Tchem RORC Nuclear receptor ROR-gamma

Protein Summary

Description

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). Isoform 2: Essential for thymopoiesis and the development of several secondary lymphoid tissues, including lymph nodes and Peyer's patches. Required for the generation of LTi (lymphoid tissue inducer) cells. Regulates thymocyte survival through DNA-binding on ROREs of target gene promoter regions and recruitment of coactivaros via the AF-2. Also plays a key role, downstream of IL6 and TGFB and synergistically with RORA, for lineage specification of uncommitted CD4(+) T-helper (T(H)) cells into T(H)17 cells, antagonizing the T(H)1 program. Probably regulates IL17 and IL17F expression on T(H) by binding to the essential enhancer conserved non-coding sequence 2 (CNS2) in the IL17-IL17F locus. May also play a role in the pre-TCR activation cascade leading to the maturation of alpha/beta T-cells and may participate in the regulation of DNA accessibility in the TCR-J(alpha) locus. 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. [provided by RefSeq, Jul 2008]

Uniprot Accession IDs

• P51449
• Q5SZR9
• Q8N5V7
• Q8NCY8

Gene Name

• RORC

Ensembl ID

• ENST00000318247
• ENSP00000327025
• ENSG00000143365
• ENST00000356728
• ENSP00000349164

Symbol

• NR1F3
• RORG
• RZRG
• TOR
• RORG
• RZRG
• IMD42
• NR1F3
• RZR-GAMMA

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	0.98
molecular function	0.95
protein domain	0.85
transcription factor	0.67
microRNA	0.64

Protein Classes

DTO Classes

Protein / Nuclear Receptor / Retinoic Acid-related Orphans / Nuclear Receptor Ror-gamma

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 200.76   (req: < 5)

Gene RIFs: 124   (req: <= 3)

Antibodies: 759   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 200.76   (req: >= 5)

Gene RIFs: 124   (req: > 3)

Antibodies: 759   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 30

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 1544

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0