Tyrosine-protein kinase CSK - Rattus norvegicus (Rat)

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P32577 (CSK_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified May 29, 2013. Version 133. History...

Clusters with 100%, 90%, 50% identity |

Documents (2) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended name:
Tyrosine-protein kinase CSK
EC=2.7.10.2

Alternative name(s):
C-Src kinase

Gene names

Name:

Csk

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	450 AA.
Sequence status	Complete.
Protein existence	Evidence 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 process	Adaptive immunity Immunity
Cellular component	Cell membrane Cytoplasm Membrane
Domain	SH2 domain SH3 domain
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Transferase Tyrosine-protein kinase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	adherens 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 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: Compara 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 positive regulation of MAP kinase activity Inferred from direct assay PubMed 10884975. Source: RGD protein autophosphorylation 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_component	Golgi apparatus Inferred from electronic annotation. Source: Compara cell-cell junction Inferred from electronic annotation. Source: Compara centrosome Inferred from electronic annotation. Source: Compara 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_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW non-membrane spanning protein tyrosine kinase activity Inferred from electronic annotation. Source: EC protein tyrosine kinase activity Inferred from direct assay PubMed 7683130. Source: RGD
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 450

450

Tyrosine-protein kinase CSK

PRO_0000088072

Regions

Domain

9 – 70

SH3

Domain

82 – 171

SH2

Domain

195 – 445

251

Protein kinase

Nucleotide binding

201 – 209

ATP By similarity

Region

9 – 70

Interaction with PTPN8 By similarity

Sites

Active site

314

Proton acceptor By similarity

Binding site

222

ATP By similarity

Amino acid modifications

Modified residue

184

Phosphotyrosine By similarity

Modified residue

304

Phosphotyrosine By similarity

Modified residue

364

Phosphoserine; by PKA By similarity

Modified residue

416

Phosphotyrosine

Secondary structure

450

Helix Strand Turn

Details...

Sequences

Sequence

Length

Mass (Da)

Tools

P32577 [UniParc].

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

FASTA

450

50,746

        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' referencesShow '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.

IPI

IPI00188950.

PIR

S15094.

RefSeq

NP_001025210.1. NM_001030039.1.

UniGene

Rn.2759.

3D structure databases

PDBe
RCSB PDB
PDBj

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	[»]

ProteinModelPortal

P32577.

SMR

P32577. Positions 6-450.

ModBase

Search...

Protein-protein interaction databases

MINT

MINT-1535121.

STRING

10116.ENSRNOP00000026358.

PTM databases

PhosphoSite

P32577.

Proteomic databases

PaxDb

P32577.

PRIDE

P32577.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSRNOT00000026358; ENSRNOP00000026358; ENSRNOG00000019374.

GeneID

315707.

KEGG

rno:315707.

UCSC

RGD:1308800. rat.

Organism-specific databases

CTD

1445.

RGD

1308800. Csk.

Phylogenomic databases

eggNOG

COG0515.

GeneTree

ENSGT00600000084126.

HOGENOM

HOG000233858.

HOVERGEN

HBG008761.

InParanoid

P32577.

K05728.

OMA

QDEFFRS.

OrthoDB

EOG44BB23.

Enzyme and pathway databases

BRENDA

2.7.10.2. 5301.

Gene expression databases

Genevestigator

P32577.

GermOnline

ENSRNOG00000019374. Rattus norvegicus.

Family and domain databases

Gene3D

3.30.505.10. 1 hit.

InterPro

IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_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]

Pfam

PF07714. Pkinase_Tyr. 1 hit.
PF00017. SH2. 1 hit.
PF00018. SH3_1. 1 hit.
[Graphical view]

PRINTS

PR00401. SH2DOMAIN.
PR00109. TYRKINASE.

SMART

SM00252. SH2. 1 hit.
SM00326. SH3. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]

SUPFAM

SSF56112. Kinase_like. 1 hit.
SSF50044. SH3. 1 hit.

PROSITE

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]

ProtoNet

Search...

Other

BindingDB

P32577.

ChEMBL

CHEMBL4365.

EvolutionaryTrace

P32577.

NextBio

669700.

Entry information

Entry name

CSK_RAT

Accession

Primary (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:	May 29, 2013
This is version 133 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Relevant documents

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Secondary structure

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents