Summary

Name RORC
Full Name Nuclear receptor ROR-gamma
Synonyms Nuclear receptor RZR-gamma, Nuclear receptor subfamily 1 group F member 3, RAR-related orphan receptor C, Retinoid-related orphan receptor-gamma | NR1F3, RORG, RZRG
Primary ID P51449
Links - -
Type protein
Relations 6
Pathways Circadian clock, T-Lymphocyte: IL6, T-Lymphocyte: TGF beta
Function Nuclear receptor that binds DNA as a monomer to ROR response elements (RORE) containing a single core motif half-site 5'-AGGTCA-3' preceded by a short A-T-rich sequence. Key regulator of cellular differentiation, immunity, peripheral circadian rhythm as well as lipid, steroid, xenobiotics and glucose metabolism (PubMed:19381306, PubMed:19965867, PubMed:22789990, PubMed:26160376, PubMed:20203100). Considered to have intrinsic transcriptional activity, have some natural ligands like oxysterols that act as agonists (25-hydroxycholesterol) or inverse agonists (7-oxygenated sterols), enhancing or repressing the transcriptional activity, respectively (PubMed:19965867, PubMed:22789990). Recruits distinct combinations of cofactors to target gene regulatory regions to modulate their transcriptional expression, depending on the tissue, time and promoter contexts. Regulates the circadian expression of clock genes such as CRY1, ARNTL/BMAL1 and NR1D1 in peripheral tissues and in a tissue-selective manner. Competes with NR1D1 for binding to their shared DNA response element on some clock genes such as ARNTL/BMAL1, CRY1 and NR1D1 itself, resulting in NR1D1-mediated repression or RORC-mediated activation of the expression, leading to the circadian pattern of clock genes expression. Therefore influences the period length and stability of the clock. Involved in the regulation of the rhythmic expression of genes involved in glucose and lipid metabolism, including PLIN2 and AVPR1A (PubMed:19965867). Negative regulator of adipocyte differentiation through the regulation of early phase genes expression, such as MMP3. Controls adipogenesis as well as adipocyte size and modulates insulin sensitivity in obesity. In liver, has specific and redundant functions with RORA as positive or negative modulator of expression of genes encoding phase I and Phase II proteins involved in the metabolism of lipids, steroids and xenobiotics, such as SULT1E1. Also plays also a role in the regulation of hepatocyte glucose metabolism through the regulation of G6PC1 and PCK1 (PubMed:19965867). Regulates the rhythmic expression of PROX1 and promotes its nuclear localization (PubMed:19381306, PubMed:19965867, PubMed:22789990, PubMed:26160376, PubMed:20203100). Plays an indispensable role in the induction of IFN-gamma dependent anti-mycobacterial systemic immunity (PubMed:26160376).

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Relations

Regulator Mechanism target score
+ up-regulates img/indirect-activation.png RORC 0.626
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png RORC 0.44
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/indirect-activation.png Th17 0.7
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity by expression img/direct-activation.png transcriptional regulation ARNTL 0.522
Publications: 1 Organism: Homo Sapiens
Pathways:Circadian clock
+ down-regulates img/indirect_inhibition.png RORC 0.276
Publications: 1
+ up-regulates img/direct-activation.png transcriptional regulation IL17A 0.564
Publications: 1 Organism: Homo Sapiens