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Escherichia coli K-12 substr. MG1655 Protein: MprA DNA-binding transcriptional repressor



Gene: mprA Accession Numbers: EG10603 (EcoCyc), b2684, ECK2678

Synonyms: emrR

Regulation Summary Diagram: ?

Component of:
MprA-CCCP
MprA-2,4-dinitrophenol

Subunit composition of MprA DNA-binding transcriptional repressor = [MprA]2

Summary:
The "E. coli multidrug resistance regulator" [Lomovskaya92, Lomovskaya95], EmrR, negatively regulates the transcription of genes that code for multidrug resistance pumps that extrude structurally unrelated antimicrobial agents from the cell [Lomovskaya95, Rodionov01] and possibly it also represses a gene that codes for a porin [Rodionov01]. When EmrR is overexpressed (the emrR gene in multicopy), it is able to repress the marRAB operon, which encodes two transcriptional regulators [Sulavik95].

EmrR, which is also known as MprA, "microcin production regulation, locus A" [delCastillo90], has also been shown to be a repressor of plasmid-encoded genes involved in microcin biosynthesis [delCastillo90, delCastillo91, Mao98]. Microcins are low-molecular-weight polypeptide antibiotics [Asensio76].

The EmrR dimer binds 2,4-dinitrophenol, carbonyl cyanide m-chlorophenylhydrazone (CCCP), and carbonyl cyanide p-(trifluoro-methoxy)phenylhydrazone, predicted ligands of the EmrAB pump, with high affinity [Brooun99]. Binding of these agents interferes with the ability of EmrR to bind DNA [Xiong00]. This dimeric protein [Brooun99] recognizes and binds an imperfect inverted repeat DNA sequence [Xiong00].

EmrR belongs to the MarR family of transcriptional regulators [Sulavik95], which respond to a variety of phenolic compounds and are found in gram-positive and gram-negative species as well as in mycobacteria [Sulavik95]. The proteins of this family have a helix-turn-helix DNA-binding motif at the center [Dalrymple97], while the ligand-binding domain is possibly located at the N-terminal domain [Brooun99]. EmrR shows 28% and 47% identity and similarity, respectively, to the MarR protein [Sulavik95].

Overproduction of EmrR from a multicopy plasmid causes a mutator phenotype that includes an increase in frameshift and base substitution mutations [Yang04b].

emrR is the first gene of the emrRAB operon whose transcription is induced by antimicrobial agents such as salicylic acid, CCCP, and nalidixic acid, among others; induction requires the repressor of the operon EmrR [Lomovskaya95]. Expression of emrR is not osmoregulated [delCastillo91].

Reviews: [Lewis01, Grkovic02, Miller96].

Locations: cytosol

Map Position: [2,808,792 -> 2,809,322] (60.54 centisomes)
Length: 531 bp / 176 aa

Molecular Weight of Polypeptide: 20.563 kD (from nucleotide sequence)

Molecular Weight of Multimer: 54 kD (experimental) [Brooun99]

Unification Links: ASAP:ABE-0008834 , CGSC:33255 , EchoBASE:EB0598 , EcoGene:EG10603 , EcoliWiki:b2684 , ModBase:P0ACR9 , OU-Microarray:b2684 , PortEco:mprA , PR:PRO_000023279 , Pride:P0ACR9 , Protein Model Portal:P0ACR9 , RefSeq:NP_417169 , RegulonDB:EG10603 , SMR:P0ACR9 , String:511145.b2684 , UniProt:P0ACR9

Relationship Links: InterPro:IN-FAMILY:IPR000835 , InterPro:IN-FAMILY:IPR011991 , InterPro:IN-FAMILY:IPR023187 , Pfam:IN-FAMILY:PF01047 , Prints:IN-FAMILY:PR00598 , Prosite:IN-FAMILY:PS01117 , Prosite:IN-FAMILY:PS50995 , Smart:IN-FAMILY:SM00347

In Reactions of unknown directionality:

Not in pathways:
MprA + carbonylcyanide m-chlorophenylhydrazone = MprA-CCCP
MprA + 2,4-dinitrophenol = MprA-2,4-dinitrophenol

Gene-Reaction Schematic: ?

Genetic Regulation Schematic: ?

GO Terms:

Biological Process: GO:0006351 - transcription, DNA-templated Inferred from experiment Inferred by computational analysis [UniProtGOA11, Xiong00, Brooun99]
GO:0045892 - negative regulation of transcription, DNA-templated Inferred from experiment [Sulavik95]
GO:0046677 - response to antibiotic Inferred from experiment [Lomovskaya95]
GO:0006355 - regulation of transcription, DNA-templated Inferred by computational analysis [UniProtGOA11, GOA01]
Molecular Function: GO:0003677 - DNA binding Inferred from experiment Inferred by computational analysis [UniProtGOA11, Xiong00]
GO:0003700 - sequence-specific DNA binding transcription factor activity Inferred by computational analysis [GOA01]
Cellular Component: GO:0005829 - cytosol Inferred from experiment Inferred by computational analysis [DiazMejia09, Ishihama08]
GO:0005622 - intracellular Inferred by computational analysis [GOA01]

MultiFun Terms: cell processes protection drug resistance/sensitivity
extrachromosomal plasmid related
information transfer RNA related Transcription related
regulation genetic unit regulated operon
regulation type of regulation transcriptional level repressor

DNA binding site length: 21 base-pairs

Symmetry: Inverted Repeat

Regulated Transcription Units (3 total): ?

Notes:

Essentiality data for mprA knockouts: ?

Growth Medium Growth? T (°C) O2 pH Osm/L Growth Observations
LB enriched Yes 37 Aerobic 6.95   Yes [Gerdes03, Comment 1]
LB Lennox Yes 37 Aerobic 7   Yes [Baba06, Comment 2]
M9 medium with 1% glycerol Yes 37 Aerobic 7.2 0.35 Yes [Joyce06, Comment 3]
MOPS medium with 0.4% glucose Yes 37 Aerobic 7.2 0.22 Yes [Baba06, Comment 2]

Credits:
Created 05-Sep-2006 by Keseler I , SRI International
Curated 05-Sep-2006 by Keseler I , SRI International
Last-Curated ? 09-Jan-2009 by Gama-Castro S , UNAM


Subunit of: MprA-CCCP

Subunit composition of MprA-CCCP = [MprA][carbonylcyanide m-chlorophenylhydrazone]

Citations: [Brooun99]

Sequence Length: 176 AAs

In Reactions of unknown directionality:

Not in pathways:
MprA + carbonylcyanide m-chlorophenylhydrazone = MprA-CCCP

MultiFun Terms: cell processes protection drug resistance/sensitivity
extrachromosomal plasmid related
information transfer RNA related Transcription related
regulation genetic unit regulated operon
regulation type of regulation transcriptional level repressor


Subunit of: MprA-2,4-dinitrophenol

Subunit composition of MprA-2,4-dinitrophenol = [MprA][2,4-dinitrophenol]

Citations: [Brooun99]

Sequence Length: 176 AAs

In Reactions of unknown directionality:

Not in pathways:
MprA + 2,4-dinitrophenol = MprA-2,4-dinitrophenol

MultiFun Terms: cell processes protection drug resistance/sensitivity
extrachromosomal plasmid related
information transfer RNA related Transcription related
regulation genetic unit regulated operon
regulation type of regulation transcriptional level repressor


Sequence Features

Feature Class Location Citations Comment
Conserved-Region 26 -> 160
[UniProt09]
UniProt: HTH marR-type;


Gene Local Context (not to scale): ?

Transcription Unit:

Notes:

History:
10/20/97 Gene b2684 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG10603; confirmed by SwissProt match.


References

Asensio76: Asensio C, Perez-Diaz JC (1976). "A new family of low molecular weight antibiotics from enterobacteria." Biochem Biophys Res Commun 69(1);7-14. PMID: 4071

Baba06: Baba T, Ara T, Hasegawa M, Takai Y, Okumura Y, Baba M, Datsenko KA, Tomita M, Wanner BL, Mori H (2006). "Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection." Mol Syst Biol 2;2006.0008. PMID: 16738554

Brooun99: Brooun A, Tomashek JJ, Lewis K (1999). "Purification and ligand binding of EmrR, a regulator of a multidrug transporter." J Bacteriol 181(16);5131-3. PMID: 10438794

Dalrymple97: Dalrymple BP, Swadling Y (1997). "Expression of a Butyrivibrio fibrisolvens E14 gene (cinB) encoding an enzyme with cinnamoyl ester hydrolase activity is negatively regulated by the product of an adjacent gene (cinR)." Microbiology 143 ( Pt 4);1203-10. PMID: 9141683

delCastillo90: del Castillo I, Gomez JM, Moreno F (1990). "mprA, an Escherichia coli gene that reduces growth-phase-dependent synthesis of microcins B17 and C7 and blocks osmoinduction of proU when cloned on a high-copy-number plasmid." J Bacteriol 172(1);437-45. PMID: 2152912

delCastillo91: del Castillo I, Gonzalez-Pastor JE, San Millan JL, Moreno F (1991). "Nucleotide sequence of the Escherichia coli regulatory gene mprA and construction and characterization of mprA-deficient mutants." J Bacteriol 173(12);3924-9. PMID: 1840583

DiazMejia09: Diaz-Mejia JJ, Babu M, Emili A (2009). "Computational and experimental approaches to chart the Escherichia coli cell-envelope-associated proteome and interactome." FEMS Microbiol Rev 33(1);66-97. PMID: 19054114

Gerdes03: Gerdes SY, Scholle MD, Campbell JW, Balazsi G, Ravasz E, Daugherty MD, Somera AL, Kyrpides NC, Anderson I, Gelfand MS, Bhattacharya A, Kapatral V, D'Souza M, Baev MV, Grechkin Y, Mseeh F, Fonstein MY, Overbeek R, Barabasi AL, Oltvai ZN, Osterman AL (2003). "Experimental determination and system level analysis of essential genes in Escherichia coli MG1655." J Bacteriol 185(19);5673-84. PMID: 13129938

GOA01: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

Grkovic02: Grkovic S, Brown MH, Skurray RA (2002). "Regulation of bacterial drug export systems." Microbiol Mol Biol Rev 66(4);671-701, table of contents. PMID: 12456787

Ishihama08: Ishihama Y, Schmidt T, Rappsilber J, Mann M, Hartl FU, Kerner MJ, Frishman D (2008). "Protein abundance profiling of the Escherichia coli cytosol." BMC Genomics 9;102. PMID: 18304323

Joyce06: Joyce AR, Reed JL, White A, Edwards R, Osterman A, Baba T, Mori H, Lesely SA, Palsson BO, Agarwalla S (2006). "Experimental and computational assessment of conditionally essential genes in Escherichia coli." J Bacteriol 188(23);8259-71. PMID: 17012394

Lewis01: Lewis K (2001). "In search of natural substrates and inhibitors of MDR pumps." J Mol Microbiol Biotechnol 3(2);247-54. PMID: 11321580

Lomovskaya92: Lomovskaya O, Lewis K (1992). "Emr, an Escherichia coli locus for multidrug resistance." Proc Natl Acad Sci U S A 1992;89(19);8938-42. PMID: 1409590

Lomovskaya95: Lomovskaya O, Lewis K, Matin A (1995). "EmrR is a negative regulator of the Escherichia coli multidrug resistance pump EmrAB." J Bacteriol 1995;177(9);2328-34. PMID: 7730261

Mao98: Mao W, Siegele DA (1998). "Genetic analysis of the stationary phase-induced mcb operon promoter in Escherichia coli." Mol Microbiol 27(2);415-24. PMID: 9484896

Miller96: Miller PF, Sulavik MC (1996). "Overlaps and parallels in the regulation of intrinsic multiple-antibiotic resistance in Escherichia coli." Mol Microbiol 21(3);441-8. PMID: 8866468

Rodionov01: Rodionov DA, Gelfand MS, Mironov AA, Rakhmaninova AB (2001). "Comparative approach to analysis of regulation in complete genomes: multidrug resistance systems in gamma-proteobacteria." J Mol Microbiol Biotechnol 3(2);319-24. PMID: 11321589

Sulavik95: Sulavik MC, Gambino LF, Miller PF (1995). "The MarR repressor of the multiple antibiotic resistance (mar) operon in Escherichia coli: prototypic member of a family of bacterial regulatory proteins involved in sensing phenolic compounds." Mol Med 1995;1(4);436-46. PMID: 8521301

UniProt09: UniProt Consortium (2009). "UniProt version 15.8 released on 2009-10-01 00:00:00." Database.

UniProtGOA11: UniProt-GOA (2011). "Gene Ontology annotation based on manual assignment of UniProtKB keywords in UniProtKB/Swiss-Prot entries."

Xiong00: Xiong A, Gottman A, Park C, Baetens M, Pandza S, Matin A (2000). "The EmrR protein represses the Escherichia coli emrRAB multidrug resistance operon by directly binding to its promoter region." Antimicrob Agents Chemother 44(10);2905-7. PMID: 10991887

Yang04b: Yang H, Wolff E, Kim M, Diep A, Miller JH (2004). "Identification of mutator genes and mutational pathways in Escherichia coli using a multicopy cloning approach." Mol Microbiol 53(1);283-95. PMID: 15225322

Other References Related to Gene Regulation

Hirakawa03a: Hirakawa H, Nishino K, Hirata T, Yamaguchi A (2003). "Comprehensive studies of drug resistance mediated by overexpression of response regulators of two-component signal transduction systems in Escherichia coli." J Bacteriol 185(6);1851-6. PMID: 12618449

Viveiros07: Viveiros M, Dupont M, Rodrigues L, Couto I, Davin-Regli A, Martins M, Pages JM, Amaral L (2007). "Antibiotic stress, genetic response and altered permeability of E. coli." PLoS ONE 2;e365. PMID: 17426813


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Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
Page generated by SRI International Pathway Tools version 18.5 on Sun Dec 21, 2014, biocyc14.