Serine/threonine-protein kinase Chk1

Serine/threonine-protein kinase 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 DNA11535615,12399544,12446774,14559997,14988723,15311285,15650047,15665856,32357935. May also negatively regulate cell cycle progression during unperturbed cell cycles11535615,12399544,12446774,14559997,14988723,15311285,15650047,15665856. This regulation is achieved by a number of mechanisms that together help to preserve the integrity of the genome11535615,12399544,12446774,14559997,14988723,15311285,15650047,15665856. Recognizes the substrate consensus sequence [R-X-X-S/T]11535615,12399544,12446774,14559997,14988723,15311285,15650047,15665856. Binds to and phosphorylates CDC25A, CDC25B and CDC25C12676583,12676925,12759351,14559997,14681206,19734889,9278511. 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 CDC25C9278511. Phosphorylation of CDC25A at 'Ser-76', 'Ser-124', 'Ser-178', 'Ser-279' and 'Ser-293' promotes proteolysis of CDC25A12676583,12676925,12759351,14681206,19734889,9278511. 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 CDCD25A19734889,20090422,9278511. Inhibition of CDC25 leads to increased inhibitory tyrosine phosphorylation of CDK-cyclin complexes and blocks cell cycle progression9278511. Also phosphorylates NEK618728393. 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 recombination15665856. 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 proliferation10673501,15659650,16511572. Also promotes repair of DNA cross-links through phosphorylation of FANCE17296736. Binds to and phosphorylates TLK1 at 'Ser-743', which prevents the TLK1-dependent phosphorylation of the chromatin assembly factor ASF1A12660173,12955071. This may enhance chromatin assembly both in the presence or absence of DNA damage12660173,12955071. May also play a role in replication fork maintenance through regulation of PCNA18451105. May regulate the transcription of genes that regulate cell-cycle progression through the phosphorylation of histones (By similarity). Phosphorylates histone H3.1 (to form H3T11ph), which leads to epigenetic inhibition of a subset of genes (By similarity). May also phosphorylate RB1 to promote its interaction with the E2F family of transcription factors and subsequent cell cycle arrest17380128. Phosphorylates SPRTN, promoting SPRTN recruitment to chromatin31316063. Reduces replication stress and activates the G2/M checkpoint, by phosphorylating and inactivating PABIR1/FAM122A and promoting the serine/threonine-protein phosphatase 2A-mediated dephosphorylation and stabilization of WEE1 levels and activity33108758

Endogenous repressor of isoform 1, interacts with, and antagonizes CHK1 to promote the S to G2/M phase transition

Quoted from UniProt’s FUNCTION annotation for O14757 (reviewed). The superscript numbers are UniProt’s own PubMed citations, kept in the sentence and in order, each linking to the paper it names.

What it acts with

STRING’s highest-confidence human functional partners. The combined score mixes several kinds of evidence, so each channel is shown separately — a partner supported by experiment is a different claim from one supported only by text mining, and for a receptor this is where its coupling appears as evidence rather than as assertion.

Where it sits in the cell

• Nucleoplasm
• Vesiclesadditional

Human Protein Atlas, by antibody immunofluorescence in cell lines — a different assay from the expression figures below, which are RNA.

UniProt, curated Nucleus · Chromosome · Cytoplasm · Cytoplasm, cytoskeleton, microtubule organizing center, centrosome

Expression by cell type

Single cell type RNA, the 9 highest of those the Human Protein Atlas reports for this gene. Transcript, not protein, and a cell type rather than a tissue.

• Oocytes142.8 nCPM
• Erythrocyte progenitors99.8 nCPM
• Epididymal basal cells91.9 nCPM
• Early primary spermatocytes87.2 nCPM
• Megakaryocyte progenitors87.2 nCPM
• Monocyte progenitors74.3 nCPM
• Differentiating spermatogonia65.4 nCPM
• Extravillous trophoblasts47.2 nCPM
• Megakaryocyte-Erythroid progenitors47.2 nCPM

Expression by tissue

The tissues this gene is enriched in, by consensus RNA. A tissue absent from this list is one the Atlas does not call specific for this gene, which is not the same as absent from it.

• seminal vesicle28.7 nTPM
• bone marrow24.9 nTPM
• lymphoid tissue19.5 nTPM