SLC16A5 Membrane Protein Introduction

Introduction of SLC16A5

Human monocarboxylate transporter 6 (SLC16A5) is a member of the MCT family, which comprises 14 members and was first cloned from a placenta cDNA library. SLC16A5 shares 38% identity with MCT4 at the amino acid level. Northern blot analysis revealed that SLC16A5 mRNA is highly expressed in the kidney and placenta. SLC16A5 transports bumetanide, nateglinide, but not L-lactic acid or L-tryptophan, which are typical substrates for MCT1–MCT4 and T-type amino acid transporter 1, respectively.

Function of SLC16A5 Membrane Protein

SLC16A5 is involved in the disposition of various drugs, including bumetanide and nateglinide. The uptake of bumetanide via SLC16A5 has been shown to be pH and membrane potential sensitive, but not proton gradient dependent, and the substrate specificity of SLC16A5 is different from those of the other MCTs. Under the condition of membrane depolarization, the presence of bicarbonate or diminution of the inward proton gradient did not affect the uptake of bumetanide via SLC16A5, suggesting that SLC16A5 is neither a proton-coupled transporter nor an OH or HCO₃ exchanger. The transport of nateglinide via SLC16A5 was increased in neutral pH, which suggests that SLC16A5 may contribute to absorption in the lower intestine. SLC16A5 is inhibited by azosemide and torasemide, which have an anionic sulfonamide moiety but not a carboxylate moiety, suggesting that a carboxylate group may not be essential for affinity to SLC16A5. Bumetanide and nateglinide should be good tools for investigating the functional properties of SLC16A5 and the differences of substrate recognition sites among MCT isoforms.

Fig.1 Proposed structure of SLC16A5 membrane protein. (Jones, 2017)

Application of SLC16A5 Membrane Protein in Literature

1. Jones R.S., et al. Quercetin, Morin, Luteolin, and Phloretin Are Dietary Flavonoid Inhibitors of Monocarboxylate Transporter 6. Mol. Pharm. 2017, 14(9):2930-2936. PubMed ID: 28513167
   
   

   The results of this article suggest that dietary aglycon flavonoids may significantly alter the pharmacokinetics and pharmacodynamics of bumetanide and other SLC16A5 specific substrates, and may represent potential substrates for SLC16A5.

2. Murakami Y., et al. (2005) Functional characterization of human monocarboxylate transporter 6 (SLC16A5). Drug Metab. Disposition. 2005, 33(12):1845. PubMed ID: 16174808
   
   

   Authors in this article identify bumetanide as an SLC16A5 ligand for the first time. Meanwhile, SLC16A5 transports bumetanide in a pH- and membrane potential-sensitive but not proton gradient-dependent manner, and the substrate specificity of SLC16A5 is different from those of the other MCTs.

3. Drögemöller B.I., et al. Association Between SLC16A5 Genetic Variation and Cisplatin-Induced Ototoxic Effects in Adult Patients With Testicular Cancer. JAMA Oncology. 2017, 3(11):1558-1562. PubMed ID: 28448657
   
   

   This article reports that a protein-coding variation of SLC16A5 may play a role in the cisplatin-induced ototoxic effects and provides insight into the molecular mechanisms of this adverse drug reaction in adult patients with germ cell testicular cancer.

4. Kohyama N., et al. Characterization of Monocarboxylate Transporter 6: Expression in Human Intestine and Transport of the Antidiabetic Drug Nateglinide. Drug Metab. Disposition. 2013, 41(11):1883. PubMed ID: 23935065
   
   

   The results of this article suggest that SLC16A5 may be involved in the intestinal absorption of nateglinide, although other transporters are also likely involved.

5. Sugito K., et al. Identification of aberrant methylation regions in neuroblastoma by screening of tissue-specific differentially methylated regions. Pediatric Blood & Cancer. 2012, 60(3):383-389.
   
   

   The authors in this article apply the MassARRAY EpiTYPER system to demonstrate that the methylation level of SLC16A5 is low compared to the control adrenal medullas. The SLC16A5 methylation level is associated with age at diagnosis, disease stage, and Shimada classification but not with MYCN amplification.

SLC16A5 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-SLC16A5 antibody development services.

• Magic™ Membrane Protein Production Platform
• Magic™ Anti-Membrane Protein Antibody Discovery Platform

Creative Biolabs was founded by scientists who are dedicated to being a research institute as well as a leading custom service provider in the field of membrane protein, we have won a good reputation among our worldwide customers for successfully accomplishing numerous challenging projects including generation of many functional membrane proteins. Please feel free to contact us for more information.

Reference

1. Jones RS., et al. (2017) Quercetin, Morin, Luteolin, and Phloretin Are Dietary Flavonoid Inhibitors of Monocarboxylate Transporter 6. Mol. Pharm. 14(9):2930-2936.

All listed services and products are For Research Use Only. Do Not use in any diagnostic or therapeutic applications.