIN1. Interacts with RHOH. Interacts (via SH2 domain) with SCIMP By similarity.By similarity

    Protein-protein interaction databases

    BioGridi261119. 2 interactions.
    IntActiP32577. 2 interactions.
    MINTiMINT-1535121.
    STRINGi10116.ENSRNOP00000026358.

    Structurei

    Secondary structure

    1
    450
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi13 – 186
    Beta strandi23 – 275
    Beta strandi35 – 417
    Beta strandi47 – 515
    Beta strandi57 – 615
    Helixi62 – 643
    Beta strandi65 – 673
    Beta strandi77 – 793
    Helixi89 – 957
    Beta strandi103 – 1086
    Beta strandi110 – 1123
    Beta strandi115 – 1217
    Beta strandi123 – 13412
    Beta strandi137 – 1448
    Beta strandi146 – 1483
    Helixi149 – 15810
    Beta strandi163 – 1653
    Helixi179 – 1857
    Helixi192 – 1943
    Beta strandi195 – 2039
    Beta strandi205 – 21410
    Beta strandi217 – 22610
    Helixi231 – 24111
    Beta strandi251 – 2566
    Beta strandi262 – 2676
    Helixi274 – 2818
    Turni283 – 2853
    Helixi288 – 30720
    Helixi317 – 3193
    Beta strandi320 – 3223
    Beta strandi328 – 3303
    Turni350 – 3523
    Helixi355 – 3595
    Helixi365 – 38016
    Turni381 – 3833
    Turni392 – 3943
    Helixi395 – 4006
    Helixi413 – 42210
    Helixi427 – 4293
    Helixi433 – 44513
    Turni446 – 4494

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1K9AX-ray2.50A/B/C/D/E/F1-450[»]
    2RSYNMR-A80-173[»]
    ProteinModelPortaliP32577.
    SMRiP32577. Positions 6-450.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP32577.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini9 – 7062SH3PROSITE-ProRule annotationAdd
    BLAST
    Domaini82 – 17190SH2PROSITE-ProRule annotationAdd
    BLAST
    Domaini195 – 445251Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni9 – 7062Interaction with PTPN8By similarityAdd
    BLAST

    Domaini

    The architecture of this protein is similar to that of Src-family kinases (SFKs) with one N-terminal SH3 domain, one SH2 domain, and a C-terminal kinase domain.By similarity

    Sequence similaritiesi

    Belongs to the protein kinase superfamily. Tyr protein kinase family. CSK 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.
    GeneTreeiENSGT00750000117264.
    HOGENOMiHOG000233858.
    HOVERGENiHBG008761.
    InParanoidiP32577.
    KOiK05728.
    OMAiERLLCPP.
    OrthoDBiEOG7SV0V5.
    PhylomeDBiP32577.
    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.
    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.

    P32577-1 [UniParc]FASTAAdd to Basket

    « Hide

    MSAIQASWPS GTECIAKYNF HGTAEQDLPF CKGDVLTIVA VTKDPNWYKA    50
    KNKVGREGII PANYVQKREG VKAGTKLSLM PWFHGKITRE QAERLLYPPE 100
    TGLFLVREST NYPGDYTLCV SCEGKVEHYR IMYHASKLSI DEEVYFENLM 150
    QLVEHYTTDA DGLCTRLIKP KVMEGTVAAQ DEFYRSGWAL NMKELKLLQT 200
    IGKGEFGDVM LGDYRGNKVA VKCIKNDATA QAFLAEASVM TQLRHSNLVQ 250
    LLGVIVEEKG GLYIVTEYMA KGSLVDYLRS RGRSVLGGDC LLKFSLDVCE 300
    AMEYLEGNNF VHRDLAARNV LVSEDNVAKV SDFGLTKEAS STQDTGKLPV 350
    KWTAPEALRE KKFSTKSDVW SFGILLWEIY SFGRVPYPRI PLKDVVPRVE 400
    KGYKMDAPDG CPPAVYDVMK NCWHLDAATR PTFLQLREQL EHIRTHELHL 450
    Length:450
    Mass (Da):50,746
    Last modified:October 1, 1993 - v1
    Checksum:i393DC8D737DAC67A
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X58631 mRNA. Translation: CAA41484.1.
    BC098863 mRNA. Translation: AAH98863.1.
    PIRiS15094.
    RefSeqiNP_001025210.1. NM_001030039.1.
    XP_006243225.1. XM_006243163.1.
    XP_006243226.1. XM_006243164.1.
    XP_006243227.1. XM_006243165.1.
    UniGeneiRn.2759.

    Genome annotation databases

    EnsembliENSRNOT00000026358; ENSRNOP00000026358; ENSRNOG00000019374.
    GeneIDi315707.
    KEGGirno:315707.
    UCSCiRGD:1308800. rat.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X58631 mRNA. Translation: CAA41484.1 .
    BC098863 mRNA. Translation: AAH98863.1 .
    PIRi S15094.
    RefSeqi NP_001025210.1. NM_001030039.1.
    XP_006243225.1. XM_006243163.1.
    XP_006243226.1. XM_006243164.1.
    XP_006243227.1. XM_006243165.1.
    UniGenei Rn.2759.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1K9A X-ray 2.50 A/B/C/D/E/F 1-450 [» ]
    2RSY NMR - A 80-173 [» ]
    ProteinModelPortali P32577.
    SMRi P32577. Positions 6-450.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 261119. 2 interactions.
    IntActi P32577. 2 interactions.
    MINTi MINT-1535121.
    STRINGi 10116.ENSRNOP00000026358.

    Chemistry

    BindingDBi P32577.
    ChEMBLi CHEMBL4365.

    PTM databases

    PhosphoSitei P32577.

    Proteomic databases

    PaxDbi P32577.
    PRIDEi P32577.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSRNOT00000026358 ; ENSRNOP00000026358 ; ENSRNOG00000019374 .
    GeneIDi 315707.
    KEGGi rno:315707.
    UCSCi RGD:1308800. rat.

    Organism-specific databases

    CTDi 1445.
    RGDi 1308800. Csk.

    Phylogenomic databases

    eggNOGi COG0515.
    GeneTreei ENSGT00750000117264.
    HOGENOMi HOG000233858.
    HOVERGENi HBG008761.
    InParanoidi P32577.
    KOi K05728.
    OMAi ERLLCPP.
    OrthoDBi EOG7SV0V5.
    PhylomeDBi P32577.
    TreeFami TF351634.

    Enzyme and pathway databases

    BRENDAi 2.7.10.2. 5301.

    Miscellaneous databases

    EvolutionaryTracei P32577.
    NextBioi 669700.
    PROi P32577.

    Gene expression databases

    Genevestigatori P32577.

    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.
    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. "Cloning of a complementary DNA for a protein-tyrosine kinase that specifically phosphorylates a negative regulatory site of p60c-src."
      Nada S., Okada M., McAuley A., Cooper J.A., Nakagawa H.
      Nature 351:69-72(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE.
    2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Thymus.
    3. "CSK: a protein-tyrosine kinase involved in regulation of src family kinases."
      Okada M., Nada S., Yamanashi Y., Yamamoto T., Nakagawa H.
      J. Biol. Chem. 266:24249-24252(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN PHOSPHORYLATION OF LYN AND FYN.
    4. "Regulation of c-Fgr protein kinase by c-Src kinase (CSK) and by polycationic effectors."
      Ruzzene M., James P., Brunati A.M., Donella-Deana A., Pinna L.A.
      J. Biol. Chem. 269:15885-15891(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN PHOSPHORYLATION OF FGR.
    5. "Transmembrane phosphoprotein Cbp regulates the activities of Src-family tyrosine kinases."
      Kawabuchi M., Satomi Y., Takao T., Shimonishi Y., Nada S., Nagai K., Tarakhovsky A., Okada M.
      Nature 404:999-1003(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH PAG1.
    6. "Mechanism of Csk-mediated down-regulation of Src family tyrosine kinases in epidermal growth factor signaling."
      Matsuoka H., Nada S., Okada M.
      J. Biol. Chem. 279:5975-5983(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH PAG1.

    Entry informationi

    Entry nameiCSK_RAT
    AccessioniPrimary (citable) accession number: P32577
    Secondary accession number(s): Q4G003
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 1, 1993
    Last sequence update: October 1, 1993
    Last modified: October 1, 2014
    This is version 143 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3