VDR - vitamin D receptor | Elisa - Clia - Antibody - Protein

Background

The Vitamin D receptor (VDR) is a member of the nuclear receptor family of transcription factors. It mediates the effects of vitamin D, a critical hormone for calcium homeostasis and bone metabolism. The VDR gene is located on chromosome 12q13.11. Vitamin D, upon being converted to its active form (1,25-dihydroxyvitamin D3 or calcitriol), binds to VDR, enabling the receptor to regulate gene expression. VDR influences the expression of over 900 genes involved in various biological processes, including cellular growth, immune function, and inflammation. Defects in VDR function can lead to several diseases, such as rickets, osteoporosis, and autoimmune disorders.

Protein Structure

• DNA-Binding Domain (DBD): VDR contains a highly conserved DBD that allows it to bind to specific DNA sequences called vitamin D response elements (VDREs) in the promoters of target genes. This domain consists of two zinc finger motifs, which stabilize the receptor’s interaction with DNA.
• Ligand-Binding Domain (LBD): The LBD of VDR is responsible for binding to its ligand, calcitriol. This domain also facilitates heterodimerization with the retinoid X receptor (RXR), which is essential for the receptor’s function.
• N-Terminal Domain: This region varies in length and sequence and is involved in the regulation of receptor activity.
• C-Terminal Domain: Important for transactivation, it includes activation function 2 (AF-2), which interacts with coactivators and corepressors to regulate gene transcription.

Classification and Subtypes

VDR belongs to the nuclear receptor superfamily, specifically the NR1I subfamily, which includes:

1. NR1I1: Pregnane X receptor (PXR).
2. NR1I2: Constitutive androstane receptor (CAR).

Function and Biological Significance

• Calcium Homeostasis and Bone Metabolism: VDR regulates the absorption of calcium and phosphate in the intestine, critical for maintaining bone density and structure.
• Cell Proliferation and Differentiation: By modulating gene expression, VDR influences cell cycle regulation, promoting the differentiation of cells, particularly in the skin and immune system.
• Immune Function: VDR plays a significant role in the immune response, influencing the activity of T and B lymphocytes and macrophages, thereby impacting conditions like autoimmune diseases and infections.
• Anti-Cancer Effects: VDR activation has been associated with anti-proliferative effects in various cancer cells, suggesting a protective role against cancer development and progression.

Clinical Issues

• Vitamin D Deficiency: Insufficient levels of vitamin D can impair VDR function, leading to bone diseases like rickets in children and osteomalacia or osteoporosis in adults.
• Autoimmune Diseases: Variants in the VDR gene have been linked to increased susceptibility to autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, and type 1 diabetes.
• Cancer: Altered VDR expression or function has been observed in several cancers, including breast, prostate, and colorectal cancers. VDR's role in regulating cell proliferation and apoptosis makes it a potential target for cancer therapy.
• Cardiovascular Diseases: Emerging evidence suggests that VDR may influence cardiovascular health, with vitamin D deficiency being associated with an increased risk of hypertension, atherosclerosis, and other cardiovascular conditions.

Summary

The Vitamin D receptor (VDR) is a pivotal nuclear receptor involved in regulating a multitude of genes critical for calcium homeostasis, immune function, and cellular differentiation. Its structure includes distinct domains for DNA binding and ligand interaction, facilitating its role as a transcription factor. VDR's biological significance spans various physiological processes, with implications for bone health, immune response, and cancer. Clinically, VDR dysfunction or deficiency in vitamin D can lead to significant health issues, including bone diseases, autoimmune disorders, and increased cancer risk. Understanding VDR's mechanisms and effects continues to be crucial for developing therapeutic interventions for these conditions.