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Protein

Tyrosine-protein kinase CSK

Gene

Csk

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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

  • ATP binding Source: UniProtKB-KW
  • non-membrane spanning protein tyrosine kinase activity Source: GO_Central
  • proline-rich region binding Source: BHF-UCL
  • protein phosphatase binding Source: BHF-UCL
  • protein tyrosine kinase activity Source: RGD
  • receptor binding Source: GO_Central

GO - Biological processi

  • adherens junction organization Source: RGD
  • brain development Source: RGD
  • cell migration Source: GO_Central
  • cellular response to peptide hormone stimulus Source: RGD
  • innate immune response Source: GO_Central
  • morphogenesis of an epithelium Source: GO_Central
  • negative regulation of bone resorption Source: RGD
  • negative regulation of cell proliferation Source: RGD
  • negative regulation of ERK1 and ERK2 cascade Source: RGD
  • negative regulation of Golgi to plasma membrane protein transport Source: Ensembl
  • negative regulation of interleukin-6 production Source: RGD
  • negative regulation of kinase activity Source: RGD
  • negative regulation of low-density lipoprotein particle clearance Source: RGD
  • negative regulation of phagocytosis Source: RGD
  • oligodendrocyte differentiation Source: RGD
  • peptidyl-tyrosine autophosphorylation Source: GO_Central
  • positive regulation of MAP kinase activity Source: RGD
  • protein autophosphorylation Source: RGD
  • protein phosphorylation Source: RGD
  • regulation of Fc receptor mediated stimulatory signaling pathway Source: RGD
  • transmembrane receptor protein tyrosine kinase signaling pathway Source: GO_Central
Complete GO annotation...

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.
ReactomeiREACT_272857. GAB1 signalosome.
REACT_314992. Integrin alphaIIb beta3 signaling.
REACT_316530. Phosphorylation of CD3 and TCR zeta chains.
REACT_352796. PD-1 signaling.

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 Componenti: 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

  • cell-cell junction Source: Ensembl
  • cytoplasm Source: RGD
  • extracellular exosome Source: Ensembl
  • extrinsic component of cytoplasmic side of plasma membrane Source: GO_Central
  • membrane raft Source: RGD
Complete GO annotation...

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; by autocatalysisBy similarity

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

GenevisibleiP32577. RN.

Interactioni

Subunit structurei

Homodimer (via SH3-domain). Interacts with PTPN22. 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. 3 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 – 186Combined sources
Beta strandi23 – 275Combined sources
Beta strandi35 – 417Combined sources
Beta strandi47 – 515Combined sources
Beta strandi57 – 615Combined sources
Helixi62 – 643Combined sources
Beta strandi65 – 673Combined sources
Beta strandi77 – 793Combined sources
Helixi89 – 957Combined sources
Beta strandi103 – 1086Combined sources
Beta strandi110 – 1123Combined sources
Beta strandi115 – 1217Combined sources
Beta strandi123 – 13412Combined sources
Beta strandi137 – 1448Combined sources
Beta strandi146 – 1483Combined sources
Helixi149 – 15810Combined sources
Beta strandi163 – 1653Combined sources
Helixi179 – 1857Combined sources
Helixi192 – 1943Combined sources
Beta strandi195 – 2039Combined sources
Beta strandi205 – 21410Combined sources
Beta strandi217 – 22610Combined sources
Helixi231 – 24111Combined sources
Beta strandi251 – 2566Combined sources
Beta strandi262 – 2676Combined sources
Helixi274 – 2818Combined sources
Turni283 – 2853Combined sources
Helixi288 – 30720Combined sources
Helixi317 – 3193Combined sources
Beta strandi320 – 3223Combined sources
Beta strandi328 – 3303Combined sources
Turni350 – 3523Combined sources
Helixi355 – 3595Combined sources
Helixi365 – 38016Combined sources
Turni381 – 3833Combined sources
Turni392 – 3943Combined sources
Helixi395 – 4006Combined sources
Helixi413 – 42210Combined sources
Helixi427 – 4293Combined sources
Helixi433 – 44513Combined sources
Turni446 – 4494Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
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 PTPN22By 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.
GeneTreeiENSGT00760000119011.
HOGENOMiHOG000233858.
HOVERGENiHBG008761.
InParanoidiP32577.
KOiK05728.
OMAiVWPSGTE.
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

        10         20         30         40         50
MSAIQASWPS GTECIAKYNF HGTAEQDLPF CKGDVLTIVA VTKDPNWYKA
60 70 80 90 100
KNKVGREGII PANYVQKREG VKAGTKLSLM PWFHGKITRE QAERLLYPPE
110 120 130 140 150
TGLFLVREST NYPGDYTLCV SCEGKVEHYR IMYHASKLSI DEEVYFENLM
160 170 180 190 200
QLVEHYTTDA DGLCTRLIKP KVMEGTVAAQ DEFYRSGWAL NMKELKLLQT
210 220 230 240 250
IGKGEFGDVM LGDYRGNKVA VKCIKNDATA QAFLAEASVM TQLRHSNLVQ
260 270 280 290 300
LLGVIVEEKG GLYIVTEYMA KGSLVDYLRS RGRSVLGGDC LLKFSLDVCE
310 320 330 340 350
AMEYLEGNNF VHRDLAARNV LVSEDNVAKV SDFGLTKEAS STQDTGKLPV
360 370 380 390 400
KWTAPEALRE KKFSTKSDVW SFGILLWEIY SFGRVPYPRI PLKDVVPRVE
410 420 430 440 450
KGYKMDAPDG CPPAVYDVMK NCWHLDAATR PTFLQLREQL EHIRTHELHL
Length:450
Mass (Da):50,746
Last modified:October 1, 1993 - v1
Checksum:i393DC8D737DAC67A
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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_006243164.2.
UniGeneiRn.2759.

Genome annotation databases

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

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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_006243164.2.
UniGeneiRn.2759.

3D structure databases

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

Protein-protein interaction databases

BioGridi261119. 3 interactions.
IntActiP32577. 2 interactions.
MINTiMINT-1535121.
STRINGi10116.ENSRNOP00000026358.

Chemistry

BindingDBiP32577.
ChEMBLiCHEMBL4365.

PTM databases

PhosphoSiteiP32577.

Proteomic databases

PaxDbiP32577.
PRIDEiP32577.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi1445.
RGDi1308800. Csk.

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00760000119011.
HOGENOMiHOG000233858.
HOVERGENiHBG008761.
InParanoidiP32577.
KOiK05728.
OMAiVWPSGTE.
OrthoDBiEOG7SV0V5.
PhylomeDBiP32577.
TreeFamiTF351634.

Enzyme and pathway databases

BRENDAi2.7.10.2. 5301.
ReactomeiREACT_272857. GAB1 signalosome.
REACT_314992. Integrin alphaIIb beta3 signaling.
REACT_316530. Phosphorylation of CD3 and TCR zeta chains.
REACT_352796. PD-1 signaling.

Miscellaneous databases

EvolutionaryTraceiP32577.
NextBioi669700.
PROiP32577.

Gene expression databases

GenevisibleiP32577. RN.

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]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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: June 24, 2015
This is version 152 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

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 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.