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GcvA DNA-binding transcriptional dual regulator

Synonyms: GcvA-Glycine, GcvA-Purine, GcvA
Summary:
Glycine cleavage A, GcvA, is a repressor of the glycine cleavage enzyme system, which is a secondary pathway for production of C1 units |CITS: [8188587]|. It is negatively autoregulated, and it coordinately activates transcription of a small-RNA divergent gene |CITS: [7665470][10972807]|.
In the absence of glycine and the presence of GcvR, GcvA represses operons involved in the glycine cleavage system |CITS: [7665470][10972807][11495998]|. GcvR is an accessory protein that binds directly to GcvA, bending DNA to form a repression complex (GcvA/GcvR) in the regulatory region of the gcvT operon |CITS: [11495998]|.
Glycine binds directly to GcvR to disrupt or block the association of the GcvA/GcvR complex, whereas purines appear to promote the formation of the repression complex through an unknown mechanism |CITS: [12101307][11495998]|. GcvA also activates transcription of the gcv genes, via interaction with the α or σ subunits of RNA polymerase |CITS: [15621456]|.
This transcriptional dual regulator, which belongs to the LysR-family |CITS: [8188587]|, has two domains: the amino-terminal domain, which appears to be involved in transcription activation and in DNA binding through its helix-turn-helix subdomain, and the carboxy-terminal domain, involved in GcvR interaction |CITS: [9733689][11495998]|.
The GcvA binding sites do not show a clear conservation in their sequences except for a short 5'-CTAAT-3' region |CITS: [7665470]|. Read more >


Transcription factor      
TF conformation(s):
Name Conformation Type TF-Effector Interaction Type Apo/Holo Conformation Evidence (Confirmed, Strong, Weak) References
GcvA Functional   Apo [BPP], [GEA], [SM] [1], [2]
GcvA-Glycine Non-Functional Allosteric Holo [BPP], [GEA], [SM] [1], [2]
GcvA-Purine Non-Functional Allosteric Holo [BPP], [GEA], [SM] [1], [2]
Evolutionary Family: LysR
Sensing class: Sensing external and internal signals
Connectivity class: Local Regulator
Gene name: gcvA
  Genome position: 2941650-2942567
  Length: 918 bp / 305 aa
Operon name: gcvA
TU(s) encoding the TF:
Transcription unit        Promoter
gcvA
gcvAp


Regulon       
Regulated gene(s) gcvA, gcvB, gcvH, gcvP, gcvT
Multifun term(s) of regulated gene(s) MultiFun Term (List of genes associated to the multifun term)
amino acids (4)
formyl-THF biosynthesis (4)
Transcription related (1)
activator (1)
repressor (1)
Read more >
Regulated operon(s) gcvA, gcvB, gcvTHP
First gene in the operon(s) gcvA, gcvB, gcvT
Simple and complex regulons CRP,FNR,GcvA,Lrp,PurR
GcvA
Simple and complex regulatory phrases Regulatory phrase (List of promoters regulated by the phrase)
[GcvA,-](2)
[GcvA,+-](1)
[GcvA,+](1)


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
  GcvA repressor gcvAp Sigma70 -14.0 -86.0 gcvA
agaagctcaaCGGACAATTTATAATggctcagatt
2942646 2942660 [AIBSCS], [BCE], [BPP], [GEA], [HIBSCS], [IC] [3], [4], [5], [6], [7], [8]
  GcvA repressor gcvAp Sigma70 9.0 -64.0 gcvA
aatggctcagATTAAAAAAACTAATaggttacata
2942624 2942638 [BCE], [GEA], [HIBSCS], [SM] [3], [4], [5], [6], [7], [8]
  GcvA activator gcvBp Sigma70 -65.0 -65.0 gcvB
tatgtaacctATTAGTTTTTTTAATctgagccatt
2942624 2942638 [BCE], [GEA], [HIBSCS], [SM] [3], [4], [5], [6], [7], [8]
  GcvA activator gcvBp Sigma70 -43.0 -43.0 gcvB
aatctgagccATTATAAATTGTCCGttgagcttct
2942646 2942660 [AIBSCS], [BCE], [BPP], [GEA], [HIBSCS], [IC] [3], [4], [5], [6], [7], [8]
  GcvA dual gcvTp Sigma70 -258.0 -363.0 gcvT, gcvH, gcvP
ttttcctcatTTGAAATAAACTAATttcacctccg
3051023 3051037 [BCE], [BPP], [GEA], [HIBSCS], [SM] [3], [5], [7], [8], [9], [10], [11], [12]
  GcvA dual gcvTp Sigma70 -226.0 -331.0 gcvT, gcvH, gcvP
ccgttttcgcATTATATTTTCTAATgccattattt
3050991 3051005 [BCE], [BPP], [GEA], [HIBSCS], [SM] [3], [5], [7], [8], [9], [10], [11], [12]
  GcvA repressor gcvTp Sigma70 -66.0 -171.0 gcvT, gcvH, gcvP
ttgcatttttTAACCATAAGCTAATgtgatgatca
3050831 3050845 [BCE], [BPP], [GEA], [HIBSCS], [SM] [3], [4], [5], [7], [8], [13]
  GcvA repressor gcvTp Sigma70 -44.0 -149.0 gcvT, gcvH, gcvP
aatgtgatgaTCAATTTTACCTTATggttaacagt
3050809 3050823 [BCE], [BPP], [GEA], [HIBSCS], [IC], [SM] [3], [4], [5], [7], [8], [13]


Alignment and PSSM for GcvA TFBSs    

Aligned TFBS of GcvA   
  Sequence
  CAGATTAAAAA
  CATTATAAATT
  CATAAGGTAAA
  CATAAGCTAAT
  CATTAGAAAAT
  CATTTGAAATA

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

 [BPP] Binding of purified proteins

 [GEA] Gene expression analysis

 [SM] Site mutation

 [AIBSCS] Automated inference based on similarity to consensus sequences

 [BCE] Binding of cellular extracts

 [HIBSCS] Human inference based on similarity to consensus sequences

 [IC] Inferred by curator



Reference(s)    

 [1] Ghrist AC., Heil G., Stauffer GV., 2001, GcvR interacts with GcvA to inhibit activation of the Escherichia coli glycine cleavage operon., Microbiology. 147(Pt 8):2215-21

 [2] Heil G., Stauffer LT., Stauffer GV., 2002, Glycine binds the transcriptional accessory protein GcvR to disrupt a GcvA/GcvR interaction and allow GcvA-mediated activation of the Escherichia coli gcvTHP operon., Microbiology. 148(Pt 7):2203-14

 [3] Jourdan AD., Stauffer GV., 1999, Genetic analysis of the GcvA binding site in the gcvA control region., Microbiology. 145 ( Pt 8):2153-62

 [4] McArthur SD., Pulvermacher SC., Stauffer GV., 2006, The Yersinia pestis gcvB gene encodes two small regulatory RNA molecules., BMC Microbiol. 6:52

 [5] Stauffer LT., Stauffer GV., 2005, GcvA interacts with both the alpha and sigma subunits of RNA polymerase to activate the Escherichia coli gcvB gene and the gcvTHP operon., FEMS Microbiol Lett. 242(2):333-8

 [6] Urbanowski ML., Stauffer LT., Stauffer GV., 2000, The gcvB gene encodes a small untranslated RNA involved in expression of the dipeptide and oligopeptide transport systems in Escherichia coli., Mol Microbiol. 37(4):856-68

 [7] Wilson RL., Stauffer GV., 1994, DNA sequence and characterization of GcvA, a LysR family regulatory protein for the Escherichia coli glycine cleavage enzyme system., J Bacteriol. 176(10):2862-8

 [8] Wilson RL., Urbanowski ML., Stauffer GV., 1995, DNA binding sites of the LysR-type regulator GcvA in the gcv and gcvA control regions of Escherichia coli., J Bacteriol. 177(17):4940-6

 [9] Jourdan AD., Stauffer GV., 1998, Mutational analysis of the transcriptional regulator GcvA: amino acids important for activation, repression, and DNA binding., J Bacteriol. 180(18):4865-71

 [10] Stauffer LT, Stauffer GV,, 1998, Roles for GcvA-binding sites 3 and 2 and the Lrp-binding region in gcvT::lacZ expression in Escherichia coli., Microbiology 144 ( Pt 10)():2865-72

 [11] Stauffer LT., Stauffer GV., 1998, Spacing and orientation requirements of GcvA-binding sites 3 and 2 and the Lrp-binding region for gcvT::lacZ expression in Escherichia coli., Microbiology. 144 ( Pt 5):1417-22

 [12] Wilson RL., Steiert PS., Stauffer GV., 1993, Positive regulation of the Escherichia coli glycine cleavage enzyme system., J Bacteriol. 175(3):902-4

 [13] Wonderling LD., Urbanowski ML., Stauffer GV., 2000, GcvA binding site 1 in the gcvTHP promoter of Escherichia coli is required for GcvA-mediated repression but not for GcvA-mediated activation., Microbiology. 146 ( Pt 11):2909-18



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