Mammalian kidney and liver are critical in maintaining physiological ionic environment. Kidney specializes in removing toxins, drugs, and other organic anions from the blood by a process called "renal secretion". Besides kidney, anionic substrates are also transported in other organs, e.g., choroid plexus, eye, airway, and placenta. Several multispecific OATs (OAT1-3, OAT-K1 and OATK2) and OATPs (organic anion transporting polypeptides; oatp1-3), have been cloned and characterized from various tissues. OATPs family of proteins are very similar in sequence and secondary protein structure (up to 12 transmembrane domains with cytoplasmic N and C-terminus). Rat Kidney PAH transporter, termed OAT1 or ROAT1, encodes a protein of 551 aa. Human OAT1 (hOAT1) is 563 aa and its alternatively spliced isoform hOAT2 is 550 aa (missing 13 aa from 523-533 aa). OAT1 has wide substrate selectivity, covering endogenous substrates such as cyclic nucleotides, prostaglandin and uric acid, and a variety of drugs (e.g., antibiotics, non-steroidal anti-inflammatory drugs, diuretics, anti-neoplastic drug, and a uricosuric drug). OAT1 has been localized on the basolateral membrane of the proximal tubule in the kidney. Weak expression was also detected in brain. OAT1 has ~95 identity with mouse NKT, an ortholog of rat OAT1.
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