Recombinant Human DNA mismatch repair protein Msh6 (MSH6), Truncated

Uniprot Id

P52701

Target Species

Human

Target Name

MSH6

Target Full Name

DNA mismatch repair protein Msh6

Target 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.

Target Involvement

Hereditary non-polyposis colorectal cancer 5 (HNPCC5); Endometrial cancer (ENDMC); Mismatch repair cancer syndrome (MMRCS); Colorectal cancer (CRC)

Target Subcellular Location

Nucleus. Chromosome. Note=Associates with H3K36me3 via its PWWP domain.

Target Protein Families

DNA mismatch repair MutS family

Target Research Area

Epigenetics and Nuclear Signaling

Target Synonyms

DNA mismatch repair protein Msh6; G/T mismatch binding protein; G/T mismatch-binding protein; GTBP; GTMBP; hMSH6; HNPCC 5; HNPCC5; HSAP; MSH 6; MSH6; MSH6_HUMAN; mutS (E. coli) homolog 6; MutS alpha 160 kDa subunit; MutS homolog 6 (E. coli); mutS homolog 6; MutS-alpha 160 kDa subunit; p160; Sperm associated protein

Target Background

This gene encodes a member of the DNA mismatch repair MutS family. In E. coli, the MutS protein helps in the recognition of mismatched nucleotides prior to their repair. A highly conserved region of approximately 150 aa, called the Walker-A adenine nucleotide binding motif, exists in MutS homologs. The encoded protein heterodimerizes with MSH2 to form a mismatch recognition complex that functions as a bidirectional molecular switch that exchanges ADP and ATP as DNA mismatches are bound and dissociated. Mutations in this gene may be associated with hereditary nonpolyposis colon cancer, colorectal cancer, and endometrial cancer. Transcripts variants encoding different isoforms have been described.