Chk1
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. Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. NIM1 subfamily. Expressed ubiquitously with the most abundant expression in thymus, testis, small intestine and colon. 3 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.
Protein type: CAMK group; CAMKL family; CHK1 subfamily; EC 2.7.11.1; Kinase, protein; Protein kinase, CAMK; Protein kinase, Ser/Thr (non-receptor); Tumor suppressor
Molecular Function: ATP binding; histone H3T11 kinase activity; metal ion binding; protein binding; protein domain specific binding; protein kinase activity; protein serine kinase activity; protein serine/threonine kinase activity
Biological Process: apoptotic process; apoptotic process involved in development; cellular response to caffeine; cellular response to mechanical stimulus; cellular response to organic substance; chromatin remodeling; DNA damage checkpoint signaling; DNA damage response; DNA repair; G2/M transition of mitotic cell cycle; inner cell mass cell proliferation; intracellular signal transduction; mitotic G2 DNA damage checkpoint signaling; mitotic G2/M transition checkpoint; negative regulation of DNA biosynthetic process; negative regulation of G2/M transition of mitotic cell cycle; negative regulation of gene expression, epigenetic; negative regulation of mitotic nuclear division; nucleus organization; peptidyl-threonine phosphorylation; positive regulation of cell cycle; protein phosphorylation; regulation of cell population proliferation; regulation of double-strand break repair via homologous recombination; regulation of gene expression; regulation of mitotic centrosome separation; signal transduction in response to DNA damage
