MSH6 - DNA mismatch repair protein Msh6 - human protein (Function)
 
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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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1 216 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.  
8
  • UniProtKB
GO molecular function 
Contributes to ADP bindingdefinition[GO:0043531]  
1
  • HGNC
Contributes to ATP bindingdefinition[GO:0005524]  
1
  • HGNC
Contributes to ATPase activitydefinition[GO:0016887]  
1
  • HGNC
Chromatin bindingdefinition[GO:0003682] silver  
1
  • Ortholog Compara
DNA-dependent ATPase activitydefinition[GO:0008094]  
1
  • RefGenome
Contributes to double-stranded DNA bindingdefinition[GO:0003690]  
1
  • HGNC
Contributes to four-way junction DNA bindingdefinition[GO:0000400]  
1
  • HGNC
Contributes to guanine/thymine mispair bindingdefinition[GO:0032137]  
2
  • HGNC
Contributes to magnesium ion bindingdefinition[GO:0000287]  
1
  • HGNC
Methylated histone bindingdefinition[GO:0035064]  
1
  • UniProtKB
Contributes to mismatched DNA bindingdefinition[GO:0030983]  
4
  • UniProtKB
  • HGNC
Contributes to MutLalpha complex bindingdefinition[GO:0032405]  
1
  • HGNC
Contributes to oxidized purine DNA bindingdefinition[GO:0032357]  
2
  • HGNC
Contributes to protein bindingdefinition[GO:0005515]  
8
  • IntAct
  • HGNC
  • UniProtKB
Not  Protein homodimerization activitydefinition[GO:0042803]  
1
  • UniProtKB
Contributes to single guanine insertion bindingdefinition[GO:0032142]  
1
  • HGNC
Contributes to single thymine insertion bindingdefinition[GO:0032143]  
1
  • HGNC
GO biological process 
ATP catabolic processdefinition[GO:0006200]  
2
  • GOC
  • RefGenome
Determination of adult lifespandefinition[GO:0008340]  
1
  • Ortholog Curator
DNA repairdefinition[GO:0006281]  
1
  • BHF-UCL
Intrinsic apoptotic signaling pathwaydefinition[GO:0097193]  
1
  • Ortholog Curator
Intrinsic apoptotic signaling pathway in response to DNA damagedefinition[GO:0008630]  
2
  • RefGenome
  • Ortholog Curator
Isotype switchingdefinition[GO:0045190]  
2
  • RefGenome
  • Ortholog Curator
Not  Maintenance of DNA repeat elementsdefinition[GO:0043570]  
1
  • BHF-UCL
Meiotic mismatch repairdefinition[GO:0000710]  
2
  • Ortholog Curator
  • RefGenome
Mismatch repairdefinition[GO:0006298]  
4
  • MGI
  • UniProtKB
  • HGNC
Negative regulation of DNA recombinationdefinition[GO:0045910]  
1
  • BHF-UCL
Positive regulation of helicase activitydefinition[GO:0051096]  
1
  • BHF-UCL
Reciprocal meiotic recombinationdefinition[GO:0007131]  
1
  • RefGenome
Response to UVdefinition[GO:0009411]  
2
  • Ortholog Curator
  • RefGenome
Somatic hypermutation of immunoglobulin genesdefinition[GO:0016446]  
2
  • Ortholog Curator
  • RefGenome
Somatic recombination of immunoglobulin gene segmentsdefinition[GO:0016447]  
1
  • Ortholog 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  
According to Reactome, this protein belongs to the following pathway:
Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha)  REACT_228145  
 

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