nickel-responsive transcriptional regulator NikR; Three members of the seed for this model, from Escherichia coli, Pseudomonas putida, and Brucella melitensis, are found associated with a nickel ABC transporter operon that acts to import nickel for use as a cofactor in urease or hydrogenase. These proteins, with characterized nickel-binding and DNA-binding domains, act as nickel-responsive transcriptional regulators. In the larger family of full-length homologs, most others both lack proximity to the nickel ABC transporter operon and form a separate clade. Several of the homologs not within the scope of this model, but rather scoring between the trusted and noise cutoffs, have been shown to bind nickel, copper, or both, and to regulate genes in response to nickel. [Regulatory functions, DNA interactions]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16131353     2 QRVTITLDDDLLETLDSLSQRRGYNNRSEAIRDILRSALAQEATQQHGTQGFAVLSYVYEHEKRDLASRIVSTQHHHHDL 81
Cdd:TIGR02793   1 QRVTITLDDDLLETLDRLIARRGYQNRSEAIRDLLRSGLQQEAAEQHGTACVAVLSYTYDHSKRDLPRRLTQTQHHHHDL 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 16131353    82 SVATLHVHINHDDCLEIAVLKGDMGDVQHFADDVIAQRGVRHGHLQCLP 130
Cdd:TIGR02793  81 SVATLHVHLDHDDCLEVSVLKGDMGDVQHFADHVIAERGVRHGHLQVLP 129

NikR C terminal nickel binding domain; NikR is a transcription factor that regulates nickel uptake. It consists of two dimeric DNA binding domains separated by a tetrameric regulatory domain that binds nickel. This domain corresponds to the C terminal regulatory domain which contains four nickel binding sites at the tetramer interface.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 16131353    54 AVLSYVYEHEKRDLASRIVSTQHHHHDLSVATLHVHINHDDCLEIAVLKGDMGDVQHFADDVIAQRGVRHGHL 126
Cdd:pfam08753   1 GTITVVYDHHQRDLSERLTDIQHEYHDLIISTLHVHLDHDNCLEVIVLKGPAEEIRELADKLRALKGVKHGKL 73

nickel-responsive transcriptional regulator NikR; Three members of the seed for this model, from Escherichia coli, Pseudomonas putida, and Brucella melitensis, are found associated with a nickel ABC transporter operon that acts to import nickel for use as a cofactor in urease or hydrogenase. These proteins, with characterized nickel-binding and DNA-binding domains, act as nickel-responsive transcriptional regulators. In the larger family of full-length homologs, most others both lack proximity to the nickel ABC transporter operon and form a separate clade. Several of the homologs not within the scope of this model, but rather scoring between the trusted and noise cutoffs, have been shown to bind nickel, copper, or both, and to regulate genes in response to nickel. [Regulatory functions, DNA interactions]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16131353     2 QRVTITLDDDLLETLDSLSQRRGYNNRSEAIRDILRSALAQEATQQHGTQGFAVLSYVYEHEKRDLASRIVSTQHHHHDL 81
Cdd:TIGR02793   1 QRVTITLDDDLLETLDRLIARRGYQNRSEAIRDLLRSGLQQEAAEQHGTACVAVLSYTYDHSKRDLPRRLTQTQHHHHDL 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 16131353    82 SVATLHVHINHDDCLEIAVLKGDMGDVQHFADDVIAQRGVRHGHLQCLP 130
Cdd:TIGR02793  81 SVATLHVHLDHDDCLEVSVLKGDMGDVQHFADHVIAERGVRHGHLQVLP 129

nickel-responsive transcriptional regulator NikR;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16131353   19 LSQRRGYNNRSEAIRDILRSALAQEATQQHGTQGFAVLSYVYEHEKRDLASRIVSTQHHHHDLSVATLHVHINHDDCLEI 98
Cdd:PRK04460  20 LIEEKGYQNRSEAIRDLIRDFLVEHEWEEGDEEVAGTVTLVYNHHVSDLAQKLTEIQHDHHDEIISSLHVHLDHHNCLEV 99

                         90       100
                 ....*....|....*....|....*...
gi 16131353   99 AVLKGDMGDVQHFADDVIAQRGVRHGHL 126
Cdd:PRK04460 100 LVLKGKAKEIKKIADRLISTKGVKHGKL 127

nickel responsive regulator; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16131353   23 RGYNNRSEAIRDILRSALAQ-EATQQHGTQGFAVLSYVYEHEKRDLASRIVSTQHHHHDLSVATLHVHINHDDCLEIAVL 101
Cdd:PRK01002  26 RGYASRSEGIRDAIRDYIIKyKWMNSMEGERVGTISVIYDHHSTGVMEKLTDIQHDYSDLIVASLHIHLDHDHCLEVIVV 105

                         90       100
                 ....*....|....*....|....*
gi 16131353  102 KGDMGDVQHFADDVIAQRGVRHGHL 126
Cdd:PRK01002 106 RGDAKEIRELTEKLMALKGVKHVKL 130

ribbon-helix-helix domains of nickel responsive transcription factor NikR, antitoxins HicB, ParD, and MazE, and similar proteins; This family includes the N-terminal domain of NikR, C-terminal domains of antitoxins HicB and ParD, as well as antitoxin MazE, and similar proteins, all of which belong to the ribbon-helix-helix (RHH) family of transcription factors. NikR is a nickel-responsive transcription factor that consists of an N-terminal DNA-binding RHH domain and a C-terminal metal-binding domain (MBD) with four nickel ions. In Helicobacter pylori, which colonizes the gastric epithelium of humans leading to gastric ulcers and gastric cancers, NikR (HpNikR) regulates multiple genes. It regulates urease, which protects H. pylori from acidic shock at low pH, by converting urea to ammonia and bicarbonate. It also plays a complex role in the intracellular physiology of nickel; occupation of nickel-binding sites results in NikR binding to its operator in the nickel permease nikABCDE promoter. Thus, there is weaker repression of NikABCDE transcription at low intracellular free nickel concentrations while strong repression prevails at higher concentrations, which would be potentially toxic. Antitoxin HicB is part of the HicAB toxin-antitoxin (TA) system, where the toxins are RNases, found in many bacteria. In the pathogen Burkholderia pseudomallei, the HicAB system plays a role in regulating the frequency of persister cells and may therefore play a role in disease. Structural studies of Yersinia pestis HicB show that it acts as an autoregulatory protein and HicA acts as an mRNase. In Escherichia coli, an excess of HicA has been shown to de-repress a HicB-DNA complex and restore transcription of HicB. Similarly, Caulobacter crescentus ParD antitoxin neutralizes the effect of cognate ParE toxin. In Bacillus subtilis, during stress conditions, antitoxin MazE binds to toxin MazF, an mRNA interferase, and inactivates it and cleaves mRNAs in a sequence-specific manner, resulting in cellular growth arrest.

                        10        20
                ....*....|....*....|....*
gi 16131353  19 LSQRRGYNNRSEAIRDILRSALAQE 43
Cdd:cd22231  18 LVKEGGYSSRSEAIRDAIRELLEEE 42