P41241 (CSK_MOUSE) Reviewed, UniProtKB/Swiss-Prot

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 › Mus

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.
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.8 Ref.9 Ref.10 Ref.11 Ref.12
Subcellular location	Cytoplasm. Cell membrane. Note: Mainly cytoplasmic, also present in lipid rafts. Ref.12
Tissue specificity	Ubiquitous, but most abundant in thymus and spleen, as well as in neonatal brain.
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.
Disruption phenotype	Mice die between day 9 and day 10 of gestation with several defects including a non-functional neural tube. SRC and FYN kinases show increased activity when CSK is missing. Ref.7
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	intracellular signal transduction Traceable author statement Ref.11. Source: HGNC negative regulation of cell proliferation Inferred from mutant phenotype. Source: MGI regulation of T cell activation Traceable author statement Ref.11. Source: HGNC
Cellular component	cell-cell junction Inferred from direct assay. Source: MGI plasma membrane Traceable author statement Ref.11. Source: HGNC
Molecular function	ATP binding Traceable author statement Ref.11. Source: HGNC non-membrane spanning protein tyrosine kinase activity Inferred from electronic annotation. Source: EC
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_0000088071

Regions

Domain

9 – 70

62

SH3

Domain

82 – 171

90

SH2

Domain

195 – 449

255

Protein kinase

Nucleotide binding

201 – 209

9

ATP By similarity

Region

9 – 70

62

Interaction with PTPN8

Sites

Active site

314

1

Proton acceptor By similarity

Binding site

222

1

ATP By similarity

Amino acid modifications

Modified residue

184

1

Phosphotyrosine By similarity

Modified residue

364

1

Phosphoserine; by PKA By similarity

Modified residue

416

1

Phosphotyrosine

Experimental info

Sequence conflict

299

1

C → L in AAA18766. Ref.1

Sequence conflict

417

1

E → D in AAA18766. Ref.1

Sequence conflict

423

1

W → S in AAA18766. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

450

Helix Strand Turn

Details...

Beta strand

13 – 18

6

Beta strand

35 – 41

7

Beta strand

43 – 51

9

Beta strand

57 – 61

5

Helix

62 – 64

3

Beta strand

65 – 67

3

Sequences

	Sequence		Length	Mass (Da)
	P41241 [UniParc]. Last modified July 27, 2011. Version 2. Checksum: E8D3EC9357B86277	FASTA	450	50,716
	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 LLKFSLDVCE 310 320 330 340 350 360 AMEYLEGNNF VHRDLAARNV LVSEDNVAKV SDFGLTKEAS STQDTGKLPV KWTAPEALRE 370 380 390 400 410 420 KKFSTKSDVW SFGILLWEIY SFGRVPYPRI PLKDVVPRVE KGYKMDAPDG CPPAVYEVMK 430 440 450 NCWHLDAATR PTFLQLREQL EHIKTHELHL

References

	« Hide 'large scale' referencesShow 'large scale' 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]	"Characterization of quantitative trait loci influencing growth and adiposity using congenic mouse strains." Farber C.R., Corva P.M., Medrano J.F. Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: CAST/Ei. Tissue: Brain.
[3]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: NOD. Tissue: Spleen.
[4]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6 and FVB/N. Tissue: Brain and Colon.
[5]	"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.
[6]	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.
[7]	"Disruption of the csk gene, encoding a negative regulator of Src family tyrosine kinases, leads to neural tube defects and embryonic lethality in mice." Imamoto A., Soriano P. Cell 73:1117-1124(1993) [PubMed: 7685657] [Abstract] Cited for: DISRUPTION PHENOTYPE.
[8]	"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.
[9]	"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.
[10]	"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.
[11]	"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.
[12]	"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.
[13]	"A novel, specific interaction involving the Csk SH3 domain and its natural ligand." Ghose R., Shekhtman A., Goger M.J., Ji H., Cowburn D. Nat. Struct. Biol. 8:998-1004(2001) [PubMed: 11685249] [Abstract] Cited for: STRUCTURE BY NMR OF 1-83.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U05247 mRNA. Translation: AAA18766.1.
AY902339 Genomic DNA. Translation: AAX90624.1.
AK156058 mRNA. Translation: BAE33565.1.
AK170815 mRNA. Translation: BAE42047.1.
BC018394 mRNA. Translation: AAH18394.1.
BC052006 mRNA. Translation: AAH52006.2.
X57242 mRNA. Translation: CAA40518.1.

IPI

IPI00112648.

PIR

I48929.

RefSeq

NP_031809.2. NM_007783.2.

UniGene

Mm.21974.
Mm.470150.

3D structure databases

PDBe
RCSB PDB
PDBj

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

ProteinModelPortal

P41241.

SMR

P41241. Positions 4-450.

ModBase

Search...

Protein-protein interaction databases

IntAct

P41241. 3 interactions.

MINT

MINT-1345201.

STRING

P41241.

PTM databases

PhosphoSite

P41241.

Proteomic databases

PRIDE

P41241.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000034863; ENSMUSP00000034863; ENSMUSG00000032312.

GeneID

12988.

KEGG

mmu:12988.

Organism-specific databases

CTD

1445.

MGI

MGI:88537. Csk.

Phylogenomic databases

eggNOG

roNOG05100.

GeneTree

ENSGT00600000084126.

HOGENOM

HBG755340.

HOVERGEN

HBG008761.

InParanoid

P41241.

OrthoDB

EOG44BB23.

Enzyme and pathway databases

BRENDA

2.7.10.2. 3474.

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.
IPR001245. Ser-Thr/Tyr_kinase.
IPR000980. SH2.
IPR001452. SH3_domain.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
[Graphical view]

Gene3D

G3DSA:3.30.505.10. SH2. 1 hit.

KO

K05728.

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

NextBio

282780.

SOURCE

Search...

Entry information

Entry name

CSK_MOUSE

Accession

Primary (citable) accession number: P41241
Secondary accession number(s): Q03143, Q80WU4, Q8VCW1

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1995
Last sequence update:	July 27, 2011
Last modified:	January 25, 2012
This is version 122 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program