The vitamin D receptor (VDR also called the calcitriol receptor) is a member of the nuclear receptor household of transcription elements.[5] Calcitriol (the lively type of vitamin D, 1,25-(OH)2vitamin D3) binds to VDR, which then types a heterodimer with the retinoid-X receptor. The VDR heterodimer then enters the nucleus and binds to Vitamin D responsive components (VDRE) in genomic DNA. VDR binding leads to expression or transrepression of many particular gene merchandise. VDR can also be concerned in microRNA-directed put up transcriptional mechanisms.[6] In people, the vitamin D receptor is encoded by the VDR gene positioned on chromosome 12q13.11.[7]
VDR is expressed in most tissues of the physique, and regulates transcription of genes concerned in intestinal and renal transport of calcium and different minerals.[8] Glucocorticoids lower VDR expression.[8] Many forms of immune cells additionally specific VDR.[9]
Contents
Operate[edit]
The VDR gene encodes the nuclear hormone receptor for vitamin D. Essentially the most potent pure agonist is calcitriol (1,25-dihydroxycholecalciferol) and the vitamin D2 homologue ercalcitriol, 1-alpha,25-dihydroergocalciferol) can also be a robust activator. Different types of vitamin D bind with decrease affinity, as does the secondary bile acid lithocholic acid. The receptor belongs to the household of trans-acting transcriptional regulatory elements and reveals similarity of sequence to the steroid and thyroid hormone receptors.[10]
Downstream targets of this nuclear hormone receptor embrace many genes concerned in mineral metabolism.[8] The receptor regulates quite a lot of different metabolic pathways, similar to these concerned within the immune response and most cancers.[9]
Evolution[edit]
Medical relevance[edit]
Mutations on this gene are related to kind II vitamin D-resistant rickets. A single nucleotide polymorphism within the initiation codon leads to an alternate translation begin web site three codons downstream. Various splicing leads to a number of transcript variants encoding the identical protein.[11] VDR gene variants appear to affect many organic endpoints, together with these associated to osteoporosis [12]
The vitamin D receptor performs an vital function in regulating the hair cycle. Lack of VDR is related to hair loss in experimental animals.[13] Experimental research have proven that the unliganded VDR interacts with regulatory areas in cWnt (wnt signaling pathway) and sonic hedgehog goal genes and is required for the induction of those pathways throughout the postnatal hair cycle.[14] These research have revealed novel actions of the unliganded VDR in regulating the post-morphogenic hair cycle.
Researchers have targeted their efforts in elucidating the function of VDR polymorphisms in several illnesses and regular phenotypes such because the HIV-1 an infection susceptibility and development or the pure getting old course of. Essentially the most outstanding findings embrace the report of VDR variants that bolster vitamin-D motion and which can be straight correlated with AIDS development charges, that VDR affiliation with development to AIDS follows an additive mannequin [15] and the function of FokI polymorphism as a danger issue for enveloped virus an infection as revealed in a meta-analysis. [16] The significance of this gene has additionally been famous within the pure getting old course of had been 3’UTR haplotypes of the gene confirmed an affiliation with longevity. [17]
Interactions[edit] – “vitamin d receptor”
Vitamin D receptor has been proven to work together with many different elements which is able to have an effect on transcription activation:
Interactive pathway map[edit]
Click on on genes, proteins and metabolites beneath to hyperlink to respective articles. [§ 1]
References[edit]