Please note: this site relies heavily on the use of javascript. Without a javascript-enabled browser, this site will not function correctly. Please enable javascript and reload the page, or switch to a different browser.
41  structures 4519  species 4  interactions 8740  sequences 51  architectures

Family: HHH (PF00633)

Summary: Helix-hairpin-helix motif

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

The Pfam group coordinates the annotation of Pfam families in Wikipedia, but we have not yet assigned a Wikipedia article to this family. If you think that a particular Wikipedia article provides good annotation, please let us know.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

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


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...

Loading domain graphics...

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 20 members:

Cdd1 DNA_pol_lambd_f DUF3173 DUF4332 DUF655 HHH HhH-GPD HHH_2 HHH_3 HHH_4 HHH_5 HHH_6 HHH_7 HHH_8 IMS_HHH PsbU RNA_pol_A_CTD T2SK TfoX_C Transposase_20

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...

View options

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
(104)
Full
(8740)
Representative proteomes NCBI
(8454)
Meta
(3232)
RP15
(624)
RP35
(1195)
RP55
(1556)
RP75
(1840)
Jalview View  View  View  View  View  View  View  View 
HTML View    View  View  View  View     
PP/heatmap 1   View  View  View  View     
Pfam viewer View  View             

1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

  Seed
(104)
Full
(8740)
Representative proteomes NCBI
(8454)
Meta
(3232)
RP15
(624)
RP35
(1195)
RP55
(1556)
RP75
(1840)
Alignment:
Format:
Order:
Sequence:
Gaps:
Download/view:

Download options

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
(104)
Full
(8740)
Representative proteomes NCBI
(8454)
Meta
(3232)
RP15
(624)
RP35
(1195)
RP55
(1556)
RP75
(1840)
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: Prosite
Previous IDs: none
Type: Motif
Author: Bateman A
Number in seed: 104
Number in full: 8740
Average length of the domain: 29.70 aa
Average identity of full alignment: 42 %
Average coverage of the sequence by the domain: 10.45 %

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 24.0 24.0
Trusted cut-off 24.0 24.0
Noise cut-off 23.9 23.9
Model length: 30
Family (HMM) version: 18
Download: download the raw HMM for this family

Species distribution

Sunburst controls

Show

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...

Loading sunburst data...

Tree controls

Hide

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

Loading...

Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.

Interactions

There are 4 interactions for this family. More...

Rad51 HhH-GPD HHH ERCC4

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 HHH domain has been found. There are 41 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.

Loading structure mapping...