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SLC47A1 Membrane Protein Introduction

Introduction of SLC47A1

SLC47A1, also known as MATE1, is a member of the MATE (multidrug and toxic compound extrusion) family of transporters. It is encoded by SLC47A1 gene and has 586 acid amino acid residues. SLC47A1 is expressed in spleen, lymph nodes, thymus, PBL, bone marrow, and fetal liver. Studies have revealed that MATE1 is an organic cation/proton exchanger involved in the transport of various cationic drugs.

Basic Information of SLC47A1
Protein Name Multidrug and toxin extrusion protein 1
Gene Name SLC47A1
Aliases MATE1
Organism Homo sapiens (Human)
UniProt ID Q96FL8
Transmembrane Times 13
Length (aa) 586
Sequence MEAPEEPAPVRGGPEATLEVRGSRCLRLSAFREELRALLVLAGPAFLVQLMVFLISFISSVFCGHLGKLELDAVTLAIAVINVTGVSVGFGLSSACDTLISQTYGSQNLKHVGVILQRSALVLLLCCFPCWALFLNTQHILLLFRQDPDVSRLTQTYVTIFIPALPATFLYMLQVKYLLNQGIVLPQIVTGVAANLVNALANYLFLHQLHLGVIGSALANLISQYTLALLLFLYILGKKLHQATWGGWSLECLQDWASFLRLAIPSMLMLCMEWWAYEVGSFLSGILGMVELGAQSIVYELAIIVYMVPAGFSVAASVRVGNALGAGDMEQARKSSTVSLLITVLFAVAFSVLLLSCKDHVGYIFTTDRDIINLVAQVVPIYAVSHLFEALACTSGGVLRGSGNQKVGAIVNTIGYYVVGLPIGIALMFATTLGVMGLWSGIIICTVFQAVCFLGFIIQLNWKKACQQAQVHANLKVNNVPRSGNSALPQDPLHPGCPENLEGILTNDVGKTGEPQSDQQMRQEEPLPEHPQDGAKLSRKQLVLRRGLLLLGVFLILLAGVRWCDHSSLQPRTLGLQAILLCQPPE

Function of SLC47A1 Membrane Protein

MATE1/SLC47A1 is an organic cation/proton exchanger located on the brush-border of the renal epithelium and the canalicular membrane of hepatocytes. It transports cationic drugs such as metformin, paraquat, or the anticancer drug, oxaliplatin from proximal tubule cells to urine. SLC47A1 has shown an important role in metformin disposition and response through mediating the transport and excretion of metformin into the urine and bile. The nonsynonymous SNPs in SLC47A1 may decrease the transport rate for metformin. While a polymorphism in the basal promoter region 130G>A enhances the promoter activity, resulting in faster metformin elimination. Besides, SLC47A1 variants also involve the regulation of response to metformin in patients with type 2 diabetes. Similarly, SLC47A1 also regulates oxaliplatin disposition. G64D and V480M variants display a decreased transport rate, while C497S variant increases the transport activity. Additionally, inhibition of SLC47A1 activity leads to the accumulation of cisplatin in kidney proximal tubular epithelial cells and this potentiates the nephrotoxicity of cisplatin.

Pathway of renal creatinine transport <em>via</em> efflux transporters SLC22A2 and SLC47A1 over the proximal tubular cell membranes from blood to urine. Fig.1 Pathway of renal creatinine transport via efflux transporters SLC22A2 and SLC47A1 over the proximal tubular cell membranes from blood to urine. (Hentig, 2016)

Application of SLC47A1 Membrane Protein in Literature

  1. Harrach S., et al. MATE1 regulates cellular uptake and sensitivity to imatinib in CML patients. Blood Cancer Journal. 2016, 6(9):e470. PubMed ID: 27635733

    The article finds that MATE1 can transport imatinib into target cells, suggesting MATE1 may involve the regulation of intracellular efficacy of imatinib.

  2. Gessner A., et al. Contribution of multidrug and toxin extrusion protein 1 (MATE1) to renal secretion of trimethylamine-N-oxide (TMAO). Sci Rep. 2018, 8(1):6659. PubMed ID: 29704007

    The experimental data indicate that MATE1 is responsible for the renal elimination of TMAO.

  3. Berg T., et al. Expression of MATE1, P-gp, OCTN1 and OCTN2, in epithelial and immune cells in the lung of COPD and healthy individuals. Respir Res. 2018, 19(1):68. PubMed ID: 29678179

    In the research, authors observe the expression of MATE1, P-gp, OCTN1 and OCTN2 in pulmonary lung epithelium, in alveolar macrophages and in other inflammatory cells.

  4. Li Q., et al. Indinavir alters the pharmacokinetics of lamivudine partially via inhibition of multidrug and toxin extrusion protein 1 (MATE1). Pharm Res. 2018, 35(1):14. PubMed ID: 29302757

    The in vivo study implicates that Indinavir could cause drug-drug interaction with lamivudine via suppression of MATE1 and additional mechanism.

  5. Cho S.K. and Chung J.Y. The MATE1 rs2289669 polymorphism affects the renal clearance of metformin following ranitidine treatment. Int J Clin Pharmacol Ther. 2016, 54(4):253-262. PubMed ID: 26784938

    Results in the study reveal that MATE1 rs2289669 may be associated with the renal clearance of metformin following ranitidine treatment.

SLC47A1 Preparation Options

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Reference

  1. Hentig N V. (2016). Clinical use of cobicistat as a pharmacoenhancer of human immunodeficiency virus therapy. Hiv/aids. 8(1): 1-16.

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