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DNA mismatch repair protein Msh3; MutS holomolog 3; divergent upstream protein; DUP; mismatch repair protein 1; MRP1 (MSH3, DUC1, DUG)
Function:
- component of the post-replicative DNA mismatch repair system (MMR)
- heterodimerizes with MSH2 to form mutS beta which binds to DNA mismatches thereby initiating DNA repair
- when bound, the mutS beta heterodimer bends the DNA helix & shields approximately 20 base pairs
- mutS beta recognizes large insertion-deletion loops (IDL) up to 13 nucleotides long
- 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, & resynthesis
- phosphorylated upon DNA damage, probably by ATM or ATR
- heterodimer consisting of MSH2-MSH3 (mutS beta)
- forms a ternary complex with mutL alpha (MLH1-PMS1)
- interacts with EXO1
Structure:
- belongs to the DNA mismatch repair mutS family, MSH3 subfamily
Pathology:
- defects in MSH3 are a cause of susceptibility to endometrial cancer
General
mutS family protein
phosphoprotein
Properties
SIZE: entity length = 1137 aa
MW = 127 kD
COMPARTMENT: cell nucleus
MOTIF: alanine-rich region {51-62}
MOTIF: alanine residue (SEVERAL)
EXO1 interaction {75-297}
MOTIF: Ser phosphorylation site {S201}
ATP-binding site
NAME: ATP-binding site
SITE: 896-903
Tyr phosphorylation site {Y1068}
References
- UniProt :accession P20585
- Atlas of Genetics & Cytogenetics in Oncology & Haematology
http://atlasgeneticsoncology.org/genes/MSH3ID341ch5q11.html
- NIEHS-SNPs
http://egp.gs.washington.edu/data/msh3/
Component-of
MutS-beta
Databases & Figures
OMIM correlations
UniProt P20585
PFAM correlations
Entrez Gene 4437
Kegg hsa:4437
mismatch repair scheme (v2)