SMART: Pfam domain HTH

HTH_AsnC-type

PFAM accession number:	PF13404
Interpro abstract (IPR000485):	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 [ (PUBMED:2040596) ]. AsnC/lrp-like proteins are present in bacteria and archaea [ (PUBMED:7770911) ]. 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 oligomerisation domain. The crystal structure of hyperthermophilic archaeal lrpA shows that the N-terminal, DNA binding domain contains a core of three alpha-helices, followed by a single beta-strand, which connects as a flexible hinge to the effector binding domain. 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 [ (PUBMED:11230123) ]. Proteins known to contain an asnC-type HTH domain include: 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 [ (PUBMED:12458218) ]. 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.
GO function:	sequence-specific DNA binding (GO:0043565)

PFAM accession number:

PF13404

Interpro abstract (IPR000485):

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 [ (PUBMED:2040596) ]. AsnC/lrp-like proteins are present in bacteria and archaea [ (PUBMED:7770911) ]. 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 oligomerisation domain.

The crystal structure of hyperthermophilic archaeal lrpA shows that the N-terminal, DNA binding domain contains a core of three alpha-helices, followed by a single beta-strand, which connects as a flexible hinge to the effector binding domain. 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 [ (PUBMED:11230123) ].

Proteins known to contain an asnC-type HTH domain include:

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 [ (PUBMED:12458218) ].
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.

GO function:

sequence-specific DNA binding (GO:0043565)

This is a PFAM domain. For full annotation and more information, please see the PFAM entry HTH_AsnC-type