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View Proteins belonging to: The Organo Anion Transporter (OAT) Family

2.A.60 The Organo Anion Transporter (OAT) Family

Proteins of the OAT family (solute carrier family 21 (previously called SLC21A; more recently designated SLCO by the HUGO Gene Nomenclature Committee (B. Hagenbuch, personal communication))) catalyze the Na+-independent facilitated transport of organic anions and cations such as bromosulfobromophthalein, prostaglandins, conjugated and unconjugated bile acids (taurocholate and cholate, respectively), steroid conjugates, thyroid hormones, anionic oligopeptides, drugs, toxins and other xenobiotics. The various paralogues in a mammal have differing but overlapping substrate specificities and tissue distributions as summarized by Hagenbuch and Meier (2003). These authors also provide a phylogenetic tree of the mammalian members of the family, showing that they fall into five recognizable subfamilies, four of which exhibit deep branching sub-subfamilies. However, all sequences within a subfamily are >60% identical while those between subfamilies are >40% identical (Hagenbuch and Meier, 2003). Therefore, these mammalian proteins are all included within a single subfamily of the TC system (TC #2.A.60.1). The detailed substrates transported and their affinities are presented by Hagenbuch and Meier (2003). As also shown by Hagenbuch and Meier, all but one (OatP4a1) of the mammalian homologues cluster together, separately from all other animal (insect and worm) homologues. OAT family homologues have been found in other animals but not outside of the animal kingdom.

These transporters have been characterized in mammals, but homologues are present in D. melanogaster, A. gambiae, and C. elegans. The mammalian OAT family proteins exhibit a high degree of tissue specificity. Mammalian homologues consist of 640-722 amino acyl residues and possess 12 putative α-helical transmembrane spanners. They may catalyze electrogenic anion uniport or more frequently, anion exchange. Conformational changes of the multispecific organic anion transporter 1 (OAT1/SLC22A6) has suggested a molecular mechanism for initial stages of drug and metabolite transport (Tsigelny et al., 2011). The OAT family is a distant family within the MFS (TC #2.A.1). Regulation of expression and function of OATps has been described (Svoboda et al., 2011).

The generalized transport reaction catalyzed by members of the OAT family is:

Anion (in) ⇌ Anion (out)

or

Anion1 (in) + Anion2 (out) ⇌ Anion1 (out) + Anion2 (in).

This family belongs to the: MFS Superfamily.
View Proteins belonging to: The Organo Anion Transporter (OAT) Family

References associated with 2.A.60 family:

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Mikkaichi, T., T. Suzuki, T. Onogawa, M. Tanemoto, H. Mizutamari, M. Okada, T. Chaki, S. Masuda, T. Tokui, N. Eto, M. Abe, F. Satoh, M. Unno, T. Hishinuma, K. Inui, S. Ito, J. Goto, and T. Abe. (2004). Isolation and characterization of a digoxin transporter and its rat homologue expressed in the kidney. Proc. Natl. Acad. Sci. USA 101: 3569-3574. 14993604
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Tirona, R.G., B.F. Leake, G. Merino, and R.B. Kim. (2001). Polymorphisms in OATP-C. Identification of multiple allelic variants associated with altered transport activity among European- and African-Americans. J. Biol. Chem. 276: 35669-35675. 11477075
Tsigelny, I.F., D. Kovalskyy, V.L. Kouznetsova, O. Balinskyi, Y. Sharikov, V. Bhatnagar, and S.K. Nigam. (2011). Conformational changes of the multispecific transporter organic anion transporter 1 (OAT1/SLC22A6) suggests a molecular mechanism for initial stages of drug and metabolite transport. Cell Biochem Biophys 61: 251-259. 21499753
van Montfoort, J.E., T.E. Schmid, I.-D. Adler, P.J. Meier, and B. Hagenbuch. (2002). Functional characterization of the mouse organic-anion-transporting polypeptide 2. Biochim. Biophys. Acta 1564: 183-188. 12101011
Wang, P., R.B. Kim, J.R. Chowdhury, and A.W. Wolkoff. (2003). The human organic anion transport protein SLC21A6 is not sufficient for bilirubin transport. J. Biol. Chem. 278: 20695-20699. 12670950
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