Gene content    
MSH6 ( by HUGO)
MutS Homolog 6
Other
MutS Homolog 6
GTBP
MutS-Alpha 160 KDa Subunit
GTMBP
G/T Mismatch-Binding Protein
p160
HNPCC5
MutS (E. Coli) Homolog 6
MutS Homolog 6 (E. Coli)
HSAP
DNA Mismatch Repair Protein Msh6
Sperm-Associated Protein
hMSH6
NCBI: 2p16    Ensembl: 2p16.3
MSH6_HUMANSize: 1360 amino acidsMass: 152786 Da

  • Subunit: 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 6 PDB 3D structures from [IMAGE] and Proteopedia [IMAGE] for MSH6: 2GFU (3D) [IMAGE] 2O8B (3D) [IMAGE] 2O8C (3D) [IMAGE] 2O8D (3D) [IMAGE] 2O8E (3D) [IMAGE] 2O8F (3D) [IMAGE]
  • Function:
    UniProtKB/Swiss-Prot Summary: MSH6_HUMAN, P52701 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
  • Similarity:
    Belongs to the DNA mismatch repair MutS family
                          
    Contains 1 PWWP domain [IMAGE]

    • Protein Domain/Family    
    Source ID Domain Name Type
    InterProIPR000313PWWP_domPWWPDomain
    IPR000432DNA_mismatch_repair_MutS_CDNA mismatch repair protein MutS, C-terminalDomain
    IPR007695DNA_mismatch_repair_MutS-lik_NDNA mismatch repair protein MutS, N-terminalDomain
    IPR007696DNA_mismatch_repair_MutS_coreMutS IIIDomain
    IPR007860DNA_mmatch_repair_MutS_con_domMutS IIDomain
    IPR007861DNA_mismatch_repair_MutS_clampMutS IVDomain
    BlocksIPB007695DNA mismatch repair protein MutSDNA mismatch repair protein MutS, N-terminal
    IPB007696MutS IIIMutS III

    Gene Ontology    
    Type Term Evidence Source Pub
    Biological Process ATP catabolic process IDA GOA 16403449
    DNA repair IDA GOA 8942985
    mismatch repair IMP GOA 8782829
    mismatch repair IDA GOA 10871409
    negative regulation of DNA recombination IDA GOA 17715146
    NOT maintenance of DNA repeat elements IMP GOA 16388310
    positive regulation of helicase activity IDA GOA 17715146
    Molecular Function contributes_to ADP binding IDA GOA 15105434
    contributes_to ATP binding IDA GOA 15105434
    contributes_to ATPase activity IDA GOA 16403449
    contributes_to double-stranded DNA binding IDA GOA 11809883
    contributes_to four-way junction DNA binding IDA GOA 12034830
    contributes_to guanine/thymine mispair binding IDA GOA 11809883
    contributes_to magnesium ion binding IDA GOA 16403449
    contributes_to mismatched DNA binding IDA GOA 11756455
    contributes_to MutLalpha complex binding IDA GOA 16403449
    contributes_to oxidized purine DNA binding IDA GOA 11756455
    contributes_to protein binding IPI GOA 16403449
    contributes_to single guanine insertion binding IDA GOA 8942985
    contributes_to single thymine insertion binding IDA GOA 8942985
    NOT protein homodimerization activity IPI GOA 8942985
    protein binding IPI GOA 10856833

    Disorder & Mutation    
    Source Disease
    SWISS-PROTEndometrial cancer (ENDMC) [MIM:608089]: A malignancy of endometrium, the mucous lining of the uterus. Most endometrial cancers are adenocarcinomas, cancers that begin in cells that make and release mucus and other fluids. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry
    SWISS-PROTMismatch repair cancer syndrome (MMRCS) [MIM:276300]: Autosomal dominant disorder characterized by malignant tumors of the brain associated with multiple colorectal adenomas. Skin features include sebaceous cysts, hyperpigmented and cafe au lait spots. Note=The disease is caused by mutations affecting the gene represented in this entry
    SWISS-PROTHereditary non-polyposis colorectal cancer 5 (HNPCC5) [MIM:614350]: An autosomal dominant disease associated with marked increase in cancer susceptibility. It is characterized by a familial predisposition to early-onset colorectal carcinoma (CRC) and extra-colonic tumors of the gastrointestinal, urological and female reproductive tracts. HNPCC is reported to be the most common form of inherited colorectal cancer in the Western world. Clinically, HNPCC is often divided into two subgroups. Type I is characterized by hereditary predisposition to colorectal cancer, a young age of onset, and carcinoma observed in the proximal colon. Type II is characterized by increased risk for cancers in certain tissues such as the uterus, ovary, breast, stomach, small intestine, skin, and larynx in addition to the colon. Diagnosis of classical HNPCC is based on the Amsterdam criteria: 3 or more relatives affected by colorectal cancer, one a first degree relative of the other two; 2 or more generation affected; 1 or more colorectal cancers presenting before 50 years of age; exclusion of hereditary polyposis syndromes. The term 'suspected HNPCC' or 'incomplete HNPCC' can be used to describe families who do not or only partially fulfill the Amsterdam criteria, but in whom a genetic basis for colon cancer is strongly suspected. Note=The disease is caused by mutations affecting the gene represented in this entry

    MSH6 cross reference    
    PubMed OMIM Entrez Gene NCKU SNP Nucleotide UniProt Genome Data Viewer HomoloGene