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MlrA DNA-binding transcriptional activator

Synonyms: MlrA
Summary:
MlrA is a regulator of curli production in an avian pathogenic Escherichia coli strain and in Salmonella enterica serovar Typhimurium [1]. Shiga toxin-encoding prophages have been observed to integrate at the mlrA gene of enterohemorrhagic E. coli []. MlrA is a member of the MerR family, containing the conserved N-terminal DNA-binding domain present in members of this family [1, 2]. On the other hand, its C-terminal domain, probably used by a yet-to-be-identified effector, showed no similarity to any of the hitherto-characterized MerR family members [2]. MlrA binds an AAAGTTGTACA(12N)TGCACAATTTT palindromic sequence and probably induces DNA underwinding, as in the case of MerR [2]. Based on the site identified on the csgDp1 promoter, sites for another four genes were identified, two of which are transcriptional regulators [2].
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Transcription factor      
TF conformation(s):
Name Conformation Type TF-Effector Interaction Type Apo/Holo Conformation Evidence (Confirmed, Strong, Weak) References
MlrA Functional   [AIFS], [APPHINH], [IEP], [IHBCE] [1], [2], [3], [4]
Evolutionary Family: MerR
Connectivity class: Local Regulator
Gene name: mlrA
  Genome position: 2214866-2215597
  Length: 732 bp / 243 aa
Operon name: mlrA
TU(s) encoding the TF:
Transcription unit        Promoter
mlrA
mlrAp


Regulon       
Regulated gene(s) cadC, csgD, csgE, csgF, csgG, ibaG, obgE, rplU, rpmA, yhbE
Multifun term(s) of regulated gene(s) MultiFun Term (List of genes associated to the multifun term)
Transcription related (2)
activator (2)
membrane (2)
translation (2)
ribosomal proteins (2)
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Regulated operon(s) cadC, csgDEFG, ibaG-murA, rplU-rpmA-yhbE-obgE
First gene in the operon(s) cadC, csgD, ibaG, rplU, rplU
Simple and complex regulons BasR,CRP,CpxR,Cra,CsgD,FliZ,H-NS,IHF,MlrA,MqsA,OmpR,RcdA,RcsAB,RstA
CadC,FNR,H-NS,LeuO,MlrA
MlrA
Simple and complex regulatory phrases Regulatory phrase (List of promoters regulated by the phrase)
[MlrA,+](4)


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 (Confirmed, Strong, Weak) References
  MlrA activator cadCp Sigma70 -201.5 -231.0 cadC
tttgccaaagAAAAATGTTCAGAAAATAATCCATGGAAAATTGTccggagcact
4362148 4362182 [BPP], [HIBSCS] [2]
  MlrA activator csgDp1 Sigma38, Sigma70 -129.5 -278.0 csgD, csgE, csgF, csgG
aaatgatagaAAAGTTGTACATTTGGTTTTTATTGCACAATTTTaaaaaatcat
1103457 1103491 [BPP], [GEA] [2]
  MlrA activator ibaGp2 Sigma24 -117.5 -201.0 ibaG
catcagcaggCAAATTATACAATTTCGCCAGGGTATACACTTTGtcgtttaccc
3336987 3337021 [BPP], [HIBSCS] [2]
  MlrA activator rplUp Sigma70 -85.5 -151.0 rplU, rpmA, yhbE, obgE
aaaaaaaacaCAACTTGTACGGTAACGTTTATCTGTGCCATTTTttcagtacaa
3333585 3333619 [BPP], [HIBSCS] [2]


Alignment and PSSM for MlrA TFBSs    

Aligned TFBS of MlrA   
  Sequence
  AAGTTGTACATTTGGTTTTTATTGCACAATTTT
  AACTTGTACGGTAACGTTTATCTGTGCCATTTT
  AAAGTGTATACCCTGGCGAAATTGTATAATTTG
  CAATTTTCCATGGATTATTTTCTGAACATTTTT

Position weight matrix (PWM).   
A	3	4	2	0	0	0	0	3	0	3	0	0	1	2	0	0	1	0	1	2	2	0	0	0	1	3	0	3	3	0	0	0	0
C	1	0	1	0	0	0	0	1	3	0	1	1	1	0	1	0	1	0	0	0	0	2	0	0	1	0	3	1	0	0	0	0	0
G	0	0	1	1	0	3	0	0	0	1	1	1	1	1	2	2	0	1	0	0	0	0	0	4	0	1	0	0	0	0	0	0	1
T	0	0	0	3	4	1	4	0	1	0	2	2	1	1	1	2	2	3	3	2	2	2	4	0	2	0	1	0	1	4	4	4	3

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    

 [AIFS] Automated inference of function from sequence

 [APPHINH] Assay of protein purified to homogeneity from its native host

 [IEP] Inferred from expression pattern

 [IHBCE] Inferred by a human based on computational evidence

 [BPP] Binding of purified proteins

 [HIBSCS] Human inference based on similarity to consensus sequences

 [GEA] Gene expression analysis



Reference(s)    

 [1] Brown PK., Dozois CM., Nickerson CA., Zuppardo A., Terlonge J., Curtiss R., 2001, MlrA, a novel regulator of curli (AgF) and extracellular matrix synthesis by Escherichia coli and Salmonella enterica serovar Typhimurium., Mol Microbiol 41(2):349-63

 [2] Ogasawara H., Yamamoto K., Ishihama A., 2010, Regulatory role of MlrA in transcription activation of csgD, the master regulator of biofilm formation in Escherichia coli., FEMS Microbiol Lett 312(2):160-8

 [3] Perez-Rueda E., Collado-Vides J., Segovia L., 2004, Phylogenetic distribution of DNA-binding transcription factors in bacteria and archaea., Comput Biol Chem 28(5-6):341-50

 [4] Shaikh N., Tarr PI., 2003, Escherichia coli O157:H7 Shiga toxin-encoding bacteriophages: integrations, excisions, truncations, and evolutionary implications., J Bacteriol 185(12):3596-605

 [5] Lindenberg S., Klauck G., Pesavento C., Klauck E., Hengge R., 2013, The EAL domain protein YciR acts as a trigger enzyme in a c-di-GMP signalling cascade in E. coli biofilm control., EMBO J 32(14):2001-14



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