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GcvA DNA-binding transcriptional dual regulator

Synonyms: GcvA-gly, GcvA, GcvA-Purine
"Glycine cleavage A," GcvA, is a repressor of the glycine cleavage enzyme system, which is a secondary pathway for production of C1 units [4]. It is negatively autoregulated, and it coordinately activates transcription of a small-RNA divergent gene [5, 9]. In the absence of glycine and the presence of GcvR, GcvA represses operons involved in the glycine cleavage system [5, 9]. 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 []. 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 [1]. GcvA also activates transcription of the gcv genes, via interaction with the α or σ subunits of RNA polymerase [8]. This transcriptional dual regulator, which belongs to the LysR-family [4], 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 [10]. The GcvA binding sites do not show a clear conservation in their sequences except for a short 5'-CTAAT-3' region [5]. 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], [HIFS], [SM] [1], [2], [3], [4], [5]
GcvA-Purine Non-Functional Allosteric Holo [BPP] [1]
GcvA-gly Non-Functional Allosteric Holo [BPP], [GEA], [SM] [1]
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

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
Simple and complex regulatory phrases Regulatory phrase (List of promoters regulated by the phrase)

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
  GcvA repressor gcvAp Sigma70 -14.0 -86.0 gcvA
2942646 2942660 [AIBSCS], [BCE], [BPP], [GEA], [HIBSCS], [IC] [4], [5], [6], [7], [8], [9]
  GcvA repressor gcvAp Sigma70 9.0 -64.0 gcvA
2942624 2942638 [BCE], [GEA], [HIBSCS], [SM] [4], [5], [6], [7], [8], [9]
  GcvA activator gcvBp Sigma70 -65.0 -65.0 gcvB
2942624 2942638 [BCE], [GEA], [HIBSCS], [SM] [4], [5], [6], [7], [8], [9]
  GcvA activator gcvBp Sigma70 -43.0 -43.0 gcvB
2942646 2942660 [AIBSCS], [BCE], [BPP], [GEA], [HIBSCS], [IC] [4], [5], [6], [7], [8], [9]
  GcvA dual gcvTp Sigma70 -258.0 -363.0 gcvT, gcvH, gcvP
3051023 3051037 [BCE], [BPP], [GEA], [HIBSCS], [SM] [4], [5], [6], [8], [10], [11], [12], [13]
  GcvA dual gcvTp Sigma70 -258.0 -363.0 gcvT, gcvH, gcvP
3051023 3051037 [BCE], [BPP], [GEA], [HIBSCS], [SM] [4], [5], [6], [8], [10], [11], [12], [13]
  GcvA dual gcvTp Sigma70 -226.0 -331.0 gcvT, gcvH, gcvP
3050991 3051005 [BCE], [BPP], [GEA], [HIBSCS], [SM] [4], [5], [6], [8], [10], [11], [12], [13]
  GcvA dual gcvTp Sigma70 -226.0 -331.0 gcvT, gcvH, gcvP
3050991 3051005 [BCE], [BPP], [GEA], [HIBSCS], [SM] [4], [5], [6], [8], [10], [11], [12], [13]
  GcvA repressor gcvTp Sigma70 -66.0 -171.0 gcvT, gcvH, gcvP
3050831 3050845 [BCE], [BPP], [GEA], [HIBSCS], [SM] [4], [5], [6], [7], [8], [14]
  GcvA repressor gcvTp Sigma70 -44.0 -149.0 gcvT, gcvH, gcvP
3050809 3050823 [BCE], [BPP], [GEA], [HIBSCS], [IC], [SM] [4], [5], [6], [7], [8], [14]

Alignment and PSSM for GcvA TFBSs    

Aligned TFBS of GcvA   

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


 [BPP] Binding of purified proteins

 [GEA] Gene expression analysis

 [HIFS] Human inference of function from sequence

 [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


 [1] 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

 [2] Okamura-Ikeda K., Ohmura Y., Fujiwara K., Motokawa Y., 1993, Cloning and nucleotide sequence of the gcv operon encoding the Escherichia coli glycine-cleavage system., Eur J Biochem 216(2):539-48

 [3] Sargentini NJ., Gularte NP., Hudman DA., 2016, Screen for genes involved in radiation survival of Escherichia coli and construction of a reference database., Mutat Res 793-794:1-14

 [4] 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

 [5] 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

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

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

 [8] 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

 [9] 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

 [10] 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

 [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] null, null, null, null

 [14] 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