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GalR DNA-binding transcriptional dual regulator

Synonyms: GalR-D-galactose, GalR
Summary:
The "Galactose repressor," GalR, is a DNA-binding transcription factor that represses transcription of the operons involved in transport and catabolism of D-galactose [1, 2, 6, 13]. Synthesis of these operons is induced when E. coli is grown in the presence of inducer (D-galactose) and the absence glucose [1, 2, 12, 13] The expression of galR is increased only in the presence of inducer [1, 2] In particular, in the absence of D-galactose, GalR represses the galETKM operon [17] In this repression system, GalR binds to two operators in the presence of HU, resulting in the formation of a repressor loop [7, 15, 17] This repressor binds in tandem to inverted repeat sequences that are 16 nucleotides long and possess conserved motifs; each dimer binds to one of these conserved sequences [2, 13] On the other hand, GalR is highly homologous in its amino acid sequence to GalS (55% identical and 88% similar); apparently both act together and are capable of cross-talk to regulate expression of the gal regulon [1, 12] For this reason these regulators bind the same operators, in the cis regulatory regions, with different affinities [18] In the presence of inductor, GalR undergoes a conformational change that reduces its affinity for the operator.
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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
GalR Functional   Apo [EXP-IDA], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS], [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [EXP-IPI] S [1], [2]
GalR-D-galactose Functional Allosteric Holo nd nd nd
Evolutionary Family: GalR/LacI
TFBs length: 16
TFBs symmetry: inverted-repeat
Sensing class: Sensing external and internal signals
Connectivity class: Local Regulator
Gene name: galR
  Genome position: 2976599-2977630
  Length: 1032 bp / 343 aa
Operon name: galR
TU(s) encoding the TF:
Transcription unit        Promoter
galR
galRp


Regulon       
Regulated gene(s) galE, galK, galM, galP, galR, galS, galT, mglA, mglB, mglC
Multifun term(s) of regulated gene(s) MultiFun Term (List of genes associated to the multifun term)
carbon compounds (10)
colanic acid (M antigen) (3)
galactose metabolism (3)
capsule (M and K antigens) (3)
membrane (2)
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Regulated operon(s) galETKM, galP, galR, galS, mglBAC
First gene in the operon(s) galE, galP, galR, galS, mglB
Simple and complex regulons CRP,FlhDC,GalR,GalS
CRP,GalR,GalS
CRP,GalR,GalS,H-NS,HU
CRP,GalR,GalS,HU
CRP,GalR,GalS,NagC
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Simple and complex regulatory phrases Regulatory phrase (List of promoters regulated by the phrase)
[GalR,+](1)
[GalR,-](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
  GalR repressor galEp Sigma38 -60.5 -86.5 galE, galT, galK, galM
ctaaattcttGTGTAAACGATTCCACtaatttattc
 792134 792149 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS], [EXP-IMP-SITE-MUTATION] C [1], [1], [2], [3], [4], [5], [5], [6], [7], [7], [8], [9], [10], [11], [12], [13]
  GalR repressor galEp Sigma38 46.5 20.5 galE, galT, galK, galM
gagagttctgGTTACCGGTGGTAGCGgttacattgg
 792028 792043 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS], [EXP-IMP-SITE-MUTATION] C [1], [1], [2], [3], [4], [5], [5], [6], [7], [7], [9], [10], [11], [12], [13], [14], [15]
  GalR repressor galEp1 Sigma70 -60.5 -86.5 galE, galT, galK, galM
ctaaattcttGTGTAAACGATTCCACtaatttattc
 792134 792149 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS], [EXP-IMP-SITE-MUTATION] C [1], [1], [2], [3], [4], [5], [5], [6], [7], [7], [8], [9], [10], [11], [12], [13]
  GalR repressor galEp1 Sigma70 46.5 20.5 galE, galT, galK, galM
gagagttctgGTTACCGGTGGTAGCGgttacattgg
 792028 792043 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS], [EXP-IMP-SITE-MUTATION] C [1], [1], [2], [3], [4], [5], [5], [6], [7], [7], [9], [10], [11], [12], [13], [14], [15]
  GalR repressor galEp2 Sigma70 -55.5 -86.5 galE, galT, galK, galM
ctaaattcttGTGTAAACGATTCCACtaatttattc
 792134 792149 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS], [EXP-IMP-SITE-MUTATION] C [1], [1], [2], [3], [4], [5], [5], [6], [7], [7], [8], [9], [10], [11], [12], [13]
  GalR-D-galactose activator galEp2 Sigma70 -55.5 -86.5 galE, galT, galK, galM
ctaaattcttGTGTAAACGATTCCACtaatttattc
 792134 792149 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS], [EXP-IMP-SITE-MUTATION] C [1], [1], [2], [3], [4], [5], [5], [6], [7], [7], [8], [9], [10], [11], [12], [13]
  GalR repressor galEp2 Sigma70 51.5 20.5 galE, galT, galK, galM
gagagttctgGTTACCGGTGGTAGCGgttacattgg
 792028 792043 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS], [EXP-IMP-SITE-MUTATION] C [1], [2], [3], [4], [5], [5], [6], [7], [7], [9], [10], [11], [12], [13], [14], [15]
  GalR-D-galactose repressor galPp Sigma70 -243.5 -272.5 galP
atcatcacaaCTGAAACCGATTACACcaaccacaac
 3088004 3088019 [COMP-AINF-SIMILAR-TO-CONSENSUS], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS], [EXP-IMP-SITE-MUTATION] C [16], [16]
  GalR-D-galactose repressor galPp Sigma70 -207.5 -236.5 galP
agacaaagatTTGTAATATTTTCATAttattattcg
 3088040 3088055 [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] S [16], [16]
  GalR-D-galactose repressor galPp Sigma70 -178.5 -207.5 galP
ttattcggttTTCACAGTTGTTACATttcttttcag
 3088069 3088084 [COMP-AINF-SIMILAR-TO-CONSENSUS], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS], [EXP-IMP-SITE-MUTATION] C [16], [16]
  GalR-D-galactose repressor galPp Sigma70 -107.5 -136.5 galP
tgatgatataACTCAATTATTTTCATgcacttaaat
 3088140 3088155 [COMP-AINF-SIMILAR-TO-CONSENSUS], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS], [EXP-IMP-SITE-MUTATION] C [16], [16]
  GalR repressor galPp Sigma70 -61.5 -90.5 galP
ataaatgttaGTGTAAGCGATTACACtgatgtgatt
 3088186 3088201 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS], [EXP-IMP-SITE-MUTATION] C [1], [1], [6], [13], [16], [16]
  GalR repressor galPp Sigma70 136.5 107.5 galP
cctggatatcGGTGTAATTGCTGGCGcactgccgtt
 3088383 3088398 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS], [EXP-IMP-SITE-MUTATION] C [1], [1], [6], [13], [16], [16]
  GalR-D-galactose repressor galRp Sigma70 8.5 -22.5 galR
cactgaaagaATGTAAGCGTTTACCCactaaggtat
 2976569 2976584 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] S [2], [2], [6], [6]
  GalR repressor galSp Sigma70 -61.5 -103.5 galS
aacaaaacggCTGTAACCGTTTCCATtgctgtgact
 2241764 2241779 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-HINF-SIMILAR-TO-CONSENSUS] W [2], [2], [13]
  GalR repressor galSp Sigma70 91.5 49.5 galS
ctggcgtctcTGTGGCAACGGTTTCCcgggtgctca
 2241612 2241627 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-HINF-SIMILAR-TO-CONSENSUS] W [2], [2], [6], [13]
  GalR repressor mglBp Sigma70 -59.5 -277.5 mglB, mglA, mglC
aaatcaggcgATGTAACCGCTTTCAAtctgtgagtg
 2240618 2240633 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-HINF-SIMILAR-TO-CONSENSUS] W [1], [1], [6], [13]
  GalR repressor mglBp2 Sigma38 -59.5 -277.5 mglB, mglA, mglC
aaatcaggcgATGTAACCGCTTTCAAtctgtgagtg
 2240618 2240633 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-HINF-SIMILAR-TO-CONSENSUS] W [1], [1], [6], [13]


Alignment and PSSM for GalR TFBSs    

Aligned TFBS of GalR   
  Sequence
  CAGATTGAAAGCGGTTAC
  GTTAGTGTAAGCGATTAC
  AGCAATGGAAACGGTTAC
  ATTAGTGGAATCGTTTAC
  AAGAATGTAAGCGTTTAC
  CTCTGTGGCAACGGTTTC
  ACCGGTGGTAGCGGTTAC
  GTTGGTGTAATCGGTTTC
  CAGTGCGCCAGCAATTAC
  GGTTTTCACAGTTGTTAC
  AAGATTTGTAATATTTTC
  GTGCATGAAAATAATTGA

Position weight matrix (PWM). GalR matrix-quality result    
A	5	4	0	6	3	0	0	3	7	12	4	0	3	3	0	0	8	1
C	3	1	3	1	0	1	1	1	3	0	0	9	0	0	0	0	0	11
G	4	2	5	2	6	0	10	5	0	0	6	0	8	6	0	0	1	0
T	0	5	4	3	3	11	1	3	2	0	2	3	1	3	12	12	3	0

Consensus    
;	consensus.strict             	gtgagTGgaAgCGgTTaC
;	consensus.strict.rc          	GTAACCGCTTCCACTCAC
;	consensus.IUPAC              	vwbagTGgmArCGgTTaC
;	consensus.IUPAC.rc           	GTAACCGYTKCCACTVWB
;	consensus.regexp             	[acg][at][cgt]agTGg[ac]A[ag]CGgTTaC
;	consensus.regexp.rc          	GTAACCG[CT]T[GT]CCACT[ACG][AT][CGT]

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    

 [EXP-IDA] Inferred from direct assay

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

 [EXP-IEP-GENE-EXPRESSION-ANALYSIS] Gene expression analysis

 [EXP-IPI] Inferred from physical interaction

 [COMP-HINF-SIMILAR-TO-CONSENSUS] A person inferred or reviewed a computer inference of sequence function based on similarity to a consensus sequence.

 [EXP-IMP-SITE-MUTATION] Site mutation

 [COMP-AINF-SIMILAR-TO-CONSENSUS] Automated inference based on similarity to consensus sequences


Reference(s)    

 [1] Geanacopoulos M., Adhya S., 1997, Functional characterization of roles of GalR and GalS as regulators of the gal regulon., J Bacteriol 179(1):228-34

 [2] Weickert MJ., Adhya S., 1993, Control of transcription of gal repressor and isorepressor genes in Escherichia coli., J Bacteriol 175(1):251-8

 [3] Lia G., Bensimon D., Croquette V., Allemand JF., Dunlap D., Lewis DE., Adhya S., Finzi L., 2003, Supercoiling and denaturation in Gal repressor/heat unstable nucleoid protein (HU)-mediated DNA looping., Proc Natl Acad Sci U S A 100(20):11373-7

 [4] Lyubchenko YL., Shlyakhtenko LS., Aki T., Adhya S., 1997, Atomic force microscopic demonstration of DNA looping by GalR and HU., Nucleic Acids Res 25(4):873-6

 [5] Perez N., Rehault M., Amouyal M., 2000, A functional assay in Escherichia coli to detect non-assisted interaction between galactose repressor dimers., Nucleic Acids Res 28(18):3600-4

 [6] Semsey S., Krishna S., Sneppen K., Adhya S., 2007, Signal integration in the galactose network of Escherichia coli., Mol Microbiol 65(2):465-76

 [7] Semsey S., Tolstorukov MY., Virnik K., Zhurkin VB., Adhya S., 2004, DNA trajectory in the Gal repressosome., Genes Dev 18(15):1898-907

 [8] Choy HE., Hanger RR., Aki T., Mahoney M., Murakami K., Ishihama A., Adhya S., 1997, Repression and activation of promoter-bound RNA polymerase activity by Gal repressor., J Mol Biol 272(3):293-300

 [9] Kar S., Adhya S., 2001, Recruitment of HU by piggyback: a special role of GalR in repressosome assembly., Genes Dev 15(17):2273-81

 [10] Mandal N., Su W., Haber R., Adhya S., Echols H., 1990, DNA looping in cellular repression of transcription of the galactose operon., Genes Dev 4(3):410-8

 [11] Virnik K., Lyubchenko YL., Karymov MA., Dahlgren P., Tolstorukov MY., Semsey S., Zhurkin VB., Adhya S., 2003, "Antiparallel" DNA loop in gal repressosome visualized by atomic force microscopy., J Mol Biol 334(1):53-63

 [12] Weickert MJ., Adhya S., 1992, Isorepressor of the gal regulon in Escherichia coli., J Mol Biol 226(1):69-83

 [13] Weickert MJ., Adhya S., 1993, The galactose regulon of Escherichia coli., Mol Microbiol 10(2):245-51

 [14] Lewis DE., Geanacopoulos M., Adhya S., 1999, Role of HU and DNA supercoiling in transcription repression: specialized nucleoprotein repression complex at gal promoters in Escherichia coli., Mol Microbiol 31(2):451-61

 [15] Semsey S., Geanacopoulos M., Lewis DE., Adhya S., 2002, Operator-bound GalR dimers close DNA loops by direct interaction: tetramerization and inducer binding., EMBO J 21(16):4349-56

 [16] El Qaidi S., Allemand F., Oberto J., Plumbridge J., 2009, Repression of galP, the galactose transporter in Escherichia coli, requires the specific regulator of N-acetylglucosamine metabolism., Mol Microbiol 71(1):146-57

 [17] Aki T., Adhya S., 1997, Repressor induced site-specific binding of HU for transcriptional regulation., EMBO J 16(12):3666-74

 [18] Brown MP, Shaikh N, Brenowitz M, Brand L, 1994, The allosteric interaction between D-galactose and the Escherichia coli galactose repressor protein., J Biol Chem, 269(17):12600 None

 [19] Golding A, Weickert MJ, Tokeson JP, Garges S, Adhya S, 1991, A mutation defining ultrainduction of the Escherichia coli gal operon., J Bacteriol, 173(19):6294 10.1128/jb.173.19.6294-6296.1991

 [20] Singh P, Bagchi D, Pal SK, 2018, Ultrafast dynamics-driven biomolecular recognition where fast activities dictate slow events., J Biosci, 43(3):485 None

 [21] Zhu F, San KY, Bennett GN, 2020, Improved succinate production from galactose-rich feedstocks by engineered Escherichia coli under anaerobic conditions., Biotechnol Bioeng, 117(4):1082 10.1002/bit.27254


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