Rorc

GeneName

RORC

Summary

RORC, also known as TOR, is a 58 kDa nuclear receptor and transcription factor that plays a pivotal role in regulating various biological processes. It is primarily localised in the nucleus and is involved in DNA-binding activities, specifically as a transcription factor for RNA polymerase II. RORC is essential for the development of adipose tissue, lymph nodes, and Peyer's patches, and it influences T-helper cell differentiation, particularly T-helper 17 cells. Additionally, it modulates circadian rhythms and regulates metabolic processes related to glucose and steroids, responding to sterol levels in the cellular environment.

Importance

RORC is relevant to: - Immune responses and autoimmunity through its role in T-helper 17 cell differentiation and function. - Metabolic disorders, as it is involved in adipose tissue development and glucose metabolism regulation. - Circadian biology, given its influence on the regulation of circadian rhythms and gene expression. - Cancer research, due to its function in transcription regulation which can affect tumour growth and development.

Top Products

For researchers investigating RORC, we recommend the well-cited monoclonal antibody, Anti-ROR gamma antibody [162C2a] (ab58670). This antibody is particularly noted for its performance in Western blotting (WB) and has garnered 6 citations, reflecting its reliability and acceptance in the research community. This product is an excellent choice for those looking to achieve consistent and reproducible results in their studies of RORC.

Abcam Product Citation Summary

The use of the Abcam antibody ab58670 for detecting RORC in human samples highlights its relevance in studying gene regulation and transcription factors in various biological contexts.

Abcam Product Citation Table

Developmental stage

In 3T3-L1 cells, sharp decline at mRNA and protein levels upon induction of adipocyte differentiation. Isoform 2 is detected in the immediate vicinity of vessels among small clusters of CD45(+) cells as early as 12.5 dpc. At 16.5 dpc, isoform 2 is expressed exclusively in tight clusters of cells found in lymph node anlagen, in the submucosal region of the intestine and around central vessels in the spleen.

Domain

The AF-2 (activation function-2) motif is required for recruiting coregulators containing LXXLL motifs such as NCOA1 and NCOA2.

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. 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. Recruits distinct combinations of cofactors to target gene regulatory regions to modulate their transcriptional expression, depending on the tissue, time and promoter contexts (PubMed:17666523, PubMed:19381306, PubMed:19965867, PubMed:21853531, PubMed:22789990, PubMed:23723244). Regulates the circadian expression of clock genes such as CRY1, BMAL1 and NR1D1 in peripheral tissues and in a tissue-selective manner (PubMed:22753030). Competes with NR1D1 for binding to their shared DNA response element on some clock genes such as 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 (PubMed:22753030). Involved in the regulation of the rhythmic expression of genes involved in glucose and lipid metabolism, including PLIN2 and AVPR1A. 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 (PubMed:21853531). Also plays a role in the regulation of hepatocyte glucose metabolism through the regulation of G6PC1 and PCK1. Regulates the rhythmic expression of PROX1 and promotes its nuclear localization. Plays an indispensable role in the induction of IFN-gamma dependent anti-mycobacterial systemic immunity (By similarity).

Isoform 2

Nuclear receptor essential for thymopoiesis and the development of several secondary lymphoid tissues, including lymph nodes and Peyer's patches (PubMed:10602018, PubMed:14691482, PubMed:16148126, PubMed:9881970). Required for the generation of LTi (lymphoid tissue inducer) cells (PubMed:14691482). Regulates thymocyte survival through DNA-binding on ROREs of target gene promoter regions and recruitment of coactivaros via the AF-2 (PubMed:16148126). 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 (PubMed:16990136, PubMed:18164222, PubMed:26607793). 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 (PubMed:16990136, PubMed:18164222, PubMed:26607793). Plays a key role in tolerance to gut microbiota and foreign antigens in food by mediating differentiation of peripherally-induced regulatory T-cells (pTreg), which suppress inflammatory responses to commensal microorganisms and food proteins (PubMed:36070798, PubMed:36071167, PubMed:36071169, PubMed:40185101, PubMed:40298935). Specifically expressed in antigen-presenting cell populations, such as (1) type 3 innate lymphoid cells (ILC3s), which are required for tolerance to gut microbiota, (2) Thetis cells, also named Janus cells, which are enriched in gut lymph nodes during early life and are required for oral tolerance, and (3) a subset of dendritic cells (PubMed:36070798, PubMed:36071167, PubMed:36071169, PubMed:40185101, PubMed:40298935). Following activation by an unknown ligand in antigen-presenting cells, promotes recruitment of transcription regulators, such as PRDM16 or ZBTB46, and drives differentiation of pTreg cells, which maintain immune tolerance and prevent autoimmune diseases (PubMed:35831503, PubMed:40228524). 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 (PubMed:10602018).

Sequence Similarities

Belongs to the nuclear hormone receptor family. NR1 subfamily.

Tissue Specificity

Expressed in immature Vgamma2 gamma-delta T-cells (at protein level) (PubMed:23562159). Expressed in the liver (PubMed:17666523, PubMed:22753030). Expressed in the heart (PubMed:17666523). Expressed in the kidney, jejunum, and brown adipose tissue (PubMed:22753030).

Isoform 1

Expressed in muscle and the thymus (PubMed:10602018, PubMed:9881970). Expressed in the brain, heart, kidney, liver, and lung (PubMed:9881970). Expressed in testes (PubMed:10602018). Not expressed in the spleen or bone marrow (PubMed:9881970).

Isoform 2

Expressed in the thymus, primarily in immature thymocytes, including Vgamma2 gamma-delta T-cells (at protein levels) (PubMed:10602018, PubMed:9881970). Also expressed in a subset of mature T(H)17 cells (PubMed:18164222). Not expressed in the spleen or bone marrow (PubMed:9881970).

Cellular localization

• Nucleus

Alternative names

Nr1f3, Rorg, Thor, Rorc, Nuclear receptor ROR-gamma, Nuclear receptor RZR-gamma, Nuclear receptor subfamily 1 group F member 3, RAR-related orphan receptor C, Retinoid-related orphan receptor-gamma, Thymus orphan receptor, TOR

Database links

swissprot:P51450 entrezGene:19885

Other research areas

• Epigenetics
• Immuno-oncology