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

The ArAE family consists of bacterial and eukaryotic members from plants, yeast and protozoans. The bacterial proteins are of 655 to 755 amino acyl residues 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. 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 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 database, 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.



This family belongs to the MFS Superfamily.

 

References:

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.

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.

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.

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.

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.

Examples:

TC#NameOrganismal TypeExample
2.A.85.1.1

YccS of unknown specificity

Bacteria

YccS of E. coli (720 aas) (P75870)

 
2.A.85.1.2

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)

 
2.A.85.1.3

YhfK of unknown specificity

Bacteria

YhfK of E. coli (P45537)

 
2.A.85.1.4

Fusaric acid resistance protein

Bacteria

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

Bacteria

YdhK of Escherichia coli O157:H7

 
Examples:

TC#NameOrganismal TypeExample
2.A.85.10.1

Fusaric acid resistance protein homologue

Actinobacteria

FusB homologue of Streptomyces coelicolor

 
2.A.85.10.2

FusB homologue

Acctinobacteria

FusB homologue of Streptomyces coelicolor

 
Examples:

TC#NameOrganismal TypeExample
2.A.85.11.1

Uncharacterized protein of 1406 aas

Red algae

UP of Galdieria sulphuraria

 
2.A.85.11.2

Uncharacterized protein of 1365 aas

Red algae

UP of Galdieria sulphuraria

 
2.A.85.11.3

Uncharacterized protein of 1638 aas

Red algae

UP of Galdieria sulphuraria

 
2.A.85.11.4

Uncharacterized protein of 1269 aas and 11 - 14 TMSs.

UP of Chlamydomonas reinhardtii (Chlamydomonas smithii)

 
Examples:

TC#NameOrganismal TypeExample
2.A.85.2.1

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).

Plants

Orf1 of Arabidopsis thaliana (560 aas) (O49696)

 
2.A.85.2.2

Putative protein

Plants

Orf5 of Arabidopsis thaliana (533 aas) (Q9SX23)

 
2.A.85.2.3

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).

Plants

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)
 
2.A.85.2.5

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).

Plants

ALMT1 of Triticum aestivum (Q76LB2)

 
2.A.85.2.6Putative aluminum-activated malate transporter 3 (AtALMT3)PlantsALMT3 of Arabidopsis thaliana
 
2.A.85.2.7

The vacuolar ALMT9.  Citrate is an open channel blocker.  There are probably four subunits, and TMS5 contributes to pore formation (Zhang et al. 2013).

Plants

ALMT9 of Arabidopsis thaliana

 
Examples:

TC#NameOrganismal TypeExample
2.A.85.3.1

Hypothetical protein

Yeast

Ydg8 of Schizosaccharomyces pombe (977 aas) (Q10495)

 
2.A.85.3.2

Uncharacterized protein of 1125 aas

Yeast

UP of Saccharomyces cerevisiae

 
2.A.85.3.3

Uncharacterized protein of 1219 aas

Yeast

UP of Saccharomyces cerevisiae

 
2.A.85.3.4

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

Yeast

Protein of Komagataella pastoris

 
2.A.85.3.5

Uncharacterized protein of 1040 aas

Fungi

UP of Gloeophyllum trabeum (Brown rot fungus)

 
Examples:

TC#NameOrganismal TypeExample
2.A.85.4.1

Lantibiotic protection protein, MutG

Bacteria

MutG of Aerococcus viridans (D4YEF0)

 
2.A.85.4.2

YgaE

Bacteria

YgaE of Bacillus subtilis (P71083)

 
2.A.85.4.3

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

Firmicutes

DUF939 protein of Clostridium methylpentosum

 
Examples:

TC#NameOrganismal TypeExample
2.A.85.5.1

5 or 6 TMS 'half sized', YqjA

Bacteria

YqjA of Bacillus subtilis (322 aas) (P54538)

 
Examples:

TC#NameOrganismal TypeExample
2.A.85.6.1

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).

Bacteria

MdtO of E. coli (P32715)

 
Examples:

TC#NameOrganismal TypeExample
2.A.85.7.1

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

Bacteria

FusC of E. coli (P33011)

 
2.A.85.7.2

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

Bacteria

MutG of Psychrobacter sp. 1501 (F5SU14)

 
Examples:

TC#NameOrganismal TypeExample
2.A.85.8.1

Putative integral membrane protein

 

Actinobacteria

Putative integral membrane protein of Streptomyces coelicolor
 
Examples:

TC#NameOrganismal TypeExample
2.A.85.9.1

Actinobacteria