PROSITE documentation PDOC00542
LuxR-type HTH domain signature and profile


The luxR-type HTH domain is a DNA-binding, helix-turn-helix (HTH) domain of about 65 amino acids, present in transcription regulators of the LuxR/FixJ family of response regulators. The domain is named after Vibrio fischeri luxR, a transcriptional activator for quorum-sensing control of luminescence. LuxR-type HTH domain proteins occur in bacteria and in chloroplasts of algae. The DNA-binding HTH domain is usually located in the C-terminal part; the N-terminal part can contain an autoinducer binding domain or a response regulatory domain (see <PDOC50110>). Most luxR-type regulators act as transcription activators, but some can be repressors or have a dual role for different sites. LuxR-type HTH regulators control a wide variety of activities in various biological processes.

Several structures of luxR-type HTH proteins have been resolved and show that the DNA-binding domain is formed by a four-helix bundle (see <PDB:1P4W>). The helix-turn-helix motif comprises the second and third helices, which are being called the scaffold and the recognition helix, respectively. The HTH is involved in DNA-binding into the major groove, where the N-terminal part of the recognition helix makes most DNA-contacts. The fourth helix is involved in dimerization of gerE and traR. Signalling events by one of the four activation mechanisms described below lead to multimerization of the regulator. The regulators bind DNA as multimers [1,2,3,4].

LuxR-type HTH proteins can be activated by one of four different mechanisms:

I. Regulators which belong to a two-component sensory transduction system where the protein is activated by its phosphorylation, generally on an aspartate residue, by a transmembrane kinase. Some proteins that belong to this category are:

  • Rhizobiaceae fixJ, a global regulator inducing the expression of nitrogen-fixation genes in microaerobiosis.
  • Escherichia coli and Salmonella typhimurium uhpA, activates the uhpT gene for hexose phosphate transport.
  • Escherichia coli narL and narP, activate the nitrate reductase operon.
  • Escherichia coli evgA, modulates the expression of several drug exporter genes.
  • Enterobacteria rcsB, involved in the regulation of exopolysaccharide biosynthesis in enteric and plant pathogenesis.
  • Bordetella pertussis bvgA, plays a role in virulence.
  • Bacillus subtilis comA, plays a role in the expression of late-expressing competence genes.
  • Rhodobacter capsulatus dctR, controls the expression of C4-dicarboxylate transport genes.
  • Bacillus subtilis degU, activates extracellular proteases genes.
  • Escherichia coli and Salmonella typhimurium fimZ, indirectly involved in antibiotic resistance and expression of type 1 fimbriae.
  • Pseudomonas fluorescens gacA, involved in the regulation of secondary metabolism.
  • Pseudomonas aeruginosa glpR, activates genes of the glycerol metabolic pathway.
  • Rhizobiaceae nodW, probably regulates the transcription of genes involved in the nodulation process.

II. Regulators which are activated when bound to autoinducer molecules such as N-(3-oxohexanoyl)-L-homoserine lactone (OHHL) (see <PDOC00731>), a mechanism which can be involved in quorum sensing systems. Some proteins that belong to this category are:

  • Vibrio fischeri luxR, activates the bioluminescence operon.
  • Agrobacterium tumefaciens traR, involved in the regulation of Ti plasmid transfer.
  • Erwinia carotovora carR, plays a role in the control of the biosynthesis of carbapenem antibiotics.
  • Erwinia carotovora expR, acts in virulence (soft rot disease) through the activation of genes for plant tissue macerating enzymes.
  • Pseudomonas aeruginosa lasR, activates the elastase gene (lasB).
  • Erwinia chrysanthemi echR and Erwinia stewartii esaR.
  • Pseudomonas aureofaciens phzR, a positive regulator of phenazine antibiotic production.
  • Pseudomonas aeruginosa rhlR, activates the rhlAB operon as well as the lasB gene.
  • Yersinia enterocolitica yenR.

III. Autonomous effector domain regulators, without a regulatory domain, represented by gerE [2].

  • Bacillus subtilis gerE, a transcription activator and repressor for the regulation of spore formation.

IV. Multiple ligands binding regulators, exemplified by malT.

  • Escherichia coli malT, activates the maltose operon. MalT binds ATP and maltotriose.

The 'helix-turn-helix' DNA-binding motif of these proteins is located in the C-terminal section of the sequence. The pattern we use to detect these proteins starts three residues downstream of the N-terminal extremity of the helix-turn-helix motif and extends one residue downstream of its C-terminal extremity. We also developed a profile that covers the entire luxR-type HTH DNA-binding domain, including helices 1 and 4, and which allows a more sensitive detection.

Last update:

April 2006 / Pattern revised.


Technical section

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

HTH_LUXR_2, PS50043; LuxR-type HTH domain profile  (MATRIX)

HTH_LUXR_1, PS00622; LuxR-type HTH domain signature  (PATTERN)


1AuthorsEgland K.A. Greenberg E.P.
TitleQuorum sensing in Vibrio fischeri: analysis of the LuxR DNA binding region by alanine-scanning mutagenesis.
SourceJ. Bacteriol. 183:382-386(2001).
PubMed ID11114939

2AuthorsDucros V.M.-A. Lewis R.J. Verma C.S. Dodson E.J. Leonard G. Turkenburg J.P. Murshudov G.N. Wilkinson A.J. Brannigan J.A.
TitleCrystal structure of GerE, the ultimate transcriptional regulator of spore formation in Bacillus subtilis.
SourceJ. Mol. Biol. 306:759-771(2001).
PubMed ID11243786

3AuthorsVannini A. Volpari C. Gargioli C. Muraglia E. Cortese R. De Francesco R. Neddermann P. Marco S.D.
TitleThe crystal structure of the quorum sensing protein TraR bound to its autoinducer and target DNA.
SourceEMBO J. 21:4393-4401(2002).
PubMed ID12198141

4AuthorsPristovsek P. Sengupta K. Lohr F. Schafer B. von Trebra M.W. Ruterjans H. Bernhard F.
TitleStructural analysis of the DNA-binding domain of the Erwinia amylovora RcsB protein and its interaction with the RcsAB box.
SourceJ. Biol. Chem. 278:17752-17759(2003).
PubMed ID12740396

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