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GlaR DNA-binding transcriptional repressor

Synonyms: GlaR, GlaR-glutarate
Summary:
The transcription factor CsiR, for "Carbon starvation induced Regulator," was initially identified as a repressor that controls the transcription of genes involved in the degradation and transport of 4-aminobutyrate (GABA) for utilization as a source of nitrogen [4, 6]. However, CsiR does not appear to respond directly to the presence of GABA [4], and later reports suggested that it does not affect expression of gabDTP [6, 7]. CsiR represses transcription from the csiD promoter during stationary phase [6]. Currently, no DNA-binding sites for this regulator have been reported in the literature [6]. csiR expression is induced at stationary phase, but is not autoregulated and not dependent on σS [6]. A csiR mutant (gabC1) has the ability to utilize γ-aminobutyrate (GABA) as the sole source of nitrogen [4]. In an experiment using directed cell evolution of a ΔpanD mutant (containing a damaged CoA biosynthesis pathway), a pathway for β-alanine biosynthesis via uracil degradation emerged.
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Transcription factor      
TF conformation(s):
Name Conformation Type TF-Effector Interaction Type Apo/Holo Conformation Evidence (Confirmed, Strong, Weak) References
GlaR Functional   Apo [APPHINH], [IMP] [1], [2], [3], [4], [5]
GlaR-glutarate Non-Functional   Holo nd nd
Evolutionary Family: GntR
Connectivity class: Local Regulator
Gene name: glaR
  Genome position: 2795674-2796336
  Length: 663 bp / 220 aa
Operon name: glaR
TU(s) encoding the TF:
Transcription unit        Promoter
CsiR
 


Regulon       
Regulated gene(s) gabD, gabP, gabT, glaH, lhgD
Multifun term(s) of regulated gene(s) MultiFun Term (List of genes associated to the multifun term)
aminobutyrate catabolism (2)
putrescine catabolism (2)
amino acids (2)
carbon compounds (1)
Porters (Uni-, Sym- and Antiporters) (1)
Regulated operon(s) glaH-lhgD-gabDTP
First gene in the operon(s) glaH
Simple and complex regulons CRP,GlaR,H-NS,Lrp,ppGpp
Simple and complex regulatory phrases Regulatory phrase (List of promoters regulated by the phrase)
[GlaR,-](1)


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
  GlaR repressor csiDp Sigma38 -32.0 -90.0 glaH, lhgD, gabD, gabT, gabP
tatgtcgcttTTGTGCGCATTTTTcagaaatgta
 2788889 2788902 [BPP], [CV(CHIP-SV/GEA/ROMA)], [CV(GEA/ROMA)], [GEA], [IEP] [2], [6]
  GlaR repressor csiDp Sigma38 -13.0 -71.0 glaH, lhgD, gabD, gabT, gabP
tttttcagaaATGTAGATATTTTTagattatggc
 2788908 2788921 [BPP], [CV(CHIP-SV/GEA/ROMA)], [CV(GEA/ROMA)], [GEA], [IEP] [2], [6]



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 (Confirmed, Strong, Weak) References
  GlaR activator nd tu nd
gaaagcggcgAATATCGATATTTAAtggcgctaac
3877705 3877720 3877712.0 nd , , [1]
  GlaR activator nd tu nd
tgaagcgattGAAAATATCGACAACattcagcctg
3225803 3225818 3225810.0 nd , , [1]
  GlaR activator nd tu nd
agcaaagcccCTAAATATATACAATttagcgatca
2041850 2041865 2041857.0 nd , , [1]
  GlaR activator yadN tu nd
ttatattgcgAATATAAATATTTTCtgaaaatcat
157223 157238 157230.0 nd , , [1]
  GlaR activator nd tu nd
ccctgatgggCAAAACATCTATGATacacgcaatt
4391540 4391555 4391547.0 nd , , [1]
  GlaR activator smg tu nd
gttttgagcgAGAAGATATCTACAAtgccctgcta
3432340 3432355 3432347.0 nd , , [1]
  GlaR repressor nd tu nd
cctttggtttTATTATCGTCATTATggcccgccag
2465606 2465621 2465613.0 nd , , [1]
  GlaR repressor chaBC tu nd
cgtctcatgcCCAGGATATCTATAAagaagcgttc
1272181 1272196 1272188.0 nd , , [1]
  GlaR repressor nd tu nd
cgtggcgtggTTTGTCTATATTGTGctgctgtggg
2748613 2748628 2748620.0 nd , , [1]
  GlaR repressor ydcK tu nd
aaacgctatgCGCAAATATCGTCTAagtgaagaac
1500432 1500447 1500439.0 nd , , [1]
  GlaR repressor nd tu nd
acctgacactGGATGTAAACATTATcgatttccca
3169200 3169215 3169207.0 nd , , [1]
  GlaR repressor nd tu nd
gataaaaactGTTATCTATGTATACttttaaaccc
1434613 1434628 1434620.0 nd , , [1]
  GlaR repressor nd tu nd
aagtaacaatGAAAAAAATTGCTATtgtgggtgcc
1747133 1747148 1747140.0 nd , , [1]
  GlaR repressor yqhC tu nd
ggttgcgtctCAATGTCGATATTTTgcagttacag
3154845 3154860 3154852.0 nd , , [1]
  GlaR repressor nd tu nd
accaaaaatgAATATCGATGTTTTTtgctttttct
1256356 1256371 1256363.0 nd , , [1]
  GlaR repressor yjfY tu nd
accaccaggcCAGAAATATGGACGAtgtgcaaagc
4424691 4424706 4424698.0 nd , , [1]
  GlaR repressor nd tu nd
tattgattaaATGAATGTCTATCTTcgtttccatc
4101601 4101616 4101608.0 nd , , [1]
  GlaR repressor nd tu nd
tgtttattacCGGTGTCGCTATTTTgaacatccag
1217378 1217393 1217385.0 nd , , [1]
  GlaR repressor yccU tu nd
tcatacttacTAACATATAGACATAtttcccgctt
1027840 1027855 1027847.0 nd , , [1]
  GlaR repressor chaA tu nd
cgtctcatgcCCAGGATATCTATAAagaagcgttc
1272181 1272196 1272188.0 nd , , [1]
  GlaR repressor nd tu nd
atggtttggcAGCTATCTACGTTTCtggcagaaac
491053 491068 491060.0 nd , , [1]
  GlaR repressor nd tu nd
tcctgaatggATTGACTTTTTTATCcaaccacact
2782942 2782957 2782949.0 nd , , [1]
  GlaR repressor nd tu nd
ccctgatgggCAAAACATCTATGATacacgcaatt
4391540 4391555 4391547.0 nd , , [1]
  GlaR repressor nd tu nd
gctttctatcATTGTAGATAAAAGCtatgccccga
1631374 1631389 1631381.0 nd , , [1]
  GlaR repressor nd tu nd
ggcgatcaatATCGTCGGCATTTAAttccagggcc
4473760 4473775 4473767.0 nd , , [1]


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


Evidence    

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

 [IMP] Inferred from mutant phenotype

 [BPP] Binding of purified proteins

 [CV(CHIP-SV/GEA/ROMA)] cross validation(CHIP-SV/GEA/ROMA)

 [CV(GEA/ROMA)] cross validation(GEA/ROMA)

 [GEA] Gene expression analysis

 [IEP] Inferred from expression pattern

 [AIBSPD] Automated inference based on sequence pattern discovery

 [CE] ChIP-seq evidence

 [RE] RNA-seq evidence

 [MCIBSPD] Manually curated inference based on sequence pattern discovery


Reference(s)    

 [1] Aquino P., Honda B., Jaini S., Lyubetskaya A., Hosur K., Chiu JG., Ekladious I., Hu D., Jin L., Sayeg MK., Stettner AI., Wang J., Wong BG., Wong WS., Alexander SL., Ba C., Bensussen SI., Bernstein DB., Braff D., Cha S., Cheng DI., Cho JH., Chou K., Chuang J., Gastler DE., Grasso DJ., Greifenberger JS., Guo C., Hawes AK., Israni DV., Jain SR., Kim J., Lei J., Li H., Li D., Li Q., Mancuso CP., Mao N., Masud SF., Meisel CL., Mi J., Nykyforchyn CS., Park M., Peterson HM., Ramirez AK., Reynolds DS., Rim NG., Saffie JC., Su H., Su WR., Su Y., Sun M., Thommes MM., Tu T., Varongchayakul N., Wagner TE., Weinberg BH., Yang R., Yaroslavsky A., Yoon C., Zhao Y., Zollinger AJ., Stringer AM., Foster JW., Wade J., Raman S., Broude N., Wong WW., Galagan JE., 2017, Coordinated regulation of acid resistance in Escherichia coli., BMC Syst Biol 11(1):1

 [2] Knorr S., Sinn M., Galetskiy D., Williams RM., Wang C., Muller N., Mayans O., Schleheck D., Hartig JS., 2018, Widespread bacterial lysine degradation proceeding via glutarate and L-2-hydroxyglutarate., Nat Commun 9(1):5071

 [3] Metzer E., Halpern YS., 1990, In vivo cloning and characterization of the gabCTDP gene cluster of Escherichia coli K-12., J Bacteriol 172(6):3250-6

 [4] Schneider BL., Ruback S., Kiupakis AK., Kasbarian H., Pybus C., Reitzer L., 2002, The Escherichia coli gabDTPC operon: specific gamma-aminobutyrate catabolism and nonspecific induction., J Bacteriol 184(24):6976-86

 [5] Zaboura M., Halpern YS., 1978, Regulation of gamma-aminobutyric acid degradation in Escherichia coli by nitrogen metabolism enzymes., J Bacteriol 133(2):447-51

 [6] Metzner M., Germer J., Hengge R., 2004, Multiple stress signal integration in the regulation of the complex sigma S-dependent csiD-ygaF-gabDTP operon in Escherichia coli., Mol Microbiol 51(3):799-811

 [7] Aquino P, Honda B, Jaini S, Lyubetskaya A, Hosur K, Chiu JG, Ekladious I, Hu D, Jin L, Sayeg MK, Stettner AI, Wang J, Wong BG, Wong WS, Alexander SL, Ba C, Bensussen SI, Bernstein DB, Braff D, Cha S, Cheng DI, Cho JH, Chou K, Chuang J, Gastler DE, Grasso DJ, Greifenberger JS, Guo C, Hawes AK, Israni DV, Jain SR, Kim J, Lei J, Li H, Li D, Li Q, Mancuso CP, Mao N, Masud SF, Meisel CL, Mi J, Nykyforchyn CS, Park M, Peterson HM, Ramirez AK, Reynolds DS, Rim NG, Saffie JC, Su H, Su WR, Su Y, Sun M, Thommes MM, Tu T, Varongchayakul N, Wagner TE, Weinberg BH, Yang R, Yaroslavsky A, Yoon C, Zhao Y, Zollinger AJ, Stringer AM, Foster JW, Wade J, Raman S, Broude N, Wong WW, Galagan JE, 2017, Coordinated regulation of acid resistance in Escherichia coli., BMC Syst Biol, 2017 Jan 6

 [8] Pontrelli S., Fricke RCB., Teoh ST., Lavina WA., Putri SP., Fitz-Gibbon S., Chung M., Pellegrini M., Fukusaki E., Liao JC., 2018, Metabolic repair through emergence of new pathways in Escherichia coli., Nat Chem Biol 14(11):1005-1009


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