MUTSd DNA-binding domain of DNA mismatch repair MUTS family
SMART ACC:	SM000533
Description:	-
InterPro ACC:	IPR007696
InterPro abstract:	This entry represents the core domain (domain 3) found in proteins of the MutS family. The core domain of MutS adopts a multi-helical structure comprised of two subdomains, which are interrupted by the clamp domain. Two of the helices in the core domain comprise the levers that extend towards the DNA. This domain is found associated with and . The aligned region corresponds with domain III … expand This entry represents the core domain (domain 3) found in proteins of the MutS family. The core domain of MutS adopts a multi-helical structure comprised of two subdomains, which are interrupted by the clamp domain. Two of the helices in the core domain comprise the levers that extend towards the DNA. This domain is found associated with and . The aligned region corresponds with domain III, which is central to the structure of Thermus aquaticus MutS as characterised in [ PUBMED:11048710 ]. 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 35 562 MUTSd domains in 35 556 proteins in SMART's NRDB database.

Taxonomic distribution of proteins containing MUTSd domains

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

Predicted cellular role

Binding / catalysis:	DNA-binding

Relevant references for this domain

Primary literature for the MUTSd 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 MUTSd 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

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 MUTSd domain which could be assigned to a KEGG orthologous group, and not all proteins containing MUTSd 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

InterPro	IPR007696
PROSITE	DNA_MISMATCH_REPAIR_2
Pfam	MutS_N