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Escherichia coli K-12 substr. MG1655 Transporter: copper / silver efflux system

Synonyms: CusCFBA

Subunit composition of copper / silver efflux system = [CusC]3[CusB]6[CusF][CusA]3
         copper / silver efflux system - outer membrane porin = CusC (summary available)
         copper / silver efflux system - membrane fusion protein = CusB (summary available)
         copper / silver efflux system - periplasmic binding protein and metallochaperone = CusF (extended summary available)
         copper / silver efflux system - membrane subunit = CusA (summary available)

Summary:
The cusCFBA operon in E. coli K-12 encodes proteins that function together as a copper/silver efflux system. CusCBA is a tripartite complex that spans both the inner and outer membrane and, along with the periplasmic chaperone CusF, functions to export copper and silver ions from both the the cytoplasm and the periplasm to the extracellular environment. CusC forms a channel in the outer membrane, CusB is a member of the membrane fusion protein (MFP) family and CusA is a resistance-nodulation-division (RND) permease. CusF is the periplasmic copper binding protein [Franke01, Grass01, Franke03, Bagai08]. The function of a membrane fusion protein like CusB may be to bring the outer membrane factor, CusC, closer to the resistance-nodulation-division permease, CusA.

Through it's efflux function, CusCFBA helps to protect E. coli K-12 from high levels of exogenous copper and silver however its primary physiological role may be to export endogenous copper(I) ions that accumulate in the periplasm under anaerobic amino acid limitation (a host-relevant environment). Free Cu(I) accumulates in the periplasmic space of E. coli grown under anaerobic amino acid limitation largely due to lack of methionine which is the principal intracellular Cu(I) chelator, although anaerobiosis will also favor the accumulation of Cu(I) over Cu(II). ΔcopA and/or ΔcusC mutants show compromised growth during fumarate respiration under anaerobic and amino acid-limited conditions possibly due to Cu(I) induced damage to the Fe-S clusters of fumarate reductase [Fung13].

CusA contains 12 transmembrane (TM) segments and a large periplasmic domain formed from two loops located between TM1 and 2 and TM7 and 8 [Nishino01, Su11]. As an RND transporter, CusA probably forms trimers in vivo, but it forms a mixture of oligomers in detergent solution [Stroebel07, Su11]. The amino acids M573, M623, M672, D405, E412, and A399 of CusA are essential for copper tolerance [Franke03].

CusB is monomeric in solution [Bagai07]. The amino acids M21, M36, and M38 of CusB are involved in metal binding - mutations at these sites result in reduced Ag(I) binding affinity and show reduced copper tolerance [Bagai07].

A co-crystal structure of the CusBA complex has been resolved at 2.9Å. The trimeric CusA permease directly contacts with 6 CusB molecules which form a hexameric funnel-like structure [Su11]. Crystal structures of CusBA in complex with copper(I) are also available [Su12].

Copper and silver extrusion through CusCFBA is dependent upon the proton-motive-force [Li97]. Selectable silver resistance is mediated by the CusCFBA system [Lok08]. An in-frame chromosomal deletion mutant of cusA yielded a silver-sensitive E. coli mutant strain which did not differ in copper resistance to its isogenic parent [Franke01, Gupta01]. When combined with a mutation in cueO which is responsible for copper tolerance under aerobic conditions, cusA, cusB, cusC, and cusF mutants are copper-sensitive [Franke03]. Overexpression of cusA reversed the L-cysteine-induced growth inhibition of a tnaA mutant [Yamada06]. Overexpression also reduced levels of intracellular L-cysteine [Yamada06]. Induced expression of cusAB from a plasmid results in resistance to fosfomycin [Nishino01]. The phenotypes of cusA and copA mutants are not additive, so it has been suggested that the CusCFBA system may only be involved in export of copper and silver from the periplasm [Grass01].

The cusCFBA operon is induced upon addition of CuSO4 [Yamamoto05a] or ZnSO4 [Lee05d]. Induction is dependent upon the CusRS two-component system [Munson00, Yamamoto05a]. Northern hybridization, RT-PCR, primer extension analyses, and expression of an operon fusion indicate that cusCFBA mRNA is induced by the presence of silver and copper ions [Franke01]. CusF appears in the periplasmic space after induction with CuCl2 [Franke03]. cusB expression is induced by indole [Hirakawa05].

Reviews: [Rensing03, Nies03, Silver03, Su11a, Long12, Mealman12, Delmar13]
Comment: [Outten13]

Citations: [Franz08, Bleuel05, Outten01a]

Relationship Links: PDB:Structure:3NE5

Gene-Reaction Schematic: ?

GO Terms:

Molecular Function: GO:0005375 - copper ion transmembrane transporter activity Inferred from experiment [Franke03]
GO:0015080 - silver ion transmembrane transporter activity Inferred from experiment [Lok08]
Cellular Component: GO:0030313 - cell envelope Inferred by computational analysis Inferred from experiment [Su11]

Credits:
Curated 12-Nov-2008 by Johnson A , JCVI
Last-Curated ? 02-Feb-2014 by Mackie A , Macquarie University


Enzymatic reaction of: export of Cu+ (copper / silver efflux system)


Enzymatic reaction of: Export of Ag+ (copper / silver efflux system)


Subunit of copper / silver efflux system: copper / silver efflux system - outer membrane porin

Synonyms: IbeB, CusC, YlcB, AgrC

Gene: cusC Accession Numbers: G6320 (EcoCyc), b0572, ECK0564

Locations: outer membrane

Sequence Length: 457 AAs

Molecular Weight: 50.27 kD (from nucleotide sequence)

GO Terms:

Biological Process: GO:0006878 - cellular copper ion homeostasis Inferred from experiment [Franke03]
GO:0010272 - response to silver ion Inferred from experiment [Franke01, Lok08]
GO:0010273 - detoxification of copper ion Inferred from experiment [Franke03]
GO:0018345 - protein palmitoylation Inferred from experiment [Kulathila11]
GO:0046688 - response to copper ion Inferred from experiment [Franke03, Munson00, Yamamoto05a]
GO:0060003 - copper ion export Inferred from experiment [Franke03, Franke01]
GO:0070207 - protein homotrimerization Inferred from experiment [Kulathila11]
GO:0006810 - transport Inferred by computational analysis [UniProtGOA11, GOA01]
GO:0006811 - ion transport Inferred by computational analysis [UniProtGOA11]
Molecular Function: GO:0005375 - copper ion transmembrane transporter activity Inferred from experiment [Franke03]
GO:0005507 - copper ion binding Inferred from experiment [Franke03]
GO:0005515 - protein binding Inferred from experiment [Franke03]
GO:0019992 - diacylglycerol binding Inferred from experiment [Kulathila11]
GO:0005215 - transporter activity Inferred by computational analysis [GOA01]
GO:0008289 - lipid binding Inferred by computational analysis [GOA01]
GO:0015288 - porin activity Inferred by computational analysis [UniProtGOA11]
Cellular Component: GO:0009279 - cell outer membrane Inferred by computational analysis [UniProtGOA11a, UniProtGOA11, DiazMejia09, Munson00]
GO:0016020 - membrane Inferred by computational analysis [UniProtGOA11, GOA01]
GO:0016021 - integral component of membrane Inferred by computational analysis [UniProtGOA11]
GO:0046930 - pore complex Inferred by computational analysis [UniProtGOA11]

MultiFun Terms: cell structure membrane
extrachromosomal transposon related

Unification Links: DIP:DIP-9347N , EcoliWiki:b0572 , ModBase:P77211 , PR:PRO_000022351 , Pride:P77211 , Protein Model Portal:P77211 , RefSeq:NP_415104 , SMR:P77211 , String:511145.b0572 , Swiss-Model:P77211 , UniProt:P77211

Relationship Links: InterPro:IN-FAMILY:IPR003423 , InterPro:IN-FAMILY:IPR010131 , PDB:Structure:3PIK , Pfam:IN-FAMILY:PF02321 , Prosite:IN-FAMILY:PS51257

Summary:
CusC is an outer membrane factor involved in the detoxification of copper and silver ions in E. coli as part of the CusCFBA copper/silver efflux system. A crystal structure of CusC has been solved to 2.3 Å. The CusC trimer forms a large continuous internal cavity with a cylindrical shape. Each monomer contributes 4 β strands to the outer membrane β barrel structure and 4 α helices to the periplasmic α barrel. The structure also suggests that CusC contains membrane anchoring acyl chains at the N-terminal cysteine residue of each monomer [Kulathila11]

Essentiality data for cusC 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]

Subunit of copper / silver efflux system: copper / silver efflux system - membrane fusion protein

Synonyms: CusB, YlcD, AgrB

Gene: cusB Accession Numbers: G6322 (EcoCyc), b0574, ECK0566

Locations: periplasmic space, membrane

Sequence Length: 407 AAs

Molecular Weight: 44.305 kD (from nucleotide sequence)

GO Terms:

Biological Process: GO:0006878 - cellular copper ion homeostasis Inferred from experiment [Franke03, Bagai07]
GO:0010272 - response to silver ion Inferred from experiment [Franke01, Lok08]
GO:0010273 - detoxification of copper ion Inferred from experiment [Franke03, Bagai07]
GO:0015679 - plasma membrane copper ion transport Inferred from experiment [Franke03]
GO:0046688 - response to copper ion Inferred from experiment [Franke03, Franke01, Yamamoto05a, Bagai07]
GO:0060003 - copper ion export Inferred from experiment [Franke03]
GO:0006810 - transport Inferred by computational analysis [UniProtGOA11]
GO:0006811 - ion transport Inferred by computational analysis [UniProtGOA11]
GO:0006825 - copper ion transport Inferred by computational analysis [UniProtGOA11]
GO:0055085 - transmembrane transport Inferred by computational analysis [GOA01]
Molecular Function: GO:0005375 - copper ion transmembrane transporter activity Inferred from experiment [Franke03]
GO:0005507 - copper ion binding Inferred from experiment [Bagai07]
GO:0005515 - protein binding Inferred from experiment [Arifuzzaman06, Franke03]
GO:0046914 - transition metal ion binding Inferred from experiment [Bagai08, Bagai07]
Cellular Component: GO:0030288 - outer membrane-bounded periplasmic space Inferred from experiment [Su09a]
GO:0016020 - membrane Inferred by computational analysis [GOA01]

MultiFun Terms: cell processes protection drug resistance/sensitivity
transport Accessory Factors Involved in Transport

Unification Links: DIP:DIP-9346N , EcoliWiki:b0574 , ModBase:P77239 , PR:PRO_000022350 , Pride:P77239 , Protein Model Portal:P77239 , RefSeq:NP_415106 , SMR:P77239 , String:511145.b0574 , UniProt:P77239

Relationship Links: InterPro:IN-FAMILY:IPR006143 , PDB:Structure:3H94 , PDB:Structure:3NE5 , PDB:Structure:3OOC , PDB:Structure:3OPO , PDB:Structure:3OW7 , PDB:Structure:3T51 , PDB:Structure:3T53 , PDB:Structure:3T56 , PDB:Structure:4DNR , PDB:Structure:4DNT , PDB:Structure:4DOP

Summary:
CusB is a membrane fusion protein involved in the detoxification of copper and silver ions in E. coli as part of the CusCFBA copper/silver efflux system. Crystal structures of CusB in the absence and presence of silver and copper ions have been described [Su09a]. Cus B consists of 4 major domains: 3 β-strand domains and one α-helical domain [Su09a]. Two distinct conformations of CusB were found in single crystals suggesting that CusB exhibits conformational flexibility [Su09a].

Citations: [Silver03]

Essentiality data for cusB 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]

Subunit of copper / silver efflux system: copper / silver efflux system - periplasmic binding protein and metallochaperone

Synonyms: CusX, CusF, YlcC, ORF110, AgrF

Gene: cusF Accession Numbers: G6321 (EcoCyc), b0573, ECK0565

Locations: periplasmic space

Sequence Length: 110 AAs

Molecular Weight: 12.251 kD (from nucleotide sequence)

Molecular Weight: 10.0 kD (experimental) [Franke03]

GO Terms:

Biological Process: GO:0006878 - cellular copper ion homeostasis Inferred from experiment [Franke03]
GO:0010043 - response to zinc ion Inferred from experiment [Lee05d]
GO:0010272 - response to silver ion Inferred from experiment [Franke01, Lok08]
GO:0010273 - detoxification of copper ion Inferred from experiment [Franke03]
GO:0046688 - response to copper ion Inferred from experiment [Franke01, Yamamoto05a]
Molecular Function: GO:0005507 - copper ion binding Inferred from experiment [Franke03, Astashkin05, Loftin05, Kittleson06, Loftin07, Xue08]
GO:0005515 - protein binding Inferred from experiment [Franke03]
GO:0016530 - metallochaperone activity Inferred from experiment [Bagai08]
GO:0016531 - copper chaperone activity Inferred from experiment [Bagai08]
GO:0046914 - transition metal ion binding Inferred from experiment [Bagai08, Kittleson06, Loftin07]
GO:0046872 - metal ion binding Inferred by computational analysis [UniProtGOA11]
Cellular Component: GO:0030288 - outer membrane-bounded periplasmic space Inferred from experiment Inferred by computational analysis [DiazMejia09, Franke03]
GO:0042597 - periplasmic space Inferred by computational analysis Inferred from experiment [Franke03, UniProtGOA11a, UniProtGOA11]

MultiFun Terms: cell processes adaptations
transport

Unification Links: DIP:DIP-9350N , EcoliWiki:b0573 , PR:PRO_000022352 , Protein Model Portal:P77214 , RefSeq:NP_415105 , SMR:P77214 , String:511145.b0573 , Swiss-Model:P77214 , UniProt:P77214

Relationship Links: InterPro:IN-FAMILY:IPR021647 , PDB:Structure:1zeq , PDB:Structure:2qcp , PDB:Structure:2vb2 , PDB:Structure:2vb3 , PDB:Structure:3E6Z , Pfam:IN-FAMILY:PF11604

Summary:
CusF is a periplasmic binding protein involved in the detoxification of copper and silver ions in E. coli as part of the CusCFBA copper/silver efflux system.

CusF forms a five-stranded β-barrel and has been crystallized in its apo form as well as with bound Ag(I) or Cu(I) [Loftin05, Loftin07, Xue08]. CusF is a metallochaperone that specifically binds Ag(I) and Cu(I), but not Cu(II) [Kittleson06] despite earlier evidence regarding binding of Cu(II) [Astashkin05]. CusF transfers metal directly to CusB for export [Bagai08]. CusF is a pink copper-binding protein and binds one copper ion per monomer [Franke03]. The histidine residue at position 58 and the two methionine residues at positions 69 and 71 are essential for copper/silver binding [Franke03, Kittleson06]. Cu(I) binding also involves a strong interaction between the metal ion and the aromatic ring of a tryptophan residue at position 44 [Xue08, Loftin09, Chakravorty11]. The UV-vis spectrum of copper-containing CusF showed an absorption-maximum around 510 nm, which has not been reported for any other copper protein [Franke03].

Comment: [Franz08]

Citations: [Bagchi13]

Essentiality data for cusF 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]

Subunit of copper / silver efflux system: copper / silver efflux system - membrane subunit

Synonyms: YbdE, AgrA

Gene: cusA Accession Numbers: EG12367 (EcoCyc), b0575, ECK0567

Locations: inner membrane

Sequence Length: 1047 AAs

Molecular Weight: 114.71 kD (from nucleotide sequence)

GO Terms:

Biological Process: GO:0006878 - cellular copper ion homeostasis Inferred from experiment [Grass01]
GO:0010272 - response to silver ion Inferred from experiment [Franke01, Gupta01, Lok08]
GO:0010273 - detoxification of copper ion Inferred from experiment [Franke03, Grass01]
GO:0015673 - silver ion transport Inferred from experiment [Gupta01]
GO:0015679 - plasma membrane copper ion transport Inferred from experiment [Franke03, Grass01]
GO:0046688 - response to copper ion Inferred from experiment [Franke03, Franke01, Yamamoto05a]
GO:0060003 - copper ion export Inferred from experiment [Franke03, Grass01]
GO:1902601 - silver ion transmembrane transport Inferred from experiment [Gupta01]
GO:0006810 - transport Inferred by computational analysis [UniProtGOA11, GOA01]
GO:0006811 - ion transport Inferred by computational analysis [UniProtGOA11]
GO:0006812 - cation transport Inferred by computational analysis [GOA01]
GO:0006825 - copper ion transport Inferred by computational analysis [UniProtGOA11]
Molecular Function: GO:0005375 - copper ion transmembrane transporter activity Inferred from experiment [Franke03, Grass01]
GO:0005507 - copper ion binding Inferred by computational analysis Inferred from experiment [Franke03]
GO:0005515 - protein binding Inferred from experiment [Franke03]
GO:0015080 - silver ion transmembrane transporter activity Inferred from experiment [Gupta01]
GO:0005215 - transporter activity Inferred by computational analysis [GOA01]
GO:0008324 - cation transmembrane transporter activity Inferred by computational analysis [GOA01]
Cellular Component: GO:0005886 - plasma membrane Inferred from experiment Inferred by computational analysis [UniProtGOA11a, UniProtGOA11, DiazMejia09, Daley05, Long10]
GO:0016021 - integral component of membrane Inferred from experiment Inferred by computational analysis [UniProtGOA11, GOA01, Long10]
GO:0016020 - membrane Inferred by computational analysis [UniProtGOA11, GOA01]

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

Unification Links: DIP:DIP-9345N , EcoliWiki:b0575 , ModBase:P38054 , PR:PRO_000022349 , Pride:P38054 , Protein Model Portal:P38054 , RefSeq:NP_415107 , String:511145.b0575 , UniProt:P38054

Relationship Links: InterPro:IN-FAMILY:IPR001036 , InterPro:IN-FAMILY:IPR004763 , InterPro:IN-FAMILY:IPR027463 , PDB:Structure:3K07 , PDB:Structure:3K0I , PDB:Structure:3KSO , PDB:Structure:3KSS , PDB:Structure:3NE5 , PDB:Structure:3T51 , PDB:Structure:3T53 , PDB:Structure:3T56 , PDB:Structure:4DNR , PDB:Structure:4DNT , PDB:Structure:4DOP , Pfam:IN-FAMILY:PF00873 , Prints:IN-FAMILY:PR00702

Summary:
CusA is a member of the Resistance-Nodulation-Cell Division (RND) Transporter Superfamily and is involved in the detoxification of copper and silver ions in E. coli as part of the CusCFBA copper/silver efflux system.

Crystal structures suggest that CusA uses methionine pairs or clusters to export copper and silver ions from both the cytoplasm and the periplasm [Long10]. Purified CusA reconstituted into liposomes is able to transport silver ions [Su11a]. Transport is abolished in CusA mutants in which key methionine residues have been substituted and a model for transport involving a stepwise methionine shuttle has been proposed [Su11a].

Citations: [Silver03]

Essentiality data for cusA 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]

References

Arifuzzaman06: Arifuzzaman M, Maeda M, Itoh A, Nishikata K, Takita C, Saito R, Ara T, Nakahigashi K, Huang HC, Hirai A, Tsuzuki K, Nakamura S, Altaf-Ul-Amin M, Oshima T, Baba T, Yamamoto N, Kawamura T, Ioka-Nakamichi T, Kitagawa M, Tomita M, Kanaya S, Wada C, Mori H (2006). "Large-scale identification of protein-protein interaction of Escherichia coli K-12." Genome Res 16(5);686-91. PMID: 16606699

Astashkin05: Astashkin AV, Raitsimring AM, Walker FA, Rensing C, McEvoy MM (2005). "Characterization of the copper(II) binding site in the pink copper binding protein CusF by electron paramagnetic resonance spectroscopy." J Biol Inorg Chem 10(3);221-30. PMID: 15770503

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

Bagai07: Bagai I, Liu W, Rensing C, Blackburn NJ, McEvoy MM (2007). "Substrate-linked conformational change in the periplasmic component of a Cu(I)/Ag(I) efflux system." J Biol Chem 282(49);35695-702. PMID: 17893146

Bagai08: Bagai I, Rensing C, Blackburn NJ, McEvoy MM (2008). "Direct metal transfer between periplasmic proteins identifies a bacterial copper chaperone." Biochemistry 47(44);11408-14. PMID: 18847219

Bagchi13: Bagchi P, Morgan MT, Bacsa J, Fahrni CJ (2013). "Robust affinity standards for Cu(I) biochemistry." J Am Chem Soc 135(49);18549-59. PMID: 24298878

Bleuel05: Bleuel C, Grosse C, Taudte N, Scherer J, Wesenberg D, Krauss GJ, Nies DH, Grass G (2005). "TolC is involved in enterobactin efflux across the outer membrane of Escherichia coli." J Bacteriol 187(19);6701-7. PMID: 16166532

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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

Franke01: Franke S, Grass G, Nies DH (2001). "The product of the ybdE gene of the Escherichia coli chromosome is involved in detoxification of silver ions." Microbiology 2001;147(Pt 4);965-72. PMID: 11283292

Franke03: Franke S, Grass G, Rensing C, Nies DH (2003). "Molecular analysis of the copper-transporting efflux system CusCFBA of Escherichia coli." J Bacteriol 185(13);3804-12. PMID: 12813074

Franz08: Franz KJ (2008). "Copper shares a piece of the pi." Nat Chem Biol 4(2);85-6. PMID: 18202673

Fung13: Fung DK, Lau WY, Chan WT, Yan A (2013). "Copper efflux is induced during anaerobic amino acid limitation in Escherichia coli to protect iron-sulfur cluster enzymes and biogenesis." J Bacteriol 195(20);4556-68. PMID: 23893112

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."

Grass01: Grass G, Rensing C (2001). "Genes involved in copper homeostasis in Escherichia coli." J Bacteriol 183(6);2145-7. PMID: 11222619

Gupta01: Gupta A, Phung LT, Taylor DE, Silver S (2001). "Diversity of silver resistance genes in IncH incompatibility group plasmids." Microbiology 147(Pt 12);3393-402. PMID: 11739772

Hirakawa05: Hirakawa H, Inazumi Y, Masaki T, Hirata T, Yamaguchi A (2005). "Indole induces the expression of multidrug exporter genes in Escherichia coli." Mol Microbiol 55(4);1113-26. PMID: 15686558

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

Kittleson06: Kittleson JT, Loftin IR, Hausrath AC, Engelhardt KP, Rensing C, McEvoy MM (2006). "Periplasmic metal-resistance protein CusF exhibits high affinity and specificity for both CuI and AgI." Biochemistry 45(37);11096-102. PMID: 16964970

Kulathila11: Kulathila R, Indic M, van den Berg B (2011). "Crystal structure of Escherichia coli CusC, the outer membrane component of a heavy metal efflux pump." PLoS One 6(1);e15610. PMID: 21249122

Lee05d: Lee LJ, Barrett JA, Poole RK (2005). "Genome-wide transcriptional response of chemostat-cultured Escherichia coli to zinc." J Bacteriol 187(3);1124-34. PMID: 15659689

Li97: Li XZ, Nikaido H, Williams KE (1997). "Silver-resistant mutants of Escherichia coli display active efflux of Ag+ and are deficient in porins." J Bacteriol 179(19);6127-32. PMID: 9324262

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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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