NR2E - nuclear receptor subfamily 2 group E member | Elisa - Clia - Antibody - Protein

Background

Nuclear receptor subfamily 2 group E members, specifically NR2E1 (also known as TLX) and NR2E3 (also known as PNR), are orphan nuclear receptors that play critical roles in neurodevelopment, vision, and other physiological processes. These receptors are particularly important in the central nervous system and the retina. NR2E1 is essential for brain development, influencing neural stem cell proliferation and differentiation, whereas NR2E3 is crucial for photoreceptor development and maintenance in the retina.

Protein Structure

NR2E receptors share the common structural features of nuclear receptors:

• N-terminal Domain (NTD): This region is variable and often involved in transcriptional regulation.
• DNA-binding Domain (DBD): Comprising two zinc finger motifs, this highly conserved region is responsible for binding to specific DNA sequences known as response elements.
• Hinge Region: Provides structural flexibility and contributes to the receptor’s ability to enter the nucleus.
• Ligand-binding Domain (LBD): This domain binds potential endogenous ligands or synthetic molecules, playing a role in receptor dimerization and the recruitment of co-regulators.
• C-terminal Domain: Involved in additional regulatory interactions, it can influence the receptor's activity and stability.

Classification and Subtypes

NR2E receptors belong to the nuclear receptor superfamily, classified under subfamily 2, group E. The main members include:

• NR2E1 (TLX): Predominantly expressed in the brain and involved in neural development and stem cell regulation.
• NR2E3 (PNR): Mainly expressed in the retina, playing a vital role in photoreceptor differentiation and function.

Function and Biological Significance

NR2E receptors serve as transcription factors that regulate gene expression in various biological contexts:

• Neurodevelopment: NR2E1 is crucial for brain development, regulating neural stem cell maintenance, proliferation, and differentiation. It helps ensure proper formation and function of the cerebral cortex.
• Vision: NR2E3 is essential for the development and function of photoreceptors in the retina. It regulates the balance between rod and cone cells, which are critical for vision.
• Stem Cell Regulation: Both NR2E1 and NR2E3 play roles in maintaining the balance between stem cell proliferation and differentiation in their respective tissues.

Clinical Issues

• Neurodevelopmental Disorders: Dysregulation or mutations in NR2E1 are associated with developmental brain disorders, including microcephaly and cognitive deficits.
• Retinal Degeneration: Mutations in NR2E3 are linked to retinal diseases such as enhanced S-cone syndrome (ESCS) and retinitis pigmentosa, leading to progressive vision loss.
• Cancer: Abnormal expression of NR2E1 has been implicated in gliomas and other neural-derived tumors, suggesting a role in oncogenesis.

Summary

NR2E members, particularly NR2E1 (TLX) and NR2E3 (PNR), are critical orphan nuclear receptors with significant roles in neurodevelopment and vision. These receptors function as transcription factors, modulating gene expression essential for the development and maintenance of neural and retinal cells. Understanding their molecular mechanisms and associated clinical issues provides insight into potential therapeutic targets for neurodevelopmental disorders, retinal diseases, and certain cancers.