InterPro : IPR014626

Name  Signal transduction response regulator, modified HD-GYP domain-containing, putative Short Name  Sig_transdc_resp-reg_put
Type  Family Description  Two-component signal transduction systems enable bacteria to sense, respond, and adapt to a wide range of environments, stressors, and growth conditions []. Some bacteria can contain up to as many as 200 two-component systems that need tight regulation to prevent unwanted cross-talk []. These pathways have been adapted to response to a wide variety of stimuli, including nutrients, cellular redox state, changes in osmolarity, quorum signals, antibiotics, and more []. Two-component systems are comprised of a sensor histidine kinase (HK) and its cognate response regulator (RR) []. The HK catalyses its own auto-phosphorylation followed by the transfer of the phosphoryl group to the receiver domain on RR; phosphorylation of the RR usually activates an attached output domain, which can then effect changes in cellular physiology, often by regulating gene expression. Some HK are bifunctional, catalysing both the phosphorylation and dephosphorylation of their cognate RR. The input stimuli can regulate either the kinase or phosphatase activity of the bifunctional HK.A variant of the two-component system is the phospho-relay system. Here a hybrid HK auto-phosphorylates and then transfers the phosphoryl group to an internal receiver domain, rather than to a separate RR protein. The phosphoryl group is then shuttled to histidine phosphotransferase (HPT) and subsequently to a terminal RR, which can evoke the desired response [, ].This entry represents a group of signal transduction response regulators which contain a modified version of the HD-GYP domain as an output domain.Response regulators of the microbial two-component signal transduction systems typically consist of an N-terminal CheY-like receiver (phosphoacceptor) domain and a C-terminal output (usually DNA-binding) domain. In response to an environmental stimulus, a phosphoryl group is transferred from the His residue of sensor histidine kinase to an Asp residue in the CheY-like receiver domain of the cognate response regulator [, , ]. Phosphorylation of the receiver domain induces conformational changes that activate an associated output domain, which in turn triggers the response. Phosphorylation-induced conformational changes in response regulator molecule have been demonstrated in direct structural studies []. For more information on the receiver domain, please see .HD-GYP is a conserved domain found in response regulator modules of various signal transduction systems. The involvement of the HD-GYP domain in signal transduction was originally proposed on the basis of its association with CheY-like and other signal transduction domains []and was later directly demonstrated experimentally by showing that RpfG is involved in regulation of the biosynthesis of extracellular endoglucanase and polysaccharide [].A modification of the HD-GYP domain, which is found in this group, , , and several smaller groups, lacks the conserved distal portion of the domain and has certain substitutions in the characteristic metal-binding residues []of the HD superfamily phosphohydrolases, which likely render it catalytically inactive. Note that the prototypical HD domain () is not recognised in many members of this group.The exact mode of action and targets of the HD-GYP output domain are not known []. HD-GYP proteins are associated to the HD domain superfamily of metal-dependent phosphohydrolases; HD designates the principal conserved residues implicated in metal binding and catalysis []. The version of the HD-type domain present in members of (and in some other groups) has many additional highly conserved residues, including a conserved GYP motif, and is therefore called HD-GYP [, ].It has been noted that the highly conserved sequence of the HD-GYP domain suggests high substrate specificity []. On the basis of its association with the GGDEF diguanylate cyclase domain, it has been also predicted that the HD-GYP domain may be involved in the metabolism of cyclic diguanylate or in dephosphorylation of some phosphotransfer domain [].

Sequence Features

GO Displayer


InterPro protein domain ID --> Contigs



0 Child Features

2 Contains

Id Name Short Name Type
IPR001789 Signal transduction response regulator, receiver domain Sig_transdc_resp-reg_receiver Domain
IPR013976 Metal-dependent hydrolase HDOD HDOD Domain

0 Found In

0 Parent Features

13 Publications

First Author Title Year Journal Volume Pages
Wolanin PM Histidine protein kinases: key signal transducers outside the animal kingdom. 2002 Genome Biol 3 REVIEWS3013
Stock AM Two-component signal transduction. 2000 Annu Rev Biochem 69 183-215
Skerker JM Two-component signal transduction pathways regulating growth and cell cycle progression in a bacterium: a system-level analysis. 2005 PLoS Biol 3 e334
Laub MT Specificity in two-component signal transduction pathways. 2007 Annu Rev Genet 41 121-45
Varughese KI Molecular recognition of bacterial phosphorelay proteins. 2002 Curr Opin Microbiol 5 142-8
Hoch JA Keeping signals straight in phosphorelay signal transduction. 2001 J Bacteriol 183 4941-9
Galperin MY Novel domains of the prokaryotic two-component signal transduction systems. 2001 FEMS Microbiol Lett 203 11-21
West AH Histidine kinases and response regulator proteins in two-component signaling systems. 2001 Trends Biochem Sci 26 369-76
Aravind L The HD domain defines a new superfamily of metal-dependent phosphohydrolases. 1998 Trends Biochem Sci 23 469-72
Kern D Structure of a transiently phosphorylated switch in bacterial signal transduction. 1999 Nature 402 894-8
Grebe TW The histidine protein kinase superfamily. 1999 Adv Microb Physiol 41 139-227
Galperin MY A specialized version of the HD hydrolase domain implicated in signal transduction. 1999 J Mol Microbiol Biotechnol 1 303-5
Slater H A two-component system involving an HD-GYP domain protein links cell-cell signalling to pathogenicity gene expression in Xanthomonas campestris. 2000 Mol Microbiol 38 986-1003

To cite PlanMine, please refer to the following publication:

Rozanski, A., Moon, H., Brandl, H., Martín-Durán, J. M., Grohme, M., Hüttner, K., Bartscherer, K., Henry, I., & Rink, J. C.
PlanMine 3.0—improvements to a mineable resource of flatworm biology and biodiversity
Nucleic Acids Research, gky1070. doi:10.1093/nar/gky1070 (2018)