The calcitriol receptor, more commonly known as the vitamin D receptor (VDR) and also known as NR1I1 (nuclear receptor subfamily 1, group I, member 1), is a member of the nuclear receptor family of transcription factors. [5] Calcitriol, the active form of vitamin D, binds to the VDR, which then forms a heterodimer with the retinoid-X receptor. This then binds to hormone response elements on DNA resulting in expression or transrepression of specific gene products. The VDR not only regulates transcriptional responses but also involved in microRNA-directed post transcriptional mechanisms. [6] In humans, the vitamin D receptor is encoded by the VDR gene. [7]
Glucocorticoids are known to decrease expression of VDR, which is expressed in most tissues of the body and regulate intestinal transport of calcium, iron and other minerals. [8]
The VDR gene encodes the nuclear hormone receptor for vitamin D3. This receptor also functions as a receptor for the secondary bile acid lithocholic acid. The receptor belongs to the family of trans-acting transcriptional regulatory factors and shows similarity of sequence to the steroid and thyroid hormone receptors. [9]
Downstream targets of this nuclear hormone receptor are involved principally in mineral metabolism though the receptor regulates a variety of other metabolic pathways, such as those involved in the immune response and cancer. [10]
Mutations in this gene are associated with type II vitamin D-resistant rickets. A single nucleotide polymorphism in the initiation codon results in an alternate translation start site three codons downstream. Alternative splicing results in multiple transcript variants encoding the same protein. [11] VDR gene variants seem to influence many biological endpoints, including those related to osteoporosis [12]
The vitamin D receptor plays an important role in regulating the hair cycle. Loss of VDR is associated with hair loss in experimental animals. [13] Experimental studies have shown that the unliganded VDR interacts with regulatory regions in cWnt (wnt signaling pathway) and sonic hedgehog target genes and is required for the induction of these pathways during the postnatal hair cycle. [14] These studies have revealed novel actions of the unliganded VDR in regulating the post-morphogenic hair cycle.
Calcitriol receptor has been shown to interact with
Click on genes, proteins and metabolites below to link to respective articles. [§ 1]
Androgen insensitivity syndrome (AIS) is an intersex condition that results in the partial or complete inability of the cell to respond to androgens. The unresponsiveness of the cell to the presence of androgenic hormones can impair or prevent the masculinization of male genitalia in the developing fetus, as well as impairing or preventing the development of male secondary sexual characteristics at puberty, but does not significantly impair female genital or sexual development. As such, the insensitivity to androgens is clinically significant only when it occurs in genetic males. Clinical phenotypes in these individuals range from a typical male habitus with mild spermatogenic defect or reduced secondary terminal hair, to a full female habitus, despite the presence of a Y-chromosome.
Calcitriol is the active form of vitamin D, normally made in the kidney. A manufactured form is used to treat kidney disease with low blood calcium, hyperparathyroidism due to kidney disease, low blood calcium due to hypoparathyroidism, osteoporosis, osteomalacia, and familial hypophosphatemia. It is taken by mouth or by injection into a vein.
The glucocorticoid receptor also known as NR3C1 is the receptor to which cortisol and other glucocorticoids bind.
The thyroid hormone receptor (TR) is a type of nuclear receptor that is activated by binding thyroid hormone. TRs act as transcription factors, ultimately affecting the regulation of gene transcription and translation. These receptors also have non-genomic effects that lead to second messenger activation, and corresponding cellular response.
Estrogen receptor alpha (ERα), also known as NR3A1, is one of two main types of estrogen receptor, a nuclear receptor that is activated by the sex hormone estrogen. In humans, ERα is encoded by the gene ESR1.
The mineralocorticoid receptor, also known as the aldosterone receptor or nuclear receptor subfamily 3, group C, member 2, (NR3C2) is a protein that in humans is encoded by the NR3C2 gene that is located on chromosome 4q31.1-31.2.
The nuclear receptor coactivator 2 also known as NCoA-2 is a protein that in humans is encoded by the NCOA2 gene. NCoA-2 is also frequently called glucocorticoid receptor-interacting protein 1 (GRIP1), steroid receptor coactivator-2 (SRC-2), or transcriptional mediators/intermediary factor 2 (TIF2).
The nuclear receptor coactivator 3 also known as NCOA3 is a protein that, in humans, is encoded by the NCOA3 gene. NCOA3 is also frequently called 'amplified in breast 1' (AIB1), steroid receptor coactivator-3 (SRC-3), or thyroid hormone receptor activator molecule 1 (TRAM-1).
The nuclear receptor co-repressor 1 also known as thyroid-hormone- and retinoic-acid-receptor-associated co-repressor 1 (TRAC-1) is a protein that in humans is encoded by the NCOR1 gene.
Homeobox expressed in ES cells 1, also known as homeobox protein ANF, is a homeobox protein that in humans is encoded by the HESX1 gene.
Retinoid X receptor alpha (RXR-alpha), also known as NR2B1 is a nuclear receptor that in humans is encoded by the RXRA gene.
Retinoic acid receptor alpha (RAR-α), also known as NR1B1 is a nuclear receptor that in humans is encoded by the RARA gene.
Nuclear receptor-interacting protein 1 (NRIP1) also known as receptor-interacting protein 140 (RIP140) is a protein that in humans is encoded by the NRIP1 gene.
COUP-TFII, also known as NR2F2 is a protein that in humans is encoded by the NR2F2 gene. The COUP acronym stands for chicken ovalbumin upstream promoter.
Thyroid hormone receptor beta (TR-beta) also known as nuclear receptor subfamily 1, group A, member 2 (NR1A2), is a nuclear receptor protein that in humans is encoded by the THRB gene.
Mediator of RNA polymerase II transcription subunit 1 also known as DRIP205 or Trap220 is a subunit of the Mediator complex and is a protein that in humans is encoded by the MED1 gene. MED1 functions as a nuclear receptor coactivator.
Heterogeneous nuclear ribonucleoproteins C1/C2 is a protein that in humans is encoded by the HNRNPC gene.
Nuclear receptor coactivator 6 is a protein that in humans is encoded by the NCOA6 gene.
Nuclear receptor coregulators are a class of transcription coregulators that have been shown to be involved in any aspect of signaling by any member of the nuclear receptor superfamily. A comprehensive database of nuclear receptor coregulators can be found at the Nuclear Receptor Signaling Atlas website.
Vitamin D response element (VDRE) is a DNA sequence that is found in the promoter region of vitamin D regulated genes. The receptor for 1,25(OH)2D (VDR) binds to and regulates the expression of some genes.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.