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 |
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.
Fig.1 Effect of TAF, TDF, cobicistat, and ritonavir on transporters in the renal proximal tubule. (Crutchley, 2016)
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.
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.
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.
This article showed that the increased glutamate efflux at OAT2 could be the main benefit of benzoate treatment in patients with urea cycle defects.
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.
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