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 654680600    2 QRITITIEDDLLAEIDAAAEARGYQNRSEIIRDLARAGLQQSTEDTAQtGQCVAGLVYVYDHASRDLSKRLVQEFHGHHD 81
Cdd:TIGR02793   1 QRVTITLDDDLLETLDRLIARRGYQNRSEAIRDLLRSGLQQEAAEQHG-TACVAVLSYTYDHSKRDLPRRLTQTQHHHHD 79

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 654680600   82 LALATLHVHLDDNNCMEMTALRGDAAEVRHFADHIIAERGVRYGRVVMIP 131
Cdd:TIGR02793  80 LSVATLHVHLDHDDCLEVSVLKGDMGDVQHFADHVIAERGVRHGHLQVLP 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 654680600   57 LVYVYDHASRDLSKRLVQEFHGHHDLALATLHVHLDDNNCMEMTALRGDAAEVRHFADHIIAERGVRYGRVVM 129
Cdd:pfam08753   3 ITVVYDHHQRDLSERLTDIQHEYHDLIISTLHVHLDHDNCLEVIVLKGPAEEIRELADKLRALKGVKHGKLTL 75

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 654680600    2 QRITITIEDDLLAEIDAAAEARGYQNRSEIIRDLARAGLQQSTEDTAQtGQCVAGLVYVYDHASRDLSKRLVQEFHGHHD 81
Cdd:TIGR02793   1 QRVTITLDDDLLETLDRLIARRGYQNRSEAIRDLLRSGLQQEAAEQHG-TACVAVLSYTYDHSKRDLPRRLTQTQHHHHD 79

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 654680600   82 LALATLHVHLDDNNCMEMTALRGDAAEVRHFADHIIAERGVRYGRVVMIP 131
Cdd:TIGR02793  80 LSVATLHVHLDHDDCLEVSVLKGDMGDVQHFADHVIAERGVRHGHLQVLP 129

nickel-responsive transcriptional regulator NikR;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 654680600   3 RITITIEDDLLAEIDAAAEARGYQNRSEIIRDLARAGLQQStEDTAQTGQCVAGLVYVYDHASRDLSKRLVQEFHGHHDL 82
Cdd:PRK04460   4 RFGVSLDSDLLEKFDELIEEKGYQNRSEAIRDLIRDFLVEH-EWEEGDEEVAGTVTLVYNHHVSDLAQKLTEIQHDHHDE 82

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 654680600  83 ALATLHVHLDDNNCMEMTALRGDAAEVRHFADHIIAERGVRYGRVVMIPTGE 134
Cdd:PRK04460  83 IISSLHVHLDHHNCLEVLVLKGKAKEIKKIADRLISTKGVKHGKLVMTTTGE 134

nickel responsive regulator; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 654680600   1 MQRITITIEDDLLAEIDAAAEARGYQNRSEIIRDLARAGLQQSTEDTAQTGQCVAGLVYVYDHASRDLSKRLVQEFHGHH 80
Cdd:PRK01002   4 MMRISISLPDKLLGEFDEIIEERGYASRSEGIRDAIRDYIIKYKWMNSMEGERVGTISVIYDHHSTGVMEKLTDIQHDYS 83

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 654680600  81 DLALATLHVHLDDNNCMEMTALRGDAAEVRHFADHIIAERGVRYGRVVMIPTGE 134
Cdd:PRK01002  84 DLIVASLHIHLDHDHCLEVIVVRGDAKEIRELTEKLMALKGVKHVKLTTMVPGG 137

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        30        40
                 ....*....|....*....|....*....|....*....|.
gi 654680600   2 QRITITIEDDLLAEIDAAAEARGYQNRSEIIRDLARAGLQQ 42
Cdd:cd22231    1 ERISVSLPEELLEELDELVKEGGYSSRSEAIRDAIRELLEE 41

ribbon-helix-helix domains of transcription repressor CopG, nickel responsive transcription factor NikR, and similar proteins; This family includes the ribbon-helix-helix (RHH) domains of transcriptional repressor CopG, nickel-responsive transcription factor NikR, several antitoxins such as Shewanella oneidensis CopA(SO), Burkholderia pseudomallei HicB, and Caulobacter crescentus ParD, and similar proteins. CopG, a homodimeric RHH protein of around 45 residues, constitutes one of the smallest natural transcriptional repressors characterized and is the prototype of a series of repressor proteins encoded by plasmids that exhibit a similar genetic structure at their leading strand initiation and control regions. It is involved in the control of plasmid copy number. NikR, which consists of the N-terminal DNA-binding RHH domain and the C-terminal metal-binding domain (MBD) with four nickel ions, regulates several genes; in Helicobacter pylori, NikR regulates the urease enzyme under extreme acidic conditions, and is involved in the intracellular physiology of nickel. Protein HicB is part of the HicAB toxin-antitoxin (TA) system, where the toxins are RNases, found in many bacteria. In Burkholderia pseudomallei, the HicAB system may play a role in disease by regulating the frequency of persister cells, while in Yersinia pestis HicB acts as an autoregulatory protein that inhibits HicA, which 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. The CopG family RHH domain, represented by this model, forms a homodimer and binds DNA.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 654680600   2 QRITITIEDDLLAEIDAAAEARGyQNRSEIIRDLARAGLQQST 44
Cdd:cd21631    1 KRVTIKLDDELLERLDELARKRG-VSRSELIREALREYLERLE 42

HicB_like antitoxin of bacterial toxin-antitoxin system; This is a family of HicB-like antitoxins.

                          10        20        30
                  ....*....|....*....|....*....|....*..
gi 654680600    2 QRITITIEDDLLAEIDAAAEARGyQNRSEIirdLARA 38
Cdd:pfam15919  90 ERINITLPRRVLRRIDAYAKAAG-ETRSGF---LARA 122