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SLC22A7 Membrane Protein Introduction

Introduction of SLC22A7

Solute carrier family 22 member 7 (SLC22A7), also known as organic anion transporter 2 (OAT2), is a protein that in humans is encoded by the gene SLC22A7. It is involved in the transport of various organic substances of both endogenous and exogenous origin in a sodium-independent manner. SLC22A7 proteins comprise 546, 548, and 539 amino acids, depending on splice variants. It has been shown that SLC22A7 is expressed predominantly in the liver, and to a lesser extent in kidney, lung and various other tissues in humans. SLC22A7 can catalyze both uptake and efflux of glutamate.

Basic Information of SLC22A7
Protein Name Solute carrier family 22 member 7
Gene Name SLC22A7
Aliases Novel liver transporter, Organic anion transporter 2, hOAT2
Organism Homo sapiens (Human)
UniProt ID Q9Y694
Transmembrane Times 12
Length (aa) 563
Sequence MGFEELLEQVGGFGPFQLRNVALLALPRVLLPLHFLLPIFLAAVPAHRCALPGAPANFSHQDVWLEAHLPREPDGTLSSCLRFAYPQALPNTTLGEERQSRGELEDEPATVPCSQGWEYDHSEFSSTIATESQWDLVCEQKGLNRAASTFFFAGVLVGAVAFGYLSDRFGRRRLLLVAYVSTLVLGLASAASVSYVMFAITRTLTGSALAGFTIIVMPLELEWLDVEHRTVAGVLSSTFWTGGVMLLALVGYLIRDWRWLLLAVTLPCAPGILSLWWVPESARWLLTQGHVKEAHRYLLHCARLNGRPVCEDSFSQEAVSKVAAGERVVRRPSYLDLFRTPRLRHISLCCVVVWFGVNFSYYGLSLDVSGLGLNVYQTQLLFGAVELPSKLLVYLSVRYAGRRLTQAGTLLGTALAFGTRLLVSSDMKSWSTVLAVMGKAFSEAAFTTAYLFTSELYPTVLRQTGMGLTALVGRLGGSLAPLAALLDGVWLSLPKLTYGGIALLAAGTALLLPETRQAQLPETIQDVERKSAPTSLQEEEMPMKQVQN

Function of SLC22A7 Membrane Protein

SLC22A7 is the second OAT family member to be identified. It can mediate Na+-independent transport of acetylsalicylate, prostaglandin E2 (PGE2), alpha-ketoglutarate, methotrexate, p-aminohippuric acid (PAH), and cephalosporin antibiotics. The substrate specificity of SLC22A7 is much narrower than those of SLC22A6 and SLC22A8. In human kidney, SLC22A7 is localized at the basolateral membrane of the proximal tubules. SLC22A7 has emerged as the primary transporter for many endogenous and exogenous organic anions and cations, including a number of therapeutic drugs. Like SLC22A6 and SLC22A8, SLC22A7 can accommodate a variety of organic anions and indeed has also been shown to transport a number of pharmacologically active agents. SLC22A7 has been increasingly recognized in terms of its role in drug disposition. Well-characterized drug substrates of SLC22A7 include numerous antibiotics, antivirals, antimetabolites, H-2 receptor antagonists, diuretics, nonsteroidal anti-inflammatory drugs, topoisomerase inhibitor, endogenous prostaglandins and hormones.

Effect of TAF, TDF, cobicistat, and ritonavir on transporters in the renal proximal tubule. Fig.1 Effect of TAF, TDF, cobicistat, and ritonavir on transporters in the renal proximal tubule. (Crutchley, 2016)

Application of SLC22A7 Membrane Protein in Literature

  1. Marada V.V., et al. Interaction of human organic anion transporter 2 (OAT2) and sodium taurocholate cotransporting polypeptide (NTCP) with antineoplastic drugs. Pharmacol Res. 2015, 91: 78-87. PubMed ID: 25481222

    Authors in this article found that the accumulation of irinotecan was diminished in the presence of cGMP, the substrate used to functionally characterize OAT2, suggesting specificity of this uptake and the fact that OAT2 mediated uptake of irinotecan.

  2. Shen H., et al. Characterization of Organic Anion Transporter 2 (SLC22A7): A Highly Efficient Transporter for Creatinine and Species-Dependent Renal Tubular Expression. Drug Metab Dispos. 2015, 43(7): 984-993. PubMed ID: 25904762

    This article emphasized the important role of OAT2 in renal secretion and possible reabsorption of creatinine, suggesting a molecular basis for potential species difference in the transporter handling of creatinine.

  3. Lepist E.I., et al. Contribution of the organic anion transporter OAT2 to the renal active tubular secretion of creatinine and mechanism for serum creatinine elevations caused by cobicistat. Kidney Int. 2014, 86(2): 350-357. PubMed ID: 24646860

    This article demonstrated that the elevated serum creatinine in patients taking cobicistat might be likely a result of OCT2 transport, facilitating intracellular accumulation, and MATE1 inhibition.

  4. Pfennig T., et al. Benzoic acid and specific 2-oxo acids activate hepatic efflux of glutamate at OAT2. Biochim Biophys Acta. 2013, 1828(2): 491-498. PubMed ID: 22981274

    This article showed that the increased glutamate efflux at OAT2 could be the main benefit of benzoate treatment in patients with urea cycle defects.

  5. Fork C., et al. OAT2 catalyses efflux of glutamate and uptake of orotic acid. Biochem J. 2011, 436(2): 305-312. PubMed ID: 21446918

    This article revealed that a specific OAT2 inhibitor could alleviate glutamate exo-toxicity in acute brain conditions by lowering plasma glutamate and thus promoting brain-to-blood efflux of glutamate.

SLC22A7 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-SLC22A7 antibody development services.


Creative Biolabs' skillful scientists are glad to leverage our expertise and advanced technologies to help you with the member protein research. If you are interested, please feel free to contact us for more details.

Reference

  1. Crutchley R D, et al. (2016). Evaluating the role of atazanavir/cobicistat and darunavir/cobicistat fixed-dose combinations for the treatment of HIV-1 infection. HIV/AIDS Research and Palliative Care. 8: 47-65.

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