MSH6 - DNA mismatch repair protein Msh6 - human protein (Function)
 
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Protein
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MSH6 »  DNA mismatch repair protein Msh6
 
Protein also known as:  G/T mismatch-binding protein (GTBP).
Gene name:  MSH6
Entry whose protein(s) existence is based on evidence at protein level
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1 210 4
GENE REF ISO

Function

 show evidences
Overview 
Component of the post-replicative DNA mismatch repair system (MMR). Heterodimerizes with MSH2 to form MutS alpha, which binds to DNA mismatches thereby initiating DNA repair. When bound, MutS alpha bends the DNA helix and shields approximately 20 base pairs, and recognizes single base mismatches and dinucleotide insertion-deletion loops (IDL) in the DNA. After mismatch binding, forms a ternary complex with the MutL alpha heterodimer, which is thought to be responsible for directing the downstream MMR events, including strand discrimination, excision, and resynthesis. ATP binding and hydrolysis play a pivotal role in mismatch repair functions. The ATPase activity associated with MutS alpha regulates binding similar to a molecular switch: mismatched DNA provokes ADP-->ATP exchange, resulting in a discernible conformational transition that converts MutS alpha into a sliding clamp capable of hydrolysis-independent diffusion along the DNA backbone. This transition is crucial for mismatch repair. MutS alpha may also play a role in DNA homologous recombination repair. Recruited on chromatin in G1 and early S phase via its PWWP domain that specifically binds trimethylated 'Lys-36' of histone H3 (H3K36me3): early recruitment to chromatin to be replicated allowing a quick identification of mismatch repair to initiate the DNA mismatch repair reaction.  
7
  • CuratedUniProtKB
GO molecular function 
Contributes to ADP bindingdefinition[GO:0043531]  
1
  • IDAHGNC
Contributes to ATP bindingdefinition[GO:0005524]  
1
  • IDAHGNC
Contributes to ATPase activitydefinition[GO:0016887]  
1
  • IDAHGNC
Chromatin bindingdefinition[GO:0003682] silver  
  • IEAOrtholog Compara
DNA-dependent ATPase activitydefinition[GO:0008094] silver  
  • IBARefGenome
Contributes to double-stranded DNA bindingdefinition[GO:0003690]  
1
  • IDAHGNC
Contributes to four-way junction DNA bindingdefinition[GO:0000400]  
1
  • IDAHGNC
Contributes to guanine/thymine mispair bindingdefinition[GO:0032137]  
2
  • IDAHGNC
Contributes to magnesium ion bindingdefinition[GO:0000287]  
1
  • IDAHGNC
Methylated histone bindingdefinition[GO:0035064]  
1
  • IDAUniProtKB
Contributes to mismatched DNA bindingdefinition[GO:0030983]  
4
  • IDAUniProtKB
  • IDAHGNC
Contributes to MutLalpha complex bindingdefinition[GO:0032405]  
1
  • IDAHGNC
Contributes to oxidized purine DNA bindingdefinition[GO:0032357]  
2
  • IDAHGNC
Contributes to protein bindingdefinition[GO:0005515]  
7
  • IPIHGNC
  • IPIUniProtKB
  • IPIIntAct
Not  Protein homodimerization activitydefinition[GO:0042803]  
1
  • IPIUniProtKB
Contributes to single guanine insertion bindingdefinition[GO:0032142]  
1
  • IDAHGNC
Contributes to single thymine insertion bindingdefinition[GO:0032143]  
1
  • IDAHGNC
GO biological process 
ATP catabolic processdefinition[GO:0006200]  
1
  • IDAGOC
  • IBARefGenome
Determination of adult lifespandefinition[GO:0008340]  
  • ISSOrtholog Curator
DNA repairdefinition[GO:0006281]  
1
  • IDABHF-UCL
Intrinsic apoptotic signaling pathwaydefinition[GO:0097193]  
  • ISSOrtholog Curator
Intrinsic apoptotic signaling pathway in response to DNA damagedefinition[GO:0008630]  
  • IBARefGenome
  • ISSOrtholog Curator
Isotype switchingdefinition[GO:0045190]  
  • IBARefGenome
  • ISSOrtholog Curator
Not  Maintenance of DNA repeat elementsdefinition[GO:0043570]  
1
  • IMPBHF-UCL
Meiotic mismatch repairdefinition[GO:0000710]  
  • IBARefGenome
  • ISSOrtholog Curator
Mismatch repairdefinition[GO:0006298]  
4
  • IGIMGI
  • IDAUniProtKB
  • IDAHGNC
Negative regulation of DNA recombinationdefinition[GO:0045910]  
1
  • IDABHF-UCL
Positive regulation of helicase activitydefinition[GO:0051096]  
1
  • IDABHF-UCL
Reciprocal meiotic recombinationdefinition[GO:0007131] silver  
  • IBARefGenome
Response to UVdefinition[GO:0009411]  
  • ISSOrtholog Curator
  • IBARefGenome
Somatic hypermutation of immunoglobulin genesdefinition[GO:0016446]  
  • ISSOrtholog Curator
  • IBARefGenome
Somatic recombination of immunoglobulin gene segmentsdefinition[GO:0016447]  
  • ISSOrtholog Curator
Pathways 
According to KEGG, this protein belongs to the following pathways:
Colorectal cancer  hsa05210+2956  
Mismatch repair  hsa03430+2956  
Pathways in cancer  hsa05200+2956  
 

Keywords

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

Further external links

GeneWiki: MSH6
GenomeRNAi: 2956
PRO: PR:P52701