Identification of FAME (Factor Associated with Metabolism and Energy) interactome

Using comparative genomics, we discovered that a previously uncharacterized gene (1700011H14RIK/C14ORF105/CCDC198) hereby named FAME (Factor Associated with Metabolism and Energy) shows an unusually high rate of evolutionary divergence in birds and mammals. By comparing SNVs, we identified gene-flow of FAME from Neandertals into modern humans. FAME knockout animals demonstrated increased body weight and decreased energy expenditure, corresponding to GWAS linking FAME with higher BMI, diabetes-related pathologies, and macular degeneration in humans. The analysis of gene expression and subcellular localization revealed that FAME is a membrane-bound protein enriched in kidneys. Although a gene knockout resulted in structurally normal kidneys, we detected higher Albumin in urine and lowered ferritin in the blood. The experiment confirmed interactions between FAME and ferritin and showed co-localization in vesicular and plasma membranes. Overall, our results show that FAME plays a role in tuning metabolite excretion and energy expenditure, partly explaining why it evolves at a high rate in birds and mammals. Here, we provide data related to identification of FAME interactome using the co-immunoprecipitation method.