InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: CHEK1

Summary

InnateDB Protein

IDBP-384441.4

Last Modified

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

Gene Symbol

CHEK1

Protein Name

CHK1 checkpoint homolog (S. pombe)

Synonyms

CHK1;

Species

Homo sapiens

Ensembl Protein

ENSP00000412504

InnateDB Gene

IDBG-75536 (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. Phosphorylation of CDC25A at 'Ser-178' and 'Thr-507' and phosphorylation of CDC25C at 'Ser-216' creates binding sites for 14-3-3 proteins which inhibit CDC25A and CDC25C. Phosphorylation of CDC25A at 'Ser-76', 'Ser- 124', 'Ser-178', 'Ser-279' and 'Ser-293' promotes proteolysis of CDC25A. Phosphorylation of CDC25A at 'Ser-76' primes the protein for subsequent phosphorylation at 'Ser-79', 'Ser-82' and 'Ser-88' by NEK11, which is required for polyubiquitination and degradation of CDCD25A. 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 at 'Ser-743', 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. 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.Isoform 2: Endogenous repressor of isoform 1, interacts with, and antagonizes CHK1 to promote the S to G2/M phase transition.

Subcellular Localization

Nucleus. Cytoplasm. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. 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.

Disease Associations

Tissue Specificity

Expressed ubiquitously with the most abundant expression in thymus, testis, small intestine and colon. {ECO:0000269PubMed:9278511, ECO:0000269PubMed:9382850}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 109 experimentally validated interaction(s) in this database.
They are also associated with 1 interaction(s) predicted by orthology.

Experimentally validated
Total	109 [view]
Protein-Protein	102 [view]
Protein-DNA	4 [view]
Protein-RNA	0
DNA-DNA	3 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	1 [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:0006260	DNA replication
GO:0006281	DNA repair
GO:0006468	protein phosphorylation
GO:0006974	cellular response to DNA damage stimulus
GO:0006975	DNA damage induced protein phosphorylation
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:0018107	peptidyl-threonine phosphorylation
GO:0031572	G2 DNA damage checkpoint
GO:0035407	histone H3-T11 phosphorylation
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:0090399	replicative senescence
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:0005813	centrosome
GO:0005829	cytosol
GO:0043231	intracellular membrane-bounded organelle

Protein Structure and Domains

PDB ID

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