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P41241 (CSK_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 146. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | 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
Protein-tyrosine kinase MPK-2
p50CSK
Gene names
Name:Csk
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

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.

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 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 electronic annotation. Source: Ensembl

brain development

Inferred from electronic annotation. Source: Ensembl

cellular response to peptide hormone stimulus

Inferred from electronic annotation. Source: Ensembl

immune system process

Inferred from electronic annotation. Source: UniProtKB-KW

intracellular signal transduction

Traceable author statement Ref.11. Source: HGNC

negative regulation of ERK1 and ERK2 cascade

Inferred from electronic annotation. Source: Ensembl

negative regulation of Golgi to plasma membrane protein transport

Inferred from electronic annotation. Source: Ensembl

negative regulation of bone resorption

Inferred from electronic annotation. Source: Ensembl

negative regulation of cell proliferation

Inferred from mutant phenotype PubMed 15861137. Source: MGI

negative regulation of interleukin-6 production

Inferred from electronic annotation. Source: Ensembl

negative regulation of kinase activity

Inferred from electronic annotation. Source: Ensembl

negative regulation of low-density lipoprotein particle clearance

Inferred from electronic annotation. Source: Ensembl

negative regulation of phagocytosis

Inferred from electronic annotation. Source: Ensembl

oligodendrocyte differentiation

Inferred from electronic annotation. Source: Ensembl

peptidyl-tyrosine phosphorylation

Traceable author statement Ref.11. Source: GOC

positive regulation of MAP kinase activity

Inferred from electronic annotation. Source: Ensembl

protein autophosphorylation

Inferred from electronic annotation. Source: Ensembl

protein phosphorylation

Traceable author statement Ref.11. Source: HGNC

regulation of Fc receptor mediated stimulatory signaling pathway

Inferred from electronic annotation. Source: Ensembl

regulation of T cell activation

Traceable author statement Ref.11. Source: HGNC

   Cellular_componentGolgi apparatus

Inferred from electronic annotation. Source: Ensembl

cell-cell junction

Inferred from direct assay PubMed 15861137. Source: MGI

centrosome

Inferred from electronic annotation. Source: Ensembl

membrane raft

Inferred from electronic annotation. Source: Ensembl

plasma membrane

Traceable author statement Ref.11. Source: HGNC

   Molecular_functionATP binding

Traceable author statement Ref.11. Source: HGNC

non-membrane spanning protein tyrosine kinase activity

Inferred from electronic annotation. Source: UniProtKB-EC

protein binding

Inferred from physical interaction Ref.11. Source: HGNC

protein tyrosine kinase activity

Traceable author statement Ref.11. Source: HGNC

transferase activity

Traceable author statement Ref.11. Source: HGNC

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 450449Tyrosine-protein kinase CSK
PRO_0000088071

Regions

Domain9 – 7062SH3
Domain82 – 17190SH2
Domain195 – 449255Protein kinase
Nucleotide binding201 – 2099ATP By similarity
Region9 – 7062Interaction with PTPN8

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

Experimental info

Sequence conflict2991C → L in AAA18766. Ref.1
Sequence conflict4171E → D in AAA18766. Ref.1
Sequence conflict4231W → S in AAA18766. Ref.1

Secondary structure

........... 450
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P41241 [UniParc].

Last modified July 27, 2011. Version 2.
Checksum: E8D3EC9357B86277

FASTA45050,716
        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 

« Hide

References

« Hide '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] [Europe PMC] [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. expand/collapse author list , 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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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, IDENTIFICATION BY 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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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.
CCDSCCDS23228.1.
PIRI48929.
RefSeqNP_031809.2. NM_007783.2.
XP_006510864.1. XM_006510801.1.
XP_006510865.1. XM_006510802.1.
XP_006510866.1. XM_006510803.1.
UniGeneMm.21974.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1JEGNMR-A1-83[»]
ProteinModelPortalP41241.
SMRP41241. Positions 4-450.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid198936. 9 interactions.
IntActP41241. 6 interactions.
MINTMINT-1345201.

Chemistry

BindingDBP41241.

PTM databases

PhosphoSiteP41241.

Proteomic databases

MaxQBP41241.
PaxDbP41241.
PRIDEP41241.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000034863; ENSMUSP00000034863; ENSMUSG00000032312.
GeneID12988.
KEGGmmu:12988.
UCSCuc009pvk.1. mouse.

Organism-specific databases

CTD1445.
MGIMGI:88537. Csk.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00750000117264.
HOGENOMHOG000233858.
HOVERGENHBG008761.
InParanoidQ8VCW1.
KOK05728.
OMAERLLCPP.
OrthoDBEOG7SV0V5.
TreeFamTF351634.

Enzyme and pathway databases

BRENDA2.7.10.2. 3474.

Gene expression databases

BgeeP41241.
CleanExMM_CSK.
GenevestigatorP41241.

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

EvolutionaryTraceP41241.
NextBio282780.
PROP41241.
SOURCESearch...

Entry information

Entry nameCSK_MOUSE
AccessionPrimary (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: July 9, 2014
This is version 146 of the entry and version 2 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

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot