2.A.60.1.5
Organic anion transporter, OATP2, OAT1B1, SLCO1B1 or OATP1B1 (LST-1) (SLC21A6; S01) (substrates: mono- and bis-glucuronosyl bilirubin, sulfobromophthalein, taurocholate (Km = 14 μM), estrone sulfate, dehydroepiandrosterone sulfate, estradiol-17 β-D-glucuronide and other conjugated steroids (i.e., estrone 3-sulfate), leukotriene C₄, eicosanoids (i.e., prostaglandin E₂, thromboxane B₂, leucotriene C₄ and leucotriene E₄), thyroid hormones (i.e., thyroxine and triiodothyronine), other organic anions, drugs, β-lactam antibiotics, ochratoxin, xenobiotics, ouabain, valsartan and pravastatin). OatP-C/1B1(SLC21A) (Hogg et al. 2015; Qi et al. 2017). The bile acid (cholic acid) uptake transporter, OatP-C (transports cholic acid without symport with GSH) (Briz et al., 2006; Degorter et al., 2012). Amino acids in TMS2 essential for estrone-3-sulfate transport have been identified (Li et al., 2012).  OATP1B1 exhibits polymorphism related to neonatal hyperbilirubinemia (Zhang et al. 2010).  Tyr258 and Trp259 in TMS6 play different roles in substrate specificity (Huang et al. 2013).  Cyclic ABP aromatic ring substituents like the chloro-phenyl-thio groups increase their ability to inhibit OATP-mediated transport (Herfindal et al. 2014).  TMS11 influences substrate binding, stability and trafficking (Hong et al. 2015).  Transports danoprevir (hepatitis C virus protease inhibitor) (Brennan et al. 2015).  Residues have been identified that are involved in modulating transport kinetics, and this participation strongly depends on the substrate used in the assay (Gruetz et al. 2016). A 336A mutant is detained in the Golgi apparatus and the Y338A mutant exhibited accelerated protein degradation compared to that of the wild-type, but conservative replacement of Y338 withphenylalanine resulted in recovery of uptake and expression. Thus, the NPXY motif between TMSs 6 and 7 is essential for stable localization of OATP1B1 in the plasma membrane (Wang et al. 2019). SLCO1B1 rs2291075 may be a genetic locus associated with tacrolimus metabolism (Wu et al. 2021). Leucine heptad motifs within TMSs affect the function and oligomerization (Ni et al. 2021). Deep mutational scanning (DMS) has been used to determine the functional effects of variants that have been observed in the SLCO1B1 gene (Zhang et al. 2021). TMSs 2, 4 and 11 appear to be crucial for proper membrane localization and function of OATP1B1. Four of the studied variants were identified as loss-of-function variants and as such could make the individual harboring these variants susceptible to altered pharmacokinetics and adverse effects of substrate drugs (Kiander et al. 2021). Machine learning models have been used to identify novel inhibitors which include abamectin, asiaticoside, berbamine, doramectin, mobocertinib, and umbralisib (Lane et al. 2022). SLCO1B1 variants give rise to psychotic disorders (Häkkinen et al. 2023). The double-leucine motifs sffect internalization, stability, and function of OAT1B1 (Wang et al. 2023).