Tbio MLH1 DNA mismatch repair protein Mlh1

Protein Summary

Description

Heterodimerizes with PMS2 to form MutL alpha, a component of the post-replicative DNA mismatch repair system (MMR). 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. Heterodimerizes with MLH3 to form MutL gamma which plays a role in meiosis. The protein encoded by this gene can heterodimerize with mismatch repair endonuclease PMS2 to form MutL alpha, part of the DNA mismatch repair system. When MutL alpha is bound by MutS beta and some accessory proteins, the PMS2 subunit of MutL alpha introduces a single-strand break near DNA mismatches, providing an entry point for exonuclease degradation. The encoded protein is also involved in DNA damage signaling and can heterodimerize with DNA mismatch repair protein MLH3 to form MutL gamma, which is involved in meiosis. This gene was identified as a locus frequently mutated in hereditary nonpolyposis colon cancer (HNPCC). [provided by RefSeq, Aug 2017]

Uniprot Accession IDs

• P40692
• B4DI13
• B4DQ11
• E9PCU2

Gene Name

• MLH1

Ensembl ID

• ENST00000231790
• ENSP00000231790
• ENSG00000076242
• ENST00000435176
• ENSP00000402564
• ENST00000455445
• ENSP00000398272
• ENST00000458205
• ENSP00000402667
• ENST00000536378
• ENSP00000444286
• ENST00000539477
• ENSP00000443665

Symbol

• COCA2
• FCC2
• COCA2
• HNPCC
• hMLH1
• HNPCC2

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
disease perturbation	1
molecular function	0.99
kinase perturbation	0.93
protein domain	0.92
biological process	0.9

Protein Classes

PANTHER Classes

Protein / Nucleic Acid Binding / Dna Binding Protein / Dna Mismatch Repair Protein Mlh1

DTO Classes

Protein / Nucleic Acid Binding / Dna Binding Protein / Dna Mismatch Repair Protein Mlh1

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: 3452.29   (req: < 5)

Gene RIFs: 772   (req: <= 3)

Antibodies: 654   (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: 3452.29   (req: >= 5)

Gene RIFs: 772   (req: > 3)

Antibodies: 654   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 24

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