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49  structures 4333  species 2  interactions 5408  sequences 62  architectures

Family: MutS_I (PF01624)

Summary: MutS domain I

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MutS domain I Provide feedback

This domain is found in proteins of the MutS family (DNA mismatch repair proteins) and is found associated with PF00488 PF05188 PF05192 and PF05190. The MutS family of proteins is named after the Salmonella typhimurium MutS protein involved in mismatch repair; other members of the family included the eukaryotic MSH 1,2,3, 4,5 and 6 proteins. These have various roles in DNA repair and recombination. Human MSH has been implicated in non-polyposis colorectal carcinoma (HNPCC) and is a mismatch binding protein [2]. The aligned region corresponds with globular domain I, which is involved in DNA binding, in Thermus aquaticus MutS as characterised in [4].

Literature references

  1. Tachiki H, Kato R, Masui R, Hasegawa K, Itakura H, Fukuyama K, Kuramitsu S; , Nucleic Acids Res 1998;26:4153-4159.: Domain organization and functional analysis of Thermus thermophilus MutS protein [published erratum appears in Nucleic Acids Res 1998 Oct 15;26(20):following 4789] PUBMED:9722634 EPMC:9722634

  2. Jiricny J; , Trends Genet 1994;10:164-168.: Colon cancer and DNA repair: have mismatches met their match? PUBMED:8036718 EPMC:8036718

  3. New L, Liu K, Crouse GF; , Mol Gen Genet 1993;239:97-108.: The yeast gene MSH3 defines a new class of eukaryotic MutS homologues. PUBMED:8510668 EPMC:8510668

  4. Obmolova G, Ban C, Hsieh P, Yang W; , Nature 2000;407:703-710.: Crystal structures of mismatch repair protein MutS and its complex with a substrate DNA. PUBMED:11048710 EPMC:11048710


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR007695

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 N-terminal domain of proteins in the MutS family of DNA mismatch repair proteins, as well as closely related proteins. The N-terminal domain of MutS is responsible for mismatch recognition and forms a 6-stranded mixed beta-sheet surrounded by three alpha-helices, which is similar to the structure of tRNA endonuclease. 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.

Gene Ontology

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Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the NCBI sequence database, and our metagenomics sequence database. More...

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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

  Seed
(60)
Full
(5408)
Representative proteomes NCBI
(4546)
Meta
(1040)
RP15
(529)
RP35
(978)
RP55
(1330)
RP75
(1586)
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Format an alignment

  Seed
(60)
Full
(5408)
Representative proteomes NCBI
(4546)
Meta
(1040)
RP15
(529)
RP35
(978)
RP55
(1330)
RP75
(1586)
Alignment:
Format:
Order:
Sequence:
Gaps:
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We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

  Seed
(60)
Full
(5408)
Representative proteomes NCBI
(4546)
Meta
(1040)
RP15
(529)
RP35
(978)
RP55
(1330)
RP75
(1586)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download   Download  

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Pfam-B_800 (release 4.1)
Previous IDs: MutS;MutS_N;
Type: Domain
Author: Bashton M, Bateman A, Studholme, DJ
Number in seed: 60
Number in full: 5408
Average length of the domain: 110.20 aa
Average identity of full alignment: 40 %
Average coverage of the sequence by the domain: 13.01 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 20.6 20.6
Trusted cut-off 20.6 20.6
Noise cut-off 20.4 20.5
Model length: 113
Family (HMM) version: 15
Download: download the raw HMM for this family

Species distribution

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Interactions

There are 2 interactions for this family. More...

MutS_I MutS_III

Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the MutS_I domain has been found. There are 49 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

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