MLH1 - DNA mismatch repair protein Mlh1 - human protein (Function)
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MLH1 »  DNA mismatch repair protein Mlh1
Protein also known as:  MutL protein homolog 1.
Gene name:  MLH1
Entry whose protein(s) existence is based on evidence at protein level
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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-MSH6) 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.  
  • CuratedUniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524] silver  
  • IEAInterPro 2 GO
ATPase activitydefinition[GO:0016887] silver  
  • IBARefGenome
Guanine/thymine mispair bindingdefinition[GO:0032137] silver  
  • IEAOrtholog Compara
Contributes to MutSalpha complex bindingdefinition[GO:0032407]  
Contributes to protein bindingdefinition[GO:0005515]  
  • IPIIntAct
  • IPIUniProtKB
Contributes to single-stranded DNA bindingdefinition[GO:0003697]  
GO biological process 
ATP catabolic processdefinition[GO:0006200] silver  
  • IBARefGenome
Double-strand break repair via nonhomologous end joiningdefinition[GO:0006303] silver  
  • IEAOrtholog Compara
Intrinsic apoptotic signaling pathway in response to DNA damagedefinition[GO:0008630] silver  
  • IEAOrtholog Compara
Isotype switchingdefinition[GO:0045190] silver  
  • IEAOrtholog Compara
Male meiosis chromosome segregationdefinition[GO:0007060] silver  
  • IEAOrtholog Compara
Meiotic metaphase I plate congressiondefinition[GO:0043060] silver  
  • IEAOrtholog Compara
Mismatch repairdefinition[GO:0006298]  
Negative regulation of mitotic recombinationdefinition[GO:0045950] silver  
  • IEAOrtholog Compara
Nuclear-transcribed mRNA poly(A) tail shorteningdefinition[GO:0000289] silver  
  • IEAOrtholog Compara
Oogenesisdefinition[GO:0048477] silver  
  • IEAOrtholog Compara
Resolution of meiotic recombination intermediatesdefinition[GO:0000712] silver  
  • IEAOrtholog Compara
Somatic hypermutation of immunoglobulin genesdefinition[GO:0016446] silver  
  • IBARefGenome
Spermatogenesisdefinition[GO:0007283] silver  
  • IEAOrtholog Compara
Spindle midzone assembly involved in meiosisdefinition[GO:0051257] silver  
  • IEAOrtholog Compara
Synapsisdefinition[GO:0007129] silver  
  • IEAOrtholog Compara
According to KEGG, this protein belongs to the following pathways:
Colorectal cancer  hsa05210+4292  
Endometrial cancer  hsa05213+4292  
Fanconi anemia pathway  hsa03460+4292  
Mismatch repair  hsa03430+4292  
Pathways in cancer  hsa05200+4292  
According to Reactome, this protein belongs to the following pathway:
Meiotic recombination  REACT_27271  


Biological process 
Cell cycle  definition   [KW-0131]
DNA damage  definition   [KW-0227]
DNA repair  definition   [KW-0234]
Technical term 
Reference proteome  definition   [KW-1185]

Further external links

GeneWiki: MLH1
GenomeRNAi: 4292
PRO: PR:P40692