Biomarker: CHK1

Histology type: endometrial serous carcinomas

Stage: risk

Country: USA

Region: Rochester, Minnesota

Study type: retrospective study

Followed up time :

Subgroup 1 name : USC

Subgroup 1 number: 36

Subgroup 2 name: TCGA data set USC

Subgroup 2 number: 109

Conclusion: Results showed that higher CHK1 (Checkpoint kinase 1) expression was associated with a decreased risk of progression and death, after adjusting for stage

Sample type : tissue

Sample method: immunohistochemistry

Expression pattern : high expression

Expression elevation: Expression was evaluated by considering the percentage of cells exhibiting immunoreaction, as well as the localization of signalling (nuclear and/or cytoplasmic).

Statictics: Mean (SD);Range

Cohort age: 72.2± 9.0;54.8–89.8

Subgroup 1 age: 58.5 ;38–81

Subgroup 2 age: 46;38–73

Funtion Uniprot: 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 (PubMed:11535615, PubMed:12446774, PubMed:12399544, PubMed:14559997, PubMed:14988723, PubMed:15311285, PubMed:15665856, PubMed:15650047, PubMed:32357935). May also negatively regulate cell cycle progression during unperturbed cell cycles (PubMed:11535615, PubMed:12446774, PubMed:12399544, PubMed:14559997, PubMed:14988723, PubMed:15311285, PubMed:15665856, PubMed:15650047). This regulation is achieved by a number of mechanisms that together help to preserve the integrity of the genome (PubMed:11535615, PubMed:12446774, PubMed:12399544, PubMed:14559997, PubMed:14988723, PubMed:15311285, PubMed:15665856, PubMed:15650047). Recognizes the substrate consensus sequence [R-X-X-S/T] (PubMed:11535615, PubMed:12446774, PubMed:12399544, PubMed:14559997, PubMed:14988723, PubMed:15311285, PubMed:15665856, PubMed:15650047). Binds to and phosphorylates CDC25A, CDC25B and CDC25C (PubMed:9278511, PubMed:12676583, PubMed:14681206, PubMed:12676925, PubMed:12759351, PubMed:19734889, PubMed:14559997). 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 (PubMed:9278511). Phosphorylation of CDC25A at 'Ser-76', 'Ser-124', 'Ser-178', 'Ser-279' and 'Ser-293' promotes proteolysis of CDC25A (PubMed:9278511, PubMed:12676583, PubMed:14681206, PubMed:12676925, PubMed:12759351, PubMed:19734889). 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 (PubMed:9278511, PubMed:19734889, PubMed:20090422). Inhibition of CDC25 leads to increased inhibitory tyrosine phosphorylation of CDK-cyclin complexes and blocks cell cycle progression (PubMed:9278511). Also phosphorylates NEK6 (PubMed:18728393). 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 (PubMed:15665856). 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 (PubMed:10673501, PubMed:15659650, PubMed:16511572). Also promotes repair of DNA cross-links through phosphorylation of FANCE (PubMed:17296736). Binds to and phosphorylates TLK1 at 'Ser-743', which prevents the TLK1-dependent phosphorylation of the chromatin assembly factor ASF1A (PubMed:12660173, PubMed:12955071). This may enhance chromatin assembly both in the presence or absence of DNA damage (PubMed:12660173, PubMed:12955071). May also play a role in replication fork maintenance through regulation of PCNA (PubMed:18451105). 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 arrest (PubMed:17380128). Phosphorylates SPRTN, promoting SPRTN recruitment to chromatin (PubMed:31316063). 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 activity (PubMed:33108758).By Similarity27 Publications Isoform 2 Endogenous repressor of isoform 1, interacts with, and antagonizes CHK1 to promote the S to G2/M phase transition.

UniProt ID: O14757

UniProt Link: https://www.uniprot.org/uniprotkb/O14757/entry

Biological function from UniProt: #Cell cycle #DNA damage #DNA repair

Molecular function from UniProt:

Tissue specificity from UniProt: Expressed ubiquitously with the most abundant expression in thymus, testis, small intestine and colon.

Subcellular UniProt: #Chromosome #Cytoplasm #Cytoskeleton #Nucleus

Alternative name from UniProt:

Catalytic activity: ATP + L-seryl-[protein] = ADP + H+ + O-phospho-L-seryl-[protein],ATP + L-threonyl-[protein] = ADP + H+ + O-phospho-L-threonyl-[protein].

Activity regulation: Activated through phosphorylation predominantly by ATR but also by ATM in response to DNA damage or inhibition of DNA replication (PubMed:11390642, PubMed:12588868, PubMed:12676583, PubMed:12676962, PubMed:15665856, PubMed:19716789). Activation is modulated by several mediators including CLSPN, BRCA1 and FEM1B (PubMed:11836499, PubMed:12766152, PubMed:16963448, PubMed:19330022). Proteolytic cleavage at the C-terminus by SPRTN during normal DNA replication activates the protein kinase activity (PubMed:31316063).

Recommended name: Serine/threonine-protein kinase Chk1

Gene name from HGNC: CHEK1 (CHK1)

HPA class: Cancer-related genes Enzymes Metabolic proteins Plasma proteins

AlphaFold DB: O14757

AlphaFold Link: https://alphafold.ebi.ac.uk/entry/O14757

HPA link: https://www.proteinatlas.org/ENSG00000149554-CHEK1

Tissue specificity RNA from HPA: Tissue enhanced (bone marrow, lymphoid tissue, seminal vesicle)

Single cell type specificity Cell type enhanced (Spermatogonia, Spermatocytes, Extravillous trophoblasts, Erythroid cells, Cholangiocytes)

Immune cell specificity: Immune cell enhanced (T-reg)

Subcellular summary HPA #Chromosome #Cytoplasm #Cytoskeleton #Nucleus

Cancer prognostic summary HPA Prognostic marker in renal cancer (unfavorable), pancreatic cancer (unfavorable), liver cancer (unfavorable) and colorectal cancer (favorable)

Pathology link: https://www.proteinatlas.org/ENSG00000149554-CHEK1/pathology/

Pathology endo: https://www.proteinatlas.org/ENSG00000149554-CHEK1/pathology/endometrial+cancer

Expression figure legend: Immunohistochemistry-based protein profiling of uterine serous carcinomas (UCS) patients

Expression figure link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076151/figure/Fig2/

Survival figure legend: Kaplan–Meier curves for progression-free survival (a) and overall survival (b), according to stage

Survival curve link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076151/figure/Fig1/

OMIM: 603078

OMIM link2: https://www.omim.org/entry/603078

HGNC ID: HGNC:1925

HGNC link: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:1925