SLC22A8 Membrane Protein Introduction

Introduction of SLC22A8

Solute carrier family 22 member 8 (SLC22A8), or organic anion transporter 3 (OAT3), is a protein that in humans is encoded by the SLC22A8 gene. It is a multispecific organic anion drug transporter expressed in renal proximal tubule cells, endothelial cells of the brain, and cells of the choroid plexus. SLC22A8 shares several characteristics with SLC22A6 and other related transporters, including the presence of 12 membrane-spanning helices with several consensus extracellular glycosylation and intracellular protein kinase C sites.

Basic Information of SLC22A8
Protein Name	Solute carrier family 22 member 8
Gene Name	SLC22A8
Aliases	Organic anion transporter 3, hOAT3
Organism	Homo sapiens (Human)
UniProt ID	Q8TCC7
Transmembrane Times	12
Length (aa)	542
Sequence	MTFSEILDRVGSMGHFQFLHVAILGLPILNMANHNLLQIFTAATPVHHCRPPHNASTGPWVLPMGPNGKPERCLRFVHPPNASLPNDTQRAMEPCLDGWVYNSTKDSIVTEWDLVCNSNKLKEMAQSIFMAGILIGGLVLGDLSDRFGRRPILTCSYLLLAASGSGAAFSPTFPIYMVFRFLCGFGISGITLSTVILNVEWVPTRMRAIMSTALGYCYTFGQFILPGLAYAIPQWRWLQLTVSIPFFVFFLSSWWTPESIRWLVLSGKSSKALKILRRVAVFNGKKEEGERLSLEELKLNLQKEISLAKAKYTASDLFRIPMLRRMTFCLSLAWFATGFAYYSLAMGVEEFGVNLYILQIIFGGVDVPAKFITILSLSYLGRHTTQAAALLLAGGAILALTFVPLDLQTVRTVLAVFGKGCLSSSFSCLFLYTSELYPTVIRQTGMGVSNLWTRVGSMVSPLVKITGEVQPFIPNIIYGITALLGGSAALFLPETLNQPLPETIEDLENWSLRAKKPKQEPEVEKASQRIPLQPHGPGLGSS

Function of SLC22A8 Membrane Protein

SLC22A8 is a predominant component of the renal organic anion transport apparatus believed to account for the transport of one-third to one-half of the most commonly prescribed drugs (i.e., penicillins, nonsteroidal anti-inflammatory drugs, cephalosporins, angiotensin-converting enzyme inhibitors, diuretics, smallpox and HIV antivirals, methotrexate, and statins) as well as many toxins. SLC22A8 is expressed specifically in renal proximal tubule cells, where it facilitates the uptake of a broad array of endogenous and exogenous anions from the blood, across the tubular basolateral membrane, into the tubular cells. The cellular uptake of organic anions is coupled, via anionic exchange, to the efflux of dicarboxylates down their concentration gradient, a gradient maintained indirectly through the action of the sodium-potassium pump. SLC22A8, in particular, plays a crucial role in the elimination of a variety of substrates, especially those anionic and hydrophilic compounds that rely heavily on renal secretion.

Fig.1 Transcellular movement of organic cations (OCs) and organic anions (OAs) in kidney proximal tubule epithelial cells. (Nigam, 2015)

Application of SLC22A8 Membrane Protein in Literature

Davenport J.M. Effect of uptake transporters OAT3 and OATP1B1 and efflux transporter MRP2 on the pharmacokinetics of eluxadoline. J Clin Pharmacol. 2015, 55(5): 534-542. PubMed ID: 25491493

This article reveals that OATP1B1-mediated hepatic uptake of eluxadoline plays a major role in its absorption and disposition, whereas OAT3-mediated basolateral uptake in the proximal renal tubules and MRP2-mediated canalicular and renal tubular apical efflux play only minor roles in its overall disposition.
Lungkaphin A., et al. Impaired insulin signaling affects renal organic anion transporter 3 (Oat3) function in streptozotocin-induced diabetic rats. PLoS One. 2014, 9(5): e96236. PubMed ID: 24801871

This article demonstrates that the decreases in both function and expression of renal Oat3 in diabetes are associated with PI3K / PKC / Akt / PKB signaling pathway.
Imamura Y., et al. 6β-Hydroxycortisol is an endogenous probe for evaluation of drug-drug interactions involving a multispecific renal organic anion transporter, OAT3/SLC22A8, in healthy subjects. Drug Metab Dispos. 2014, 42(4): 685-694. PubMed ID: 24487120

This article verifies that OAT3 plays a significant role in the urinary excretion of 6β-OHF.
Wu W., et al. Multispecific drug transporter Slc22a8 (Oat3) regulates multiple metabolic and signaling pathways. Drug Metab Dispos. 2013, 41(10): 1825-1834. PubMed ID: 23920220

This article verifies that OAT3 is essential for the handling of dietary flavonoids and antioxidants.
Yee S.W., et al. Reduced renal clearance of cefotaxime in Asians with a low-frequency polymorphism of OAT3 (SLC22A8). J Pharm Sci. 2013, 102(9): 3451-3457. PubMed ID: 23649425

This article demonstrates that a low-frequency reduced-function polymorphism of OAT3 is associated with reduced cefotaxime CLR and CL(sec).

SLC22A8 Preparation Options

To obtain the soluble and functional target protein, the versatile Magic™ membrane protein production platform in Creative Biolabs enables many flexible options, from which you can always find a better match for your particular project. Aided by our versatile Magic™ anti-membrane protein antibody discovery platform, we also provide customized anti-SLC22A8 antibody development services.

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Reference

Nigam S K, et al. (2015). Handling of Drugs, Metabolites, and Uremic Toxins by Kidney Proximal Tubule Drug Transporters. Clin J Am Soc Nephrol. 10: 2039-2049.

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