PROSITE documentation PDOC00520
AsnC-type HTH domain signature and profile


The asnC-type HTH domain is a DNA-binding, helix-turn-helix (HTH) domain of about 60 amino acids present in transcription regulators of the asnC/lrp family. This family of prokaryotic regulators is named after Escherichia coli asnC and Leucine-responsive Regulatory Protein (lrp), which are a regulator of asparagine synthesis and a global regulator of various operons, respectively [1]. AsnC/lrp-like proteins are present in bacteria and archaea [2]. The DNA-binding asnC-type HTH domain occurs usually in the N-terminal part. The C-terminal part can contain an effector-binding domain and/or an oligomerization domain. Regulators of the asnC/lrp family can be dimers, tetramers, octamers and hexadecamers [3,4]. These proteins regulate amino acid metabolism and related processes. Lrp is a global regulator of E. coli, involved in amino acid metabolism and pili synthesis by affecting transcription of at least 10% of its genes. Most lrp homologues appear to be specific regulators of amino acid metabolism [4]. Various amino acids act as specific effectors and can either activate or repress transcription of metabolic enzymes. Many asnC/lrp-like proteins can also repress their own expression [4,5,6].

The crystal structure of hyperthermophilic archaeal lrpA shows that the N-terminal, DNA binding domain contains a core of three α-helices, followed by a single β-strand, which connects as a flexible hinge to the effector binding domain (see <PDB:1I1G>). The second and third helices, connected via a turn, comprise the helix-turn-helix motif. Helix 3 is termed the recognition helix as it binds the DNA major groove, like in other HTHs. Most E. coli lrp DNA binding mutants are positioned in the lrpA structure on the HTH and three are on the hinge [3].

Some proteins known to contain an asnC-type HTH domain:

  • Escherichia coli Leucine-responsive Regulatory Protein (lrp), a global transcriptional regulator of 35-75 different genes involved in amino acid biosynthesis, amino acid degradation, transport or pili formation. Binding of leucine by lrp can stimulate or reduce the regulatory effect of activation for some operons or repression for others. Lrp negatively autoregulates the lrp gene, independently of leucine.
  • Salmonella typhimurium lrp, a global leucine-responsive regulator involved in branched-chain amino acid biosynthesis, pili formation and plasmid virulence.
  • Escherichia coli asnC, a specific asparagine-dependent transcriptional activator of asparagine biosynthesis. AsnC is also an asparagine- independent repressor of its own transcription.
  • Pseudomonas putida bkdR, a specific autoregulatory transcriptional regulator, involved in catabolism of branched-chain amino acids.
  • Agrobacterium tumefaciens putR, a specific proline-responsive regulator of proline catabolism.
  • Bacillus subtilis lrpA/lrpB and lrpC, transcriptional regulators involved in serine-glycine interconversion, sporulation and amino acid metabolism. LrpC binds to a specific DNA structure and wraps and overwinds the DNA [7].
  • Bacillus subtilis azlB, a specific transcriptional repressor of branched- chain amino acid transport.
  • Pyrococcus furiosus lrpA, a putative lrp with negative autoregulation.
  • Zymomonas mobilis grp, a repressor of the glutamate uptake operon.

The pattern we use to detect these proteins spans the complete helix-turn-helix motif and extends one residue downstream and one upstream of the HTH extremities. The profile we developed covers the entire asnC-type DNA binding domain, from the first helix to the end of the hinge.

Last update:

January 2004 / Text revised; profile added.


Technical section

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

HTH_ASNC_2, PS50956; AsnC-type HTH domain profile  (MATRIX)

HTH_ASNC_1, PS00519; AsnC-type HTH domain signature  (PATTERN)


1AuthorsWillins D.A. Ryan C.W. Platko J.V. Calvo J.M.
TitleCharacterization of Lrp, and Escherichia coli regulatory protein that mediates a global response to leucine.
SourceJ. Biol. Chem. 266:10768-10774(1991).
PubMed ID2040596

2AuthorsKyrpides N.C. Ouzounis C.A.
TitleThe eubacterial transcriptional activator Lrp is present in the archaeon Pyrococcus furiosus.
SourceTrends Biochem. Sci. 20:140-141(1995).
PubMed ID7770911

3AuthorsLeonard P.M. Smits S.H.J. Sedelnikova S.E. Brinkman A.B. de Vos W.M. van der Oost J. Rice D.W. Rafferty J.B.
TitleCrystal structure of the Lrp-like transcriptional regulator from the archaeon Pyrococcus furiosus.
SourceEMBO J. 20:990-997(2001).
PubMed ID11230123

4AuthorsBrinkman A.B. Ettema T.J.G. de Vos W.M. van der Oost J.
TitleThe Lrp family of transcriptional regulators.
SourceMol. Microbiol. 48:287-294(2003).
PubMed ID12675791

5AuthorsFriedberg D. Midkiff M. Calvo J.M.
TitleGlobal versus local regulatory roles for Lrp-related proteins: Haemophilus influenzae as a case study.
SourceJ. Bacteriol. 183:4004-4011(2001).
PubMed ID11395465

6AuthorsOuhammouch M. Dewhurst R.E. Hausner W. Thomm M. Geiduschek E.P.
TitleActivation of archaeal transcription by recruitment of the TATA-binding protein.
SourceProc. Natl. Acad. Sci. U.S.A. 100:5097-5102(2003).
PubMed ID12692306

7AuthorsBeloin C. Jeusset J. Revet B. Mirambeau G. Le Hegarat F. Le Cam E.
TitleContribution of DNA conformation and topology in right-handed DNA wrapping by the Bacillus subtilis LrpC protein.
SourceJ. Biol. Chem. 278:5333-5342(2003).
PubMed ID12458218

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