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PaaX DNA-binding transcriptional repressor

Synonyms: PaaX, PaaX-phenylacetyl-CoA
Summary:
The "phenylacetic acid" regulator [5], PaaX, is a transcriptional repressor that participates in controlling transcriptional regulation of genes involved in the catabolism of an aromatic compound, phenylacetic acid (PA) [1]. When PaaX is overexpressed, it causes elevated levels of mutations in the genome; therefore, it is a candidate to regulate DNA replication, recombination, or repair [6]. PaaX contains a helix-turn-helix motif for DNA binding that is similar to the motif found in the N terminal of members of the GntR family of transcriptional regulators [5]. Members of this family share similar N-terminal DNA-binding domains but are classified into four subfamilies according to their divergence in their C-terminal domains, which are involved in effector binding and oligomerization [7]. Homology with PaaX has been found in other bacteria, such as Pseudomonas putida, Bacillus halodurans, and Arthrobacter sp., among others [1]. The majority of work concerning PaaX has been done in E.
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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
PaaX Functional   Apo nd nd nd
PaaX-phenylacetyl-CoA Non-Functional   Holo nd nd nd
Evolutionary Family: PaaX
TFBs length: 15
TFBs symmetry: inverted-repeat
Sensing class: Using internal synthesized signals
Connectivity class: Local Regulator
Gene name: paaX
  Genome position: 1463539-1464489
  Length: 951 bp / 316 aa
Operon name: paaXY
TU(s) encoding the TF:
Transcription unit        Promoter
paaXY
paaXp


Regulon       
Regulated gene(s) paaA, paaB, paaC, paaD, paaE, paaF, paaG, paaH, paaI, paaJ, paaK, paaX, paaY, paaZ
Multifun term(s) of regulated gene(s) MultiFun Term (List of genes associated to the multifun term)
carbon compounds (13)
metabolism (1)
Transcription related (1)
repressor (1)
Regulated operon(s) paaABCDEFGHIJK, paaXY, paaZ
First gene in the operon(s) paaA, paaX, paaZ
Simple and complex regulons CRP,IHF,PaaX
CRP,IHF,PaaX,SlyA
PaaX
Simple and complex regulatory phrases Regulatory phrase (List of promoters regulated by the phrase)
[PaaX,-](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
  PaaX repressor paaAp Sigma70 30.0 -33.0 paaA, paaB, paaC, paaD, paaE, paaF, paaG, paaH, paaI, paaJ, paaK
taaaacaatgTGATTCGTGTTTTTAATTAATTCACGAAAACTGGAATCGtaaaggtgat
 1453875 1453913 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-DAP-SEQ], [EXP-IDA-BINDING-OF-CELLULAR-EXTRACTS], [EXP-IMP-SITE-MUTATION] C [1], [1], [2], [2], [3]
  PaaX repressor paaXp Sigma70 10.5 -20.5 paaX, paaY
acctgtgctaTGATTCATAAATCACAACAATAACAACAGACTGAAGCGAatgagtaaac
 1463500 1463538 [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] S [4], [4]
  PaaX repressor paaZp nd -6.5 -34.5 paaZ
tttgctttttATGATTCGCGATTTAACTATTAGCAACAGAAATGTGAAACAtctggagagt
 1453657 1453697 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-DAP-SEQ], [EXP-IDA-BINDING-OF-CELLULAR-EXTRACTS], [EXP-IMP-SITE-MUTATION] C [1], [1], [2], [2], [3]


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


Evidence    

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

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

 [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

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


Reference(s)    

 [1] Ferrandez A., Garcia JL., Diaz E., 2000, Transcriptional regulation of the divergent paa catabolic operons for phenylacetic acid degradation in Escherichia coli., J Biol Chem 275(16):12214-22

 [2] Kim HS., Kang TS., Hyun JS., Kang HS., 2004, Regulation of penicillin G acylase gene expression in Escherichia coli by repressor PaaX and the cAMP-cAMP receptor protein complex., J Biol Chem 279(32):33253-62

 [3] 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

 [4] Fernandez C., Diaz E., Garcia JL., 2014, Insights on the regulation of the phenylacetate degradation pathway from Escherichia coli., Environ Microbiol Rep 6(3):239-50

 [5] Ferrandez A., Minambres B., Garcia B., Olivera ER., Luengo JM., Garcia JL., Diaz E., 1998, Catabolism of phenylacetic acid in Escherichia coli. Characterization of a new aerobic hybrid pathway., J Biol Chem 273(40):25974-86

 [6] Yang H., Wolff E., Kim M., Diep A., Miller JH., 2004, Identification of mutator genes and mutational pathways in Escherichia coli using a multicopy cloning approach., Mol Microbiol 53(1):283-95

 [7] Rigali S., Derouaux A., Giannotta F., Dusart J., 2002, Subdivision of the helix-turn-helix GntR family of bacterial regulators in the FadR, HutC, MocR, and YtrA subfamilies., J Biol Chem 277(15):12507-15

 [8] del Peso-Santos T, Bartolomé-Martín D, Fernández C, Alonso S, García JL, Díaz E, Shingler V, Perera J, 2006, Coregulation by phenylacetyl-coenzyme A-responsive PaaX integrates control of the upper and lower pathways for catabolism of styrene by Pseudomonas sp. strain Y2., J Bacteriol, 188(13):4812 10.1128/JB.00176-06

 [9] Rojas-Altuve A, Carrasco-López C, Hernández-Rocamora VM, Sanz JM, Hermoso JA, 2011, Crystallization and preliminary X-ray diffraction studies of the transcriptional repressor PaaX, the main regulator of the phenylacetic acid degradation pathway in Escherichia coli W., Acta Crystallogr Sect F Struct Biol Cryst Commun, 67(Pt 10):1278 10.1107/S1744309111029873


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