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TCID	Name	Organismal Type	Example
2.A.6.1: The Heavy Metal Efflux (HME) Family
2.A.6.1.1	Heavy metal (Ni² and Co²) efflux pump, CnrA. Functions with CnrB (TC# 8.A.1.2.1) and CnrC (TC# 1.B.17.2.1) (Grass et al. 2000; Tibazarwa et al. 2000).	Gram-negative bacteria	CnrA of Cupriavidus (Ralstonia; Alcaligenes) metallidurans (eutrophus or eutropha) (P37972)
2.A.6.1.2	Heavy metal (Co²; Zn²; Cd²) efflux pump, CzcAB. Functions with CzcC (P13509; 1.B.17.2.2).	Gram-negative bacteria	CzcA/CzcB of Cupriavidus (Ralstonia; Alcaligenes) metallidurans (eutriphus or eutropha) CzcA (P13511) CzcB (P13510)
2.A.6.1.3	Silver ion (Ag⁺)-specific efflux pump	Gram-negative bacteria	SilA of Salmonella typhimurium
2.A.6.1.4	Cu⁺/Ag⁺ efflux pump, CusABCF (may pump ions from the periplasm to the external medium); CusF is a periplasmic Cu⁺/Ag⁺ binding receptor essential for full resistance (Franke et al., 2003). Bagai et al. (2007) reported that CusB (MFP) binds one molecule of Ag⁺ or Cu⁺ via four conserved methionines and induces a substrate-linked conformational change (Bagai et al., 2007). The crystal structures of CusB are available (Su et al., 2009). The crystal structure of the CusAB complex has been solved (PDB# 3K07) (Su et al., 2011a). CusC is listed under TC# 1.B.17.3.5. The metal-binding methionines play a role in restricting the substrates to monovalent heavy metals (Conroy et al., 2010). It has been reported to export L-cysteine (Yamada et al., 2006). Crystal structures of the CusA efflux pump suggested that methionine residues in a 3-methionine cluster, bind the metal as a transport intermediate (Long et al., 2010). Four methionine pairs in the transmembrane region, and one in the periplasmic domain may comprise the channel. Cu⁺ is exported from the cytoplasm to the extracellular space. The Cus efflux system removes Cu⁺ and Ag⁺ from both the cell cytoplasm and the periplasm via a "methionine shuttle" (Su et al., 2011b).	Gram-negative bacteria	CusCFBA of E. coli: CusA (RND) CusB (MFP) CusC (OMF) (see 1.B.17.3.5) CusF (BP)
2.A.6.1.5	The Zn²⁺, Cd²⁺, Pb²⁺ exporter, CzcCBA1 (induced by Zn²⁺, Cd²⁺, Pb²⁺, Ni²⁺, Co²⁺ and Hg²⁺ (Leedjarv et al., 2007))	Bacteria	CzcCBA1 of Pseudomonas putida CzcA1 (RND) (Q88RT6) CzcB1 (MFP) (Q88RT5) CzcC1 (OMF) (Q88RT4)
2.A.6.1.6	The Zn²⁺-specific exporter, ZneABC. The ZneB MFP plays an active role in substrate efflux through metal binding and release. Its 2.8 Å structure is available (De Angelis et al., 2010).	Proteobacteria	ZneABC of Cupriavidus (Ralstonia) metallidurans (eutrophus or eutropha) ZneC (DMF) (Q1LCD9) ZneA (RND) (Q1LCD8) ZneB (MFP) (Q1LCD7)
2.A.6.1.7	Putative Zn²⁺ exporter, Cus1ABC (induced by Zn²⁺; Moraleda-Muñoz et al., 2010)	δ-Proteobacteria	Cus1ABC of Myxococcus xanthus Cus1A (RND) (Q1DDM9) Cus1B (MFP) (Q1DDM8) Cus1C (OMF) (Q1DDM7)
2.A.6.1.8	Putative Cu²⁺ exporter, Cus2ABC (induced by Cu²⁺; Moraleda-Muñoz et al., 2010)	δ-Proteobacteria	Cus2ABC of Myxococcus xanthus Cus2A (RND) (Q1DDM4) Cus2B (MFP) (Q1DDM3) Cus2C (OMF) (Q1DDM2)
2.A.6.1.9	Putative heavy metal (Me²⁺) exporter, Czc1ABC (induced by heavy metals, but not Cu²⁺; Moraleda-Muñoz et al., 2010)	α-Proteobacteria	Czc1ABC of Myxococcus xanthus Czc1A (RND) (Q1D6S7) Czc1B (MFP) (Q1D6S8) Czc1C (OMF) (Q1D6S9)
2.A.6.1.10	Putative Cu²⁺ exporter, Czc2ABC. (induced by Cu²⁺ and other heavy metal ions; Moraleda-Muñoz et al., 2010)	δ-Proteobacteria	Czc2AB of Myxococcus xanthus Czc2A (RND) (Q1D665) Czc2B (MFP) (Q1D664)
2.A.6.1.11	Putative metal ion exporter (induced by starvation; Moraleda-Muñoz et al., 2010)	δ-Proteobacteria	Czc3ABC of Myxococcus xanthus Czc3A (RND) (Q1CVN2) Czc3B (MFP) (Q1CVN1) Czc3C (OMF) (Q1CVN0)
2.A.6.1.12	NccABC Ni²,Co², Cd²resistance efflux pump (Schmidt and Schlegel, 1994).	Gram-negative bacteria	NccABC of Alcaligenes xylosoxidans NccA (RND) (Q44586) NccB (MFP) (Q44585) NccC (OMF) (Q44584)
2.A.6.1.13	CzrABC Cd²⁺, Zn²⁺ resistance efflux pump (Hassan et al., 1999).	Gram-negative bacteria	CzrABC of Pseudomonas aeruginosa CzrA (RND) (Q9RLI8) CzrB (MFP) (Q9RLI9) CzrC (OMF) (Q9RLJ0)
2.A.6.1.14	CznABC Cd²⁺, Zn²⁺, Ni²⁺ resistance efflux pump. Required for urea modulation and gastric colonization (Stähler et al., 2006).	Gram-negative bacteria	CznABC of Helicobacter pylori CznA (RND) (O25622) CznB (MFP) (O25623) CznC (OMF) (O25624)
2.A.6.1.15	The CzrCBA operon is induced by Cd²⁺ and Zn²⁺. CzrCBA transports Cd²⁺, Zn²⁺, and Co²⁺ but not Ni²⁺ (Valencia et al., 2013, in press).	Bacteria	CzrCBA of Caulobacter crescentus NA1000 CzrA (RND) (B8H146) CzrB (MFP) (B8H144) CzrC (OMF) (B8H143)
2.A.6.1.16	The NczCBA operon is induced maximally by Ni²⁺ and Co²⁺, moderately by Zn²⁺ but not by Cd²⁺. NczCBA transports Ni²⁺ Co²⁺and probably Zn²⁺ (Valencia et al., 2013, in press).	Bacteria	NczCBA of Caulobacter crescentus NA1000 NczA (RND) (B8GZE9) NczB (MFP) (B8GZE8) NczC (OMF) (B8GZE7)
2.A.6.1.17	Zn² exporter, ZniA. Functions with an MFP and an OMF (Nies,2013, in Microbial Efflux Pumps, EW Yu, Q Zhang and MH Brown, editors, Caister Acadmic Press, 2013).	Proteobacteria	ZniA of Cupriavidus metallidurans
2.A.6.1.18	Ni², Co² exporter, NimA. Functions with an MFP and an OMF (Nies, 2013, in Microbial Efflux Pumps, EW Yu, Q Zhang and MH Brown, editors, Caister Acadmic Press, 2013).	Proteobacteria	NimA of Cupriavidus metallidurans
2.A.6.2: The (Largely Gram-negative Bacterial) Hydrophobe/Amphiphile Efflux-1 (HAE1) Family
2.A.6.2.1	Multidrug (acriflavin, doxorubicin, ethidium, rhodamine 6G, SDS, deoxycholate) resistance pump [required for normal chromosomal condensation and segregation as well as cell division] (Lau and Zgurskaya, 2005). Exports L-cysteine (Yamada et al., 2006).	Gram-negative bacteria	AcrEF (EnvCD) of E. coli AcrE (MFP) (P24180) AcrF (EnvD) (RND) (P24181)
2.A.6.2.2	Multidrug/dye/detergent/bile salt/organic solvent resistance pump (substrates include: chloramphenicol, tetracycline, erythromycin, nalidixic acid, fusidic acid, fluoroquinolones, lipophilic β-lactams, norfloxacin, doxorubicin, novobiocin, rifampin, trimethoprim, acriflavin, crystal violet, ethidium, disinfectants rhodamine-6G, TPP, benzalkonium, SDS, Triton X-100, deoxycholate/bile salts/organic solvents (alkanes), growth inhibitory steroid hormones (estradiola and progesterone), and phospholipids) (Elkins and Mullis, 2006) (Lateral entry of substrate from the lipid bilayer into AcrB and its homologues has been proposed.) (Yu et al., 2003a; 2003b) [Asymmetric trimer structure: Seeger et al., 2006]. Structure of a complex with YajC known (Törnroth-Horsefield et al., 2007). A covalently linked trimer of AcrB provides evidence for a peristaltic pump, alternative access, rotation mechanism (Takatsuka and Nikaido, 2009;Nikaido and Takatsuka, 2009; Pos, 2009) Further evidence for a rotatory mechanisms stems from kinetic analyses for cephalosporin efflux which can exhibit positive cooperativity (Nagano and Nikaido, 2009). May also export signaling molecules for cell-cell communication (Yang et al., 2006). The substrates may be captured in the lower cleft region of AcrB, then transported through the binding pocket, the gate and finally to the AcrB funnel that connects AcrB to TolC (Husain & Nikaido et al., 2010).	Gram-negative bacteria	AcrAB of E. coli AcrA (MFP) (P31223) AcrB (RND) (P31224)
2.A.6.2.3	Isoflavenoid efflux pump, IfeB	Gram-negative bacteria	IfeB of Agrobacterium tumefaciens
2.A.6.2.4	The multidrug resistance pump, AdeDE (exports amikacin, ceftazidime, chloramphenicol, ciprofloxacin, erythromycin, ethidium bromide, meropenem, rifampin, and tetracycline) (Chau et al., 2004).	Gram negative bacteria	AdeDE of Acinetobacter sp. 4356 AdeD (Q67GM1) AdeE (Q8GKU1)
2.A.6.2.5	Fatty acid, bile salt, gonadal steroid, antibacterial peptide efflux pump, MtrCDE (Kamal et al., 2007). Opening of the outer membrane protein channel, MtrE, in the tripartite efflux pump, MtrCDE, is induced by interaction with the membrane fusion partner, MtrC (Janganan et al., 2011).	Gram-negative bacteria	MtrCDE of Neisseria gonorrhoeae: MtrC (MFP) (P43505) MtrD (RND) (Q51073) MtrE (OMF) (Q51006)
2.A.6.2.6	Multiple drug; N-(3-oxododecanoyl)- L-homoserine lactone autoinducer efflux pump, MexB (functions with MexA (an MFP, 8.A.1) and OprM (an OMF, 1.B.17; see 2.A.6.2.21). All three interact with each other. MexA promotes assembly and stability of the complex (Nehme and Poole, 2007)). Exports β-lactams, fluoroquinolones, tetracycline, macrolides, chloramphenicol, biocides, and a toxic indole compound, CBR-4830, that targets the MreB actin (Robertson et al., 2007). Confers tolerance to tea tree oil and its monoterpene components Terpinen-4-ol, 1,8-cineole and α-terpineol (Papadopoulos et al., 2008) as well as the antimicrobial peptide, colistin (Pamp et al., 2008) (Mao et al., 2002; Poole, 2008). The crystal structure has been solved at 3.0Å resolution (Sennhauser et al., 2009). The MexA-OprM complex has an elongated cylindrical appearance (Trépout et al., 2010). Mutations affecting export of antibiotics with cytoplasmic targets have been identified (Ohene-Agyei et al. 2012).	Gram-negative bacteria	MexAB of Pseudomonas aeruginosa MexA (P52477) MexB (P52002)
2.A.6.2.7	Multidrug efflux pump, AcrD (exports aminoglycosides (amikacin, gentamicin, neomycin, kanamycin and tobramycin) as well as anionic detergents (SDS and deoxycholate) and growth inhibitory steroid hormones (estradiol and progesterone)(Elkins and Mullis, 2006)) (exports aminoglycosides from the periplasm as well as the cytoplasm) (Aires and Nikaido, 2005). (Also contributes to copper and zinc resistance; regulation is mediated by BaeSR, and indole, Cu²⁺ and Zn²⁺ induce (Nishino et al., 2007)). Exports L-cysteine (Yamada et al., 2006).	Gram-negative bacteria	AcrD of E. coli (P24177)
2.A.6.2.8	Multidrug efflux pump, ArpB (exports tetracycline, chloramphenicol, carbenicillin, streptomycin, erythromycin, novobiocin, etc.)	Gram-negative bacteria	ArpB of Pseudomonas putida
2.A.6.2.9	Solvent efflux pump, TtgABC (extrudes toluene, styrene, m-xylene, ethylbenzene and propylbenzene) (Teran et al., 2007).	Gram-negative bacteria	TtgABC of Pseudomonas putida: TtgA (Q9WWZ9) TtgB (O52248) TtgC (Q9WWZ8)
2.A.6.2.10	Solvent efflux pump, TtgDEF (extrudes only toluene and styrene) (Teran et al., 2007).	Gram-negative bacteria	TtgDEF of Pseudomonas putida: TtgD (Q9KWV5) TtgE (Q9KWV4) TtgF (Q9KWV3)
2.A.6.2.11	Solvent and antibiotic efflux pump, TtgGHI (SrpABC) (Kieboom et al. 1998; Terán et al., 2007) (solvents extruded include toluene, styrene, m-xylene, ethylbenzene and propylbenzene) (Teran et al., 2007). TtgGHI is the same as SrpABC (Kieboom et al., 1998)	Gram-negative bacteria	TtgGHI of Pseudomonas putida TtgG (Q93PU5) TtgH (Q93PU4) TtgI (Q93PU3)
2.A.6.2.12	Heteromeric multidrug/detergent resistance protein YegN/YegO (MdtB/MdtC) of E. coli (exports nalidixic acid, norfloxacin, cloxicillin, enoxacin, kanamycin, benzalkonium, bile salts, SDS and deoxycholate). It forms a complex with MdtA (an MFP, TC# 8.A.1.6.2). Drug resistance depends on the simultaneous presence of all three proteins (Baranova and Nikaido, 2002). (Also contributes to copper and zinc resistance; regulation is mediated by BaeSR, and indole, Cu² and Zn² induce (Nishino et al., 2007)). MdtB:C stoichiometry = 2:1; MdtB and MdtC may play different roles (Kim et al., 2010), MdtB transporting the proton and MdtC transporting the drug (Kim and Nikaido 2012).	Bacteria	MdtB/MedtC of E. coli MdtB (YegN) (P76398) MdtC (YegO) (P76399)
2.A.6.2.13	Multidrug/dye/detergent resistance protein, YhiV or MdtF (exports erythromycin, doxorubicin, crystal violet, ethidium, rhodamine 6G, TPP, benzalkonium, SDS, deoxycholate and growth inhibitory steroid hormones (estradiol and progesterone)(Elkins and Mullis, 2006))	Bacteria	YhiV of E. coli
2.A.6.2.14	SmeVWX MDR efflux pump. Drugs include chloramphenicol, quinolones, tetracyclines and aminoglycosides, but not β-lactams and erythromycin (Chen et al., 2011).	Proteobacteria	SmeVWX of Stenotrophomonas maltophilia SmeV (MFP) (B2FLY3) SmeW (RND) (B2FLY4) SmeX (OMF) (B2FLY6)
2.A.6.2.15	Multidrug efflux pump, MexD (exports β-lactams, fluoroquinolones, tetracycline, macrolides, chloramphenicol, biocides, including levofloxacin, carbenicillin, aztreonam, ceftazidime, cefepime, cefoperazone, piperacillin, erythromycin, azithromyein, chloramphenicol, etc.; Mao et al., 2002). Functions with MexC (MFP) and OprJ (OMF) (Mao et al., 2002; Poole, 2008).	Bacteria	MexD of Pseudomonas aeruginosa
2.A.6.2.16	Multidrug efflux pump, MexF (exports fluoroquinolones, chloramphenicol, biocides, xenobiotics and chloramphenicol; functions with MexE (MFP) and OprN (OMF)) (Kohler et al., 1997; Poole, 2008)	Bacteria	MexF of Pseudomonas aeruginosa (AAG05882)
2.A.6.2.17	Multidrug efflux pump, MexK (exports fluoroquinolones, tetracycline, macrolides, chloramphenicol; biocides, and triclosan [with MexJ but without OprM] as well as tetracycline, erythromycin [requiring both MexJ and OprM]; Chuanchuen et al., 2002). Can function with OpmH (BAC24099) instead of OprM (Poole, 2008).	Bacteria	MexK of Pseudomonas aeruginosa
2.A.6.2.18	The polycyclic aromatic hydrocarbon (phenanthrene; anthacene; fluoranthene)/drug (chloramphenicol; naldixic acid) exporter, EmhABC (Hearn et al., 2003; 2006)	Bacteria	EmhABC of Pseudomonas fluorescens EmhA (Q6V6X9) EmhB (Q6V6X8) EmhC (Q6V6X7)
2.A.6.2.19	The multidrug efflux pump, EefABC (exports chloramphenicol, ciprofloxacin, erythromycin, tetracycline and doxycycline) (Masi et al., 2005). EefC exhibits low ionic selectivity (Masi et al., 2007).	Bacteria	EefABC of Enterobacter aerogenes EefA (MFP) (Q8GC84) EefB (RND) (Q8GC83) EefC (OMF) (Q8GC82)
2.A.6.2.20	The toxoflavin (a phytotoxin) exporter, ToxGHI (Kim et al., 2004)	Bacteria	ToxGHI of Burkholderia glumae ToxG (MFP) (AAV52812) ToxH (RND) (AAV52813) ToxI (OMF) (AAV52814)
2.A.6.2.21	The multidrug (aminoglycosides, β-lactams, fluoroquinolones, macrolides, chloramphenicol, tetracycline, erythromycin, ofloxacin, etc.) efflux pump, MexXY-OprM (Jeannot et al., 2005)	Gram-negative bacteria	MexXY-OprM of Pseudomonas aeruginosa MexX, BAA34299 MexY, BAA34300 OprM, Q51487
2.A.6.2.22	The conjugated and unconjugated bile (bile-inducible)/multidrug (ethidium, ciprofloxacin, norfloxacin, tetracycline, cefotaxime, rifampicin, erythromycin, chloramphenicol, salicylate; drug-noninducible) efflux pump (Lin et al., 2005)	Bacteria	CmeABC of Campylobacter jejuni CmeA (MFP) (AAL74244) CmeB (RND) (AAL74245) CmeC (OMF) (AAL74246)
2.A.6.2.23	The multidrug (β-lactams, aminoglycerides (gentamycin and streptomycin) macrolides (erythromycin) and dye (acriflavin)) efflux pump, BpeAB-OprB (Chan et al., 2004; Chan and Chua, 2005). It also exports acyl homoserine lactones including N-octanoyl-homoserine lactone, N-decanoyl-homoserine lactone, N-(3-hydroxy)-octanoyl-homoserine lactone, N-(3-hydroxy)-decanoyl-homoserine lactone, N-(3-oxo)-decanoyl-homoserine lactone, and N-(3-oxo)-tetradecanoyl-homoserine lactone (Chan et al., 2007).	Gram-negative bacteria	BpeAB-OprB of Burkholderia pseudomallei BpeA (MFP) (AAQ94109) BpeB (RND) (AAQ94110) OprB (OMF) (AAQ94111)
2.A.6.2.24	The multidrug (aminoglycosides (e.g., streptomycin, gentamycin, neomycin, tobramycin, kanamycin and spectinomycin) and macrolides (e.g., erythromycin and clarithromycin, but not lincosamide and clindamycin)) efflux pump, AmrAB-OprA (Moore et al., 1999)	Gram-negative bacteria	AmrAB-OprA of Burkholderia pseudomallei AmrA (MFP) AAC27753 AmrB (RND) AAC27754 OprA (OMF)
2.A.6.2.25	The gold (Au²⁺) resistance efflux pump, GesABC (induced by GolS in the presence of Au²⁺; also mediates drug resistance when induced by Au²⁺ (Pontel et al., 2007). Also exports a variety of organic chemicals including chloramphenicol (Conroy et al., 2010).	Bacteria	GesABC of Salmonella enterica GesA (MFP) (Q8ZRG8) GesB (RND) (Q8ZRG9) GesC (OMF) (Q8ZRH0)
2.A.6.2.26	The multidrug efflux pump, VmeAB-VpoC (Matsuo et al., 2007).	Bacteria	VmeAB-VpoC of Vibrio parahaemolyticus: VmeA (MFP) (Q2AAU4) VmeB (RND) (Q2AAU3) VpoC (OMF) (Q87SJ8)
2.A.6.2.27	The Triclosan resistance efflux pump TriABC-OpmH (the only known RND pump requiring two MFPs) (Mima et al., 2007)	Bacteria	TriABC-OpmH of Pseudomonas aeruginosa TriA (MFP) (Q9I6X6) TriB (MFP) (Q9I6X5) TriC (RND) (Q9I6X4) OpmH (OMF) (Q9HUJ1)
2.A.6.2.28	Multidrug resistance efflux pump	Proteobacteria	AcrAB of Francisella tularensis AcrA (A4KT88) AcrB (A7YV33)
2.A.6.2.29	The AdeIJK MDR pump (contributes to resistance to β-lactams, chloramphenicol, tetracycline, erythromycin, lincosamides, fluoroquinolines, fusidic acid, tigecycline, novobiocin, rifampin, trimethoprim, acridine, safranin, pyronine, and sodium dodecyl sulfate) (Damier-Piolle et al., 2008)	Bacteria	AdeIJK of Acinetobacter baumannii AdeI (MFP) (Q2FD95) AdeJ (RND) (Q24LT7) AdeK (OMF) (Q24LT6)
2.A.6.2.30	VexEF-TolC mediates resistance to various antimicrobials; ethidium efflux is Na⁺-dependent (Rahman et al., 2007)	Gram-negative bacteria	VexEF / TolC of Vibrio cholerae VexE (MFP) (A6P7H2) VexF (RND) (A6P7H3) TolC (OMF) (Q9K2Y1)
2.A.6.2.31	Multidrug efflux pump, SdeAB-HasF (mediates fluoroquinolone efflux) (Begic and Worobec, 2008) (HasF is > 60% identical to TolC of E. coli (1.B.17.1.1))	Gram-negative bacteria	SdeAB-HasF of Serratia marcescens SdeA (MFP) (Q79MP5) SdeB (RND) (Q84GI9) HasF (OMF) (Q6GW09)
2.A.6.2.32	Multidrug efflux pump, MexHI OpmD (exports fluoroquinolones; Poole, 2008).	Bacteria	MexHI OpmD of Pseudomonas aeruginosa MexH (MFP) (Q9HWH5) MexI (RND) (Q9HWH4) OpmD (OMF) (Q9HWH3)
2.A.6.2.33	Multidrug efflux pump, MexVW OmpM (exports fluoroquinolones, microlides, chloramphenicol, and tetracycline) (Poole, 2008).	Bacteria	MexW of Pseudomonas aeruginosa MexW (RND) (Q9HW27)
2.A.6.2.34	Multidrug efflux pump, MexPQ-OpmE; export fluoroquinolones, tetracycline, macrolides and chloramphenicol (Poole, 2008)	Bacteria	MexPQ-OpmE of Pseudomonas aeruginosa MexP (MFP) (Q9HY86) MexQ (RND) (Q4LDT6) OpmE (OMF) (Q9HY88)
2.A.6.2.35	Multidrug efflux pump, MexMN-OprM; exports chloramphenicol (Poole, 2008)	Bacteria	MexMN-OprM of Pseudomonas aeruginosa MexM (MFP) (Q9I3R2) MexN (RND) (Q4LDT8)
2.A.6.2.36	Multidrug/detergent exporter. VexB (Bina et al., 2008b).	Bacteria	VexB of Vibrio cholerae (Q9KVI2)
2.A.6.2.37	Detergent exporter, VexD (Bina et al., 2008b).	Bacteria	VexD of Vibrio cholerae (A6P7H1)
2.A.6.2.38	Detergent exporter, VexK (Bina et al., 2008b).	Bacteria	VexK of Vibrio cholerae (Q9KRG9)
2.A.6.2.39	THe MuxABC-OpmB multidrug (aztreonam, macrolides, novobiocin and tetracycline) resistance efflux pump complex (with two RND-type proteins (MuxB and MuxC)), both required for activity (Mima et al., 2009).	Bacteria	MuxABC-OpmB complex of Pseudomonas aeruginosa MuxA (MFP) (PA2528) (Q9I0V5) MuxB (RND) (PA2527) (Q9I0V6) MuxC (RND) (PA2526) (Q9I0V7) OpmB (OMF) (Q9I0V8)
2.A.6.2.40	MDR pump, AdeABC. Exports chloramphenicol and tetracycline (Hassan et al., 2011).	Bacteria	AdeABC of Acinetobacter baumannii AdeA (MFP) (Q2FD71) AdeB (RND) (Q2FD70) AdeC (OMF) (Q2FD69)
2.A.6.2.41	SmeABC MDR efflux pump. Drugs include Ciprofloxacin (Cho et al., 2012).	Proteobacteria	SmeABC of Stenotrophomonas maltophilia SmeA (MFP) (Q9RBY9) SmeB (RND) (Q9RBY8) SmeC (OMF) (Q9RBY7)
2.A.6.2.42	SmeDEF MDR efflux pump. Mediates resistance to a wide range of drugs including ethidium bromide and norfloxacin (Alonso and Martínez, 2000). Regulated by SmeT and activated by insertion of the transposon, IS1246 (Gould and Avison, 2006).	Proteobacteria	SmeDEF of Stenotrophomonas maltophilia SmeD (MFP) (Q9F241) SmeE (RND) (Q9F240) SmeF (OMF) (Q9F239)
2.A.6.2.43	Multidrug resistance pump, SmeJK. Shown to export teracycline, minocycline, ciprofloxacin and levofloxacin (Gould et al., 2012).	Bacteria	SmeJK of Stenotrophomonas maltophilia D457 SmeJ (I0KTJ0) SmeK (I0KTJ1)
2.A.6.2.44	Multidrug efflux pump, AdeFGH. Mediates high level resistance to chloramphenicol, clindamycin, fluoroquinolones, and trimethoprim and decreased susceptibility to tetracycline-tigecycline and sulfonamides; susceptibility to β-lactams, erythromycin, aminoglycosides and rifampin was not affected. It also mediates increased resistance to ethidium bromide, safranin O, acridine orange, trimethoprim and sulfamethoxazole (Coyne et al. 2010).	γ-Proteobacteria	AdeFGH of Acinetobacter baumannii AdeF (MFP) (Q2FD82) AdeG (RND) (Q2FD81) AdeH (OMF) (Q2FD80)
2.A.6.3: The Putative Nodulation Factor Exporter (NFE) Family
2.A.6.3.1	Putative lipooligosaccharide nodulation factor exporter, NolG (1065 aas; previously thought to be 3 ORFs, NolGHI, an artifact due to sequencing errors and consequent frameshifting (Baev et al. 1991; Ardourel et al. 1994).	Gram-negative bacteria	NolG of Rhizobium meliloti (P25197)
2.A.6.3.2	NolG homologue, Atu4636	α-Proteobacteria	NolG of Agrobacterium tumefaciens (A9CGX6)
2.A.6.3.3	NolG homologue	γ-Proteobacteria	NolG of Acinetobacter baumanii (E8PBU7)
2.A.6.3.4	NolG homologue	δ-Proteobacteria	NolG of Myxococcus xanthus (Q1DEX6)
2.A.6.3.5	NolG homologue	Cyanobacteria	NolG of Synechococcus sp. PCC7335 (B4WH09)
2.A.6.3.6	NolG homologue	Firmicutes	NolG of Oceanobacillus iheyensis (Q8CX78)
2.A.6.3.7	Putative Cu² exporter, Cus3ABC. Induced by Cu²; Moraleda-Muñoz et al., 2010)	δ-Proteobacteria	Cus3ABC of Myxococcus xanthus Cus3A (RND) (Q1CZ65) Cus3B (MFP) (Q1CZ64) Cus3C (OMF) (Q1CZ66)
2.A.6.3.8	Efflux pump for antifungal and antibacterial syringopeptin and syringmycin lipodepsipeptides (see 1.D.35) as well as acriflavin, erythromycin and tetracycline, PseABC (Kang and Gross 2005).	Proteobacteria	PseABC of Pseudomonas syringae PseA (OMF) (L8NE56) PseB (MFP) (L8NGR5) PseC (RND) (L8NFZ8)
2.A.6.4: The SecDF (SecDF) Family
2.A.6.4.1	The secretory accessory proteins, SecDF. The first periplasmic domain of SecDF has been crystallized (Echizen et al., 2011). SecDF appears to function as a pmf-driven H⁺ transporter that functions as a chaperone to achieve ATP-dependent protein translocation (Tsukazaki et al., 2011).	Bacteria	SecDF of E. coli; SecD; SecF
2.A.6.4.2	Protein translocase subunit SecDF	Bacteria	SecDF of Bacillus subtilis
2.A.6.4.3	Protein translocase subunit SecDF	Bacteria	SecDF of Thermus thermophilus
2.A.6.5: The (Gram-positive Bacterial Putative) Hydrophobe/Amphiphile Efflux-2 (HAE2) Family
2.A.6.5.1	The antibiotic actinorhodin transport-associated protein, ActII3	Gram-positive bacteria	ActII3 of Streptomyces coelicolor
2.A.6.5.2	The phthiocerol dimycocerosate (PDIM) lipid exporter, MmpL7. Also confers high level isoniazid efflux and resistance (Pasca et al., 2005).	Gram-positive bacteria	MmpL7 of Mycobacterium tuberculosis ( P65370)
2.A.6.5.3	The putative glycopeptidolipid exporter, TmtpC (most similar to MmpL of M. leprae; implicated in sliding motility). May function with the MmpS4 protein of Mucobacterium smegmatis (A0QPN7) to form a scaffold for coupled biosynthesis and transport (Deshayes et al., 2010).	Gram-positive bacteria	TmtpC of Mycobacterium smegmatis
2.A.6.5.4	sulfolipid, 2,3-diacyl-α, α'-D-trehalose-2'-sulfate (sulfatide precursor) exporter, MmpL8 (Domenech et al., 2004; Seeliger et al. 2012 Seeliger et al. 2012).	Gram-positive bacteria	MmpL8 of Mycobacterium tuberculosis (CAB10022)
2.A.6.5.5	Mycobacterial heme acquisition system, Rv0202c - Rv0207c. Takes up free heme and heme from hemoglobin as an iron source. May function with Rv0206c (MmpL3; TC#2.A.6.5.6) and Rv0202c (Tullius et al., 2011). However, see description of MmpL3 (2.A.6.5.6)	Actinobacteria	Heme uptake system of Mycobacterium tuberculosis MmpL11 (P65374)
2.A.6.5.6	MmpL3 (Rv0206; 944 aas) May function with MmpL11 (TC# 2.A.6.5.5) (Tullius et al., 2011). MmpL3 exports trehalose monomycolate, involved in mycolic acid donation to the cell wall core (Tahlan et al., 2012). SQ109, a 1,2,-diamine related to ethambutol is an inhibitor of MmpL3 (Tahlan et al., 2012).	Bacteria	MmpL3 of Mycobacterium tuberculosis (O53657)
2.A.6.5.7	Siderophore export transporter, MmpL4 (Wells et al. 2013). Functions with MmpS4 (TC#8.A.35.1.1) which is essential for transport activity. MmpL4/MmpS4 and MmpL5/MmpS5 (TC# 2.A.6.5.8 and TC# 8.A.35.1.2, respectively) are two siderophore exporters that overlap in function (Wells et al. 2013).	Actinobacteria	MmpL4 of Mycobacterium tuberculosis
2.A.6.5.8	Siderophore exporter, MmpL5. Functions with MmpS5, and both proteins are essential for transport activitiy (Wells et al. 2013).	Actinobacteria	MmpL5 of Mycobacterium tuberculosis
2.A.6.6: The Eukaryotic (Putative) Sterol Transporter (EST) Family
2.A.6.6.1	Niemann-Pick C1 AND C2 disease proteins together may form a lipid/cholesterol exporter from lysosomes to other cellular sites (Sleat et al., 2004). NPC1 deficiency causes lysosomal retention of cholesterol, sphingolipids, phospholipids, and glycolipids (Infante et al. 2008 a). NPC1 binds cholesterol, 25-hydroxycholesterol and various oxysterols (Infante et al. 2008 b; Liu et al., 2009 ). Soluble NPC2 binds cholesterol, and then passes it to the N-terminal domain of membranous NPC1 (Abi-Mosleh et al., 2009). Cholesterol trafficking in Niemann-Pick C-deficient cells is reviewed by Peake and Vance (2010).	Animals	NPC1 and NPC2 of Homo sapiens NPC1 (AAH63302) NPC2 (AAH02532)
2.A.6.6.2	Patched (Ptc) segmentation polarity protein	Animals	"Patched" of Drosophila melanogaster
2.A.6.6.3	Yeast membrane protein YPL006w	Protein, yeast	YPL006w of Saccharomyces cerevisiae
2.A.6.6.4	SREBP cleavage-activating protein, SCAP	Animals	SCAP of Cricetulus griseus
2.A.6.6.5	3-hydroxy-3-methylglutaryl (HMG)-CoA reductase	Animals	HMG-CoA reductase of Homo sapiens
2.A.6.6.6	Liver/intestinal enterocyte brush border Niemann-Pick C1 like 1 (NPC1L1) protein; responsible for ezetimibe-sensitive absorption of luminal lipids and cholesterol via a transport mechanism (Altmann et al., 2004; Davies et al., 2005; Liscum, 2007, Dixit et al. 2007). NPC1L1-dependent sterol uptake seems to be a clathrin-mediated endocytic process and is regulated by cellular cholesterol content (Betters and Yu, 2010; Jia et al., 2011). Dietary cholesterol induces trafficking of the intestinal NPC1L1 from the brush boarder to endosomes (Skov et al. 2011). It distributes on the brush border membranes of enterocytes and the canalicular membranes of hepatocytes. It is the target of ezetimibe, a hypocholesterolemic drug which blocks internalization of NPC1L1 and cholesterol in the mouse small intestine (Wang and Song 2012; Xie et al. 2012).	Animals	NPC1L1 of Homo sapiens (NP_037521)
2.A.6.6.7	Niemann-Pick C-type protein (NPC) (1342 aas; 16 putative TMSs in a 1+3+1+5+1+5 arrangement)	Slime molds	NPC of Dictyostelium discoideum (Q9TVK6)
2.A.6.6.8	Niemann-Pick C1 protein homologue-1, Ncr1; contains a sterol sensing domain. Catalyzes intracellular cholesterol release from endocytic organelles.	Animals	Ncr-1 of Caenorhabditis elegans (Q19127)
2.A.6.6.9	Niemann-Pick C1 protein homologue-2, Ncr2; contains a sterol sensing domain. Catalyzes intracellular cholesterol release from endocytic organelles.	Animals	Ncr-2 of Caenorhabditis elegans (P34389)
2.A.6.7: The (Largely Archaeal Putative) Hydrophobe/Amphiphile Efflux-3 (HAE3) Family
2.A.6.7.1	Gene AF1229	Archaea	ORF in Archaeoglobus fulgidus
2.A.6.7.2	Gene MJ1562	Archaea	ORF in Methanococcus jannaschii
2.A.6.7.3	Bacterial HAE3 family member	Proteobacteria	HAE3 family member of Myxococcus xanthus
2.A.6.7.4	Bacterial HAE3 family member	Proteobacteria	HAE3 family member of Myxococcus xanthus
2.A.6.7.5	Hopanoid biosynthesis associated RND transporter like protein, HpnN. Required for hopanoid localization to the outer membrane (Doughty et al. 2011).	α-Proteobacteria	Putative hopanoid transporter of Rhodopseudomonas palustris
2.A.6.7.6	Putative RND lipid exporter	Planctomycetes	RND exporter of Rhodopirellula baltica
2.A.6.8: The Brominated, Aryl Polyene Pigment Exporter (APPE) Family
2.A.6.8.1	Xanthomonadin (brominated, aryl polyene pigment) exporter (to its outer membrane site), ORF4	Bacteria	ORF4 in the pig (pigment) gene locus of Xanthomonas oryzae pv. oryzae
2.A.6.8.2	RND transporter. Encoded in a 17 cistron operon that appears in pathogenic proteobacteria including pathogenic E. coli strains, but not non-pathogenic E. coli strains like K12. May be involved in host associations (EE Allen, personal communication)	γ-Proteobacteria	RND transporter of E. coli
2.A.6.9: The Dispatched (Dispatched) Family
2.A.6.9.1	Dispatched, putative exporter of the cholesterol-modified peptide, hedgehog; sterol sensor protein (Ma et al., 2002). Loss prevents hedgehog signaling. (Nakano et al., 2004; Higgins, 2007).	Animals	Dispatched of Drosophila melanogaster (AAF_23397)
2.A.6.9.2	Protein dispatched homolog 1 (MdispA)	Animals	Disp1 of Mus musculus