biostudies-literatureUnknown16Song W<h4>Introduction</h4>MTNR1A and MTNR1B, crucial for regulating circadian rhythms and various physiological processes, have well- established biological significance. The role of MRAP2, a single transmembrane accessory protein, in modulating the pharmacological activity of melatonin receptors remains unclear.<h4>Methods</h4>We first examined the evolutionary profiles of melatonin receptors and MRAP2 by protein sequence alignment and synteny analysis. Bulk RNA-seq was then employed to analyze the expression distribution of these genes. Next, we performed co-immunoprecipitation and Bimolecular Fluorescence Complementation (BiFC) assays to investigate the interaction of MRAP2 with melatonin receptors. We also recruited the GloSensor luminescence assay to assess the impact of MRAP2 on the Gi siFrontiers in endocrinology1593345https://www.ebi.ac.uk/biostudies/studies/S-EPMC12158745biostudies-literaturePharmacological modulation of MRAP2 protein on murine melatonin receptor signaling.PMC12158745Li YLiu LLyu JZhang YXiao YDu YChen YWang XXu HZhang CSong WJin LfalsePharmacological modulation of MRAP2 protein on murine melatonin receptor signaling.<h4>Introduction</h4>MTNR1A and MTNR1B, crucial for regulating circadian rhythms and various physiological processes, have well- established biological significance. The role of MRAP2, a single transmembrane accessory protein, in modulating the pharmacological activity of melatonin receptors remains unclear.<h4>Methods</h4>We first examined the evolutionary profiles of melatonin receptors and MRAP2 by protein sequence alignment and synteny analysis. Bulk RNA-seq was then employed to analyze the expression distribution of these genes. Next, we performed co-immunoprecipitation and Bimolecular Fluorescence Complementation (BiFC) assays to investigate the interaction of MRAP2 with melatonin receptors. We also recruited the GloSensor luminescence assay to assess the impact of MRAP2 on the Gi si2025-01-01T00:00:00Z20252026-04-25T03:30:58.951Z2026-04-25T03:22:58.33ZS-EPMC121587454051047210.3389/fendo.2025.1593345