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83  structures 7335  species 0  interactions 23844  sequences 299  architectures

Family: MutS_V (PF00488)

Summary: MutS domain V

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MutS domain V 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 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 domain V of Thermus aquaticus MutS as characterised in [4] which contains a Walker A motif, and is structurally similar to the ATPase domain of ABC transporters.

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

Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR000432

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 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.

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

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

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Pfam Clan

This family is a member of clan P-loop_NTPase (CL0023), which has the following description:

AAA family proteins often perform chaperone-like functions that assist in the assembly, operation, or disassembly of protein complexes [2].

The clan contains the following 245 members:

6PF2K AAA AAA-ATPase_like AAA_10 AAA_11 AAA_12 AAA_13 AAA_14 AAA_15 AAA_16 AAA_17 AAA_18 AAA_19 AAA_2 AAA_21 AAA_22 AAA_23 AAA_24 AAA_25 AAA_26 AAA_27 AAA_28 AAA_29 AAA_3 AAA_30 AAA_31 AAA_32 AAA_33 AAA_34 AAA_35 AAA_5 AAA_6 AAA_7 AAA_8 AAA_9 AAA_PrkA ABC_ATPase ABC_tran ABC_tran_Xtn Adeno_IVa2 Adenylsucc_synt ADK AFG1_ATPase AIG1 APS_kinase Arf ArsA_ATPase ATP-synt_ab ATP_bind_1 ATP_bind_2 ATPase ATPase_2 Bac_DnaA BCA_ABC_TP_C Beta-Casp bpMoxR BrxC_BrxD BrxL_ATPase Cas_Csn2 Cas_St_Csn2 CbiA CBP_BcsQ CDC73_C CENP-M CFTR_R CLP1_P CMS1 CoaE CobA_CobO_BtuR CobU cobW CPT CSM2 CTP_synth_N Cytidylate_kin Cytidylate_kin2 DAP3 DEAD DEAD_2 divDNAB DLIC DNA_pack_C DNA_pack_N DNA_pol3_delta DNA_pol3_delta2 DnaB_C dNK DO-GTPase1 DO-GTPase2 DUF1611 DUF2075 DUF2326 DUF2478 DUF257 DUF2813 DUF3584 DUF463 DUF4914 DUF5906 DUF6079 DUF815 DUF835 DUF87 DUF927 Dynamin_N Dynein_heavy Elong_Iki1 ELP6 ERCC3_RAD25_C Exonuc_V_gamma FeoB_N Fer4_NifH Flavi_DEAD FTHFS FtsK_SpoIIIE G-alpha Gal-3-0_sulfotr GBP GBP_C GpA_ATPase GpA_nuclease GTP_EFTU Gtr1_RagA Guanylate_kin GvpD_P-loop HDA2-3 Helicase_C Helicase_C_2 Helicase_C_4 Helicase_RecD HerA_C Herpes_Helicase Herpes_ori_bp Herpes_TK HydF_dimer HydF_tetramer Hydin_ADK IIGP IPPT IPT iSTAND IstB_IS21 KAP_NTPase KdpD Kinase-PPPase Kinesin KTI12 LAP1_C LpxK MCM MeaB MEDS Mg_chelatase Microtub_bd MipZ MMR_HSR1 MMR_HSR1_C MobB MukB Mur_ligase_M MutS_V Myosin_head NACHT NAT_N NB-ARC NOG1 NTPase_1 NTPase_P4 ORC3_N P-loop_TraG ParA Parvo_NS1 PAXNEB PduV-EutP PhoH PIF1 Ploopntkinase1 Ploopntkinase2 Ploopntkinase3 Podovirus_Gp16 Polyoma_lg_T_C Pox_A32 PPK2 PPV_E1_C PRK PSY3 Rad17 Rad51 Ras RecA ResIII RHD3_GTPase RhoGAP_pG1_pG2 RHSP RNA12 RNA_helicase Roc RsgA_GTPase RuvB_N SbcC_Walker_B SecA_DEAD Senescence Septin Sigma54_activ_2 Sigma54_activat SKI SMC_N SNF2-rel_dom SpoIVA_ATPase Spore_III_AA SRP54 SRPRB SulA Sulfotransfer_1 Sulfotransfer_2 Sulfotransfer_3 Sulfotransfer_4 Sulfotransfer_5 Sulphotransf SWI2_SNF2 T2SSE T4SS-DNA_transf TerL_ATPase Terminase_3 Terminase_6N Thymidylate_kin TIP49 TK TmcA_N TniB Torsin TraG-D_C tRNA_lig_kinase TrwB_AAD_bind TsaE UvrB UvrD-helicase UvrD_C UvrD_C_2 Viral_helicase1 VirC1 VirE YqeC Zeta_toxin Zot


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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...


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.

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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: Prosite
Previous IDs: mutS;MutS_C;
Type: Domain
Sequence Ontology: SO:0000417
Author: Finn RD , Studholme DJ
Number in seed: 28
Number in full: 23844
Average length of the domain: 181.6 aa
Average identity of full alignment: 34 %
Average coverage of the sequence by the domain: 21.85 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 30.2 30.2
Trusted cut-off 30.2 30.2
Noise cut-off 30.1 30.1
Model length: 188
Family (HMM) version: 24
Download: download the raw HMM for this family

Species distribution

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Colour assignments

Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence


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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_V domain has been found. There are 83 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 sequence.

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AlphaFold Structure Predictions

The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.

Protein Predicted structure External Information
A0A044S2A3 View 3D Structure Click here
A0A044S8D7 View 3D Structure Click here
A0A044TQY9 View 3D Structure Click here
A0A044U217 View 3D Structure Click here
A0A077YUP8 View 3D Structure Click here
A0A077YWG3 View 3D Structure Click here
A0A077ZB74 View 3D Structure Click here
A0A077ZDQ8 View 3D Structure Click here
A0A0D2DCC5 View 3D Structure Click here
A0A0D2DRK1 View 3D Structure Click here
A0A0D2DSS7 View 3D Structure Click here
A0A0D2F1R8 View 3D Structure Click here
A0A0D2GH01 View 3D Structure Click here
A0A0D2GT02 View 3D Structure Click here
A0A0H3GWS4 View 3D Structure Click here
A0A0K0EF71 View 3D Structure Click here
A0A0K0EKW7 View 3D Structure Click here
A0A0K0EKX1 View 3D Structure Click here
A0A0K0EPS7 View 3D Structure Click here
A0A0K0JNX6 View 3D Structure Click here
A0A0K0JT65 View 3D Structure Click here
A0A0N4U3R2 View 3D Structure Click here
A0A0N4U3R8 View 3D Structure Click here
A0A0N4UHB4 View 3D Structure Click here
A0A0N4UP89 View 3D Structure Click here
A0A0P0XWQ1 View 3D Structure Click here
A0A0R0ER15 View 3D Structure Click here
A0A0R0GPT1 View 3D Structure Click here
A0A0R0I5C6 View 3D Structure Click here
A0A0R0J136 View 3D Structure Click here
A0A0R0L9U5 View 3D Structure Click here
A0A0R4IAE0 View 3D Structure Click here
A0A158Q6I6 View 3D Structure Click here
A0A175VV93 View 3D Structure Click here
A0A175VXM2 View 3D Structure Click here
A0A175VXT7 View 3D Structure Click here
A0A175WDV7 View 3D Structure Click here
A0A175WFZ4 View 3D Structure Click here
A0A1C1C723 View 3D Structure Click here
A0A1C1CE67 View 3D Structure Click here