Tyrosine-protein kinase CSK - Mus musculus (Mouse)

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Reviewed, UniProtKB/Swiss-Prot P41241 (CSK_MOUSE)

Last modified February 9, 2010. Version 104. History...

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein names

Recommended name:
    Tyrosine-protein kinase CSK
    EC=2.7.10.2
Alternative name(s):
    C-Src kinase
    Protein-tyrosine kinase MPK-2
    p50CSK

Gene names

Name:

Csk

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

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

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Protein attributes

Sequence length	450 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

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General annotation (Comments)

Function	Specifically phosphorylates 'Tyr-504' on LCK, which acts as a negative regulatory site. Can also act on the LYN and FYN kinases.
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Subunit structure	Interacts with phosphorylated SIT1 and LIME1 By similarity. Interacts with PTPN8. Interacts with phosphorylated PAG1 and TGFB1I1. Ref.4 Ref.5 Ref.6 Ref.7 Ref.8
Subcellular location	Cytoplasm. Cell membrane. Note: Mainly cytoplasmic, also present in lipid rafts. Ref.8
Tissue specificity	Ubiquitous, but most abundant in thymus and spleen, as well as in neonatal brain.
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.

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Ontologies

Keywords
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 Direct protein sequencing
Gene Ontology (GO)
Biological process	intracellular signaling cascade Ref.7 Traceable author statement. Source: HGNC negative regulation of cell proliferation Inferred from genetic interaction. Source: MGI protein amino acid phosphorylation Ref.7 Traceable author statement. Source: HGNC regulation of T cell activation Ref.7 Traceable author statement. Source: HGNC
Cellular component	cell-cell junction Inferred from direct assay. Source: MGI cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ATP binding Ref.7 Traceable author statement. Source: HGNC non-membrane spanning protein tyrosine kinase activity Inferred from electronic annotation. Source: EC protein binding Ref.7 Inferred from physical interaction. Source: HGNC
Complete GO annotation...

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 450

450

Tyrosine-protein kinase CSK

PRO_0000088071

Regions

Domain

9 – 70

SH3

Domain

82 – 171

SH2

Domain

195 – 449

255

Protein kinase

Nucleotide binding

201 – 209

ATP By similarity

Region

9 – 70

Interaction with PTPN8

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

416

Phosphotyrosine; by autocatalysis By similarity

Secondary structure

450

Helix Strand Turn

Details...

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Sequences

Sequence

Length

Mass (Da)

Tools

P41241-1 [UniParc].

Last modified February 1, 1995. Version 1.
Checksum: D1B22772A7F3928C
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FASTA

450

50,613

        10         20         30         40         50         60 
MSAIQAAWPS 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 LLKFSLDVLE 

       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 
NCSHLDAATR PTFLQLREQL EHIKTHELHL

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References

[1]	"Ctk: a protein-tyrosine kinase related to Csk that defines an enzyme family." Klages S., Adam D., Class K., Fargnoli J., Bolen J.B., Penhallow R.C. Proc. Natl. Acad. Sci. U.S.A. 91:2597-2601(1994) [PubMed: 7511815] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[2]	"An Eph-related receptor protein tyrosine kinase gene segmentally expressed in the developing mouse hindbrain." Gilardi-Hebenstreit P., Nieto M.A., Frain M., Mattei M.-G., Chestier A., Wilkinson D.G., Charnay P. Oncogene 7:2499-2506(1992) [PubMed: 1281307] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 316-367. Strain: C57BL/6. Tissue: Embryonic brain.
[3]	Lubec G., Sunyer B., Chen W.-Q. Submitted (JAN-2009) to UniProtKB Cited for: PROTEIN SEQUENCE OF 338-347, MASS SPECTROMETRY. Strain: OF1. Tissue: Hippocampus.
[4]	"Association of inhibitory tyrosine protein kinase p50csk with protein tyrosine phosphatase PEP in T cells and other hemopoietic cells." Cloutier J.-F., Veillette A. EMBO J. 15:4909-4918(1996) [PubMed: 8890164] [Abstract] Cited for: INTERACTION WITH PTPN8.
[5]	"Characterization of a focal adhesion protein, Hic-5, that shares extensive homology with paxillin." Thomas S.M., Hagel M., Turner C.E. J. Cell Sci. 112:181-190(1999) [PubMed: 9858471] [Abstract] Cited for: INTERACTION WITH TGFB1I1.
[6]	"Fyn is essential for tyrosine phosphorylation of Csk-binding protein/phosphoprotein associated with glycolipid-enriched microdomains in lipid rafts in resting T cells." Yasuda K., Nagafuku M., Shima T., Okada M., Yagi T., Yamada T., Minaki Y., Kato A., Tani-Ichi S., Hamaoka T., Kosugi A. J. Immunol. 169:2813-2817(2002) [PubMed: 12218089] [Abstract] Cited for: INTERACTION WITH PAG1.
[7]	"Phosphorylation-dependent regulation of T-cell activation by PAG/Cbp, a lipid raft-associated transmembrane adaptor." Davidson D., Bakinowski M., Thomas M.L., Horejsi V., Veillette A. Mol. Cell. Biol. 23:2017-2028(2003) [PubMed: 12612075] [Abstract] Cited for: INTERACTION WITH PAG1.
[8]	"Cbp deficiency alters Csk localization in lipid rafts but does not affect T-cell development." Xu S., Huo J., Tan J.E.-L., Lam K.-P. Mol. Cell. Biol. 25:8486-8495(2005) [PubMed: 16166631] [Abstract] Cited for: INTERACTION WITH PAG1, SUBCELLULAR LOCATION.
+	Additional computationally mapped references.

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Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U05247 mRNA. Translation: AAA18766.1.
X57242 mRNA. Translation: CAA40518.1.

IPI

IPI00112648.

PIR

I48929.

UniGene

Mm.21974
Mm.470150

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1JEG	NMR	-	A	1-83	[»]

SMR

P41241. Positions 6-450.

ModBase

Search...

Protein-protein interaction databases

STRING

P41241.

PTM databases

PhosphoSite

P41241.

Proteomic databases

PRIDE

P41241.

Genome annotation databases

Ensembl

ENSMUST00000034863; ENSMUSP00000034863; ENSMUSG00000032312; Mus musculus. [Genome view]

Organism-specific databases

MGI

MGI:88537. Csk.

Phylogenomic databases

eggNOG

roNOG05100.

HOGENOM

HBG755340.

HOVERGEN

P41241.

InParanoid

P41241.

Enzyme and pathway databases

BRENDA

2.7.10.2. 244.

Gene expression databases

ArrayExpress

P41241.

Bgee

P41241.

CleanEx

MM_CSK.

Genevestigator

P41241.

GermOnline

ENSMUSG00000032312. Mus musculus.

Family and domain databases

InterPro

IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR000980. SH2.
IPR001452. SH3_domain.
IPR015778. Tyr_kinase_non-rcpt_Csk.
IPR020635. Tyr_Pkinase_cat_dom.
IPR020685. Tyr_prot_kinase.
IPR008266. Tyr_prot_kinase_AS.
[Graphical view]

Gene3D

G3DSA:3.30.505.10. SH2. 1 hit.

PANTHER

PTHR23256:SF264. Csk_ProtTyrKin. 1 hit.
PTHR23256. Tyr_prot_kinase. 1 hit.

Pfam

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

PRINTS

PR00401. SH2DOMAIN.

SMART

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

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 Resources

SOURCE

Search...

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Entry information

Entry name

CSK_MOUSE

Accession

Primary (citable) accession number: P41241
Secondary accession number(s): Q03143

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1995
Last sequence update:	February 1, 1995
Last modified:	February 9, 2010
This is version 104 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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