MSH2
UniProt ID: P43246
Entrez ID: 4436
Protein name: DNA mismatch repair protein Msh2 (hMSH2) (MutS protein homolog 2)
External links: UniprotKB HGNC RefSeq COSMIC
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FUNCTION: 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 shield...
FUNCTION: 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. {ECO:0000269|PubMed:10078208, ECO:0000269|PubMed:10660545, ECO:0000269|PubMed:15064730, ECO:0000269|PubMed:17611581, ECO:0000269|PubMed:21120944, ECO:0000269|PubMed:26300262, ECO:0000269|PubMed:9564049, ECO:0000269|PubMed:9822679, ECO:0000269|PubMed:9822680}.
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GO - Biological processes (BP):
B cell differentiation [GO:0030183]; B cell mediated immunity [GO:0019724]; determination of adult lifespan [GO:0008340]; DNA repair [GO:0006281]; double-strand break repair [GO:0006302]; germ cell development [GO:0007281]; intrinsic apoptotic signaling pathway in response to DNA damage by p53 class...
B cell differentiation [GO:0030183]; B cell mediated immunity [GO:0019724]; determination of adult lifespan [GO:0008340]; DNA repair [GO:0006281]; double-strand break repair [GO:0006302]; germ cell development [GO:0007281]; intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator [GO:0042771]; in utero embryonic development [GO:0001701]; isotype switching [GO:0045190]; maintenance of DNA repeat elements [GO:0043570]; male gonad development [GO:0008584]; mismatch repair [GO:0006298]; mitotic intra-S DNA damage checkpoint signaling [GO:0031573]; mitotic recombination [GO:0006312]; negative regulation of DNA recombination [GO:0045910]; negative regulation of neuron apoptotic process [GO:0043524]; oxidative phosphorylation [GO:0006119]; positive regulation of helicase activity [GO:0051096]; positive regulation of isotype switching to IgA isotypes [GO:0048298]; positive regulation of isotype switching to IgG isotypes [GO:0048304]; postreplication repair [GO:0006301]; protein localization to chromatin [GO:0071168]; response to UV-B [GO:0010224]; response to X-ray [GO:0010165]; somatic hypermutation of immunoglobulin genes [GO:0016446]; somatic recombination of immunoglobulin gene segments [GO:0016447]; somatic recombination of immunoglobulin genes involved in immune response [GO:0002204]
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GO - Molecular function (MF):
ATP binding [GO:0005524]; ATP-dependent activity, acting on DNA [GO:0008094]; ATP hydrolysis activity [GO:0016887]; centromeric DNA binding [GO:0019237]; chromatin binding [GO:0003682]; damaged DNA binding [GO:0003684]; DNA binding [GO:0003677]; enzyme binding [GO:0019899]; guanine/thymine mispair b...
ATP binding [GO:0005524]; ATP-dependent activity, acting on DNA [GO:0008094]; ATP hydrolysis activity [GO:0016887]; centromeric DNA binding [GO:0019237]; chromatin binding [GO:0003682]; damaged DNA binding [GO:0003684]; DNA binding [GO:0003677]; enzyme binding [GO:0019899]; guanine/thymine mispair binding [GO:0032137]; protein C-terminus binding [GO:0008022]; protein homodimerization activity [GO:0042803]; protein kinase binding [GO:0019901]
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GO - Cellular component (CC):
chromosome, telomeric region [GO:0000781]; membrane [GO:0016020]; MutSalpha complex [GO:0032301]; MutSbeta complex [GO:0032302]; nucleoplasm [GO:0005654]; nucleus [GO:0005634]...
chromosome, telomeric region [GO:0000781]; membrane [GO:0016020]; MutSalpha complex [GO:0032301]; MutSbeta complex [GO:0032302]; nucleoplasm [GO:0005654]; nucleus [GO:0005634]
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MSH2
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*NOTE: the Kaplan plots were collected from OncoLnc