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Q9Z265 (CHK2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 125. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | 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:
Serine/threonine-protein kinase Chk2

EC=2.7.11.1
Alternative name(s):
CHK2 checkpoint homolog
Checkpoint kinase 2
Gene names
Name:Chek2
Synonyms:Chk2, Rad53
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length546 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest, activation of DNA repair and apoptosis in response to the presence of DNA double-strand breaks. May also negatively regulate cell cycle progression during unperturbed cell cycles. Following activation, phosphorylates numerous effectors preferentially at the consensus sequence [L-X-R-X-X-S/T]. Regulates cell cycle checkpoint arrest through phosphorylation of CDC25A, CDC25B and CDC25C, inhibiting their activity. Inhibition of CDC25 phosphatase activity leads to increased inhibitory tyrosine phosphorylation of CDK-cyclin complexes and blocks cell cycle progression. May also phosphorylate NEK6 which is involved in G2/M cell cycle arrest. Regulates DNA repair through phosphorylation of BRCA2, enhancing the association of RAD51 with chromatin which promotes DNA repair by homologous recombination. Also stimulates the transcription of genes involved in DNA repair (including BRCA2) through the phosphorylation and activation of the transcription factor FOXM1. Regulates apoptosis through the phosphorylation of p53/TP53, MDM4 and PML. Phosphorylation of p53/TP53 at 'Ser-20' by CHEK2 may alleviate inhibition by MDM2, leading to accumulation of active p53/TP53. Phosphorylation of MDM4 may also reduce degradation of p53/TP53. Also controls the transcription of pro-apoptotic genes through phosphorylation of the transcription factor E2F1. Tumor suppressor, it may also have a DNA damage-independent function in mitotic spindle assembly by phosphorylating BRCA1. Its absence may be a cause of the chromosomal instability observed in some cancer cells. Ref.3

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Cofactor

Magnesium.

Enzyme regulation

Activated through phosphorylation at Thr-68 by ATM in response to DNA double-strand breaks. Activation is modulated by several mediators including MDC1 and TP53BP1. Induces homodimerization with exchange of the T-loop/activation segment between protomers and transphosphorylation of the protomers. The autophosphorylated kinase dimer is fully active. Negatively regulated by PPM1D through dephosphorylation of Thr-68 By similarity.

Subunit structure

Homodimer. Homodimerization is part of the activation process but the dimer may dissociate following activation. Interacts with PML. Interacts with TP53. Interacts with RB1; phosphorylates RB1. Interacts with BRCA1. Interacts (phosphorylated at Thr-68) with MDC1; requires ATM-mediated phosphorylation of CHEK2. Interacts with TP53BP1; modulates CHEK2 phosphorylation at Thr-68 in response to ionizing radiation. Interacts with CDC25A; phosphorylates CDC25A and mediates its degradation in response to ionizing radiation. Interacts with CUL1; mediates CHEK2 ubiquitination and regulation By similarity.

Subcellular location

NucleusPML body By similarity. Nucleusnucleoplasm. Note: Recruited into PML bodies together with TP53 By similarity.

Tissue specificity

Ubiquitously expressed with higher levels in the thymus, spleen and colon (at protein level). Ref.3

Post-translational modification

Phosphorylated. Phosphorylated at Ser-82 by PLK3 in response to DNA damage, promoting phosphorylation at Thr-77 by ATM and the G2/M transition checkpoint. Phosphorylation at Thr-77 induces homodimerization. Autophosphorylates at Thr-387 and Thr-391 in the T-loop/activation segment upon dimerization to become fully active. DNA damage-induced autophosphorylation at Ser-383 induces CUL1-mediated ubiquitination and regulates the pro-apoptotic function. Phosphorylation at Ser-460 also regulates ubiquitination. Phosphorylated by PLK4 By similarity.

Ubiquitinated. CUL1-mediated ubiquitination regulates the pro-apoptotic function. Ubiquitination may also regulate protein stability. Ubiquitinated by RNF8 via 'Lys-48'-linked ubiquitination By similarity.

Disruption phenotype

No overt morphological phenotype but apoptosis and cell cycle arrest induced by ionizing radiation are abolished. Ref.3

Sequence similarities

Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. CHK2 subfamily.

Contains 1 FHA domain.

Contains 1 protein kinase domain.

Ontologies

Keywords
   Biological processApoptosis
Cell cycle
Cell division
DNA damage
DNA repair
Mitosis
Transcription
Transcription regulation
   Cellular componentNucleus
   LigandATP-binding
Magnesium
Metal-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMPhosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processDNA damage induced protein phosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

G2/M transition of mitotic cell cycle

Inferred from sequence or structural similarity. Source: UniProtKB

apoptotic process

Inferred from mutant phenotype PubMed 18614044. Source: MGI

cellular protein catabolic process

Inferred from electronic annotation. Source: Ensembl

cellular response to DNA damage stimulus

Inferred from sequence or structural similarity. Source: UniProtKB

double-strand break repair

Inferred from sequence or structural similarity. Source: UniProtKB

intrinsic apoptotic signaling pathway in response to DNA damage

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of transcription, DNA-templated

Inferred from sequence or structural similarity. Source: UniProtKB

protein autophosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

protein stabilization

Inferred from electronic annotation. Source: Ensembl

regulation of protein catabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of transcription, DNA-templated

Inferred from sequence or structural similarity. Source: UniProtKB

response to gamma radiation

Inferred from direct assay PubMed 14744935. Source: MGI

signal transduction in response to DNA damage

Inferred from direct assay PubMed 14744935. Source: MGI

signal transduction involved in intra-S DNA damage checkpoint

Inferred from sequence or structural similarity. Source: UniProtKB

spindle assembly involved in mitosis

Inferred from sequence or structural similarity. Source: UniProtKB

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentPML body

Inferred from sequence or structural similarity. Source: UniProtKB

chromosome, telomeric region

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein homodimerization activity

Inferred from sequence or structural similarity. Source: UniProtKB

protein serine/threonine kinase activity

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 546546Serine/threonine-protein kinase Chk2
PRO_0000085859

Regions

Domain117 – 17963FHA
Domain224 – 490267Protein kinase
Nucleotide binding231 – 2388ATP By similarity
Nucleotide binding306 – 3127ATP By similarity
Nucleotide binding355 – 3562ATP By similarity
Region372 – 39827T-loop/activation segment By similarity

Sites

Active site3511Proton acceptor By similarity
Binding site2531ATP By similarity
Binding site3721ATP By similarity

Amino acid modifications

Modified residue681Phosphothreonine; by MLTK By similarity
Modified residue711Phosphoserine; by PLK3 By similarity
Modified residue771Phosphothreonine; by ATM and MLTK By similarity
Modified residue821Phosphoserine; by PLK3 By similarity
Modified residue3831Phosphoserine; by autocatalysis By similarity
Modified residue3871Phosphothreonine; by autocatalysis By similarity
Modified residue3911Phosphothreonine; by autocatalysis By similarity
Modified residue4601Phosphoserine By similarity

Sequences

Sequence LengthMass (Da)Tools
Q9Z265 [UniParc].

Last modified May 1, 1999. Version 1.
Checksum: A7949EFB5572CDAA

FASTA54661,088
        10         20         30         40         50         60 
MKSHHQSHSS TSSKAHDSAS CSQSQGGFSQ PQGTPSQLHE LSQYQGSSSS STGTVPSSSQ 

        70         80         90        100        110        120 
SSHSSSGTLS SLETVSTQEL CSIPEDQEPE EPGPAPWARL WALQDGFSNL DCVNDNYWFG 

       130        140        150        160        170        180 
RDKSCEYCFD GPLLRRTDKY RTYSKKHFRI FREMGPKNCY IVYIEDHSGN GTFVNTELIG 

       190        200        210        220        230        240 
KGKRCPLSNN SEIALSLCRN KVFVFFDLTV DDQSVYPKEL RDEYIMSKTL GSGACGEVKM 

       250        260        270        280        290        300 
AFERKTCQKV AIKIISKRRF ALGSSREADT APSVETEIEI LKKLNHPCII KIKDVFDAED 

       310        320        330        340        350        360 
YYIVLELMEG GELFDRVVGN KRLKEATCKL YFYQMLVAVQ YLHENGIIHR DLKPENVLLS 

       370        380        390        400        410        420 
SQEEDCLIKI TDFGQSKILG ETSLMRTLCG TPTYLAPEVL VSNGTAGYSR AVDCWSLGVI 

       430        440        450        460        470        480 
LFICLSGYPP FSEHKTQVSL KDQITSGKYN FIPEVWTDVS EEALDLVKKL LVVDPKARLT 

       490        500        510        520        530        540 
TEEALNHPWL QDEYMKKKFQ DLLVQEKNSV TLPVAPAQTS SQKRPLELEV EGMPSTKRLS 


VCGAVL 

« Hide

References

« Hide 'large scale' references
[1]"Linkage of ATM to cell cycle regulation by the Chk2 protein kinase."
Matsuoka S., Huang M., Elledge S.J.
Science 282:1893-1897(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[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].
Strain: NMRI.
Tissue: Mammary gland.
[3]"Chk2 is a tumor suppressor that regulates apoptosis in both an ataxia telangiectasia mutated (ATM)-dependent and an ATM-independent manner."
Hirao A., Cheung A., Duncan G., Girard P.M., Elia A.J., Wakeham A., Okada H., Sarkissian T., Wong J.A., Sakai T., De Stanchina E., Bristow R.G., Suda T., Lowe S.W., Jeggo P.A., Elledge S.J., Mak T.W.
Mol. Cell. Biol. 22:6521-6532(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE, FUNCTION IN APOPTOSIS, TISSUE SPECIFICITY.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF086905 mRNA. Translation: AAC83694.1.
BC056617 mRNA. Translation: AAH56617.1.
RefSeqNP_057890.1. NM_016681.3.
XP_006535132.1. XM_006535069.1.
XP_006535133.1. XM_006535070.1.
UniGeneMm.279308.

3D structure databases

ProteinModelPortalQ9Z265.
SMRQ9Z265. Positions 94-537.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid206143. 6 interactions.
IntActQ9Z265. 4 interactions.

PTM databases

PhosphoSiteQ9Z265.

Proteomic databases

PaxDbQ9Z265.
PRIDEQ9Z265.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000066160; ENSMUSP00000066679; ENSMUSG00000029521.
GeneID50883.
KEGGmmu:50883.
UCSCuc008yrw.1. mouse.

Organism-specific databases

CTD11200.
MGIMGI:1355321. Chek2.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00710000106821.
HOGENOMHOG000233016.
HOVERGENHBG108055.
InParanoidQ9Z265.
KOK06641.
OMALNSFGTA.
OrthoDBEOG7C5M7Z.
PhylomeDBQ9Z265.
TreeFamTF101082.

Enzyme and pathway databases

BRENDA2.7.11.1. 3474.

Gene expression databases

ArrayExpressQ9Z265.
BgeeQ9Z265.
CleanExMM_CHEK2.
GenevestigatorQ9Z265.

Family and domain databases

Gene3D2.60.200.20. 1 hit.
InterProIPR000253. FHA_dom.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
IPR008984. SMAD_FHA_domain.
[Graphical view]
PfamPF00498. FHA. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTSM00240. FHA. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF49879. SSF49879. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEPS50006. FHA_DOMAIN. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio307865.
PROQ9Z265.
SOURCESearch...

Entry information

Entry nameCHK2_MOUSE
AccessionPrimary (citable) accession number: Q9Z265
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: May 1, 1999
Last modified: April 16, 2014
This is version 125 of the entry and version 1 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

MGD cross-references

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