Summary: HhH-GPD superfamily base excision DNA repair protein
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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 . This includes endonuclease III, EC:22.214.171.124 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  that is a thymine DNA glycosylase. The family also includes DNA-3-methyladenine glycosylase II EC:126.96.36.199 and other members of the AlkA family.
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
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.
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Biological process||base-excision repair (GO:0006284)|
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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 T2SSK TfoX_C Transposase_20
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Curation and family details
|Seed source:||Pfam-B_854 (release 2.1)|
|Number in seed:||52|
|Number in full:||56495|
|Average length of the domain:||139.90 aa|
|Average identity of full alignment:||23 %|
|Average coverage of the sequence by the domain:||49.50 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null --hand HMM SEED
search method: hmmsearch -Z 80369284 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||21|
|Download:||download the raw HMM for this family|
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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-GPD domain has been found. There are 124 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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