TCDB is operated by the Saier Lab Bioinformatics Group

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.

References associated with 2.A.96 family:

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. 12634328
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:. 34575058
Ferrada, E. and G. Superti-Furga. (2022). A structure and evolutionary-based classification of solute carriers. iScience 25: 105096. 36164651
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. 16531087
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. 17233767
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. 12966084
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. 29679102
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. 14968426
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. 17395151
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. 18302536
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. 23844911
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] 30333234
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] 30844266