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). There are 10 AceTr homologues in Candida albicans, but only two of them have been shown to be acetate uptake porters. The acetate uptake transporter family motif 'NPAPLGL(M/S)' is essential for substrate uptake (Ribas et al. 2019). The roles of AceTr family porters in Candida Pathogenesis has been reviewed (Alves et al. 2020). Insights into the acetate uptake transporter (AceTr) family by unveiling amino acid residues critical for specificity and activity has appeared (Rendulić et al. 2021).
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.
Ato1, Ato2, Ato3, and Ato6 in Candida albicans exhibit distinct cellular localization and expression levels in the plasma membrane, depending on the presence or absence of monocarboxylates. Deletion of ATO1 impaired Ato2 and Ato3 protein expression and caused ER retention of a distinct form of Ato2, suggesting a central regulatory role for Ato1 in the Ato transport system. This family has three consecutive 6-helix transport domains and a unique C-terminal fusion with Sua5/YciO/YrdC, an enzyme involved in tRNA modification (Ghuaemi et al., 2025 - 2026, personal communication).
References:
Acetate/succinate/H+ transporter (symporter), 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.
Bacteria
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.
Yeast
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)
The acetate permease, Ady2 (Ato1) is required for normal sporulation; it is phosphorylated in mitochondria (Paiva et al., 2004). This family has three consecutive 6-helix transport domains and a unique C-terminal fusion with Sua5/YciO/YrdC, an enzyme involved in tRNA modification.
Yeast
Ady2 of Saccharomyces cerevisiae (P25613)
The ammonium exporter (ammonium outward transporter 2), Ato2 or Fun34 (Guaragnella and Butow, 2003; Ricicová et al., 2007)
Yeast
Ato3 of Saccharomyces cerevisiae (Q12359)
Meiotically up-regulated gene 86 protein, Mug86
Mug86 of Schizosaccharomyces pombe
Ammonia transport outward protein 2, ATO2
Uncharacterized protein of 182 aas and 6 TMSs.
UP of Acholeplasma modicum
Uncharacterized protein of 200 aas and 6 TMSs.
UP of Methanosarcina soligelidi
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)