biostudies-literatureTambe VNCI NIH HHSNIGMS NIH HHSNIH HHS100007https://www.ebi.ac.uk/biostudies/studies/S-EPMC11934288biostudies-literatureUnknown107(2)Organic anion transporting polypeptide (OATP) 1B1 is crucial for hepatic uptake of many drugs and endogenous substrates. The clinically relevant OATP1B1 c.521 T>C (V174A) polymorphism exhibits reduced transport activity in vitro and in vivo in humans. Previously, we reported increased total phosphorylation of V174A-OATP1B1 compared to wild-type (WT)-OATP1B1, although the differentially phosphorylated sites remain to be identified. Lysine-acetylation, a key posttranslational modification (PTM), has not been investigated in OATP1B1. This study aimed to identify differential PTMs of WT-OATP1B1 and V174A-OATP1B1 by quantitatively comparing the relative abundance of modified peptides using liquid chromatography-tandem mass spectrometry-based proteomics and to assess the impact of these PTMs on Molecular pharmacologyRegulation of organic anion transporting polypeptide 1B1 transport function by concurrent phosphorylation and lysine-acetylation: A novel posttranslational regulation mechanism.PMC11934288R01 GM094268R01 GM146956S10 OD024999P30 CA225520Tambe VXu CSoderblom EJYue WKayesh RAditya VfalseRegulation of organic anion transporting polypeptide 1B1 transport function by concurrent phosphorylation and lysine-acetylation: A novel posttranslational regulation mechanism.Organic anion transporting polypeptide (OATP) 1B1 is crucial for hepatic uptake of many drugs and endogenous substrates. The clinically relevant OATP1B1 c.521 T>C (V174A) polymorphism exhibits reduced transport activity in vitro and in vivo in humans. Previously, we reported increased total phosphorylation of V174A-OATP1B1 compared to wild-type (WT)-OATP1B1, although the differentially phosphorylated sites remain to be identified. Lysine-acetylation, a key posttranslational modification (PTM), has not been investigated in OATP1B1. This study aimed to identify differential PTMs of WT-OATP1B1 and V174A-OATP1B1 by quantitatively comparing the relative abundance of modified peptides using liquid chromatography-tandem mass spectrometry-based proteomics and to assess the impact of these PTMs on 2025-01-01T00:00:00Z2025 Feb2025-07-11T03:04:03.066Z2025-07-11T03:04:03.066ZS-EPMC119342884002351410.1016/j.molpha.2024.100007