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



Gene: nagC Accession Numbers: EG10636 (EcoCyc), b0676, ECK0664

Synonyms: nagR, transcriptional repressor of nag (N-acetylglucosamine) operon

Regulation Summary Diagram: ?

Component of: NagC-NAcGlc-6-P

Summary:
The NagC, "N-acetylglucosamine," transcriptional dual regulator participates in regulating the phosphotransferase system (PTS) [Pennetier08]. Its function is to coordinate the biosynthesis of the amino sugars, D-glucosamine (GlcN) and N-acetylglucosamine (GlcNAc) with their catabolism [Plumbridge91a, Plumbridge01a, Plumbridge01, Plumbridge04].

The specific inducer for NagC is GlcNAc-6-P, the product of GlcNAc transport by the PTS [Plumbridge91a, Plumbridge01a]. NagC is displaced from its DNA targets by interacting with GlcNAc-6-P [Plumbridge91a].

Based on the structure of Mlc DNA-binding transcriptional repressor, models for the three-dimensional structure of NagC and for the binding of GlcNAc-6-P were developed [Pennetier08].

The Nag regulon consists of two divergent operons, nagE and nagBACD. nagC encodes the repressor of this regulon. Its localization within the inducible nagBACD operon is unusual, since most transcriptional dual regulators are located near the loci they control [Plumbridge91a].

NagC is present at low levels within the bacterial cell [Plumbridge91a].

The consensus sequence for the NagC-binding site has been determined via combination of native site comparisons, operator mutagenesis, and selection of DNA-binding fragments, [Plumbridge01]. The dual function of NagC requires it to bind simultaneously to two operators in order to form a DNA loop [Plumbridge01a]. The strictly conserved TT/AA motif, located in both ends of the center of symmetry, is probably the major recognition point for NagC [Plumbridge01].

NagC is a member of the ROK (repressor, ORFs, kinases) (NagC/XylR) family of proteins, which contains at least two distinct classes of proteins, xylose repressor (XylR) and a series of glucose/fructose kinases [Titgemeyer94, Hansen02].

NagC is similar to Mlc transcriptional dual regulator [Cho05]. However, they have different specificities for select binding sites [Plumbridge01].

NagC has a helix-turn-helix motif in its N-terminal part [Pennetier08].

Citations: [Plumbridge89, Peri90, Plumbridge91]

Gene Citations: [Plumbridge91, Plumbridge89, Vogler89, Rogers88]

Locations: cytosol

Map Position: [699,597 <- 700,817] (15.08 centisomes)
Length: 1221 bp / 406 aa

Molecular Weight of Polypeptide: 44.541 kD (from nucleotide sequence)

pI: 7.21

Unification Links: ASAP:ABE-0002299 , CGSC:31479 , DIP:DIP-35984N , EchoBASE:EB0630 , EcoGene:EG10636 , EcoliWiki:b0676 , ModBase:P0AF20 , OU-Microarray:b0676 , PortEco:nagC , PR:PRO_000023338 , Pride:P0AF20 , Protein Model Portal:P0AF20 , RefSeq:NP_415202 , RegulonDB:EG10636 , SMR:P0AF20 , String:511145.b0676 , Swiss-Model:P0AF20 , UniProt:P0AF20

Relationship Links: InterPro:IN-FAMILY:IPR000600 , InterPro:IN-FAMILY:IPR000835 , InterPro:IN-FAMILY:IPR011991 , Pfam:IN-FAMILY:PF00480 , Pfam:IN-FAMILY:PF01047 , Prosite:IN-FAMILY:PS01125

In Paralogous Gene Group: 118 (7 members)

In Reactions of unknown directionality:

Not in pathways:
N-acetyl-D-glucosamine 6-phosphate + NagC = NagC-NAcGlc-6-P

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, Pennetier08]
GO:0005975 - carbohydrate metabolic process Inferred by computational analysis [UniProtGOA11a]
GO:0006351 - transcription, DNA-templated Inferred by computational analysis [UniProtGOA11a]
Molecular Function: GO:0003677 - DNA binding Inferred from experiment Inferred by computational analysis [UniProtGOA11a, Plumbridge01]
GO:0003700 - sequence-specific DNA binding transcription factor activity Inferred by computational analysis [GOA01a]
Cellular Component: GO:0005622 - intracellular Inferred by computational analysis [GOA01a]
GO:0005829 - cytosol Inferred by computational analysis [DiazMejia09]

MultiFun Terms: information transfer RNA related Transcription related
metabolism central intermediary metabolism amino sugar conversions
regulation genetic unit regulated operon
regulation type of regulation posttranscriptional translation attenuation and efficiency
regulation type of regulation transcriptional level activator
regulation type of regulation transcriptional level repressor

DNA binding site length: 23 base-pairs

Symmetry: Inverted Repeat

Consensus DNA Binding Sequence: tTTatTTcgcgacgcgAAatAan

Regulated Transcription Units (20 total): ?

Notes:

Essentiality data for nagC 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:
Last-Curated ? 02-Apr-2008 by Santos-Zavaleta A , UNAM


Subunit of: NagC-NAcGlc-6-P

Synonyms: NagR, B0676, NagC

Subunit composition of NagC-NAcGlc-6-P = [N-acetyl-D-glucosamine 6-phosphate][NagC]
         NagC DNA-binding transcriptional dual regulator = NagC (extended summary available)

Sequence Length: 406 AAs

Relationship Links: Pfam:IN-FAMILY:PF00480

In Reactions of unknown directionality:

Not in pathways:
N-acetyl-D-glucosamine 6-phosphate + NagC = NagC-NAcGlc-6-P

MultiFun Terms: information transfer RNA related Transcription related
metabolism central intermediary metabolism amino sugar conversions
regulation genetic unit regulated operon
regulation type of regulation posttranscriptional translation attenuation and efficiency
regulation type of regulation transcriptional level activator
regulation type of regulation transcriptional level repressor


Sequence Features

Feature Class Location Citations Comment
DNA-Binding-Region 35 -> 44
[UniProt10b]
UniProt: H-T-H motif; Non-Experimental Qualifier: by similarity;
Sequence-Conflict 203 -> 204
[Plumbridge89, UniProt10]
Alternate sequence: EH → DD; UniProt: (in Ref. 1; CAA32354);


Gene Local Context (not to scale): ?

Transcription Units:

Notes:

History:
10/20/97 Gene b0676 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG10636; 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

Cho05: Cho S, Shin D, Ji GE, Heu S, Ryu S (2005). "High-level recombinant protein production by overexpression of Mlc in Escherichia coli." J Biotechnol 119(2);197-203. PMID: 15916829

Condemine05: Condemine G, Berrier C, Plumbridge J, Ghazi A (2005). "Function and expression of an N-acetylneuraminic acid-inducible outer membrane channel in Escherichia coli." J Bacteriol 187(6);1959-65. PMID: 15743943

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

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

Hansen02: Hansen T, Reichstein B, Schmid R, Schonheit P (2002). "The first archaeal ATP-dependent glucokinase, from the hyperthermophilic crenarchaeon Aeropyrum pernix, represents a monomeric, extremely thermophilic ROK glucokinase with broad hexose specificity." J Bacteriol 184(21);5955-65. PMID: 12374829

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

Pennetier08: Pennetier C, Dominguez-Ramirez L, Plumbridge J (2008). "Different regions of Mlc and NagC, homologous transcriptional repressors controlling expression of the glucose and N-acetylglucosamine phosphotransferase systems in Escherichia coli, are required for inducer signal recognition." Mol Microbiol 67(2);364-77. PMID: 18067539

Peri90: Peri KG, Goldie H, Waygood EB (1990). "Cloning and characterization of the N-acetylglucosamine operon of Escherichia coli." Biochem Cell Biol 68(1);123-37. PMID: 2190615

Plumbridge01: Plumbridge J (2001). "DNA binding sites for the Mlc and NagC proteins: regulation of nagE, encoding the N-acetylglucosamine-specific transporter in Escherichia coli." Nucleic Acids Res 29(2);506-14. PMID: 11139621

Plumbridge01a: Plumbridge J (2001). "Regulation of PTS gene expression by the homologous transcriptional regulators, Mlc and NagC, in Escherichia coli (or how two similar repressors can behave differently)." J Mol Microbiol Biotechnol 3(3);371-80. PMID: 11361067

Plumbridge04: Plumbridge J, Pellegrini O (2004). "Expression of the chitobiose operon of Escherichia coli is regulated by three transcription factors: NagC, ChbR and CAP." Mol Microbiol 52(2);437-49. PMID: 15066032

Plumbridge89: Plumbridge JA (1989). "Sequence of the nagBACD operon in Escherichia coli K12 and pattern of transcription within the nag regulon." Mol Microbiol 1989;3(4);505-15. PMID: 2668691

Plumbridge91: Plumbridge J, Kolb A (1991). "CAP and Nag repressor binding to the regulatory regions of the nagE-B and manX genes of Escherichia coli." J Mol Biol 1991;217(4);661-79. PMID: 1848637

Plumbridge91a: Plumbridge JA (1991). "Repression and induction of the nag regulon of Escherichia coli K-12: the roles of nagC and nagA in maintenance of the uninduced state." Mol Microbiol 1991;5(8);2053-62. PMID: 1766379

Plumbridge95: Plumbridge J (1995). "Co-ordinated regulation of amino sugar biosynthesis and degradation: the NagC repressor acts as both an activator and a repressor for the transcription of the glmUS operon and requires two separated NagC binding sites." EMBO J 1995;14(16);3958-65. PMID: 7545108

Rogers88: Rogers MJ, Ohgi T, Plumbridge J, Soll D (1988). "Nucleotide sequences of the Escherichia coli nagE and nagB genes: the structural genes for the N-acetylglucosamine transport protein of the bacterial phosphoenolpyruvate: sugar phosphotransferase system and for glucosamine-6-phosphate deaminase." Gene 1988;62(2);197-207. PMID: 3284790

Sohanpal04: Sohanpal BK, El-Labany S, Lahooti M, Plumbridge JA, Blomfield IC (2004). "Integrated regulatory responses of fimB to N-acetylneuraminic (sialic) acid and GlcNAc in Escherichia coli K-12." Proc Natl Acad Sci U S A 101(46);16322-7. PMID: 15534208

Sohanpal07: Sohanpal BK, Friar S, Roobol J, Plumbridge JA, Blomfield IC (2007). "Multiple co-regulatory elements and IHF are necessary for the control of fimB expression in response to sialic acid and N-acetylglucosamine in Escherichia coli K-12." Mol Microbiol 63(4);1223-36. PMID: 17238917

Titgemeyer94: Titgemeyer F, Reizer J, Reizer A, Saier MH (1994). "Evolutionary relationships between sugar kinases and transcriptional repressors in bacteria." Microbiology 140 ( Pt 9);2349-54. PMID: 7952186

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

UniProt10b: 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."

Vogler89: Vogler AP, Lengeler JW (1989). "Analysis of the nag regulon from Escherichia coli K12 and Klebsiella pneumoniae and of its regulation." Mol Gen Genet 219(1-2);97-105. PMID: 2693951

Other References Related to Gene Regulation

Harley87: Harley CB, Reynolds RP (1987). "Analysis of E. coli promoter sequences." Nucleic Acids Res 15(5);2343-61. PMID: 3550697

Plumbridge93: Plumbridge J, Kolb A (1993). "DNA loop formation between Nag repressor molecules bound to its two operator sites is necessary for repression of the nag regulon of Escherichia coli in vivo." Mol Microbiol 10(5);973-81. PMID: 7934873

Plumbridge96: Plumbridge J (1996). "How to achieve constitutive expression of a gene within an inducible operon: the example of the nagC gene of Escherichia coli." J Bacteriol 178(9);2629-36. PMID: 8626331

Plumbridge98b: Plumbridge J, Kolb A (1998). "DNA bending and expression of the divergent nagE-B operons." Nucleic Acids Res 26(5);1254-60. PMID: 9469834


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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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