Biomarker: MSH6

Histology type: endometrial carcinoma

Country: Japan

Region: Tokorozawa

Study type: retrospective study

Followed up time :

Subgroup 1 name : retained

Subgroup 1 number: 164

Subgroup 2 name: loss

Subgroup 2 number: 27

Conclusion: MMR-related proteins expression was identified as an independent prognostic factor for OS, suggesting that MMR was a key biomarker for further investigations of endometrial cancers.

Sample type : tissue

Sample method: immunohistochemistry

Expression pattern : loss

Expression elevation: For all of the four markers detection, a nuclear immunoreaction was taken into account for evaluation. The lesions were considered as positive for each marker if tumor cells in the interest area showed immunoreactive intensity stronger than or equal to positive controls. The lesions were considered as negative for each marker if tumor cells showed complete loss of immunoreaction. Cases that at least one of four proteins was judged as negative were assigned to MMR-deficient cases and the remainder cases were assigned to MMR-retained cases.

Funtion Uniprot: Component of the post-replicative DNA mismatch repair system (MMR). Heterodimerizes with MSH2 to form MutS alpha, which binds to DNA mismatches thereby initiating DNA repair. When bound, MutS alpha bends the DNA helix and shields approximately 20 base pairs, and recognizes single base mismatches and dinucleotide insertion-deletion loops (IDL) in the DNA. After mismatch binding, forms a ternary complex with the MutL alpha heterodimer, which is thought to be responsible for directing the downstream MMR events, including strand discrimination, excision, and resynthesis. ATP binding and hydrolysis play a pivotal role in mismatch repair functions. The ATPase activity associated with MutS alpha regulates binding similar to a molecular switch: mismatched DNA provokes ADP-->ATP exchange, resulting in a discernible conformational transition that converts MutS alpha into a sliding clamp capable of hydrolysis-independent diffusion along the DNA backbone. This transition is crucial for mismatch repair. MutS alpha may also play a role in DNA homologous recombination repair. Recruited on chromatin in G1 and early S phase via its PWWP domain that specifically binds trimethylated 'Lys-36' of histone H3 (H3K36me3): early recruitment to chromatin to be replicated allowing a quick identification of mismatch repair to initiate the DNA mismatch repair reaction.

UniProt ID: P52701

UniProt Link: https://www.uniprot.org/uniprotkb/P52701/entry

Biological function from UniProt: #DNA damage #DNA repair #Host-virus interaction

Molecular function from UniProt:

Subcellular UniProt: #Chromosome #Nucleus

Alternative name from UniProt:

Recommended name: DNA mismatch repair protein Msh6

Gene name from HGNC: MSH6 (GTBP)

HPA class: Cancer-related genes Disease related genes Human disease related genes Plasma proteins

AlphaFold DB: P52701

AlphaFold Link: https://alphafold.ebi.ac.uk/entry/P52701

HPA link: https://www.proteinatlas.org/ENSG00000116062-MSH6

Tissue specificity RNA from HPA: Low tissue specificity

Tissue expression from HPA: Ubiquitous nuclear expression.

Single cell type specificity Cell type enhanced (Granulosa cells, Theca cells)

Immune cell specificity: Low immune cell specificity

Subcellular summary HPA Located in Nucleoplasm, Golgi apparatus, Vesicles (CCD Transcript)

Cancer prognostic summary HPA Prognostic marker in renal cancer (unfavorable), endometrial cancer (unfavorable) and liver cancer (unfavorable)

Pathology link: https://www.proteinatlas.org/ENSG00000116062-MSH6/pathology

Pathology endo: https://www.proteinatlas.org/ENSG00000116062-MSH6/pathology/endometrial+cancer

Survival figure legend: Kaplan-Meier survival curves of all cases according to mismatch repair (MMR) status. (

Survival curve link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4302284/figure/F1/

Phenotype ID: 614350 $ 608089 $ 619097 $ 114500$

Disease: Hereditary non-polyposis colorectal cancer 5 (HNPCC5) $Endometrial cancer (ENDMC) $ Mismatch repair cancer syndrome 3 (MMRCS3)

Note1: The disease is caused by variants affecting the gene represented in this entry $Disease susceptibility is associated with variants affecting the gene represented in this entry $The disease is caused by variants affecting the gene represented in this entry $

OMIM: 600678

OMIM link1: https://www.omim.org/entry/614350 $https://www.omim.org/entry/608089 $ https://www.omim.org/entry/619097 $

OMIM link2: https://www.omim.org/entry/600678

HGNC ID: HGNC:7329

HGNC link: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:7329