Nuclear receptor subfamily 4 group A member 3 (NR4A3) (NR4A3)

Nuclear receptor subfamily 4 group A member 3 (NR4A3), also known as Neuron-derived orphan receptor 1 (NOR1), is a member of the NR4A orphan nuclear receptor family that functions as an activity-dependent transcription factor (UniProt P41153). It is rapidly induced by a variety of physiological stimuli, including growth factors and cytokines, and plays a pivotal role in regulating cell cycle progression, apoptosis, and systemic metabolism (PubMed: 24011540). In oncology, NR4A3 is a critical driver of extraskeletal myxoid chondrosarcoma (EMC), where it is frequently found as a fusion protein resulting from chromosomal translocations, most commonly EWSR1-NR4A3 (PubMed: 15188353). Conversely, in the context of hematology, NR4A3 acts as a potent tumor suppressor; its loss or downregulation is a key event in the pathogenesis of acute myeloid leukemia (AML) (PubMed: 28235200). Beyond cancer, NR4A3 is involved in vascular biology, where it regulates the proliferation of vascular smooth muscle cells and the inflammatory response in atherosclerotic lesions (PubMed: 17065454). Although it is classified as an orphan receptor because it lacks a known endogenous ligand, its activity can be modulated by small molecules like 6-mercaptopurine and synthetic agonists, making it an attractive target for therapeutic intervention in metabolic and malignant disorders.

Other names

Neuron-derived orphan receptor 1NOR1Mitogen-induced orphan receptorMINORChondrosarcoma-associated gene proteinCHNTranslocated in extraskeletal myxoid chondrosarcomaTEC

Modulation of transcriptional activity by binding as a monomer to NGFI-B response elements (NBRE) or as a homodimer/heterodimer to Nur-responsive elements (NurRE) to regulate downstream gene expression.