2.A.85 The Aromatic Acid Exporter (ArAE) Family

The ArAE family consists of bacterial, archaeal and eukaryotic members for exampele, from plants, yeast and protozoans. The bacterial proteins are of 655 to 755 aas and exhibit a repeat sequence due to an internal gene duplication event with residue positions 1-180 exhibiting 6 putative TMSs, residue positions, 181-320 being hydrophilic, residue positions, 320-460 exhibiting another 6 putative TMSs, and residue positions 460-660 being hydrophilic in an average hydropathy plot. There are four E. coli homologues as well as one from H. influenzae and one from Synechocystis in TCDB. At least two ArAE family members are encoded within operons that also encode membrane fusion proteins (MFP; TC #8.A.1). This provides the basis for suggesting that these proteins catalyze efflux (Harley and Saier, 2000).

The plant proteins are of 506-560 residues and exhibit only 6 putative TMSs (residue positions 60-270 in the average hydropathy plot) followed by a long hydrophilic domain (residue positions 271-650). The P. falciparum and S. pombe proteins are 669 and 977 residues in length. The S. pombe protein has a topology resembling the bacterial proteins although it clusters phylogenetically with the eukaryotic proteins. The P. falciparum protein exhibits repeats of the hydrophilic domain but may not be a transporter. None of these eukaryotic proteins is functionally characterized.

A single bacterial member of the ArAE family has been functionally characterized (Van Dyk et al., 2004). This protein is YhcP of E. coli which depends on a membrane fusion protein (MFP family; TC #8.A.1), YhcQ, for activity. This protein proves to be a pmf-dependent para-hydroxybenzoic acid (pHBA) efflux pump (Van Dyk et al., 2004). Only a few aromatic carboxylic acids of hundreds of compounds tested proved to be substrates of the YhcQP (AaeAB) efflux pump. It may function as a 'metabolic relief valve' to relieve the toxic effects of unbalanced metabolism. Half-sized homologues are also found in the NCBI and TCDB databases, although these have not been characterized biochemically. One such protein is YqjA of Bacillus subtilis (322 aas). It has 5 or 6 TMSs (residues 17-141) followed by a 180 residue hydrophilic domain (TC #2.A.85.5.1), and is very distantly related to the full-length proteins.

The aluminium-activated malate transporters (ALMTs, see TC# 2.A.85.2) comprise a membrane protein family that demonstrates various physiological functions in plants, such as tolerance to environmental Al3+ and the regulation of stomatal movement. Dabravolski and Isayenkov 2023 summarized the knowledge about this transporter family and assess their involvement in diverse physiological processes and comprehensive regulatory mechanisms. They have conducted a thorough bioinformatic analysis to decipher the functional importance of conserved residues, structural components, and domains. Phylogenetic analyses have provided insights into the molecular evolution of ALMT family proteins, expanding their scope beyond the plant kingdom (Dabravolski and Isayenkov 2023). 

This family belongs to the Major Facilitator (MFS) Superfamily.



Dabravolski, S.A. and S.V. Isayenkov. (2023). Recent Updates on ALMT Transporters'' Physiology, Regulation, and Molecular Evolution in Plants. Plants (Basel) 12:.

Dreyer, I., J.L. Gomez-Porras, D.M. Riaño-Pachón, R. Hedrich, and D. Geiger. (2012). Molecular Evolution of Slow and Quick Anion Channels (SLACs and QUACs/ALMTs). Front Plant Sci 3: 263.

Harley, K.T. and M.H. Saier, Jr. (2000). A novel ubiquitous family of putative efflux transporters. J. Mol. Microbiol. Biotechnol. 2: 195-198.

Hoekenga, O.A., L.G. Maron, M.A. Piñeros, G.M. Cançado, J. Shaff, Y. Kobayashi, P.R. Ryan, B. Dong, E. Delhaize, T. Sasaki, H. Matsumoto, Y. Yamamoto, H. Koyama, and L.V. Kochian. (2006). AtALMT1, which encodes a malate transporter, is identified as one of several genes critical for aluminum tolerance in Arabidopsis. Proc. Natl. Acad. Sci. U.S.A. 103: 9738-9743.

Kovermann, P., S. Meyer, S. Hörtensteiner, C. Picco, J. Scholz-Starke, S. Ravera, Y. Lee, and E. Martinoia. (2007). The Arabidopsis vacuolar malate channel is a member of the ALMT family. Plant J. 52: 1169-1180.

Li, C., L. Dougherty, A.E. Coluccio, D. Meng, I. El-Sharkawy, E. Borejsza-Wysocka, D. Liang, M.A. Piñeros, K. Xu, and L. Cheng. (2020). Apple ALMT9 Requires a Conserved C-Terminal Domain for Malate Transport Underlying Fruit Acidity. Plant Physiol. 182: 992-1006.

Meyer, S., P. Mumm, D. Imes, A. Endler, B. Weder, K.A. Al-Rasheid, D. Geiger, I. Marten, E. Martinoia, and R. Hedrich. (2010). AtALMT12 represents an R-type anion channel required for stomatal movement in Arabidopsis guard cells. Plant J. 63: 1054-1062.

Motoda, H., T. Sasaki, Y. Kano, P.R. Ryan, E. Delhaize, H. Matsumoto, and Y. Yamamoto. (2007). The Membrane Topology of ALMT1, an Aluminum-Activated Malate Transport Protein in Wheat (Triticum aestivum). Plant Signal Behav 2: 467-472.

Mumm P., Imes D., Martinoia E., Al-Rasheid KA., Geiger D., Marten I. and Hedrich R. (2013). C-terminus-mediated voltage gating of Arabidopsis guard cell anion channel QUAC1. Mol Plant. 6(5):1550-63.

Paulsen, I.T., J.H. Park, P.S. Choi, and M.H. Saier, Jr. (1997). A family of Gram-negative bacterial outer membrane factors that function in the export of proteins, carbohydrates, drugs and heavy metals from Gram-negative bacteria. FEMS Microbiol. Lett. 156: 1-8.

Piñeros, M.A., G.M. Cançado, L.G. Maron, S.M. Lyi, M. Menossi, and L.V. Kochian. (2008). Not all ALMT1-type transporters mediate aluminum-activated organic acid responses: the case of ZmALMT1 - an anion-selective transporter. Plant J. 53: 352-367.

Piñeros, M.A., G.M. Cançado, and L.V. Kochian. (2008). Novel properties of the wheat aluminum tolerance organic acid transporter (TaALMT1) revealed by electrophysiological characterization in Xenopus Oocytes: functional and structural implications. Plant Physiol. 147: 2131-2146.

Qin, L., L.H. Tang, J.S. Xu, X.H. Zhang, Y. Zhu, C.R. Zhang, M.H. Wang, X.L. Liu, F. Li, F. Sun, M. Su, Y. Zhai, and Y.H. Chen. (2022). Cryo-EM structure and electrophysiological characterization of ALMT from reveal a previously uncharacterized class of anion channels. Sci Adv 8: eabm3238.

Ramesh, S.A., M. Kamran, W. Sullivan, L. Chirkova, M. Okamoto, F. Degryse, M. McLaughlin, M. Gilliham, and S.D. Tyerman. (2018). Aluminum-Activated Malate Transporters Can Facilitate GABA Transport. Plant Cell 30: 1147-1164.

Ramesh, S.A., Y. Long, A. Dashtbani-Roozbehani, M. Gilliham, M.H. Brown, and S.D. Tyerman. (2022). Picrotoxin Delineates Different Transport Configurations for Malate and γ Aminobutyric Acid through TaALMT1. Biology (Basel) 11:.

Ryan, P.R., S.D. Tyerman, T. Sasaki, T. Furuichi, Y. Yamamoto, W.H. Zhang, and E. Delhaize. (2011). The identification of aluminium-resistance genes provides opportunities for enhancing crop production on acid soils. J Exp Bot 62: 9-20.

Sasaki T., Mori IC., Furuichi T., Munemasa S., Toyooka K., Matsuoka K., Murata Y. and Yamamoto Y. (2010). Closing plant stomata requires a homolog of an aluminum-activated malate transporter. Plant Cell Physiol. 51(3):354-65.

Sasaki T., Tsuchiya Y., Ariyoshi M., Ryan PR., Furuichi T. and Yamamoto Y. (2014). A domain-based approach for analyzing the function of aluminum-activated malate transporters from wheat (Triticum aestivum) and Arabidopsis thaliana in Xenopus oocytes. Plant Cell Physiol. 55(12):2126-38.

Sulavik, M.C., C. Houseweart, C. Cramer, N. Jiwani, N. Murgolo, J. Greene, B. DiDomenico, K.J. Shaw, G.H. Miller, R. Hare, and G. Shimer. (2001). Antibiotic susceptibility profiles of Escherichia coli strains lacking multidrug efflux pump genes. Antimicrob. Agents Chemother. 45: 1126-1136.

Van Dyk, T.K., L.J. Templeton, K.A. Cantera, P.L. Sharpe, and F.S. Sariaslani. (2004). Characterization of the Escherichia coli AaeAB efflux pump: a metabolic relief valve? J. Bacteriol. 186: 7196-7204.

Wang, J., X. Yu, Z.J. Ding, X. Zhang, Y. Luo, X. Xu, Y. Xie, X. Li, T. Yuan, S.J. Zheng, W. Yang, and J. Guo. (2021). Structural basis of ALMT1-mediated aluminum resistance in Arabidopsis. Cell Res. [Epub: Ahead of Print]

Zhang J., Baetz U., Krugel U., Martinoia E. and De Angeli A. (2013). Identification of a probable pore-forming domain in the multimeric vacuolar anion channel AtALMT9. Plant Physiol. 163(2):830-43.

Zhang, W.H., P.R. Ryan, T. Sasaki, Y. Yamamoto, W. Sullivan, and S.D. Tyerman. (2008). Characterization of the TaALMT1 protein as an Al3+-activated anion channel in transformed tobacco (Nicotiana tabacum L.) cells. Plant Cell Physiol. 49: 1316-1330.

Zhou, H., Z. Hu, Y. Luo, C. Feng, and Y. Long. (2022). Multiple ALMT subunits combine to form functional anion channels: A case study for rice ALMT7. Front Plant Sci 13: 1012578.


TC#NameOrganismal TypeExample

Inner membrane protein, YccS, of unknown specificity but of 717 aas and 12 TMSs in a 6 + 6 TMS arrangement, each followed by an ~ 200 aa hydrophilic domain.


YccS of E. coli (717 aas) (P75870)


p-hydroxybenzoate efflux carrier, AaeB (Van Dyk et al., 2004). Several aromatic carboxylic acids serve as inducers of yhcRQP operon expression.

Gram-negative bacteria

AaeB (YhcP) of E. coli (655 aas) (P46481)


YhfK of unknown specificity


YhfK of E. coli (P45537)


Fusaric acid resistance protein


Fusaric acid resistance protein of Pantoea sp. aB (E0M081)

2.A.85.1.5Uncharacterized transporter YdhKBacteria

YdhK of Salmonella typhimurium

2.A.85.1.6Uncharacterized transporter YdhK


YdhK of Escherichia coli O157:H7


Uncharacterized protein of 635 aas and 9 or 10 TMSs in a 5 (or 6) + hydrophilic domain + 4 TMSs + another hydrophilic domain.  The protein shows very little sequence similarity with other members of this family.


UP of Methanosphaera stadtmanae


TC#NameOrganismal TypeExample

Fusaric acid resistance protein homologue


FusB homologue of Streptomyces coelicolor


FusB homologue


FusB homologue of Streptomyces coelicolor


TC#NameOrganismal TypeExample

Uncharacterized protein of 1406 aas

Red algae

UP of Galdieria sulphuraria


Uncharacterized protein of 1365 aas

Red algae

UP of Galdieria sulphuraria


Uncharacterized protein of 1638 aas

Red algae

UP of Galdieria sulphuraria


Uncharacterized protein of 1269 aas and 11 - 14 TMSs.

UP of Chlamydomonas reinhardtii (Chlamydomonas smithii)


TC#NameOrganismal TypeExample

Integral 6 TMS membrane protein which has been assigned to the FusC (fusaric acid) family.  It's function is not clear.

FusC of Methanoregula boonei



Uncharacterized membrane protein of 173 aas and 6 TMSs.

UP of Halothiobacillus neapolitanus (Thiobacillus neapolitanus)



Uncharacterized membrane protein of 183 aas and 6 TMSs.

UP of Odoribacter sp. 


Uncharacterized membrane protein of 232 aas and probably 6 TMSs.

UP of Magnetospirillum fulvum


Uncharacterized FUSC family protein of 181 aas and 6 TMSs in a 2 + 2 + 2 TMS arrangement.

UP of Alistipes communis


Uncharacterized FUSC family protein of 173 aas and 6 TMSs.

UP of Methanomicrobiales archaeon


Uncharacterized FUSC family protein of 171 aas and 6 TMSs.

UP of Pseudofrancisella aestuarii


Uncharacterized FUSC family protein of 106 aas and 6 TM

UP of Candidatus Acidoferrum sp.


TC#NameOrganismal TypeExample

An inorganic anion (Cl-/NO3-) transporter, ALMT12 or QUAC1 (Quickly activating Anion Channel 1), reported to be incapable of transporting organic anions, is involved in stomatal closure (Sasaki et al, 2010). It is an R-type inorganic anion channel required for stomatal movement in Arabidopsis guard cells (Meyer et al., 2010).  The C-terminal cytosolic domain mediates voltage gating (Mumm et al. 2013). QUAC1 regulates stomatal closure in response to environmental stimuli (Qin et al. 2022). See Dabravolski and Isayenkov 2023 for a review of the ALMT subfamiily.


Orf1 of Arabidopsis thaliana (560 aas) (O49696)


Putative transport protein, Orf5, of 533 aas and 7 or 8 TMSs in a 5 or 6 TMS bundle near the N-terminus, one more putative TMS near the middle, and one more near the C-terminus.


Orf5 of Arabidopsis thaliana (533 aas) (Q9SX23)


The root aluminum-activated malate efflux transporter, ALMT1 (required for aluminum tolerance) (Hoekenga et al., 2006).  Also called Quick Anion Channel, QUAC, based on activation kinetics of anion channel currents in response to voltage changes.  Evolutionary studies have been reported (Dreyer et al. 2012).  Plants respond to aluminum (Al) ions by releasing malate from their root apices via ALMT1 with malate bound to the toxic Al ions, contributing to Al tolerance (Sasaki et al. 2014). ALMT1 mediates the efflux of malate to chelate the Al3+ in acidic soils and underlies the plant's Al resistance. Wang et al. 2021 presented cryo-EM structures of AtALMT1 in the apo, malate-bound, and Al-bound states at up to 3.0 Å resolution. The AtALMT1 dimer assembles an anion channel, and each subunit contains six transmembrane helices (TMSs) as well as six cytosolic α-helices. Two pairs of Arg residues are located in the center of the channel pore and contribute to malate recognition. Al binds at the extracellular side of AtALMT1 and induces conformational changes of the TMS 1-2 loop and the TMS 5-6 loop, resulting in the opening of the extracellular gate (Wang et al. 2021). Qin et al. 2022 provided insight into the gating and modulation of the ALMT12/QUAC1 anion channel in Glycine max (soybean). Picrotoxin inhibits anion flux but not GABA flux (Ramesh et al. 2022).


ALMT1 of Arabidopsis thaliana (Q15EV0)

2.A.85.2.4The anion-selective transporter ALMT1 (transports anions) (35% identical to 2.A.85.2.3) (Pineros et al., 2008)PlantsALMT1 of Zea mays (A1XGH3)

Aluminum-stimulated anion (Malate >> NO3- > Cl-; Malate/Cl- ≈ 20) channel (Zhang et al., 2008) (67% identical to 2.A.85.2.4). Confers Al+3 resistance (Ryan et al., 2011). May also transport a variety of organic and inorganic anions (Piñeros et al. 2008). It can also transport GABA (Ramesh et al. 2018). ALMT1 has 6 TMSs with the N- and C-termini being on the external surface of the plasma membrane (Motoda et al. 2007).


ALMT1 of Triticum aestivum (Q76LB2)

2.A.85.2.6Putative aluminum-activated malate transporter 3 (AtALMT3)PlantsALMT3 of Arabidopsis thaliana

The vacuolar malate "channel", ALMT9, of 598 aas and 6 - 8 TMSs. TMSs 1 - 6 occur together near the N-terminus; putatives TMS 7 is near the middle of the protein, and putative TMS 8 is near the C-terminus. Citrate is an open channel blocker.  There are probably four subunits, and TMS5 contributes to pore formation (Zhang et al. 2013). It has higher selectivity for malate than for fumarate and exhibits weak chloride conductance (Kovermann et al. 2007). The apple ALMT9 requires a conserved C-terminal domain for malate transport, underlying fruit acidity (Li et al. 2020).


ALMT9 of Arabidopsis thaliana


Aluminum-activated malate transporter 7, ALMT7, of 462 aas and 6 or 7 TMSs in a 5 or 6 (N-terminal) + 1 or 2 TMS (C-terminal) TMS arrangement. Multiple ALMT subunits combine to form functional anion channels in rice (Zhou et al. 2022).

ALMT7 of Saccharum hybrid cultivar



TC#NameOrganismal TypeExample

Hypothetical protein


Ydg8 of Schizosaccharomyces pombe (977 aas) (Q10495)


Uncharacterized protein of 1125 aas


UP of Saccharomyces cerevisiae


Uncharacterized protein of 1219 aas


UP of Saccharomyces cerevisiae


Protein required for ubiquinone biosynthesis of 1035 aas and 14 putative TMSs


Protein of Komagataella pastoris


Uncharacterized protein of 1040 aas


UP of Gloeophyllum trabeum (Brown rot fungus)


TC#NameOrganismal TypeExample

Lantibiotic protection protein, MutG


MutG of Aerococcus viridans (D4YEF0)




YgaE of Bacillus subtilis (P71083)


DUF939 (N-terminus) with C-terminal HAD hydrolase (Cof or haloacid dehydrogenase) family IIB domain;  450 aas.


DUF939 protein of Clostridium methylpentosum


5 or 6 TMS 'half sized', YqjA


YqjA of Bacillus subtilis (322 aas) (P54538)


TC#NameOrganismal TypeExample

TC#NameOrganismal TypeExample

MdtO (YjcQ), Multidrug resistance protein (involved in resistance to puromycin, acriflavin and tetraphenyl arsonium chloride; acts with MdtN (TC# 8.A.1.1.3) and MdtP (TC# 1.B.17.3.9)) (Sulavik et al., 2001).


MdtO of E. coli (P32715)


FUSC family protein of 751 aas and 10 or 12 TMSs.

FUSC family protein of Burkholderia gladioli


FUSC family protein of 517 aas and 12 TMSs.

FUSC family protein of Gemmobacter intermedius


TC#NameOrganismal TypeExample

Fusaric acid resistance protein, FusC (YeeA; 352aas; 6 N-terminal TMSs plus a hydrophilic C-terminal cytoplasmic domain).


FusC of E. coli (P33011)


MutG lantibiotic protection protein with 6 N-terminal TMSs and a hydrophilic C-terminal domain.


MutG of Psychrobacter sp. 1501 (F5SU14)


TC#NameOrganismal TypeExample

Putative integral membrane protein



Putative integral membrane protein of Streptomyces coelicolor

FUSC family protein of 460 aas and probably 12 TMSs.

FUSC family protein of Gordonia paraffinivorans


FUSC family protein of 383 aas and 11 or 12 TMSs, with no large hydrophilic domain.

FUSC family protein of Psychrobacter faecalis


Uncharacterized protein of 376 aas and 12 probable TMSs with no hydrophilic domain.

UP of Enterococcus faecium


FUSC family protein of 361 aas and 12 probable TMSs.

Fusc family protein of Demequina subtropica


TC#NameOrganismal TypeExample



FUSC family protein of 423 aas and 6 TM

FUSC family protein of Marmoricola scoriae


FUSC family protein of 338 aas and 5 or 6 N-terminal TMSs plus a large C-terminal hydrophilic domain.

FUSC family protein of Bacillus velezensis


FUSC family protein of 374 aas and 6 N-terminal TMSs.

FUSC family protein of Microbacterium oxydans