PROSITE documentation PDOC00388
DNA mismatch repair proteins mutS family signature


Mismatch repair contributes to the overall fidelity of DNA replication [1]. It involves the correction of mismatched base pairs that have been missed by the proofreading element of the DNA polymerase complex. The sequence of some proteins involved in mismatch repair in different organisms have been found to be evolutionary related [2,3]. One of these families is called mutS [4], it consists of:

  • Prokaroytic protein mutS protein (also called hexA in Streptococcus pneumoniae). Muts is thought to carry out the mismatch recognition step of DNA repair.
  • Eukaryotic MSH1, which is involved in mitochondrial DNA repair.
  • Eukaryotic MSH2, which is involved in nuclear postreplication mismatch repair. MSH2 heterodimerizes with MSH6. In man, MSH2 is involved in a form of familial hereditary nonpolyposis colon cancer (HNPCC).
  • Eukaryotic MSH3, which is probably involved in the repair of large loops.
  • Eukaryotic MSH4, which is involved in meiotic recombination.
  • Eukaryotic MSH5, which is involved in meiotic recombination.
  • Eukaryotic MSH6 (also known as G/T mismatch binding protein), a DNA-repair protein that binds to G/T mismatches through heterodimerization with MSH2.
  • Prokaryotic protein mutS2 whose function is not yet known.
  • A coral (Sarcophyton glaucum) mitochondrial encoded mutS-like protein.

As a signature pattern for this class of mismatch repair proteins we selected a region rich in glycine and negatively charged residues. This region is found in the C-terminal section of these proteins; about 80 residues to the C-terminal of an ATP-binding site motif 'A' (P-loop) (see <PDOC00017>).

Expert(s) to contact by email:

Eisen J.A.

Last update:

December 2004 / Pattern and text revised.


Technical section

PROSITE method (with tools and information) covered by this documentation:

DNA_MISMATCH_REPAIR_2, PS00486; DNA mismatch repair proteins mutS family signature  (PATTERN)


1AuthorsModrich P.
TitleDNA mismatch correction.
SourceAnnu. Rev. Biochem. 56:435-466(1987).
PubMed ID3304141

2AuthorsHaber L.T. Walker G.C.
TitleAltering the conserved nucleotide binding motif in the Salmonella typhimurium MutS mismatch repair protein affects both its ATPase and mismatch binding activities.
SourceEMBO J. 10:2707-2715(1991).
PubMed ID1651234

3AuthorsNew L. Liu K. Crouse G.F.
TitleThe yeast gene MSH3 defines a new class of eukaryotic MutS homologues.
SourceMol. Gen. Genet. 239:97-108(1993).
PubMed ID8510668

4AuthorsEisen J.A.
TitleA phylogenomic study of the MutS family of proteins.
SourceNucleic Acids Res. 26:4291-4300(1998).
PubMed ID9722651

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