MutS Homolog 6 Native Protein | MSH6 native protein
Recombinant Human MutS Homolog 6
Sterile Filtered clear solution.
Introduction: MSH6 deficiency result in hereditary non-polyposis colorectal cancer (Lynch syndrome). HNPCC is an autosomal, dominantly inherited disease linked with rise in cancer susceptibility. MSH6 is is known by its familial predisposition to premature onset colorectal carcinoma (crc) and extra-colonic cancers of the gastrointestinal, urological and female reproductive tracts.MSH6 is involved in repairing DNA. MSH6 protein repairs mistakes that occure during DNA replication in preparation for cell division. The MSH6 protein bonds with MSH2 protein and form an active protein complex which recognizes specific parts on the DNA where mistakes have been made during DNA replication. MLH1-PMS2 protein complex, afterwards takes over with the repair. MSH6 gene is part of the set of the mismatch repair (MMR) genes.
NCBI and Uniprot Product Information
NCBI Description
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. [provided by RefSeq, Jul 2013]
Uniprot Description
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.
Protein type: DNA-binding
Chromosomal Location of Human Ortholog: 2p16
Cellular Component: nucleoplasm; nuclear chromosome; Golgi apparatus; intracellular membrane-bound organelle; nuclear chromatin; cytoplasm; plasma membrane; MutSalpha complex
Molecular Function: DNA-dependent ATPase activity; protein homodimerization activity; single thymine insertion binding; oxidized purine DNA binding; ATPase activity; magnesium ion binding; ADP binding; methylated histone residue binding; mismatched DNA binding; protein binding; four-way junction DNA binding; single guanine insertion binding; guanine/thymine mispair binding; double-stranded DNA binding; MutLalpha complex binding; chromatin binding; ATP binding
Biological Process: positive regulation of helicase activity; negative regulation of DNA recombination; mismatch repair; DNA damage response, signal transduction resulting in induction of apoptosis; meiotic recombination; somatic hypermutation of immunoglobulin genes; isotype switching; somatic recombination of immunoglobulin gene segments; determination of adult life span; DNA repair; maintenance of DNA repeat elements; response to UV; meiotic mismatch repair
Disease: Colorectal Cancer, Hereditary Nonpolyposis, Type 5; Endometrial Cancer; Mismatch Repair Cancer Syndrome
Research Articles on MSH6
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Product Notes
The MSH6 msh6 (Catalog #AAA143748) is a Native Protein produced from E Coli and is intended for research purposes only. The product is available for immediate purchase. It is sometimes possible for the material contained within the vial of "MutS Homolog 6, Native Protein" to become dispersed throughout the inside of the vial, particularly around the seal of said vial, during shipment and storage. We always suggest centrifuging these vials to consolidate all of the liquid away from the lid and to the bottom of the vial prior to opening. Please be advised that certain products may require dry ice for shipping and that, if this is the case, an additional dry ice fee may also be required.Precautions
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