SMART: Trans_reg_C domain annotation

Trans_reg_C Transcriptional regulatory protein, C terminal

SMART accession number:	SM00862
Description:	This domain is almost always found associated with the response regulator receiver domain. It may play a role in DNA binding.
Interpro abstract (IPR001867):	Bacteria and plants frequently use two-components signal transduction systems (TCSs) to adapt to environmental changes and to survive under stress conditions. Typical TCSs couple a transmembrane histidine protein kinase (HK), which detects changes in the environmnent, to a cytosolic response regulator (RR), which often alters gene expression. Most RRs contain two distinct domains: an N-terminal receiver domain and a C-terminal effector domain. The former autophosphorylates on a histidine residue on detecting an external stimulus. The phosphate is then transferred to an invariant aspartate residue in a highly conserved receiver domain of the response regulator. Phosphorylation activates a variable effector domain of the response regulator, which triggers the cellular response. The C-terminal effector domain contains DNA and RNA polymerase binding sites. Several dimers or monomers bind head to tail to small tandem repeats upstream of the genes. The RNA polymerase binding sites interact with the alpha or sigma subunit of RNA polymerase. The OmpR/PhoB subfamily is the largest subfamily of RRs. Members of the OmpR/PhoB subfamily include such diverse transcriptional regulators as Escherichia coli PhoB (of the phosphate assimilation pathway), Enterococcus faecium VanR (which controls resistance to the antibiotic vancomycin), and Agrobacterium tumefaciens VirG (involved in the establishment of crown gall tumors in plant. The C-terminal effector domain of the OmpR/PhoB subfamily RRs binds DNA. This DNA-binding domain is also found in proteins other than response regulators, such as Vibrio cholerea ToxR, a transmembrane protein involved in cholera toxin expression [ (PUBMED:9016718) (PUBMED:18052041) (PUBMED:18789936) (PUBMED:21634789) (PUBMED:24990372) (PUBMED:11934608) (PUBMED:9199401) ]. The OmpR/PhoB-type DNA-binding domain has the typical fold of the winged helix-turn-helix DNA-binding domain. The structure of the OmpR/PhoB-type DNA- binding domain consists of three alpha helices packed against two antiparallel beta sheets, an N-terminal four-stranded antiparallel beta sheet and a C- terminal hairpin. The hairpin interacts with a short stretch of beta strand, that connects helices alpha1 and alpha2, to generate a three- stranded antiparallel beta sheet. The topology for the domain is beta1-beta2- beta3-beta4-alpha1-beta5-alpha2-alpha3-beta6-beta7. The hydrophobic core of the domain is formed by sidechains contributed by each of the seven beta strands and three alpha helices [ (PUBMED:9016718) (PUBMED:18052041) (PUBMED:18789936) (PUBMED:21634789) (PUBMED:24990372) ].
GO process:	phosphorelay signal transduction system (GO:0000160), regulation of transcription, DNA-templated (GO:0006355)
GO function:	DNA binding (GO:0003677)
Family alignment:	View or

There are 247210 Trans_reg_C domains in 247128 proteins in SMART's nrdb database.

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Evolution (species in which this domain is found)
Taxonomic distribution of proteins containing Trans_reg_C domain.
This tree includes only several representative species. The complete taxonomic breakdown of all proteins with Trans_reg_C domain is also avaliable.

Click on the protein counts, or double click on taxonomic names to display all proteins containing Trans_reg_C domain in the selected taxonomic class.
Cellular role (predicted cellular role)
Cellular role: transcription
Literature (relevant references for this domain)
Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.
- Martinez-Hackert E, Stock AM
- The DNA-binding domain of OmpR: crystal structures of a winged helixtranscription factor.
- Structure. 1997; 5: 109-24
- Display abstract
- BACKGROUND: The differential expression of the ompF and ompC genes isregulated by two proteins that belong to the two component family ofsignal transduction proteins: the histidine kinase, EnvZ, and the responseregulator, OmpR. OmpR belongs to a subfamily of at least 50 responseregulators with homologous C-terminal DNA-binding domains of approximately98 amino acids. Sequence homology with DNA-binding proteins of knownstructure cannot be detected, and the lack of structural information hasprevented understanding of many of this familys functional properties.RESULTS: We have determined the crystal structure of the Escherichia coliOmpR C-terminal domain at 1.95 A resolution. The structure consists ofthree alpha helices packed against two antiparallel beta sheets. Twohelices, alpha2 and alpha3, and the ten residue loop connecting themconstitute a variation of the helix-turn-helix (HTH) motif. Helix alpha3and the loop connecting the two C-terminal beta strands, beta6 and beta7,are probable DNA-recognition sites. Previous mutagenesis studies indicatethat the large loop connecting helices alpha2 and alpha3 is the site ofinteraction with the alpha subunit of RNA polymerase. CONCLUSIONS: OmpRcbelongs to the family of 'winged helix-turn-helix' DNA-binding proteins.This relationship, and the results from numerous published mutagenesisstudies, have helped us to interpret the functions of most of thestructural elements present in this protein domain. The structure of OmpRccould be useful in helping to define the positioning of the alpha subunitof RNA polymerase in relation to transcriptional activators that are boundto DNA.
- Wietzorrek A, Bibb M
- A novel family of proteins that regulates antibiotic production instreptomycetes appears to contain an OmpR-like DNA-binding fold.
- Mol Microbiol. 1997; 25: 1181-4
- Baikalov I, Schroder I, Kaczor-Grzeskowiak M, Grzeskowiak K, Gunsalus RP, Dickerson RE
- Structure of the Escherichia coli response regulator NarL.
- Biochemistry. 1996; 35: 11053-61
- Display abstract
- The crystal structure analysis of the NarL protein provides a first look at interactions between receiver and effector domains of a full-length bacterial response regulator. The N-terminal receiver domain, with 131 amino acids, is folded into a 5-strand beta sheet flanked by 5 alpha helices, as seen in CheY and in the N-terminal domain of NTRC. The C-terminal DNA-binding domain, with 62 amino acids, is a compact bundle of 4 alpha helices, of which the middle 2 form a helix-turn-helix motif closely related to that of Drosophila paired protein and other H-T-H DNA-binding proteins. The 2 domains are connected by an alpha helix of 10 amino acids and a 13-residue flexible tether that is not visible and presumably disordered in the X-ray structure. In this unphosphorylated form of NarL, the C-terminal domain is turned against the receiver domain in a manner that would preclude DNA binding. Activation of NarL via phosphorylation of Asp59 must involve transfer of information to the interdomain interface and either rotation or displacement of the DNA-binding C-terminal domain. Docking of a B-DNA duplex against the isolated C-terminal domain in the manner observed in paired protein and other H-T-H proteins suggests a stereochemical basis for DNA sequence preference: T-R-C-C-Y (high affinity) or T-R-C-T-N (low affinity), which is close to the experimentally observed consensus sequence: T-A-C-Y-N. The NarL structure is a model for other members of the FixJ or LuxR family of bacterial transcriptional activators, and possibly to the more distant OmpR and NtrC families as well.
Structure (3D structures containing this domain)

3D Structures of Trans_reg_C domains in PDB

PDB code	Main view	Title
1gxp		PhoB effector domain in complex with pho box DNA.
1gxq		Crystal structure of the PhoB effector domain
1kgs		Crystal Structure at 1.50 A of an OmpR/PhoB Homolog from Thermotoga maritima
1odd		OMPR C-TERMINAL DOMAIN (OMPR-C) FROM ESCHERICHIA COLI
1opc		OMPR DNA-BINDING DOMAIN, ESCHERICHIA COLI
1p2f		Crystal Structure Analysis of Response Regulator DrrB, a Thermotoga maritima OmpR/PhoB Homolog
1qqi		SOLUTION STRUCTURE OF THE DNA-BINDING AND TRANSACTIVATION DOMAIN OF PHOB FROM ESCHERICHIA COLI
1ys6		Crystal structure of the response regulatory protein PrrA from Mycobacterium Tuberculosis
1ys7		Crystal structure of the response regulator protein prrA comlexed with Mg2+
2d1v		Crystal structure of DNA-binding domain of Bacillus subtilis YycF
2fez		Mycobacterium tuberculosis EmbR
2ff4		Mycobacterium tuberculosis EmbR in complex with low affinity phosphopeptide
2gwr		Crystal structure of the response regulator protein mtrA from Mycobacterium Tuberculosis
2hqn		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
2hwv		Crystal structure of an essential response regulator DNA binding domain, VicRc in Enterococcus faecalis, a member of the YycF subfamily.
2jpb		Solution Structure of OMPR-C DNA Binding Protein
2jzy		Solution structure of C-terminal effector domain of putative two-component-system response regulator involved in copper resistance from Klebsiella pneumoniae
2k4j		ArsR DNA Binding Domain
2m1b		Solution structure of the CHXR DNA-binding domain
2m87		Structural Basis of DNA Recognition by the Effector Domain of Klebsiella pneumoniae PmrA
2mlk		2MLK
2oqr		The structure of the response regulator RegX3 from Mycobacterium tuberculosis
2pmu		Crystal structure of the DNA-binding domain of PhoP
2rv8		2RV8
2z33		Solution structure of the DNA complex of PhoB DNA-binding/transactivation Domain
2zxj		Crystal structure of YycF DNA-binding domain from Staphylococcus aureus
3q9s		Crystal structure of rra(1-215) from Deinococcus Radiodurans
3q9v		Crystal structure of rra c-terminal domain(123-221) from Deinococcus radiodurans
3r0j		Structure of PhoP from Mycobacterium tuberculosis
3rjp		Crystal structure of the DNA binding domain of CovR from Streptococcus pyogenes
3t72		PhoB(E)-Sigma70(4)-(RNAP-Betha-flap-tip-helix)-DNA Transcription Activation Sub-Complex
3zq7		The Structure of DNA-binding domain of response regulator from Escherichia coli K-12
4b09		Structure of unphosphorylated BaeR dimer
4ixa		Structure of DNA-binding domain of the response regulator SaeR from Staphylococcus epidermidis
4kfc		Crystal structure of a hyperactive mutant of response regulator KdpE complexed to its promoter DNA
4kny		Crystal structure of the response regulator KdpE complexed to DNA in an active-like conformation
4nhj		4NHJ
4qwq		4QWQ
4s04		4S04
4s05		4S05
4u88		4U88
4uht		4UHT
5dcl		5DCL
5dcm		5DCM
5ed4		5ED4

Links (links to other resources describing this domain)
PFAM Trans_reg_C
INTERPRO IPR001867

PFAM	Trans_reg_C
INTERPRO	IPR001867

Trans_reg_C

Taxonomic distribution of proteins containing Trans_reg_C domain.

3D Structures of Trans_reg_C domains in PDB