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2.A.82 The Organic Solute Transporter (OST) Family

Members of the OST (Slc51) family have been characterized from the little skate, Raja erinacea (Wang et al., 2001), humans and mouse (Seward et al., 2003). Each system consists of two polypeptide chains, α and β. For the human, the α-subunit is of 340 aas with 7 putative TMSs while the β-subunit is of 128 aas with 1 putative TMS near the N-terminus (residues 40-56). The beta subunit is required not only for heterodimerization and trafficking but also for function (Christian et al., 2012).  The functions of the extracellular, transmembrane and cytoplasmic domains have been reported where only the transmembrane domain plus 15 associated amino acy residues are essential for activity (Christian and Hinkle 2017).

Neither OSTα (OSTa) nor OSTβ (OSTb) alone has activity, but the two together transport a variety of organic compounds, mostly anions. Transport of estrone-3-sulfate is Na+-independent, ATP-independent, saturable and inhibited by other steroids and anionic drugs. Bile acids, taurocholate, digoxin and prostaglandin E1 are substrates, but estradiol 17β-D-glucuronide and p-aminohippurate are not. The two proteins are highly expressed in many human tissues. The β-subunit is not required to target the α-subunit to the plasma membrane, but coexpression of both genes is required to convert OSTα to the mature glycosylated protein in enterocyte basolateral membranes and possibly for trafficking through the golgi apparatus (Dawson et al., 2005). OSTαβ proteins are made in a variety of tissues including the small intestine, colon, liver, biliary tract, kidney, and adrenal gland. In polarized epithelial cells, they are localized on the basolateral membrane and function in the export or uptake of bile acids and steroids (Dawson et al., 2010). Homologues of OSTα are found in many eukaryotes including animals (both vertebrates and invertebrates), plants, fungi and slime molds. Homologues of OSTβ are found only in vertebrate animals.

TC Blast reveals that the human OSTα protein shows limited sequence similarity with the YhhT protein of E. coli (P37622) (30% identity in 100 residues with 4 gaps). YhhT is in the PerM family (TC #9.B.22). PerM homologues are found in bacteria and archaea but not eukaryotes. They also have 7 putative TMSs.

The transport reaction catalyzed by OSTα/OSTβ is:

organic anion (out) ⇌ organic anion (in)

References associated with 2.A.82 family:

Ballatori, N., W.V. Christian, S.G. Wheeler, and C.L. Hammond. (2013). The heteromeric organic solute transporter, OSTα-OSTβ/SLC51: A transporter for steroid-derived molecules. Mol Aspects Med 34: 683-692. 23506901
Christian WV., Li N., Hinkle PM. and Ballatori N. (2012). beta-Subunit of the Ostalpha-Ostbeta organic solute transporter is required not only for heterodimerization and trafficking but also for function. J Biol Chem. 287(25):21233-43. 22535958
Christian, W.V. and P.M. Hinkle. (2017). Global functions of extracellular, transmembrane and cytoplasmic domains of organic solute transporter β subunit. Biochem. J. [Epub: Ahead of Print] 28455390
Dawson, P.A., M. Hubbert, J. Haywood, A.L. Craddock, N. Zerangue, W.V. Christian, and N. Ballatori. (2005). The heteromeric organic solute transporter α-β, Ostα-Ostβ, is an ileal basolateral bile acid transporter. J. Biol. Chem. 280: 6960-6968. 15563450
Dawson, P.A., M.L. Hubbert, and A. Rao. (2010). Getting the mOST from OST: Role of organic solute transporter, OSTα-OSTbeta, in bile acid and steroid metabolism. Biochim. Biophys. Acta. 1801: 994-1004. 20538072
Seward, D.J., A.S. Koh, J.L. Boyer, and N. Ballatori. (2003). Functional complementation between a novel mammalian polygenic transport complex and an evolutionarily ancient organic solute transporter, OSTα-OSTβ. J. Biol. Chem. 278: 27473-27482. 12719432
Wang, W., D.J. Seward, L. Li, J.L. Boyer, and N. Ballatori. (2001). Expression cloning of two genes that together mediate organic solute and steroid transport in the liver of a marine vertebrate. Proc. Natl. Acad. Sci. USA 98: 9431-9436. 11470901