Home | Contact

Most prokaryotic signal-transduction systems and a few eukaryotic pathways use phosphotransfer schemes involving two conserved components, a histidine protein kinase (HK) (see <PDOC50109>) and a response regulator protein (RR). The HK, which is regulated by environmental stimuli, autophosphorylates at a histidine residue, creating a high-energy phosphoryl group that is subsequently transferred to an aspartate residue in the RR. Most RRs consist of two domains: a conserved N-terminal regulatory domain and a variable C-terminal effector domain. Phosphorylation of the regulatory domain induces a conformational change that results in activation of an associated domain that effects the response. The regulatory domains of RRs have three activities. First they interact with phosphorylated HKs and catalyze transfer of a phosphoryl group to one of their own Asp residues. Second, they catalyze autodephosphorylation. And finally they regulate the activities of their associated effector domains in a phosphorylation-dependent manner. The regulatory domains, often called receiver domains, can also be found within hybrid histidine kinases or as isolated proteins within phosphorelay pathways. In these contexts, the receiver domains are not physically connected to effector domains and play no direct role in regulating effector domain function.

The RR domain has a doubly wound five-stranded α/β fold consisting of about 125 residues (see <PDB:2CHY>). This fold consists a central five-stranded parallel β sheet flanked on both faces by five amphipathic α helices. Residues that are highly conserved in all RR domains are clustered in two regions: an active-site cleft formed by loops that extend from the C-terminal ends of β strands 1, 3 and 5, and a pair of residues that form a diagonal path extending across the molecule from the active site. The active site is a conserved acidic pocket and contains the phosphorylatable aspartate residue [1,2,3].

The profile we developed covers the entire RR domain.

January 2002 / First entry.

PROSITE method (with tools and information) covered by this documentation:

RESPONSE_REGULATORY, PS50110; Response regulatory domain profile  (MATRIX)

Sequences known to belong to this class detected by the profile: ALL Other sequence(s) detected in Swiss-Prot: NONE

• Domain architecture view of Swiss-Prot proteins matching PS50110 • Retrieve an alignment of Swiss-Prot true positive hits:   Clustal format, color, condensed view  / Clustal format, color  / Clustal format, plain text  / Fasta format • Retrieve the sequence logo from the alignment • Taxonomic tree view of all Swiss-Prot/TrEMBL entries matching PS50110 • Retrieve a list of all Swiss-Prot/TrEMBL entries matching PS50110 • Scan Swiss-Prot/TrEMBL entries against PS50110 • view ligand binding statistics

Matching PDB structures: 1A04 1A0O 1A2O 1AB5 ... [ALL]

1	Authors	Stock A.M., Robinson V.L., Goudreau P.N.
	Title	Two-component signal transduction.
	Source	Annu. Rev. Biochem. 69:183-215(2000).
	PubMed ID	10966457
	DOI	10.1146/annurev.biochem.69.1.183

2	Authors	West A.H., Stock A.M.
	Title	Histidine kinases and response regulator proteins in two-component signaling systems.
	Source	Trends Biochem. Sci. 26:369-376(2001).
	PubMed ID	11406410

3	Authors	Foussard M., Cabantous S., Pedelacq J.-D., Guillet V., Tranier S., Mourey L., Birck C., Samama J.-P.
	Title	The molecular puzzle of two-component signaling cascades.
	Source	Microbes Infect. 3:417-424(2001).
	PubMed ID	11369279

PROSITE is copyright. It is produced by the SIB Swiss Institute Bioinformatics. There are no restrictions on its use by non-profit institutions as long as its content is in no way modified. Usage by and for commercial entities requires a license agreement. For information about the licensing scheme send an email to

Prosite License or see: prosite_license.html.


View entry in original PROSITE document format
View entry in raw text format (no links)

SIB Swiss Institute of Bioinformatics | Disclaimer