Organic anion transporter

Thank you for visiting nature. You are using a organic anion transporter version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser or turn off compatibility mode in Internet Explorer. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Thank you for visiting nature. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser or turn off compatibility mode in Internet Explorer. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. Furthermore, OAT1 is also involved in key physiological events such as the remote inter-organ communication. Despite its significance, the knowledge about h OAT1 structure and the transport mechanism at the atomic level remains fragmented owing to the lack of resolved structures.

Organic anion transporter

Federal government websites often end in. The site is secure. The organic anion transporter OAT subfamily, which constitutes roughly half of the SLC22 solute carrier 22 transporter family, has received a great deal of attention because of its role in handling of common drugs antibiotics, antivirals, diuretics, nonsteroidal anti-inflammatory drugs , toxins mercury, aristolochic acid , and nutrients vitamins, flavonoids. Oats are expressed in many tissues, including kidney, liver, choroid plexus, olfactory mucosa, brain, retina, and placenta. Recent metabolomics and microarray data from Oat1 [ Slc22a6 , originally identified as NKT novel kidney transporter ] and Oat3 Slc22a8 knockouts, as well as systems biology studies, indicate that this pathway plays a central role in the metabolism and handling of gut microbiome metabolites as well as putative uremic toxins of kidney disease. Oats may also play a major role in interorganismal communication via movement of small molecules across the intestine, placental barrier, into breast milk, and volatile odorants into the urine. The role of various Oat isoforms in systems physiology appears quite complex, and their ramifications are discussed in the context of remote sensing and signaling. Modeling, mutagenesis, and other studies are consistent with the view that these transmembrane proteins are composed of about — amino acids comprising 12 transmembrane domains 69 , , , Figure 1. A: illustration of the predicted topology of organic anion transporters. Although the initial focus in this field was on the kidney, the OATs have been localized to almost all barrier epithelia of the body, as well as endothelium and other cells, and have demonstrated roles in the regulated transcellular movement of numerous small organic anionic molecules across these epithelial barriers and between body fluid compartments i. While prototypical members of this transporter family are capable of the bidirectional movement of substrates, most of the Oats are generally viewed as facilitating the movement of organic anions into the epithelial cells influx transporters. Some interesting aspects of this family of transport proteins discussed in more detail later include the following: range of substrates drugs, toxins, metabolites, regulatory molecules , substrate overlap, embryonic expression , , , postnatal maturation, evolutionary conservation 71 , , , transcriptional regulation, genomic clustering of family members 70 , , , as well as the association of single nucleotide polymorphisms SNPs with metabolic disease such as disorders of uric acid and alterations in drug handling 12 , 66 , 71 , 83 , , , , Prior to the cloning of NKT Novel Kidney Transporter, now called organic anion transporter 1 or OAT1, and also designated as SLC22A6 , the Oat pathway had been the subject of much investigation, particularly from the viewpoint of kidney physiology, over many decades.

Mol Pharmacol 67 : —, They mediate the transport of a variety of endogenous and exogenous substrates through the cellular membrane[ 3 ]. Annu Rev Physiol 51 : —,

Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human Hs , mouse Mm and rat Rn. Show » « Hide. Organic anion transporters OATs are non-selective transporters prominent in the kidney, placenta and blood-brain barrier. Handb Exp Pharmacol , :

Federal government websites often end in. The site is secure. The organic anion transporter OAT subfamily, which constitutes roughly half of the SLC22 solute carrier 22 transporter family, has received a great deal of attention because of its role in handling of common drugs antibiotics, antivirals, diuretics, nonsteroidal anti-inflammatory drugs , toxins mercury, aristolochic acid , and nutrients vitamins, flavonoids. Oats are expressed in many tissues, including kidney, liver, choroid plexus, olfactory mucosa, brain, retina, and placenta. Recent metabolomics and microarray data from Oat1 [ Slc22a6 , originally identified as NKT novel kidney transporter ] and Oat3 Slc22a8 knockouts, as well as systems biology studies, indicate that this pathway plays a central role in the metabolism and handling of gut microbiome metabolites as well as putative uremic toxins of kidney disease. Oats may also play a major role in interorganismal communication via movement of small molecules across the intestine, placental barrier, into breast milk, and volatile odorants into the urine.

Organic anion transporter

Federal government websites often end in. The site is secure. They are expressed in many tissues, such as the liver and kidney, and mediate the absorption and excretion of many endogenous and exogenous substances, including various drugs. Most are composed of 12 transmembrane polypeptide chains with the C-terminus and the N-terminus located in the cell cytoplasm. OATs and OATPs are abundantly expressed in the liver, where they mainly promote the uptake of various endogenous substrates such as bile acids and various exogenous drugs such as antifibrotic and anticancer drugs. However, differences in the locations of glycosylation sites, phosphorylation sites, and amino acids in the OAT and OATP structures lead to different substrates being transported to the liver, which ultimately results in their different roles in the liver.

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A key question in deciphering the mechanism of secondary active transporters is how ligand binding drives the conformational changes in the protein Download as PDF Printable version. The communication within motifs is demonstrated by the strength of hydrogen bonds. From the cover: identification of natural products as inhibitors of human organic anion transporters OAT1 and OAT3 and their protective effect on mercury-induced toxicity. This high percentage of sequence identity suggests that these four genes are likely to have been generated from recent sequential gene duplication events Figure 9 Furthermore, gene set enrichment analysis showed that OAT2 expression was significantly associated with mitochondrial oxidoreductase activity and fatty acid metabolism. Some of these side chains overlap with site 1, such as Phe and Tyr, alanine substitutions of which are transport deficient in our assay Fig. Olfactory mucosa-expressed organic anion transporter, Oat6, manifests high affinity interactions with odorant organic anions. Annu Rev Physiol 51 : —, Similar to Oat1 23 , expression of Oat6 in rat olfactory epithelium can be induced by in vivo exposure to dexamethasone Parker View author publications. The range of Oat1 drug, toxin, and metabolite substrates is now well established by in vitro and in vivo studies and has been thoroughly described in several excellent recent reviews on the topic 34 , ,

Members of the Organo Anion Transporter OAT Family organic-anion-transporting polypeptides , OATP are membrane transport proteins or 'transporters' that mediate the transport of mainly organic anions across the cell membrane. Therefore, OATPs are present in the lipid bilayer of the cell membrane, acting as the cell's gatekeepers.

Using the lens of the Remote Sensing and Signaling Hypothesis, we have tried to provide a systems biology perspective on organic anion transporters without sacrificing the specifics. Protein Sci. About this article. Figure 1. Drug Metab Dispos 35 : —, Introduction Major facilitator superfamily MFS proteins belong to the solute carrier SLC superfamily, one of the most important classes of membrane transporters. An untargeted metabolomics analysis strategy used to identify endogenous substrates of the Oats is depicted , Liver cancer is one of the most common causes of cancer death worldwide. SLC22A9 Hs. Histol Histopathol 25 : —, Volatile odorants excreted into the urine can potentially be transported or sensed in the olfactory mucosa of another animal. The absence of a robust h OAT1 OF model precludes the thorough atomistic rationalization of substrate binding events as well as the investigation of lipid-protein interactions, which have been shown to be of major importance for several MFS transporters and other membrane proteins by either experimental or computational techniques 30 , 31 , 32 ,