The many bacterial transcription regulation proteins which bind DNA through a 'helix-turn-helix' motif can be classified into subfamilies on the basis of sequence similarities. One of these subfamilies groups together the following proteins [1,2,3]:

• aarP, a transcriptional activator of the 2'-N-acetyltransferase gene in Providencia stuartii.
• ada, an Escherichia coli and Salmonella typhimurium bifunctional protein that repairs alkylated guanine in DNA by transferring the alkyl group at the O(6) position to a cysteine residue in the enzyme. The methylated protein acts a positive regulator of its own synthesis and of the alkA, alkB and aidB genes.
• adaA, a Bacillus subtilis bifunctional protein that acts both as a transcriptional activator of the ada operon and as a methylphosphotriester- DNA alkyltransferase.
• adiY, an Escherichia coli protein of unknown function.
• aggR, the transcriptional activator of aggregative adherence fimbria I expression in enteroaggregative Escherichia coli.
• appY, a protein which acts as a transcriptional activator of acid phosphatase and other proteins during the deceleration phase of growth and acts as a repressor for other proteins that are synthesized in exponential growth or in the stationary phase.
• araC, the arabinose operon regulatory protein, which activates the transcription of the araBAD genes.
• cafR, the Yersinia pestis F1 operon positive regulatory protein.
• celD, the Escherichia coli cel operon repressor.
• cfaD, a protein which is required for the expression of the CFA/I adhesin of enterotoxigenic Escherichia coli.
• csvR, a transcriptional activator of fimbrial genes in enterotoxigenic Escherichia coli.
• envY, the porin thermoregulatory protein, which is involved in the control of the temperature-dependent expression of several Escherichia coli envelope proteins such as ompF, ompC, and lamB.
• exsA, an activator of exoenzyme S synthesis in Pseudomonas aeruginosa.
• fapR, the positive activator for the expression of the 987P operon coding for the fimbrial protein in enterotoxigenic Escherichia coli.
• hrpB, a positive regulator of pathogenicity genes in Burkholderia solanacearum.
• invF, the Salmonella typhimurium invasion operon regulator.
• marA, which may be a transcriptional activator of genes involved in the multiple antibiotic resistance (mar) phenotype.
• melR, the melibiose operon regulatory protein, which activates the transcription of the melAB genes.
• mixE, a Shigella flexneri protein necessary for secretion of ipa invasins.
• mmsR, the transcriptional activator for the mmsAB operon in Pseudomonas aeruginosa.
• msmR, the multiple sugar metabolism operon transcriptional activator in Streptococcus mutans.
• pchR, a Pseudomonas aeruginosa activator for pyochelin and ferripyochelin receptor.
• perA, a transcriptional activator of the eaeA gene for intimin in enteropathogenic Escherichia coli.
• pocR, a Salmonella typhimurium regulator of the cobalamin biosynthesis operon.
• pqrA, from Proteus vulgaris.
• rafR, the regulator of the raffinose operon in Pediococcus pentosaceus.
• ramA, from Klebsiella pneumoniae.
• rhaR, the Escherichia coli and Salmonella typhimurium L-rhamnose operon transcriptional activator.
• rhaS, an Escherichia coli and Salmonella typhimurium positive activator of genes required for rhamnose utilization.
• rns, a protein which is required for the expression of the cs1 and cs2 adhesins of enterotoxigenic Escherichia coli.
• rob, a protein which binds to the right arm of the replication origin oriC of the Escherichia coli chromosome.
• soxS, a protein that, with the soxR protein, controls a superoxide response regulon in Escherichia coli.
• tetD, a protein from transposon TN10.
• tcpN or toxT, the Vibrio cholerae transcriptional activator of the tcp operon involved in pilus biosynthesis and transport.
• thcR, a probable regulator of the thc operon for the degradation of the thiocarbamate herbicide EPTC in Rhodococcus sp. strain NI86/21.
• ureR, the transcriptional activator of the plasmid-encoded urease operon in Enterobacteriaceae.
• virF and lcrF, the Yersinia virulence regulon transcriptional activator.
• virF, the Shigella transcriptional factor of invasion related antigens ipaBCD.
• xylR, the Escherichia coli xylose operon regulator.
• xylS, the transcriptional activator of the Pseudomonas putida TOL plasmid (pWWO, pWW53 and pDK1) meta operon (xylDLEGF genes).
• yfeG, an Escherichia coli hypothetical protein.
• yhiW, an Escherichia coli hypothetical protein.
• yhiX, an Escherichia coli hypothetical protein.
• yidL, an Escherichia coli hypothetical protein.
• yijO, an Escherichia coli hypothetical protein.
• yuxC, a Bacillus subtilis hypothetical protein.
• yzbC, a Bacillus subtilis hypothetical protein.

Except for celD, all of these proteins seem to be positive transcriptional factors. Their size range from 107 (soxS) to 529 (yzbC) residues.

The helix-turn-helix motif is located in the third quarter of most of the sequences; the N-terminal and central regions of these proteins are presumed to interact with effector molecules and may be involved in dimerization. The minimal DNA binding domain, which spans roughly 100 residues and comprises the HTH motif contains another region with similarity to classical HTH domain. However, it contains an insertion of one residue in the turn-region.

A signature pattern was derived from the region that follows the first HTH domain and that includes the totality of the putative second HTH domain. A more sensitive detection of members of the araC family is available through the use of a profile which spans the minimal DNA-binding region of 100 residues.