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Escherichia coli K-12 substr. MG1655 Transporter: glutamic acid:4-aminobutyrate antiporter



Gene: gadC Accession Numbers: G6786 (EcoCyc), b1492, ECK1486

Synonyms: acsA, xasA, GadC GABA APC transporter, glutamic acid:γ-aminobutyrate antiporter

Regulation Summary Diagram: ?

Summary:
GadC, a glutamic acid:γ-aminobutyrate antiporter, is part of the glutamate-dependent acid resistance system 2 (AR2) which confers resistance to extreme acid conditions. When cells are grown at pH 2.5 with glutamate, the internal pH reaches 4.2 which reflects the pH optimum of the glutamate decarboxylases [Richard04a]. Insertional inactivation of the gadC gene results in sensitivity to extreme acid conditions (pH 2-3) and eliminated glutamic acid enhancement of acid resistance [Hersh96]. The gadC gene is located downstream of the gadB gene encoding glutamic acid decarboxylase [Hersh96]. GadC mediates export of γ-aminobutyrate in exchange for glutamic acid. GadC is a member of the APC superfamily of amino acid transporters. AR2 also protects the cell during anaerobic phosphate starvation when glutamate is available by preventing damage from weak acids produced from carbohydrate fermentation. gadABC mutants have reduced viability after anaerobic phosphate starvation compared to wild-type [Moreau07].

Regulation has been described [Ma03]. Expression of gadA and gadBC is induced by GadE and GadXW [Takada07].

YhiE, GadC, Slp-YhiF, HdeA, and HdeD are involved in the resistance to low pH observed upon overexpression of ydeO [Masuda03].

Citations: [Lin95b, De99d, Tramonti06]

Gene Citations: [De99d, CastanieCornet01, Waterman03, Shimada07]

Locations: inner membrane

Map Position: [1,566,978 <- 1,568,513] (33.77 centisomes)
Length: 1536 bp / 511 aa

Molecular Weight of Polypeptide: 55.077 kD (from nucleotide sequence)

Unification Links: ASAP:ABE-0004973 , DIP:DIP-48121N , EchoBASE:EB2350 , EcoGene:EG12456 , EcoliWiki:b1492 , OU-Microarray:b1492 , PortEco:gadC , Pride:P63235 , Protein Model Portal:P63235 , RefSeq:NP_416009 , RegulonDB:G6786 , SMR:P63235 , String:511145.b1492 , UniProt:P63235

Relationship Links: InterPro:IN-FAMILY:IPR002293 , InterPro:IN-FAMILY:IPR004759 , Panther:IN-FAMILY:PTHR11785 , PDB:Structure:4DJI , PDB:Structure:4DJK , Pfam:IN-FAMILY:PF00324 , Pfam:IN-FAMILY:PF13520

In Paralogous Gene Group: 180 (2 members)

Gene-Reaction Schematic: ?

Genetic Regulation Schematic: ?

GO Terms:

Biological Process: GO:0051454 - intracellular pH elevation Inferred from experiment [Hersh96]
GO:0003333 - amino acid transmembrane transport Inferred by computational analysis [GOA01a]
GO:0006810 - transport Inferred by computational analysis [UniProtGOA11a]
GO:0006865 - amino acid transport Inferred by computational analysis [UniProtGOA11a, GOA01a]
Molecular Function: GO:0015171 - amino acid transmembrane transporter activity Inferred by computational analysis [GOA01a]
GO:0015297 - antiporter activity Inferred by computational analysis [UniProtGOA11a, Hersh96]
Cellular Component: GO:0005886 - plasma membrane Inferred from experiment Inferred by computational analysis [UniProtGOA11, UniProtGOA11a, DiazMejia09, Zhang07, Daley05]
GO:0016020 - membrane Inferred by computational analysis [UniProtGOA11a, GOA01a]
GO:0016021 - integral component of membrane Inferred by computational analysis [UniProtGOA11a, GOA01a]

MultiFun Terms: cell structure membrane
transport Electrochemical potential driven transporters Porters (Uni-, Sym- and Antiporters)

Essentiality data for gadC 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]
Yes [Feist07, Comment 4]

Credits:
Last-Curated ? 16-Apr-2007 by Johnson A , TIGR


Enzymatic reaction of: glutamic acid:4-aminobutyrate antiporter

Synonyms: glutamate:4-aminobutyrate antiport


Sequence Features

Feature Class Location Citations Comment
Transmembrane-Region 15 -> 35
[UniProt10]
UniProt: Helical;; Non-Experimental Qualifier: potential;
Transmembrane-Region 42 -> 62
[UniProt10]
UniProt: Helical;; Non-Experimental Qualifier: potential;
Transmembrane-Region 94 -> 114
[UniProt10]
UniProt: Helical;; Non-Experimental Qualifier: potential;
Transmembrane-Region 128 -> 148
[UniProt10]
UniProt: Helical;; Non-Experimental Qualifier: potential;
Transmembrane-Region 158 -> 178
[UniProt10]
UniProt: Helical;; Non-Experimental Qualifier: potential;
Transmembrane-Region 201 -> 221
[UniProt10]
UniProt: Helical;; Non-Experimental Qualifier: potential;
Transmembrane-Region 240 -> 260
[UniProt10]
UniProt: Helical;; Non-Experimental Qualifier: potential;
Transmembrane-Region 292 -> 312
[UniProt10]
UniProt: Helical;; Non-Experimental Qualifier: potential;
Transmembrane-Region 336 -> 356
[UniProt10]
UniProt: Helical;; Non-Experimental Qualifier: potential;
Transmembrane-Region 367 -> 387
[UniProt10]
UniProt: Helical;; Non-Experimental Qualifier: potential;
Transmembrane-Region 413 -> 433
[UniProt10]
UniProt: Helical;; Non-Experimental Qualifier: potential;
Transmembrane-Region 446 -> 466
[UniProt10]
UniProt: Helical;; Non-Experimental Qualifier: potential;


Gene Local Context (not to scale): ?

Transcription Units:

Notes:

History:
Markus Krummenacker on Tue Oct 14, 1997:
Gene object created from Blattner lab Genbank (v. M52) entry.


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

CastanieCornet01: Castanie-Cornet MP, Foster JW (2001). "Escherichia coli acid resistance: cAMP receptor protein and a 20 bp cis-acting sequence control pH and stationary phase expression of the gadA and gadBC glutamate decarboxylase genes." Microbiology 2001;147(Pt 3);709-15. PMID: 11238978

Daley05: Daley DO, Rapp M, Granseth E, Melen K, Drew D, von Heijne G (2005). "Global topology analysis of the Escherichia coli inner membrane proteome." Science 308(5726);1321-3. PMID: 15919996

De99d: De Biase D, Tramonti A, Bossa F, Visca P (1999). "The response to stationary-phase stress conditions in Escherichia coli: role and regulation of the glutamic acid decarboxylase system." Mol Microbiol 32(6);1198-211. PMID: 10383761

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

Feist07: Feist AM, Henry CS, Reed JL, Krummenacker M, Joyce AR, Karp PD, Broadbelt LJ, Hatzimanikatis V, Palsson BO (2007). "A genome-scale metabolic reconstruction for Escherichia coli K-12 MG1655 that accounts for 1260 ORFs and thermodynamic information." Mol Syst Biol 3;121. PMID: 17593909

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."

Hersh96: Hersh BM, Farooq FT, Barstad DN, Blankenhorn DL, Slonczewski JL (1996). "A glutamate-dependent acid resistance gene in Escherichia coli." J Bacteriol 1996;178(13);3978-81. PMID: 8682809

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

Lin95b: Lin J, Lee IS, Frey J, Slonczewski JL, Foster JW (1995). "Comparative analysis of extreme acid survival in Salmonella typhimurium, Shigella flexneri, and Escherichia coli." J Bacteriol 177(14);4097-104. PMID: 7608084

Ma03: Ma Z, Gong S, Richard H, Tucker DL, Conway T, Foster JW (2003). "GadE (YhiE) activates glutamate decarboxylase-dependent acid resistance in Escherichia coli K-12." Mol Microbiol 49(5);1309-20. PMID: 12940989

Masuda03: Masuda N, Church GM (2003). "Regulatory network of acid resistance genes in Escherichia coli." Mol Microbiol 48(3);699-712. PMID: 12694615

Moreau07: Moreau PL (2007). "The lysine decarboxylase CadA protects Escherichia coli starved of phosphate against fermentation acids." J Bacteriol 189(6);2249-61. PMID: 17209032

Richard04a: Richard H, Foster JW (2004). "Escherichia coli glutamate- and arginine-dependent acid resistance systems increase internal pH and reverse transmembrane potential." J Bacteriol 186(18);6032-41. PMID: 15342572

Shimada07: Shimada T, Hirao K, Kori A, Yamamoto K, Ishihama A (2007). "RutR is the uracil/thymine-sensing master regulator of a set of genes for synthesis and degradation of pyrimidines." Mol Microbiol 66(3);744-57. PMID: 17919280

Takada07: Takada A, Umitsuki G, Nagai K, Wachi M (2007). "RNase E is required for induction of the glutamate-dependent acid resistance system in Escherichia coli." Biosci Biotechnol Biochem 71(1);158-64. PMID: 17213667

Tramonti06: Tramonti A, De Canio M, Delany I, Scarlato V, De Biase D (2006). "Mechanisms of transcription activation exerted by GadX and GadW at the gadA and gadBC gene promoters of the glutamate-based acid resistance system in Escherichia coli." J Bacteriol 188(23);8118-27. PMID: 16980449

UniProt10: UniProt Consortium (2010). "UniProt version 2010-07 released on 2010-06-15 00:00:00." 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."

Waterman03: Waterman SR, Small PL (2003). "Transcriptional expression of Escherichia coli glutamate-dependent acid resistance genes gadA and gadBC in an hns rpoS mutant." J Bacteriol 185(15);4644-7. PMID: 12867478

Zhang07: Zhang N, Chen R, Young N, Wishart D, Winter P, Weiner JH, Li L (2007). "Comparison of SDS- and methanol-assisted protein solubilization and digestion methods for Escherichia coli membrane proteome analysis by 2-D LC-MS/MS." Proteomics 7(4);484-93. PMID: 17309111

Other References Related to Gene Regulation

Bradley07: Bradley MD, Beach MB, de Koning AP, Pratt TS, Osuna R (2007). "Effects of Fis on Escherichia coli gene expression during different growth stages." Microbiology 153(Pt 9);2922-40. PMID: 17768236

CastanieCornet07: Castanie-Cornet MP, Treffandier H, Francez-Charlot A, Gutierrez C, Cam K (2007). "The glutamate-dependent acid resistance system in Escherichia coli: essential and dual role of the His-Asp phosphorelay RcsCDB/AF." Microbiology 153(Pt 1);238-46. PMID: 17185552

Giangrossi05: Giangrossi M, Zattoni S, Tramonti A, De Biase D, Falconi M (2005). "Antagonistic role of H-NS and GadX in the regulation of the glutamate decarboxylase-dependent acid resistance system in Escherichia coli." J Biol Chem 280(22);21498-505. PMID: 15795232

Hirakawa10: Hirakawa H, Hayashi-Nishino M, Yamaguchi A, Nishino K (2010). "Indole enhances acid resistance in Escherichia coli." Microb Pathog 49(3);90-4. PMID: 20470880

Itou09: Itou J, Eguchi Y, Utsumi R (2009). "Molecular mechanism of transcriptional cascade initiated by the EvgS/EvgA system in Escherichia coli K-12." Biosci Biotechnol Biochem 73(4);870-8. PMID: 19352034

Johnson11: Johnson MD, Burton NA, Gutierrez B, Painter K, Lund PA (2011). "RcsB Is Required for Inducible Acid Resistance in Escherichia coli and Acts at gadE-Dependent and -Independent Promoters." J Bacteriol 193(14);3653-6. PMID: 21571995

Krin10: Krin E, Danchin A, Soutourina O (2010). "Decrypting the H-NS-dependent regulatory cascade of acid stress resistance in Escherichia coli." BMC Microbiol 10;273. PMID: 21034467

Ma02: Ma Z, Richard H, Tucker DL, Conway T, Foster JW (2002). "Collaborative regulation of Escherichia coli glutamate-dependent acid resistance by two AraC-like regulators, GadX and GadW (YhiW)." J Bacteriol 2002;184(24);7001-12. PMID: 12446650

Marzan13: Marzan LW, Hasan CM, Shimizu K (2013). "Effect of acidic condition on the metabolic regulation of Escherichia coli and its phoB mutant." Arch Microbiol 195(3);161-71. PMID: 23274360

Moen09: Moen B, Janbu AO, Langsrud S, Langsrud O, Hobman JL, Constantinidou C, Kohler A, Rudi K (2009). "Global responses of Escherichia coli to adverse conditions determined by microarrays and FT-IR spectroscopy." Can J Microbiol 55(6);714-28. PMID: 19767843

Pesavento08: Pesavento C, Becker G, Sommerfeldt N, Possling A, Tschowri N, Mehlis A, Hengge R (2008). "Inverse regulatory coordination of motility and curli-mediated adhesion in Escherichia coli." Genes Dev 22(17);2434-46. PMID: 18765794

Pesavento12: Pesavento C, Hengge R (2012). "The global repressor FliZ antagonizes gene expression by σS-containing RNA polymerase due to overlapping DNA binding specificity." Nucleic Acids Res 40(11);4783-93. PMID: 22323519

Tramonti02: Tramonti A, Visca P, De Canio M, Falconi M, De Biase D (2002). "Functional characterization and regulation of gadX, a gene encoding an AraC/XylS-like transcriptional activator of the Escherichia coli glutamic acid decarboxylase system." J Bacteriol 2002;184(10);2603-13. PMID: 11976288

Tramonti08: Tramonti A, De Canio M, De Biase D (2008). "GadX/GadW-dependent regulation of the Escherichia coli acid fitness island: transcriptional control at the gadY-gadW divergent promoters and identification of four novel 42 bp GadX/GadW-specific binding sites." Mol Microbiol 70(4);965-82. PMID: 18808381

Tucker03: Tucker DL, Tucker N, Ma Z, Foster JW, Miranda RL, Cohen PS, Conway T (2003). "Genes of the GadX-GadW regulon in Escherichia coli." J Bacteriol 185(10);3190-201. PMID: 12730179

Yoshida93: Yoshida T, Ueguchi C, Yamada H, Mizuno T (1993). "Function of the Escherichia coli nucleoid protein, H-NS: molecular analysis of a subset of proteins whose expression is enhanced in a hns deletion mutant." Mol Gen Genet 237(1-2);113-22. PMID: 8455549


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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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