RORC Protein, Human (His, SUMO)

ROR gamma T is a nuclear receptor that binds as a monomer to ROR response elements (ROREs) containing a single core motif half-site 5'-AGGTCA-3' preceded by a short A-T-rich sequence. It serves as a key regulator of cellular differentiation, immunity, peripheral circadian rhythm, and the metabolism of lipids, steroids, xenobiotics, and glucose. The receptor exhibits intrinsic transcriptional activity and interacts with natural ligands such as oxysterols (e.g., 25-hydroxycholesterol as an agonist and 7-oxygenated sterols as inverse agonists), which modulate its transcriptional output. Depending on tissue, temporal, and promoter contexts, ROR gamma T recruits distinct cofactor combinations to target gene regulatory regions to fine-tune their expression. It competes with NR1D1 for binding to shared DNA response elements on clock genes (e.g., BMAL1, CRY1, NR1D1), driving circadian oscillations in peripheral tissues. Additionally, it regulates adipocyte differentiation, hepatocyte glucose metabolism, and IFN-gamma-dependent anti-mycobacterial immunity. It is essential for thymopoiesis, secondary lymphoid tissue development (e.g., lymph nodes, Peyer's patches), and the differentiation of Th17 cells, where it synergizes with RORA to antagonize the Th1 program.