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P32577 (CSK_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 142. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | 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:
Tyrosine-protein kinase CSK

EC=2.7.10.2
Alternative name(s):
C-Src kinase
Gene names
Name:Csk
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length450 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 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. Ref.3 Ref.4

Catalytic activity

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

Subunit structure

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. Ref.5 Ref.6

Subcellular location

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

Tissue specificity

Enriched in lymphoid tissues.

Domain

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.

Post-translational modification

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

Sequence similarities

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

Contains 1 protein kinase domain.

Contains 1 SH2 domain.

Contains 1 SH3 domain.

Ontologies

Keywords
   Biological processAdaptive immunity
Immunity
   Cellular componentCell membrane
Cytoplasm
Membrane
   DomainSH2 domain
SH3 domain
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Transferase
Tyrosine-protein kinase
   PTMAcetylation
Phosphoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processadherens junction organization

Inferred from expression pattern PubMed 15389520. Source: RGD

brain development

Inferred from expression pattern PubMed 7529760. Source: RGD

cellular response to peptide hormone stimulus

Inferred from direct assay PubMed 17071733. Source: RGD

immune system process

Inferred from electronic annotation. Source: UniProtKB-KW

negative regulation of ERK1 and ERK2 cascade

Inferred from direct assay PubMed 9325302. Source: RGD

negative regulation of Golgi to plasma membrane protein transport

Inferred from electronic annotation. Source: Ensembl

negative regulation of bone resorption

Inferred from direct assay PubMed 10411542. Source: RGD

negative regulation of cell proliferation

Inferred from direct assay PubMed 10411542. Source: RGD

negative regulation of interleukin-6 production

Inferred from direct assay PubMed 10411542. Source: RGD

negative regulation of kinase activity

Inferred from direct assay PubMed 10411542. Source: RGD

negative regulation of low-density lipoprotein particle clearance

Inferred from direct assay PubMed 10884975. Source: RGD

negative regulation of phagocytosis

Inferred from direct assay PubMed 10884975. Source: RGD

oligodendrocyte differentiation

Inferred from expression pattern PubMed 15504915. Source: RGD

peptidyl-tyrosine phosphorylation

Inferred from direct assay PubMed 7683130. Source: GOC

positive regulation of MAP kinase activity

Inferred from direct assay PubMed 10884975. Source: RGD

protein autophosphorylation

Inferred from direct assay PubMed 7683130. Source: RGD

protein phosphorylation

Inferred from direct assay PubMed 7683130. Source: RGD

regulation of Fc receptor mediated stimulatory signaling pathway

Inferred from direct assay PubMed 9325302. Source: RGD

   Cellular_componentGolgi apparatus

Inferred from electronic annotation. Source: Ensembl

cell-cell junction

Inferred from electronic annotation. Source: Ensembl

centrosome

Inferred from electronic annotation. Source: Ensembl

cytoplasm

Inferred from direct assay PubMed 10411542. Source: RGD

membrane raft

Inferred from direct assay PubMed 15322113. Source: RGD

plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

non-membrane spanning protein tyrosine kinase activity

Inferred from electronic annotation. Source: UniProtKB-EC

proline-rich region binding

Inferred from physical interaction PubMed 8890164. Source: BHF-UCL

protein phosphatase binding

Inferred from physical interaction PubMed 8890164. Source: BHF-UCL

protein tyrosine kinase activity

Inferred from direct assay PubMed 7683130. Source: RGD

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 450449Tyrosine-protein kinase CSK
PRO_0000088072

Regions

Domain9 – 7062SH3
Domain82 – 17190SH2
Domain195 – 445251Protein kinase
Nucleotide binding201 – 2099ATP By similarity
Region9 – 7062Interaction with PTPN8 By similarity

Sites

Active site3141Proton acceptor By similarity
Binding site2221ATP By similarity

Amino acid modifications

Modified residue21N-acetylserine By similarity
Modified residue1841Phosphotyrosine By similarity
Modified residue3041Phosphotyrosine By similarity
Modified residue3641Phosphoserine; by PKA By similarity
Modified residue4161Phosphotyrosine

Secondary structure

........................................................................... 450
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P32577 [UniParc].

Last modified October 1, 1993. Version 1.
Checksum: 393DC8D737DAC67A

FASTA45050,746
        10         20         30         40         50         60 
MSAIQASWPS GTECIAKYNF HGTAEQDLPF CKGDVLTIVA VTKDPNWYKA KNKVGREGII 

        70         80         90        100        110        120 
PANYVQKREG VKAGTKLSLM PWFHGKITRE QAERLLYPPE TGLFLVREST NYPGDYTLCV 

       130        140        150        160        170        180 
SCEGKVEHYR IMYHASKLSI DEEVYFENLM QLVEHYTTDA DGLCTRLIKP KVMEGTVAAQ 

       190        200        210        220        230        240 
DEFYRSGWAL NMKELKLLQT IGKGEFGDVM LGDYRGNKVA VKCIKNDATA QAFLAEASVM 

       250        260        270        280        290        300 
TQLRHSNLVQ LLGVIVEEKG GLYIVTEYMA KGSLVDYLRS RGRSVLGGDC LLKFSLDVCE 

       310        320        330        340        350        360 
AMEYLEGNNF VHRDLAARNV LVSEDNVAKV SDFGLTKEAS STQDTGKLPV KWTAPEALRE 

       370        380        390        400        410        420 
KKFSTKSDVW SFGILLWEIY SFGRVPYPRI PLKDVVPRVE KGYKMDAPDG CPPAVYDVMK 

       430        440        450 
NCWHLDAATR PTFLQLREQL EHIRTHELHL 

« Hide

References

« Hide 'large scale' references
[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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X58631 mRNA. Translation: CAA41484.1.
BC098863 mRNA. Translation: AAH98863.1.
PIRS15094.
RefSeqNP_001025210.1. NM_001030039.1.
XP_006243225.1. XM_006243163.1.
XP_006243226.1. XM_006243164.1.
XP_006243227.1. XM_006243165.1.
UniGeneRn.2759.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1K9AX-ray2.50A/B/C/D/E/F1-450[»]
2RSYNMR-A80-173[»]
ProteinModelPortalP32577.
SMRP32577. Positions 6-450.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid261119. 2 interactions.
IntActP32577. 2 interactions.
MINTMINT-1535121.
STRING10116.ENSRNOP00000026358.

Chemistry

BindingDBP32577.
ChEMBLCHEMBL4365.

PTM databases

PhosphoSiteP32577.

Proteomic databases

PaxDbP32577.
PRIDEP32577.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000026358; ENSRNOP00000026358; ENSRNOG00000019374.
GeneID315707.
KEGGrno:315707.
UCSCRGD:1308800. rat.

Organism-specific databases

CTD1445.
RGD1308800. Csk.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00750000117264.
HOGENOMHOG000233858.
HOVERGENHBG008761.
InParanoidP32577.
KOK05728.
OMAERLLCPP.
OrthoDBEOG7SV0V5.
PhylomeDBP32577.
TreeFamTF351634.

Enzyme and pathway databases

BRENDA2.7.10.2. 5301.

Gene expression databases

GenevestigatorP32577.

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.
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

EvolutionaryTraceP32577.
NextBio669700.
PROP32577.

Entry information

Entry nameCSK_RAT
AccessionPrimary (citable) accession number: P32577
Secondary accession number(s): Q4G003
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1993
Last sequence update: October 1, 1993
Last modified: April 16, 2014
This is version 142 of the entry and version 1 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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references