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Protein

Tyrosine-protein kinase CSK

Gene

Csk

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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).By similarity

Catalytic activityi

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotationBy similarity

Cofactori

Mg2+By similarity, Mn2+By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei222ATPPROSITE-ProRule annotation1
Active sitei314Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi201 – 209ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: HGNC
  • identical protein binding Source: MGI
  • metal ion binding Source: UniProtKB-KW
  • non-membrane spanning protein tyrosine kinase activity Source: GO_Central
  • proline-rich region binding Source: Ensembl
  • protein kinase A catalytic subunit binding Source: MGI
  • protein phosphatase binding Source: Ensembl
  • protein tyrosine kinase activity Source: UniProtKB
  • receptor binding Source: GO_Central
  • transferase activity Source: HGNC

GO - Biological processi

Keywordsi

Molecular functionKinase, Transferase, Tyrosine-protein kinase
Biological processAdaptive immunity, Immunity
LigandATP-binding, Magnesium, Manganese, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.10.2 3474
ReactomeiR-MMU-180292 GAB1 signalosome
R-MMU-202427 Phosphorylation of CD3 and TCR zeta chains
R-MMU-354192 Integrin alphaIIb beta3 signaling
R-MMU-389948 PD-1 signaling
R-MMU-5674135 MAP2K and MAPK activation

Names & Taxonomyi

Protein namesi
Recommended name:
Tyrosine-protein kinase CSK (EC:2.7.10.2By similarity)
Alternative name(s):
C-Src kinase
Protein-tyrosine kinase MPK-2
p50CSK
Gene namesi
Name:Csk
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 9

Organism-specific databases

MGIiMGI:88537 Csk

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Disruption phenotypei

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.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00000880712 – 450Tyrosine-protein kinase CSKAdd BLAST449

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylserineBy similarity1
Modified residuei184PhosphotyrosineBy similarity1
Modified residuei304PhosphotyrosineBy similarity1
Modified residuei364Phosphoserine; by PKABy similarity1
Modified residuei416Phosphotyrosine; by autocatalysisBy similarity1

Post-translational modificationi

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

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP41241
MaxQBiP41241
PaxDbiP41241
PeptideAtlasiP41241
PRIDEiP41241

PTM databases

iPTMnetiP41241
PhosphoSitePlusiP41241

Expressioni

Tissue specificityi

Ubiquitous, but most abundant in thymus and spleen, as well as in neonatal brain.

Gene expression databases

BgeeiENSMUSG00000032312
CleanExiMM_CSK
ExpressionAtlasiP41241 baseline and differential
GenevisibleiP41241 MM

Interactioni

Subunit structurei

Homodimer (via SH3-domain) (By similarity). Interacts with PTPN22 (PubMed:8890164). 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 (PubMed:9858471, PubMed:12218089, PubMed:12612075, PubMed:16166631). Interacts with SRCIN1 (By similarity). Interacts with RHOH (By similarity). Interacts (via SH2 domain) with SCIMP (By similarity).By similarity5 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi19893633 interactors.
CORUMiP41241
IntActiP41241 37 interactors.
MINTiP41241
STRINGi10090.ENSMUSP00000034863

Structurei

Secondary structure

1450
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi13 – 18Combined sources6
Beta strandi35 – 41Combined sources7
Beta strandi43 – 51Combined sources9
Beta strandi57 – 61Combined sources5
Helixi62 – 64Combined sources3
Beta strandi65 – 67Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1JEGNMR-A1-83[»]
ProteinModelPortaliP41241
SMRiP41241
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP41241

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini9 – 70SH3PROSITE-ProRule annotationAdd BLAST62
Domaini82 – 171SH2PROSITE-ProRule annotationAdd BLAST90
Domaini195 – 449Protein kinasePROSITE-ProRule annotationAdd BLAST255

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni9 – 70Interaction with PTPN221 PublicationAdd BLAST62

Domaini

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

Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family. CSK subfamily.PROSITE-ProRule annotation

Keywords - Domaini

SH2 domain, SH3 domain

Phylogenomic databases

eggNOGiKOG0197 Eukaryota
COG0515 LUCA
GeneTreeiENSGT00760000119011
HOGENOMiHOG000233858
HOVERGENiHBG008761
InParanoidiP41241
KOiK05728
OMAiWALNMKD
OrthoDBiEOG091G05PB
TreeFamiTF351634

Family and domain databases

CDDicd09937 SH2_csk_like, 1 hit
Gene3Di3.30.505.101 hit
InterProiView protein in InterPro
IPR035026 CSK
IPR035027 Csk-like_SH2
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR001245 Ser-Thr/Tyr_kinase_cat_dom
IPR000980 SH2
IPR036860 SH2_dom_sf
IPR036028 SH3-like_dom_sf
IPR001452 SH3_domain
IPR008266 Tyr_kinase_AS
IPR020635 Tyr_kinase_cat_dom
PANTHERiPTHR24418:SF307 PTHR24418:SF307, 1 hit
PfamiView protein in Pfam
PF07714 Pkinase_Tyr, 1 hit
PF00017 SH2, 1 hit
PF00018 SH3_1, 1 hit
PRINTSiPR00401 SH2DOMAIN
PR00109 TYRKINASE
SMARTiView protein in SMART
SM00252 SH2, 1 hit
SM00326 SH3, 1 hit
SM00219 TyrKc, 1 hit
SUPFAMiSSF50044 SSF50044, 1 hit
SSF55550 SSF55550, 1 hit
SSF56112 SSF56112, 1 hit
PROSITEiView protein in 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

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P41241-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSAIQAAWPS GTECIAKYNF HGTAEQDLPF CKGDVLTIVA VTKDPNWYKA
60 70 80 90 100
KNKVGREGII PANYVQKREG VKAGTKLSLM PWFHGKITRE QAERLLYPPE
110 120 130 140 150
TGLFLVREST NYPGDYTLCV SCEGKVEHYR IMYHASKLSI DEEVYFENLM
160 170 180 190 200
QLVEHYTTDA DGLCTRLIKP KVMEGTVAAQ DEFYRSGWAL NMKELKLLQT
210 220 230 240 250
IGKGEFGDVM LGDYRGNKVA VKCIKNDATA QAFLAEASVM TQLRHSNLVQ
260 270 280 290 300
LLGVIVEEKG GLYIVTEYMA KGSLVDYLRS RGRSVLGGDC LLKFSLDVCE
310 320 330 340 350
AMEYLEGNNF VHRDLAARNV LVSEDNVAKV SDFGLTKEAS STQDTGKLPV
360 370 380 390 400
KWTAPEALRE KKFSTKSDVW SFGILLWEIY SFGRVPYPRI PLKDVVPRVE
410 420 430 440 450
KGYKMDAPDG CPPAVYEVMK NCWHLDAATR PTFLQLREQL EHIKTHELHL
Length:450
Mass (Da):50,716
Last modified:July 27, 2011 - v2
Checksum:iE8D3EC9357B86277
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti299C → L in AAA18766 (PubMed:7511815).Curated1
Sequence conflicti417E → D in AAA18766 (PubMed:7511815).Curated1
Sequence conflicti423W → S in AAA18766 (PubMed:7511815).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS23228.1
PIRiI48929
RefSeqiNP_001291690.1, NM_001304761.1
NP_031809.2, NM_007783.3
XP_006510864.1, XM_006510801.3
XP_006510865.1, XM_006510802.3
UniGeneiMm.21974

Genome annotation databases

EnsembliENSMUST00000034863; ENSMUSP00000034863; ENSMUSG00000032312
ENSMUST00000215396; ENSMUSP00000150590; ENSMUSG00000032312
ENSMUST00000217314; ENSMUSP00000150984; ENSMUSG00000032312
GeneIDi12988
KEGGimmu:12988
UCSCiuc009pvk.2 mouse

Similar proteinsi

Entry informationi

Entry nameiCSK_MOUSE
AccessioniPrimary (citable) accession number: P41241
Secondary accession number(s): Q03143, Q80WU4, Q8VCW1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: July 27, 2011
Last modified: March 28, 2018
This is version 182 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome