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77  structures 8005  species 0  interactions 15597  sequences 112  architectures

Family: HHH (PF00633)

Summary: Helix-hairpin-helix motif

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Helix-hairpin-helix motif Provide feedback

The helix-hairpin-helix DNA-binding motif is found to be duplicated in the central domain of RuvA [2]. The HhH domain of DisA, a bacterial checkpoint control protein, is a DNA-binding domain [5].

Literature references

  1. Doherty AJ, Serpell LC, Ponting CP; , Nucleic Acids Res 1996;24:2488-2497.: The helix-hairpin-helix DNA-binding motif: a structural basis for non-sequence-specific recognition of DNA. PUBMED:8692686 EPMC:8692686

  2. Rafferty JB, Sedelnikova SE, Hargreaves D, Artymiuk PJ, Baker PJ, Sharples GJ, Mahdi AA, Lloyd RG, Rice DW; , Science 1996;274:415-421.: Crystal structure of DNA recombination protein RuvA and a model for its binding to the Holliday junction. PUBMED:8832889 EPMC:8832889

  3. Denver DR, Swenson SL, Lynch M; , Mol Biol Evol 2003;20:1603-1611.: An evolutionary analysis of the helix-hairpin-helix superfamily of DNA repair glycosylases. PUBMED:12832627 EPMC:12832627

  4. Shao X, Grishin NV; , Nucleic Acids Res 2000;28:2643-2650.: Common fold in helix-hairpin-helix proteins. PUBMED:10908318 EPMC:10908318

  5. Witte G, Hartung S, Buttner K, Hopfner KP; , Mol Cell. 2008;30:167-178.: Structural biochemistry of a bacterial checkpoint protein reveals diadenylate cyclase activity regulated by DNA recombination intermediates. PUBMED:18439896 EPMC:18439896

Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR000445

The HhH motif is a stretch of approximately 20 amino acids that is present in prokaryotic and eukaryotic non-sequence-specific DNA binding proteins [ PUBMED:7664751 , PUBMED:9973609 , PUBMED:9987128 ]. The HhH motif is similar to, but distinct from, the HtH motif. Both of these motifs have two helices connected by a short turn. In the HtH motif the second helix binds to DNA with the helix in the major groove. This allows the contact between specific base and residues throughout the protein. In the HhH motif the second helix does not protrude from the surface of the protein and therefore cannot lie in the major groove of the DNA. Crystallographic studies suggest that the interaction of the HhH domain with DNA is mediated by amino acids located in the strongly conserved loop (L-P-G-V) and at the N-terminal end of the second helix [ PUBMED:7664751 ]. This interaction could involve the formation of hydrogen bonds between protein backbone nitrogens and DNA phosphate groups [ PUBMED:8692686 ]. The structural difference between the HtH and HhH domains is reflected at the functional level: whereas the HtH domain, found primarily in gene regulatory proteins and binds DNA in a sequence specific manner, the HhH domain is rather found in proteins involved in enzymatic activities and binds DNA with no sequence specificity [ PUBMED:8692686 ].

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 HHH (CL0198), which has the following description:

This superfamily includes Helix-hairpin-helix DNA-binding domains.

The clan contains the following 23 members:

Cdd1 DNA_pol_B_N DNA_pol_lambd_f DUF3173 DUF3701 DUF4332 DUF655 HHH HhH-GPD HHH_2 HHH_3 HHH_4 HHH_5 HHH_6 HHH_7 HHH_8 HHH_9 IMS_HHH PsbU RNA_pol_A_CTD T2SSK TfoX_C Transposase_20


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 (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB 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.

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Representative proteomes UniProt

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

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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: none
Type: Motif
Sequence Ontology: SO:0001067
Author: Bateman A
Number in seed: 87
Number in full: 15597
Average length of the domain: 29.40 aa
Average identity of full alignment: 44 %
Average coverage of the sequence by the domain: 9.92 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 57096847 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 24.0 24.0
Trusted cut-off 24.0 24.0
Noise cut-off 23.9 23.9
Model length: 30
Family (HMM) version: 25
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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This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

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The tree shows the occurrence of this domain across different species. More...


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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 HHH domain has been found. There are 77 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
A0A0R0H8M8 View 3D Structure Click here
A0A1D6ITB2 View 3D Structure Click here
A0A1D8PE92 View 3D Structure Click here
A4HTS3 View 3D Structure Click here
B8JJK1 View 3D Structure Click here
B9DFZ0 View 3D Structure Click here
C6KSY9 View 3D Structure Click here
D3ZAQ9 View 3D Structure Click here
D4A4E8 View 3D Structure Click here
F1Q4Q1 View 3D Structure Click here
F1QBP9 View 3D Structure Click here
K7LPH0 View 3D Structure Click here
K7LT72 View 3D Structure Click here
O35980 View 3D Structure Click here
P07903 View 3D Structure Click here
P07992 View 3D Structure Click here
P0A8G0 View 3D Structure Click here
P0AB83 View 3D Structure Click here
P17802 View 3D Structure Click here
P31378 View 3D Structure Click here
P54137 View 3D Structure Click here
P71728 View 3D Structure Click here
P78549 View 3D Structure Click here
P9WQ09 View 3D Structure Click here
P9WQ11 View 3D Structure Click here
Q09907 View 3D Structure Click here
Q10159 View 3D Structure Click here
Q2FYH8 View 3D Structure Click here
Q2G299 View 3D Structure Click here
Q2G2W0 View 3D Structure Click here
Q3TGW2 View 3D Structure Click here
Q4CPV5 View 3D Structure Click here
Q4CY47 View 3D Structure Click here
Q4D017 View 3D Structure Click here
Q4D1V9 View 3D Structure Click here
Q4E5B4 View 3D Structure Click here
Q58030 View 3D Structure Click here
Q58900 View 3D Structure Click here
Q86K43 View 3D Structure Click here
Q8R5G2 View 3D Structure Click here
Q99P21 View 3D Structure Click here
Q9SIC4 View 3D Structure Click here
Q9UIF7 View 3D Structure Click here
Q9VIH0 View 3D Structure Click here