RXR (Retinoid X Receptor)
RXR and its Brothers

Author: Gianpiero Pescarmona
Date: 05/12/2007



The retinoid X receptor is a type of nuclear receptor that is activated by 9-cis retinoic acid.
There are three retinoic X receptors (RXR): RXR-alpha, RXR-beta, and RXR-gamma, encoded by the RXRA, RXRB, RXRG genes, respectively.
RXR heterodimerizes with subfamily 1 nuclear receptors including CAR, FXR, LXR, PPAR, PXR, RAR, TR, and VDR.
As with other type II nuclear receptors, the RXR heterodimer in the absence of ligand is bound to hormone response elements complexed with corepressor protein. Binding of agonist ligands to RXR results in dissociation of corepressor and recruitment of coactivator protein, which, in turn, promotes transcription of the downstream target gene into mRNA and eventually protein.




When relevant for the function

  • Primary structure
  • Secondary structure
  • Tertiary structure
  • Quaternary structure

Protein Aminoacids Percentage (Width 700 px)


mRNA synthesis
protein synthesis

post-translational modifications


cellular localization,
biological function

Retinoic acid signaling and the evolution of chordates, 2006

RXR heterodimers are either activatory or inhibitory of protein transcription

  • Enzymes
BRENDA - The Comprehensive Enzyme Information System"URL":
KEGG Pathways"URL":
Human Metabolome Database"URL":
  • Cell signaling and Ligand transport
  • Structural proteins




1. FUNCTION: Nuclear hormone receptor. Involved in the retinoic acid response pathway. Binds 9-cis retinoic acid (9C-RA). ARF6 acts as a key regulator of the tissue-specific adipocyte P2 (aP2) enhancer (By similarity).
2. SUBUNIT: Homodimer or forms a heterodimer with peroxisome proliferator activated receptor gamma called adipocyte-specific transcription factor ARF6. Interacts with NCOA3 and NCOA6 coactivators, leading to a strong increase of transcription of target genes (By similarity). Interacts with SFPQ. Interacts with HCV core protein. Interacts with PELP1. Interacts with SENP6.
3. INTERACTION: O60869:EDF1; NbExp=1; IntAct=EBI-78598, EBI-781301; P55345:HRMT1L1; NbExp=1; IntAct=EBI-78598, EBI-78458; Q9JLI4:Ncoa6 (xeno); NbExp=1; IntAct=EBI-78598, EBI-286271;
5. TISSUE SPECIFICITY: Highly expressed in liver, also found in lung, kidney and heart.
6. DOMAIN: Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal steroid-binding domain.
7. PTM: Sumoylated on Lys-108; which negatively regulates transcriptional activity. Desumoylated specifically by SENP6.
8. SIMILARITY: Belongs to the nuclear hormone receptor family. NR2 subfamily.
9. SIMILARITY: Contains 1 nuclear receptor DNA-binding domain.
10. WEB RESOURCE: Name=Wikipedia; Note=Retinoid X receptor entry; URL=


  1. FUNCTION: Nuclear hormone receptor. Involved in the retinoic acid response pathway. Binds 9-cis retinoic acid (9C-RA).
  3. ALTERNATIVE PRODUCTS: Event=Alternative splicing; Named isoforms=2; Comment=Additional isoforms seem to exist; Name=Long; IsoId=P28702-1; Sequence=Displayed; Name=Short; IsoId=P28702-2; Sequence=Not described;
  4. TISSUE SPECIFICITY: Expressed in a variety of tumor cell lines.
  5. DOMAIN: Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal steroid-binding domain.
  6. SIMILARITY: Belongs to the nuclear hormone receptor family. NR2 subfamily.
  7. SIMILARITY: Contains 1 nuclear receptor DNA-binding domain

RXR molecular biology

Nuclear import

Nuclear Import of the Retinoid X Receptor, the Vitamin D Receptor, and Their Mutual Heterodimer 2005

RXR import to Mitochondria

RXR shortened form and mitochondrial uptake

Retinoid X receptor regulates Nur77/TR3-dependent apoptosis [corrected] by modulating its nuclear export and mitochondrial targeting. 2004

figure from: Endocrine regulation of mitochondrial activity: involvement of truncated RXRalpha and c-Erb Aalpha1 proteins. 2003

Limited Degradation of Retinoid X Receptor by Calpain 1996

Tumor necrosis factor-alpha-inducible IkappaBalpha proteolysis mediated by cytosolic m-calpain. A mechanism parallel to the ubiquitin-proteasome pathway for nuclear factor-kappab activation. 1999

Oxidative stress decreases G protein-coupled receptor kinase 2 in lymphocytes via a calpain-dependent mechanism. 1999

The parkinsonian neurotoxin rotenone activates calpain and caspase-3 leading to motoneuron degeneration in spinal cord of Lewis rats.

Using helix 3 and helix 12 mutants of VDR and
RXR, we provide functional evidence that liganded VDR allosterically modifies
RXR from an apo(unliganded)- to a holo(liganded)-receptor conformation, in the
absence of RXR ligand (with retinoid X receptor (RXR). The RXR-VDR heterodimer in contrast to other members...VDR-mediated transactivation by liganded RXR-VDR has not been fully characterized...unique facet of the intermolecular RXR-VDR interaction, where RXR actively participates...)

VDR TR3 similarities

Thyroid hormones and muscle differentiation

Decreased Retinoid X Receptor-{alpha} Protein Expression in Basal Cells Occurs in the Early Stage of Human Prostate Cancer Development 2004

Peroxisome Proliferator-Activated Receptor -β/δ, -γ Agonists and ResveratrolModulate Hypoxia Induced Changes in Nuclear Receptor Activators ofMuscle OxidativeMetabolism 2010

Polyclonal anti-RXR{alpha} (D-20) sc-553 ({Delta}N 197), anti-RXRß (C-20), anti-RXR{gamma} (Y-20), and anti-p34 cdc2 kinase (H-297) antibodies and polyclonal anti-phospho p44/p42 MAPK (ERK1/ERK2) antibody were from Santa Cruz Biotechnology, Inc. (Santa Cruz Biotechnology, CA) and Cell Signaling Technology (Beverly, MA), respectively.

RXR proliferation

Retinol RXR

Thyroid hormone resistance and increased metabolic rate in the RXR-gamma-deficient mouse. 2000

  • Abstract
    Vitamin A and retinoids affect pituitary-thyroid function through suppression of serum thyroid-stimulating hormone (TSH) levels and TSH-beta subunit gene expression. We have previously shown that retinoid X receptor-selective (RXR-selective) ligands can suppress serum TSH levels in vivo and TSH-beta promoter activity in vitro. The RXR-gamma isotype has limited tissue distribution that includes the thyrotrope cells of the anterior pituitary gland. In this study, we have performed a detailed analysis of the pituitary-thyroid function of mice lacking the gene for the RXR-gamma isotype. These mice had significantly higher serum T4 levels and TSH levels than did wild-type (WT) controls. Treatment of RXR-gamma-deficient and WT mice with T3 suppressed serum TSH and T4 levels in both groups, but RXR-gamma-deficient mice were relatively resistant to exogenous T3. RXR-gamma-deficient mice had significantly higher metabolic rates than did WT controls, suggesting that these animals have a pattern of central resistance to thyroid hormone. RXR-gamma, which is also expressed in skeletal muscle and the hypothalamus, may have a direct effect on muscle metabolism, regulation of food intake, or thyrotropin-releasing hormone levels in the hypothalamus. In conclusion, the RXR-gamma isotype appears to contribute to the regulation of serum TSH and T4 levels and to affect peripheral metabolism through regulation of the hypothalamic-pituitary-thyroid axis or through direct effects on skeletal muscle.
2012-04-29T16:37:31 - Gianpiero Pescarmona

Selenium induces RXR


RXR oxygen

RXR Hypoxia

RXR Upregulation


Calpain RXR

Coenzyme Q RXR

Cancer RXR

Cross-species global and subset gene expression profiling identifies genes involved in prostate cancer response to selenium, 2004

IGFBP3 and RXR-alpha are expressed in the prostate, induced by selenium, and downregulated in prostate cancer

Zinc RXR

RXR and cell life span

Therapeutic potential of retinoid x receptor modulators for the treatment of the metabolic syndrome.2007

  • RXR has been shown to have diverse physiological functions using RXR knockout (KO) mouse models (reviewed in. Loss of RXRα results in much more severe phenotype than the loss of either RXRβ or RXRγ. Loss of RXRα function in the mouse germ line results in embryonic lethality (E13.5–16.5) due to defects of the cardiac ventricles and placenta, as well as ocular abnormalities. Additional functions of RXRα have been identified when the receptor has been selectively deleted from specific tissues in mature animals. Loss of RXRα function in adipose tissue results in altered preadipocyte differentiation and resistance to obesity, though this is thought to be attributable to the absence of functional RXRα/PPARγ heterodimers in adipose tissue. Loss of RXRα function in skin results in multiple phenotypic characteristics such as alopecia, hair follicle degeneration, and dermal cysts, and although some of these phenotypic characteristics are similar to the loss of function of the vitamin D receptor (VDR−/−), there are abnormalities in epidermal proliferation and differentiation in the RXRα−/− model that are not accounted for in the VDR−/− model. Loss of RXRα in the liver perturbs multiple metabolic pathways mediated by LXRα, PPARα, CARβ, PXR, and FXR. Interestingly, many, but not all, of the defects in lipid metabolism in liver-specific RXRα−/− mice are similar to those in LXR−/− mice, suggesting that RXRα:LXR plays an important role in hepatic lipid metabolism. The phenotype of RXRα−/− in liver also shows similarities to PPARα−/− mice, suggesting that the phenotype in each is attributable to a loss of functional RXRα:PPARα heterodimers. Furthermore, when RXRα is absent in the liver of adult mice, the regenerative capacity of hepatocytes is impaired, and the hepatocytes have a shorter lifespan compared to wild-type animals. Absence of RXRα in prostate produces a marked alteration in the profile of secretory proteins as well as preneoplastic lesions

Selenium RXR

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