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MSH6 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. Heterodimer consisting of MSH2-MSH6 (MutS alpha). Forms 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. Belongs to the DNA mismatch repair MutS family. 2 isoforms of the human protein are produced by alternative splicing. Note: This description may include information from UniProtKB.
Protein type: DNA-binding
Chromosomal Location of Human Ortholog: 2p16.3
Cellular Component: cytosol; Golgi apparatus; intracellular membrane-bound organelle; MutSalpha complex; nuclear chromatin; nucleoplasm
Molecular Function: ADP binding; ATP binding; ATPase activity; chromatin binding; DNA-dependent ATPase activity; double-stranded DNA binding; four-way junction DNA binding; guanine/thymine mispair binding; magnesium ion binding; methylated histone residue binding; mismatched DNA binding; MutLalpha complex binding; oxidized purine DNA binding; protein binding; protein homodimerization activity; single guanine insertion binding; single thymine insertion binding
Biological Process: determination of adult lifespan; DNA damage response, signal transduction resulting in induction of apoptosis; DNA repair; isotype switching; maintenance of DNA repeat elements; meiotic mismatch repair; mismatch repair; negative regulation of DNA recombination; positive regulation of helicase activity; positive regulation of isotype switching; response to UV; somatic hypermutation of immunoglobulin genes; somatic recombination of immunoglobulin gene segments; viral process
Disease: Colorectal Cancer, Hereditary Nonpolyposis, Type 5; Endometrial Cancer; Mismatch Repair Cancer Syndrome
Reference #:  P52701 (UniProtKB)
Alt. Names/Synonyms: DNA mismatch repair protein Msh6; G/T mismatch-binding protein; GTBP; GTMBP; hMSH6; HNPCC5; HSAP; MSH6; mutS homolog 6 (E. coli); MutS-alpha 160 kDa subunit; p160; sperm-associated protein
Gene Symbols: MSH6
Molecular weight: 152,786 Da
Basal Isoelectric point: 6.5  Predict pI for various phosphorylation states
Protein-Specific Antibodies or siRNAs from Cell Signaling Technology® Total Proteins
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