MLH1 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. Belongs to the DNA mismatch repair MutL/HexB family. Colon, lymphocytes, breast, lung, spleen, testis, prostate, thyroid, gall bladder and heart. 3 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.
Protein type: Cell cycle regulation; DNA repair, damage; Tumor suppressor
Chromosomal Location of mouse Ortholog: 9 F3|9 60.92 cM
Cellular Component:  chiasma; chromosome; condensed chromosome; condensed nuclear chromosome; late recombination nodule; male germ cell nucleus; mismatch repair complex; MutLalpha complex; nucleoplasm; nucleus; synaptonemal complex
Molecular Function:  ATP binding; ATPase activity; chromatin binding; enzyme binding; guanine/thymine mispair binding; mismatched DNA binding; nucleotide binding
Biological Process:  cell cycle; cellular response to DNA damage stimulus; DNA repair; double-strand break repair via nonhomologous end joining; female meiosis chromosome segregation; homologous chromosome segregation; intrinsic apoptotic signaling pathway in response to DNA damage; isotype switching; male meiosis chromosome segregation; male meiotic nuclear division; meiotic cell cycle; meiotic chromosome segregation; meiotic metaphase I plate congression; meiotic spindle midzone assembly; meiotic telomere clustering; mismatch repair; negative regulation of mitotic recombination; nuclear-transcribed mRNA poly(A) tail shortening; oogenesis; positive regulation of isotype switching to IgA isotypes; positive regulation of isotype switching to IgG isotypes; reciprocal meiotic recombination; resolution of meiotic recombination intermediates; response to bacterium; somatic hypermutation of immunoglobulin genes; somatic recombination of immunoglobulin gene segments; somatic recombination of immunoglobulin genes involved in immune response; spermatogenesis; synapsis
Reference #:  Q9JK91 (UniProtKB)
Alt. Names/Synonyms: 1110035C23Rik; AI317206; AI325952; AI561766; colon cancer, nonpolyposis type 2; DNA mismatch repair protein Mlh1; Mlh1; mutL homolog 1; mutL homolog 1 (E. coli); MutL protein homolog 1
Gene Symbols: Mlh1
Molecular weight: 84,670 Da
Basal Isoelectric point: 5.44  Predict pI for various phosphorylation states
Protein-Specific Antibodies, siRNAs or Recombinant Proteins from Cell Signaling Technology® Total Proteins
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Protein Structure Not Found.

Cross-references to other databases:  AlphaFold  |  STRING  |  Reactome  |  BioGPS  |  Pfam  |  Phospho.ELM  |  NetworKIN  |  UniProtKB  |  Entrez-Gene  |  Ensembl Gene