The domain within your query sequence starts at position 158 and ends at position 485; the E-value for the MUTSd domain shown below is 9.4e-40.

RSNHTLFGVLNYTKTAGGSRRLRSNILEPLVDVETISMRLDCVQELLQDEELFFGLQSVI
SRFLDTEQLLSVLVQIPKQDTVNAAESKITNLIYLKHTLELVEPLKVTLKNCSTPLLRAY
YGSLEDHRFGLILDKIKTVINDDARYMKGCLNMRTQKCYAVRSNISEFLDIARRTYTEIV
DDIAGMIAQLAEKYSLPLRTSFSSSRGFFIQMTTDCAALSSDQLPSEFIKISKVKNSYSF
TSADLIKMNERCQESLREIYHMTYMIVCKLLSEIYEHIHCLYKLSDTVSMLDMLLSFAHA
CTLSDYVRPEFTDTLAIKQGWHPILEKI

MUTSd

DNA-binding domain of DNA mismatch repair MUTS family

• SMART accession number: SM00533
• Description: -
• Interpro abstract (IPR007696):

  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.

  MutS is a modular protein with a complex structure [ (PUBMED:11048711) ], and is composed of:

  • N-terminal mismatch-recognition domain, which is similar in structure to tRNA endonuclease.
  • Connector domain, which is similar in structure to Holliday junction resolvase ruvC.
  • Core domain, which is composed of two separate subdomains that join together to form a helical bundle; from within the core domain, two helices act as levers that extend towards (but do not touch) the DNA.
  • Clamp domain, which is inserted between the two subdomains of the core domain at the top of the lever helices; the clamp domain has a beta-sheet structure.
  • ATPase domain (connected to the core domain), which has a classical Walker A motif.
  • HTH (helix-turn-helix) domain, which is involved in dimer contacts.

  The MutS family of proteins is named after the Salmonella typhimurium MutS protein involved in mismatch repair. Homologues of MutS have been found in many species including eukaryotes (MSH 1, 2, 3, 4, 5, and 6 proteins), archaea and bacteria, and together these proteins have been grouped into the MutS family. Although many of these proteins have similar activities to the E. coli MutS, there is significant diversity of function among the MutS family members. Human MSH has been implicated in non-polyposis colorectal carcinoma (HNPCC) and is a mismatch binding protein [ (PUBMED:8036718) ].This diversity is even seen within species, where many species encode multiple MutS homologues with distinct functions [ (PUBMED:9722651) ]. Inter-species homologues may have arisen through frequent ancient horizontal gene transfer of MutS (and MutL) from bacteria to archaea and eukaryotes via endosymbiotic ancestors of mitochondria and chloroplasts [ (PUBMED:17965091) ].

  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 Pfam:PF00488, Pfam:PF05188, Pfam:PF01624 and Pfam:PF05190. The aligned region corresponds with domain III, which is central to the structure of Thermus aquaticus MutS as characterised in [ (PUBMED:11048710) ].

• GO process: mismatch repair (GO:0006298)
• GO function: ATP binding (GO:0005524), mismatched DNA binding (GO:0030983)

There are 35562 MUTSd domains in 35556 proteins in SMART's nrdb database.

Cellular role (predicted cellular role)

Binding / catalysis: DNA-binding

Literature (relevant references for this domain)

Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.

• New L, Liu K, Crouse GF
• The yeast gene MSH3 defines a new class of eukaryotic MutS homologues.
• Mol Gen Genet. 1993; 239: 97-108

We have identified a gene in Saccharomyces cerevisiae, MSH3, whose predicted protein product shares extensive sequence similarity with bacterial proteins involved in DNA mismatch repair as well as with the predicted protein product of the Rep-3 gene of mouse. MSH3 was obtained by performing a polymerase chain reaction on yeast genomic DNA using degenerate oligonucleotide primers designed to anneal with the most conserved regions of a gene that would be homologous to Rep-3 and Salmonella typhimurium mutS. MSH3 seems to play some role in DNA mismatch repair, inasmuch as its inactivation results in an increase in reversion rates of two different mutations and also causes an increase in postmeiotic segregation. However, the effect of MSH3 disruption on reversion rates and postmeiotic segregation appears to be much less than that of previously characterized yeast DNA mismatch repair genes. Alignment of the MSH3 sequence with all of the known MutS homologues suggests that its primary function may be different from the role of MutS in repair of replication errors. MSH3 appears to be more closely related to the mouse Rep-3 gene and other similar eukaryotic mutS homologues than to the yeast gene MSH2 and other mutS homologues that are involved in replication repair. We suggest that the primary function of MSH3 may be more closely related to one of the other known functions of mutS, such as its role in preventing recombination between non-identical sequences.

Disease (disease genes where sequence variants are found in this domain)

SwissProt sequences and OMIM curated human diseases associated with missense mutations within the MUTSd domain.

Protein	Disease
DNA mismatch repair protein Msh2 (P43246) (SMART)	OMIM:120435: Colorectal cancer, hereditary nonpolyposis, type 1 OMIM:114500: Ovarian cancer ; Muir-Torre syndrome OMIM:158320:

Metabolism (metabolic pathways involving proteins which contain this domain)

% proteins involved	KEGG pathway ID	Description
98.15	map05210	Colorectal cancer
1.85	map00190	Oxidative phosphorylation

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

Structure (3D structures containing this domain)

3D Structures of MUTSd domains in PDB

PDB code	Title
1e3m	The crystal structure of E. coli MutS binding to DNA with a G:T mismatch
1ewq	CRYSTAL STRUCTURE TAQ MUTS COMPLEXED WITH A HETERODUPLEX DNA AT 2.2 A RESOLUTION
1ewr	CRYSTAL STRUCTURE OF TAQ MUTS
1fw6	CRYSTAL STRUCTURE OF A TAQ MUTS-DNA-ADP TERNARY COMPLEX
1ng9	E.coli MutS R697A: an ATPase-asymmetry mutant
1nne	Crystal Structure of the MutS-ADPBeF3-DNA complex
1oh5	THE CRYSTAL STRUCTURE OF E. COLI MUTS BINDING TO DNA WITH A C:A MISMATCH
1oh6	THE CRYSTAL STRUCTURE OF E. COLI MUTS BINDING TO DNA WITH AN A:A MISMATCH
1oh7	THE CRYSTAL STRUCTURE OF E. COLI MUTS BINDING TO DNA WITH A G:G MISMATCH
1oh8	THE CRYSTAL STRUCTURE OF E. COLI MUTS BINDING TO DNA WITH AN UNPAIRED THYMIDINE
1w7a	ATP bound MutS
1wb9	Crystal Structure of E. coli DNA Mismatch Repair enzyme MutS, E38T mutant, in complex with a G.T mismatch
1wbb	Crystal structure of E. coli DNA mismatch repair enzyme MutS, E38A mutant, in complex with a G.T mismatch
1wbd	Crystal structure of E. coli DNA mismatch repair enzyme MutS, E38Q mutant, in complex with a G.T mismatch
2o8b	human MutSalpha (MSH2/MSH6) bound to ADP and a G T mispair
2o8c	human MutSalpha (MSH2/MSH6) bound to ADP and an O6-methyl-guanine T mispair
2o8d	human MutSalpha (MSH2/MSH6) bound to ADP and a G dU mispair
2o8e	human MutSalpha (MSH2/MSH6) bound to a G T mispair, with ADP bound to MSH2 only
2o8f	human MutSalpha (MSH2/MSH6) bound to DNA with a single base T insert
2wtu	Crystal structure of Escherichia coli MutS in complex with a 16 basepair oligo containing an A.A mismatch.
3k0s	Crystal structure of E.coli DNA mismatch repair protein MutS, D693N mutant, in complex with GT mismatched DNA
3thw	Human MutSbeta complexed with an IDL of 4 bases (Loop4) and ADP
3thx	Human MutSbeta complexed with an IDL of 3 bases (Loop3) and ADP
3thy	Human MutSbeta complexed with an IDL of 2 bases (Loop2) and ADP
3thz	Human MutSbeta complexed with an IDL of 6 bases (Loop6) and ADP
3zlj	CRYSTAL STRUCTURE OF FULL-LENGTH E.COLI DNA MISMATCH REPAIR PROTEIN MUTS D835R MUTANT IN COMPLEX WITH GT MISMATCHED DNA
5akb	5AKB
5akc	5AKC
5akd	5AKD

Links (links to other resources describing this domain)

• PROSITE: DNA_MISMATCH_REPAIR_2
• PFAM: MutS_N
• INTERPRO: IPR007696