Tbio MSH6 DNA mismatch repair protein Msh6

Protein Summary

Description

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. 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 Accession IDs

• P52701
• B4DF41
• B4E3I4
• F5H2F9
• O43706
• O43917
• Q8TCX4
• Q9BTB5
• hMSH6

Gene Name

• MSH6

Ensembl ID

• ENST00000234420
• ENSP00000234420
• ENSG00000116062
• ENST00000538136
• ENSP00000438580
• ENST00000540021
• ENSP00000446475
• ENST00000614496
• ENSP00000477844

Symbol

• GTBP
• GTBP
• HSAP
• p160
• GTMBP
• HNPCC5

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
interacting protein	1
molecular function	1
protein complex	1
hub protein	0.99
protein domain	0.99

Protein Classes

PANTHER Classes

Protein / Nucleic Acid Binding / Dna Binding Protein / Dna Mismatch Repair Protein Msh6

DTO Classes

Protein / Nucleic Acid Binding / Dna Binding Protein / Dna Mismatch Repair Protein Msh6

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 1160.15   (req: < 5)

Gene RIFs: 232   (req: <= 3)

Antibodies: 590   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 1160.15   (req: >= 5)

Gene RIFs: 232   (req: > 3)

Antibodies: 590   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 29

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0