SLCO2B1 Membrane Protein Introduction

Introduction of SLCO2B1

SLCO2B1, solute carrier organic anion transporter family member 2B1, owns 12 transmembrane domains and is encoded by the SLCO2B1 gene in humans. It belongs to the organic anion-transporting polypeptide family of membrane proteins. This gene is conserved in chimpanzee, cow, rat, chicken, dog, mouse, Rhesus monkey, C.elegans, zebrafish, and frog. It has been reported that 192 organisms have orthologs with this gene. It’s broadly expressed in lung, liver, and 23 other tissues, and is involved in the uptake of sulfated steroids in placent and sodium-independent transport of organic anions.

Function of SLCO2B1 Membrane Protein

SLCO2B1 is also known as SLC21A9 which belongs to the 12-membrane-spanning superfamily of solute carriers. SLCO2B1 is an organic anion transporter and mediates uptake of sulfated steroids in placent and sodium-independent transport of organic anions, such as the prostaglandins PGD2, PGE1, PGE2, taurocholate, thromboxane B2, leukotriene C4, and iloprost. In addition, high expression of SLCO2B1 is reported to be involved in the resistance to androgen deprivation therapy in patients with prostate cancer. Also, SLCO2B1 expression level can be a potential prognostic biomarker for prostate cancer. The gene variants are associated with pathologic responses in prostate cancer, suggesting their potential role as biomarkers for abiraterone treatment. Moreover, SLCO2B1 variants are associated with prostate cancer progression and overall survival in patients treated with androgen deprivation. SLCO2B1 suppression can prevent gastrointestinal toxicity treated with anticancer drug SN-38. SLCO2B1 also plays a functional role in modulating the pathophysiological actions of prostaglandins.

Fig.1 Topology of SLCO2B1. (Bian, 2016)

Application of SLCO2B1 Membrane Protein in Literature

1. Terakawa T., et al. High expression of SLCO2B1 is associated with prostate cancer recurrence after radical prostatectomy. Oncotarget. 2018, 9(18): 14207-14218. PubMed ID: 29581838
   
   

   This article demonstrates that the SLCO2B1 expression level can be a prognostic biomarker for prostate cancer.

2. Mostaghel E.A., et al. Association of Tissue Abiraterone Levels and SLCO Genotype with Intraprostatic Steroids and Pathologic Response in Men with High-Risk Localized Prostate Cancer. Clin Cancer Res. 2017, 23(16): 4592-4601. PubMed ID: 28389510
   
   

   This article indicates that SLCO gene variants are associated with pathologic responses in prostate cancer, and these variants can be potential biomarkers for abiraterone treatment.

3. Wang X., et al. Association of SLCO2B1 Genotypes With Time to Progression and Overall Survival in Patients Receiving Androgen-Deprivation Therapy for Prostate Cancer. J Clin Oncol. 2016, 34(4): 352-9. PubMed ID: 26668348
   
   

   This article shows the SLCO2B1 variants are associated with prostate cancer progression and overall survival in patients treated with androgen deprivation.

4. Fujita D., et al. Organic Anion Transporting Polypeptide (OATP)2B1 Contributes to Gastrointestinal Toxicity of Anticancer Drug SN-38, Active Metabolite of Irinotecan Hydrochloride. Drug Metab Dispos. 2016, 44(1): 1-7. PubMed ID: 26526067
   
   

   This article shows that SLCO2B1 suppression can prevent gastrointestinal toxicity treated with anticancer drug SN-38.

5. Furihata T., et al. Differential inhibition features of direct-acting anti-hepatitis C virus agents against human organic anion transporting polypeptide 2B1. Int J Antimicrob Agents. 2015, 46(4): 381-8. PubMed ID: 26163159
   
   

   This article shows that simeprevir and asunaprevir can inhibit the function of SLCO2B1 and these inhibitions may result in clinically relevant drug-drug interactions when used with SLCO2B1 substrates.

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Reference

1. Bian J, et al. (2016). Tryptophan Residue Located at the Middle of Putative Transmembrane Domain 11 Is Critical for the Function of Organic Anion Transporting Polypeptide 2B1. Mol Pharm. 13(10): 3553-3563.

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