Tbio MSH2 DNA mismatch repair protein Msh2

Protein Summary

Description

Component of the post-replicative DNA mismatch repair system (MMR). Forms two different heterodimers: MutS alpha (MSH2-MSH6 heterodimer) and MutS beta (MSH2-MSH3 heterodimer) which binds to DNA mismatches thereby initiating DNA repair. When bound, heterodimers bend the DNA helix and shields approximately 20 base pairs. MutS alpha recognizes single base mismatches and dinucleotide insertion-deletion loops (IDL) in the DNA. MutS beta recognizes larger insertion-deletion loops up to 13 nucleotides long. After mismatch binding, MutS alpha or beta 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. Recruits DNA helicase MCM9 to chromatin which unwinds the mismatch containg DNA strand (PubMed:26300262). 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. In melanocytes may modulate both UV-B-induced cell cycle regulation and apoptosis. This locus is frequently mutated in hereditary nonpolyposis colon cancer (HNPCC). When cloned, it was discovered to be a human homolog of the E. coli mismatch repair gene mutS, consistent with the characteristic alterations in microsatellite sequences (RER+ phenotype) found in HNPCC. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]

Uniprot Accession IDs

• P43246
• B4E2Z2
• O75488
• hMSH2

Gene Name

• MSH2

Ensembl ID

• ENST00000233146
• ENSP00000233146
• ENSG00000095002
• ENST00000543555
• ENSP00000442697

Symbol

• FCC1
• COCA1
• HNPCC
• LCFS2
• hMSH2
• HNPCC1

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological term	1
interacting protein	1
molecular function	1
biological process	0.99
hub protein	0.99

Protein Classes

PANTHER Classes

Protein / Nucleic Acid Binding / Dna Binding Protein / Dna Mismatch Repair Protein Msh2

DTO Classes

Protein / Nucleic Acid Binding / Dna Binding Protein / Dna Mismatch Repair Protein Msh2

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: 2028.1   (req: < 5)

Gene RIFs: 535   (req: <= 3)

Antibodies: 613   (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: 2028.1   (req: >= 5)

Gene RIFs: 535   (req: > 3)

Antibodies: 613   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 37

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