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Escherichia coli K-12 substr. MG1655 Protein: MetR DNA-binding transcriptional dual regulator
Inferred from experimentInferred by computational analysis



Gene: metR Accession Numbers: EG10591 (EcoCyc), b3828, ECK3822

Regulation Summary Diagram

Regulation summary diagram for metR

Component of: MetR-L-homocysteine

Subunit composition of MetR DNA-binding transcriptional dual regulator = [MetR]2

Summary:
MetR participates in controlling several genes involved in methionine biosynthesis [Weissbach91] and a gene involved in protection against nitric oxide [MembrilloHernan98].

Homocysteine, an intermediate in the biosynthesis of methionine [Urbanowski89], binds to MetR and enhances the activity of some MetR-activated promoters (i.e., metE and glyA) by enhancing the affinity in DNA-binding sites [Lorenz96, Weissbach91]. But homocysteine is also able to decrease the activity of other promoters that are activated (i.e., metH, metA, and hmp) or repressed (i.e., metR) by MetR [Urbanowski89, Cai89a, Weissbach91]. The glyA and hmp genes are transcribed divergently and have a common regulatory region that contains two MetR DNA-binding sites. When homocysteine is present, MetR binds to two MetR sites and activates glyA and represses hmp transcription, but in the absence of homocysteine MetR binds only one site and activates hmp and represses glyA transcription [MembrilloHernan98].

MetR appears to first bind DNA and then homocysteine causes the effect on transcription [Cai89a]. The nitrosated compound S-nitrosoglutathione (GSNO) removes homocysteine by nitrosation [MembrilloHernan98].

The RNA polymerase and MetR interact for transcription activation, but distinct residues of RNA polymerase are involved in different promoters because the MetR-binding sites are located at different positions [Fritsch00, Lorenz96]|. MetR, as a dimer [Cai89], recognizes and binds a DNA sequence with dyad symmetry [Cai89, Lorenz95].

MetR belongs to the LysR family of transcriptional regulators [Schell93]. The members of this family have three domains: the N-terminal domain, which contains a helix-turn-helix motif for DNA binding, a central domain involved in coinducer recognition, and a C-terminal domain required for both DNA binding and coinducer response [Schell93].

It has been proposed that MetR has in the N-terminal domain a leucine zipper motif characteristic of many eukaryotic DNA-binding proteins used for protein dimerization [Maxon90]. Mutations in leucines of this motif inactivated MetR [Maxon90], but a role of MetR dimerization for this motif has not been demonstrated [Maxon90].

metR and metE are divergently transcribed from overlapping promoters [Cai89].

Citations: [Maxon89, Daniels92]

Locations: cytosol

Map Position: [4,011,863 <- 4,012,816] (86.43 centisomes, 311°)
Length: 954 bp / 317 aa

Molecular Weight of Polypeptide: 35.629 kD (from nucleotide sequence)

pI: 8.11

Unification Links: ASAP:ABE-0012506, CGSC:18163, DIP:DIP-10198N, EchoBASE:EB0586, EcoGene:EG10591, EcoliWiki:b3828, Mint:MINT-1262668, ModBase:P0A9F9, OU-Microarray:b3828, PortEco:metR, PR:PRO_000023220, Pride:P0A9F9, Protein Model Portal:P0A9F9, RefSeq:NP_418272, RegulonDB:EG10591, SMR:P0A9F9, String:511145.b3828, UniProt:P0A9F9

Relationship Links: InterPro:IN-FAMILY:IPR000847, InterPro:IN-FAMILY:IPR005119, InterPro:IN-FAMILY:IPR011991, Pfam:IN-FAMILY:PF00126, Pfam:IN-FAMILY:PF03466, Prints:IN-FAMILY:PR00039, Prosite:IN-FAMILY:PS50931

In Paralogous Gene Group: 6 (42 members)

Reactions known to both consume and produce the compound:

Not in pathways:
MetR + L-homocysteine ↔ MetR-L-homocysteine

Gene-Reaction Schematic

Gene-Reaction Schematic

Genetic Regulation Schematic

Genetic regulation schematic for metR


GO Terms:
Biological Process:
Inferred from experimentInferred by computational analysisGO:0006355 - regulation of transcription, DNA-templated [UniProtGOA11a, GOA01a, MembrilloHernan98]
Inferred by computational analysisGO:0006351 - transcription, DNA-templated [UniProtGOA11a]
Inferred by computational analysisGO:0008652 - cellular amino acid biosynthetic process [UniProtGOA11a]
Inferred by computational analysisGO:0009086 - methionine biosynthetic process [UniProtGOA11a]
Molecular Function:
Inferred from experimentInferred by computational analysisGO:0003677 - DNA binding [UniProtGOA11a, Cai89]
Inferred from experimentGO:0016597 - amino acid binding [Cai89]
Inferred by computational analysisGO:0003700 - transcription factor activity, sequence-specific DNA binding [GOA01a]
Cellular Component:
Inferred by computational analysisGO:0005737 - cytoplasm [UniProtGOA11, UniProtGOA11a]
Inferred by computational analysisGO:0005829 - cytosol [DiazMejia09]

MultiFun Terms: information transferRNA relatedTranscription related
metabolismbiosynthesis of building blocksamino acidsmethionine
regulationgenetic unit regulatedoperon
regulationtype of regulationtranscriptional levelactivator
regulationtype of regulationtranscriptional levelrepressor

DNA binding site length: 15 base-pairs

Symmetry: Inverted Repeat

Consensus DNA Binding Sequence: aTGAAaaattTTCAt

Regulated Transcription Units (2 total):

Notes:

Transcription-unit diagram

Transcription-unit diagram

Essentiality data for metR knockouts:

Growth Medium Growth? T (°C) O2 pH Osm/L Growth Observations
LB enrichedYes 37 Aerobic 6.95   Yes [Gerdes03, Comment 1]
LB LennoxYes 37 Aerobic 7   Yes [Baba06, Comment 2]
M9 medium with 0.4% glucoseNo 37 Aerobic 7.2 0.27 No [Patrick07, Comment 3]
M9 medium with 1% glycerolNo 37 Aerobic 7.2 0.35 No [Joyce06]
MOPS medium with 0.4% glucoseYes 37 Aerobic 7.2 0.22 Yes [Baba06, Comment 2]

Credits:
Created 19-Feb-2009 by Gama-Castro S, UNAM


Subunit of: MetR-L-homocysteine

Inferred from experimentInferred by computational analysis

Subunit composition of MetR-L-homocysteine = [(MetR)2][L-homocysteine]
         MetR DNA-binding transcriptional dual regulator = (MetR)2 (extended summary available)

Citations: [Lorenz96 , Schell93, Cai89, Lorenz95, Urbanowski89]

Sequence Length: 317 AAs

Reactions known to both consume and produce the compound:

Not in pathways:
MetR + L-homocysteine ↔ MetR-L-homocysteine

MultiFun Terms: information transferRNA relatedTranscription related
metabolismbiosynthesis of building blocksamino acidsmethionine
regulationgenetic unit regulatedoperon
regulationtype of regulationtranscriptional levelactivator
regulationtype of regulationtranscriptional levelrepressor

DNA binding site length: 15 base-pairs

Symmetry: Inverted Repeat

Consensus DNA Binding Sequence: aTGAAaaattTTCAt

Regulated Transcription Units (4 total):

Notes:

Transcription-unit diagram

Transcription-unit diagram

Transcription-unit diagram

Transcription-unit diagram


Sequence Features

Protein sequence of MetR with features indicated

Feature Class Location Citations Comment
Conserved-Region 1 -> 59
Inferred by computational analysis[UniProt15]
UniProt: HTH lysR-type.
Pfam PF00126 5 -> 63
Inferred by computational analysis[Finn14]
HTH_1 : Bacterial regulatory helix-turn-helix protein, lysR family
Sequence-Conflict 19
Inferred by curator[Maxon89, UniProt15]
UniProt: (in Ref. 5).
DNA-Binding-Region 19 -> 38
Inferred by computational analysis[UniProt15]
UniProt: H-T-H motif.
Pfam PF03466 86 -> 288
Inferred by computational analysis[Finn14]
LysR_substrate : LysR substrate binding domain [More...]


Gene Local Context (not to scale -- see Genome Browser for correct scale)

Transcription Units

Transcription-unit diagram

Transcription-unit diagram

Transcription-unit diagram

Notes:

History:
10/20/97 Gene b3828 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG10591; confirmed by SwissProt match.


References

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

Cai89: Cai XY, Maxon ME, Redfield B, Glass R, Brot N, Weissbach H (1989). "Methionine synthesis in Escherichia coli: effect of the MetR protein on metE and metH expression." Proc Natl Acad Sci U S A 1989;86(12);4407-11. PMID: 2543976

Cai89a: Cai XY, Redfield B, Maxon M, Weissbach H, Brot N (1989). "The effect of homocysteine on MetR regulation of metE, metR and metH expression in vitro." Biochem Biophys Res Commun 163(1);79-83. PMID: 2673243

Daniels92: Daniels DL, Plunkett G, Burland V, Blattner FR (1992). "Analysis of the Escherichia coli genome: DNA sequence of the region from 84.5 to 86.5 minutes." Science 1992;257(5071);771-8. PMID: 1379743

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

Finn14: Finn RD, Bateman A, Clements J, Coggill P, Eberhardt RY, Eddy SR, Heger A, Hetherington K, Holm L, Mistry J, Sonnhammer EL, Tate J, Punta M (2014). "Pfam: the protein families database." Nucleic Acids Res 42(Database issue);D222-30. PMID: 24288371

Fritsch00: Fritsch PS, Urbanowski ML, Stauffer GV (2000). "Role of the RNA polymerase alpha subunits in MetR-dependent activation of metE and metH: important residues in the C-terminal domain and orientation requirements within RNA polymerase." J Bacteriol 182(19);5539-50. PMID: 10986259

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

GOA01a: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

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

Lorenz95: Lorenz E, Stauffer GV (1995). "Characterization of the MetR binding sites for the glyA gene of Escherichia coli." J Bacteriol 1995;177(14);4113-20. PMID: 7608086

Lorenz96: Lorenz E, Stauffer GV (1996). "RNA polymerase, PurR and MetR interactions at the glyA promoter of Escherichia coli." Microbiology 1996;142 ( Pt 7);1819-24. PMID: 8757744

Maxon89: Maxon ME, Redfield B, Cai XY, Shoeman R, Fujita K, Fisher W, Stauffer G, Weissbach H, Brot N (1989). "Regulation of methionine synthesis in Escherichia coli: effect of the MetR protein on the expression of the metE and metR genes." Proc Natl Acad Sci U S A 1989;86(1);85-9. PMID: 2643109

Maxon90: Maxon ME, Wigboldus J, Brot N, Weissbach H (1990). "Structure-function studies on Escherichia coli MetR protein, a putative prokaryotic leucine zipper protein." Proc Natl Acad Sci U S A 1990;87(18);7076-9. PMID: 2205852

MembrilloHernan98: Membrillo-Hernandez J, Coopamah MD, Channa A, Hughes MN, Poole RK (1998). "A novel mechanism for upregulation of the Escherichia coli K-12 hmp (flavohaemoglobin) gene by the 'NO releaser', S-nitrosoglutathione: nitrosation of homocysteine and modulation of MetR binding to the glyA-hmp intergenic region." Mol Microbiol 29(4);1101-12. PMID: 9767577

Patrick07: Patrick WM, Quandt EM, Swartzlander DB, Matsumura I (2007). "Multicopy suppression underpins metabolic evolvability." Mol Biol Evol 24(12);2716-22. PMID: 17884825

Schell93: Schell MA (1993). "Molecular biology of the LysR family of transcriptional regulators." Annu Rev Microbiol 47;597-626. PMID: 8257110

UniProt15: UniProt Consortium (2015). "UniProt version 2015-08 released on 2015-07-22." Database.

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

UniProtGOA11a: UniProt-GOA (2011). "Gene Ontology annotation based on manual assignment of UniProtKB keywords in UniProtKB/Swiss-Prot entries."

Urbanowski89: Urbanowski ML, Stauffer GV (1989). "Role of homocysteine in metR-mediated activation of the metE and metH genes in Salmonella typhimurium and Escherichia coli." J Bacteriol 171(6);3277-81. PMID: 2656646

Weissbach91: Weissbach H, Brot N (1991). "Regulation of methionine synthesis in Escherichia coli." Mol Microbiol 1991;5(7);1593-7. PMID: 1943695

Other References Related to Gene Regulation

Jafri95: Jafri S, Urbanowski ML, Stauffer GV (1995). "A mutation in the rpoA gene encoding the alpha subunit of RNA polymerase that affects metE-metR transcription in Escherichia coli." J Bacteriol 177(3);524-9. PMID: 7836282

Urbanowski89a: Urbanowski ML, Stauffer GV (1989). "Genetic and biochemical analysis of the MetR activator-binding site in the metE metR control region of Salmonella typhimurium." J Bacteriol 1989;171(10);5620-9. PMID: 2676984


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Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
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