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)



This family belongs to the Transporter-Opsin-G protein-coupled receptor (TOG) Superfamily.

 

References:

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.

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.

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]

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.

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.

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.

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.

Examples:

TC#NameOrganismal TypeExample
2.A.82.1.1The organic solute transporter, OSTα/OSTβ (transports taurocholate, estrone sulfate, digoxin, and prostaglandin E2)AnimalsOSTα/OSTβ of the little skate, Raja erinacea
OSTα (AAK14805)
OSTβ (AAK14806)
 
2.A.82.1.2

The organic solute transporter OSTα/OSTβ or SLC51A/SLC51B (transports the same anions as the 2.A.82.1.1 system) (The ileal enterocyte basolateral bile acid transporter; uses facilitated diffusion vian an anion:anion antiport mechanism with sulfate or bicarbonate as the counter anion) (Dawson et al., 2005).  Transports steroid-derived molecules as well as glycine and taurine conjugated bile acids (Ballatori et al. 2013).  Heterodimerization increases stability, facilitates post-translational modification and is required for delivery to the plasma membrane.  This system is essential for intestinal bile acid and dietary lipid absorption (Ballatori et al. 2013).

Animals

OSTα/OSTβ of Homo sapiens
OSTα (AAP23993)
OSTβ (AAP23992)

 
2.A.82.1.3Transmembrane protein 184B (Putative MAPK-activating protein FM08)AnimalsTMEM184B of Homo sapiens
 
2.A.82.1.4Organic solute transporter alpha-like protein C18A3.4WormC18A3.4 of Caenorhabditis elegans
 
2.A.82.1.5

Ostα subunit homologue

Stramenophiles

Ostα of Thalassiosira oceanica

 
2.A.82.1.6

Uncharacterized protein of 335 aas and 7 TMSs.

UP of Oreochromis niloticus (Nile tilapia) (Tilapia nilotica)

 
2.A.82.1.7

Uncharacteerized protein of 356 aas and 8 TMSs.

UP of Entamoeba histolytica