Homo sapiens Protein: CHEK1 | |||||||||||||||||||||||||||||||||||
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Summary | |||||||||||||||||||||||||||||||||||
InnateDB Protein | IDBP-591559.3 | ||||||||||||||||||||||||||||||||||
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 | ENSP00000432890 | ||||||||||||||||||||||||||||||||||
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.
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Gene Ontology | |||||||||||||||||||||||||||||||||||
Molecular Function |
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Biological Process |
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Cellular Component |
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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 |
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PFAM |
PF00069
PF07714 |
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PRINTS |
PR00109
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PIRSF | |||||||||||||||||||||||||||||||||||
SMART |
SM00220
SM00219 |
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TIGRFAMs | |||||||||||||||||||||||||||||||||||
Post-translational Modifications | |||||||||||||||||||||||||||||||||||
Modification | |||||||||||||||||||||||||||||||||||
Cross-References | |||||||||||||||||||||||||||||||||||
SwissProt | O14757 | ||||||||||||||||||||||||||||||||||
PhosphoSite | PhosphoSite-O14757 | ||||||||||||||||||||||||||||||||||
TrEMBL | Q6W8P8 | ||||||||||||||||||||||||||||||||||
UniProt Splice Variant | |||||||||||||||||||||||||||||||||||
Entrez Gene | 1111 | ||||||||||||||||||||||||||||||||||
UniGene | Hs.595920 | ||||||||||||||||||||||||||||||||||
RefSeq | XP_006718822 | ||||||||||||||||||||||||||||||||||
HUGO | HGNC:1925 | ||||||||||||||||||||||||||||||||||
OMIM | 603078 | ||||||||||||||||||||||||||||||||||
CCDS | CCDS8459 | ||||||||||||||||||||||||||||||||||
HPRD | 04356 | ||||||||||||||||||||||||||||||||||
IMGT | |||||||||||||||||||||||||||||||||||
EMBL | AB032387 AB451222 AB451345 AF016582 AF032874 AF527555 AK292549 AK293143 AK299783 AP001132 AY304548 BC004202 BC017575 CH471065 JF289264 | ||||||||||||||||||||||||||||||||||
GenPept | AAB88852 AAC51736 AAH04202 AAH17575 AAM78553 AAQ76038 AEB71796 BAA84577 BAF85238 BAG56691 BAG61665 BAG70036 BAG70159 EAW67644 | ||||||||||||||||||||||||||||||||||