MSH2
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. 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. Heterodimer consisting of MSH2-MSH6 (MutS alpha) or MSH2- MSH3 (MutS beta). Both heterodimer form a ternary complex with MutL alpha (MLH1-PMS1). Interacts with EXO1. Part of the BRCA1- associated genome surveillance complex (BASC), which contains BRCA1, MSH2, MSH6, MLH1, ATM, BLM, PMS2 and the RAD50-MRE11-NBS1 protein complex. This association could be a dynamic process changing throughout the cell cycle and within subnuclear domains. Interacts with ATR. Interacts with SLX4/BTBD12; this interaction is direct and links MutS beta to SLX4, a subunit of different structure-specific endonucleases. Interacts with SMARCAD1. Ubiquitously expressed. Belongs to the DNA mismatch repair MutS family. Note: This description may include information from UniProtKB.
Molecular Function: protein homodimerization activity; dinucleotide repeat insertion binding; single thymine insertion binding; ATPase activity; magnesium ion binding; loop DNA binding; Y-form DNA binding; enzyme binding; four-way junction DNA binding; single guanine insertion binding; guanine/thymine mispair binding; double-stranded DNA binding; ATP binding; single-stranded DNA binding; protein C-terminus binding; DNA-dependent ATPase activity; double-strand/single-strand DNA junction binding; oxidized purine DNA binding; ADP binding; protein kinase binding; mismatched DNA binding; centromeric DNA binding; protein binding; DNA binding; MutLalpha complex binding; dinucleotide insertion or deletion binding
Biological Process: determination of adult life span; response to organic cyclic substance; maintenance of DNA repeat elements; germ cell development; positive regulation of helicase activity; double-strand break repair; negative regulation of neuron apoptosis; cell cycle arrest; DNA damage response, signal transduction by p53 class mediator resulting in induction of apoptosis; response to X-ray; oxidative phosphorylation; response to drug; negative regulation of DNA recombination; mismatch repair; in utero embryonic development; postreplication repair; somatic hypermutation of immunoglobulin genes; male gonad development; isotype switching; DNA repair; response to amino acid stimulus; meiotic mismatch repair; response to UV-B; B cell mediated immunity; intra-S DNA damage checkpoint; B cell differentiation; meiotic gene conversion; somatic recombination of immunoglobulin gene segments; spermatogenesis; negative regulation of meiotic recombination
SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.
