A Comprehensive Analysis and Prediction of Sub-Cellular Localization of Human Nuclear Receptors

Abstract

The Nuclear Receptor (NR) superfamily comprises of conserved ligand-modulated intracellular transcription factors which in the presence of their cognate ligands activate a plethora of signaling networks, thereby commencing their respective transcription functions. All NRs are nuclear when liganded or active. However, their localization may differ between nucleus and cytoplasm when unliganded or inactive. NRs control a majority of physiological processes in body ranging from metabolism to reproduction and development. Hitherto, in case of humans, 48 NRs have been identified which are localized either in cytosolic, nuclear or both compartments of the cell. Sub-cellular localization of proteins has great relevance in relation to their function. However, specific sub-cellular localization patterns of human NRs are clouded with ambiguity and are mostly ridden with controversy, with only a few of them being well-studied and established under specific physiological conditions. In the present study, we attempted to bridge the gap and attempted to draw conclusions in relation to sub-cellular localization of human NRs based on published experimental data and by in-silico prediction methods. This comprehensive analysis may not only be useful to draw conclusions on their control of physiological processes but may also open new avenues towards understanding of the molecular basis of NR-mediated diseases attributed to their mislocalization and malfunctioning.