m6A Target Gene Information

General Information of the m6A Target Gene (ID: M6ATAR00482)
Target Name DNA mismatch repair protein Msh6 (MSH6)
Synonyms
hMSH6; G/T mismatch-binding protein; GTBP; GTMBP; MutS protein homolog 6; MutS-alpha 160 kDa subunit; p160; GTBP
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Gene Name MSH6
Family DNA mismatch repair MutS family. {ECO:0000305}.
Function
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. {ECO:0000269|PubMed:10078208, ECO:0000269|PubMed:10660545, ECO:0000269|PubMed:15064730, ECO:0000269|PubMed:21120944, ECO:0000269|PubMed:23622243, ECO:0000269|PubMed:9564049, ECO:0000269|PubMed:9822679, ECO:0000269|PubMed:9822680}.
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Gene ID 2956
Uniprot ID
MSH6_HUMAN
HGNC ID
HGNC:7329
Ensembl Gene ID
ENSG00000116062
KEGG ID
hsa:2956
Full List of m6A Methylation Regulator of This Target Gene and Corresponding Disease/Drug Response(s)
MSH6 can be regulated by the following regulator(s), and cause disease/drug response(s). You can browse detail information of regulator(s) or disease/drug response(s).
Browse Regulator
Browse Disease
Methyltransferase-like 5 (METTL5) [WRITER]
 Regulator Info 
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [1]
Response Summary knocking down METTL5 could significantly activate apoptosis and inhibit endometrial carcinoma(EC) development via MMR administration.METTL5 expression in UCEC tumor tissue was increased, and UCEC patients with high METTL5 expression had worse prognostic outcomes. METTL5 knockdown induced the MSH2, DNA mismatch repair protein Msh6 (MSH6) and PMS2 expression in MMR.
Target Regulation Up regulation
Responsed Disease Endometrial cancer ICD-11: 2C76
 Disease Info 
Pathway Response Mismatch repair hsa03430
Cell Process DNA mismatch repair
Microsatellite instability
In-vitro Model CP-H058 (Normal endometrial cells)
KLE Endometrial adenocarcinoma Homo sapiens CVCL_1329
RL95-2 Endometrial adenosquamous carcinoma Homo sapiens CVCL_0505
Ishikawa Endometrial adenocarcinoma Homo sapiens CVCL_2529
ECC-1 Endometrial Cancer Homo sapiens CVCL_7260
In-vivo Model The male BALB/c nude mice were randomized divide into two groups, each group including six 4 weeks old nude mice. Investigators were blinded to the treatment groups during data collection and subsequent data analysis. In the subcutaneous xenograft model, 5 × 105 cells were subcutaneously injected in the right flanks of nude mice. In the orthotopic intracranial mouse model, each mouse was intracranially injected with 1 × 105 luciferase transfected U87MG cells in 10 uL PBS solution.
Endometrial cancer [ICD-11: 2C76]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [1]
Response Summary knocking down METTL5 could significantly activate apoptosis and inhibit endometrial carcinoma(EC) development via MMR administration.METTL5 expression in UCEC tumor tissue was increased, and UCEC patients with high METTL5 expression had worse prognostic outcomes. METTL5 knockdown induced the MSH2, DNA mismatch repair protein Msh6 (MSH6) and PMS2 expression in MMR.
Responsed Disease Endometrial cancer [ICD-11: 2C76]
Target Regulator Methyltransferase-like 5 (METTL5) WRITER
 Regulator Info 
Target Regulation Up regulation
Pathway Response Mismatch repair hsa03430
Cell Process DNA mismatch repair
Microsatellite instability
In-vitro Model CP-H058 (Normal endometrial cells)
KLE Endometrial adenocarcinoma Homo sapiens CVCL_1329
RL95-2 Endometrial adenosquamous carcinoma Homo sapiens CVCL_0505
Ishikawa Endometrial adenocarcinoma Homo sapiens CVCL_2529
ECC-1 Endometrial Cancer Homo sapiens CVCL_7260
In-vivo Model The male BALB/c nude mice were randomized divide into two groups, each group including six 4 weeks old nude mice. Investigators were blinded to the treatment groups during data collection and subsequent data analysis. In the subcutaneous xenograft model, 5 × 105 cells were subcutaneously injected in the right flanks of nude mice. In the orthotopic intracranial mouse model, each mouse was intracranially injected with 1 × 105 luciferase transfected U87MG cells in 10 uL PBS solution.
References
Ref 1 The potential role of methyltransferase-like 5 in deficient mismatch repair of uterine corpus endometrial carcinoma. Bioengineered. 2022 Mar;13(3):5525-5536. doi: 10.1080/21655979.2022.2036912.