Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites MAYBE down
12/28 - 12/31
for maintenance.
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites MAYBE down
12/28 - 12/31
for maintenance.
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites MAYBE down
12/28 - 12/31
for maintenance.
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites MAYBE down
12/28 - 12/31
for maintenance.
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites MAYBE down
12/28 - 12/31
for maintenance.
twitter

Escherichia coli K-12 substr. MG1655 Polypeptide: MelR DNA-binding transcriptional dual regulator



Gene: melR Accession Numbers: EG11230 (EcoCyc), b4118, ECK4111

Regulation Summary Diagram: ?

Component of: MelR-Melibiose transcriptional activator (extended summary available)

Citations: [Webster87, Webster89, Caswell92, Williams94]

Gene Citations: [Bourgerie97, Michan95, Caswell92]

Locations: cytosol

Map Position: [4,338,743 <- 4,339,651] (93.51 centisomes)
Length: 909 bp / 302 aa

Molecular Weight of Polypeptide: 34.928 kD (from nucleotide sequence)

pI: 8.27

Unification Links: ASAP:ABE-0013486 , CGSC:18166 , EchoBASE:EB1212 , EcoGene:EG11230 , EcoliWiki:b4118 , ModBase:P0ACH8 , OU-Microarray:b4118 , PortEco:melR , PR:PRO_000023199 , Pride:P0ACH8 , Protein Model Portal:P0ACH8 , RefSeq:NP_418542 , RegulonDB:EG11230 , SMR:P0ACH8 , String:511145.b4118 , UniProt:P0ACH8

Relationship Links: InterPro:IN-FAMILY:IPR008917 , InterPro:IN-FAMILY:IPR009057 , InterPro:IN-FAMILY:IPR011051 , InterPro:IN-FAMILY:IPR014710 , InterPro:IN-FAMILY:IPR018060 , InterPro:IN-FAMILY:IPR018062 , InterPro:IN-FAMILY:IPR020449 , Prints:IN-FAMILY:PR00032 , Prosite:IN-FAMILY:PS00041 , Prosite:IN-FAMILY:PS01124 , Smart:IN-FAMILY:SM00342

In Paralogous Gene Group: 22 (29 members)

In Reactions of unknown directionality:

Not in pathways:
MelR + melibiose = MelR-melibiose

Gene-Reaction Schematic: ?

Genetic Regulation Schematic: ?

GO Terms:

Biological Process: GO:0006355 - regulation of transcription, DNA-templated Inferred from experiment Inferred by computational analysis [UniProtGOA11a, GOA01a, Belyaeva00]
GO:0006351 - transcription, DNA-templated Inferred by computational analysis [UniProtGOA11a]
Molecular Function: GO:0003677 - DNA binding Inferred from experiment Inferred by computational analysis [UniProtGOA11a, GOA01a, Wade01]
GO:0003700 - sequence-specific DNA binding transcription factor activity Inferred by computational analysis [GOA01a]
GO:0043565 - sequence-specific DNA binding Inferred by computational analysis [GOA01a]
Cellular Component: GO:0005829 - cytosol Inferred by computational analysis [DiazMejia09]

MultiFun Terms: information transfer RNA related Transcription related
metabolism carbon utilization carbon compounds
regulation genetic unit regulated operon
regulation type of regulation transcriptional level activator

DNA binding site length: 18 base-pairs

Symmetry: Asymmetric

Consensus DNA Binding Sequence: ATTCCCATAAACTCAGAT

Regulated Transcription Units (2 total): ?

Notes:

Essentiality data for melR 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:
Revised 23-May-2011 by Brito D


Subunit of: MelR-Melibiose transcriptional activator

Synonyms: B4118, MelR, MelR-melibiose

Subunit composition of MelR-Melibiose transcriptional activator = [MelR][melibiose]
         MelR DNA-binding transcriptional dual regulator = MelR

Summary:
MelR, "melibiose regulator," is a transcription factor involved in disaccharide melibiose degradation. It coregulates with CRP, a global transcriptional regulator [Wade01, Belyaeva00, Webster88]. These regulators bind cooperatively to activate transcription of the operon involved in transport and catabolism of melibiose. Synthesis of this operon is induced when Escherichia coli is grown on melibiose in the absence of glucose. Gene induction occurs when the physiological inducer, melibiose, binds to the MelR regulator and when cellular cyclic AMP levels are high.

In the presence of melibiose, MelR binds in tandem to repeat sequences in the melR/melAB intergenic region to activate transcription by overlapping the -35 box of the promoter melAp. The binding targets for MelR consist of 18-nucleotide-long repeat sequences that possess conserved motifs; each monomer binds to one of these conserved sequences [Belyaeva00, Wade01, Tamai00].

MelR binds to five target sites in the melAp region. MelR binds to the less-conserved site (-42.5) with less strength; this binding occurs only in the presence of melibiose, and it is absolutely required for expression of melAp [Belyaeva00]. MelR binding to the distal site (-237.5) has been shown to down-regulate the expression of melRp and melAp [Kahramanoglou06, Wade00].

In the absence of melibiose, MelR is unable to activate melAp, but it regulates its own expression by repressing melRp and melAp simultaneously [Belyaeva00, Tobes02, Gallegos97]. Melibiose triggers MelR-dependent activation of melAp and relieves MelR-dependent repression of melRp [Gallegos97, Tobes02]. The melAB operon is located upstream of melR and in the opposite direction.

This regulator belongs to the AraC/XylS family of activators and occurs as both a monomer and a homodimer. It is composed of two domains: the carboxy-terminal domain, which contains the DNA-binding region, and the amino-terminal domain, which is responsible for dimerization and l-arabinose binding [Michan95, Webster89, Caswell92, Bourgerie97, Grainger03].

Sequence Length: 302 AAs

Molecular Weight: 34.928 kD (from nucleotide sequence)

Relationship Links: Pfam:IN-FAMILY:PF00165

In Reactions of unknown directionality:

Not in pathways:
MelR + melibiose = MelR-melibiose

GO Terms:

Biological Process: GO:2000144 - positive regulation of DNA-templated transcription, initiation Inferred from experiment [Belyaeva00]
Molecular Function: GO:0001046 - core promoter sequence-specific DNA binding Inferred from experiment [Belyaeva00]

MultiFun Terms: information transfer RNA related Transcription related
metabolism carbon utilization carbon compounds
regulation genetic unit regulated operon
regulation type of regulation transcriptional level activator

DNA binding site length: 18 base-pairs

Symmetry: Asymmetric

Consensus DNA Binding Sequence: ATTCCCATAAACTCAGAT

Regulated Transcription Units (2 total): ?

Notes:


Sequence Features

Feature Class Location Citations Comment
DNA-Binding-Region 210 -> 229
[UniProt10a]
UniProt: H-T-H motif; Non-Experimental Qualifier: by similarity;
Mutagenesis-Variant 222
[UniProt10]
Alternate sequence: N → A; UniProt: No effect;
Mutagenesis-Variant 269
[UniProt10]
Alternate sequence: R → G; UniProt: No effect;
Mutagenesis-Variant 271
[UniProt10]
Alternate sequence: S → A; UniProt: 50% reduced activity;
Mutagenesis-Variant 272
[UniProt10]
Alternate sequence: S → N; UniProt: 75% reduced activity;


Gene Local Context (not to scale): ?

Transcription Units:

Notes:

History:
10/20/97 Gene b4118 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG11230.


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

Belyaeva00: Belyaeva TA, Wade JT, Webster CL, Howard VJ, Thomas MS, Hyde EI, Busby SJ (2000). "Transcription activation at the Escherichia coli melAB promoter: the role of MelR and the cyclic AMP receptor protein." Mol Microbiol 36(1);211-22. PMID: 10760178

Bourgerie97: Bourgerie SJ, Michan CM, Thomas MS, Busby SJ, Hyde EI (1997). "DNA binding and DNA bending by the MelR transcription activator protein from Escherichia coli." Nucleic Acids Res 1997;25(9);1685-93. PMID: 9108148

Caswell92: Caswell R, Williams J, Lyddiatt A, Busby S (1992). "Overexpression, purification and characterization of the Escherichia coli MelR transcription activator protein." Biochem J 1992;287 ( Pt 2);493-9. PMID: 1445207

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

Gallegos97: Gallegos MT, Schleif R, Bairoch A, Hofmann K, Ramos JL (1997). "Arac/XylS family of transcriptional regulators." Microbiol Mol Biol Rev 61(4);393-410. PMID: 9409145

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."

Grainger03: Grainger DC, Belyaeva TA, Lee DJ, Hyde EI, Busby SJ (2003). "Binding of the Escherichia coli MelR protein to the melAB promoter: orientation of MelR subunits and investigation of MelR-DNA contacts." Mol Microbiol 48(2);335-48. PMID: 12675795

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

Kahramanoglou06: Kahramanoglou C, Webster CL, El-Robh MS, Belyaeva TA, Busby SJ (2006). "Mutational analysis of the Escherichia coli melR gene suggests a two-state concerted model to explain transcriptional activation and repression in the melibiose operon." J Bacteriol 188(9);3199-207. PMID: 16621812

Michan95: Michan CM, Busby SJ, Hyde EI (1995). "The Escherichia coli MelR transcription activator: production of a stable fragment containing the DNA-binding domain." Nucleic Acids Res 23(9);1518-23. PMID: 7784205

Samarasinghe08: Samarasinghe S, El-Robh MS, Grainger DC, Zhang W, Soultanas P, Busby SJ (2008). "Autoregulation of the Escherichia coli melR promoter: repression involves four molecules of MelR." Nucleic Acids Res 36(8);2667-76. PMID: 18346968

Tamai00: Tamai E, Belyaeva TA, Busby SJ, Tsuchiya T (2000). "Mutations that increase the activity of the promoter of the Escherichia coli melibiose operon improve the binding of MelR, a transcription activator triggered by melibiose." J Biol Chem 275(22);17058-63. PMID: 10747919

Tobes02: Tobes R, Ramos JL (2002). "AraC-XylS database: a family of positive transcriptional regulators in bacteria." Nucleic Acids Res 30(1);318-21. PMID: 11752325

UniProt10: UniProt Consortium (2010). "UniProt version 2010-11 released on 2010-11-02 00:00:00." Database.

UniProt10a: UniProt Consortium (2010). "UniProt version 2010-07 released on 2010-06-15 00:00:00." Database.

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

Wade00: Wade JT, Belyaeva TA, Hyde EI, Busby SJ (2000). "Repression of the Escherichia coli melR promoter by MelR: evidence that efficient repression requires the formation of a repression loop." Mol Microbiol 36(1);223-9. PMID: 10760179

Wade01: Wade JT, Belyaeva TA, Hyde EI, Busby SJ (2001). "A simple mechanism for co-dependence on two activators at an Escherichia coli promoter." EMBO J 20(24);7160-7. PMID: 11742992

Webster87: Webster C, Kempsell K, Booth I, Busby S (1987). "Organisation of the regulatory region of the Escherichia coli melibiose operon." Gene 59(2-3);253-63. PMID: 2830169

Webster88: Webster C, Gaston K, Busby S (1988). "Transcription from the Escherichia coli melR promoter is dependent on the cyclic AMP receptor protein." Gene 1988;68(2);297-305. PMID: 2851497

Webster89: Webster C, Gardner L, Busby S (1989). "The Escherichia coli melR gene encodes a DNA-binding protein with affinity for specific sequences located in the melibiose-operon regulatory region." Gene 1989;83(2);207-13. PMID: 2684786

Williams94: Williams J, Michan C, Webster C, Busby S (1994). "Interactions between the Escherichia coli MelR transcription activator protein and operator sequences at the melAB promoter." Biochem J 1994;300 ( Pt 3);757-63. PMID: 8010957

Other References Related to Gene Regulation

Caswell92a: Caswell R, Webster C, Busby S (1992). "Studies on the binding of the Escherichia coli MelR transcription activator protein to operator sequences at the MelAB promoter." Biochem J 287 ( Pt 2);501-8. PMID: 1445208

Elrobh13: Elrobh MS, Webster CL, Samarasinghe S, Durose D, Busby SJ (2013). "Two DNA sites for MelR in the same orientation are sufficient for optimal MelR-dependent repression at the Escherichia coli melR promoter." FEMS Microbiol Lett 338(1);62-7. PMID: 23066992

Howard02: Howard VJ, Belyaeva TA, Busby SJ, Hyde EI (2002). "DNA binding of the transcription activator protein MelR from Escherichia coli and its C-terminal domain." Nucleic Acids Res 30(12);2692-700. PMID: 12060687

Otsuka96: Otsuka J, Watanabe H, Mori KT (1996). "Evolution of transcriptional regulation system through promiscuous coupling of regulatory proteins with operons; suggestion from protein sequence similarities in Escherichia coli." J Theor Biol 1996;178(2);183-204. PMID: 8729576

Zheng04: Zheng D, Constantinidou C, Hobman JL, Minchin SD (2004). "Identification of the CRP regulon using in vitro and in vivo transcriptional profiling." Nucleic Acids Res 32(19);5874-93. PMID: 15520470


Report Errors or Provide Feedback
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 Fri Dec 26, 2014, biocyc13.