REC

cheY-homologous receiver domain

• SMART accession number: SM00448
• Description: CheY regulates the clockwise rotation of E. coli flagellar motors. This domain contains a phosphoacceptor site that is phosphorylated by histidine kinase homologues.
• Interpro abstract (IPR001789):

  Two-component signal transduction systems enable bacteria to sense, respond, and adapt to a wide range of environments, stressors, and growth conditions (PUBMED:16176121). Some bacteria can contain up to as many as 200 two-component systems that need tight regulation to prevent unwanted cross-talk (PUBMED:18076326). 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 (PUBMED:12372152). Two-component systems are comprised of a sensor histidine kinase (HK) and its cognate response regulator (RR) (PUBMED:10966457). 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 (PUBMED:11934609), (PUBMED:11489844).

  Bipartite response regulator proteins are involved in a two-component signal transduction system in bacteria, and certain eukaryotes like protozoa, that functions to detect and respond to environmental changes (PUBMED:7699720). These systems have been detected during host invasion, drug resistance, motility, phosphate uptake, osmoregulation, and nitrogen fixation, amongst others (PUBMED:12015152). The two-component system consists of a histidine protein kinase environmental sensor that phosphorylates the receiver domain of a response regulator protein; phosphorylation induces a conformational change in the response regulator, which activates the effector domain, triggering the cellular response (PUBMED:10966457). The domains of the two-component proteins are highly modular, but the core structures and activities are maintained.

  The response regulators act as phosphorylation-activated switches to affect a cellular response, usually by transcriptional regulation. Most of these proteins consist of two domains, an N-terminal response regulator receiver domain, and a variable C-terminal effector domain with DNA-binding activity. This entry represents the response regulator receiver domain, which belongs to the CheY family, and receives the signal from the sensor partner in the two-component system.

• GO process: regulation of transcription, DNA-dependent (GO:0006355), two-component signal transduction system (phosphorelay) (GO:0000160)
• GO function: two-component response regulator activity (GO:0000156)

There are 29227 REC domains in 28024 proteins in SMART's nrdb database.

Cellular role (predicted cellular role)

Cellular role: signalling

Literature (relevant references for this domain)

Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.

• Pao GM, SaierMHJ r
• Response regulators of bacterial signal transduction systems: selective domain shuffling during evolution.
• J Mol Evol. 1995; 40: 136-54

Response regulators of bacterial sensory transduction systems generally consist of receiver module domains covalently linked to effector domains. The effector domains include DNA binding and/or catalytic units that are regulated by sensor kinase-catalyzed aspartyl phosphorylation within their receiver modules. Most receiver modules are associated with three distinct families of DNA binding domains, but some are associated with other types of DNA binding domains, with methylated chemotaxis protein (MCP) demethylases, or with sensor kinases. A few exist as independent entities which regulate their target systems by noncovalent interactions. In this study the molecular phylogenies of the receiver modules and effector domains of 49 fully sequenced response regulators and their homologues were determined. The three major, evolutionarily distinct, DNA binding domains found in response regulators were evaluated for their phylogenetic relatedness, and the phylogenetic trees obtained for these domains were compared with those for the receiver modules. Members of one family (family 1) of DNA binding domains are linked to large ATPase domains which usually function cooperatively in the activation of E. coli sigma 54-dependent promoters or their equivalents in other bacteria. Members of a second family (family 2) always function in conjunction with the E. coli sigma 70 or its equivalent in other bacteria. A third family of DNA binding domains (family 3) functions by an uncharacterized mechanism involving more than one sigma factor. These three domain families utilize distinct helix-turn-helix motifs for DNA binding. The phylogenetic tree of the receiver modules revealed three major and several minor clusters of these domains. The three major receiver module clusters (clusters 1, 2, and 3) generally function with the three major families of DNA binding domains (families 1, 2, and 3, respectively) to comprise three classes of response regulators (classes 1, 2, and 3), although several exceptions exist. The minor clusters of receiver modules were usually, but not always, associated with other types of effector domains. Finally, several receiver modules did not fit into a cluster. It was concluded that receiver modules usually diverged from common ancestral protein domains together with the corresponding effector domains, although domain shuffling, due to intragenic splicing and fusion, must have occurred during the evolution of some of these proteins. Multiple sequence alignments of the 49 receiver modules and their various types of effector domains, together with other homologous domains, allowed definition of regions of striking sequence similarity and degrees of conservation of specific residues. Sequence data were correlated with structure/function when such information was available.(ABSTRACT TRUNCATED AT 250 WORDS)

• Volz K
• Structural conservation in the CheY superfamily.
• Biochemistry. 1993; 32: 11741-53

• Stock JB, Stock AM, Mottonen JM
• Signal transduction in bacteria.
• Nature. 1990; 344: 395-400

Cells display a remarkable ability to respond to small fluctuations in their surroundings. In simple microbial systems, information from sensory receptors feeds into a circuitry of regulatory proteins that transfer high energy phosphoryl groups from histidine to aspartate side chains. This phosphotransfer network couples environmental signals to an array of response elements that control cell motility and regulate gene expression.

• Stock AM, Mottonen JM, Stock JB, Schutt CE
• Three-dimensional structure of CheY, the response regulator of bacterial chemotaxis.
• Nature. 1989; 337: 745-9

Homologies among bacterial signal transduction proteins suggest that a common mechanism mediates processes such as chemotaxis, osmoregulation, sporulation, virulence, and responses to nitrogen, phosphorous and oxygen deprivation. A common kinase-mediated phosphotransfer reaction has recently been identified in chemotaxis, nitrogen regulation, and osmoregulation. In chemotaxis, the CheA kinase passes a phosphoryl group to the cytoplasmic protein CheY, which functions as a phosphorylation-activated switch that interacts with flagellar components to regulate motility. We report here the X-ray crystal structure of the Salmonella typhimurium CheY protein. The determination of the structure was facilitated by the use of site-specific mutagenesis to engineer heavy-atom binding sites. CheY is a single-domain protein composed of a doubly wound five-stranded parallel beta-sheet. The phosphoacceptor site in CheY is probably a cluster of aspartic-acid side chains near the C-terminal edge of the beta-sheet. The pattern of sequence similarity of CheY with components of other regulatory systems can be interpreted in the light of the CheY structure and supports the view that this family of proteins have a common structural motif and active site.

• Drlica K, Rouviere-Yaniv J
• Histonelike proteins of bacteria.
• Microbiol Rev. 1987; 51: 301-19

Metabolism (metabolic pathways involving proteins which contain this domain)

% proteins involved	KEGG pathway ID	Description
77.92	map02020	Two-component system - General
16.71	map02030	Bacterial chemotaxis - General
4.51	map03090	Type II secretion system
0.24	map00240	Pyrimidine metabolism
0.14	map00230	Purine metabolism
0.05	map00620	Pyruvate metabolism
0.05	map04910	Insulin signaling pathway
0.05	map00010	Glycolysis / Gluconeogenesis
0.05	map00710	Carbon fixation
0.05	map04930	Type II diabetes mellitus
0.05	map00540	Lipopolysaccharide biosynthesis
0.02	map00260	Glycine, serine and threonine metabolism
0.02	map00680	Methane metabolism
0.02	map00562	Inositol phosphate metabolism
0.02	map00190	Oxidative phosphorylation
0.02	map00630	Glyoxylate and dicarboxylate metabolism
0.02	map02010	ABC transporters - General
0.02	map00632	Benzoate degradation via CoA ligation
0.02	map00633	Trinitrotoluene degradation

This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with REC domain which could be assigned to a KEGG orthologous group, and not all proteins containing REC domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.

Structure (3D structures containing this domain)

3D Structures of REC domains in PDB

PDB code	Title
1a04	The structure of the nitrate/nitrite response regulator protein narl in the monoclinic c2 crystal form
1a0o	Chey-binding domain of chea in complex with chey
1a2o	Structural basis for methylesterase cheb regulation by a phosphorylation-activated domain
1ab5	Structure of chey mutant f14n, v21t
1ab6	Structure of chey mutant f14n, v86t
1b00	Phob receiver domain from escherichia coli
1bdj	Complex structure of hpt domain and chey
1c4w	1.9 a structure of a-thiophosphonate modified chey d57c
1cey	Assignments, secondary structure, global fold, and dynamics of chemotaxis y protein using three-and four-dimensional heteronuclear (13c,15n) nmr spectroscopy
1chn	Magnesium binding to the bacterial chemotaxis protein chey results in large conformational changes involving its functional surface
1cye	Three dimensional structure of chemotactic che y protein in aqueous solution by nuclear magnetic resonance methods
1d4z	Crystal structure of chey-95iv, a hyperactive chey mutant
1d5w	Phosphorylated fixj receiver domain
1dbw	Crystal structure of fixj-n
1dc7	Structure of a transiently phosphorylated "switch" in bacterial signal transduction
1dc8	Structure of a transiently phosphorylated "switch" in bacterial signal transduction
1dcf	Crystal structure of the receiver domain of the ethylene receptor of arabidopsis thaliana
1dck	Structure of unphosphorylated fixj-n complexed with mn2+
1dcm	Structure of unphosphorylated fixj-n with an atypical conformer (monomer a)
1djm	Solution structure of bef3-activated chey from escherichia coli
1dz3	Domain-swapping in the sporulation response regulator spo0a
1e6k	Two-component signal transduction system d12a mutant of chey
1e6l	Two-component signal transduction system d13a mutant of chey
1e6m	Two-component signal transduction system d57a mutant of chey
1eay	Chey-binding (p2) domain of chea in complex with chey from escherichia coli
1ehc	Structure of signal transduction protein chey
1f4v	Crystal structure of activated chey bound to the n-terminus of flim
1f51	A transient interaction between two phosphorelay proteins trapped in a crystal lattice reveals the mechanism of molecular recognition and phosphotransfer in singal transduction
1ffg	Chey-binding domain of chea in complex with chey at 2.1 a resolution
1ffs	Chey-binding domain of chea in complex with chey from crystals soaked in acetyl phosphate
1ffw	Chey-binding domain of chea in complex with chey with a bound imido diphosphate
1fqw	Crystal structure of activated chey
1fsp	Nmr solution structure of bacillus subtilis spo0f protein, structures
1hey	Investigating the structural determinants of the p21-like triphosphate and mg2+ binding site
1i3c	Response regulator for cyanobacterial phytochrome, rcp1
1j56	Minimized average structure of beryllofluoride-activated ntrc receiver domain: model structure incorporating active site contacts
1jbe	1.08 a structure of apo-chey reveals meta-active conformation
1jlk	Crystal structure of the mn(2+)-bound form of response regulator rcp1
1k66	Crystal structure of the cyanobacterial phytochrome response regulator, rcpb
1k68	Crystal structure of the phosphorylated cyanobacterial phytochrome response regulator rcpa
1kgs	Crystal structure at 1.50 a of an ompr/phob homolog from thermotoga maritima
1kmi	Crystal structure of an e.coli chemotaxis protein, chez
1krw	Solution structure and backbone dynamics of beryllofluoride- activated ntrc receiver domain
1krx	Solution structure of beryllofluoride-activated ntrc receiver domain: model structures incorporating active site contacts
1l5y	Crystal structure of mg2+ / bef3-bound receiver domain of sinorhizobium meliloti dctd
1l5z	Crystal structure of the e121k substitution of the receiver domain of sinorhizobium meliloti dctd
1m5t	Crystal structure of the response regulator divk
1m5u	Crystal structure of the response regulator divk. structure at ph 8.0 in the apo-form
1mav	Crystal structure of the response regulator divk at ph 6.0 in complex with mn2+
1mb0	Crystal structure of the response regulator divk at ph 8.0 in complex with mn2+
1mb3	Crystal structure of the response regulator divk at ph 8.5 in complex with mg2+
1mih	A role for chey glu 89 in chez-mediated dephosphorylation of the e. coli chemotaxis response regulator chey
1mvo	Crystal structure of the phop receiver domain from bacillus subtilis
1nat	Crystal structure of spoof from bacillus subtilis
1ntr	Solution structure of the n-terminal receiver domain of ntrc
1nxo	Micarec ph7.0
1nxp	Micarec ph4.5
1nxs	Micarec ph4.9
1nxt	Micarec ph 4.0
1nxv	Micarec ph 4.2
1nxw	Micarec ph 5.1
1nxx	Micarec ph 5.5
1ny5	Crystal structure of sigm54 activator (aaa+ atpase) in the inactive state
1oxb	Complex between ypd1 and sln1 response regulator domain in space group p2(1)2(1)2(1)
1oxk	Complex between ypd1 and sln1 response regulator domain in space group p3(2)
1p2f	Crystal structure analysis of response regulator drrb, a thermotoga maritima ompr/phob homolog
1p6q	Nmr structure of the response regulator chey2 from sinorhizobium meliloti, complexed with mg++
1p6u	Nmr structure of the bef3-activated structure of the response regulator chey2-mg2+ from sinorhizobium meliloti
1pey	Crystal structure of the response regulator spo0f complexed with mn2+
1pux	Nmr solution structure of bef3-activated spo0f, 20 conformers
1qkk	Crystal structure of the receiver domain and linker region of dctd from sinorhizobium meliloti
1qmp	Phosphorylated aspartate in the crystal structure of the sporulation response regulator, spo0a
1rnl	The nitrate/nitrite response regulator protein narl from narl
1s8n	Crystal structure of rv1626 from mycobacterium tuberculosis
1sd5	Crystal structure of rv1626
1srr	Crystal structure of a phosphatase resistant mutant of sporulation response regulator spo0f from bacillus subtilis
1tmy	Chey from thermotoga maritima (apo-i)
1u0s	Chemotaxis kinase chea p2 domain in complex with response regulator chey from the thermophile thermotoga maritima
1u8t	Crystal structure of chey d13k y106w alone and in complex with a flim peptide
1udr	Chey mutant with lys 91 replaced by asp, lys 92 replaced by ala, ile 96 replaced by lys and ala 98 replaced by leu (stabilizing mutations in helix 4)
1vlz	Uncoupled phosphorylation and activation in bacterial chemotaxis: the 2.1 angstrom structure of a threonine to isoleucine mutant at position 87 of chey
1w25	Response regulator pled in complex with c-digmp
1xhe	Crystal structure of the receiver domain of redox response regulator arca
1xhf	Crystal structure of the bef3-activated receiver domain of redox response regulator arca
1yio	Crystallographic structure of response regulator styr from pseudomonas fluorescens
1ymu	Signal transduction protein chey mutant with met 17 replaced by gly (m17g)
1ymv	Signal transduction protein chey mutant with phe 14 replaced by gly, ser 15 replaced by gly, and met 17 replaced by gly
1ys6	Crystal structure of the response regulatory protein prra from mycobacterium tuberculosis
1ys7	Crystal structure of the response regulator protein prra comlexed with mg2+
1zdm	Crystal structure of activated chey bound to xe
1zes	Bef3- activated phob receiver domain
1zgz	Crystal structure of the receiver domain of tmao respiratory system response regulator torr
1zh2	Crystal structure of the calcium-bound receiver domain of kdp potassium transport system response regulator kdpe
1zh4	Crystal structure of the mg+2/bef3-bound receiver domain of kdp potassium transport system response regulator kdpe
1zit	Structure of the receiver domain of ntrc4 from aquifex aeolicus
1zn2	Low resolution structure of response regulator styr
1zy2	Crystal structure of the phosphorylated receiver domain of the transcription regulator ntrc1 from aquifex aeolicus
2a9o	Crystal structures of an activated yycf homologue, the essential response regulator from s.pneumoniae in complex with bef3 and the effect of ph on bef3 binding, possible phosphate in the active site
2a9p	Medium resolution bef3 bound rr02-rec
2a9q	Low resolution structure rr02-rec on bef3 bound
2a9r	Rr02-rec phosphate in the active site
2ayx	Solution structure of the e.coli rcsc c-terminus (residues 700-949) containing linker region and phosphoreceiver domain
2ayz	Solution structure of the e.coli rcsc c-terminus (residues 817-949) containing phosphoreceiver domain
2b1j	Crystal structure of unphosphorylated chey bound to the n- terminus of flim
2b4a	Crystal structure of bh3024 protein (10175646) from bacillus halodurans at 2.42 a resolution
2che	Structure of the mg2+-bound form of chey and mechanism of phosphoryl transfer in bacterial chemotaxis
2chf	Structure of the mg2+-bound form of chey and the mechanism of phosphoryl transfer in bacterial chemotaxis
2chy	Three-dimensional structure of chey, the response regulator of bacterial chemotaxis
2fka	Crystal structure of mg(2+) and bef(3)(-)-bound chey in complex with chez(200-214) solved from a f432 crystal grown in caps (ph 10.5)
2flk	Crystal structure of chey in complex with chez(200-214) solved from a f432 crystal grown in caps (ph 10.5)
2flw	Crystal structure of mg2+ and bef3- ound chey in complex with chez 200-214 solved from a f432 crystal grown in hepes (ph 7.5)
2fmf	Crystal structure of chey in complex with chez 200-214 solved from a f432 crystal grown in hepes (ph 7.5)
2fmh	Crystal structure of mg2+ and bef3- bound chey in complex with chez 200-214 solved from a f432 crystal grown in tris (ph 8.4)
2fmi	Crystal structure of chey in complex with chez 200-214 solved from a f432 crystal grown in tris (ph 8.4)
2fmk	Crystal structure of mg2+ and bef3- bound chey in complex with chez 200-214 solved from a p2(1)2(1)2 crystal grown in mes (ph 6.0)
2fsp	Nmr solution structure of bacillus subtilis spo0f protein, minimized average structure
2ftk	Berylloflouride spo0f complex with spo0b
2gkg	Receiver domain from myxococcus xanthus social motility protein frzs
2gwr	Crystal structure of the response regulator protein mtra from mycobacterium tuberculosis
2hqo	Structure of a atypical orphan response regulator protein revealed a new phosphorylation-independent regulatory mechanism
2hqr	Structure of a atypical orphan response regulator protein revealed a new phosphorylation-independent regulatory mechanism
2i6f	Receiver domain from myxococcus xanthus social motility protein frzs
2id7	1.75 a structure of t87i phosphono-chey
2id9	1.85 a structure of t87i/y106w phosphono-chey
2idm	2.00 a structure of t87i/y106w phosphono-chey
2iyn	The co-factor-induced pre-active conformation in phob
2j48	Nmr structure of the pseudo-receiver domain of the cika protein.
2jb9	Phob response regulator receiver domain constitutively- active double mutant d10a and d53e.
2jba	Phob response regulator receiver domain constitutively- active double mutant d53a and y102c.
2jk1
2jrl	Solution structure of the beryllofluoride-activated ntrc4 receiver domain dimer
2jvi	Nmr solution structure of the hyper-sporulation response regulator spo0f mutant h101a from bacillus subtilis
2jvj	Nmr solution structure of the hyper-sporulation response regulator spo0f mutant i90a from bacillus subtilis
2jvk	Nmr solution structure of the hyper-sporulation response regulator spo0f mutant l66a from bacillus subtilis
2nt3	Receiver domain from myxococcus xanthus social motility protein frzs (y102a mutant)
2nt4	Receiver domain from myxococcus xanthus social motility protein frzs (h92f mutant)
2oqr	The structure of the response regulator regx3 from mycobacterium tuberculosis
2pkx	E.coli response regulator phop receiver domain
2pl1	Berrylium fluoride activated receiver domain of e.coli phop
2pl9	Crystal structure of chey-mg(2+)-bef(3)(-) in complex with chez(c19) peptide solved from a p2(1)2(1)2 crystal
2pln	Crystal structure analysis of hp1043, an orphan resonse regulator of h. pylori
2pmc	Crystal structure of chey-mg(2+) in complex with chez(c15) peptide solved from a p1 crystal
2qr3	Crystal structure of the n-terminal signal receiver domain of two-component system response regulator from bacteroides fragilis
2qsj	Crystal structure of a luxr family dna-binding response regulator from silicibacter pomeroyi
2qv0	Crystal structure of the response regulatory domain of protein mrke from klebsiella pneumoniae
2qvg	The crystal structure of a two-component response regulator from legionella pneumophila
2qxy	Crystal structure of a response regulator from thermotoga maritima
2qzj	Crystal structure of a two-component response regulator from clostridium difficile
2r25	Complex of ypd1 and sln1-r1 with bound mg2+ and bef3-
2rdm	Crystal structure of response regulator receiver protein from sinorhizobium medicae wsm419
2rjn	Crystal structure of an uncharacterized protein q2bku2 from neptuniibacter caesariensis
2tmy	Chey from thermotoga maritima (apo-ii)
2v0n	Activated response regulator pled in complex with c-digmp and gtp-alpha-s
2vuh
2vui
2zay	Crystal structure of response regulator from desulfuromonas acetoxidans
2zwm
3a0r
3a0u
3a10
3b2n	Crystal structure of dna-binding response regulator, luxr family, from staphylococcus aureus
3bre	Crystal structure of p.aeruginosa pa3702
3c3m	Crystal structure of the n-terminal domain of response regulator receiver protein from methanoculleus marisnigri jr1
3c3w	Crystal structure of the mycobacterium tuberculosis hypoxic response regulator dosr
3c97	Crystal structure of the response regulator receiver domain of a signal transduction histidine kinase from aspergillus oryzae
3cfy	Crystal structure of signal receiver domain of putative luxo repressor protein from vibrio parahaemolyticus
3cg0	Crystal structure of signal receiver domain of modulated diguanylate cyclase from desulfovibrio desulfuricans g20, an example of alternate folding
3cg4	Crystal structure of response regulator receiver domain protein (chey-like) from methanospirillum hungatei jf-1
3chy	Crystal structure of escherichia coli chey refined at 1.7- angstrom resolution
3cnb	Crystal structure of signal receiver domain of dna binding response regulator protein (merr) from colwellia psychrerythraea 34h
3crn	Crystal structure of response regulator receiver domain protein (chey-like) from methanospirillum hungatei jf-1
3cu5	Crystal structure of a two component transcriptional regulator arac from clostridium phytofermentans isdg
3cwo	A beta/alpha-barrel built by the combination of fragments from different folds
3cz5	Crystal structure of two-component response regulator, luxr family, from aurantimonas sp. si85-9a1
3dge
3dgf
3dzd
3eod
3eq2
3eqz
3eul
3f6c
3f7a
3f7n
3fft
3ffw
3ffx
3fgz
3gl9
3grc
3gt7
3h5i
3hdg
3hdv
3heb
3hv2
3i42
3i5a
3ilh
3jte
3kcn
3kht
3tmy	Chey from thermotoga maritima (mn-iii)
4tmy	Chey from thermotoga maritima (mg-iv)
5chy	Structure of chemotaxis protein chey
6chy	Structure of chemotaxis protein chey

Links (links to other resources describing this domain)

• PFAM: response_reg
• INTERPRO: IPR001789