2.A.1.19.4
The polyspecific organic anion, cation and neutral molecule transporter, Oat1 (Slc22a6) (transports neutral compounds such as cardiac glycosides [i.e., ouabain] and steroids [i.e., aldosterone; cortisol; dexamethasone]; cationic compounds such as N-propylajmalinium, and anionic compounds such as p-aminohippurate, dicarboxylates, cyclic nucleotides, prostaglandins, urate, β-lactam antibiotics, nonsteroidal anti-inflammatory drugs, diuretics, bile salts and steroid conjugates [i.e., estrone-3-sulfate and estradiol-17-glucuronide]) transporter (H⁺ symporter or uniporter) Probably catalyzes organic anion (uptake):dicarboxylate (efflux) antiport in the basolateral membrane of kidney proximal tubules) (Eraly et al., 2003a,b). A 3-dimensional model of OAT1 has led to the identification of residues involved in differential transport of substrates such as p-aminohippurate and cidofovir (Perry et al., 2006). Oat1 transports many antiviral agents (Truong et al., 2008).  The human orthologue (Q4U2R8; 563aas) has been shown to be a multispecific organic anion transporter on the basolateral membrane of the proximal tubule in human kidney (Hosoyamada et al. 1999). A substrate binding hinge domain is required for transport-related structural changes (Egenberger et al., 2012). Transports environmental toxins and clinically important drugs including anti-HIV therapeutics, anti-tumor drugs, antibiotics, anti-hypertensives, and anti-inflammatories (Duan et al., 2011). hOAT1 has two GXXXG motifs in TMSs 2 and 5 which play critical roles in stability (Duan et al., 2011).  Both OAT1 and OAT3 of humans are inhibited by caffeic acid (Ki ~ 17 μM) (Uwai et al. 2011).