Colon Cancer MSH2 Mismatch Repair Protein

OMIM identified the MSH2 protein as a mismatch repair protein that, if mutated, can lead to unrepaired DNA damage and colon cancer. MSH2 was found to be homologous to E. coli Muts gene. Purified MSH2 protein binds specifically to DNA containing insertion-deletion loop-type (IDL) mismatched nucleotides.



NCBI conserved domain database Blast search (rpsblast) using Homo sapien MSH2 protein (AAB59565) reported MSH2 to be a member of the MutS DNA mismatch repair family. The molecular function of MSH2 is DNA and ATP-binding and the biological process is mismatch repair.


Domain relatives found from the rpsblast search include: MutS domain I found in proteins of the MutS family (DNA mismatch repair protein), MutS domain II also in the MutS family, MutSd DNA-binding domain of the MutS mismatch repair family, and MutS domain V of the MutS family, which was found to contain a Walker A motif structurally similar to ATPase domain in ABC transporters. Other members of the MutS family include Eukaryotic MSH1, 2, 3, 4, 5, and 6 proteins.


EMBL-EBI search also identified MSH2 as a mismatch repair protein with a dual role in DNA repair and apoptosis. Many proteins that are involved in DNA repair processes also play roles in apoptosis, preventing carcinogenesis when DNA damage is too accessive to repair. MSH2 functions in the nucleus as a heterodimer with MSH6 to replace mispaired bases.



The domains identified by the Human Protein Reference Database include MUTSd (aa's 321-645), and MUTSac (aa's 662-849) of the MUTs family of DNA mismatch repair proteins. MUTSac is the ATPase binding domain of MSH2.


The coiled coil (aa's 552-580) motif for MSH2 was identified by the Human Protein Reference Database. Coiled coil is a protein domain that forms a bundle of two or three alpha helices.



The COILS program predicts coiled coil regions in proteins and calculates the probability that the sequence will adopt a coiled-coil conformation.








Interprotein database search identified 5 domains for MSH2.

DNA mismatch repair protein MutS, C-terminal

DNA mismatch repair protein MutS, N-terminal

MutS III

MutS II

MutSIV