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TCID	Name	Domain	Kingdom/Phylum	Protein(s)
2.A.66.1: The Multi Antimicrobial Extrusion (MATE) Family
2.A.66.1.1	Drug:Na⁺ antiporter (norfloxacin, ethidium, kanamycin, ciprofloxin, streptomycin efflux pump), NorM. Transport is dependent on Na⁺, and several essential residiues have been identified. Specifically, Asp32, Glu251, and Asp367 are involved in the Na⁺-dependent drug transport process. (Otsuka et al. 2005).	Bacteria	Pseudomonadota	NorM of Vibrio parahaemolyticus (O82855)
2.A.66.1.2	Drug:Na⁺ antiporter, VcmA (exports norfloxacin, ciprofloxacin, ofloxacin, daunomycin, doxorubicin, streptomycin, kanamycin, ethidium, 4',6'-diamidino-2-phenylindole, Hoechst 33342 and acriflavin). The 3-d x-ray structure (3.65Å resolution) is available (He et al., 2010). Ion binding and internal hydration have been studied by molecular dynamics simulations (Vanni et al., 2012). NorM simultaneously couples drug export to the sodium-motive force and the proton-motive force. Residues involved and protein regions that play important roles in Na⁺ or H⁺ binding have been identified (Jin et al. 2014). Na⁺- and H⁺-driven conformational changes are facilitated by a network of polar residues in the N-terminal domain cavity, whereas conserved carboxylates buried in the C-terminal domain are critical for stabilizing the drug-bound state. These results establish the role of ion-coupled conformational dynamics in the functional cycle and implicate H⁺ in the doxorubicin release mechanism (Claxton et al. 2018).	Bacteria	Pseudomonadota	VcmA (NorM) of Vibrio cholerae non-01
2.A.66.1.3	Multidrug-resistance efflux pump, NorM (MdtK, NorE or YdhE) (Nishino and Yamaguchi 2001). Exports chloramphenicol, norfloxacin, enoxacin, phosphomycin, doxorubicin, trimethoprim, ethidium, deoxycholate, etc (Long et al., 2008). May also export signals for cell-cell communication (Yang et al., 2006).	Bacteria	Pseudomonadota	NorM (YdhE) of E. coli
2.A.66.1.4	DNA damage-inducible protein F, DinF. Protects against oxidative stress and bile salts, possibly by pumping relevant compounds out of the cytoplasm (Rodríguez-Beltrán et al. 2012).	Bacteria	Pseudomonadota	DinF of E. coli
2.A.66.1.5	Ethionine resistance protein, ERC1, of 581 aas and 11 TMSs in a 6 + 5 TMS arrangement. It catalyzes S-adenosyl methionine (SAM) accumulation in Sake yeast (Kanai et al. 2017).	Eukaryota	Fungi, Ascomycota	ERC1 (YHR032w) of Saccharomyces cerevisiae
2.A.66.1.6	Drug (norfloxacin, ciprofoxacin, ethidium, tetramethylammonium, pyrrolidinone, polyvinylpyrrolidone) resistance pump, Alf5 or DTOXIFICATION 19, DTX19, of 427 aas and 12 TMSs. Note: A. thaliana has 56 MATE transporters (Takanashi et al. 2013).	Eukaryota	Viridiplantae, Streptophyta	Alf5 of Arabidopsis thaliana
2.A.66.1.7	Cationic drug (4',6'-diamidino-2-phenylindole (DAPI), tetraphenylphosphonium (TPP), acriflavin, ethidium):Na⁺ antiporter, VmrA of 447 aas and 12 TMSs.	Bacteria	Pseudomonadota	VmrA of Vibrio parahaemolyticus
2.A.66.1.8	Plasma membrane efflux pump, AtDTX1, for plant alkaloids, drugs (e.g., norfloxacin), antibiotics and Cd²⁺ (Li et al. 2002).	Eukaryota	Viridiplantae, Streptophyta	AtDTX1 of Arabidopsis thaliana
2.A.66.1.9	Drug (norfloxacin, polymyxin B) resistance efflux pump, NorM, of 462 aas and 12 TMSs.	Bacteria	Pseudomonadota	NorM of Burkholderia vietnamiensis
2.A.66.1.10	Na-dependent cationic drug (ethidium, acriflavine, 2-N-methyl ellipticinium, berberine, norfloxacin, ciprofloxacin, rhodamine 6G, crystal violet, doxorubicin, novobiocin, enoxacin, and tetraphenylphosphonium chloride) efflux pump, NorM (Long et al. 2008). 3-d structures of the N. gonorrheae NorM transporter (96% identical to the N. miningitidis protein) have been solved complexed with three different substrates in a multidrug cavity and Cs (4HUN; Lu et al. 2013). Lu et al. an identified an uncommon cation-π interaction in the Na⁺-binding site located outside the drug-binding cavity and validated the biological relevance of both the substrate- and cation-binding sites by conducting drug resistance and transport assays. Additionally, they observed a potential rearrangement of at least two transmembrane helices upon Na⁺-induced drug export. They suggested that Na⁺ triggers multidrug extrusion by inducing protein conformational changes rather than by directly competing for the substrate-binding amino acids. However, see 2.A.66.1.32 where the opposite was concluded for a homologue that functions by drug:H⁺ antiport.	Bacteria	Pseudomonadota	NorM of Neisseria meningitidis
2.A.66.1.11	The Enhanced Disease Susceptibility Protein (EDS5), also called the Salicylate Induction Deficient (Sid1) protein; a chloroplast isochorismate exporter that exports isochorismate from the plastid to the cytosol (Rekhter et al. 2019).	Eukaryota	Viridiplantae, Streptophyta	EDS5 of Arabidopsis thaliana chloroplasts
2.A.66.1.12	Drug:H⁺ antiporter (benzalkonium chloride, fluoroquinolone, ethidium bromide, acriflavin, tetraphenylphosphonium chloride efflux pump), PmpM (He et al., 2004)	Bacteria	Pseudomonadota	PmpM of Pseudomonas aeruginosa (Q9I3Y3)
2.A.66.1.13	Drug (monovalent and divalent biocides; fluoroquinolones including norfloxacin and ciprofloxacin) efflux pump, SvrA (MepA) (Kaatz et al., 2006). Also exports tigecycline (McAleese et al., 2005).	Bacteria	Bacillota	SvrA of Staphylococcus aureus (Q2G140)
2.A.66.1.14	Human MATE1 electroneutral organocation:H antiporter (transports tetraethylammonium, TEA, and cimetidine as well as cisplatin and oxaliplatin) (Yonezawa et al., 2006). MATE1 also exports chloroquine across the luminal membrane (Müller et al., 2011). It has an established 13 TMS topology with the "extra" TMS in an extracellular C-terminal region that is not essential for function (Zhang et al., 2012). Also exports 1-methyl-4-phenylpyridinium (MPP), N-methylnicotinamide (NMN), metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfate, acyclovir, cimetidine, ganciclovir and the zwitterionic cephalosporin, cephalexin and cephradin (Nigam 2015). Seems to also play a role in the uptake of oxaliplatin (a platinum anticancer agent). Able to transport paraquat (PQ or N,N-dimethyl-4-4'-bipiridinium); a widely used herbicid. Responsible for the secretion of cationic drugs across the brush border membranes (Tanihara et al. 2007).	Eukaryota	Metazoa, Chordata	SLC47A1 of Homo sapiens
2.A.66.1.15	Electroneutral Multidrug & Toxin Extrusion-1 organic cation:H⁺ antiporter (MATE-1). Exports tetraethylammonium (TEA) and cimetidine, and probably other organic cations, such as 1-methyl-4-phenylpyridinium, amiloride, imipramine, and quinidine (Ohta et al., 2006).	Eukaryota	Metazoa, Chordata	MATE-1 of Rattus norvegicus (Q5I0E9)
2.A.66.1.16	Electroneutral organic cation:H⁺ antiporter MATE2 (Hiasa et al., 2007). 50% identical to MATE1; 2.A.66.1.15. OCT3 and MATE2 genetic polymorphisms can give rise to poor responses to metformin in type 2 diabetes mellitus (Naem et al. 2024).	Eukaryota	Metazoa, Chordata	MATE2 of Mus musculus (Q3V050)
2.A.66.1.17	MATE efflux pump, MatE	Eukaryota	Ciliophora	MatE of Tetrahymena thermophila
2.A.66.1.18	MATE1b (mediates tetraethylammonium (TEA) uptake with properties similar to that of mMATE1; localized in renal brush border membranes (Kobara et al., 2008)).	Eukaryota	Metazoa, Chordata	MATE1b of Mus musculus (Q8K0H1)
2.A.66.1.19	JAT1 (transports nicotine and anabasine, and other alkaloids, such as hyoscyamine and berberine, but not flavonoids) (Morita et al., 2009).	Eukaryota	Viridiplantae, Streptophyta	JAT1 of Nicotiana tabacum (B7ZGMO)
2.A.66.1.20	Multidrug and Toxin Extrusion Protein 2, MATE-2 (catalyzes drug:H⁺antiport; broad specificity, low affinity (50-3000 μM) for organic cationic and anionic compounds (Tanihara et al., 2007)).	Eukaryota	Metazoa, Chordata	SLC47A2 of Homo sapiens
2.A.66.1.21	H⁺-coupled multidrug efflux pump, AbeM (most like 2.A.66.1.2, NorM of Vibrio cholerae) (Su et al., 2005). Exports norfloxacin, ciprofloxacin, DAPI, acriflavin, Hoechst 33342, daunorubicin, doxorubicin, and ethidium (Su et al., 2005) as well as carbapenem (AlQumaizi et al. 2022).	Bacteria	Pseudomonadota	AbeM of Acinetobacter baumannii (Q5FAM9)
2.A.66.1.22	Quinolone:H⁺antiporter, EmmdR. Substates include benzalkonium chloride, norfloxacin, ciprofloxacin, levofloxacin, ethidium bromide, acriflavine, rhodamine 6G and trimethoprim.	Bacteria	Pseudomonadota	EmmdR of Enterobacter cloacae (D5CJ69)
2.A.66.1.23	MDR efflux pump, YeeO (NorA) (81.8% identical to 2.A.66.1.22). Transports dipeptides (see 2.A.1.2.55) (Hayashi et al., 2010). Also exports both flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD). However, significant amounts of flavins were trapped intracellularly when YeeO was produced. Wild-type E. coli secretes 3 flavins (riboflavin, FMN, and FAD), so it must have additional flavin transporters (McAnulty and Wood 2014).	Bacteria	Pseudomonadota	YeeO of E. coli (P76352)
2.A.66.1.24	FRD3 efflux pump for citrate; involved in iron homeostasis. Localized to the pericycle and vascular cylinder of roots; loads citrate into xylem tissues facilitating iron transport from the roots to the shoots; null mutants are sterile (Green and Rogers 2004; Roschzttardtz et al., 2011; Green and Rogers 2004; Roschzttardtz et al., 2011; Durrett et al., 2007).	Eukaryota	Viridiplantae, Streptophyta	FRD3 of Arabidopsis thaliana (Q9SFB0)
2.A.66.1.25	Probable multidrug resistance protein YoeA	Bacteria	Bacillota	YoeA of Bacillus subtilis
2.A.66.1.26	Uncharacterized transporter MJ0709	Archaea	Euryarchaeota	MJ0709 of Methanocaldococcus jannaschii
2.A.66.1.27	Probable multidrug resistance protein NorM (Multidrug-efflux transporter)	Bacteria	Pseudomonadota	NorM of Caulobacter crescentus
2.A.66.1.28	Probable multidrug resistance protein NorM (Multidrug-efflux transporter)	Bacteria	Thermotogota	NorM of Thermotoga maritima
2.A.66.1.29	MATE exporter protein	Bacteria	Myxococcota	MATE exporter protein of Myxococcus xanthus
2.A.66.1.30	Ciprofloxacin export permease, AbeM2	Bacteria	Pseudomonadota	AbeM2 of Acinetobacter baumannii
2.A.66.1.31	Ciprofloxacin efflux pump, AbeM4 (Eijkelkamp et al. 2011).	Bacteria	Pseudomonadota	AbeM4 of Acinetobacter baumannii
2.A.66.1.32	Multidrug:proton antiporter of the DinF subfamily. The structure has been solved to 3.2 Å resolution with and without the substrate, Rhodamine 6 G. The 12 TMSs show asymmetry with a membrane-embedded substrate-binding chamber. Direct competition between the H⁺ and the substrate during transport was suggested (Lu et al. 2013). However, the opposite was suggested for a sodium antiporter (see TC# 2.A.66.1.10).	Bacteria	Bacillota	DinF-like MDR pump of Bacillus halodurans
2.A.66.1.33	MDR efflux pump for quinolones (moxifloxacin, ciprofloxacin and levofloxacin) of 456 aas, DinF (Tocci et al. 2013).	Bacteria	Bacillota	DinF of Streptococcus pneumoniae
2.A.66.1.34	MATE MDR exporter of 411 aas, SP2065 (Tocci et al. 2013). Exports novobiocin.	Bacteria	Bacillota	SP2065 of Streptococcus pneumoniae
2.A.66.1.35	Citrate-specific transporter of 538 aas, MATE1. Necessary for iron supply to the nodule infection zone (Takanashi et al. 2013).	Eukaryota	Viridiplantae, Streptophyta	MATE1 of Lotus japonicus
2.A.66.1.36	Multidrug exporter, DinF, of 457 aas. Exports various toxic compounds, including antibiotics, phytoalexins, and detergents. Mutants are less virulent on the tomato plant than the wild-type strain (Brown et al. 2007).	Bacteria	Pseudomonadota	DinF of Ralstonia solanacearum (Pseudomonas solanacearum)
2.A.66.1.37	Multidrug resistance protein, CdeA of 441 aas. Exports ethidium bromide, fluoroquinolone and acriflavin but had no effect on susceptibility to the following antibiotics: norfloxacin, ciprofloxacin, gentamicin, erythromycin, tetracyclin, and chloramphenicol (Dridi et al. 2004). May be a Na⁺ antiporter.	Bacteria	Bacillota	CdeA of Clostridium difficile
2.A.66.1.38	Homologue of Mte1 of Tricholomp vaccinum of 588 aas which mediates detoxification of xenobiotics and metal ions such as Cu, Li, Al, and Ni, as well as secondary plant metabolites (Schlunk et al. 2015).	Eukaryota	Fungi, Basidiomycota	Mte1 homologue of Moniliophthora roreri (Cocoa frosty pod rot fungus) (Crinipellis roreri)
2.A.66.1.39	Jasmonate-inducible alkaloid transporter-2, JAT2.Transports nicotine and other alkaloids into the tonoplast vacuole for sequestration (Chen et al. 2015; Shitan et al. 2014).			JAT2 of Nicotiana tabacum
2.A.66.1.40	Putative MDR or polysaccharide exporter of 514 aas and 12 TMSs	Bacteria	Spirochaetota	Exporter of Treponema succinifaciens
2.A.66.1.41	Na⁺-coupled multidrug efflux pump, PdrM (Hashimoto et al. 2013). Confers resistance to several antibacterial agents including norfloxacin, acriflavine, and 4',6-diamidino-2-phenylindole (DAPI).	Bacteria	Bacillota	PdrM of Streptococcus pneumoniae
2.A.66.1.42	Paralytic shellfish toxin (PST; including saxitoxin (STX)) exporter, SxtM, of 464 aas (Soto-Liebe et al. 2013). These toxins, which block Na⁺ channels, are produced by cyanobacteria and dinoflagellates, and >30 such natural alkaloids are known (Soto-Liebe et al. 2012).	Bacteria	Cyanobacteriota	SxtM of Cylindrospermopsis raciborskii
2.A.66.1.43	MATE1 of 563 aas and 12 TMSs. Involved in aluminum resistance (Maron et al. 2013).	Eukaryota	Viridiplantae, Streptophyta	MATE1 of Zea mays (Maize)
2.A.66.1.44	Transparent Testa 12 (TT12), also called Protein DETOXIFICATION, is a valuolar transporter of proanthocyanidins (PAs). It transports these compounds from the cytoplasm into the vacuolar lumen (Gao et al. 2015).	Eukaryota	Viridiplantae, Streptophyta	TT12 of Gossypium hirsutum (Upland cotton) (Gossypium mexicanum)
2.A.66.1.45	Damage inducible multidrug resistance protein F, DinF of 455 aas and 12 TMSs. An x-ray structure is available (Radchenko et al. 2015).	Archaea	Euryarchaeota	DinF of Pyrococcus furiosus
2.A.66.1.46	Saxitoxin, STX, exporter, SxtF; also exports fluoroquinolone, suggesting it is an MDR pump (Ongley et al. 2016).	Bacteria	Cyanobacteriota	SxtF of Cylindrospermopsis raciborskii
2.A.66.1.47	Saxitoxin, STX, exporter, SxtM; also exports fluoroquinolone, suggesting it is an MDR pump (Ongley et al. 2016).	Bacteria	Cyanobacteriota	SxtM of Aphanizomenon sp. NH-5 (Anabaena circinalis)
2.A.66.1.48	MATE transporter. ClbM, of 479 aas and 12 TMSs, ClbM. Exports precolibactin, a genotoxin made by a polyketide complex in E. coli, that generates double strand breaks in the DNA (Mousa et al. 2016). The 3-d structure is available (PDB# 4Z3N).	Bacteria	Pseudomonadota	ClbM of E. coli
2.A.66.1.49	MATE family transporter of 475 aas and 12 TMSs in a 6 + 6 TMS pseudosymmetic arrangement. The 3-d structure has been determined at 2.9 Å resolution (Tanaka et al. 2017). The protein possesses a negatively charged internal pocket with an outward-facing shape. This structure was determined for the C. sativa orthologue of the C. rubella protein, the sequence of which is 94% identical to the one provided here.	Eukaryota	Viridiplantae, Streptophyta	CasMATE of Capsella rubella
2.A.66.1.50	Detoxification protein, DTX35, of 614 aas and 12 TMSs, also called FLOWER FLAVONOID TRANSPORTER (FFT), encodes a MATE family transporter in Arabidopsis thaliana. FFT (AtDTX35) is highly transcribed in floral tissues, the transcript being localized to epidermal guard cells, including those of the anthers, stigma, siliques and nectaries (Thompson et al. 2010). The absence of FFT affects flavonoid levels in the plant. Moreover, root growth, seed development and germination, and pollen development, release and viability are all affected (Thompson et al. 2010). Also functions as a chloride channel, which, together with DTX33, is essential for turgor regulation (Zhang et al. 2017). Involved in floral development (Song et al. 2017). Dietary ilavonoid absorption facilitates the development and utilization of functional foods or dietary supplements (Fu et al. 2024).	Eukaryota	Viridiplantae, Streptophyta	DTX35 of Arabidopsis thaliana
2.A.66.1.51	Multidrug resistance efflux pump, Detoxification 48, DTX48. Functions as a multidrug and toxin extrusion transporter. Contributes to iron homeostasis during stress responses and senescence (Seo et al. 2012). Overexpression of DTX48 alters shoot developmental programs leading to a loss of apical dominance phenotype (Wang et al. 2015).	Eukaryota	Viridiplantae, Streptophyta	DTX48 of Arabidopsis thaliana (Mouse-ear cress)
2.A.66.1.52	Detoxification protein 14, DTX14, of 485 aas and 12 TMSs. This MATE family (MOP superfamily) proter extrduces xenobiotics from the cell. It's 3-d structure is known to 2.6 Å resolution (Miyauchi et al. 2017). Its carboxy-terminal lobe (C-lobe) contains an extensive hydrogen-bonding network with well-conserved acidic residues, as demonstrated by structure-based mutational analyses. The analyses suggest that the transport mechanism involves a structural change of transmembrane helix 7, induced by the formation of a hydrogen-bonding network upon the protonation of the conserved acidic residue in the C-lobe (Miyauchi et al. 2017).	Eukaryota	Viridiplantae, Streptophyta	DTX14 of Arabidopsis thaliana
2.A.66.1.53	Citrate exporter, MATE1 or DETOXIFICATION, of 553 aas and 12 probable TMSs. It's activity gives rise to aluminum (Al³⁺) tolerance (Garcia-Oliveira et al. 2014). 98% identical to the rye and barley orthologs (Zhou et al. 2013).	Eukaryota	Viridiplantae, Streptophyta	MATE1 of Tritium aestivum (Wheat)
2.A.66.1.54	MATE2 or Detoxification 47 (DTX47) of 543 aas and 12 TMSs. The orthologs from several plants have been sequenced and characterized (i.e., wheat; potato) (Li et al. 2018). This protein may be a citrate and salicylate exporter and promote resistance to aluminum (Al³⁺) (Garcia-Oliveira et al. 2018). It may also transport cyanidine-3-glucoside (anthocyanin) (Saad et al. 2023).	Eukaryota	Viridiplantae, Streptophyta	MATE2 of Arabidopsis thaliana
2.A.66.1.55	MATE drug:sodium symporter of 461 aas and 12 TMSs. Several crystal structures are known (3VVO, 3VVP, 3VVR, 3VVS, 6FHZ, 6GWH) in several distinct apo-form conformations, and in complexes with a derivative of the antibacterial drug norfloxacin and three in vitro selected thioether-macrocyclic peptides, at 1.8 - 3.0 Å resolutions. The structures, combined with functional analyses, showed that the protonation of Asp 41 on the N-terminal lobe induces the bending of TMS1, which in turn collapses the N-lobe cavity, thereby extruding the substrate drug to the extracellular space. Moreover, the macrocyclic peptides bind the central cleft in distinct manners, which correlate with their inhibitory activities (Tanaka et al. 2013). The Na⁺-binding site, in the N-lobe of this transporter, is selective against K⁺, weakly specific against H⁺, and broadly conserved among prokaryotic MATEs (Ficici et al. 2018). The inward-facing state was obtained after crystallization in the presence of native lipids (Zakrzewska et al. 2019). The transition from the outward-facing state to the inward-facing state involves rigid body movements of TMSs 2-6 and 8-12 to form an inverted V, facilitated by a loose binding of TMS1 and TMS7 to their respective bundles and their conformational flexibility. The inward-facing structure of PfMATE in combination with the outward-facing one supports an alternating access mechanism for MATE family transporters (Zakrzewska et al. 2019).	Archaea	Euryarchaeota	MOP superfamily transporter of Pyrococcus furiosus
2.A.66.1.56	MATE transporter,DETOXIFICATION 4, DTX4 or At2g04070, of 476 aas and 12 TMSs. May transport alkaloids, heavy metals, bile salts, organic acids amd organic amines (Li et al. 2018).	Eukaryota	Viridiplantae, Streptophyta	DTX4 of Arabidopsis thaliana (Mouse-ear cress)
2.A.66.1.57	DETOXIFICATION 41, DTX41, TDS3, TT12 of 507 aas and 12 TMSs. Acts as a flavonoid/H⁺-antiporter that controls the vacuolar sequestration of flavonoids in the seed coat endothelium (Debeaujon et al. 2001; Marinova et al. 2007). May also transport the anthocyanin cyanidin-3-O-glucoside (Marinova et al. 2007) and epicatechin 3'-O-glucoside (Zhao and Dixon 2009). These results have been confirmed in Daucus carota and other plants (Saad et al. 2023). A similar protein in Petunia hybrida, PhMATE1 transports antocyanins (flavanoids involved in flower color) and has 11 TMSs (Yuan et al. 2023). Soybean oil may facilitate interactions with flavonoids to form more stable and compact fatty acid-flavonoid complexes (Fu et al. 2024).	Eukaryota	Viridiplantae, Streptophyta	DTX41 of Arabidopsis thaliana (Mouse-ear cress)
2.A.66.1.58	Detoxification-50, DTX50, of 505 aas and 12 TMSs. It catalyzes abscisic acid efflux and modulates ABA sensitivity as well as drought tolerance (Zhang et al. 2014). It may also function in heavy metal ion and drug export (Sailer et al. 2018; Li et al. 2002). Its ortholog in cucumber, the vacuolar MATE/DTX protein, exports cucurbitacin C, and its gene is co-regulated with bitterness biosynthesis in cucumber (Ma et al. 2023).	Eukaryota	Viridiplantae, Streptophyta	DTX50 of Arabidopsis thaliana
2.A.66.1.59	The Activated Disease Susceptibility 1, ADS1 (DTX51, ABS3, ADP1, NIC4), putative exporter of 532 aas and 12 TMSs. ADS1 negatively regulates the accumulation of the plant immune activator salicylic acid as well as cognate Pathogenesis-Related 1 (PR1) gene expression which influences microbial pathogenesis (Sun et al. 2011). It may be a salicylate exporter.	Eukaryota	Viridiplantae, Streptophyta	ADS1 of Arabidopsis thaliana
2.A.66.1.60	Probable multidrug resistence efflux pump of 452 aas and 12 TMSs in a 6 + 6 TMS arrangement.	Archaea	Candidatus Lokiarchaeota	MDR pump of Candidatus Prometheoarchaeum syntrophicum
2.A.66.1.61	Vacuolar nicotine exporter (from the cytoplasm into the vacuole), the NtMATE2 transporter, also designated the DETOXIFICATION 40-like protein, of 500 aas and 12 TMSs in a 6 + 6 TMS arrangement. NtMATE2 is located in the vacuole membrane of the tobacco plant root and is involved in the transport of nicotine, a secondary or specialized metabolic compound in Solanaceae ((Shoji et al. 2009). The crystal structures of NtMATE2 in its outward-facing forms have been determined (Tanaka et al. 2021). The overall structure has a bilobate V-shape with pseudo-symmetrical assembly of the N- and C-lobes. In one crystal structure, the C-lobe cavity of NtMATE2 interacts with an unidentified molecule that may mimic a substrate. NtMATE2-specific conformational transitions imply that an unprecedented movement of the transmembrane alpha-helix 7 (TMS7) is related to the release of the substrate into the vacuolar lumen (Tanaka et al. 2021).	Eukaryota	Viridiplantae, Streptophyta	NtMATE2 of Nicotiana tabacum (common tobacco)
2.A.66.1.62	MATE family toxin extrusion protein 3 (Mate3/Slc47a2.1) of 590 aas and 13 TMSs in a 2 + 4 + 2 + 4 + 1 (C-terminal) TMSs. The 2 + 4 TMSs are repeated twice and comprise the usual 6 TMS repeat unit. its gene is highly expressed in the kidneys, intestine, testes, and brain of males. It interacts with xenobiotic compounds, suggesting a role in the efflux of toxic compounds (Vujica et al. 2023). These autors also showed that this porter interacts with and may export dozens of polutants in an aqueous environment.	Eukaryota	Metazoa, Chordata	MATE family protein of Danio rerio
2.A.66.1.63	MATE efflux family protein, DTX5 or MATE5, of 479 aas and 12 TMSs, preferentially transports different astringencies of proanthocyanidins (PAs) in persimmon (Liu et al. 2023). DkDTX5/MATE5 binds PA precursors via Ser-84, demostrating an association between the transporter and PA variation (Liu et al. 2023).	Eukaryota	Viridiplantae, Streptophyta	MATE5 of Triticum urartu
2.A.66.2: The Polysaccharide Transport (PST) Family
2.A.66.2.1	Lipopolysaccharide (possibly the O-antigen side chain intermediate) exporter	Bacteria	Pseudomonadota	RfbX1 of E. coli
2.A.66.2.2	Probable succinoglycan exporter	Bacteria	Pseudomonadota	ExoT of Rhizobium meliloti
2.A.66.2.3	Undecaprenol-pyrophosphate O-antigen flippase WzxE	Bacteria	Pseudomonadota	WzxE of E. coli (P0AAA7)
2.A.66.2.4	Probable acetan exporter	Bacteria	Pseudomonadota	AceE of Acetobacter xylinus
2.A.66.2.5	Capsular polysaccharide exporter	Bacteria	Bacillota	CapF of Staphylococcus aureus
2.A.66.2.6	Teichuronic acid exporter, TuaB (YvhB)	Bacteria	Bacillota	TuaB of Bacillus subtilis
2.A.66.2.7	Lipopolysaccharide (colanic acid) exporter, WzxC	Bacteria	Pseudomonadota	WzxC of E. coli
2.A.66.2.8	Exopolysaccharide (Amylovoran) exporter, AmsL	Bacteria	Pseudomonadota	AmsL of Erwinia amylovora
2.A.66.2.10	The O-antigent transporter homologue, Mth347	Archaea	Euryarchaeota	Mth347 of Methanobacterium thermoautotrophicum(O26447)
2.A.66.2.11	Exopolysaccharide exporter, EpsE (Huang and Schell, 1995)	Bacteria	Pseudomonadota	EpsE of Ralstonia solanacearum (Q45411)
2.A.66.2.12	Isoprenoid lipid sugar glycan flippase, Wzx (note: Wzx forms a complex with Wzy and Wzz for assembly of periplasmic O-antigen) (Marolda et al., 2006). Wzx has a 12 TMS topology (Cunneen and Reeves, 2008). WzyE (450aas; 12 TMSs; TC#9.B.128.1.1; B614D1) is called the enterobacterial common antigen (ECA) polysaccharide chain elongation polymerase (Marolda et al., 2006). The structure of Wzz has been determined by cryoEM (Collins et al. 2017).	Bacteria	Pseudomonadota	Wzx of E. coli (Q1L811)
2.A.66.2.13	Unknown PST protein	Bacteria	Pseudomonadota	Unknown PST protein of Alteromonadales bacterium (A0XZ57)
2.A.66.2.14	The 14 TMS SpoVB protein (possibly catalyzes lipid-linked oligosaccharide transport across the cytoplasmic membrane; required for proper cell wall biosynthesis) (Vasudevan et al., 2009).	Bacteria	Bacillota	The SpoVB protein of Bacillus subtilis (Q00758)
2.A.66.2.15	Anionic O-antigen (undecaprenyl pyrophosphate-linked anionic O-Ag) subunit flippase, Wzx. Translocates from the inner to the outer leaflets of the inner membrane. The topology has been studied (Ormazabal et al. 2010).	Bacteria	Pseudomonadota	Wzx of Pseudomonas aeruginosa (G3XD19)
2.A.66.2.16	Capsular polysaccharide exporter, CpsU (428aas; 12 TMSs).	Bacteria	Bacillota	CpsU of Streptococcus thermophilus (Q8KUK6)
2.A.66.2.17	Sporulation protein YkvU	Bacteria	Bacillota	YkvU of Bacillus subtilis
2.A.66.2.18	O-antigen transmembrane translocase, Wzx (Franklin et al. 2011). In S. enterica groups B, D2 and E, Wzx translocation exhibits specificity for the repeat-unit structure, as variants with single sugar differences are translocated with lower efficiency, and little long-chain O antigen is produced. It appears that Wzx translocases are specific for their O antigen for normal levels of translocation (Hong et al. 2012).	Bacteria	Pseudomonadota	Wzx of Salmonella enterica subsp. enterica
2.A.66.2.19	O-antigen transmembrane translocase, Wzx (Franklin et al. 2011). For S. enterica groups B, D2 and E, Wzx translocation exhibits specificity for the repeat-unit structure, as variants with single sugar differences are translocated with lower efficiency, and little long-chain O antigen is produced. It appears that Wzx translocases are specific for their O antigen for normal levels of translocation (Hong et al. 2012).	Bacteria	Pseudomonadota	Wzx of Salmonella typhimurium subsp. houtenae
2.A.66.2.20	PST family homologue of 14 TMSs	Bacteria	Chlamydiota	Hypothetical protein of Parachlamydia acanthamoebae
2.A.66.2.21	Putative polysaccharide transporter	Bacteria	Spirochaetota	Putative polysaccharide transporter of Leptospira interrogans
2.A.66.2.22	Choline-derivatized teichoic acid exporter (flippase), TacF of495 aas. TacF is responsible for the choline dependent growth phenotype (Damjanovic et al. 2007).	Bacteria	Bacillota	TacF of Streptococcus pneumoniae
2.A.66.2.23	Xanthan precursor exporter of 499 aas and 14 TMSs, GumJ (Bianco et al. 2014).	Bacteria	Pseudomonadota	GumJ of Xanthomonas campestris
2.A.66.2.24	Putative polysaccharide exporter of 471 aas and 14 TMSs	Bacteria	Pseudomonadota	UP of E. coli
2.A.66.2.25	Polysaccharide export protein of 572 aas and 12 TMSs.	Bacteria	Candidatus Beckwithbacteria	PS exporter of Candidatus Beckwithbacteria bacterium
2.A.66.2.26	Uncharacterized MOP superfamily member of 456 aas and 12 TMSs.	Bacteria	Pseudomonadota	UP of Parvularcula oceani
2.A.66.2.27	Putative flippase of 416 aas and 12 TMSs.	Bacteria	Pseudomonadota	Flippase of Candidatus Marithrix sp. Canyon 246
2.A.66.2.28	Uncharacterized protein of 435 aas and 13 TMSs.	Bacteria	Bacillota	UP of Bacillus wiedmannii
2.A.66.2.29	Uncharacterized polysaccharide precursor flippase of 476 aas and 14 TMSs.	Bacteria	Bacillota	UP of Clostridium botulinum
2.A.66.2.30	Uncharacterized putative carbohydrate-lipid flippase of 486 aas and 14 TMSs in a 6 + 2 + 6 arrangement.	Bacteria	Bacteroidota	UP of Bacteroides timonensis
2.A.66.2.31	Uncharacterized protein of 455 aas and 14 TMSs.	Bacteria	Bacillota	UP of Exiguobacterium sp. KRL4
2.A.66.2.32	Probable polysaccharide biosynthesis transport proteinof 433 aas and 12 TMSs [Candidatus Amesbacteria bacterium	Bacteria	Candidatus Amesbacteria	PS transporter of Candidatus Amesbacteria bacterium
2.A.66.3: The Oligosaccharidyl-lipid Flippase (OLF) Family
2.A.66.3.1	The OLF (Rft1 protein) of Saccharomyces cerevisiae. May play a role in phospholipid flipping from the inner leaflet of the plasma membrane to the outer leaflet (Chauhan et al. 2016).	Eukaryota	Fungi, Ascomycota	Rft1 of Saccharomyces cerevisiae
2.A.66.3.2	Endoplasmic reticular RFT1 protein, a Man(5)GlcNAc(2)-PP-dolichol translocation protein of 541 aas and 12 TMSs in a 6 + 6 TMS arrangement. It is probably an ntramembrane glycolipid transporter that operates in the biosynthetic pathway of dolichol-linked oligosaccharides, the glycan precursors employed in protein asparagine (N)-glycosylation. The sequential addition of sugars to dolichol pyrophosphate produces dolichol-linked oligosaccharides containing up to fourteen sugars, including two GlcNAcs, nine mannoses and three glucoses. Once assembled, the oligosaccharide is transferred from the lipid to nascent proteins by oligosaccharyltransferases. The assembly of dolichol-linked oligosaccharides begins on the cytosolic side of the endoplasmic reticulum membrane and finishes in its lumen. RFT1 could mediate the translocation of the cytosolically oriented intermediate DolPP-GlcNAc2Man5, produced by ALG11, into the ER lumen where dolichol-linked oligosaccharides assembly continues (Haeuptle et al. 2008, Vleugels et al. 2009). Rft1 is associated with congenital disorder of glycosylation, RFT1-CDG (Hirata et al. 2024).	Eukaryota	Metazoa, Chordata	RFT1 of Homo sapiens (Q96AA3)
2.A.66.3.3	Nuclear division RFT1 homologue	Eukaryota	Viridiplantae, Streptophyta	RFT1 homologue of Arabidopsis arenosa (Q6V5B3)
2.A.66.3.4	Uncharacterized protein, RFT1 homologue, of 469 aas and 14 TMSs.	Eukaryota	Ciliophora	RFT1 homologue of Paramecium tetraurelia (A0D5K0)
2.A.66.4: The Mouse Virulence Factor (MVF) Family
2.A.66.4.1	The mouse virulence factor, MviN. (May flip the Lipid II peptidoglycan precursor from the cytoplasmic side of the inner membrane to the periplasmic surface) (Vasudevan et al., 2009). MviN, a putative lipid flippase (Fay and Dworkin, 2009). In E. coli, MviN is an essential protein which when defective results in the accumulation of polyprenyl diphosphate-N-acetylmuramic acid-(pentapeptide)-N-acetyl-glucosamine. This may be the peptidoglycan intermediated exported via MviN (Inoue et al. 2008). It is essential for the growth of several bacteria.	Bacteria	Pseudomonadota	MviN of Salmonella typhimurium (P37169)
2.A.66.4.2	Putative virulence factor, MviN (21% identity with 2.A.66.4.1)	Bacteria	Spirochaetota	MviN of Borrelia garinii (Q65ZW3)
2.A.66.4.3	Peptidoglycan biosynthesis protein MurJ (Ruiz 2008 ). A 3-d structural model showed a solvent-exposed cavity within the plane of the membrane (Butler et al. 2013). MurJ has 14 TMSs, and specific charged residues localized in the central cavity are essential for function. This structural homology model suggests that MurJ functions as an essential transporter in PG biosynthesis (Butler et al. 2013). Based on an in vivo assay, MurJ is a flippase for the lipid-linked cell wall precursors, polyisoprenoid-linked disaccharide-peptapeptides (Sham et al. 2014). There is controversy about the role of this porter and FtsW/RodA which on the basis of an in vitro assay, were thought to be flippases for the same intermediate (Young 2014). MurJ, the bacterial lipid II flippase, functions by an alternating-access mechanism (Kumar et al. 2019). The crystal structure of MurJ in a "squeezed" form, distinct from its inward- and outward-facing forms, has been published (Kohga et al. 2022). These authors reported two crystal structures of inward-facing forms from Arsenophonus endosymbiont MurJ and a crystal structure of E. coli MurJ in a "squeezed" form, which lacks a cavity to accommodate the substrate, mainly because of the increased proximity of transmembrane helices 2 and 8. Molecular dynamics simulations support the hypothesis that the squeezed form is an intermediate conformation (Kohga et al. 2022).	Bacteria	Pseudomonadota	MurJ of Escherichia coli
2.A.66.4.4	MviN. Essential for peptidoglycan biosynthesis (Gee et al. 2012).	Bacteria	Actinomycetota	MviN of Mycobacterium tuberculosis
2.A.66.4.5	MviN; LuxO regulated for induction during the early logarithmic and stationary phase of growth (Cao et al. 2010).	Bacteria	Pseudomonadota	MviN of Vibrio alginolyticus
2.A.66.4.6	Uncharacterized protein	Bacteria	Pseudomonadota	UP of E. coli
2.A.66.4.7	Probable peptidoglycan-lipid II flippase, MurJ or MviN; essential for cell wall synthesis and viability (Mohamed and Valvano 2014).	Bacteria	Pseudomonadota	MurJ of Burkholderia cenocepacia
2.A.66.4.8	MurJ (MviV) of 475 aas and 14 TMSs. Kuk et al. 2016 presented a crystal structure of MurJ from Thermosipho africanus in an inward-facing conformation at 2.0-A resolution. A hydrophobic groove is formed by two C-terminal transmembrane helices, which leads into a large central cavity that is mostly cationic. Their results suggest that alternating access is important for MurJ function, which may be applicable to other MOP superfamily transporters (Kuk et al. 2016).	Bacteria	Thermotogota	MurJ of Thermosipho africanus
2.A.66.5: The Agrocin 84 Antibiotic Exporter (AgnG) Family
2.A.66.5.1	The agrocin 84 exporter, AgnG	Bacteria	Pseudomonadota	AgnG of Agrobacterium tumefaciens (Q676G9)
2.A.66.5.2	AgnG homologue 1 (433aas; 12TMSs; (2)₆)	Bacteria	Pseudomonadota	AgnG homologue 1 of Nitrococcus mobilis (A4BUA1)
2.A.66.5.3	AgnG homologue 2 (448aas; 12TMSs; (2)₆. Probable polysaccharide exporter.	Bacteria	Cyanobacteriota	AgnG homologue 2 of Lyngbya sp. PCC8106 (A0YL48)
2.A.66.6: The Putative Exopolysaccharide Exporter (EPS-E) Family
2.A.66.6.1	Putative exopolysaccharide transporter with two subunits, PelFG (PelF has 507 aas and 1 N-terminal TMS, while PelG has 456 aas and 12 TMSs) (Vasseur et al., 2007)	Bacteria	Pseudomonadota	PelFG of Pseudomonas aeruginosa (Q02PM3)
2.A.66.6.2	Fusion protein (986 aas): Glycosyl transferase group 1 (residues 1-550); putative transporter (flippase) (residue 551-986; 12(6+6) TMSs)	Bacteria	Pseudomonadota	Fusion protein of Ralstonia solanacearum (EAP70965)
2.A.66.7: Putative O-Unit Flippase (OUF) Family
2.A.66.7.1	Putative O-unit flippase (OUF1)	Bacteria	Pseudomonadota	OUF1 of Pseudomonas fluorescens (Q4K6F5)
2.A.66.8: Unknown MOP-1 (U-MOP1) Family (Most closely related to the OLF Family (2.A.66.3))
2.A.66.8.1	Hypothetical protein (598aas with 12-14TMSs; probably 14 with the central 2 being of low hydrokphobicity) The topologies and sequence similarities of subfamily 8 is like that of subfamily 3.	Eukaryota	Euglenozoa	Hypothetical protein of Trypanosoma brucei (Q383B3)
2.A.66.8.2	Hypothetical protein (729aas; 14TMSs ?)	Eukaryota	Euglenozoa	Hypothetical protein of Leishmania infantum (A4I3X2)
2.A.66.9: The Progressive Ankylosis (Ank) Family
2.A.66.9.1	The progressive ankylosis (ANK) protein (AnkH; SLC62A1) gives rise to craniometaphyseal bone dysplasia in man. This 12 TMS protein was reported to transport pyrophosphate, but a more recent report suggests it transports ATP instead of pyrophosphate (Szeri et al. 2022). It is expressed in the primary ciliary/basal body complex of kidney and bone tissues (Nürnberg et al., 2001; Carr et al. 2009). It is critical for the regulation of pyrophosphate, and gain of function ANK mutations are associated with calcium pyrophosphate deposition disease (Mitton-Fitzgerald et al. 2016).	Eukaryota	Metazoa, Chordata	AnkH of Homo sapiens (Q9HCJ1)
2.A.66.9.2	Hypothetical protein, Pcar_0400	Bacteria	Thermodesulfobacteriota	Pcar_0400 of Pelobacter carbinolicus (Q3A7I4)
2.A.66.9.3	Ank family member	Bacteria	Thermodesulfobacteriota	Ank protein of Desulfuromonas acetoxidans (Q1K211)
2.A.66.10: LPS Precursor Flippase (LPS-F) Family
2.A.66.10.1	Wzx isoprenoid-linked O-antigen precursor glycan translocase. A 12 TMS topology with N- and C-termini in the cytoplasm has been established, and functionally important residues have been identified (Marolda et al. 2010). A substrate:proton antiport mechanism has been established (Islam et al. 2013). The Wzx/Wzy pathway produces repeat-units of mostly 3-8 sugars on the cytosolic face of the cytoplasmic membrane that is translocated by the Wzx flippase to the periplasmic face and is polymerized by Wzy polymerase to give long-chain polysaccharides (Hong et al. 2023).	Bacteria	Pseudomonadota	Wzx of E. coli O157:H7 str 1125
2.A.66.11: Uncharacterized MOP-11 (U-MOP11) Family

2.A.66.11.1	Uncharacterized protein	Bacteria	Actinomycetota	Uncharacterized protein of Streptomyces coelicolor
2.A.66.11.2	Uncharacterized protein	Bacteria	Pseudomonadota	Uncharacterized protein of Beggiatoa alba
2.A.66.12: Uncharacterized MOP-12 (U-MOP12) Family

2.A.66.12.1	Uncharacterized MOP superfamily member of 506 aas and 14 TMSs. Subfamily 2.A.66.12 may be most closely related to 2.A.66.2, suggesting that these proteins are glycolipid flippases.	Bacteria	Myxococcota	U-MOP family 12 member-1 of Myxococcus xanthus
2.A.66.12.2	Uncharacterized MOP superfamily member of 1049 aas and 14 or 15 TMSs	Bacteria	Bacteroidota	U-MOP family 12 member-2
2.A.66.12.3	Uncharacterized MOP superfamily member of 489 aas and 14 TMSs	Archaea	Euryarchaeota	U-MOP family 12 member-3
2.A.66.12.4	Uncharacterized MOP superfamily member of 487 aas and 14 TMSs	Archaea	Euryarchaeota	U-MOP superfamily protein
2.A.66.12.5	Uncharacterized MOP superfamily of 488 aas and 14 TMSs	Archaea	Euryarchaeota	U-MOP superfamily member
2.A.66.12.6	Putative polysaccharide exporter of 449 aas, YghQ.	Bacteria	Pseudomonadota	YghQ of E. coli
2.A.66.12.7	The succinoglycan biosynthesis transporter homologue, Mth342	Archaea	Euryarchaeota	Mth342 of Methanobacterium thermoautotrophicum (O26442)
2.A.66.12.8	Putative Wzx flippase of 499 aas and 14 TMSs (Hug et al. 2016).	Bacteria	Candidatus Peregrinibacteria	Wzx of Candidatus Peribacter riflensis
2.A.66.12.9	Uncharacterized flippase of 516 aas and 14 TMSs	Archaea	Candidatus Thermoplasmatota	UP of Cuniculiplasma divulgatum
2.A.66.12.10	Uncharacterized protein of 452 aas and 12 TMSs.	Bacteria	Pseudomonadota	UP of Parvularcula oceani
2.A.66.12.11	Uncharacterized putative flippase of 496 aas and 14 TMSs.	Bacteria	Bacteroidota	UP of Cyclobacterium lianum
2.A.66.12.12	Exopolysaccharide flippase, Wzx_eps (MXAN_7416) of 490 aas and 14 TMSs in a 6 + 2 + 6 TMS arrangement. The gene encoding this transporter is adjacent to two genes encoding EpsZ (MXAN_7415; TC# 9.B.18.1.6), a glycosyl transferase that initiates repeat unit synthesis, and an outer membrane exopolysaccharide export protein, Opx or EpsY (MXAN_7417; TC# 1.B.18.3.9) (Pérez-Burgos et al. 2020).	Bacteria	Myxococcota	Wzx_eps of Myxococcus xanthus