Summary: MutS family domain IV
MutS family domain IV Provide feedback
This domain is found in proteins of the MutS family (DNA mismatch repair proteins) and is found associated with PF01624 PF05188 PF05192 and PF00488. 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 . The aligned region corresponds in part with globular domain IV, which is involved in DNA binding, in Thermus aquaticus MutS as characterised in .
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
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This tab holds annotation information from the InterPro database.
InterPro entry IPR007861
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 clamp domain (domain 4) found in proteins of the MutS family. The clamp domain is inserted within the core domain at the top of the lever helices. It has a beta-sheet structure [PUBMED:11048710].
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Molecular function||ATP binding (GO:0005524)|
|mismatched DNA binding (GO:0030983)|
|Biological process||mismatch repair (GO:0006298)|
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We make a range of alignments for each Pfam-A family:
- the curated alignment from which the HMM for the family is built
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- Representative Proteomes (RPs) at 15%, 35%, 55% and 75% co-membership thresholds
- alignment generated by searching the NCBI sequence database using the family HMM
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Curation and family details
|Seed source:||Members of PF01624|
|Number in seed:||51|
|Number in full:||5085|
|Average length of the domain:||92.30 aa|
|Average identity of full alignment:||34 %|
|Average coverage of the sequence by the domain:||10.61 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||13|
|Download:||download the raw HMM for this family|
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We determine these interactions using iPfam, which considers the interactions between residues in three-dimensional protein structures and maps those interactions back to Pfam families. You can find more information about the iPfam algorithm in the journal article that accompanies the website.
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_IV domain has been found. There are 48 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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