NR2C - nuclear receptor subfamily 2 group C member | Elisa - Clia - Antibody - Protein

Background

The nuclear receptor subfamily 2 group C members, including NR2C1 and NR2C2, are orphan nuclear receptors that play pivotal roles in various biological processes such as development, metabolism, and cellular differentiation. NR2C1 (also known as TR2) and NR2C2 (also known as TR4) are crucial in embryonic development and are expressed in various tissues including the testis, prostate, brain, and kidney. These receptors regulate gene expression by binding to specific DNA sequences and interacting with co-regulators to modulate transcription.

Protein Structure

The structure of NR2C receptors follows the typical organization of nuclear receptors, comprising:

• N-terminal Domain (NTD): Variable in length and sequence, involved in modulating transcriptional activity.
• DNA-binding Domain (DBD): Highly conserved, consisting of two zinc finger motifs that facilitate specific binding to DNA response elements.
• Hinge Region: Provides flexibility between the DBD and LBD, playing a role in nuclear localization.
• Ligand-binding Domain (LBD): Binds to potential endogenous ligands or synthetic molecules, involved in receptor dimerization and recruitment of co-regulatory proteins.
• C-terminal Domain: Involved in additional regulatory interactions and modulating receptor activity.

Classification and Subtypes

NR2C receptors belong to the nuclear receptor superfamily and are classified under subfamily 2, group C. The main members include:

• NR2C1 (TR2): Expressed predominantly in the reproductive system and involved in spermatogenesis.
• NR2C2 (TR4): Broadly expressed in various tissues and implicated in lipid metabolism, central nervous system function, and development.

Function and Biological Significance

NR2C receptors function as transcription factors regulating a variety of physiological processes:

• Development: Both NR2C1 and NR2C2 are essential during embryogenesis and organ development. They regulate genes involved in cell proliferation and differentiation.
• Metabolism: NR2C2 plays a significant role in lipid and glucose metabolism, influencing energy homeostasis and metabolic syndrome.
• Reproduction: NR2C1 is critical for normal spermatogenesis and male fertility. It regulates genes essential for germ cell development.
• Central Nervous System: NR2C2 is involved in neural development and function, impacting learning, memory, and neuroprotection.

Clinical Issues

• Metabolic Disorders: Dysregulation of NR2C2 is associated with metabolic syndromes such as obesity, type 2 diabetes, and hyperlipidemia.
• Reproductive Health: Mutations or altered expression of NR2C1 can lead to male infertility due to impaired spermatogenesis.
• Neurological Disorders: Abnormalities in NR2C2 function are linked to neurodevelopmental and neurodegenerative diseases, highlighting its role in maintaining neural health.

Summary

NR2C members, NR2C1 (TR2) and NR2C2 (TR4), are critical orphan nuclear receptors involved in regulating development, metabolism, reproduction, and neural functions. They operate by modulating gene transcription through DNA binding and interaction with co-regulatory proteins. Understanding their roles in physiological and pathological conditions opens avenues for therapeutic interventions targeting metabolic, reproductive, and neurological disorders.