InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Chek2

Summary

InnateDB Protein

IDBP-190637.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

Chek2

Protein Name

CHK2 checkpoint homolog (S. pombe)

Synonyms

Cds1; CHK2; HUCDS1; Rad53;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000066679

InnateDB Gene

IDBG-190635 (Chek2)

Protein Structure

UniProt Annotation

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. {ECO:0000269PubMed:12192050}.

Subcellular Localization

Nucleus, PML body {ECO:0000250}. Nucleus, nucleoplasm. Note=Recruited into PML bodies together with TP53. {ECO:0000250}.

Disease Associations

Tissue Specificity

Ubiquitously expressed with higher levels in the thymus, spleen and colon (at protein level). {ECO:0000269PubMed:12192050}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 6 experimentally validated interaction(s) in this database.
They are also associated with 59 interaction(s) predicted by orthology.

Experimentally validated
Total	6 [view]
Protein-Protein	6 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	59 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004672	protein kinase activity
GO:0004674	protein serine/threonine kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016301	kinase activity
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0019901	protein kinase binding
GO:0031625	ubiquitin protein ligase binding
GO:0042802	identical protein binding
GO:0042803	protein homodimerization activity
GO:0046872	metal ion binding

Biological Process

GO:0000077	DNA damage checkpoint
GO:0000086	G2/M transition of mitotic cell cycle
GO:0006302	double-strand break repair
GO:0006351	transcription, DNA-templated
GO:0006355	regulation of transcription, DNA-templated
GO:0006468	protein phosphorylation
GO:0006915	apoptotic process
GO:0006974	cellular response to DNA damage stimulus
GO:0006975	DNA damage induced protein phosphorylation
GO:0008630	intrinsic apoptotic signaling pathway in response to DNA damage
GO:0010332	response to gamma radiation
GO:0042176	regulation of protein catabolic process
GO:0042770	signal transduction in response to DNA damage
GO:0044257	cellular protein catabolic process
GO:0045893	positive regulation of transcription, DNA-templated
GO:0046777	protein autophosphorylation
GO:0050821	protein stabilization
GO:0072428	signal transduction involved in intra-S DNA damage checkpoint
GO:0090307	spindle assembly involved in mitosis

Cellular Component

GO:0000781	chromosome, telomeric region
GO:0016605	PML body

Protein Structure and Domains

PDB ID

MGI:1355321

InterPro

IPR000253 Forkhead-associated (FHA) domain
IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine- /dual specificity protein kinase, catalytic domain
IPR008984 SMAD/FHA domain
IPR011009 Protein kinase-like domain
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM

PF00498
PF00069
PF07714

PRINTS

PR00109

PIRSF

SMART

SM00240
SM00220
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt