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121  structures 4824  species 5  interactions 13897  sequences 76  architectures

Family: HhH-GPD (PF00730)

Summary: HhH-GPD superfamily base excision DNA repair protein

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.

HhH-GPD superfamily base excision DNA repair protein Provide feedback

This family contains a diverse range of structurally related DNA repair proteins. The superfamily is called the HhH-GPD family after its hallmark Helix-hairpin-helix and Gly/Pro rich loop followed by a conserved aspartate [2]. This includes endonuclease III, EC:4.2.99.18 and MutY an A/G-specific adenine glycosylase, both have a C terminal 4Fe-4S cluster. The family also includes 8-oxoguanine DNA glycosylases such as P53397. The methyl-CPG binding protein MBD4 Q9Z2D7 also contains a related domain [1] that is a thymine DNA glycosylase. The family also includes DNA-3-methyladenine glycosylase II EC:3.2.2.21 and other members of the AlkA family.

Literature references

  1. Hendrich B, Hardeland U, Ng HH, Jiricny J, Bird A; , Nature 1999;401:301-304.: The thymine glycosylase MBD4 can bind to the product of deamination at methylated CpG sites. PUBMED:10499592 EPMC:10499592

  2. Bruner SD, Norman DP, Verdine GL; , Nature 2000;403:859-866.: Structural basis for recognition and repair of the endogenous mutagen 8-oxoguanine in DNA. PUBMED:10706276 EPMC:10706276


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR003265

Endonuclease III (EC) is a DNA repair enzyme which removes a number of damaged pyrimidines from DNA via its glycosylase activity and also cleaves the phosphodiester backbone at apurinic / apyrimidinic sites via a beta-elimination mechanism [PUBMED:7773744, PUBMED:9032058]. The structurally related DNA glycosylase MutY recognises and excises the mutational intermediate 8-oxoguanine-adenine mispair [PUBMED:1328155]. The 3-D structures of Escherichia coli endonuclease III [PUBMED:1411536] and catalytic domain of MutY [PUBMED:9846876] have been determined. The structures contain two all-alpha domains: a sequence-continuous, six-helix domain (residues 22-132) and a Greek-key, four-helix domain formed by one N-terminal and three C-terminal helices (residues 1-21 and 133-211) together with the [Fe4S4] cluster. The cluster is bound entirely within the C-terminal loop by four cysteine residues with a ligation pattern Cys-(Xaa)6-Cys-(Xaa)2-Cys-(Xaa)5-Cys which is distinct from all other known Fe4S4 proteins. This structural motif is referred to as a [Fe4S4] cluster loop (FCL) [PUBMED:7664751]. Two DNA-binding motifs have been proposed, one at either end of the interdomain groove: the helix-hairpin-helix (HhH) and FCL motifs (see INTERPRO). The primary role of the iron-sulphur cluster appears to involve positioning conserved basic residues for interaction with the DNA phosphate backbone by forming the loop of the FCL motif [PUBMED:7664751, PUBMED:10900127].

The HhH-GPD domain gets its name from its hallmark helix-hairpin-helix and Gly/Pro rich loop followed by a conserved aspartate. This domain is found in a diverse range of structurally related DNA repair proteins that include: endonuclease III, EC and DNA glycosylase MutY, an A/G-specific adenine glycosylase. Both of these enzymes have a C-terminal iron-sulphur cluster loop (FCL). The methyl-CPG binding protein (MBD4) also contain a related domain that is a thymine DNA glycosylase. The family also includes DNA-3-methyladenine glycosylase II EC, 8-oxoguanine DNA glycosylases and other members of the AlkA family.

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 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
(72)
Full
(13897)
Representative proteomes NCBI
(10642)
Meta
(6191)
RP15
(1240)
RP35
(2398)
RP55
(3196)
RP75
(3791)
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1Cannot generate PP/Heatmap alignments for seeds; no PP data available

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

Format an alignment

  Seed
(72)
Full
(13897)
Representative proteomes NCBI
(10642)
Meta
(6191)
RP15
(1240)
RP35
(2398)
RP55
(3196)
RP75
(3791)
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
(72)
Full
(13897)
Representative proteomes NCBI
(10642)
Meta
(6191)
RP15
(1240)
RP35
(2398)
RP55
(3196)
RP75
(3791)
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_854 (release 2.1)
Previous IDs: Endonuclease_3;
Type: Domain
Author: Bateman A
Number in seed: 72
Number in full: 13897
Average length of the domain: 138.90 aa
Average identity of full alignment: 24 %
Average coverage of the sequence by the domain: 47.70 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null --hand HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 21.9 21.9
Trusted cut-off 21.9 21.9
Noise cut-off 21.8 21.8
Model length: 108
Family (HMM) version: 20
Download: download the raw HMM for this family

Species distribution

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Interactions

There are 5 interactions for this family. More...

OGG_N EndIII_4Fe-2S HhH-GPD HHH AlkA_N

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-GPD domain has been found. There are 121 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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