Tbio PMS2 Mismatch repair endonuclease PMS2

Protein Summary

Description

Component of the post-replicative DNA mismatch repair system (MMR). Heterodimerizes with MLH1 to form MutL alpha. DNA repair is initiated by MutS alpha (MSH2-MSH6) or MutS beta (MSH2-MSH3) binding to a dsDNA mismatch, then MutL alpha is recruited to the heteroduplex. Assembly of the MutL-MutS-heteroduplex ternary complex in presence of RFC and PCNA is sufficient to activate endonuclease activity of PMS2. It introduces single-strand breaks near the mismatch and thus generates new entry points for the exonuclease EXO1 to degrade the strand containing the mismatch. DNA methylation would prevent cleavage and therefore assure that only the newly mutated DNA strand is going to be corrected. MutL alpha (MLH1-PMS2) interacts physically with the clamp loader subunits of DNA polymerase III, suggesting that it may play a role to recruit the DNA polymerase III to the site of the MMR. Also implicated in DNA damage signaling, a process which induces cell cycle arrest and can lead to apoptosis in case of major DNA damages. The protein encoded by this gene is a key component of the mismatch repair system that functions to correct DNA mismatches and small insertions and deletions that can occur during DNA replication and homologous recombination. This protein forms heterodimers with the gene product of the mutL homolog 1 (MLH1) gene to form the MutL-alpha heterodimer. The MutL-alpha heterodimer possesses an endonucleolytic activity that is activated following recognition of mismatches and insertion/deletion loops by the MutS-alpha and MutS-beta heterodimers, and is necessary for removal of the mismatched DNA. There is a DQHA(X)2E(X)4E motif found at the C-terminus of the protein encoded by this gene that forms part of the active site of the nuclease. Mutations in this gene have been associated with hereditary nonpolyposis colorectal cancer (HNPCC; also known as Lynch syndrome) and Turcot syndrome. [provided by RefSeq, Apr 2016]

Uniprot Accession IDs

• P54278
• B2R610
• Q52LH6
• Q5FBW9
• Q5FBX1
• Q5FBX2
• Q75MR2

Gene Name

• PMS2

Ensembl ID

• ENST00000265849
• ENSP00000265849
• ENSG00000122512
• ENST00000382321
• ENSP00000371758
• ENST00000643595
• ENSP00000494497

Symbol

• PMSL2
• MLH4
• PMSL2
• HNPCC4
• PMS2CL

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
molecular function	1
protein domain	0.97
histone modification site profile	0.81
transcription factor binding site profile	0.81
tissue sample	0.77

Protein Classes

PANTHER Classes

Protein / Nucleic Acid Binding / Dna Binding Protein / Mismatch Repair Endonuclease Pms2

DTO Classes

Protein / Nucleic Acid Binding / Dna Binding Protein / Mismatch Repair Endonuclease Pms2

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: 791.91   (req: < 5)

Gene RIFs: 147   (req: <= 3)

Antibodies: 465   (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: 791.91   (req: >= 5)

Gene RIFs: 147   (req: > 3)

Antibodies: 465   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 8

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