MLH1
MLH1 Gene Summary
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]
Details
| Type | Protein Coding |
| Official Symbol | MLH1 |
| Official Name | mutL homolog 1 [Source:HGNC Symbol;Acc:HGNC:7127] |
| Ensembl ID | ENSG00000076242 |
| Bio databases IDs | |
| Aliases | mutL homolog 1 |
| Synonyms | 1110035C23Rik,AI317206,COCA2,FCC2,hMLH1,HNPCC,HNPCC2,LYNCH2,MMRCS1,mutL homolog 1 |
| Species | Human, homo_sapiens |
Protein Domains
A protein domain is a distinct structural or functional region within a protein that can evolve, function, and exist independently of the rest of the protein chain. These domains often fold into stable, three-dimensional structures and are associated with specific biological functions, such as binding to DNA, other proteins, or small molecules.
- dimerization domain
- Histidine kinase-like ATPase domain
- DNA mismatch repair protein Mlh1 C-terminus
- DNA mismatch repair protein, C-terminal domain
- nuclear localization sequence
- TopoII_MutL_Trans
- enzyme binding
- chromatin binding
- enzyme
- protein binding
- enzyme activator activity
- binding protein
- single-stranded DNA binding
- double-stranded DNA binding
- DNA mismatch repair protein MutL
Pathways
Biological processes and signaling networks where the MLH1 gene plays a role, providing insight into its function and relevance in health or disease.
Top Findings
The most significant associations for this gene, including commonly observed domains, pathway involvement, and functional highlights based on current data.
binds
- PMS2
- NONO
- MAGEA8
- Pms2
- APEX1
- EXO1
- NAA40
- KPNA2
- MSH2
- MAD2L1
disease
- metastasis
- neoplasia
- breast cancer
- gastric cancer
- hereditary nonpolyposis colorectal cancer type 2
- Lynch syndrome
- hereditary cancer-predisposing syndrome
- epithelial cancer
- epithelial neoplasia
- cancer
regulated by
- vorinostat
- geldanamycin
- SMARCB1
- GNAI2
- E2F1
- TP53
- tretinoin
- CREBBP
- CASP3
- epigallocatechin-gallate
regulates
- NFkB (complex)
- TP53
- CDK1
- adenosine triphosphate
- CHEK1
- TOPBP1
- APC
- PMS2
- CCND1
- EXO1
role in cell
- proliferation
- expression in
- replication in
- quantity
- growth
- apoptosis
- cell death
- activation in
- formation
- survival
Subcellular Expression
Locations within the cell where the protein is known or predicted to be active, providing insight into its function and cellular context.
- Nucleus
- nuclear fraction
- ND10 structure
- Cytoplasm
- nuclear foci
- chromosome
- nucleoplasm
- chromatin foci
- synaptonemal complexes
Gene Ontology Annotations
Describes the biological processes, cellular components, and molecular functions associated with the MLH1 gene, providing context for its role in the cell.
BIOLOGICAL PROCESS
Functions and activities the gene product is involved in
- male meiosis chromosome segregation
- spermatogenesis
- resolution of meiotic recombination intermediates
- positive regulation of isotype switching to IgG isotypes
- DNA damage response, signal transduction resulting in induction of apoptosis
- negative regulation of mitotic recombination
- mismatch repair
- double-strand break repair via nonhomologous end joining
- synapsis
- nuclear-transcribed mRNA poly(A) tail shortening
- positive regulation of isotype switching to IgA isotypes
- meiotic metaphase I plate congression
- spindle midzone assembly involved in meiosis
- meiotic telomere clustering
- response to bacterium
- oogenesis
- female meiosis chromosome segregation
- somatic hypermutation of immunoglobulin genes
- isotype switching
CELLULAR COMPONENT
Where in the cell the gene product is active
- chiasma
- nucleus
- late recombination nodule
- membrane
- MutLalpha complex
- chromosome
- synaptonemal complex
- male germ cell nucleus
- nucleoplasm
MOLECULAR FUNCTION
What the gene product does at the molecular level
- MutSalpha complex binding
- ATPase activity
- ATP binding
- protein binding
- chromatin binding
- guanine/thymine mispair binding
- enzyme binding
- single-stranded DNA binding