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NhaR DNA-binding transcriptional activator

Synonyms: NhaR, NhaR-Na+
Summary:
The transcription factor NhaR, for "Na+/H+ antiporter Regulator," is dependent on Na+ and controls the transcription of genes involved in adaptation to Na+ and alkaline pH [1, 2, 3, 11, 12, 13, 14], response to adverse conditions [7, 8] and biofilm formation [9, 10] This regulator belongs to the LysR family. NhaR is composed of two domains: the amino-terminal domain, which contains the DNA-binding region, and the carboxy-terminal domain, which is possibly responsible for inducer binding [15]. In systematic studies of oligomerization, it was shown that some members of the LysR family, like NhaR, interact with other members of the family to form heterodimers, but the physiological significance of this is unknown [16]. The binding targets for NhaR are 17 nucleotides long.
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Transcription factor      
TF conformation(s):
Name Conformation Type TF-Effector Interaction Type Apo/Holo Conformation Evidence Confidence level (C: Confirmed, S: Strong, W: Weak) References
NhaR Non-Functional   Apo [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS], [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [EXP-IPI] S [1], [2]
NhaR-Na+ Functional Allosteric Holo [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS], [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [EXP-IPI] S [1], [2]
Evolutionary Family: LysR
TFBs length: 17
Sensing class: External sensing using transported metabolites
Connectivity class: Local Regulator
Gene name: nhaR
  Genome position: 18715-19620
  Length: 906 bp / 301 aa
Operon name: nhaAR
TU(s) encoding the TF:
Transcription unit        Promoter
nhaAR
nhaAp1
nhaAR
nhaAp2
nhaR
 


Regulon       
Regulated gene(s) nhaA, nhaR, osmC, pgaA, pgaB, pgaC, pgaD
Multifun term(s) of regulated gene(s) MultiFun Term (List of genes associated to the multifun term)
biosynthesis of macromolecules (cellular constituents) (3)
pH (2)
Porters (Uni-, Sym- and Antiporters) (1)
membrane (1)
Transcription related (1)
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Regulated operon(s) nhaAR, osmC, pgaABCD
First gene in the operon(s) nhaA, osmC, pgaA
Simple and complex regulons H-NS,Lrp,NhaR,RcsB
H-NS,NhaR
NhaR,OmpR
Simple and complex regulatory phrases Regulatory phrase (List of promoters regulated by the phrase)
[NhaR,+](3)


Transcription factor regulation    


Transcription factor binding sites (TFBSs) arrangements
      

  Functional conformation Function Promoter Sigma factor Central Rel-Pos Distance to first Gene Genes Sequence LeftPos RightPos Evidence Confidence level (C: Confirmed, S: Strong, W: Weak) References
  NhaR-Na+ activator nhaAp1 Sigma70 -66.0 -97.0 nhaA, nhaR
ttcttcaataGCTCGTAAAAAACGAATtattcctaca
 17384 17400 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [EXP-DAP-SEQ], [EXP-IDA-BINDING-OF-CELLULAR-EXTRACTS], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] C [1], [1], [2], [2], [3], [3], [4], [5], [5], [6]
  NhaR-Na+ activator nhaAp1 Sigma70 -44.0 -75.0 nhaA, nhaR
cgaattattcCTACACTATAATCTGATtttaacgatg
 17406 17422 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [EXP-DAP-SEQ], [EXP-IDA-BINDING-OF-CELLULAR-EXTRACTS], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] C [1], [1], [2], [2], [3], [3], [4], [5], [5], [6]
  NhaR-Na+ activator nhaAp1 Sigma70 -34.0 -65.0 nhaA, nhaR
ctacactataATCTGATTTTAACGATGattcgtgcgg
 17416 17432 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [EXP-DAP-SEQ], [EXP-IDA-BINDING-OF-CELLULAR-EXTRACTS], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] C [1], [1], [2], [2], [3], [3], [5], [5], [6]
  NhaR-Na+ activator nhaAp1 Sigma70 -3.0 -34.0 nhaA, nhaR
gtgcggggtaAAATAGTAAAAACGATCTattcacctga
 17447 17464 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [EXP-IDA-BINDING-OF-CELLULAR-EXTRACTS], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] S [1], [1], [2], [2], [3], [3], [4], [5], [5]
  NhaR-Na+ activator osmCp1 Sigma70 -42.0 -71.0 osmC
gccggattttATTCGGAATATCCTGCTTatcctcgtgc
 1556546 1556563 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [EXP-DAP-SEQ], [EXP-IDA-BINDING-OF-CELLULAR-EXTRACTS], [EXP-IMP-SITE-MUTATION] C [6], [7], [7], [8], [8]
  NhaR-Na+ activator pgaAp nd -63.0 -297.0 pgaA, pgaB, pgaC, pgaD
tcatcaggacTTTCGAAAAATCCGAAAtcatgcatcg
 1092578 1092594 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-DAP-SEQ], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] C [6], [9], [10], [10]
  NhaR-Na+ activator pgaAp nd -41.0 -275.0 pgaA, pgaB, pgaC, pgaD
cgaaatcatgCATCGGAATTTACTGATttaattattt
 1092556 1092572 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-DAP-SEQ], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] C [6], [9], [10], [10]


Alignment and PSSM for NhaR TFBSs    

Aligned TFBS of NhaR   
  Sequence
  TTATTCGGAATATCCTGCTTA
  TGCATCGGAATTTACTGATTT
  TAGCTCGTAAAAAACGAATTA
  TCCTACACTATAATCTGATTT
  ACTTTCGAAAAATCCGAAATC
  TAAAATAGTAAAAACGATCTA

Position weight matrix (PWM). NhaR matrix-quality result    
A	1	2	2	2	2	0	2	1	4	6	3	5	3	3	0	0	3	4	1	0	3
C	0	2	2	1	0	5	0	1	0	0	0	0	0	2	6	0	0	1	1	0	1
G	0	1	1	0	0	0	4	3	0	0	0	0	0	0	0	3	3	0	0	0	0
T	5	1	1	3	4	1	0	1	2	0	3	1	3	1	0	3	0	1	4	6	2

Consensus    
;	consensus.strict             	tccttCGgaAaaaaCggatTa
;	consensus.strict.rc          	TAATCCGTTTTTTCCGAAGGA
;	consensus.IUPAC              	tmmwwCRgwAwawmCkratTw
;	consensus.IUPAC.rc           	WAATYMGKWTWTWCYGWWKKA
;	consensus.regexp             	t[ac][ac][at][at]C[AG]g[at]A[at]a[at][ac]C[gt][ag]atT[at]
;	consensus.regexp.rc          	[AT]AAT[CT][AC]G[GT][AT]T[AT]T[AT]C[CT]G[AT][AT][GT][GT]A

PWM logo   


 


Evolutionary conservation of regulatory elements    
     Note: Evolutionary conservation of regulatory interactions and promoters is limited to gammaproteobacteria.
TF-target gene evolutionary conservation
Promoter-target gene evolutionary conservation


Evidence    

 [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] Binding of purified proteins

 [EXP-IEP-GENE-EXPRESSION-ANALYSIS] Gene expression analysis

 [EXP-IPI] Inferred from physical interaction

 [EXP-DAP-SEQ] high throughput DNA Affinity Purification (DAP) Sequencing

 [EXP-IDA-BINDING-OF-CELLULAR-EXTRACTS] Binding of cellular extracts

 [EXP-IMP-SITE-MUTATION] Site mutation

 [COMP-HINF-SIMILAR-TO-CONSENSUS] A person inferred or reviewed a computer inference of sequence function based on similarity to a consensus sequence.


Reference(s)    

 [1] Carmel O., Rahav-Manor O., Dover N., Shaanan B., Padan E., 1997, The Na+-specific interaction between the LysR-type regulator, NhaR, and the nhaA gene encoding the Na+/H+ antiporter of Escherichia coli., EMBO J 16(19):5922-9

 [2] Rahav-Manor O., Carmel O., Karpel R., Taglicht D., Glaser G., Schuldiner S., Padan E., 1992, NhaR, a protein homologous to a family of bacterial regulatory proteins (LysR), regulates nhaA, the sodium proton antiporter gene in Escherichia coli., J Biol Chem 267(15):10433-8

 [3] Carmel O., Dover N., Rahav-Manor O., Dibrov P., Kirsch D., Karpel R., Schuldiner S., Padan E., 1994, A single amino acid substitution (Glu134-->Ala) in NhaR1 increases the inducibility by Na+ of the product of nhaA, a Na+/H+ antiporter gene in Escherichia coli., EMBO J 13(8):1981-9

 [4] Dover N., Higgins CF., Carmel O., Rimon A., Pinner E., Padan E., 1996, Na+-induced transcription of nhaA, which encodes an Na+/H+ antiporter in Escherichia coli, is positively regulated by nhaR and affected by hns., J Bacteriol 178(22):6508-17

 [5] Dover N., Padan E., 2001, Transcription of nhaA, the main Na(+)/H(+) antiporter of Escherichia coli, is regulated by Na(+) and growth phase., J Bacteriol 183(2):644-53

 [6] Baumgart LA, Lee JE, Salamov A, Dilworth DJ, Na H, Mingay M, Blow MJ, Zhang Y, Yoshinaga Y, Daum CG, O'Malley RC, 2021, Persistence and plasticity in bacterial gene regulation., Nat Methods, 18(12):1499 10.1038/s41592-021-01312-2

 [7] Sturny R., Cam K., Gutierrez C., Conter A., 2003, NhaR and RcsB independently regulate the osmCp1 promoter of Escherichia coli at overlapping regulatory sites., J Bacteriol 185(15):4298-304

 [8] Toesca I., Perard C., Bouvier J., Gutierrez C., Conter A., 2001, The transcriptional activator NhaR is responsible for the osmotic induction of osmC(p1), a promoter of the stress-inducible gene osmC in Escherichia coli., Microbiology 147(Pt 10):2795-803

 [9] Cerca N., Jefferson KK., 2008, Effect of growth conditions on poly-N-acetylglucosamine expression and biofilm formation in Escherichia coli., FEMS Microbiol Lett 283(1):36-41

 [10] Goller C., Wang X., Itoh Y., Romeo T., 2006, The cation-responsive protein NhaR of Escherichia coli activates pgaABCD transcription, required for production of the biofilm adhesin poly-beta-1,6-N-acetyl-D-glucosamine., J Bacteriol 188(23):8022-32

 [11] Padan E, Schuldiner S, 1993, Na+/H+ antiporters, molecular devices that couple the Na+ and H+ circulation in cells., J Bioenerg Biomembr, 25(6):647 10.1007/BF00770252

 [12] Padan E., Gerchman Y., Rimon A., Rothman A., Dover N., Carmel-Harel O., 1999, The molecular mechanism of regulation of the NhaA Na+/H+ antiporter of Escherichia coli, a key transporter in the adaptation to Na+ and H+., Novartis Found Symp 221:183-96: discussion 196-9

 [13] Padan E, Schuldiner S, 1994, Molecular physiology of the Na+/H+ antiporter in Escherichia coli., J Exp Biol, 196(None):443 10.1242/jeb.196.1.443

 [14] Rowbury RJ., Goodson M., Humphrey TJ., 1994, Sodium chloride induces an NhaA/NhaR-independent acid sensitivity at neutral external pH in Escherichia coli., Appl Environ Microbiol 60(5):1630-4

 [15] Henikoff S., Haughn GW., Calvo JM., Wallace JC., 1988, A large family of bacterial activator proteins., Proc Natl Acad Sci U S A 85(18):6602-6

 [16] Knapp GS, Hu JC, 2010, Specificity of the E. coli LysR-type transcriptional regulators., PLoS One, 5(12):e15189 10.1371/journal.pone.0015189

 [17] Novichkov PS, Laikova ON, Novichkova ES, Gelfand MS, Arkin AP, Dubchak I, Rodionov DA, 2010, RegPrecise: a database of curated genomic inferences of transcriptional regulatory interactions in prokaryotes., Nucleic Acids Res, 38(Database issue):D111 10.1093/nar/gkp894


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