The HD domain, named after the conserved doublet of predicted catalytic
residues, is found in a wide range of bacterial, archaeal and eukaryotic
proteins. It defines a superfamily of phosphohydrolases that can catalyze both
metal-dependent and -independent phosphomonoesterase and phosphodiesterase
reactions for a broad range of substrates [1,2]:
- Bacterial dGTPase.
- Bacterial polyA polymerases.
- Bacterial CCA-adding enzymes, catalyze the addition and repair of the
essential 3'-terminal CCA sequence in tRNAs without using a nucleic acid
- Bacterial uridylyl transferases (GlnD).
- Bacterial stringent-response guanosine polyphosphate [ppgpp(p)] hydrolase/
- Fungal cyanamide lyase.
The HD-domain proteins appear to be involved in nucleic acid and nucleotide
metabolism, signal transduction and possibly other functions. They are diverse
in terms of both domain architecture and phylogenetic distribution; each of
the completely sequenced genomes encodes more than one version of this domain.
The HD domain is composed of a bundle of α helices with a 5-helix core
(see <PDB:2PAR>). Although all HD domains share key design features, a
striking diversity of catalytic centres have been identified, containing no
metal, mono-, bi- or trinuclear metal binding sites [2,3].
A distinct version of this domain, HD-GYP, contains a number of additional
highly conserved residues. The spectrum of the domains that are associated
with HD-GYP in multidomain proteins suggests that it is probably involved in
signal transduction. The HD-GYP family of HD proteins so far is lacking in
archaea and eukaryotes. The HD-GYP domain is likely to be a conserved scaffold
whose main role is to allow protein-protein interactions with partner GGDEF
domains (see <PDOC50887>) while achieving (a) different function(s) through
diversification of the active-site cavity and the N-terminal regulatory
- Xanthomonas campestris RpfG, a multi-phenotype protein involved in
virulence, motility and biofilm regulation. It functions as cyclic di-
3',5'-GMP (c-di-GMP) degrading phosphodiesterase.
- Persephonella marina PmGH, a cyclic di-3',5'-GMP (c-di-GMP)
- Bdellovibrio bacteriovorus Bd1817, a catalytically inactive protein.
- Pseudomonas aeruginosa PA4781 protein, a phosphodiesterase involved in
cyclic di-3',5'-GMP (c-di-GMP) degradation.
- Pseudomonas aeruginosa PA4108 protein,
- Vibrio cholerae VCA0861, contains tandem HD and HD-GYP domains .
In addition to the HD domain 5-helix core, the HD-GYP domain contains two
extra C-terminal helices (see <PDB:4MCW>) [3,5,7,8].
The HD-related output domain (HDOD) is a protein domain of unknown function.
Proteins containing the HDOD are widespread in diverse bacteria; it can be
present as a stand-alone domain, and also associated with other domains, such
as response regulatory (RR) (see <PDOC50110>), GGDEF (see <PDOC50887>), and
EAL (see <PDOC50883>), suggesting a role in regulation and signaling [9,10]:
- Campylobacter jejuni virulence factor CJ048, a stand-alone HDOD containing
protein required for motility and involved in colonization of the chick
- Xanthomonas campestris pv. campestris (Xcc) GsmR (general stress and
motility regulator), plays a role in the general stress response of Xcc and
is involved in the expression of genes responsible for flagellum synthesis.
It has a RR domain at the N-terminus and a C-terminal HDOD.
- Xanthomonas campestris pv. campestris (Xcc) HdpA, contains a HDOD at the N-
terminus and a GGDEF domain at the C-terminus.
- Xanthomonas campestris pv. campestris (Xcc) HdpB, a stand-alone HDOD
The HDOD domain folds into a complex arrangement of α helices (see
The profiles we developed cover respectively the core HD domain and the entire
HD-GYP and HDOD domains.
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