InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Chek1

Summary

InnateDB Protein

IDBP-623897.3

Last Modified

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

Gene Symbol

Chek1

Protein Name

checkpoint kinase 1 homolog (S. pombe)

Synonyms

C85740; Chk1; rad27;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000134388

InnateDB Gene

IDBG-149248 (Chek1)

Protein Structure

UniProt Annotation

Function

Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest and activation of DNA repair in response to the presence of DNA damage or unreplicated DNA. May also negatively regulate cell cycle progression during unperturbed cell cycles. This regulation is achieved by a number of mechanisms that together help to preserve the integrity of the genome. Recognizes the substrate consensus sequence [R-X-X-S/T]. Binds to and phosphorylates CDC25A, CDC25B and CDC25C. This inhibits their activity through proteasomal degradation, nucleo-cytoplasmic shuttling and inhibition by proteins of the 13-3-3 family. Inhibition of CDC25 leads to increased inhibitory tyrosine phosphorylation of CDK-cyclin complexes and blocks cell cycle progression. Also phosphorylates NEK6. Binds to and phosphorylates RAD51 at 'Thr-309', which promotes the release of RAD51 from BRCA2 and enhances the association of RAD51 with chromatin, thereby promoting DNA repair by homologous recombination. Phosphorylates multiple sites within the C-terminus of TP53, which promotes activation of TP53 by acetylation and promotes cell cycle arrest and suppression of cellular proliferation. Also promotes repair of DNA cross-links through phosphorylation of FANCE. Binds to and phosphorylates TLK1, which prevents the TLK1-dependent phosphorylation of the chromatin assembly factor ASF1A. This may enhance chromatin assembly both in the presence or absence of DNA damage. May also play a role in replication fork maintenance through regulation of PCNA (By similarity). May regulate the transcription of genes that regulate cell-cycle progression through the phosphorylation of histones. Phosphorylates histone H3.1 (to form H3T11ph), which leads to epigenetic inhibition of a subset of genes. May also phosphorylate RB1 to promote its interaction with the E2F family of transcription factors and subsequent cell cycle arrest. {ECO:0000250, ECO:0000269PubMed:10859163, ECO:0000269PubMed:10859164, ECO:0000269PubMed:15261141, ECO:0000269PubMed:18243098}.

Subcellular Localization

Nucleus {ECO:0000250}. Cytoplasm {ECO:0000250}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000250}. Note=Nuclear export is mediated at least in part by XPO1/CRM1. Also localizes to the centrosome specifically during interphase, where it may protect centrosomal CDC2 kinase from inappropriate activation by cytoplasmic CDC25B (By similarity). {ECO:0000250}.

Disease Associations

Tissue Specificity

Found in all adult tissues tested. Elevated expression in testis, lung and spleen. 15.5 day old embryos show ubiquitous expression with strong expression in brain, liver, kidney, pancreas, intestine, thymus and lung. {ECO:0000269PubMed:9278511}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 11 experimentally validated interaction(s) in this database.
They are also associated with 67 interaction(s) predicted by orthology.

Experimentally validated
Total	11 [view]
Protein-Protein	11 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	67 [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:0016772	transferase activity, transferring phosphorus-containing groups
GO:0035402	histone kinase activity (H3-T11 specific)

Biological Process

GO:0000077	DNA damage checkpoint
GO:0000086	G2/M transition of mitotic cell cycle
GO:0006281	DNA repair
GO:0006468	protein phosphorylation
GO:0006974	cellular response to DNA damage stimulus
GO:0006975	DNA damage induced protein phosphorylation
GO:0010468	regulation of gene expression
GO:0010569	regulation of double-strand break repair via homologous recombination
GO:0010767	regulation of transcription from RNA polymerase II promoter in response to UV-induced DNA damage
GO:0010972	negative regulation of G2/M transition of mitotic cell cycle
GO:0018107	peptidyl-threonine phosphorylation
GO:0031572	G2 DNA damage checkpoint
GO:0035407	histone H3-T11 phosphorylation
GO:0042127	regulation of cell proliferation
GO:0045839	negative regulation of mitosis
GO:0046602	regulation of mitotic centrosome separation
GO:0048096	chromatin-mediated maintenance of transcription
GO:0071260	cellular response to mechanical stimulus
GO:0071310	cellular response to organic substance
GO:0071313	cellular response to caffeine
GO:2000279	negative regulation of DNA biosynthetic process
GO:2000615	regulation of histone H3-K9 acetylation

Cellular Component

GO:0000781	chromosome, telomeric region
GO:0000785	chromatin
GO:0000794	condensed nuclear chromosome
GO:0005615	extracellular space
GO:0005634	nucleus
GO:0005654	nucleoplasm
GO:0005657	replication fork
GO:0005737	cytoplasm
GO:0005813	centrosome
GO:0043231	intracellular membrane-bounded organelle

Protein Structure and Domains

PDB ID

MGI:1202065

InterPro

IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine- /dual specificity protein kinase, catalytic domain
IPR011009 Protein kinase-like domain
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM

PF00069
PF07714

PRINTS

PR00109

PIRSF

SMART

SM00220
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt