2.A.96 The Acetate Uptake Transporter (AceTr) Family

YaaH is an E. coli protein of 188aas with 6 putative TMSs. It has homologues in other bacteria, archaea, several fungi and protozoa. S. cerevisiae has 3 paralogues (YCR010c, YDR384c and YNR002c). The homlogue, AcpA, of Aspergillus nidulans, has been shown to be an acetate uptake porter in germinating conidia under conditions when the substrate is not protonated (Robellet et al., 2008). Another homologue of A. nidulans, AlcS, is much more distantly related but is of unknown transport function (Flipphi et al., 2006). In Saccharomyces cerevisiae, the orothologue of AcpA is Ady2 (50% identical).  Evidence indicates that several other homologues are acetate porters (see proteins). Members of this family have the SLC53 fold (Ferrada and Superti-Furga 2022).

SatP (YaaH) of E. coli has been preliminarily identified as a succinate-acetate/proton symporter. Sun et al. 2018 reported the crystal structure of SatP at 2.8 Å resolution, which revealed a hexameric UreI-like channel structure. It has six TMSs surrounding the central channel pore in each protomer and three conserved hydrophobic residues, FLY, located in the middle of the TMS region for pore constriction. According to single-channel conductance recordings, performed with purified SatP reconstituted into lipid bilayers, three conserved polar residues in TMS1, facing the periplasmic side, are closely associated with acetate translocation activity (Sun et al. 2018).  Wu et al. 2019 suggested that channel opening results from the repacking of key residues, such as Gln50 and Phe17, as well as the subsequent outward movement of all transmembrane helices. Their simulations suggested that acetate is always surrounded by several water molecules when passing through the channel. A high energy barrier of 15 kcal/mol was measured.  This fact and the results observed for fungal homologues suggest that a carrier mechanism rather than a channel mechanism is operative.



Augstein, A., K. Barth, M. Gentsch, S.D. Kohlwein, and G. Barth. (2003). Characterization, localization and functional analysis of Gpr1p, a protein affecting sensitivity to acetic acid in the yeast Yarrowia lipolytica. Microbiology 149: 589-600.

Dong, X.Q., J.Y. Lin, P.F. Wang, Y. Li, J. Wang, B. Li, J. Liao, and J.X. Lu. (2021). Solid-State NMR Studies of the Succinate-Acetate Permease from Citrobacter Koseri in Liposomes and Native Nanodiscs. Life (Basel) 11:.

Ferrada, E. and G. Superti-Furga. (2022). A structure and evolutionary-based classification of solute carriers. iScience 25: 105096.

Flipphi, M., X. Robellet, E. Dequier, X. Leschelle, B. Felenbok, and C. Vélot. (2006). Functional analysis of alcS, a gene of the alc cluster in Aspergillus nidulans. Fungal Genet Biol 43: 247-260.

Gentsch, M., M. Kuschel, S. Schlegel, and G. Barth. (2007). Mutations at different sites in members of the Gpr1/Fun34/YaaH protein family cause hypersensitivity to acetic acid in Saccharomyces cerevisiae as well as in Yarrowia lipolytica. FEMS Yeast Res 7: 380-390.

Guaragnella, N. and R.A. Butow. (2003). ATO3 encoding a putative outward ammonium transporter is an RTG-independent retrograde responsive gene regulated by GCN4 and the Ssy1-Ptr3-Ssy5 amino acid sensor system. J. Biol. Chem. 278: 45882-45887.

Guo, H., T. Huang, J. Zhao, H. Chen, and G. Chen. (2018). Fungi short-chain carboxylate transporter: shift from microbe hereditary functional component to metabolic engineering target. Appl. Microbiol. Biotechnol. 102: 4653-4662.

Paiva, S., F. Devaux, S. Barbosa, C. Jacq, and M. Casal. (2004). Ady2p is essential for the acetate permease activity in the yeast Saccharomyces cerevisiae. Yeast 21: 201-210.

Ricicová, M., H. Kucerová, L. Váchová, and Z. Palková. (2007). Association of putative ammonium exporters Ato with detergent-resistant compartments of plasma membrane during yeast colony development: pH affects Ato1p localisation in patches. Biochim. Biophys. Acta. 1768: 1170-1178.

Robellet, X., M. Flipphi, S. Pégot, A.P. Maccabe, and C. Vélot. (2008). AcpA, a member of the GPR1/FUN34/YaaH membrane protein family, is essential for acetate permease activity in the hyphal fungus Aspergillus nidulans. Biochem. J. 412: 485-493.

Sa-Pessoa J., Paiva S., Ribas D., Silva IJ., Viegas SC., Arraiano CM. and Casal M. (2013). SATP (YaaH), a succinate-acetate transporter protein in Escherichia coli. Biochem J. 454(3):585-95.

Sun, P., J. Li, X. Zhang, Z. Guan, Q. Xiao, C. Zhao, M. Song, Y. Zhou, L. Mou, M. Ke, L. Guo, J. Geng, and D. Deng. (2018). Crystal structure of the bacterial acetate transporter SatP reveals that it forms a hexameric channel. J. Biol. Chem. [Epub: Ahead of Print]

Wu, M., L. Sun, Q. Zhou, Y. Peng, Z. Liu, and S. Zhao. (2019). Molecular Mechanism of Acetate Transport through the Acetate Channel SatP. J Chem Inf Model. [Epub: Ahead of Print]


TC#NameOrganismal TypeExample

Acetate/succinate transporter, SatP or YaaH of 196 aas and 6 TMSs (Sá-Pessoa et al. 2013).  It is specific for acetate (a monocarboxylate) and for succinate (a dicarboxylate), with affinity constants at pH 6.0 of 1.24 ± 0.13 mM for acetate and 1.18 ± 0.10 mM for succinate. In glucose grown-cells, the ΔyaaH mutant is compromised for the uptake of both labelled acetic and succinic acids. YaaH, together with ActP, previously described as an acetate transporter, affect the use of acetic acid as a sole carbon and energy source. Both genes have to be deleted simultaneously to abolish acetate transport. The uptake of acetate and succinate was restored when yaaH was expressed in trans in ΔyaaH ΔactP cells. YaaH amino acid residues Leu131 and Ala164 are important for the enhanced ability to transport lactate (Sá-Pessoa et al. 2013). The 3-d structure has been determined to 2.8 Å resolution showing that it is a hexamer with each protomer having a central pore surrounded by 6 TMSs (Sun et al. 2018) (see family description for more details). Wu et al. 2019 suggested that channel opeining involves repacking of key residues, such as Gln50 and Phe17, as well as the subsequent outward movement of all transmembrane helices. Their simulations suggested that acetate is always surrounded by several water molecules when passing through the anion channel, and a high energy barrier of 15 kcal/mol was observed (Wu et al. 2019). SatP from Citrobacter koseri (92% identical to the E. coli ortholog) in liposomes and native nanodiscs has been examined structurally using solid state NMR, revealing the common helical structures in their transmembrane domains (Dong et al. 2021). It is not certain that SatP is a carrier or a channel.


SatP (YaaH) of E. coli (P0AC98)


GPR1/FUN34/YaaH family of 298 aas and 6 TMSs.

GPR1 protein of Angomonas deanei


Accumulation of dyads protein 2, Ady2, or ATO acetate uptake porter of 277 aas and 6 TMSs in a 3 + 3 TMS arrangement.

Ady2 of Kluyveromyces marxianus (Candida Kefyr), yeast


Uncharacterized protein of 223 aas and 6 TMSs in a 3 + 3 TMS arrangement.

UP of Thamnidium elegans


SatP/GPR1/FUN34/YaaH family transporter of 189 aas and 6 TMSs.

GPR1 of Streptacidiphilus neutrinimicus


Uncharacterized protein of 208 aas and 6 TMSs in a 3 + 3 TMS arrangement.

UP of Syntrophomonadaceae bacterium (anaerobic digester metagenome)


Gpr1/YarL1 glyoxylate pathway regulator.  Plays a role in acetate sensitivity (Augstein et al. 2003; Gentsch et al. 2007).  Probably an acetate transporter.


Gpr1 of Yarrowia lipolytica (P41943)


The acetate permease, AcpA (Robellet et al., 2008). (induced by acetate, ethanol and ethyl acetate). This systems and its orthologs in fungi have been reviewed (Guo et al. 2018).

Filamentous fungi

AcpA of Emericella (Aspergillus) nidulans (Q5B2K4)

2.A.96.1.4The acetate permease, Ady2, required for normal sporulation; phosphorylated in mitochondria (Paiva et al., 2004)


Ady2 of Saccharomyces cerevisiae (P25613)


The ammonium exporter (ammonium outward transporter 2), Ato2 or Fun34 (Guaragnella and Butow, 2003Ricicová et al., 2007)


Ato3 of Saccharomyces cerevisiae (Q12359)


Meiotically up-regulated gene 86 protein, Mug86


Mug86 of Schizosaccharomyces pombe


Ammonia transport outward protein 2, ATO2

FungiATO2 of Saccharomyces cerevisiae

Uncharacterized protein of 182 aas and 6 TMSs.

UP of Acholeplasma modicum


Uncharacterized protein of 200 aas and 6 TMSs.

UP of Methanosarcina soligelidi


TC#NameOrganismal TypeExample

Ethanol-induced protein AlcS (6 TMSs.  May be distantly related to the second half (TMSs 7-12)) of APC family member, 3.A.3.3.4. This subfamily is absent from yeast and bacteria (Flipphi et al., 2006).

Filamentous fungi

AlcS of Emericella (Aspergillus) nidulans (Q460G9)


GPR1 protein of 259 aas and 6 TMSs.

GPR1 protein of Lentinula edodes


Uncharacterized protein of 309 aas with a 100 residue hydrophilic N-terminus, and a 6 TMS C-terminal region.

UP of Mycosphaerella eumusae (Pseudocercospora eumusae)