TCDB is operated by the Saier Lab Bioinformatics Group
TCIDNameDomainKingdom/PhylumProtein(s)
2.A.7.1:  The 4 TMS Small Multidrug Resistance (SMR) Family

Properties of the SMR family proteins have been reviewed (OE Burata et al., 2022; PMID 36100040).

2.A.7.1.1









Small multidrug efflux pump, Smr (QacC, QacD, Ebr).  Substrates: (1) aromatic dyes (e.g., ethidium bromide), (2) quaternary amines (e.g., the disinfectant benzalkonium) and (3) derivatives of tetraphenylphosphonium (TPP) (Fuentes et al. 2005). Unassembled monomers of the SMR family exist in a dynamic equilibrium where the N-terminal TMS flips in and out of the membrane, with rates that depend on dimerization and the polypeptide sequence (Seurig et al. 2019). Additional substrates include guanidinium and metformin metabolites such as guanylurea (Lucero et al. 2023).

Bacteria
Bacillota
Smr of Staphylococcus aureus
2.A.7.1.2









Small multidrug efflux pump (substrates: isoniazid, tetraphenylphosphonium (TPP), erythromycin, ethidium bromide, acriflavine, safranin O and pyronin Y) (Rodrigues et al. 2013).

Bacteria
Actinomycetota
Mmr of Mycobacterium tuberculosis (P69926)
2.A.7.1.3









Small cationic multidrug efflux pump (substrates: cationic lipophilic drugs), EmrE. This pump confers resistance to a wide range of disinfectants and dyes known as quaternary cation compounds (QCCs). The 3-D structure of the dimeric EmrE shows opposite orientation of the two subunits in the membrane (Chen et al., 2007), and this conclusion has been confirmed (Fleishman et al. 2006; Lehner et al. 2008; Lloris-Garcerá et al. 2013). There may be a single intermediate state in which the substrate is occluded and immobile (Basting et al., 2008).  Direct interaction between substrates (tetraphenylphosphonium, TPP+ and MTP+) and Glu14 in TMS1 has been demonstrated using solid state NMR (Ong et al. 2013). A Gly90X6Gly97 motif is important for dimer formation (Elbaz et al., 2008).  Two models may account for the opposite (inverted) orientations of the two identical subunits. A post-translational model posits that topology remains malleable after synthesis and becomes fixed once the dimer forms. A second, co-translational model, posits that the protein inserts in both topologies in equal proportions (Woodall et al. 2015).  Protonation of E14 leads to rotation and tilt of transmembrane helices 1-3 in conjunction with repacking of loops, conformational changes that alter the coordination of the bound substrate and modulate its access to the binding site from the lipid bilayer. The transport model that emerges posits a proton-bound, but occluded, resting state. Substrate binding from the inner leaflet of the bilayer releases the protons and triggers alternating access between inward- and outward-facing conformations of the substrate-loaded transporter, thus enabling antiport without dissipation of the proton gradient (Dastvan et al. 2016). TMS4 is the known dimerization domain of EmrE (Julius et al. 2017). Few conserved residues are essential for drug polyselectivity. Aromatic QCC selection involves a greater portion of conserved residues compared to other QCCs (Saleh et al. 2018).
     The topologies of helical membrane proteins are generally defined during insertion of the transmembrane helices, yet topology can change after insertion. In EmrE, topology flipping occurs so that the populations in both orientations equalize. Woodall et al. 2017 demonstrated that when EmrE is forced to insert in a distorted topology, topology flipping of the first TMS can occur, and topological malleability also extends to the C-terminal helix; even complete inversion of the entire EmrE protein can occur after the full protein is translated and inserted. Thus, topological rearrangements appear to be possible during biogenesis. Subtle but significant differences in the sizes of EmrE with different QCC ligands bound has been reported (Qazi and Turner 2018). The two Glu14 residues in the dimer have independent pKa values and are not electrostatically coupled (Li et al. 2021). High level cell-free expression and specific labeling of EmrE has been achieved (Klammt et al. 2004). Cotranslational folding and assembly of the dimeric E. coli EmrE has been documented (Mermans et al. 2022). Harmane binding can uncoupled proton flux through EmrE. In E. coli, EmrE-mediated dissipation of the transmembrane pH gradient provides the mechanism underlying the in vivo phenotype of harmane susceptibility (Spreacker et al. 2022).

Bacteria
Pseudomonadota
EmrE of E. coli
2.A.7.1.4









Quaternary ammonium compound (cetylpyridinium, cetyldimethyl ethylammonium, hexadecyltrimethyl ammonium) efflux pump, SugE, of 105 aas and 4 TMSs.  High level cell-free expression and specific labeling of EmrE has been achieved (Klammt et al. 2004).

Bacteria
Pseudomonadota
SugE of E. coli (P69937)
2.A.7.1.5









The heterooligomeric drug resistance efflux pump, YkkCD (substrates: ethidium bromide, proflavin, tetraphenylarsonium chloride, crystal violet, pyronin Y, methylviologen, cetylperdinium chloride, streptomycin, tetracycline, chloramphenicol, phosphonomycin)
Bacteria
Bacillota
YkkCD of Bacillus subtilis
2.A.7.1.6









The heterooligomeric drug resistance efflux pump, EbrAB (substrates: ethidium bromide, acriflavin, pyronin Y, and safranin O) (Zhang et al., 2007).
Bacteria
Bacillota
EbrAB of Bacillus subtilis
2.A.7.1.7









The drug resistance efflux pump, Hsmr (Ninio and Schuldiner, 2003) (exports ethidium, acriflavin tetraphenylphosphonium (TPP) and other cationic drugs).  Inhibited by a peptide with the sequence of TMS4 (Poulsen and Deber 2012). TMS4-TMS4 interactions may constitute the highest affinity locus for dimerization (Poulsen et al. 2009).

Archaea
Euryarchaeota
Hsmr of Halobacterium salinarum (B0R6K7)
2.A.7.1.8









The putative heterodimeric SMR efflux pump, NepAB, encoded in a nicotine degradation plasmid, pAO1 (Baitsch et al., 2001; Brandsch, 2006); [probably exports methylamine; may also export excess nicotine, methylamine and/or the intermediate of nicotine catabolism, N-methyl-aminobutyrate] (Ganas et al. 2007). Uptake (Km=6μM) occurs by facilitated diffusion (Ganas and Brandsch, 2009).

Bacteria
Actinomycetota
NepAB of Arthrobacter nicotinovorans:
NepA (116 aas; Q8GAI5)
NepB (166 aas; Q8GAI6)
2.A.7.1.9









The spermidine exporter, MdtIJ (MdtIJ = YdgEF) (Higashi et al., 2008).  Catalyzes the export of spermidine and putrescine, and confers resistance to deoxycholate and SDS (Nishino and Yamaguchi 2001). It can be induced by these polyamines and bile salts. Details of the induction mechanism are known (Leuzzi et al. 2015).

Bacteria
Pseudomonadota
MdtJI of E. coli
MdtJ (P69213)
MdtI (P69210)
2.A.7.1.10









SugE Supressor of GroEL/ES (He et al., 2011). Confers resistance to cetyltrimethylammonium bromide, cetylpyridinium chloride, tetraphenylphosphonium, benzalkonium chloride, ethidium bromide, and sodium dodecyl sulfate. 

 

Bacteria
Pseudomonadota
SugE of Enterobacter cloacae (D5CES3)
2.A.7.1.11









Small MDR pump, AbeS (53% identical to EmrE of E. coli; TC# 2.A.7.1.3). Exports chloramphenicol, ciprofloxacin, erythromycin, novobiocin, acridine orange, acriflavine, benzalkonium chloride, DAPI, deoxycholate, ethidium bromide, sodium dodecyl sulfate (SDS), tetraphenylphosphonium and others (Srinivasan et al., 2009; Lytvynenko et al. 2015).  Purified AbeS binds tetraphenylphosphonium with nanomolar affinity and exhibits electrogenic transport of 1-methyl-4-phenylpyridinium after reconstitution into liposomes (Lytvynenko et al. 2016).

Bacteria
Pseudomonadota
AbeS of Acinetobacter baumannii (Q2FD83)
2.A.7.1.12









Small multidrug resistance (SMR) protein of 118 aas and 4 TMSs

Bacteria
Pseudomonadota
SMR of Pseudomonas psychrotolerans
2.A.7.1.13









Uncharacterized small multidrug resistance protein of 118 aas and 4 TMSs

Bacteria
Pseudomonadota
UP of Paraburkholderia phenoliruptrix
2.A.7.1.14









Uncharacterized protein of 123 aas and 4 TMSs

Bacteria
Myxococcota
UP of Sorangium cellulosum (Polyangium cellulosum)
2.A.7.1.15









SMR family protein of 116 aas and 4 TMSs

Bacteria
Actinomycetota
SMR protein of Lyngbya aestuarii
2.A.7.1.16









Small multidrug resistance (SMR) family member of 116 aas and 4 TMSs.

Bacteria
Candidatus Wolfebacteria
Smr of Candidatus Wolfebacteria bacterium
2.A.7.1.17









Putative quaternary amonium transporterof 124 aas and 4 TMSs.

Viruses
Bamfordvirae, Nucleocytoviricota
DMT transporter of Chrysochromulina ericina virus
2.A.7.1.18









Putative QacE family quaternary ammonium compound efflux (SMR-type) transporter of 108 aas and 4 TMSs.

Bacteria
Bacillota
QacE-type exporter of Lysinibacillus xylanilyticus
2.A.7.2:  The 5 TMS Bacterial/Archaeal Transporter (BAT) Family
2.A.7.2.1









Hypothethical protein
Bacteria
Pseudomonadota
Ycb6 of Pseudomonas denitrificans
2.A.7.2.2









Hypothethical protein
Archaea
Euryarchaeota
Orf of Pyrococcus abyssi
2.A.7.2.3









Uncharacterized protein of 156 aas and 5 TMSs

Eukaryota
Fungi, Mucoromycota
UP of Rhizophagus irregularis (Arbuscular mycorrhizal fungus) (Glomus intraradices)
2.A.7.2.4









Pyridoxamine-phosphate oxidase (PNPO; N-terminal) with a C-terminal DMT family domain of 4 - 5 TMSs (Guerin et al. 2015).

Eukaryota
Fungi, Ascomycota
PNPO of Penicillium digitatum (Green mold)
2.A.7.2.5









Uncharacterized protein of 138 aas and 5 TMSs.

Archaea
Euryarchaeota
UP of Haloterrigena thermotolerans
2.A.7.2.6









Uncharacterized protein of 142 aas and 5 TMSs

Bacteria
Pseudomonadota
UP of Pseudomonas aeruginosa
2.A.7.2.7









Uncharacterized protein of 137 aas and 5 TMSs.

Archaea
Euryarchaeota
UP of Natrinema versiforme
2.A.7.2.8









Uncharacterized protein of 136 aas and 5 TMSs.

Archaea
Euryarchaeota
UP of Haloarcula vallismortis
2.A.7.3:  The 10 TMS Drug/Metabolite Exporter (DME) Family
2.A.7.3.1









Putative acetate efflux pump, MadN (Berg et al. 1997).

Bacteria
Thermodesulfobacteriota
MadN of Malonomonas rubra
2.A.7.3.2









YdeD (EamA) efflux pump for O-acetylserine, cysteine, asparagine and glutamine (Dassler et al., 2000; Franke et al. 2003)

Bacteria
Pseudomonadota
YdeD of E. coli
2.A.7.3.3









PecM of 297 aas and 9 or 10 TMSs. Probable blue pigment (indigoidine) exporter (Rouanet and Nasser 2001).

Bacteria
Pseudomonadota
PecM of Erwinia chrysanthemi
2.A.7.3.4









YwfM
Bacteria
Bacillota
YwfM of Bacillus subtilis
2.A.7.3.5









Yf33
Archaea
Euryarchaeota
Yf33 of Archaeoglobus fulgidus
2.A.7.3.6









RhtA (YbiF) Threonine/Homoserine Exporter (may export other amino acids including proline, serine, cysteine, histidine and several amino acid analogues, based on resistance phenotypes (Livshits et al., 2003))

Bacteria
Pseudomonadota
RhtA (YbiF) of Escherichia coli (P0AA67)
2.A.7.3.7









The S-adenosylmethionine uptake transporter, Sam (Tucker et al., 2003) (may function by an exchange mechanism (i.e., S-adenosyl-
methionine/S-adenosylhomocysteine exchange))
Bacteria
Pseudomonadota
Sam (RPO76) of Rickettsia prowazekii
2.A.7.3.8









10 TMS DMT superfamily member of unknown function. In an operon with glucan biosynthesis protein C and the AgnG (2.A.66.5.1) exporter. Regulated by RpiR (ribose regulator). 

Bacteria
Pseudomonadota
Permease of Agrobacterium tumefaciens (A9CFB8)
2.A.7.3.9









10 TMS DMT superfamily member of unknown function.

Bacteria
Pseudomonadota
Permease of Vibriocholerae (A2P528)
2.A.7.3.10









DUF6 domain protein of unknown function

Bacteria
Actinomycetota
DUF6 protein of Rhodococccus erythropolis (C3JHC4)
2.A.7.3.11









Putative porter, SACE_6693, of unknown function

Bacteria
Actinomycetota
SACE_6693 of Saccharopolyspora erythraea (A4FP84)
2.A.7.3.12









10 TMS YicL protein of 307aas; function unknown, but may export δ-levulinate or protoporphyrin IX (Kanjo et al., 2001).

Bacteria
Pseudomonadota
YicL of E.coli (P31437)
2.A.7.3.13









Putative Drug/Metabolite Exporter

Bacteria
Pseudomonadota
DME of  Mannheimia haemolytica (A7JQ96)
2.A.7.3.14









Putative Drug/Metabolite Exporter

Bacteria
Pseudomonadota
DME of Comamonas testeroni (D8D9B1)
2.A.7.3.15









Putative DUF6 protein

Bacteria
Pseudomonadota
DUF6 protein of Xanthomonas vesicatoria (F0BFS6)
2.A.7.3.16









DMT Superfamily member

Bacteria
Chlamydiota
DMT member of Chlamydia trachomatis (D6YX63)
2.A.7.3.17









Putative transporter of 10 TMSs (TMSs 5-10 are possibly homologous to TMSs 1-6 out of 6 TMSs in LanG (9.A.29.1.1)). LanG shows limited sequence similarity to ABC porters as well.

Bacteria
Chlamydiota
Putative transporter of Chlamydophila abortus (Q5L5M5)
2.A.7.3.18









DUF6 homologue, YhbE of 412 aas and 10 TMSs.  Encoded by a gene that precedes the Obg GTPase involved in cell division and cell cycle control (Verstraeten et al. 2015). obg is expressed from an operon encoding two ribosomal proteins.  The operon's expression varies with growth phase and is dependent on the transcriptional regulators, ppGpp and DksA (Maouche et al. 2016).

Bacteria
Pseudomonadota
YhbE of E. coli (E1ILD8)
2.A.7.3.19









Possible L-alanine exporter, YtfF (Hori et al., 2011).

Bacteria
Pseudomonadota
YtfF of E. coli (P39314)
2.A.7.3.20









S-adenosylmethionine/S-adenosylhomocysteine transporter (SAM/SAH transporter) (SAMHT; CTL843).  May function in SAM uptake and SAH export, perhaps by an SAM/SAH antiport mechanism (Binet et al. 2011).

Bacteria
Chlamydiota
SAMHT of Chlamydia trachomatis serovar L2
2.A.7.3.21









Putative permease of 295 aas and 10 TMSs

Bacteria
Spirochaetota
Permease of Leptospira biflexa
2.A.7.3.22









YedA transporter of 306 aas and 10 TMSs.  Probably exports amino acids and/or other metabolites (Zakataeva et al. 2006). Mutation of the yedA gene protects the cells against toxic levels of methionine (Radi et al. 2022).

Bacteria
Pseudomonadota
YedA of E. coli (P0AA70)
2.A.7.3.23









Uncharacterized transporter BU281

Bacteria
Pseudomonadota
BU281 of Buchnera aphidicola subsp. Acyrthosiphon pisum
2.A.7.3.24









Uncharacterized transporter YdeK

Bacteria
Bacillota
YdeK of Bacillus subtilis
2.A.7.3.25









Protein PagO

Bacteria
Pseudomonadota
PagO of Salmonella typhimurium
2.A.7.3.26









Cystine exporter, YijE, of 301 aas and 10 TMSs (Yamamoto et al. 2015).

Bacteria
Pseudomonadota
YijE of Escherichia coli
2.A.7.3.27









Uncharacterized transporter BUsg_270
Bacteria
Pseudomonadota
BUsg_270 of Buchnera aphidicola subsp. Schizaphis graminum
2.A.7.3.28









Uncharacterized transporter AF_0266
Archaea
Euryarchaeota
AF_0266 of Archaeoglobus fulgidus
2.A.7.3.29









Uncharacterized transporter YoaV

Bacteria
Bacillota
YoaV of Bacillus subtilis
2.A.7.3.30









Uncharacterized transporter HI_0976.1
Bacteria
Pseudomonadota
HI_0976.1 of Haemophilus influenzae
2.A.7.3.31









Uncharacterized transporter ydeD
Bacteria
Bacillota
YdeD of Bacillus subtilis
2.A.7.3.32









Uncharacterized transporter YdfC

Bacteria
Bacillota
YdfC of Bacillus subtilis
2.A.7.3.33









DME family member

Bacteria
Actinomycetota
DME family member of Streptomyces coelicolor
2.A.7.3.34









DME family member

Bacteria
Actinomycetota
DME family member of Streptomyces coelicolor
2.A.7.3.35









Uncharacterized transporter YetK

Bacteria
Bacillota
YetK of Bacillus subtilis
2.A.7.3.36









Uncharacterized transporter AF_0510
Archaea
Euryarchaeota
AF_0510 of Archaeoglobus fulgidus
2.A.7.3.37









The DUF6 domain transporter homologue, TrH3 (299 aas; 10 TMSs in a 2 + 8 arrangement)
Bacteria
Pseudomonadota
TrH3 of Candidatus Pelagibacter ubique (Q4FKW8)
2.A.7.3.38









Uncharacterized transporter YrdR

Bacteria
Bacillota
YrdR of Bacillus subtilis
2.A.7.3.39









Putative transporter

Bacteria
Actinomycetota
Putative transporter of Streptomyces coelicolor
2.A.7.3.40









Putative transporter

Bacteria
Myxococcota
Putative transporter of Myxococcus xanthus
2.A.7.3.41









Hypothetical protein, HP 

Bacteria
Actinomycetota
HP of Streptomyces coelicolor (Q9AK99)
2.A.7.3.42









Putative riboflavin porter, ImpX. Regulated by FMN riboswitch (Vitreschak et al. 2002)

Bacteria
Bacillota
ImpX of Bacillus clausii (Q5WDG6)
2.A.7.3.43









Uncharacterized transporter

Bacteria
Actinomycetota
Uncharacterized protein of Streptomyces coelicolor
2.A.7.3.44









Hypothetical protein of 302 aas and 10 TMSs

Archaea
Euryarchaeota
HP of Halarcula hispanica
2.A.7.3.45









Hypothetical protein of 363 aas and 10 TMSs

Bacteria
Planctomycetota
HP of Rhodopirellula baltica
2.A.7.3.46









Hypothetical protein

Bacteria
Planctomycetota
HP of Rhodopirellula baltica
2.A.7.3.47









10 TMS DME homologue of 280 aas

Archaea
Euryarchaeota
DME homologue of Pyrococcus abyssi
2.A.7.3.48









Multidrug resistance pump, EmrE

Bacteria
Actinomycetota
EmrE of Blastococcus saxobsidens
2.A.7.3.49









Peptidase S8 & S53 Subtilisin/kexin/sedolisin.  Has an N-terminal 10 (or 11) TMSs followed by a large hydrophilic domain that includes the protease domain. 

Bacteria
Actinomycetota
Peptidase with N-terminal 10 TMSs of Micromonospora aurantiaca
2.A.7.3.50









Uncharacterized protein of 13 putative TMSs

Eukaryota
Rhodophyta
Putative porter of Galdieria sulphuraria
2.A.7.3.51









Putative permease of 494 aas

Eukaryota
Rhodophyta
Putative permease of Cyanidioschyzon merolae
2.A.7.3.52









Putative permease of 277 aas

Bacteria
Deinococcota
Putative permease of Thermus oshimai
2.A.7.3.53









Putative permease of 467 aas and 10 TM

Eukaryota
Bacillariophyta
Putative permease of Thalassiosira oceanica
2.A.7.3.54









Riboflavin uptake transporter, RibN of 302 aas and 10 putative TMSs (García Angulo et al. 2013).

Bacteria
Pseudomonadota
RibN of Rhizobium legumenosarum
2.A.7.3.55









Riboflavin transporter, RibN, of 284 aas and 8 putative TMSs (García Angulo et al. 2013).

Bacteria
Pseudomonadota
RibN of Ochrobactrum anthropi
2.A.7.3.56









Riboflavin uptake porter, RibN, of 284 aas and 10 TMSs (García Angulo et al. 2013).

Bacteria
Pseudomonadota
RibN of Vibrio cholerae
2.A.7.3.57









Putative permease of 299 aas and 10 TMSs

Bacteria
Bacteroidota
UP of Bacteroides thetaiotaomicron
2.A.7.3.58









Possible transporter of polar amino acids including glutamate, glutamine and aspartate, DmeA. It complements a sepJ mutation in Anabaena (TC# 2.A.7.23.2), and SepJ complements a dmeA mutation. Alternatively, and less likely, it could be an activator of an ABC transporter catalyzing uptake of these amino acids (Escudero et al. 2015).

Bacteria
Cyanobacteriota
DmeA of Synechococcus elongatus (strain PCC 7942) (Anacystis nidulans R2)
2.A.7.3.59









Uncharacterized protein of 347 aas and 10 TMSs

Bacteria
Spirochaetota
UP of Treponema denticola
2.A.7.3.60









Uncharacterized protein of 306 aas and 10 TMSs.

Bacteria
Pseudomonadota
UP of Bradyrhizobium japonicum
2.A.7.3.61









Putative transporter, YigM, of 299 aas and 10 TMSs.

Bacteria
Pseudomonadota
YigM of E. coli
2.A.7.3.62









Uncharacterized DMT porter of 332 aas and 10 TMSs

Bacteria
Bdellovibrionota
UP of Bdellovibrio exovorus
2.A.7.3.63









DMT family transporter of 352 aas and 10 TMSs

Bacteria
Pseudomonadota
UP of Cupriavidus gilardii
2.A.7.3.64









Uncharacterized protein of 304 aas and 10 TMSs

Bacteria
Bdellovibrionota
UP of Bdellovibrio exovorus
2.A.7.3.65









Riboflavin (vitamin B2) uptake porter, ImpX, of 301 aas and 10 TMSs. the Khalf for riboflavin uptake was 20 µM. Transport experiments suggested that the energy source is the proton motive force (Rodionova et al. 2019).

Bacteria
Bdellovibrionota
ImpX of Bdellovibrio exovorus
2.A.7.3.66









Amino acid and toxic analogue exporter, YddG of 298 aas and 10 establsihed TMSs.  The 3-d x-ray structures (PD# 5I20) of this protein and a homologue (TC# 3.A.7.17.2) have been determined at 2.4 Å resolution, showing the outward facing conformation of a basket shaped structure with a central substrate binding cavity (Tsuchiya et al. 2016).

Pseudomonadota
YddG of Starkeya novella, an α-proteobacterium
2.A.7.3.67









PecM (YedA) of 294 aas and 10 TMSs.  Promotes invasion and intracellular survival of enteropathogenic E. coli (EPEC) cells (Burska and Fletcher 2014).

Bacteria
Pseudomonadota
PecM of E. coli
2.A.7.3.68









Uncharacterized protein of 303 aas and 10 TMSs

Bacteria
Pseudomonadota
UP of Methylobacterium nodulans
2.A.7.3.69









Uncharacterized protein of 279 aas and 9 TMSs

Bacteria
Pseudomonadota
UP of Methylophaga lonarensis
2.A.7.3.70









10 TMS DMT superfamily member

Bacteria
Planctomycetota
DMT member of Rhodopirellula baltica
2.A.7.3.71









Riboflavin uptake transporter of 299 aas and 10 TMSs, ImpX (Gutiérrez-Preciado et al. 2015). 

Bacteria
Fusobacteriota
ImpX of Fusobacterium nucleatum
2.A.7.3.72









Uncharacterized DMT superfamily protein of 277 aas and 10 TMSs

Bacteria
Candidatus Beckwithbacteria
UP of Candidatus Beckwithbacteria bacterium
2.A.7.3.73









Uncharacterized protein of 290 aas and 10 TMSs.

Bacteria
Candidatus Beckwithbacteria
UP of Candidatus Beckwithbacteria bacterium
2.A.7.3.74









The putative tryptophan efflux protein, YcbK

Bacteria
Bacillota
YcbK of Bacillus subtilis (P42243)
2.A.7.3.75









SepJ, a novel composite protein of 751 aas needed for cellular filament integrity, proper heterocyst development and N2 fixation. It has a C-terminal DME family domain (Flores et al., 2007). Mullineaux et al. (2008) have proposed that this protein (SepJ; FraG) may be a channel-forming protein for transfer of metabolites between cells.  However, it may instead be a polar amino acid transporter since DmeA of Synecococcus (TC# 2.A.7.3.58) complements a defect in SepJ (E. Flores, unpubished observations).

Bacteria
Cyanobacteriota
SepJ of Anabaena sp. PCC7120 (Q8YUK6)
2.A.7.3.76









Uncharacterized DMT family protein of 297 aas and 10 TMSs

Bacteria
Pseudomonadota
UP of Pseudoalteromonas luteoviolacea
2.A.7.3.77









Uncharacterized DMT member of 341 aas and 10 TMSs.

Bacteria
Pseudomonadota
UP of Parvularcula oceani
2.A.7.3.78









Uncharacterized protein of 303 aas and 10 TMSs.

Bacteria
Pseudomonadota
UP of Parvularcula oceani
2.A.7.3.79









Uncharacterized putative DMT family protein of 313 aas and 10 TMSs

Bacteria
Bacillota
UP of Lactobacillus similis
2.A.7.3.80









Co2+/Ni2+ efflux porter of 351 aas and 10 TMSs, CnrT. 74% identical to TC# 2.A.7.3.63, anonther protein of the DMT superfamily of unknown function (Nies 2003).

Bacteria
Pseudomonadota
CnrT of Cupriavidus metallidurans (Ralstonia metallidurans)
2.A.7.3.81









SepJ of 751 aas and 10 C-terminal domains with an N-terminal SMC (structural maintenance of chromosomes) domain and a central DUF4775 domain, before the 10 TMS DMT domain.  It may transport asp, glu and gln, or it may activate an ABC-type transporter of this specificity (Escudero et al. 2015). It may be a part of the cyanobacterial intercellular septum together with FraC (P46078) and FraD (P46079).

Bacteria
Cyanobacteriota
SepJ of Anabaena sp. 90
2.A.7.3.82









Riboflavin (RF) uptake porter, ImpX, of 302 aas and 10 TMSs.  Functional complementation, growth inhibition experiments, direct uptake experiments and inhibition studies, suggesting a high degree of specificity for RF uptake (Rodionova et al. 2019). The EC50 for growth with RF was estimated to be in the range 0.5-1 µM, estimated from the half-maximal RF concentration supporting the growth of a RF auxotrophic Escherichia coli strain, but the Khalf for RF uptake was 20 µM. Transport experiments suggested that the energy source is the proton motive force, but that NaCl stimulates uptake (Rodionova et al. 2019).

Bacteria
Bdellovibrionota
ImpX of Bdellovibrio exovorus JSS
2.A.7.3.83









Uncharacterized protein of 318 aas and 10 TMSs

Archaea
Candidatus Heimdallarchaeota
UP of Candidatus Heimdallarchaeota archaeon B3_Heim (marine sediment metagenome)
2.A.7.3.84









DMT family metabolite transporter of 311 aas and 10 TMSs.

Bacteria
DMT transporter of Patescibacteria group bacterium
2.A.7.3.85









Uncharacterized protein of 148 aas and 5 TMSs.

Bacteria
UP of Parcubacteria group bacterium GW2011_GWC2_52_8c (groundwater metagenome)
2.A.7.3.86









Uncharacterized protein of 300 aas and 10 TMSs

Bacteria
Candidatus Beckwithbacteria
UP of Candidatus Beckwithbacteria bacterium
2.A.7.3.87









Triose-P (PEP; glycerate-3-P and glycerate-2-P) of 302 aas and 10 TMSs .

Bacteria
Bacillota
Triose-P transporter of Lysinibacillus xylanilyticus .
2.A.7.3.88









DMT putative drug resistance efflux pump of 320 aas and 10 TMSs in a 2 + 3 + 2 + 3 TMS arrangement (Chanket et al. 2024).

Bacteria
Bacillota
DMT drug efflux pump of Clostridioides difficile (strain 630) (Peptoclostridium difficile)
2.A.7.4:  The Plant Amino Acid Transporter (UMAMIT) (formerly the P-DME) Family

The P-DME (UMAMIT) family is a large subset of the DME family. All of these proteins are derived from plants, and they cluster loosely together on a phylogenetic tree that includes all members of the DME and P-DME families. All of these proteins are predicted by various methods to have 10 TMSs. If this suggestion proves to be correct, then the two halves of these proteins will have opposite orientation in the membrane. The P-DME family members have been called UMAMIT, and form large gene families in Arabidopsis (47 members) and rice (53 members). The few characterized members from Arabidopsis mediate amino acid export from the cytosol, with two of them shown to function as facilitators. They can be found in the plasma membrane (Ladwig et al 2012, Muller et al 2015, Besnard et al 2016, 2018) or the vacuolar membrane (Ranocha et al, 2010, Besnard et al 2018). They play multiple role in amino acid translocation between the organs of the plants, e.g. from leaves to seeds or to roots”.

2.A.7.4.1









MtN21 nodulin protein
Eukaryota
Viridiplantae, Streptophyta
MtN21 of Medicago truncatula
2.A.7.4.2









Nodulin MfN21 or UMAMIT24 of 355 aas and 10 TMSs. UMAMIT24 and UMAMIT25 function in amino acid transfer in developing seeds. Besnard et al. 2018 showed that UMAMIT24 and UMAMIT25 promote export of a broad range of amino acids. They are expressed in distinct tissues within developing seeds; UMAMIT24 is mainly expressed in the chalazal seed coat and localized on the tonoplast, whereas the plasma membrane-localized UMAMIT25 is expressed in endosperm cells.

Eukaryota
Viridiplantae, Streptophyta
MfN21 of Arabidopsis thaliana (NP_173898)
2.A.7.4.3









Nodulin MtN21/EamA-like transporter

Eukaryota
Viridiplantae, Streptophyta
Nodulin MtN21 of Arabidopsis thaliana (Q9ZUI8)
2.A.7.4.4









WAT1 (Walls are thin 1) of 389 aas and 10 TMSs in a 5 + 5 TMS arrangement. Required for secondary wall formation in fibers, especially in short days conditions. Promotes indole metabolism and transport (e.g. tryptophan, neoglucobrassicin and auxin (indole-3-acetic acid)) (Denancé et al. 2013). May prevent salicylic-acid (SA) accumulation. It exports indolebutyric acid from vacuoles (Damodaran and Strader 2019).

Eukaryota
Viridiplantae, Streptophyta
WAT1 of Arabidopsis thaliana
2.A.7.4.5









UMAMIT14 amino acid efflux transporter of 374 aas and 10 TMSs, a member of the nodulin MtN21 family. It is involved in phloem unloading in Arabidopsis roots (Besnard et al. 2016). UMAMIT14 is expressed in root pericycle and phloem cells and mediates export of a broad range of amino acids. Loss-of-function of UMAMIT14 leads to a reduced shoot-to-root and root-to-medium transfer of amino acids originating from the leaves. These fluxes were further reduced in an umamti14 umamit18 double loss-of-function mutant. Thus, UMAMIT14 is involved in phloem unloading of amino acids in roots, and both UMAMIT14 and UMAMIT18 are involved in the radial transport of amino acids in roots (Besnard et al. 2016).

Eukaryota
Viridiplantae, Streptophyta
UMAMIT14 in Arabidopsis thaliana (Mouse-ear cress)
2.A.7.4.6









Red1; UMAMIT18; WAT1-related protein At1g44800, or SIART of 370 aas and 10 TMSs. It is an L-amino acid efflux transporter that can function bidirectionally into and out of the cell (Müller et al. 2015). In Arabidopsis, SIAR1 localizes to the plasma membrane and is expressed in the vascular tissue, in the pericycle, stamen, and the chalazal seed coat of ovules and developing seeds. Mutant alleles of SIAR1 accumulate anthocyanins as a symptom of reduced amino acid content in the early stages of silique development (Ladwig et al. 2012).

 

Eukaryota
Viridiplantae, Streptophyta
Red1 of Arabidopsis thaliana (Mouse-ear cress)
2.A.7.4.7









RTP1 of 375 aas and 10 TMSs, a nodulin‐related MtN21 family endoplasmic reticulum protein that mediates susceptibility to infection by the fungi, Phytophthora parasitica and Golovinomyces cichoracearum, as well as the bacterium, Pseudomonas syringae (Pan et al. 2016). In agreement with the functions of other members of the NODULIN21 family, it probably catalyzes uptake of amino acids from the cytoplasm into the lumen of the ER.

Eukaryota
Viridiplantae, Streptophyta
RTP1 of Arabidopsis thaliana
2.A.7.4.8









USUALLY MULTIPLE AMINO ACIDS MOVE IN AND OUT TRANSPORTER (UMAMIT) family proteiin, UMAMIT29 is a glucosinolate exporters with a uniport mechanism. Loss-of-function umamit29 umamit30 umamit31 triple mutants have a very low level of seed glucosinolates, demonstrating a key role for these transporters in translocating glucosinolates into seeds. The UMAMIT uniporters facilitate glucosinolate efflux from biosynthetic cells along the electrochemical gradient into the apoplast, where the high-affinity H+-coupled glucosinolate importers GLUCOSINOLATE TRANSPORTERS (GTRs) load them into the phloem for translocation to the seeds (Xu et al. 2023).

 

Eukaryota
Viridiplantae, Streptophyta
UMAMIT29 of Arabidopsis thaliana
2.A.7.4.9









USUALLY MULTIPLE AMINO ACIDS MOVE IN AND OUT TRANSPORTER (UMAMIT) family proteiin, UMAMIT30 is a glucosinolate exporters with a uniport mechanism. Loss-of-function umamit29 umamit30 umamit31 triple mutants have a very low level of seed glucosinolates, demonstrating a key role for these transporters in translocating glucosinolates into seeds. The UMAMIT uniporters facilitate glucosinolate efflux from biosynthetic cells along the electrochemical gradient into the apoplast, where the high-affinity H+-coupled glucosinolate importers GLUCOSINOLATE TRANSPORTERS (GTRs) load them into the phloem for translocation to the seeds (Xu et al. 2023).

Eukaryota
Viridiplantae, Streptophyta
UMAMIT30 of Arabidopsis thaliana
2.A.7.4.10









USUALLY MULTIPLE AMINO ACIDS MOVE IN AND OUT TRANSPORTER (UMAMIT) family proteiin, UMAMIT31 is a glucosinolate exporters with a uniport mechanism. Loss-of-function umamit29 umamit30 umamit31 triple mutants have a very low level of seed glucosinolates, demonstrating a key role for these transporters in translocating glucosinolates into seeds. The UMAMIT uniporters facilitate glucosinolate efflux from biosynthetic cells along the electrochemical gradient into the apoplast, where the high-affinity H+-coupled glucosinolate importers GLUCOSINOLATE TRANSPORTERS (GTRs) load them into the phloem for translocation to the seeds (Xu et al. 2023).

Eukaryota
Viridiplantae, Streptophyta
UMAMIT31 of Arabidopsis thaliana
2.A.7.5:  The Glucose/Ribose Porter (GRP) Family
2.A.7.5.1









Glucose uptake permease, GlcU
Bacteria
Bacillota
GlcU (GltT) of Staphylococcus xylosus
2.A.7.5.2









Probable ribose transporter, RbsU
Bacteria
Bacillota
RbsU of Lactobacillus sakei
2.A.7.5.3









Glucose:H+ symporter, GlcU (YxfA) (high specificity, low affinity) (Castro et al., 2009). The effect of glucose stress on metabolic adaptation of Lactococcus lactis revealed that glucose stress up-regulated organic acid transport but down-regulated amino acid transport, resulted in a decrease in nitrogen metabolism (Qi et al. 2020).

Bacteria
Bacillota
GlcU of Lactococcus lactis (Q9CDF7)
2.A.7.5.4









Glucose permease, GlcU (also called YcxE). (Fiegler et al., 1999) (similar to 2.A.7.5.1).

Bacteria
Bacillota
GlcU of Bacillus subtilis (P40420)
2.A.7.5.5









The glucose uptake porter of 285 aas, GlcU (Aké et al. 2011).

Bacteria
Bacillota
GlcU of Listeria monocytogenes
2.A.7.5.6









DMT putative multidrug efflux pump of 284 aas and 10 TMSs (Chanket et al. 2024).

Bacteria
Bacillota
Putative DMT-type MDR exporter of Clostridioides difficile (strain 630) (Peptoclostridium difficile)
2.A.7.6:  The L-Rhamnose Transporter (RhaT) Family
2.A.7.6.1









Rhamnose:H+ symporter, RhaT (Garcia-Martin et al. 1992) of 344 aas and 10 TMSs in a 5 + 5 TMS arrangement (Tate and Henderson 1993).  IT belongs to the TMEM144 family. Transcriptional regulation of rhaT is due to the RhaS activator, and L-rhamnose, L-lyxose and L-mannose activate (Vía et al. 1996).

Bacteria
Pseudomonadota
RhaT of E. coli
2.A.7.6.2









L-rhamnose-proton symporter, RhaT, of 340 aas and 10 TMSs

Bacteria
Planctomycetota
RhaT of Rhodopirellula sallentina
2.A.7.6.3









L-rhamnose-proton symport protein, RhaT, of 337 aas and 10 TMSs

Bacteria
Bacteroidota
RhaT of Joostella marina
2.A.7.6.4









Uncharacterized protein of 627 aas and 8 - 10 TMSs.

Eukaryota
UP of Guillardia theta
2.A.7.7:  The Chloramphenicol-Sensitivity Protein (RarD) Family
2.A.7.7.1









The chloramphenicol-sensitive protein, RarD
Bacteria
Pseudomonadota
RarD of Pseudomonas aeruginosa
2.A.7.7.2









Protein RarD.  Involved in antibiotic resistance (Carruthers et al. 2010).

Bacteria
Pseudomonadota
RarD of Escherichia coli
2.A.7.7.3









Uncharacterized transporter HI_0680
Bacteria
Pseudomonadota
HI_0680 of Haemophilus influenzae
2.A.7.8:  The Caenorhabditis elegans ORF (CEO) Family
2.A.7.8.1









Hypothetical protein, Yrr6
Eukaryota
Metazoa, Nematoda
Yrr6 of Caenorhabditis elegans
2.A.7.8.2









TM protein 144 homologue 2 (DUF1632 homologue).

Eukaryota
Evosea
TMP144-2 of Dictyostelium discoideum (Q54V96)
2.A.7.8.3









TMEM144 protein of 345 aas and 9 TMSs in a 4 + 5 TMS arrangement. TMEM144 is up-regulated in the hypothalamus (Prentice et al. 2011).

Eukaryota
Metazoa, Chordata
TMEM144 of Homo sapiens
2.A.7.9:  The Triose-phosphate Transporter (TPT) Family
2.A.7.9.1









Chloroplast triose-P/glycerate-3-P:Pi antiporter (TPT) (phosphoenolpyruvate and 2-phosphoglycerate are poor substrates).
Eukaryota
Viridiplantae, Streptophyta
TPT of Zea mays
2.A.7.9.2









Nongreen plastid/chloroplast glucose-P/triose-P/glycerate-P:Pi antiporter (GPT) (Both glucose-6-P and glucose-1-P are substrates; other hexose-Ps may also be transported). (Exchanges phosphoenolpyruvate for inorganic phosphate (Nozawa et al., 2007)
Eukaryota
Viridiplantae, Streptophyta
GPT of Brassica oleracea
2.A.7.9.3









Chloroplast phosphoenolpyruvate:Pi antiporter (PPT) (triose-Ps and glycerate- Ps are poor substrates).
Eukaryota
Viridiplantae, Streptophyta
PPT of Zea mays
2.A.7.9.4









Sly41p (transport function unknown)
Eukaryota
Fungi, Ascomycota
Sly41p of Saccharomyces cerevisiae
2.A.7.9.5









The plastidic phosphate/triosephosphate transporter, TPT (Linka et al., 2008). TPT catalyses the strict 1:1 exchange of triose-phosphate, 3-phosphoglycerate and inorganic phosphate across the chloroplast envelope Lee et al. 2017 reported crystal structures of TPT bound to two different substrates, 3-phosphoglycerate and inorganic phosphate, in occluded conformations. The structures reveal that TPT adopts a 10-transmembrane drug/metabolite transporter fold. Both substrates are bound within the same central pocket, where conserved lysine, arginine and tyrosine residues recognize the shared phosphate group. A structural comparison with the outward-open conformation of the bacterial drug/metabolite transporter suggests a rocker-switch motion of helix bundles, and molecular dynamics simulations support a model in which this rocker-switch motion is tightly coupled to substrate binding to ensure strict 1:1 exchange. The results reveal the mechanism of sugar phosphate/phosphate exchange by TPT. TPTexports  Calvin cycle intermediates from chloroplasts and plays fundamental roles in nearly all photosynthetic eukaryotes (Lee et al. 2017).

Eukaryota
Rhodophyta
TPT Galdieria sulphuraria (B5AJT1)
2.A.7.9.6









Chloroplast Glucose-6-P/Pi antiporter-2, Gpt2

Eukaryota
Viridiplantae, Streptophyta
Gpt2 of Arabidopsis thaliana (Q94B38)
2.A.7.9.7









solute carrier family 35, member E2B, SLC35A2B, of 405 aas and 8-10 TMSs. It may take up a nucleobase-containing compounds (Yamada et al. 2017). Mutations in SLC35E2B and the Flrt3 (FLRT3; TC# 8.A.43.1.27) protein can give rise to high myopia, an eye disorder in which both environmental and genetic factors are involved (Swierkowska et al. 2021).

Eukaryota
Metazoa, Chordata
SLC35E2B of Homo sapiens
2.A.7.9.8









solute carrier family 35, member C2

Eukaryota
Metazoa, Chordata
SLC35C2 of Homo sapiens (Q8VCX2)
2.A.7.9.9









solute carrier family 35, member E1 of 410 aas and 10 TMSs. It may play a role in heroin addition (Shi et al. 2020) as well as in the nuclear rgress of Herpes Simplex Virus 1(Maeda et al. 2022).

.

Eukaryota
Metazoa, Chordata
SLC35E1 of Homo sapiens
2.A.7.9.10









solute carrier family 35, member E3

Eukaryota
Metazoa, Chordata
member E3 of Mus musculus (Q6PGC7)
2.A.7.9.11









The putative thiamine pyrophosphate transporter, SLC35E4, of 350 aas and 10 TMSs. A competing endogenous RNA network involving the gene for SLC35E4 is related to the prognosis of cholangiocarcinoma (Wang et al. 2021).

Eukaryota
Metazoa, Chordata
SLC35E4 of Homo sapiens
2.A.7.9.12









UDP-galactose, UDP-rhamnose, (and maybe UDP-glucose and UDP-fructose) transporter 2, UGAL2 (At1g76670) (Bakker et al. 2005; Rautengarten et al. 2014).

Eukaryota
Viridiplantae, Streptophyta
UGAL2 of Arabidopsis thaliana (Q9SRE4)
2.A.7.9.13









Golgi nucleotide-sugar (probable UDP-galactose/UDP-rhamnose) transporter (At1g21070; EamA superfamily member), of 335 aas and 10 TMSs.

Eukaryota
Viridiplantae, Streptophyta
At1g21070 of Arabidopsis thaliana (Q9LPU2)
2.A.7.9.14









Putative nucleotide-sugar transporter YMD8
Eukaryota
Fungi, Ascomycota
YMD8 of Saccharomyces cerevisiae
2.A.7.9.15









Solute carrier family 35 member E3 (Bladder cancer-overexpressed gene 1 protein). SLC35E3 has been identified as a target of novel‑m1061‑5p via microRNA profiling of patients with cardiovascular disease (Gao et al. 2018).

 

Eukaryota
Metazoa, Chordata
SLC35E3 of Homo sapiens
2.A.7.9.16









Solute carrier family 35 member C2, SLC35C2. (Ovarian cancer-overexpressed gene 1 protein) of 365 aas and 10 TMSs. It may play a role in the cellular response to tissue hypoxia, and may be either a GDP-fucose transporter that competes with SLC35C1 for GDP-fucose, or a factor that otherwise enhances the fucosylation of Notch and is required for optimal Notch signaling in mammalian cells (Lu et al. 2010).  It may transport GDP-fucose (Lu et al. 2023).

Eukaryota
Metazoa, Chordata
SLC35C2 of Homo sapiens
2.A.7.9.17









Probable sugar phosphate/phosphate translocator At2g25520
Eukaryota
Viridiplantae, Streptophyta
At2g25520 of Arabidopsis thaliana
2.A.7.9.18









Putative transporter C83.11
Eukaryota
Fungi, Ascomycota
SPBC83.11 of Schizosaccharomyces pombe
2.A.7.9.19









Glucose-6-phosphate/phosphate-translocator-like protein 1
Eukaryota
Viridiplantae, Streptophyta
At4g03950 of Arabidopsis thaliana
2.A.7.9.20









Golgi UDP-galactofuranose transporter, UgtA of 399 aas and 11 TMSs (Engel et al. 2009). This and several other species have two redundant transporters that can substitute for each other, UgtA and UgtB (Park et al. 2015).  Plays a role in hyphal morphogenesis, cell wall archtecture, conidiation and drug susceptibility (Engel et al. 2009). This and several other species have two redundant transporters that can substitute for each other, UgtA and UgtB (Park et al. 2015).  Plays a role in hyphal morphogenesis, cell wall archtecture, conidiation and drug susceptibility (Afroz et al. 2011).

Eukaryota
Fungi, Ascomycota
UgtA of Aspergillus niger
2.A.7.9.21









UDP-galactofuranose transporter of 400 aas and 11 TMSs, GlfB (Engel et al. 2009).  Galactofuranose-containing glycolipids and glycoproteins are in the cell envelopes of several eukaryotes where they have been shown to contribute, for example, to the virulence of the parasite Leishmania major and the fungus Aspergillus fumigatus.

Eukaryota
Fungi, Ascomycota
GlfB of Neosartorya fumigata (Aspergillus fumigatus)
2.A.7.9.22









Xylulose-5-P:Pi antiporter, Xpt or Rpt of 417 aas (Knappe et al. 2003).

Eukaryota
Viridiplantae, Streptophyta
Xpt of Arabidopsis thaliana
2.A.7.9.23









The triose-P:Pi antiporter, TPT or Ape2 of 410 aas and 10 TMSs. Transports inorganic phosphate, 3-phosphoglycerate (3-PGA), 2-phosphoglycerate (2PG) and phosphoenolpyruvate (PEP) as well as triose phosphates. Functions in the export of photoassimilates from chloroplasts during the day. In the light, triose phosphates are exported from the chloroplast stroma in counter exchange with inorganic phosphate (Pi), generated for sucrose biosynthesis in the cytosol. Involved in photosynthetic acclimation, a light response resulting in increased tolerance to high-intensity light (Knappe et al. 2003). The crylstal structures of TPT from Galdieria sulphuraria have been solved revealing the protein bound to two different substrates, 3-phosphoglycerate and inorganic phosphate, in occluded conformations.

Eukaryota
Viridiplantae, Streptophyta
TPT of Arabidopsis thaliana
2.A.7.9.24









The phosphoenolpyruvate/phosphate translocator, pPT, of 524 aas in the outer membranes of apicoplasts, vestigial plastids in apicomplexan parasites such as Plasmodium. Transports glucose-6 P and triose-3 Ps via an inorganic phosphate antiport mechanism.  Apicomplexan parasites are dependant on their apicoplasts for synthesis of various molecules that they are unable to scavenge in sufficient quantity from their host. They import carbon, energy and reducing power to drive anabolic synthesis in the organelle. pPT is targeted into the outer apicoplast membrane via a transmembrane domain that acts as a recessed signal anchor to direct the protein into the endomembrane system. A tyrosine in the cytosolic N-terminus of the protein is essential for targeting (Lim et al. 2016).

Eukaryota
Apicomplexa
pPT of Plasmodium falciparum
2.A.7.9.25









Putative triose-P (PEP, Gly-2-P and Gly-3-P) uptake porter of 342 aas and 8 - 10 TMSs.

Eukaryota
Apicomplexa
Triose-P transporter of Plasmodiium falciparum
2.A.7.9.26









Triose-P:P antiporter of 478 aas and 10 TMSs (residues 180 - 478).  The first 180 aas are strongly hydrophilic.

Eukaryota
Apicomplexa
Triose-P of Plasmodium falciparum
2.A.7.10:  The UDP-N-Acetylglucosamine:UMP Antiporter (UAA) Family
2.A.7.10.1









UDP-N-acetylglucosamine:UMP antiporter
Eukaryota
Fungi, Ascomycota
Mnn2-2 of Kluyveromyces lactis
2.A.7.10.2









The bifunctional ER-Golgi nucleotide sugar transporter with specificity for UDP-xylose and UDP-N-acetylglucosamine, SLC35B4 (Ashikov et al., 2005) for glycosylation. SLC35B4 plays a role in hepatocellular carcinoma (HCC) tumorigenesis (Jiang et al. 2022). The expression levels of SLC35B4 are higher in HCC tissues than adjacent non-tumor tissues, and SLC35B4 is important for the proliferation and tumorigenesis of HCC cells. Mechanistically, SLC35B4 is important for the O-GlcNAc modification of c-Myc and thus the stabilization of c-Myc, which is required for HCC tumorigenesis (Jiang et al. 2022). 

Eukaryota
Metazoa, Chordata
SLC35B4 of Homo sapiens
2.A.7.10.3









Golgi UDP-N-acetylglucosamine (UDP-GlcNAc) transporter.

Eukaryota
Evosea
SLC35B4 (610923) of Homo sapiens (Q869W7)
2.A.7.10.4









Endoplasmic reticular multifunctional nucleotide sugar transporter, Efr.  Substrates include GDP-fucose which can be used to fucosylate the luminar domain of the transmembrane NOTCH receptor (Ishikawa et al. 2010).

Eukaryota
Metazoa, Arthropoda
Efr of Drosophila melanogaster
2.A.7.10.5









ER/Golgi UDP-N-acetylglucosamine transporter, Yea4 of 342 aas.  Required for chitin biosynthesis (Roy et al. 2000).  Extracellular UDP-sugars promote cellular responses by interacting with widely distributed P2Y(14) receptors, and the ER/Golgi lumen constitutes a source of extracellular UDP-sugars (Sesma et al. 2009).  Yea4 therefore plays a critical role in nucleotide sugar-promoted cell signaling.

Eukaryota
Fungi, Ascomycota
Yea4 of Saccharomyces cerevisiae
2.A.7.11:  The UDP-Galactose:UMP Antiporter (UGA) Family
2.A.7.11.1









Possible UDP-galactose:UMP and documented ATP/ADP exchanger (antiporter).  Residues essential or important for activity have been identified (Chan et al. 2010). The apparent affinities of SLC35B1 for ATP/ADP on the internal face were approximately 13 times higher than those on the external side (Schwarzbaum et al. 2022). ATP/ADP exchange by SLC35B1 is not strict; other di- and trinucleotides can act as counter-substrates for ATP, although mononucleotides and nucleotide sugars were not transported. Conserved residues K117 and K120 in TMS 4 and K277 in TMS 9 play critical roles in transport. The fact that SLC35B1 can promote ATP transport in exchange for ADP or UDP suggests a more direct coupling between ATP import requirements and the need for eliminating ADP and UDP, which are generated as side products of reactions taking place in the ER-lumen (Schwarzbaum et al. 2022). SLC35B1 contributes to the uptake of UDPGA into the endoplasmic reticulum for glucuronidation catalyzed by UDP-glucuronosyltransferases (Ondo et al. 2020).

Eukaryota
Metazoa, Chordata
SLC35B1 of Homo sapiens
2.A.7.11.2









Golgi adenosine 3'-phosphate 5'-phosphosulfate transporter, slalom (functions by an exchange mechanism, essential for viability (Kamiyama et al., 2003)).
Eukaryota
Metazoa, Arthropoda
slalom of Drosophila melanogaster
(Q9VEI3)
2.A.7.11.3









Golgi adenosine 3'-phosphate 5'-phosphosulfate (PAPS):adenosine 3'-phosphate 5'-phosphate (PAP) antiporter, PAPST1 (Maszczak-Seneczko et al. 2022). (Mutations cause human inherited disorders (orthologue of 2.A.7.11.2) (Kamiyama et al., 2003). SLC35B2 is encoded by a gene that is a susceptibility gene for rheumatoid arthritis (Mo et al. 2020). 

Eukaryota
Metazoa, Chordata
SLC35B2 of Homo sapiens
2.A.7.11.4









Golgi UDP-galactose/UDP-glucose:UDP antiporter, UTr1 (Norambuena et al., 2002)
Eukaryota
Viridiplantae, Streptophyta
UTr1 of Arabidopsis thaliana
(O64503)
2.A.7.11.5









SLC35B3 translocates adenosine 3'-phosphate 5'-phosphosulfate, PAPS, the high-energy sulfate donor from the cytosol to the Golgi lumen for sulfation of glycoproteins, proteoglycans and glycolipids (Kamiyama et al. 2006). It is encoded by a gene in a signature gene set that serves as a simple proxy as a promising biomarker to predict chemoresponsiveness of muscle-invasive bladder cancer (MIBC) patients (Hepburn et al. 2021).

Eukaryota
Metazoa, Chordata
SLC35B3 of Homo sapiens
2.A.7.11.6









UDP-galactose transporter homologue 1 (Multicopy suppressor of leflunomide-sensitivity protein 6)

Eukaryota
Fungi, Ascomycota
HUT1 of Saccharomyces cerevisiae
2.A.7.11.7









UDP-galactose/UDP-glucose transporter 5 (AtUTr5)
Eukaryota
Viridiplantae, Streptophyta
UTR5 of Arabidopsis thaliana
2.A.7.11.8









UDP-glucose transporter, UGT4.  Does not transport UDP-galactose (Seino et al. 2010).

Eukaryota
Viridiplantae, Streptophyta
UGT4 of Oryza sativa
2.A.7.11.9









DMT2 of 322 aas and 10 TMSs. Propsed to transport divalent metal ions or IPP (Wunderlich 2022).

Eukaryota
Apicomplexa
DMT2 of Plasmodium falciparum
2.A.7.11.10









UDP-galactose transporter, putative, UGT, of 343 aas and probably 10 TMSs.

Eukaryota
Apicomplexa
UGT of Plasmodium falciparum
2.A.7.12:  The CMP-Sialate:CMP Antiporter (CSA) Family
2.A.7.12.1









CMP-sialic acid:CMP antiporter. Amino acid residues important for CMP-sialic acid recognition have been identified (Takeshima-Futagami et al., 2012).  Residues essential for activity have been identified (Chan et al. 2010).

Eukaryota
Metazoa, Chordata
CMP-sialic acid transporter of Mus musculus (Q61420)
2.A.7.12.2









CMP-Sialic Acid Transporter (CMP-SAT)
Eukaryota
Metazoa, Arthropoda
CMP-SAT of Aedes aegypti (Q175F9)
2.A.7.12.3









UDP-Galactose Transporter, UTR6
Eukaryota
Viridiplantae, Streptophyta
UTR6 of Arabidopsis thaliana (Q9C5H6)
2.A.7.12.4









Golgi UDP-galactose and UDP-N-acetylglucosamine:UDP antiporter, SRF-3 (Hoflich et al., 2004).
Eukaryota
Metazoa, Nematoda
SRF-3 of Caenorhabditis elegans
(Q93890)
2.A.7.12.5









Golgi UDP-galactose and UDP-N-acetylgalactosamine:UDP antiporter, UGT (Segawa et al., 2002)

Eukaryota
Metazoa, Arthropoda
UGT of Drosophila melanogaster
(Q9W4W6)
2.A.7.12.6









Golgi UDP-galactose and UDP-N-acetylgalactosamine:UDP antiporter UGT or SLC35A2 (orthologue of 2.A.7.12.5) (Segawa et al., 2002). Transports nucleotide sugars from the cytosol into Golgi vesicles where glycosyltransferases function. Residues essential for activity, and mechanisms of transport by UGT allow greater understanding of the relationship between mutations in this protein and disease (Li and Mukhopadhyay 2019). May also take up cisplatin (Girardi et al. 2020).

 

Eukaryota
Metazoa, Chordata
SLC35A2 of Homo sapiens
2.A.7.12.7









Golgi UDP-N-acetylglucosamine transporter (Ishida et al., 1999a). Conserved Glu-47 and Lys-50 residues are critical for UDP-N-acetylglucosamine/UMP antiport activity of the mouse Golgi-associated transporter (Toscanini et al. 2019). Colorectal cancer with low SLC35A3 is associated with immune infiltrates and poor prognosis (Lu et al. 2024).

Eukaryota
Metazoa, Chordata
SLC35A3 of Homo sapiens
2.A.7.12.8









UDP-galactose transporter, UGT (Had-1) (Ishida et al., 1999b)
Eukaryota
Metazoa, Chordata
UGT of Mus musculus (Q9R0M8)
2.A.7.12.9









The ER/Golgi UDP-N-acetylgalactosamine (and possibly UDP-N-acetylglucosamine) transporter C03H5.2 gene product (Caffaro et al., 2006)
Eukaryota
Metazoa, Nematoda
C03H52 of Caenorhabditis elegans (O16658)
2.A.7.12.10









The ZK896.9 Golgi apparatus nucleotide-sugar transporter (transports UDP-glucose, UDP-galactose, UDP-N-acetylglucosamine, and UDP-N-acetylgalactosamine) (Caffaro et al., 2008)

Eukaryota
Metazoa, Nematoda
ZK896.9 of Caenorhabditis elegans (O02345)
2.A.7.12.11









Golgi CMP-sialic acid:CMP exchange transporter. Used for glycosylation within the Golgi lumen. Amino acid residues important for CMP-sialic acid recognition have been identified (Takeshima-Futagami et al., 2012).  Loss of function results in ataxia, intellectual disability, and seizures, in combination with bleeding diathesis and proteinuria (Mohamed et al. 2013).  SLC35A1 and SLC35C1, have been related to congenital disorder of glycosylation II (CDG II) (Song 2013). The loss of the sialic acid transporter SLC35A1/CST and the zinc transporter SLC30A1/ZnT1 (TC# 2.A.4.2.6) affected cell survival upon infection with cytolytic vesicular stomatitis virus (VSV). Both of these transporters seem to play a role in the apoptotic response induced by VSV (Moskovskich et al. 2019). Inherited thrombocytopenia can be caused by variants in crucial genes for glycosylation including that for SLC35A1 (Marín-Quílez et al. 2023).

Eukaryota
Metazoa, Chordata
SLC35A1 of Homo sapiens
2.A.7.12.12









Putative Golgi UDP-sugar transporter, SLC35A4. A modulatory role for SLC35A4 in intracellular trafficking of SLC35A2/SLC35A3 complexes has been proposed (Sosicka et al. 2017).

Eukaryota
Metazoa, Chordata
SLC35A4 of Homo sapiens
2.A.7.12.13









Putative nucleotide-sugar transporter, C2orf18 or SLC35F6 (371aas; 9 TMSs). It may play a role in cisplatin resistance in lung adenocarcinoma (Zhou et al. 2020).

Eukaryota
Metazoa, Chordata
C2orf18 of Homo sapiens (Q8N357)
2.A.7.12.14









Probable UDP-sugar transporter protein SLC35A5 (Solute carrier family 35 member A5)
Eukaryota
Metazoa, Chordata
SLC35A5 of Homo sapiens
2.A.7.12.15









CMP-sialic acid transporter 5 (CMP-SA-Tr 5) (CMP-Sia-Tr 5)
Eukaryota
Viridiplantae, Streptophyta
At5g65000 of Arabidopsis thaliana
2.A.7.12.16









Pig Golgi-resident UDP-N-acetylglucosamine transporter of 325 aas and 10 TMSs with the N- and C-termini in the cytoplasm, SLC35A3.  Essential TMSs and residues have been identified (Andersen et al. 2007).

Eukaryota
Metazoa, Chordata
SLC35A3 of Sus scrofa (Pig)
2.A.7.12.17









Nucleoside diphosphate-sugar transporter, NGT, of 611 aas with 1- TMSs in a 5 + 2 + 3 TMS arrangement.

Eukaryota
Apicomplexa
NGT of Plasmodium falciparum
2.A.7.13:  The GDP-Mannose:GMP Antiporter (GMA) Family
2.A.7.13.1









Golgi GDP-mannose:GMP antiporter, (vanadate resistance protein), VRG4 or VIG4 (Abe et al. 1999). It is the target of a natural cyclic peptide of unknown function (SDZ 90-215) (Snyder et al. 2019).

Eukaryota
Fungi, Ascomycota
VRG4 of Saccharomyces cerevisiae (P40107)
2.A.7.13.2









Golgi GDP-mannose transporter, VRG4
Eukaryota
Fungi, Ascomycota
VRG4 of Candida albicans (Q96WN8)
2.A.7.13.3









Golgi GDP-mannose:GDP antiporter, GONST1 (Baldwin et al., 2001).

Eukaryota
Viridiplantae, Streptophyta
GONST1 of Arabidopsis thaliana
(Q941R4)
2.A.7.13.4









Golgi GDP-mannose transporter, GONST2 of 375 aas (Handford et al. 2004).

Eukaryota
Viridiplantae, Streptophyta
GONST2 of Arabidopsis thaliana
2.A.7.13.5









Putative nucleotide sugar transporter GONST3 (Protein GOLGI NUCLEOTIDE SUGAR TRANSPORTER 3) (Handford et al. 2004).

Eukaryota
Viridiplantae, Streptophyta
GONST3 of Arabidopsis thaliana
2.A.7.13.6









Golgi GDP-mannose transporter of 397 aas and 10 TMSs, Gmt1.  Necessary for capsular biosynthesis, protein gycosylation and virulence (Wang et al. 2014).

Eukaryota
Fungi, Basidiomycota
Gmt1 of Cryptococcus neoformans
2.A.7.13.7









Golgi GDP-mannose transporter, Gmt2.  Functions in capsular polysaccharide biosynthesis, protein glycosylation and virulence (Wang et al. 2014).

Eukaryota
Fungi, Basidiomycota
Gmt2 of Cryptococcus neoformans (Filobasidiella neoformans)
2.A.7.13.8









TMEM241 or SLC35D4 of the SLC35 family and of 296 aas with 10 TMSs (Luck et al. 2020). 

Eukaryota
Metazoa, Chordata
TMEM241 of Homo sapiens
2.A.7.14:  The Plant Organocation Permease (POP) Family
2.A.7.14.1









Purine/pyrimidine organocation uptake permease, AtPUP1.  A thaliana has 15 paralogues, AtPUP1 to AtPUP15 (Gillissen et al. 2000). PUP1 transports adenine and cytosine with high affinity by a pmf-dependent mechanism. Purine derivatives (e.g., hypoxanthine), phytohormones (e.g., zeatin and kinetin), and alkaloids (e.g., caffeine) are potent competitive inhibitors of adenine and cytosine uptake and are probably substrates (Gillissen et al. 2000).

Eukaryota
Viridiplantae, Streptophyta
AtPUP1 of Arabidopsis thaliana
2.A.7.14.2









Probable purine permease 18 (AtPUP18)

Eukaryota
Viridiplantae, Streptophyta
Pup18 of Arabidopsis thaliana
2.A.7.14.3









Probable purine permease 11 (AtPUP11) of 379 aas and 10 TMSs.  PUP11 positively regulates the rice seed setting rate by influencing seed development (Rong et al. 2024).

Eukaryota
Viridiplantae, Streptophyta
PUP11 of Arabidopsis thaliana
2.A.7.14.4









Purine permease 2 (AtPUP2).  PUP2 transports cytokinins (trans- and cis-zeatin, kinetin, benzyladenine, isopentenyladenine, and to a lesser extent trans-zeatin riboside)

Eukaryota
Viridiplantae, Streptophyta
PUP2 of Arabidopsis thaliana
2.A.7.14.5









Putative purine permease 15 (AtPUP15)
Eukaryota
Viridiplantae, Streptophyta
PUP15 of Arabidopsis thaliana
2.A.7.14.6









Tobacco nicotine uptake permease 1, NUP1, of 353 aas and 10 TMSs. NUP1 transports tobacco alkaloids such as nicotine, but also efficiently takes up pyridoxamine, pyridoxine and anatabine. The naturally occurring (S)-isomer of nicotine was preferentially transported over the (R)-isomer. NUP1, similar to PUP1 of A. thaiana, transported various compounds containing a pyridine ring, but the two transporters had distinct substrate preferences (Kato et al. 2015).

Eukaryota
Viridiplantae, Streptophyta
Nup1 of Nicotiana tabacum
2.A.7.15:  The UDP-glucuronate/UDP-N-acetylgalactosamine Transporter (UGnT) Family
2.A.7.15.1









The Golgi UDP-N-acetylglucosamine/UDP-glucose/GDP-mannose transporter, SQV-7-like protein SQV7L or SLC35D2, homologue of Fringe connection protein 1 (involved in Notch signalling by transporting UDP-N-acetylglucosamine) HFRC1, Slc35D1.  Transports UDP-N-acetylglucosamine (UDP-GlcNAc), UDP-glucose (UDP-Glc), and GDP-mannose (GDP-Man), with apparent Km values of 8, 2, and 0.14 μM, respectively (Suda et al. 2004). The crystal structure of an nucleotide-sugar transporter, the SLC35D2 homolog, Vrg-4 from yeast has been described, and using this crystal structure, a new model of SLC35A1, (CMP-sialic acid transporter, CST) has been derived (Hadley et al. 2019).

Eukaryota
Metazoa, Chordata
SLC35D2 of Homo sapiens
2.A.7.15.2









The Golgi transporter, SQV-7. Transports UDP-glucuronic acid, UDP-N-acetylgalactosamine, and UDP-galactose (Gal). These nucleotide sugars are competitive, alternate, noncooperative substrates. Mutant sqv-7 missense alleles result in severe reductions of these three transport activities. SQV-7 did not transport CMP-sialic acid, GDP-fucose, UDP-N-acetylglucosamine, UDP-glucose, or GDP-mannose (Berninsone et al. 2001).

Eukaryota
Metazoa, Nematoda
SQV-7 (yk46f1.5) of Caenorhabditis elegans (Q18779)
2.A.7.15.3









Endoplasmic reticulum (ER)/Golgi antiporter for UDP-glucuronic acid, UDP-N-acetylglucosamine and possibly UDP-xylose in exchange for UDP, Fringe connection (Frc) Essential for several signalling pathways including heparan sulfate and Fringe-dependent signalling (Selva et al. 2001).  Involved in glycosylation and processing of Notch (Goto et al. 2001).

Eukaryota
Metazoa, Arthropoda
Frc of Drosophila melanogaster
(Q95YI5)
2.A.7.15.4









The UDP glucuronate/UDP-N-acetylgalactosamine transporter, Slc35D1; responsible for Schneckenbecken dysplasia in humans (Hiraoka et al., 2007). Congenital disorders of glycosylation (CDGs) are a heterogeneous group of disorders with impaired glycosylation of proteins and lipids. These conditions have multisystemic clinical manifestations, resulting in gradually progressive complications including skeletal involvement and reduced bone mineral density (Lipiński et al. 2021).

Eukaryota
Metazoa, Chordata
SLC35D1 of Homo sapiens
2.A.7.15.5









The putative Golgi nucleotide-sugar transporter SLC35D3 (416aas, 10 TMSs) (Chintala et al. 2007).  SLC35D3 regulates tissue-specific autophagy and plays an important role in the increased autophagic activity required for the survival of subsets of dopaminergic neurons (Wei et al. 2016). SLC35D3 silenced cells show increased expression of genes related to fat synthesis, and increased deposition of intramuscular fat,  an abundance of lipid droplets, and an increased level of free fatty acid in the culture medium. In contrast, the siRNA decreased the expression of genes involved in fat catabolism (Li et al. 2020), suggesting a role in the transport of fatty acids or their derivatives. It may play a role during porcine intramuscular preadipocyte differentiation (Li et al. 2020).

Eukaryota
Metazoa, Chordata
SLC35D3 of Homo sapiens
2.A.7.16:  The GDP-fucose Transporter (GFT) Family
2.A.7.16.1









The GDP-fucose transporter (GFT) (defective in human leukocyte adhesion disease II) (SLC35C1) (Zhang et al. 2012).  SLC35A1 and SLC35C1, have been related to congenital disorder of glycosylation II (CDG II) (Song 2013). Triclosan activates c-Jun/miR-218-1-3p/SLC35C1 signaling to regulate the cell viability, migration, invasion and inflammatory response of trophoblast cells (Huo et al. 2022). Elevated global fucosylation characterizes human intrahepatic cholangiocarcinoma, contributing to cell growth and migration via the upregulation of the NOTCH and EGFR/NF-kB pathways (Ament et al. 2023). SLC35C1 knockdown significantly inhibited the proliferation, migration and invasive ability of glioma cells, while SLC35C1 overexpression promoted proliferation, migration, invasion and colony formation of glioma cells (Xie et al. 2023). 

 

Eukaryota
Metazoa, Chordata
SLC35C1 of Homo sapiens
2.A.7.16.2









Golgi GDP-fucose-specific transporter, Gfr or CG9620 (Luhn et al., 2004).  It is required for glycan fucosylation and can also fucosylate NOTCH, a transmembrane cell fate determining receptor (Ishikawa et al. 2010).  Another transporter, the endoplasmic reticular Efr (TC# 2.A.7.10.4), can also fucoslyate NOTCH but not glycans.

Eukaryota
Metazoa, Arthropoda
Gfr or CG9620 of Drosophila melanogaster
(Q9VHT4)
2.A.7.16.3









Uncharacterized transporter C22F8.04
Eukaryota
Fungi, Ascomycota
SPAC22F8.04 of Schizosaccharomyces pombe
2.A.7.17:  The Aromatic Amino Acid/Paraquat Exporter (ArAA/P-E) Family
2.A.7.17.1









Aromatic amino acid exporter (exports Phe, Tyr, Trp, and their toxic analogues (Doroshenko et al., 2007)). Also called the paraquat (methyl viologen) exporter, YddG (also exports benzyl viologen and possibly L-alanine; Hori et al., 2011). The topology of YddG has been shown to be 10 TMSs with N- and C- termini on the inside (Airich et al., 2010).

Bacteria
Pseudomonadota
YddG of Salmonella typhimurium
2.A.7.17.2









General amino acid exporter (probably including aromatic amino acids as well as thr, met lys, glu and others), YddG.  Its topology with 10 TMSs and both the N- and C-termini inside has been established (Airich et al. 2010). This system has been used for the export of tryptophan for commercial purposes (Wang et al. 2013).  The 3-d structures (PD# 5I20) of a homologue (TC# 2.A.7.3.66) has been determined at 2.4 Å resolution, showing the outward facing conformation of a basket shaped structure with a central substrate binding cavity (Tsuchiya et al. 2016). Mutants of the yddG gene can export phenylalanine (Radi et al. 2022).

Bacteria
Pseudomonadota
YddG of Escherichia coli
2.A.7.18:  The Choline Uptake Transporter (LicB-T) Family
2.A.7.18.1









The high-affinity choline uptake transporter, LicB
Bacteria
Pseudomonadota
LicB of Haemophilus influenzae (AAC23188)
2.A.7.18.2









The archaeal putative permease MttP 353 aas (lMA0530) possibly a methyl amine uptake porter; D.J. Ferguson, personal communication) (10 putative TMSs)

Archaea
Euryarchaeota
MttP of Methanosarcina acetivorans (Q8TTA7)
2.A.7.18.3









The archael putative permease MttP2 (MA0929) (possibly a methyl amine uptake porter; D.J Ferguson, personal communication). (9 putative TMSs; The N-terminal TMS may be missing).
Archaea
Euryarchaeota
MttP2 of Methanosarcina acetivorans (Q8TS76)
2.A.7.18.4









LicB-T family member

Bacteria
Actinomycetota
LicB-T family member of Streptomyces coelicolor
2.A.7.19:  The Nucleobase Uptake Transporter (NBUT) Family
2.A.7.19.1









Allantoin permease, UPS1 (may also transport uracil and 5-fluorouracil) (10 TMSs) (Schmidt et al., 2004)
Eukaryota
Viridiplantae, Streptophyta
UPS1 of Phaseolus vulgaris (French bean) (AAS19930)
2.A.7.19.2









The uptake transporter for allantoin (Km = 50 μM) and other oxo derivatives of nitrogen heterocyclic compounds, UPS1 (ureide:H+ symport permease) (10 TMSs; 5 paralogues in Arabidopsis).  Also transports purine degradation products such as uric acid and xanthine but not adenine (Desimone et al., 2002).

Eukaryota
Viridiplantae, Streptophyta
UPS1 of Arabidopsis thaliana
(Q9ZPR7)
2.A.7.19.3









Ureide Permease 5, UPS5 of 415 aas and 10 TMSs.  Proton-coupled transporter that transports a wide spectrum of oxo derivatives of heterocyclic nitrogen compounds, including allantoin, uric acid and xanthine, but not adenine. UPS5 mediates transport of uracil and 5-fluorouracil (a toxic uracil analog) (Schmidt et al. 2006).  Allantoin accumulation mediated by UPS5 confers salt stress tolerance (Lescano et al. 2016). AtUPS5-Long and AtUPS5-Short localization indicates that they play different roles in allantoin distribution between subcellular compartments. Thus, Lescano et al. 2019 predict that under non-stress conditions UPS5L and UPS5S may function in allantoin degradation pathway for nutrient recycling, whereas under stress conditions, both splice variants are involved in cell export via vesicles of the secretory pathway, allowing allantoin translocation from roots to shoots.

 

Eukaryota
Viridiplantae, Streptophyta
UPS5 of Arabidopsis thaliana (Mouse-ear cress)
2.A.7.19.4









Ureide permease 2, UPS2, of 398 aas and 10 TMSs. Proton-coupled transporter that transports a wide spectrum of oxo derivatives of heterocyclic nitrogen compounds, including allantoin, uric acid and xanthine, but not adenine. Mediates high affinity transport of uracil and 5-fluorouracil (a toxic uracil analog). Mediates transport of free pyrimidines and may function during early seedling development in salvage pathways, by the utilization of pyrimidines from seed storage tissue (Schmidt et al. 2004). Km for uracil = 6 μM; for xanthine = 24 μM; for allantoin = 26 μM.

Eukaryota
Viridiplantae, Streptophyta
Ups2 of Arabidopsis thaliana
2.A.7.19.5









Ureide permease 1-like protein of 483 aas and 8 TM

Eukaryota
Viridiplantae, Streptophyta
Ureide permease 1 of Prosopis alba
2.A.7.20:  The Chloroquine Resistance Transporter (PfCRT) Family
2.A.7.20.1









Chloroquine resistance transporter, PfCRT. Martin et al. (2009) have demonstrated Chloroquine transport via PfCRT. It co-transports chloroquine (CQ) or piperaquine (PPQ) and Hout of the digestive vacuole (and hence away from its site of action) via a mutant form of the parasite's CRT (Lehane and Kirk, 2010).  Many mutations give rise to resistance (Tan et al. 2014; Buppan et al. 2018). The orthologue in P. vivax is 73% identical to the P. faciparum protein and has the same function (et al. 2006). It is inhibited by verapamil, quinine, saquinavir and dibemethin 6a (Meier et al. 2018). TMS1 is involved in substrate selectivity and catalyzes chroroquine efflux (Antony et al. 2018). The vacuolar-half and membrane-spanning domains (especially TMS9) of PfCRT are more conserved, suggesting that its physiological substrate is expelled out of the parasite digestive vacuole. In the PfCRT occluded state, some evolutionary conserved sites, including positions related to drug resistance mutations, participate in a putative binding pocket located at the core of the PfCRT membrane-spanning domain (Coppée et al. 2020). pH-dependence of the P. falciparum chloroquine resistance transporter is linked to the transport cycle (Berger et al. 2023).  Several proteases are localized to the digestive vacuole and these proteases sequentially breakdown hemoglobin into small peptides, dipeptides, and amino acids. The peptides are exported into the host cytoplasm via the chloroquine-resistance transporter and an amino acid transporter has also been identified on the digestive vacuole membrane (Wiser 2024).

Eukaryota
Apicomplexa
PfCRT of Plasmodium falciparum (AF495378)
2.A.7.20.2









Crt homologue 1 (Chloroquine resistance transporter paralogue 1) (DdCRTp1)

Eukaryota
Evosea
Crtp1 of Dictyostelium discoideum
2.A.7.20.3









Uncharacterized protein of 384 aas and 11 TMSs

Eukaryota
Viridiplantae, Chlorophyta
UP of Chlamydomonas reinhardtii (Chlamydomonas smithii)
2.A.7.20.4









Chloroplastic chloroquine resistance transporter-1 of 447 aas and 10 TMSs, Clt-1.  Involved in thiol transport from the plastid to the cytosol. Transports both glutathione (GSH) and its precursor, gamma-glutamylcysteine (gamma-EC). Exhibits some functional redundancy with CLT3 in maintaining the root GSH pool (Maughan et al. 2010).

Eukaryota
Viridiplantae, Streptophyta
Clt-1 of Arabidopsis thaliana (Mouse-ear cress)
2.A.7.20.5









Chloroquine resistance transporter, Crt, of 421 aas and 10 TMSs.  It is 76% identical to 2.A.7.20.1. Genetic analyses have been performed (Pimpat et al. 2020).

Eukaryota
Apicomplexa
Crt of Plasmodium malariae
2.A.7.21:  The 5 TMS Bacterial/Archaeal Transporter-2 (BAT2) Family
2.A.7.21.1









The putative toxoflavin exporter, ToxF (co-transcribed with an RND-type toxoflavine exporter, ToxGHI; TC# 2.A.6.2.20) and reglated by a LysR transcription factor, ToxR coordinately with the toxoflavin biosynthetic enzymes  (Kim et al. 2004).

Bacteria
Pseudomonadota
ToxF of Burkholderia glumae (AAV52811)
2.A.7.21.2









Putative exporter
Bacteria
Pseudomonadota
YdcZ of E. coli (P76111)
2.A.7.21.3









Putative exporter
Archaea
Euryarchaeota
Putative exporter of Methanococcus maripaludis (CAF29821)
2.A.7.21.4









The orotate transporter, OroP (Defoor et al., 2007) (also, transports 5-fluoroorotate)
Bacteria
Bacillota
OroP of Lactococcus lactis (Q3SAW5)
2.A.7.21.5









Heterodimeric SMR-like transporter with subunits of 144 and 151 aas and 4 TMSs each.  The two encoding genes map adjacent to a LysR transcription factor and on the other side, to a RhtB homologue, that possibly exports serine, threonine, homoserine and/or homoserine lactones.  Could function in the uptake of a quorum sensing acylhomoserine lactone.

Bacteria
Pseudomonadota
UP of Klebsiella oxytoca
2.A.7.21.6









Uncharacterized protein of 159 aas and 5 TMSs.

Bacteria
Deinococcota
UP of Deinococcus maricopensis
2.A.7.21.7









Putative transporter of 339 aas and 10 TMSs, encoded within an operon with a polyketide cyclase/dehydrase.  Possibly a polyketide exporter.

Bacteria
Actinomycetota
Transporter of Isoptericola variabilis
2.A.7.21.8









Transporter of unknown function of 143 aas and 5 TMSs.  Its gene maps near a thioredoxin domain-containing oxidoreductase that may act on glycine, sarcosine and/or betaine.  Possibly the transporter acts on one of these substrates.

Bacteria
Bacillota
Transporter of Clostridium acetobutylicum
2.A.7.21.9









Putative transporter encoded within a probable operon with a ser-tRNA synthetase, serine biosynthesis enzymes, a peptidase and a MarC transporter.  May be an exporter of serine.

Bacteria
Deferribacterota
Putative serine transporter of Deferribacter desulfuricans
2.A.7.22:  The 4 TMS Small Multidrug Resistance-2 (SMR2) Family
2.A.7.22.1









4-amino-4-deoxy-L-arabinose phosphoundecaprenol flippase, ArnEF [ArnE, 111aas; 4 TMSs; PmrL; YfbW] [ArnF, 128aas; 4 TMSs; PmrM; YfbJ] Functions in modification of lipid A during biosynthesis of lipopolysaccharide. Required for resistance to polymyxin and cationic antimicrobial peptides (Yan et al., 2007).

Bacteria
Pseudomonadota
ArnEF of E. coli 
ArnE (Q47377)
ArnF (P76474) 
2.A.7.22.2









The undecaprenyl phosphate-α-aminoarabinose flippase ArnE/ArnF heterodimer from the cytoplasm to the periplasm (Yan et al., 2007).

Bacteria
Pseudomonadota
ArnEF flippase of Salmonella typhi
ArnE (P81891)
ArnF (125aas; Q8Z537)
2.A.7.22.3









Uncharacterized protein of 130 aas and 4 TMSs

Bacteria
Spirochaetota
UP of Spirochaeta smaragdina
2.A.7.24:  The Thiamine Pyrophosphate Transporter (TPPT) Family
2.A.7.24.1









The mitochondrial thiamine-repressible putative thiamine pyrophosphate (TPP) transporter, Thi74 (370 aas; 10 TMSs in a 2 + 8 arrangement) (Mojzita and Hohmann, 2006)
Eukaryota
Fungi, Ascomycota
Thi74 of Saccharomyces cerevisiae
(Q04083)
2.A.7.24.2









The DUF6-domain transporter homologue, TrH1
Eukaryota
Evosea
TrH1 of Dictyostelium discoideum (Q54E05)
2.A.7.24.3









The DUF6-domain transporter homologue, TrH2 (392 aas; 10 TMSs in a 2 + 4 + 4 arrangement)
Eukaryota
Metazoa, Nematoda
TrH2 of Caenorhabditis elegans (Q95XC7)
2.A.7.24.4









The At3g07080 DUF6 domain transporter homologue
Eukaryota
Viridiplantae, Streptophyta
At3g07080 of Arabidopsis thaliana (Q9SFT8)
2.A.7.24.5









Uncharacterized vacuolar membrane protein YML018C
Eukaryota
Fungi, Ascomycota
YML018C of Saccharomyces cerevisiae
2.A.7.24.6









The DUF6-domain-containing solute carrier family 35, member F5 (523 aas; 10 TMSs, in a 2 + 4 + 4 TMS arrangement. Expression patterns in various tissues have been studied (Nishimura et al. 2009). The oncomiR effect of miR-369-3p may be mediated through disrupting the nucleotide sugar transport activity, and that SLC35F5 is a key effector of this chemoresistance-promoting activity (Hao et al. 2017).

Eukaryota
Metazoa, Chordata
SLC35F5 of Homo sapiens
2.A.7.24.7









DUF6 domain-containing protein with 150aa N-terminal hydrophilic extension

Eukaryota
Fungi, Ascomycota
DUF6 protein of Trichophyton equinum (F2PXJ5)
2.A.7.24.8









The thiamin uptake transporter, SLC35F3. Involved in hypertension (Zhang et al. 2014; Zang et al. 2016). Its gene appears to play a role in the antiepileptic mood stabilization (AED-MS) treatment response, and may facilitate precision medicine in bipolar disease (Ho et al. 2020).

Eukaryota
Metazoa, Chordata
SLC35F3 of Homo sapiens
2.A.7.24.9









SLC family 35 member F1 (SLC35F1; also called DUF914) of 412 aas and 10 TMSs. Expression in the mouse brain has been reported (Farenholtz et al. 2019). It is a candidate gene for neurodevelopmental disorders resembling Rett syndrome (Di Fede et al. 2021).

Eukaryota
Metazoa, Chordata
SLC35F1 of Homo sapiens
2.A.7.24.10









SLC family 35 member F2 (SLC35F2; also called DUF914). It regulates cisplatin resistance and promotes malignant progression of pancreatic cancer by regulating RNA binding motif protein 14 (Zhang et al. 2022).

Eukaryota
Metazoa, Chordata
SLC35F2 of Homo sapiens
2.A.7.24.11









SLC family 35 member F2 (SLC35F2; also called DUF914)

Eukaryota
Fungi, Ascomycota
SLC35F2 of Aspergillus fumigatus
(Q4WUA9)
2.A.7.24.12









DUF914 protein, possibly anthocyanin-related protein-1 (Anm1)

Eukaryota
Viridiplantae, Streptophyta
DUF914 protein of Arabidopsis thaliana (Q948Q9)
2.A.7.24.13









Protein of unknown function (claimed to have extra cytoplasmic N- and C-termini (Västermark et al., 2011)). The 10 TMSs occur in a 6+4 arrangement.

Eukaryota
Kinetoplastida
Unknown protein of Trypanosoma brucei (Q57UU3)
2.A.7.24.14









Solute carrier family 35 member F4 of 521 aas and 10 TMSs. Exposure to violence and chronic stress may increase the risk of atopic asthma through DNA methylation of this gene in airway epithelia (Yan et al. 2020).

Eukaryota
Metazoa, Chordata
SLC35F4 of Homo sapiens
2.A.7.24.15









Uncharacterized DMT superfamily homologue

Eukaryota
Fungi, Ascomycota
Uncharacterized protein of Lodderomyces elongisporus
2.A.7.25:  The NIPA Mg2+ Uptake Permease (NIPA) Family

The NIPA family is most closely related to the U-DMT family that includes probable Mg2+ transporters (TC# 2.A.7.29) in eukaryotes.

2.A.7.25.1









The nonimprinted in Prader-Willi/Angelman syndrome, subtype 1, NIPA1 (SLC57A1) Mg2+ uptake permease (Gyimesi and Hediger 2022); it also may take up Sr2+, Fe2+ and Co2+ (329 aas; 9 or 10 TMSs) (Quamme, 2009). A causative link between NIPA1 mutations and autosomal dominant hereditary spastic paraplegia has been demonstrated (Reed et al. 2005; Fabbro et al. 2021).

Eukaryota
Metazoa, Chordata
NIPA of Homo sapiens (Q7RTP0)
2.A.7.25.2









The nonimprinted in Prader-Willi/Angelman syndrom, subtype 2, NIPA2 protein (360 aas; 9TMSs, 43% identical with NIPA1). Mg2+ transport is electrogenic, voltage-dependent, and saturable, with a KM of 0.31 mM (very selective for Mg2+). (Goytain et al. 2008). As of 2018, the function of this protein as a Mg2+ transporter was under debate (Schäffers et al. 2018).

Eukaryota
Metazoa, Chordata
NIPA2 of Homo sapiens (Q8N8Q9)
2.A.7.25.3









NIPA3 or NIPAL3 (SLC57A5) protein of 406 aas and 9 TMSs. Putative Mg2+ transporter

Eukaryota
Metazoa, Chordata
NIPA3 of Homo sapiens (Q6P499)
2.A.7.25.4









The ichthyin (ICHN; Nipal4; Nipa4; SLC57A6) autosomal recessive congenital ichthyosis (ARCI) disease Mg2+ transport protein (466 aas; 9 TMSs).  It transports Mg2+ as well as other divalent cations such as Ba2+, Mn2+, Sr2+ and Co2+, but to a much less extent than Mg2+. It may be a receptor for ligands (trioxilins A3 and B3) from the hepoxilin pathway (Lefèvre et al. 2004). Disease-causing mutations near the transport channel cavity lead to changes in channel architecture and ARCI function (Laadhar et al. 2019).

 

Eukaryota
Metazoa, Chordata
ICHN of Homo sapiens (Q0D2K0)
2.A.7.25.5









The permease-related protein (PRP) (335 aas; 9TMSs)
Eukaryota
Viridiplantae, Streptophyta
PRP of Arabidopsis thaliana (Q9LIR9)
2.A.7.25.6









Hypothetical protein (HP)
Eukaryota
Fungi, Ascomycota
HP of Neurospora crassa (Q7RWT8)
2.A.7.25.7









Protein AN62992 (691 aas; 9TMSs at the N-terminus (1-300 aas)). The C-terminal region (DUF803) is very hydrophilic.

Eukaryota
Fungi, Ascomycota
AN62992 of Aspergillus nidulans (Q5AZI1)
2.A.7.25.9









Magnesium transporter NIPA3; NIPAL1; NPAL1; SLC57A3 (NIPA-like protein 1) (Non-imprinted in Prader-Willi/Angelman syndrome region protein 3 homologue). It is a Mg2+ transporter that can also transport Sr2+, Ba2+, Fe2+ and Cu2+ (Gyimesi and Hediger 2022).  The human ortholog is 87% identical to the mouse protein.

Eukaryota
Metazoa, Chordata
Nipal1 of Mus musculus
2.A.7.25.10









NIPA-like protein 2, NIPAL2 or SLC57A4 Mg2+ transporter; also takes up Sr2+ and Ba2+. It is of 383 aas with 9 TMSs (Gyimesi and Hediger 2022).

Eukaryota
Metazoa, Chordata
NIPAL2 of Homo sapiens
2.A.7.25.11









DUF803 domain containing protein of 935 aas and 10 TMSs, with 5 TMSs at the N-terminus and 5 TMSs at the C-terminus. It may be a Mg2+/H+ antiporter (Wunderlich 2022).

Eukaryota
Fungi, Basidiomycota
DUF803 protein of Plasmodium falciparum
2.A.7.26:  The 2 or 4 TMS Small Multidrug Resistance-3 (SMR3) Family

YnfA is a 108 aa E. coli protein with 4 established TMSs and both the N- and C-termini in the periplasm (Drew et al., 2002). Its homologues are found in a broad range of Gram-negative and Gram-positive bacteria as well as archaea and eukaryotes. The sizes of bacterial homologues range from 98 aas to 132 aas, with a few exceptions. Plant proteins can be as large as 197aas. The first two TMSs are homologous to the second two in these 4 TMS proteins. A Methanosarciniae mazei homologue of 94 aas and a Geobacillus kaustophilus homologue of 104 aas have only 2 TMSs with 30 residue extensions C- and N-terminal, respectively. No functional data are available for any of its homologues. This family is the YnfA UPF0060 family.

2.A.7.26.1









YnfA of 108 aas and 4 TMSs. YnfA increases the antibiotics' resistance of E. coli strains isolated from the urinary tract, and is an SMR-like drug efflux pump (Sarkar et al. 2015).

Bacteria
Pseudomonadota
YnfA of E. coli
2.A.7.26.2









MA_3936 (4 TMSs)

Archaea
Euryarchaeota
MA_3936 of Methanosarcina acetivorans (gi#19918023)
2.A.7.26.3









Sitka Spruce 4 TMS YnfA family homologue (144aas).

Eukaryota
Viridiplantae, Streptophyta
YnfA homologue of Picea sitchensis (ADE77612)
2.A.7.26.4









Moss 4-5 TMS YnfA family homologue (197aas)

Eukaryota
Viridiplantae
YnfA homologue of Physcomitrella patens (A9T501)
2.A.7.26.5









Hypothetical protein, GK2092 (2 TMSs)

Bacteria
Bacillota
GK2092 of Geobacillus kaustophilus (Q5KY59)
2.A.7.26.6









MM_0735 (2 TMSs)

 

Archaea
Euryarchaeota
MM_0735 of Methanosarcina mazei (Q8PYW4)
2.A.7.27:  The Ca2+ Homeostasis Protein (Csg2) Family
2.A.7.27.1









Csg2 (Cls2) Ca2+ homeostasis protein. Cells lacking Csg2p accumulate Ca2+ in a pool which is exchangeable with extracellular Ca2+ . The mutant cells are Ca2+ sensitive. The protein has 410 amino acyl residues, with 9-10 TMSs. It exhibits an EF-hand Ca2+ binding motif on the lumenal side of the endoplasmic reticular membrane. It is possible that it functions in Ca2+ sequestration. It regulates the activities of CSH1 and SUR1 during mannosyl phosphorylinositol ceramid synthesis. It forms heterodimers with CSH1 and SUR1 (Beeler et al. 1994; Takita et al. 1995). Cls2p likely functions in releasing Ca2+ from the endoplasmic reticulum, somehow cooperating with calcineurin (Tanida et al. 1996). It regulates the transport and protein leves of the inositol phosphorlyceramide mannosyltransferases Csg1 and Csh1 (Uemura et al. 2007).

Eukaryota
Fungi, Ascomycota
Csg2 of Saccharomyces cerevisiae (P35206)
2.A.7.28:  The Solute Carrier 35G (SLC35G) Family
2.A.7.28.1









Solute carrier family 35 member G1 of 365 aas and 10 TMSs. Kamel et al. 2017 reviewed acute disseminated encephalomyelitis (ADEM) and suggested a role of SLC35G1.

Eukaryota
Metazoa, Chordata
SLC35G1 of Homo sapiens (Q8BY79)
2.A.7.28.2









Solute carrier family 35 member G2 of 412 aas and 10 TMSs in a 5 + 5 TMS arrangement. A novel DNA methylation-driver gene signature for long-term survival prediction of hepatitis-positive hepatocellular carcinoma patientshas been reported (Fu et al. 2022).

Eukaryota
Metazoa, Chordata
SLC35G2 of Homo sapiens
2.A.7.28.3









Solute carrier family 35 member G3

Eukaryota
Metazoa, Chordata
SLC35G3 of Homo sapiens (Q5F297)
2.A.7.28.4









Solute carrier family 35 member G4, SLC35G4, of 338 aas and 10 TMSs. May be a pseudogene; function unknown.

Eukaryota
Metazoa, Chordata
SLC35G4 of Homo sapiens
2.A.7.28.5









Solute carrier family 35 member G5, SLC35G5, of 338 aas and 10 TMSs. The gene for SLC35G5 is  commonly mutated in pre-NACT. Patients treated with neoadjuvant chemotherapy (NACT) for advanced high-grade serous ovarian carcinoma have a higher rate and shorter time to platinum-resistant recurrence (Marchocki et al. 2022).

Eukaryota
Metazoa, Chordata
SLC35G5 of Homo sapiens
2.A.7.28.6









Solute carrier family 35 member G6 of 338 aas and 10 TMSs. Endometriosis and migraines co-occur within individuals more than expected by chance, and this appears to involve mutant forms of SLC35G6 (Adewuyi et al. 2020).

Eukaryota
Metazoa, Chordata
SLC35G6 of Homo sapiens
2.A.7.28.7









Solute carrier family 35 member G3 (Acyl-malonyl-condensing enzyme 1?) (Transmembrane protein 21A) of 338 aas and 10 TMSs. The gene encoding this protein appears to have arisen by SVA-mediated retrotransposition of the SLC35G6 gene in the primate lineage.

Eukaryota
Metazoa, Chordata
SLC35G3 of Homo sapiens
2.A.7.28.8









Solute carrier family 35 member G1 (Transmembrane protein 20)
Eukaryota
Metazoa, Chordata
SLC35G1 of Homo sapiens
2.A.7.28.9









Uncharacterized transporter HP_1234
Bacteria
Campylobacterota
HP_1234 of Helicobacter pylori
2.A.7.28.10









Uncharacterized protein of 340 aas and 10 TMSs

Eukaryota
Rhodophyta
UP of Chondrus crispus (Carragheen moss) (Irish moss)
2.A.7.28.11









Uncharacterized protein of 304 aas and 10 TMSs.

Bacteria
Cyanobacteriota
UP of Prochlorococcus marinus
2.A.7.28.12









Prion-inhibition and propagation, HeLo domain of 901 aas. Contains a domain C-terminal to the transmembrane DMT domain that is homologous to that found in the family with TC# 1.C.104, the Heterokaryon Incompatibility Prion/Amyloid Protein (HET-s) Family.

Eukaryota
Fungi, Ascomycota
HeLo domain proteini of Umbilicaria pustulata
2.A.7.28.13









Pseudopaline exporter CntI (ZrmD) of 284 aas and 10 TMSs in a 5 + 5 TMS arrangement (Mégret-Cavalier et al. 2024).

Bacteria
Pseudomonadota
CntI of Pseudomonas aeruginosa
2.A.7.29:  The Uncharacterized DMT-1 (possible Mg2+ uptake porter) (U-DMT1) Family

The U-DMT1 family is most closely related to the NIPA family (TC# 2.A.7.25) that includes probable Mg2+ transporters in prokaryotes.

2.A.7.29.1









Uncharacterized DUF803 protein of 814 aas and 10 TMSs.

Eukaryota
Apicomplexa
UP of Toxoplasma gondii
2.A.7.29.2









Uncharacterized (possibly Mg2+) transport protein of 483 aas and 10 TMSs.  May have magnesium transport activity (Wunderlich 2022).

Eukaryota
Apicomplexa
UP of Plasmodium falciparum
2.A.7.29.3









Uncharacterized protein of 470 aas and 9 or 10 TMSs.

Eukaryota
Oomycota
UP of Pythium ultimum
2.A.7.29.4









Probable Mg2+ transporter. May also transport other divalent cations such as Fe2+, Sr2+, Ba2+, Mn2+ and Co2+ but to a much lesser extent than Mg2+.

Eukaryota
Viridiplantae, Streptophyta
Putative Mg2+ transporter of Glycine max (Soybean) (Glycine hispida)
2.A.7.30:  The Uncharacterized DMT-2 (U-DMT2) Family
2.A.7.30.1









Hypothetical protein of 299 aas and 10 putative TMSs

Bacteria
Planctomycetota
HP of Rhodopirellula baltica
2.A.7.30.2









Uncharacterized putative permease of 295 aas and 10 TMSs.

Bacteria
Bacteroidota
UP of Flavobacterium frigoris
2.A.7.31:  The Uncharacterized DMT-3 (U-DMT3) Family
2.A.7.31.1









10 TMS DMT Superfamily member

Bacteria
Myxococcota
DMT protein of Myxococcus xanthus (Q1DCP3)
2.A.7.31.2









10 TMS DMT Superfamily member

Bacteria
Pseudomonadota
Legionella pneumophila (A5IFT5)
2.A.7.31.3









10 TMS DMT Superfamily member

Bacteria
Pseudomonadota
DMT protein of Rhizobium torpici (L0LHM3)
2.A.7.32:  The Uncharacterized DMT-4 (U-DMT4) Family
2.A.7.32.1









The transmembrane protein TMEM234 of 164 aas and 4 TMSs.

Eukaryota
Metazoa, Chordata
TMEM234 of Homo sapiens
2.A.7.32.2









TMEM234 of 127 aas and 4 TMSs.

Eukaryota
Metazoa, Nematoda
TMEM234 of Caenorhabditis elegans
2.A.7.32.3









Uncharacterized protein of 128 aas.

Eukaryota
Evosea
UP of Dictyostelium discoideum
2.A.7.32.4









Uncharcterized protein of 182 aas and 4 TMSs

Eukaryota
Fungi, Ascomycota
UP of Pyrenophora teres
2.A.7.32.5









Uncharacterized protein of 121 aas

Eukaryota
Euglenozoa
UP of Leishmania infantum
2.A.7.32.6









TMEM234 of 234 aas and 4 TMSs in a 1 + 3 TMS arrangement. In zebrafish larvae, Tmem234 is essential for the organization and functional integrity of the pronephric glomerulus filtration barrier. Inactivation of Tmem234 expression results in foot process effacement and proteinuria. It is one of four highly podocyte-enriched proteins. Tmem234 is essential for the normal filtration barrier in the zebrafish pronephric glomerulus (Rodriguez et al. 2015).

Eukaryota
Metazoa, Chordata
TMEM234 of Danio rerio (Zebrafish)
2.A.7.33:  The Uncharacterized DMT-5 (U-DMT5) Family

Most closely related to the SMR2 Family (2.A.7.22).

2.A.7.33.1









Permease of 116 aa

Bacteria
Acidobacteriota
Permease of Solibacter usitatus
2.A.7.33.2









Uncharacterized protein of 116 aas.

Bacteria
Bacteroidota
UP of Bacteroides fragilis
2.A.7.33.3









Uncharacterized protein of 123 aas.

Bacteria
Pseudomonadota
UP of Burkholderia caribensis
2.A.7.33.4









EmaA-like transporter of 111 aas.

Bacteria
Cyanobacteriota
UP of Dactylococcopsis salina
2.A.7.33.5









Uncharacterized protein of 116 aas

Bacteria
Actinomycetota
UP of Olsenilla profusa
2.A.7.33.6









Uncharacterized protein of 114 aas and 4 TMSs

Bacteria
Bacillota
UP of Thermincola potens
2.A.7.33.7









SMR protein of 127 aas and 4 TMSs

Bacteria
Cyanobacteriota
SMR protein of Nostoc punctiforme
2.A.7.34:  The Uncharacterized DMT-6 (U-DMT6) Family
2.A.7.34.1









DUF486 transporter of 113 aas and 4 TMSs.

Bacteria
Pseudomonadota
UP of Laribacter hongknogensis
2.A.7.34.2









DUF486 transporter of 117 aas and 4 TMSs.

Bacteria
Pseudomonadota
UP of Xanthomonas campestris
2.A.7.34.3









DUF486 homologue of 122 aas

Bacteria
Bacteroidota
UP of Bacteroides fragilis
2.A.7.34.4









DUF486 homologue of 112 aas

Archaea
Euryarchaeota
UP of Methanococcus maripaludis
2.A.7.34.5









DUF486 homologue of 124 aas

Bacteria
Bacteroidota
UP of Cytophaga hutchinsonii
2.A.7.34.6









DUF486 homologue of 122 aas

Bacteria
Spirochaetota
UP of Brachyspira intermedia
2.A.7.34.7









Small multidrug resistance (SMR) protein of 116 aas

Bacteria
Acidobacteriota
SMR protein of Terriglobus saanensis
2.A.7.34.8









Uncharacterized protein of 179 aas

Eukaryota
Haptophyta
UP of Emiliania huxleyi
2.A.7.34.9









Uncharacterized protein of 146 aas

Eukaryota
UP of Guillardia theta
2.A.7.35:  The Uncharacterized DMT-7 (U-DMT7) Family
2.A.7.35.1









Membrane protein of 280 aas and 9 TMSs.

Bacteria
Actinomycetota
Membrane protein of Corynebacterium matruchotii (E0DBX6)
2.A.7.35.2









NIPA family member of 419 aas and 9 or 10 TMSs.

Bacteria
Actinomycetota
NIPA family member of Streptomyces coelicolor
2.A.7.35.3









Uncharacterized permease of 370 aas and 9 or 10 TMSs.

Bacteria
Actinomycetota
UP of Frankia sp.
2.A.7.35.4









Uncharacterized protein of 311 aas and 9 or 10 TMSs

Bacteria
Actinomycetota
UP of Kribbella flavida
2.A.7.35.5









Uncharacterized protein of 292 aas and 9 TMSs

Bacteria
Actinomycetota
UP of Streptomyces grisius
2.A.7.35.6









Uncharacterized protein of 299 aas and 9 TMSs

Bacteria
Actinomycetota
UP of Streptomyces coelicolor
2.A.7.35.7









Uncharacterized protein of 295 aas and 9 or 10 TMSs.

Bacteria
Actinomycetota
UP of Conexibacter woesei
2.A.7.35.8









Uncharacterized protein of 289 aas and 9 TMSs.

Bacteria
Actinomycetota
UP of Amycolatopsis mediterranei
2.A.7.35.9









Uncharacterized protein of 303 aas and 9 TMSs

Bacteria
Actinomycetota
UP of Thermobifida fusca
2.A.7.35.10









Uncharacterized protein of 324 aas and 9 TMSs.

Bacteria
Actinomycetota
UP of Mycobacterium intracellulare
2.A.7.36.1









EamA-like transporter of 287 aas and 10 TMSs

Bacteria
Actinomycetota
EamA-like protein of Mycobacterium chubuense  
2.A.7.36.2









Uncharacterized protein of 283 aas and 10 TMSs

Bacteria
Actinomycetota
UP of Acidothermus cellulolyticus
2.A.7.36.3









Uncharacterized protein of 275 aas and 10 TMSs

Bacteria
Actinomycetota
UP of Geodermatophilus obscurus
2.A.7.36.4









Uncharacterized protein of 291 aas and 10 TMSs

Bacteria
Deinococcota
UP of Truepera radiovictrix
2.A.7.36.5









Uncharacterized protein of 281 aas and 10 TMSs

Archaea
Euryarchaeota
UP of Methanolobus psychrophilus
2.A.7.37.1









Uncharacterized protein of 164 aas and 4 TMSs.

Bacteria
Pseudomonadota
UP of Delftia acidovorans
2.A.7.37.2









Uncharacterized protein of 132 aas and 4 TMSs.

Bacteria
Pseudomonadota
UP of Pseudomonas chlororaphis subsp. aureofaciens
2.A.7.37.3









Uncharacterized protein of 139 aas and 4 TMSs.

Bacteria
Pseudomonadota
UP of Rhizobium mesoamericanum
2.A.7.38.1









Uncharacterized protein of 301 aas and 10 or fewer TMSs.

Bacteria
Pseudomonadota
UP of Parvibaculum lavamentivorans
2.A.7.38.2









Uncharacterized protein of 343 aas and 10 TMSs

Bacteria
Pseudomonadota
UP of Agrobacterium radiobacter
2.A.7.38.3









Uncharacterized protein of 298 aas and 10 TMSs

Bacteria
Pseudomonadota
UP of Maritimibacter alkaliphilus
2.A.7.40.1









Uncharacterized protein of 292 aas and 10 TMSs.

Bacteria
Thermodesulfobacteriota
UP of Desulfobacca acetoxidans
2.A.7.40.2









Uncharacterized protein of 297 aas and 10 TMSs

Bacteria
Bacteroidota
UP of Fibrisoma limi
2.A.7.40.3









Uncharacterized protein of 324 aas and 10 TMSs

Bacteria
Pseudomonadota
UP of Methylotenera versatilis
2.A.7.40.4









DMT family transporter of 290 aas and 10 TMSs.

Bacteria
Transporter of Patescibacteria group bacterium (groundwater metagenome)
2.A.7.41.1









Uncharacterized protein of 178 aas and 4 TMSs

Bacteria
Actinomycetota
UP of Corynebacterium glutamicum
2.A.7.41.2









Uncharacterized protein of 150 aas and 4 TMSs.

Bacteria
Actinomycetota
UP of Mobilicoccus pelagius
2.A.7.41.3









Uncharacterized protein of 149 aas and 4 TMSs

Bacteria
Actinomycetota
UP of Arsenicicoccus bolidensis
         
2.A.7.41.4









Uncharacterized protein of 110 aas and 3 TMSs; possibly an incomplete sequence.

Bacteria
Actinomycetota
UP of Corynebacterium pseudogenitalium
2.A.7.41.5









Uncharacterized protein of 235 aas and 4 TMSs.

Bacteria
Actinomycetota
UP of Raineyella antarctica
2.A.7.42.1









Uncharacterized protein of 140 aas and 4 TMSs.

Bacteria
Actinomycetota
UP of Actinopolyspora alba
2.A.7.42.2









Uncharacterized protein of 139 aas and 4 TMSs

Bacteria
Actinomycetota
UP of Streptomyces rimosus
2.A.7.42.3









Uncharacterized protein of 147 aas and 4 TMSs

Bacteria
Actinomycetota
UP of Planobispora rosea
2.A.7.42.4









Uncharacterized protein of 141 aas and 4 TMSs

Bacteria
Actinomycetota
UP of Thermobispora bispora
2.A.7.42.5









Uncharacterized protein of 143 aas and 4 TMSs.

Bacteria
Actinomycetota
UP of Glycomyces arizonensis
2.A.7.42.6









Uncharacterized protein of 140 aas and 4 TMSs

Bacteria
Actinomycetota
UP of Nocardiopsis trehalosi
2.A.7.42.7









Uncharacterized protein of 149 aas and 4 TMSs

Bacteria
Actinomycetota
UP of Dietzia alimentaria
2.A.7.43.1









Uncharacterized protein of 129 aas and 4 TMSs

Bacteria
Pseudomonadota
UP of Bauldia litoralis
2.A.7.43.2









Uncharacterized protein of 121 aas and 4 TMSs.

Bacteria
Chloroflexota
UP of Dehalococcoides mccartyi
2.A.7.43.3









Uncharacterized protein of 128 aas and 4 TMSs

Archaea
Candidatus Lokiarchaeota
UP of Lokiarchaeum sp. GC14_75 (marine sediment metagenome)
2.A.7.43.4









Uncharacterized protein of 126 aas and 4 TMSs

Bacteria
Chloroflexota
UP of Dehalogenimonas alkenigignens
2.A.7.43.5









Uncharacterized protein of 130 aas and 4 TMSs in a 1 + 3 TMS arrangement, a characteristic of members of this family.

Archaea
Euryarchaeota
UP of Haloferax denitrificans
2.A.7.43.6









Uncharacterized protein of 131 aas and 4 TMSs in a 1 + 2 + 1 TMS arrangement.

Archaea
Candidatus Lokiarchaeota
UP of Candidatus Prometheoarchaeum syntrophicum
2.A.7.43.7









Uncharacterized protein of 143 aas and 4 TMSs in a 1 + 2 + 1 TMS arrangement.

Bacteria
Actinomycetota
UP of Marmoricola solisilvae
2.A.7.43.8









Uncharacterized protein of 149 aas and 4 TMSs

Bacteria
Chloroflexota
UP of Chloroflexi bacterium (marine sediment metagenome)
2.A.7.43.9









Uncharacterized protein of 482 aas and 14 TMSs in a 4 + 2 + 4 + 4 TMS arrangement.  The first 4 TMSs are homologous to proteins in subfamily 2.A.7.43, but the C-terminal region shows sequence similarity with 9.B.241.2.5, an integral membrane geranylgeranylglycerol-phosphate geranylgeranyltransferase with 9 TMSs.

Bacteria
candidate division Zixibacteria
UP of candidate division Zixibacteria bacterium HGW-Zixibacteria-1].
2.A.7.43.10









This uncharacterized protein is annotated in the NCBI database as an NAD-dependent epimerase/dehydratase family protein of 461 aas and 4 C-terminal TMSs that are homologous to the members of TC subfamily 2.A.7.43, but the rest of the protein is hydrophilic and presumable is a fusion between the N-terminal dehydratase and the C-terminal DMT domain.

 

 

Bacteria
Pseudomonadota
UP of an α-proteobacterium
2.A.7.43.11









Uncharacterized protein of 167 aas and 4 TMSs

Bacteria
Spirochaetota
UP of Leptonema illini (bioanode metagenome)
2.A.7.43.12









Uncharacterized protein of 291 aas and 8 TMSs, where the 4 TMSs of many members of this subfamily are duplicaed to give two 4 TMS domains, each with a 1 + 2 + 1 TMS arrangement.

Bacteria
Nitrospirota
UP of Nitrospiraceae bacterium (marine sediment metagenome)
2.A.7.44.1









DUF2227 family putative metal-binding protein of 156 aas and 4 TMSs in a 2 + 2 arrangement.

Archaea
Euryarchaeota
DUF2227 protein of Methanococcoides methylutens
2.A.7.44.2









Uncharacterized protein of 164 aas and 4 TMSs in a 2 + 2 arrangement.

Bacteria
Gemmatimonadota
UP of Gemmatimonadetes bacterium (sponge metagenome)
2.A.7.44.3









Uncharacterized protein of 149 aas and 4 TMSs in a 2 + 2 arrangement.

Bacteria
Deinococcota
UP of Thermus aquaticus
2.A.7.44.4









DUF2227 family putative metal-binding protein of 152 aas and 4 TMSs.

Bacteria
Abditibacteriota
DUF2227 protein of Abditibacterium utsteinense
2.A.7.44.5









Uncharacterized protein of 151 aas and 5 TMSs

Bacteria
Chloroflexota
UP of Chloroflexi bacterium
2.A.7.44.6









Uncharacterized protein of 156 aas and 3 or 4 TMSs.

Bacteria
candidate division Zixibacteria
UP of candidate division Zixibacteria bacterium
2.A.7.44.7









Metal-dependent hydrolase of 173 aas and 4 TMSs

Bacteria
Bacillota
Putative hydrolase of Butyrivibrio proteoclasticus
2.A.7.44.8









Membrane-bound metal-dependent hydrolase of 318 aas and 5 TMSs with an N-terminal YdjM domain.

Bacteria
Bacillota
Hydrolase of Calderihabitans maritimus
2.A.7.44.9









Uncharacterized protein of 190 aas and 3 or 4 TMSs

Bacteria
Candidatus Woesebacteria
UP of Candidatus Woesebacteria bacterium
2.A.7.44.10









Uncharacterized protein of 289 aas and 7 TMSs in a 1 + 1 + 1 + 2 + 2 TMS arrangement

Bacteria
Pseudomonadota
UP of Proteobacteria bacterium (phyllosphere metagenome)
2.A.7.44.11









Metal-dependent hydrolase of 317 aas and 6 TMSs in a 1 + 2 + 2 + 1 arrangement.

Bacteria
Bacillota
Hydrolase of Geosporobacter subterraneus
2.A.7.45.1









DMT!. putative organic solute transporter of 434 aas and 9 apparent TMSs in a 2 + 7 TMS arrangement (Wunderlich 2022).

Eukaryota
Apicomplexa

DMT1 of Plasmodium falciparum