InterPro domain: IPR002657

This family of proteins are found both in prokaryotes and eukaryotes. They are related to the human bile acid:sodium symporters (TC 2.A.28), which are transmembrane proteins functioning in the liver in the uptake of bile acids from portal blood plasma, a process mediated by the co-transport of Na ⁺ [ 1 ].

This entry also includes members of the ACR3 family of arsenite (As(III)) permeases, which confer resistance to arsenic by extrusion from cells [ 2 ]. They exist in prokaryotes and eukaryotes (lower plants and fungi) [ 3 , 4 ]. The ACR3 permeases have ten-transmembrane span topology [ 5 ]. Corynebacterium glutamicum has three Acr3 proteins, CgAcr3-1, CgAcr3-2, and CgAcr3-3. CgAcr3-1 is thought to be an antiporter that catalyses arsenite-proton exchange [ 6 ].

The Shewanella oneidensis Acr3 is not able to transport As(III) and confers resistance only to arsenate (As(V)) [ 7 ], whereas the Acr3 orthologue from Synechocystis mediates tolerance to As(III), As(V) and antimonite (Sb(III)) [ 8 ].

In budding yeast, overexpression of the Acr3 gene confers an arsenite- but not an arsenate-resistance phenotype [ 9 ]. Saccharomyces cerevisiae Acr3 is a plasma membrane metalloid/H+ antiporter that transports arsenite and antimonite [ 10 ].

1. Functional expression cloning and characterization of the hepatocyte Na+/bile acid cotransport system. Proc. Natl. Acad. Sci. U.S.A. 88, 10629-33
2. Properties of arsenite efflux permeases (Acr3) from Alkaliphilus metalliredigens and Corynebacterium glutamicum. J. Biol. Chem. 284, 19887-95
3. A vacuolar arsenite transporter necessary for arsenic tolerance in the arsenic hyperaccumulating fern Pteris vittata is missing in flowering plants. Plant Cell 22, 2045-57
4. Multiple cysteine residues are necessary for sorting and transport activity of the arsenite permease Acr3p from Saccharomyces cerevisiae. Biochim. Biophys. Acta 1838, 747-55
5. Transmembrane topology of the Acr3 family arsenite transporter from Bacillus subtilis. Biochim. Biophys. Acta 1778, 963-73
6. Efflux permease CgAcr3-1 of Corynebacterium glutamicum is an arsenite-specific antiporter. J. Biol. Chem. 287, 723-35
7. Investigation of the structure and function of a Shewanella oneidensis arsenical-resistance family transporter. Mol. Membr. Biol. 25, 691-705
8. Arsenic sensing and resistance system in the cyanobacterium Synechocystis sp. strain PCC 6803. J. Bacteriol. 185, 5363-71
9. Isolation of three contiguous genes, ACR1, ACR2 and ACR3, involved in resistance to arsenic compounds in the yeast Saccharomyces cerevisiae. Yeast 13, 819-28
10. Acr3p is a plasma membrane antiporter that catalyzes As(III)/H(+) and Sb(III)/H(+) exchange in Saccharomyces cerevisiae. Biochim. Biophys. Acta 1808, 1855-9