MLH1 - DNA mismatch repair protein Mlh1 - human protein (Function)
 
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Protein
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References

 
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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GENE REF ISO

Function

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Overview 
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.  
3
  • UniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524] silver  
1
  • InterPro 2 GO
ATPase activitydefinition[GO:0016887]  
1
  • RefGenome
Guanine/thymine mispair bindingdefinition[GO:0032137] silver  
1
  • Ortholog Compara
Contributes to MutSalpha complex bindingdefinition[GO:0032407]  
1
  • HGNC
Contributes to protein bindingdefinition[GO:0005515]  
15
  • IntAct
  • UniProtKB
  • HGNC
Contributes to single-stranded DNA bindingdefinition[GO:0003697]  
1
  • HGNC
GO biological process 
ATP catabolic processdefinition[GO:0006200]  
1
  • RefGenome
Double-strand break repair via nonhomologous end joiningdefinition[GO:0006303] silver  
1
  • Ortholog Compara
Intrinsic apoptotic signaling pathway in response to DNA damagedefinition[GO:0008630] silver  
1
  • Ortholog Compara
Isotype switchingdefinition[GO:0045190] silver  
1
  • Ortholog Compara
Male meiosis chromosome segregationdefinition[GO:0007060] silver  
1
  • Ortholog Compara
Meiotic metaphase I plate congressiondefinition[GO:0043060] silver  
1
  • Ortholog Compara
Meiotic spindle midzone assemblydefinition[GO:0051257] silver  
1
  • Ortholog Compara
Mismatch repairdefinition[GO:0006298]  
1
  • MGI
Negative regulation of mitotic recombinationdefinition[GO:0045950] silver  
1
  • Ortholog Compara
Nuclear-transcribed mRNA poly(A) tail shorteningdefinition[GO:0000289] silver  
1
  • Ortholog Compara
Oogenesisdefinition[GO:0048477] silver  
1
  • Ortholog Compara
Resolution of meiotic recombination intermediatesdefinition[GO:0000712] silver  
1
  • Ortholog Compara
Somatic hypermutation of immunoglobulin genesdefinition[GO:0016446]  
1
  • RefGenome
Spermatogenesisdefinition[GO:0007283] silver  
1
  • Ortholog Compara
Synapsisdefinition[GO:0007129] silver  
1
  • Ortholog Compara
Pathways 
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 pathways:
Meiotic recombination  REACT_27271  
Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta)  REACT_228019  
Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha)  REACT_228145  
 

Keywords

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