Letunic et al. (2017) Nucleic Acids Res doi: 10.1093/nar/gkx922
Letunic et al. (2020) Nucleic Acids Res doi: 10.1093/nar/gkaa937

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HTH_LACI helix_turn _helix lactose operon repressor

SMART accession number:	SM00354
Description:	-
Interpro abstract (IPR000843):	The lacI-type HTH domain is a DNA-binding, helix-turn-helix (HTH) domain of about 50-60 residues present in the lacI/galR family of transcriptional regulators involved in metabolic regulation in prokaryotes. Most of these bacterial regulators recognize sugar-inducers. The family is named after the Escherichia coli lactose operon repressor lacI and galactose operon repressor galR. LacI-type regulators are present in diverse bacterial genera, in the cytoplasm. The 'helix-turn-helix' DNA-binding motif is located in the N-terminal extremity of these transcriptional regulators. The C-terminal part of lacI-type regulators contains several regions that can be involved in (1) binding of inducers, which are sugars and their analogues and (2) oligomerization. The lac repressor is a tetramer, whilst the gal and cyt repressors are dimers. LacI-type transcriptional regulators are important in the coordination of catabolic, metabolic and transport operons [ (PUBMED:1805309) (PUBMED:1639817) ]. Several structures of lacI-type transcriptional regulators have been resolved and their DNA-binding domain encompasses a headpiece, formed by a fold of three helices, followed by a hinge region, which can form a fourth alpha helix or hinge-helix. The helix-turn-helix motif comprises the first and second helices, the second being called the recognition helix. The HTH is involved in DNA-binding into the major groove, while the hinge-helix fits into the minor groove and the complete domain specifically recognizes the operator DNA [ (PUBMED:8543068) ]. Some proteins known to contain a lacI-type HTH domain: Bacillus subtilis ccpA and ccpB, transcriptional regulators involved in the catabolic repression of several operons. Salmonella typhimurium fruR, the fructose repressor, involved in the regulation of a large number of operons encoding enzymes which take part in central pathways of carbon metabolism. Escherichia coli lacI, the lactose operon repressor, serving as a model for gene regulation. Escherichia coli purF and purR, repressors involved in the regulation of enzymes for purine nucleotide synthesis. Haemophilus influenzae galR, a repressor of the galactose operon.
GO process:	regulation of transcription, DNA-templated (GO:0006355)
GO function:	DNA binding (GO:0003677)
Family alignment:	View or CHROMA formatHMM/Web logoCLUSTALW formatMSF formatFASTA formatPIR format

There are 130174 HTH_LACI domains in 130123 proteins in SMART's nrdb database.

Click on the following links for more information.

• Evolution (species in which this domain is found)

• Taxonomic distribution of proteins containing HTH_LACI domain.

  This tree includes only several representative species. The complete taxonomic breakdown of all proteins with HTH_LACI domain is also avaliable.

  Click on the protein counts, or double click on taxonomic names to display all proteins containing HTH_LACI domain in the selected taxonomic class.

• Literature (relevant references for this domain)

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

  • Nguyen CC, SaierMHJ r
  • Phylogenetic, structural and functional analyses of the LacI-GalR family of bacterial transcription factors.
  • FEBS Lett. 1995; 377: 98-102
  • Display abstract

  • Phylogenetic tree construction for 25 sequenced members of the LacI-GalR family (LGF) of transcription factors revealed that almost all branches are similar in length, radiating essentially from a single point. This observation suggests that most of these proteins arose by duplication events which occurred at a specific time in evolutionary history, and that further duplication events were rare. Analyses of the multiple alignment of the LGF proteins lead to suggestions regarding structure-function relationships and reveal that the helix-turn-helix DNA-binding motif of LGF proteins is similar in sequence to those of numerous non-homologous DNA-binding proteins.

  • Weickert MJ, Adhya S
  • A family of bacterial regulators homologous to Gal and Lac repressors.
  • J Biol Chem. 1992; 267: 15869-74
  • Display abstract

  • We describe a family of proteins which regulate transcription of inducible genes in bacteria (GalR-LacI family). An alignment of the proteins in the GalR-LacI family is presented in which these proteins show a very high degree of similarity (60%) throughout the entire sequences. The homology is greatest among the amino-terminal DNA binding domains. Since a portion of the operator sequences occupied by these proteins is also conserved, a similar DNA structure may be required for specific recognition of DNA by members of the GalR-LacI family. Highly conserved motifs involved in effector binding and oligomerization are also identified. This compilation suggests a widespread conservation of these regulators among bacteria, and have strong implications for further study of peptide motifs in domain function, as well as pathways of protein evolution.

  • Haydon DJ, Guest JR
  • A new family of bacterial regulatory proteins.
  • FEMS Microbiol Lett. 1991; 63: 291-5
  • Display abstract

  • A new family of bacterial regulatory proteins has been identified by sequence similarity. The family contains the repressor of the Bacillus subtilis gluconate operon (GntR), the regulators for histidine utilization in Pseudomonas putida (HutCPp) and Klebsiella aerogenes (HutCKa), the repressor (FadR) of fatty acid degradation in Escherichia coli, a regulator involved in the conjugal transfer of the broad host range plasmid pIJ101 (KorA), and three proteins of unidentified function in E. coli (GenA, P30 and PhnF). The proteins share amino acid sequence similarities in a 69-residue N-terminal region. A helix-turn-helix motif is predicted in the most highly-conserved segment of each protein suggesting that they are members of a new family of helix-turn-helix DNA-binding proteins.

• Metabolism (metabolic pathways involving proteins which contain this domain)

• Click the image to view the interactive version of the map in iPath

  % proteins involved KEGG pathway ID Description 48.00 map00473 D-Alanine metabolism 48.00 map00252 Alanine and aspartate metabolism 1.33 map00030 Pentose phosphate pathway 0.67 map00710 Carbon fixation 0.67 map00720 Reductive carboxylate cycle (CO2 fixation) 0.67 map00620 Pyruvate metabolism 0.67 map00300 Lysine biosynthesis 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 HTH_LACI domain which could be assigned to a KEGG orthologous group, and not all proteins containing HTH_LACI 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 HTH_LACI domains in PDB

  PDB code	Main view	Title
  1bdh		PURINE REPRESSOR MUTANT-HYPOXANTHINE-PALINDROMIC OPERATOR COMPLEX
  1bdi		PURINE REPRESSOR MUTANT-HYPOXANTHINE-PALINDROMIC OPERATOR COMPLEX
  1cjg		NMR STRUCTURE OF LAC REPRESSOR HP62-DNA COMPLEX
  1efa		CRYSTAL STRUCTURE OF THE LAC REPRESSOR DIMER BOUND TO OPERATOR AND THE ANTI-INDUCER ONPF
  1jfs		PURINE REPRESSOR MUTANT-HYPOXANTHINE-PURF OPERATOR COMPLEX
  1jft		PURINE REPRESSOR MUTANT-HYPOXANTHINE-PURF OPERATOR COMPLEX
  1jh9		PURINE REPRESSOR MUTANT-HYPOXANTHINE-PURF OPERATOR COMPLEX
  1jwl		Structure of the Dimeric lac Repressor/Operator O1/ONPF Complex
  1jye		Structure of a Dimeric Lac Repressor with C-terminal Deletion and K84L Substitution
  1jyf		Structure of the Dimeric Lac Repressor with an 11-residue C-terminal Deletion.
  1l1m		SOLUTION STRUCTURE OF A DIMER OF LAC REPRESSOR DNA-BINDING DOMAIN COMPLEXED TO ITS NATURAL OPERATOR O1
  1lbg		LACTOSE OPERON REPRESSOR BOUND TO 21-BASE PAIR SYMMETRIC OPERATOR DNA, ALPHA CARBONS ONLY
  1lbh		INTACT LACTOSE OPERON REPRESSOR WITH GRATUITOUS INDUCER IPTG
  1lbi		LAC REPRESSOR
  1lcc		STRUCTURE OF THE COMPLEX OF LAC REPRESSOR HEADPIECE AND AN 11 BASE-PAIR HALF-OPERATOR DETERMINED BY NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY AND RESTRAINED MOLECULAR DYNAMICS
  1lcd		STRUCTURE OF THE COMPLEX OF LAC REPRESSOR HEADPIECE AND AN 11 BASE-PAIR HALF-OPERATOR DETERMINED BY NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY AND RESTRAINED MOLECULAR DYNAMICS
  1lqc		LAC REPRESSOR HEADPIECE (RESIDUES 1-56), NMR, 32 STRUCTURES
  1osl		Solution structure of a dimeric lactose DNA-binding domain complexed to a nonspecific DNA sequence
  1pnr		PURINE REPRESSOR-HYPOXANTHINE-PURF-OPERATOR COMPLEX
  1pru		PURINE REPRESSOR DNA-BINDING DOMAIN DNA BINDING
  1prv		PURINE REPRESSOR DNA-BINDING DOMAIN DNA BINDING
  1qp0		PURINE REPRESSOR-HYPOXANTHINE-PALINDROMIC OPERATOR COMPLEX
  1qp4		PURINE REPRESSOR-HYPOXANTHINE-PALINDROMIC OPERATOR COMPLEX
  1qp7		PURINE REPRESSOR MUTANT-HYPOXANTHINE-PALINDROMIC OPERATOR COMPLEX
  1qpz		PURINE REPRESSOR-HYPOXANTHINE-PALINDROMIC OPERATOR COMPLEX
  1qqa		PURINE REPRESSOR MUTANT-HYPOXANTHINE-PALINDROMIC OPERATOR COMPLEX
  1qqb		PURINE REPRESSOR MUTANT-HYPOXANTHINE-PALINDROMIC OPERATOR COMPLEX
  1rzr		crystal structure of transcriptional regulator-phosphoprotein-DNA complex
  1uxc		FRUCTOSE REPRESSOR DNA-BINDING DOMAIN, NMR, MINIMIZED STRUCTURE
  1uxd		FRUCTOSE REPRESSOR DNA-BINDING DOMAIN, NMR, 34 STRUCTURES
  1vpw		STRUCTURE OF THE PURR MUTANT, L54M, BOUND TO HYPOXANTHINE AND PURF OPERATOR DNA
  1wet		STRUCTURE OF THE PURR-GUANINE-PURF OPERATOR COMPLEX
  1zay		PURINE REPRESSOR-HYPOXANTHINE-MODIFIED-PURF-OPERATOR COMPLEX
  1zvv		Crystal structure of a ccpa-crh-dna complex
  2bjc		NMR structure of a protein-DNA complex of an altered specificity mutant of the lac repressor headpiece that mimics the gal repressor
  2hsg		Structure of transcription regulator CcpA in its DNA-free state
  2iks		Crystal structure of N-terminal truncated DNA-binding transcriptional dual regulator from Escherichia coli K12
  2jcg		Apo form of the catabolite control protein A (ccpA) from bacillus megaterium, with the DNA binding domain
  2kei		Refined Solution Structure of a Dimer of LAC repressor DNA-Binding domain complexed to its natural operator O1
  2kej		Solution structure of a dimer of LAC repressor DNA-binding domain complexed to its natural operator O2
  2kek		Solution structure of a dimer of LAC repressor DNA-binding domain complexed to its natural operator O3
  2l8n		NMR structure of the cytidine repressor DNA binding domain in presence of operator half-site DNA
  2lcv		Structure of the Cytidine Repressor DNA-Binding Domain; an alternate calculation
  2o20		Crystal structure of transcription regulator CcpA of Lactococcus lactis
  2pe5		Crystal Structure of the Lac Repressor bound to ONPG in repressed state
  2pua		CRYSTAL STRUCTURE OF THE LACI FAMILY MEMBER, PURR, BOUND TO DNA: MINOR GROOVE BINDING BY ALPHA HELICES
  2pub		CRYSTAL STRUCTURE OF THE LACI FAMILY MEMBER, PURR, BOUND TO DNA: MINOR GROOVE BINDING BY ALPHA HELICES
  2puc		CRYSTAL STRUCTURE OF THE LACI FAMILY MEMBER, PURR, BOUND TO DNA: MINOR GROOVE BINDING BY ALPHA HELICES
  2pud		CRYSTAL STRUCTURE OF THE LACI FAMILY MEMBER, PURR, BOUND TO DNA: MINOR GROOVE BINDING BY ALPHA HELICES
  2pue		CRYSTAL STRUCTURE OF THE LACI FAMILY MEMBER, PURR, BOUND TO DNA: MINOR GROOVE BINDING BY ALPHA HELICES
  2puf		CRYSTAL STRUCTURE OF THE LACI FAMILY MEMBER, PURR, BOUND TO DNA: MINOR GROOVE BINDING BY ALPHA HELICES
  2pug		CRYSTAL STRUCTURE OF THE LACI FAMILY MEMBER, PURR, BOUND TO DNA: MINOR GROOVE BINDING BY ALPHA HELICES
  3bil		Crystal structure of a probable LacI family transcriptional regulator from Corynebacterium glutamicum
  3ctp		Crystal structure of periplasmic binding protein/LacI transcriptional regulator from Alkaliphilus metalliredigens QYMF complexed with D-xylulofuranose
  3dbi		CRYSTAL STRUCTURE OF SUGAR-BINDING TRANSCRIPTIONAL REGULATOR (LACI FAMILY) FROM ESCHERICHIA COLI COMPLEXED WITH PHOSPHATE
  3e3m		Crystal structure of a LacI family transcriptional regulator from Silicibacter pomeroyi
  3edc		Crystal Structure of a 1.6-hexanediol Bound Tetrameric Form of Escherichia coli Lac-repressor Refined to 2.1 Resolution
  3h5o		The crystal structure of transcription regulator GntR from Chromobacterium violaceum
  3h5t		Crystal structure of a transcriptional regulator, Lacl family protein from Corynebacterium glutamicum
  3jvd		Crystal structure of putative transcription regulation repressor (LACI family) FROM Corynebacterium glutamicum
  3kjx		Crystal structure of a transcriptional regulator, Lacl family protein from Silicibacter pomeroyi
  3oqm		structure of ccpa-hpr-ser46p-ackA2 complex
  3oqn		Structure of ccpa-hpr-ser46-p-gntr-down cre
  3oqo		Ccpa-hpr-ser46p-syn cre
  4o5a		The crystal structure of a LacI family transcriptional regulator from Bifidobacterium animalis subsp. lactis DSM 10140
  4rzs		4RZS
  4rzt		4RZT

• Links (links to other resources describing this domain)

• PROSITE	HTH_LACI_FAMILY
  INTERPRO	IPR000843
  PFAM	lacI

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