MUTSac ATPase domain of DNA mismatch repair MUTS family
SMART ACC:	SM000534
Description:	-
InterPro ACC:	IPR000432
InterPro abstract:	This entry represents the C-terminal domain found in proteins in the MutS family of DNA mismatch repair proteins. The C-terminal region of MutS is comprised of the ATPase domain and the HTH (helix-turn-helix) domain, the latter being involved in dimer contacts. Yeast MSH3 [ PUBMED:8510668 ], bacterial proteins involved … expand This entry represents the C-terminal domain found in proteins in the MutS family of DNA mismatch repair proteins. The C-terminal region of MutS is comprised of the ATPase domain and the HTH (helix-turn-helix) domain, the latter being involved in dimer contacts. Yeast MSH3 [ PUBMED:8510668 ], bacterial proteins involved in DNA mismatch repair, and the predicted protein product of the Rep-3 gene of mouse share extensive sequence similarity. Human MSH has been implicated in non-polyposis colorectal carcinoma (HNPCC) and is a mismatch binding protein. Mismatch repair contributes to the overall fidelity of DNA replication and is essential for combating the adverse effects of damage to the genome. It involves the correction of mismatched base pairs that have been missed by the proofreading element of the DNA polymerase complex. The post-replicative Mismatch Repair System (MMRS) of Escherichia coli involves MutS (Mutator S), MutL and MutH proteins, and acts to correct point mutations or small insertion/deletion loops produced during DNA replication [ PUBMED:17919654 ]. MutS and MutL are involved in preventing recombination between partially homologous DNA sequences. The assembly of MMRS is initiated by MutS, which recognises and binds to mispaired nucleotides and allows further action of MutL and MutH to eliminate a portion of newly synthesized DNA strand containing the mispaired base [ PUBMED:17599803 ]. MutS can also collaborate with methyltransferases in the repair of O(6)-methylguanine damage, which would otherwise pair with thymine during replication to create an O(6)mG:T mismatch [ PUBMED:17951114 ]. MutS exists as a dimer, where the two monomers have different conformations and form a heterodimer at the structural level [ PUBMED:17426027 ]. Only one monomer recognises the mismatch specifically and has ADP bound. Non-specific major groove DNA-binding domains from both monomers embrace the DNA in a clamp-like structure. Mismatch binding induces ATP uptake and a conformational change in the MutS protein, resulting in a clamp that translocates on DNA. collapse
GO process:	mismatch repair (GO:0006298)
GO function:	ATP binding (GO:0005524), mismatched DNA binding (GO:0030983)
Family alignment:	View the Family alignment or the Alignment consensus sequence
There are 42 358 MUTSac domains in 42 333 proteins in SMART's NRDB database.

Taxonomic distribution of proteins containing MUTSac domains

The tree below includes only several representative species and genera. The complete taxonomic breakdown of all proteins containing MUTSac domains can be accessed here. Click the counts or percentage values to display the corresponding proteins.

Relevant references for this domain

Primary literature for the MUTSac domain is listed below. Automatically-derived, secondary literature is also available.

Disease genes where sequence variants are found in this domain

UniRef sequences and OMIM curated human diseases associated with missense mutations within the MUTSac domain.

Protein	Description	Disease / phenotype
MSH2_HUMAN		OMIM:120435 : Colorectal cancer, hereditary nonpolyposis, type 1
		OMIM:114500 : Ovarian cancer ; Muir-Torre syndrome
		OMIM:158320 : no description
MSH6_HUMAN		OMIM:600678 : {Cancer susceptibility} ; Endometrial carcinoma ; Colorectal cancer, hereditary nonpolyposis, type 5
MSH6_HUMAN		OMIM:114500 : no description

KEGG pathways involving proteins which contain this domain

This information is based on the mapping of SMART genomic protein database to KEGG orthologous groups. Percentages are related to the number of proteins containing a MUTSac domain which could be assigned to a KEGG orthologous group, and not all proteins containing MUTSac domains. Please note that proteins can be included in multiple pathways, ie. the numbers below will not add to 100%.

KEGG pathways

Some of these pathways are included in the interactive Pathways Explorer overview maps. Select an overview map and click the button below to highlight them in iPath.

KEGG orthologous groups

Some of these KOs are included in the interactive Pathways Explorer overview maps. Select an overview map and click the button below to highlight them in iPath.

3D structures in PDB containing this domain

Links to other resources describing this domain

Pfam	MutS_C
InterPro	IPR000432
PROSITE	DNA_MISMATCH_REPAIR_2