Anticorpi ROR gamma

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 G6PC 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).

The protein encoded by this gene is a DNA-binding transcription factor and is a member of the NR1 subfamily of nuclear hormone receptors. The specific functions of this protein are not known; however, studies of a similar gene in mice have shown that this gene may be essential for lymphoid organogenesis and may play an important regulatory role in thymopoiesis. In addition, studies in mice suggest that the protein encoded by this gene may inhibit the expression of Fas ligand and IL2. Two transcript variants encoding different isoforms have been found for this gene.

Isoform 1 is widely expressed in many tissues, including liver and adipose, and highly expressed in skeletal muscle. Isoform 2 is primarily expressed in immature thymocytes.

Immunodeficiency 42: An autosomal recessive primary immunodeficiency characterized by increased susceptibility to concomitant candidiasis and mycobacteriosis. Candidiasis is characterized by persistent and/or recurrent infections of the skin, nails and mucous membranes caused by organisms of the genus Candida. Mycobacteriosis is characterized by infections caused by moderately virulent mycobacterial species, such as Bacillus Calmette-Guerin (BCG) vaccine, environmental non-tuberculous mycobacteria, and by the more virulent Mycobacterium tuberculosis. IMD42 patients vaccinated with BCG are particularly at risk for developing disseminated mycobacterial infections.

Belongs to the nuclear hormone receptor family. NR1 subfamily.

Nucleus.