SLCO1B1 Membrane Protein Introduction

Introduction of SLCO1B1

SLCO1B1, solute carrier organic anion transporter family member 1B1, is also known as solute carrier family 21 member 6 (SLC21A6). It is encoded by the SLCO1B1 gene in humans and belongs to SLC21A family of solute carriers. This gene is conserved in chimpanzee, chicken, rhesus monkey and frog. 17 organisms have been reported to contain orthologs with this gene. SLCO1B1 is restricted expressed in the liver and is involved in sodium-independent uptake of organic anions.

Basic Information of SLCO1B1
Protein Name	Solute carrier organic anion transporter family member 1B1
Gene Name	SLCO1B1
Aliases	LST1, OATP1B1, OATP2, OATPC, SLC21A6
Organism	Homo sapiens (Human)
UniProt ID	Q9Y6L6
Transmembrane Times	12
Length (aa)	691
Sequence	MDQNQHLNKTAEAQPSENKKTRYCNGLKMFLAALSLSFIAKTLGAIIMKSSIIHIERRFEISSSLVGFIDGSFEIGNLLVIVFVSYFGSKLHRPKLIGIGCFIMGIGGVLTALPHFFMGYYRYSKETNINSSENSTSTLSTCLINQILSLNRASPEIVGKGCLKESGSYMWIYVFMGNMLRGIGETPIVPLGLSYIDDFAKEGHSSLYLGILNAIAMIGPIIGFTLGSLFSKMYVDIGYVDLSTIRITPTDSRWVGAWWLNFLVSGLFSIISSIPFFFLPQTPNKPQKERKASLSLHVLETNDEKDQTANLTNQGKNITKNVTGFFQSFKSILTNPLYVMFVLLTLLQVSSYIGAFTYVFKYVEQQYGQPSSKANILLGVITIPIFASGMFLGGYIIKKFKLNTVGIAKFSCFTAVMSLSFYLLYFFILCENKSVAGLTMTYDGNNPVTSHRDVPLSYCNSDCNCDESQWEPVCGNNGITYISPCLAGCKSSSGNKKPIVFYNCSCLEVTGLQNRNYSAHLGECPRDDACTRKFYFFVAIQVLNLFFSALGGTSHVMLIVKIVQPELKSLALGFHSMVIRALGGILAPIYFGALIDTTCIKWSTNNCGTRGSCRTYNSTSFSRVYLGLSSMLRVSSLVLYIILIYAMKKKYQEKDINASENGSVMDEANLESLNKNKHFVPSAGADSETHC

Function of SLCO1B1 Membrane Protein

SLCO1B1 gene encodes a sodium-independent transporter - SLCO1B1, which mediates cellular uptake of organic anions in the liver specifically. This transmembrane transporter is involved in the sodium-independent uptake of numerous endogenous compounds, such as leukotriene C4, 17-beta-glucuronosyl estradiol and bilirubin. In addition, SLCO1B1 is also involved in the removal of drug compounds including bromosulfophthalein, statins, and rifampin from the blood into the hepatocytes. If the gene encoding this protein has polymorphisms, the transporter function will be impaired. SLCO1B1 deficiency can affect methotrexate toxicity possibly through endogenous metabolites mediated communication between OAT1/OAT3 and SLCO1B1. SLCO1B1 can be used as a potential in vivo biomarker for transporter mediated drug-drug interactions. SLCO1B1 variants are associated with therapeutic response to thiazolidinediones in patients with Type 2 diabetes.

Fig.1 Model of the transmembrane pore of OATP1B1 and OATP1B3. (Gruetz, 2016)

Application of SLCO1B1 Membrane Protein in Literature

Martinez D., et al. Endogenous Metabolites-Mediated Communication Between OAT1/OAT3 and OATP1B1 May Explain the Association Between SLCO1B1 SNPs and Methotrexate Toxicity. Clin Pharmacol Ther. 2017. PubMed ID: 29285751

This article indicates that SLCO1B1 deficiency can affect methotrexate toxicity possibly through endogenous metabolites mediated communication between OAT1/OAT3 and SLCO1B1.
Yang X., et al. Interaction Effects of AFB1 and MC-LR Co-exposure with Polymorphism of Metabolic Genes on Liver Damage: focusing on SLCO1B1 and GSTP1. Sci Rep. 2017, 7(1): 16164. PubMed ID: 29170472

This article demonstrates that SLCO1B1 (T521C) is susceptible to liver damage in humans when exposed to AFB1 and/or MC-LR in rural areas of China.
Khine H., et al. Statin-associated muscle symptoms and SLCO1B1 rs4149056 genotype in patients with familial hypercholesterolemia. Am Heart J. 2016, 179: 1-9. PubMed ID: 27595674

This article indicates that SLCO1B1 rs4149056 genotype is not related to the risk of statin-associated muscle symptoms in patients with familial hypercholesterolemia.
Yee S.W., et al. Metabolomic and Genome-wide Association Studies Reveal Potential Endogenous Biomarkers for OATP1B1. Clin Pharmacol Ther. 2016, 100(5): 524-536. PubMed ID: 27447836

This article shows that SLCO1B1 can be used to represent potential in vivo biomarker for transporter mediated drug-drug interactions.
Dawed A.Y., et al. CYP2C8 and SLCO1B1 Variants and Therapeutic Response to Thiazolidinediones in Patients With Type 2 Diabetes. Diabetes Care. 2016, 39(11): 1902-1908. PubMed ID: 27271184

This article shows that SLCO1B1 variants are associated with therapeutic response to thiazolidinediones in patients with Type 2 diabetes.

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Reference

Gruetz M, et al. (2016). Analysis of amino acid residues in the predicted transmembrane pore influencing transport kinetics of the hepatic drug transporter organic anion transporting polypeptide 1B1 (OATP1B1). Biochim Biophys Acta. 1858(11): 2894-2902.

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