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ArgR DNA-binding transcriptional dual regulator

Synonyms: ArgR, ArgR-L-arginine
Summary:
ArgR complexed with L-arginine represses the transcription of several genes involved in biosynthesis and transport of arginine, transport of histidine, and its own synthesis [1, 2, 4]and activates genes for arginine catabolism [12] ArgR is also essential for a site-specific recombination reaction that resolves plasmid ColE1 multimers to monomers and is necessary for plasmid stability [17]The role of ArgR in this latter reaction may be structural [17]br>The hexamer is the active form of ArgR, and L-arginine binds to ArgR and stabilizes the hexamer [18]nd increases its DNA affinity by allosteric activation [18, 19].
ArgR belongs to the ArgR/AhrC family, whose members are widely distributed in bacteria [5] The DNA sequence which the proteins of the family recognize and to which they bind are also well-conserved among genomes [5] This DNA sequence consists of a palindromic sequence of 18 bp, called the ARG box [4, 5] An ArgR hexamer binds to a pair of these boxes that are generally separated by 3 bp [4, 8] The repressor can bind to a single box but with a greatly reduced affinity [4, 8] The ARG box generally overlaps the promoter sequence and the transcriptional start site [4] therefore, it was suggested that it represses the transcription by steric exclusion of RNA polymerase binding [11]
ArgR has two domains: the N-terminal domain, which contains a winged helix-turn-helix DNA-binding motif [20] and the C-terminal domain, which contains a motif that binds L-arginine and a motif for oligomerization [18] Based on cross-linking analysis of wild-type and mutant ArgR proteins, it has been shown that the C-terminus is more important in cer/Xer site-specific recombination than in DNA binding [21]
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Transcription factor      
TF conformation(s):
Name Conformation Type TF-Effector Interaction Type Apo/Holo Conformation Evidence (Confirmed, Strong, Weak) References
ArgR Non-Functional   Apo [BPP], [GEA], [IDA], [IPI] [1], [2], [3]
ArgR-L-arginine Functional Allosteric Holo [BPP], [GEA], [IDA], [IPI] [1], [2], [3]
Evolutionary Family: ArgR
Sensing class: Sensing external and internal signals
Connectivity class: Local Regulator
Gene name: argR
  Genome position: 3384703-3385173
  Length: 471 bp / 156 aa
Operon name: argR
TU(s) encoding the TF:
Transcription unit        Promoter
argR
argRp1
argR
argRp2


Regulon       
Regulated gene(s) argA, argB, argC, argD, argE, argF, argG, argH, argI, argR, artI, artJ, artM, artP, artQ, astA, astB, astC, astD, astE, carA, carB, gltB, gltD, gltF, hisJ, hisM, hisP, hisQ, infB, lysO, metY, nusA, pnp, rbfA, rimP, rpsO, truB
Multifun term(s) of regulated gene(s) MultiFun Term (List of genes associated to the multifun term)
arginine (19)
amino acids (6)
lysine (4)
ABC superfamily, membrane component (4)
membrane (4)
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Regulated operon(s) argA, argCBH, argD, argE, argF, argG, argI, argR, argT-hisJQMP, artJ, artPIQM, astCADBE, carAB, gltBDF, lysO, metY-rimP-nusA-infB-rbfA-truB-rpsO-pnp
First gene in the operon(s) argA, argC, argD, argE, argF, argG, argI, argR, artJ, artP, astC, carA, gltB, hisJ, lysO, metY, metY
Simple and complex regulons AdiY,ArgR,CRP,FNR,Fur,GadE,HdfR,IHF,Lrp,Nac
ArgR
ArgR,CRP
ArgR,H-NS
ArgR,NtrC
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Simple and complex regulatory phrases Regulatory phrase (List of promoters regulated by the phrase)
[ArgR,+](1)
[ArgR,-](15)


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
  ArgR-L-arginine repressor argAp Sigma70 46.5 -40.5 argA
ctgcgaaaaaACAGAATAAAAATACACTaatttcgaat
 2949193 2949210 [AIBSCS], [BPP], [GEA], [HIBSCS] [1], [4], [5]
  ArgR-L-arginine repressor argAp Sigma70 67.5 -19.5 argA
atacactaatTTCGAATAATCATGCAAAgaggtgtgcc
 2949214 2949231 [AIBSCS], [BPP], [GEA], [HIBSCS] [1], [4], [5]
  ArgR-L-arginine repressor argCp Sigma70 -3.5 -119.5 argC, argB, argH
ggtcatgataGTATCAATATTCATGCAGtatttatgaa
 4154873 4154890 [AIBSCS], [BCE], [BPP], [GEA], [SM] [1], [4], [5], [6]
  ArgR-L-arginine repressor argCp Sigma70 19.5 -97.5 argC, argB, argH
atgcagtattTATGAATAAAAATACACTaacgttgagc
 4154895 4154912 [AIBSCS], [BCE], [BPP], [GEA], [SM] [1], [4], [5], [6]
  ArgR-L-arginine repressor argDp Sigma70 -19.5 -60.5 argD
attgccatttAGTGATTTTTTATGCATAttttgtggtt
 3490232 3490249 [AIBSCS], [BPP], [GEA], [HIBSCS] [1], [4], [5]
  ArgR-L-arginine repressor argDp Sigma70 2.5 -39.5 argD
atgcatatttTGTGGTTATAATTTCACAtttgtttatg
 3490211 3490228 [AIBSCS], [BPP] [1], [4], [5]
  ArgR-L-arginine repressor argEp1 Sigma70 -6.5 -56.5 argE
gctcaacgttAGTGTATTTTTATTCATAaatactgcat
 4154895 4154912 [AIBSCS], [BCE], [BPP], [GEA], [SM] [1], [4], [5], [6]
  ArgR-L-arginine repressor argEp1 Sigma70 16.5 -34.5 argE
ttcataaataCTGCATGAATATTGATACtatcatgacc
 4154873 4154890 [AIBSCS], [BCE], [BPP], [GEA], [SM] [1], [4], [5], [6]
  ArgR-L-arginine repressor argFp Sigma70 -22.5 -57.5 argF
tggggttgcaAATGAATAATTACACATAtaaagtgaat
 290354 290371 [AIBSCS], [BCE], [BPP], [GEA] [1], [4], [5], [6], [7], [8], [9]
  ArgR-L-arginine repressor argFp Sigma70 -1.5 -36.5 argF
acacatataaAGTGAATTTTAATTCAATaagtggcgtt
 290333 290350 [AIBSCS], [BPP], [GEA], [SM] [1], [4], [5], [6], [8], [9]
  ArgR-L-arginine repressor argGp Sigma70 -125.5 -200.5 argG
ttgctaatcaTGTGAATGAATATCCAGTtcactttcat
 3318428 3318445 [AIBSCS], [BPP], [GEA], [HIBSCS] [1], [4], [5], [10]
  ArgR-L-arginine repressor argGp Sigma70 -6.5 -81.5 argG
ataaaagatgATTAAATGAAAACTCATTtattttgcat
 3318547 3318564 [AIBSCS], [BPP], [GEA], [HIBSCS] [1], [4], [5], [10]
  ArgR-L-arginine repressor argGp Sigma70 15.5 -60.5 argG
actcatttatTTTGCATAAAAATTCAGTgagagcggaa
 3318568 3318585 [AIBSCS], [BPP], [GEA], [HIBSCS] [1], [4], [5], [10]
  ArgR-L-arginine repressor argIp Sigma70 -22.5 -55.5 argI
tagacttgcaAATGAATAATCATCCATAtaaattgaat
 4478358 4478375 [AIBSCS], [BCE], [BPP], [GEA] [1], [4], [5], [6]
  ArgR-L-arginine repressor argIp Sigma70 -1.5 -34.5 argI
atccatataaATTGAATTTTAATTCATTgaggcgttag
 4478337 4478354 [AIBSCS], [BCE], [BPP], [GEA] [1], [4], [5], [6]
  ArgR-L-arginine repressor argRp1 Sigma70 -27.5 -53.5 argR
gggctgactgTTTGCATAAAAATTCATCtgtatgcaca
 3384641 3384658 [AIBSCS], [BPP], [GEA], [HIBSCS] [1], [2], [4], [5], [7]
  ArgR-L-arginine repressor argRp1 Sigma70 -7.5 -33.5 argR
aattcatctgTATGCACAATAATGTTGTatcaaccacc
 3384661 3384678 [AIBSCS], [BPP], [GEA], [HIBSCS] [1], [2], [4], [5], [7]
  ArgR-L-arginine repressor artJp Sigma70 -48.5 -99.5 artJ
tttatttcatTTAAATTATTTAATCATGtttattgcat
 900666 900683 [BPP], [GEA], [SM] [11]
  ArgR-L-arginine repressor artJp Sigma70 -27.5 -78.5 artJ
aatcatgtttATTGCATATAAATTCACTtgatggcatt
 900645 900662 [AIBSCS], [BPP], [GEA], [SM] [1], [5], [11]
  ArgR-L-arginine repressor artPp Sigma70 -50.5 -85.5 artP, artI, artQ, artM
gcgctttgctTTTAACTTTTAAAGCAGAaatattgcat
 903811 903828 [BPP], [GEA], [SM] [11]
  ArgR-L-arginine repressor artPp Sigma70 -29.5 -64.5 artP, artI, artQ, artM
aagcagaaatATTGCATAATTATTCTGTcaaaggtact
 903790 903807 [AIBSCS], [BPP], [GEA], [SM] [1], [5], [11]
  ArgR-L-arginine activator astCp2 Sigma54 -121.5 -183.5 astC, astA, astD, astB, astE
attcacccacATCGCAAACGTATTCACTttatatgcac
 1832157 1832174 [AIBSCS], [BPP], [GEA] [12]
  ArgR-L-arginine activator astCp2 Sigma54 -99.5 -161.5 astC, astA, astD, astB, astE
ttcactttatATGCACTTTAAATGCATAtggtttggtt
 1832135 1832152 [AIBSCS], [BPP], [GEA] [12]
  ArgR-L-arginine activator astCp2 Sigma54 -78.5 -140.5 astC, astA, astD, astB, astE
atgcatatggTTTGGTTATAACTCCTTGatttccagtt
 1832114 1832131 [AIBSCS], [BPP], [GEA] [12]
  ArgR-L-arginine activator astCp2 Sigma54 -47.5 -109.5 astC, astA, astD, astB, astE
tccagttagcCTCCGCCGTTTATGCACTtttatcactg
 1832083 1832100 [AIBSCS], [BPP], [GEA] [12]
  ArgR-L-arginine repressor carAp2 Sigma70 -8.5 -40.5 carA, carB
acgtcatcatTGTGAATTAATATGCAAAtaaagtgagt
 29602 29619 [AIBSCS], [BPP], [GEA], [HIBSCS], [SM] [1], [4], [5], [13], [14]
  ArgR-L-arginine repressor carAp2 Sigma70 13.5 -19.5 carA, carB
atgcaaataaAGTGAGTGAATATTCTCTggagggtgtt
 29623 29640 [AIBSCS], [BPP], [GEA], [HIBSCS], [SM] [1], [4], [5], [13], [14]
  ArgR-L-arginine repressor gltBp Sigma70 -352.0 -568.5 gltB, gltD, gltF
gcttttatcaACTGCATAATCAATCAAAattaccgaaa
 3354148 3354165 [BPP], [GEA], [HIBSCS] [15]
  ArgR-L-arginine repressor gltBp Sigma70 -331.5 -547.5 gltB, gltD, gltF
aatcaaaattACCGAAATTTCATGCATAatcacataaa
 3354169 3354186 [BPP], [GEA], [HIBSCS] [15]
  ArgR-L-arginine repressor hisJp Sigma70 -83.5 -132.5 hisJ, hisQ, hisM, hisP
ggtgcattgaAATGCATACTTAAGCATTtttaatgaaa
 2426912 2426929 [BPP], [GEA], [SM] [11]
  ArgR-L-arginine repressor hisJp Sigma70 -62.5 -111.5 hisJ, hisQ, hisM, hisP
aagcatttttAATGAAAAATAATACGTCtaacggggcg
 2426891 2426908 [AIBSCS], [BPP], [GEA], [SM] [1], [5], [11]
  ArgR-L-arginine repressor lysOp Sigma70 -55.5 -93.5 lysO
tactgctcctTATGCATAACATTTCCTTttaattgcaa
 914942 914959 [BPP], [GEA], [SM] [16]
  ArgR-L-arginine repressor lysOp Sigma70 -34.5 -72.5 lysO
tttccttttaATTGCAACTTTACTCGTCcttccgcttt
 914921 914938 [BPP], [GEA], [SM] [16]
  ArgR-L-arginine repressor metYp2 Sigma70 -201.5 -287.5 metY, rimP, nusA, infB, rbfA, truB, rpsO, pnp
ttccgctctcACTGAATTTTTATGCAAAataaatgagt
 3318568 3318585 [AIBSCS], [BPP], [GEA], [HIBSCS] [1], [4], [5], [10]
  ArgR-L-arginine repressor metYp2 Sigma70 -180.5 -266.5 metY, rimP, nusA, infB, rbfA, truB, rpsO, pnp
atgcaaaataAATGAGTTTTCATTTAATcatcttttat
 3318547 3318564 [AIBSCS], [BPP], [GEA], [HIBSCS] [1], [4], [5], [10]
  ArgR-L-arginine repressor metYp2 Sigma70 -61.5 -147.5 metY, rimP, nusA, infB, rbfA, truB, rpsO, pnp
atgaaagtgaACTGGATATTCATTCACAtgattagcaa
 3318428 3318445 [AIBSCS], [BPP], [GEA], [HIBSCS] [1], [4], [5], [10]


Alignment and PSSM for ArgR TFBSs    

Aligned TFBS of ArgR   
  Sequence
 

Position weight matrix (PWM).    
A	19	8	5	3	19	23	3	11	8	5	4	27	6	1	0	28	10	16
C	2	6	5	3	4	3	1	0	2	0	8	0	2	3	28	0	5	0
G	2	8	1	23	3	1	1	1	0	1	0	1	0	14	0	0	3	1
T	6	7	18	0	3	2	24	17	19	23	17	1	21	11	1	1	11	12

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

 [IDA] Inferred from direct assay

 [IPI] Inferred from physical interaction

 [AIBSCS] Automated inference based on similarity to consensus sequences

 [HIBSCS] Human inference based on similarity to consensus sequences

 [BCE] Binding of cellular extracts

 [SM] Site mutation


Reference(s)    

 [1] Caldara M., Charlier D., Cunin R., 2006, The arginine regulon of Escherichia coli: whole-system transcriptome analysis discovers new genes and provides an integrated view of arginine regulation., Microbiology. 152(Pt 11):3343-54

 [2] Lim DB., Oppenheim JD., Eckhardt T., Maas WK., 1987, Nucleotide sequence of the argR gene of Escherichia coli K-12 and isolation of its product, the arginine repressor., Proc Natl Acad Sci U S A. 84(19):6697-701

 [3] Szwajkajzer D., Dai L., Fukayama JW., Abramczyk B., Fairman R., Carey J., 2001, Quantitative analysis of DNA binding by the Escherichia coli arginine repressor., J Mol Biol. 312(5):949-62

 [4] Charlier D., Roovers M., Van Vliet F., Boyen A., Cunin R., Nakamura Y., Glansdorff N., Pierard A., 1992, Arginine regulon of Escherichia coli K-12. A study of repressor-operator interactions and of in vitro binding affinities versus in vivo repression., J Mol Biol. 226(2):367-86

 [5] Makarova KS., Mironov AA., Gelfand MS., 2001, Conservation of the binding site for the arginine repressor in all bacterial lineages., Genome Biol. 2(4):RESEARCH0013

 [6] Cunin R., Eckhardt T., Piette J., Boyen A., Pierard A., Glansdorff N., 1983, Molecular basis for modulated regulation of gene expression in the arginine regulon of Escherichia coli K-12., Nucleic Acids Res. 11(15):5007-19

 [7] Levitt M., 1992, Accurate modeling of protein conformation by automatic segment matching., J Mol Biol. 226(2):507-33

 [8] Tian G., Lim D., Carey J., Maas WK., 1992, Binding of the arginine repressor of Escherichia coli K12 to its operator sites., J Mol Biol. 226(2):387-97

 [9] Tian G., Maas WK., 1994, Mutational analysis of the arginine repressor of Escherichia coli., Mol Microbiol. 13(4):599-608

 [10] Krin E., Laurent-Winter C., Bertin PN., Danchin A., Kolb A., 2003, Transcription regulation coupling of the divergent argG and metY promoters in Escherichia coli K-12., J Bacteriol. 185(10):3139-46

 [11] Caldara M., Minh PN., Bostoen S., Massant J., Charlier D., 2007, ArgR-dependent Repression of Arginine and Histidine Transport Genes in Escherichia coli K-12., J Mol Biol. 373(2):251-67

 [12] Kiupakis AK., Reitzer L., 2002, ArgR-independent induction and ArgR-dependent superinduction of the astCADBE operon in Escherichia coli., J Bacteriol. 184(11):2940-50

 [13] Charlier D., Weyens G., Roovers M., Piette J., Bocquet C., Pierard A., Glansdorff N., 1988, Molecular interactions in the control region of the carAB operon encoding Escherichia coli carbamoylphosphate synthetase., J Mol Biol. 204(4):867-77

 [14] Wang H., Glansdorff N., Charlier D., 1998, The arginine repressor of Escherichia coli K-12 makes direct contacts to minor and major groove determinants of the operators., J Mol Biol. 277(4):805-24

 [15] Paul L., Mishra PK., Blumenthal RM., Matthews RG., 2007, Integration of regulatory signals through involvement of multiple global regulators: control of the Escherichia coli gltBDF operon by Lrp, IHF, Crp, and ArgR., BMC Microbiol. 7:2

 [16] Pathania A., Sardesai AA., 2015, Distinct Paths for Basic Amino Acid Export in Escherichia coli: YbjE (LysO) Mediates Export of L-Lysine., J Bacteriol. 197(12):2036-47

 [17] Stirling CJ., Szatmari G., Stewart G., Smith MC., Sherratt DJ., 1988, The arginine repressor is essential for plasmid-stabilizing site-specific recombination at the ColE1 cer locus., EMBO J. 7(13):4389-95

 [18] Van Duyne GD., Ghosh G., Maas WK., Sigler PB., 1996, Structure of the oligomerization and L-arginine binding domain of the arginine repressor of Escherichia coli., J Mol Biol. 256(2):377-91

 [19] Jin L., Xue WF., Fukayama JW., Yetter J., Pickering M., Carey J., 2005, Asymmetric allosteric activation of the symmetric ArgR hexamer., J Mol Biol. 346(1):43-56

 [20] Sunnerhagen M., Nilges M., Otting G., Carey J., 1997, Solution structure of the DNA-binding domain and model for the complex of multifunctional hexameric arginine repressor with DNA., Nat Struct Biol. 4(10):819-26

 [21] Senechal H., Delesques J., Szatmari G., 2010, Escherichia coli ArgR mutants defective in cer/Xer recombination, but not in DNA binding., FEMS Microbiol Lett. 305(2):162-9


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