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RcdA DNA-binding transcriptional dual regulator

Synonyms: RcdA, RcdA-trimethylamine N-oxide, RcdA-tris
Summary:
RcdA, also known as YbjK, belongs to the TetR family and is involved in the regulation of a number of stress response genes, biofilm formation, and transcription regulator genes [1] Genomic SELEX analysis showed that RcdA can bind to the upstream regions of 27 genes. Among these predicted targets of RcdA, six genes correspond to transcription regulators (AppY, CsgD, FimB, RcdA, Sxy, and YcgF). This indicates that a large number of genes must be regulated indirectly by these regulators. Another group of target genes includes membrane-associated stress response proteins (CsgB, NanC, OmpA, PgaA, YbjJ, YehA, and YoeA) and stress response cytoplasmic proteins (Asr and YdeI), among others [1] RcdA exhibits strong cooperative DNA binding and produces aggregates of RcdA-DNA complexes. In a specific way and with high binding affinity, this regulator recognizes and binds to sites that have closely related sequences. Furthermore, a consensus sequence has been proposed for RcdA sites. This consensus sequence shows a core binding site of 9 bp, TTGTgtACA, with inverted repeat symmetry [1] According to the analysis performed by the curator, the consensus sequence has a length of 10 bp (TTGTgtACAa).On the other hand, a dimer conformation for RcdA in solution was observed [4]. RcdA contains a HTH DNA binding motif located in its N-terminal domain, and in its C-terminal domain it contains a small cavity for ligand binding which is able to bind small molecules like trimethylamine N-oxide (TMAO) and Tris, with TMAO the preferred of these two in solution [4].
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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
RcdA Functional   nd nd nd
RcdA-trimethylamine N-oxide Non-Functional   nd nd nd
RcdA-tris Non-Functional   nd nd nd
Evolutionary Family: TetR/AcrR
TFBs length: 10
TFBs symmetry: inverted-repeat
Connectivity class: Local Regulator
Gene name: rcdA
  Genome position: 887423-887959
  Length: 537 bp / 178 aa
Operon name: rcdA
TU(s) encoding the TF:
Transcription unit        Promoter
ybjK
 


Regulon       
Regulated gene(s) asr, bluF, csgD, csgE, csgF, csgG, rmf, rsd, sulA, yagK, ydeI
Multifun term(s) of regulated gene(s) MultiFun Term (List of genes associated to the multifun term)
posttranscriptional (2)
Transcription related (2)
pH (1)
activator (1)
repressor (1)
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Regulated operon(s) asr, bluF, csgDEFG, rmf, rsd, sulA, yagK, ydeI
First gene in the operon(s) asr, bluF, csgD, rmf, rsd, sulA, yagK, ydeI
Simple and complex regulons ArcA,CRP,McbR,RcdA,SdiA,SlyA,ppGpp
ArcA,McbR,RcdA,SdiA,SlyA
BasR,BolA,BtsR,CRP,CpxR,Cra,CsgD,FliZ,H-NS,IHF,MlrA,MqsA,OmpR,RcdA,RcsAB,RstA,ppGpp
BasR,BtsR,CRP,CpxR,Cra,CsgD,FliZ,H-NS,IHF,MlrA,MqsA,OmpR,RcdA,RcsAB,RstA
H-NS,PhoB,RcdA,RstA
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Simple and complex regulatory phrases Regulatory phrase (List of promoters regulated by the phrase)
[RcdA,-](2)
[RcdA,+](8)


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
  RcdA activator asrp Sigma70 -68.5 -117.5 asr
tttattcagcGTTTGTACATAtcgttacacg
 1671254 1671264 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [IC], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS], [IC] S [1], [1]
  RcdA activator asrp Sigma70 -58.5 -107.5 asr
gtttgtacatATCGTTACACGctgaaaccaa
 1671264 1671274 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [IC], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS], [IC] S [1], [1]
  RcdA activator asrp2 Sigma38 -68.5 -117.5 asr
tttattcagcGTTTGTACATAtcgttacacg
 1671254 1671264 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [IC], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS], [IC] S [1], [1]
  RcdA activator asrp2 Sigma38 -58.5 -107.5 asr
gtttgtacatATCGTTACACGctgaaaccaa
 1671264 1671274 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [IC], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS], [IC] S [1], [1]
  RcdA activator bluFp Sigma70 -222.5 -253.5 bluF
caatagcaaaCTTGTACGAAAtatgtgtaca
 1215724 1215734 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-DAP-SEQ], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] C [1], [1], [2]
  RcdA activator bluFp Sigma70 -211.5 -242.5 bluF
ttgtacgaaaTATGTGTACAGaatgataaat
 1215713 1215723 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-DAP-SEQ], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] C [1], [1], [2]
  RcdA activator csgDp1 Sigma70 -298.5 -446.5 csgD, csgE, csgF, csgG
tgcgatatgtCTTGCGCACAAgccgtgacaa
 1103638 1103648 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [IC], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS], [IC] S [1], [1]
  RcdA activator csgDp3 Sigma38 -298.5 -446.5 csgD, csgE, csgF, csgG
tgcgatatgtCTTGCGCACAAgccgtgacaa
 1103638 1103648 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [IC], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS], [IC] S [1], [1]
  RcdA activator rmfp nd nd nd rmf
nd
 nd nd [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [EXP-GSELEX], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] S [3], [3]
  RcdA activator rsdp2 Sigma70 nd nd rsd
nd
 nd nd [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [EXP-GSELEX], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] S [3], [3]
  RcdA repressor sulAp Sigma70 33.5 5.5 sulA
ctggattgatTATGTACACTTcaggctatgc
 1020910 1020920 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] S [1], [1]
  RcdA repressor sulAp Sigma70 47.5 19.5 sulA
tacacttcagGCTATGCACATcgttcttcgt
 1020896 1020906 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] S [1], [1]
  RcdA repressor yagKp6 Sigma70 3.5 -167.5 yagK
atataatggcATTGTGTACTCttactacctg
 293111 293121 [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] S [1], [1]
  RcdA activator ydeIp5 Sigma70 nd nd ydeI
nd
 nd nd [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] S [1], [1]



High-throughput Transcription factor binding sites (TFBSs)
      

  Functional conformation Function Object name Object type Distance to first Gene Sequence LeftPos RightPos Center Position Growth Condition Evidence Confidence level (C: Confirmed, S: Strong, W: Weak) References
  RcdA activator ybjK Transcription-Unit nd
attagcaaggTTGTGTACATTtgtacacaat
887383 887393 887387.5 nd [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-DAP-SEQ], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] C [1]
  RcdA activator ybjK Transcription-Unit nd
ttgtgtacatTTGTACACAATtgcagagaga
887393 887403 887397.5 nd [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-DAP-SEQ], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] C [1]
  RcdA repressor ybjJI Transcription-Unit nd
attagcaaggTTGTGTACATTtgtacacaat
887383 887393 887387.5 nd [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-DAP-SEQ], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] C [1]
  RcdA repressor ybjJI Transcription-Unit nd
ttgtgtacatTTGTACACAATtgcagagaga
887393 887403 887397.5 nd [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-DAP-SEQ], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] C [1]
Other High-throughput regulatory interactions with weak evidence


Alignment and PSSM for RcdA TFBSs    

Aligned TFBS of RcdA   
  Sequence
  ATGTGTACAGAATG
  ATGTACAAACGCTG
  ATGTGCATAGCCTG
  AAGAGTACACAATG
  TTGCGCACAAGCCG
  ATCGTTACACGCTG
  AAGTGTACATAATC
  TTGTACGAAATATG

Position weight matrix (PWM). RcdA matrix-quality result    
A	6	2	0	1	2	0	7	2	8	2	3	4	0	0
C	0	0	1	1	0	4	0	5	0	3	1	4	1	1
G	0	0	7	1	5	0	1	0	0	2	3	0	0	7
T	2	6	0	5	1	4	0	1	0	1	1	0	7	0

Consensus    
;	consensus.strict             	atGtGcACAcgcTG
;	consensus.strict.rc          	CAGCGTGTGCACAT
;	consensus.IUPAC              	atGtGyACAsrmTG
;	consensus.IUPAC.rc           	CAKYSTGTRCACAT
;	consensus.regexp             	atGtG[ct]ACA[cg][ag][ac]TG
;	consensus.regexp.rc          	CA[GT][CT][CG]TGT[AG]CACAT

PWM logo   


 


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

 [IC] Inferred by curator

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

 [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-GSELEX] high throughput Genomic SELEX-chip evidence


Reference(s)    

 [1] Shimada T., Katayama Y., Kawakita S., Ogasawara H., Nakano M., Yamamoto K., Ishihama A., 2012, A novel regulator RcdA of the csgD gene encoding the master regulator of biofilm formation in Escherichia coli., Microbiologyopen 1(4):381-94

 [2] 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

 [3] Yoshida H., Shimada T., Ishihama A., 2018, Coordinated Hibernation of Transcriptional and Translational Apparatus during Growth Transition of Escherichia coli to Stationary Phase., mSystems 3(5)

 [4] Pietrzyk-Brzezinska AJ., Cociurovscaia A., 2021, Structures of the TetR-like transcription regulator RcdA alone and in complexes with ligands., Proteins

 [5] Sugino H, Usui T, Shimada T, Nakano M, Ogasawara H, Ishihama A, Hirata A, 2017, A structural sketch of RcdA, a transcription factor controlling the master regulator of biofilm formation., FEBS Lett, 591(13):2019 10.1002/1873-3468.12713


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