Biomarker: MSH2

Histology type: endometrial carcinoma

Country: Japan

Region: Tokorozawa

Study type: retrospective study

Followed up time :

Subgroup 1 name : retained

Subgroup 1 number: 166

Subgroup 2 name: loss

Subgroup 2 number: 25

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). Forms two different heterodimers: MutS alpha (MSH2-MSH6 heterodimer) and MutS beta (MSH2-MSH3 heterodimer) which binds to DNA mismatches thereby initiating DNA repair. When bound, heterodimers bend the DNA helix and shields approximately 20 base pairs. MutS alpha recognizes single base mismatches and dinucleotide insertion-deletion loops (IDL) in the DNA. MutS beta recognizes larger insertion-deletion loops up to 13 nucleotides long. After mismatch binding, MutS alpha or beta 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. Recruits DNA helicase MCM9 to chromatin which unwinds the mismatch containing DNA strand (PubMed:26300262). 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. In melanocytes may modulate both UV-B-induced cell cycle regulation and apoptosis

UniProt ID: P43246

UniProt Link: https://www.uniprot.org/uniprotkb/P43246/entry

Biological function from UniProt: #DNA damage #DNA repair

Molecular function from UniProt:

Tissue specificity from UniProt: Ubiquitously expressed.

Subcellular UniProt: #Chromosome #Nucleus

Alternative name from UniProt:

Recommended name: DNA mismatch repair protein Msh2

Gene name from HGNC: MSH2 (COCA1, HNPCC, HNPCC1)

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

AlphaFold DB: P43246

AlphaFold Link: https://alphafold.ebi.ac.uk/entry/P43246

HPA link: https://www.proteinatlas.org/ENSG00000095002-MSH2

Tissue specificity RNA from HPA: Low tissue specificity

Tissue expression from HPA: Ubiquitous nuclear expression.

Single cell type specificity Low cell type specificity

Immune cell specificity: Low immune cell specificity

Subcellular summary HPA Located in Nucleoplasm, Vesicles (Single cell variability, CCD Transcript)

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

Pathology link: https://www.proteinatlas.org/ENSG00000095002-MSH2/pathology

Pathology endo: https://www.proteinatlas.org/ENSG00000095002-MSH2/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: 120435$158320 $608089$ 619096$114500

Disease: Hereditary non-polyposis colorectal cancer 1 (HNPCC1) $Muir-Torre syndrome (MRTES) $Endometrial cancer (ENDMC) $Mismatch repair cancer syndrome 2 (MMRCS2) $Colorectal cancer (CRC) $

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

OMIM: 609309

OMIM link1: https://www.omim.org/entry/120435 $ https://www.omim.org/entry/158320 $ https://www.omim.org/entry/608089 $https://www.omim.org/entry/619096 $https://www.omim.org/entry/114500

OMIM link2: https://www.omim.org/entry/609309

HGNC ID: HGNC:7325

HGNC link: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:7325