HD-GYP domain (IPR037522)

Short name: HD_GYP_dom

Overlapping homologous superfamilies


Domain relationships


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 [PMID: 9868367, PMID: 18353368].

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 alpha helices with a 5-helix core. 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 [PMID: 18353368, PMID: 24176013].

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 domain is likely to be a conserved scaffold whose main role is to allow protein-protein interactions with partner GGDEF domains while achieving (a) different function(s) through diversification of the active-site cavity and the N-terminal regulatory domains [PMID: 10943560, PMID: 25691523, PMID: 23883166]. In addition to the HD domain 5-helix core, the HD-GYP domain contains two extra C-terminal helices [PMID: 24176013, PMID: 25691523, PMID: 21990613, PMID: 24236493].

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
PROSITE profiles