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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. Two isoforms of the human protein are produced by alternative splicing. Note: This description may include information from UniProtKB.
Protein type: DNA-binding; Tumor suppressor
Chromosomal Location of Human Ortholog: 2p21-p16.3
Cellular Component: membrane; MutSalpha complex; MutSbeta complex; nuclear chromosome, telomeric region; nucleoplasm
Molecular Function: ADP binding; ATP binding; ATPase activity; dinucleotide insertion or deletion binding; dinucleotide repeat insertion binding; DNA binding; DNA-dependent ATPase activity; double-strand/single-strand DNA junction binding; double-stranded DNA binding; enzyme binding; four-way junction DNA binding; guanine/thymine mispair binding; loop DNA binding; magnesium ion binding; mismatched DNA binding; MutLalpha complex binding; oxidized purine DNA binding; protein binding; protein C-terminus binding; protein homodimerization activity; protein kinase binding; single guanine insertion binding; single thymine insertion binding; single-stranded DNA binding; Y-form DNA binding
Biological Process: B cell differentiation; B cell mediated immunity; DNA damage response, signal transduction by p53 class mediator resulting in induction of apoptosis; DNA repair; double-strand break repair; intra-S DNA damage checkpoint; isotype switching; maintenance of DNA repeat elements; male gonad development; meiotic gene conversion; mismatch repair; negative regulation of DNA recombination; negative regulation of meiotic recombination; negative regulation of neuron apoptosis; positive regulation of helicase activity; postreplication repair; response to UV-B; response to X-ray; somatic hypermutation of immunoglobulin genes; somatic recombination of immunoglobulin gene segments
Disease: Lynch Syndrome I; Mismatch Repair Cancer Syndrome; Muir-torre Syndrome
Reference #:  P43246 (UniProtKB)
Alt. Names/Synonyms: COCA1; DNA mismatch repair protein Msh2; FCC1; hMSH2; HNPCC; HNPCC1; LCFS2; MSH2; mutS homolog 2, colon cancer, nonpolyposis type 1 (E. coli); MutS protein homolog 2
Gene Symbols: MSH2
Molecular weight: 104,743 Da
Basal Isoelectric point: 5.58  Predict pI for various phosphorylation states
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