RAR related orphan receptor | Elisa - Clia - Antibody - Protein

Background

RAR-related orphan receptors (RORs) are part of the nuclear receptor superfamily of transcription factors, which are key regulators of gene expression. These receptors are termed "orphan" because they were initially discovered without known endogenous ligands. The ROR family includes three members: RORα (NR1F1), RORβ (NR1F2), and RORγ (NR1F3). They play critical roles in numerous physiological processes, including circadian rhythm regulation, immune response, metabolism, and cellular differentiation. RORs are widely expressed in various tissues, such as the brain, liver, muscle, and immune cells, highlighting their diverse functional importance.

Protein Structure

• N-terminal Domain (NTD): Involved in the regulation of receptor activity through interaction with co-regulators and possibly phosphorylation sites.
• DNA-binding Domain (DBD): Contains two zinc finger motifs enabling RORs to bind to specific ROR response elements (ROREs) in the promoter regions of target genes.
• Hinge Region: Connects the DBD to the ligand-binding domain (LBD) and contributes to the receptor's structural flexibility.
• Ligand-binding Domain (LBD): Although initially considered orphan receptors, recent research suggests that various endogenous sterols may act as ligands for RORs. The LBD also interacts with co-activators and co-repressors to modulate gene transcription.

Classification and Subtypes

The ROR family is divided into three subtypes:

1. RORα (NR1F1): Involved in cerebellar development, lipid metabolism, and circadian rhythms.
2. RORβ (NR1F2): Predominantly expressed in the brain and retina, it plays a role in circadian rhythms and retinal development.
3. RORγ (NR1F3): Exists in two isoforms, RORγ1 and RORγt, with RORγt being crucial for thymocyte survival and the development of lymphoid tissues and Th17 cells in the immune system.

Function and Biological Significance

• Circadian Rhythm: RORα and RORβ are vital for maintaining circadian rhythms by regulating the expression of clock genes.
• Immune System: RORγt is essential for the differentiation of Th17 cells, which are involved in autoimmune responses and inflammation.
• Metabolism: RORα regulates lipid metabolism and is implicated in the development of metabolic disorders such as obesity and atherosclerosis.
• Development: RORβ is critical for the development of the retina and proper brain function.

Clinical Issues

• Autoimmune Diseases: Dysregulation of RORγt is linked to autoimmune diseases such as multiple sclerosis, rheumatoid arthritis, and psoriasis due to its role in Th17 cell differentiation.
• Metabolic Disorders: Altered RORα function is associated with obesity, metabolic syndrome, and cardiovascular diseases.
• Neurological Disorders: Mutations or dysregulation of RORα and RORβ are linked to neurodevelopmental disorders, including autism spectrum disorders and cerebellar ataxia.
• Cancer: Abnormal expression of RORs has been implicated in various cancers, including prostate, breast, and liver cancers.

Summary

RORs are integral transcription factors within the nuclear receptor superfamily, with critical roles in circadian rhythm, immune function, metabolism, and development. Comprising three main subtypes—RORα, RORβ, and RORγ—these receptors influence a wide range of physiological processes and are linked to several clinical conditions, including autoimmune diseases, metabolic disorders, neurological conditions, and cancers. Understanding the detailed mechanisms of RORs and their interactions with endogenous ligands provides significant insights into their potential as therapeutic targets for various diseases.