Target Information

Target General Infomation
Target ID
T13726
Former ID
TTDR01073
Target Name
Retinoic acid receptor RXR-alpha
Gene Name
RXRA
Synonyms
RXRalpha; RXRA
Target Type
Successful
Disease Cutaneous T-cell lymphoma [ICD9: 202.1, 202.2; ICD10: C84.0, C84.1]
Function
Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. The high affinity ligand for RXRs is 9-cis retinoic acid. RXRA serves as a common heterodimeric partner for a number of nuclear receptors. The RXR/RAR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3'sites known as DR1-DR5. In the absence of ligand, the RXR-RAR heterodimers associate with a multiprotein complex containing transcription corepressors that induce histone acetylation, chromatin condensation and transcriptional suppression. On ligand binding, the corepressors dissociate from the receptors and associate with the coactivators leading to transcriptional activation. The RXRA/PPARA heterodimer is required for PPARA transcriptional activity on fatty acid oxidation genes such as ACOX1 and the P450 system genes.
BioChemical Class
Zinc-finger
Target Validation
T13726
UniProt ID
P19793
Sequence
MDTKHFLPLDFSTQVNSSLTSPTGRGSMAAPSLHPSLGPGIGSPGQLHSPISTLSSPING
MGPPFSVISSPMGPHSMSVPTTPTLGFSTGSPQLSSPMNPVSSSEDIKPPLGLNGVLKVP
AHPSGNMASFTKHICAICGDRSSGKHYGVYSCEGCKGFFKRTVRKDLTYTCRDNKDCLID
KRQRNRCQYCRYQKCLAMGMKREAVQEERQRGKDRNENEVESTSSANEDMPVERILEAEL
AVEPKTETYVEANMGLNPSSPNDPVTNICQAADKQLFTLVEWAKRIPHFSELPLDDQVIL
LRAGWNELLIASFSHRSIAVKDGILLATGLHVHRNSAHSAGVGAIFDRVLTELVSKMRDM
QMDKTELGCLRAIVLFNPDSKGLSNPAEVEALREKVYASLEAYCKHKYPEQPGRFAKLLL
RLPALRSIGLKCLEHLFFFKLIGDTPIDTFLMEMLEAPHQMT
Drugs and Mode of Action
Drug(s) Bexarotene Drug Info Approved Cutaneous T-cell lymphoma [536739], [539848]
Inhibitor (5BETA)-PREGNANE-3,20-DIONE Drug Info [551374]
2-chloro-5-nitro-N-phenylbenzamide Drug Info [551374]
AGN-34 Drug Info [527690]
Tributylstannanyl Drug Info [551374]
Modulator Bexarotene Drug Info [556264]
Agonist CD3254 Drug Info [526251]
methoprene acid Drug Info [533651]
phytanic acid Drug Info [534113]
[3H]9-cis-retinoic acid Drug Info [534000]
Antagonist LG100754 Drug Info [526108]
PA451 Drug Info [526387]
UVI3003 Drug Info [527278]
Pathways
KEGG Pathway PPAR signaling pathway
PI3K-Akt signaling pathway
Thyroid hormone signaling pathway
Adipocytokine signaling pathway
Non-alcoholic fatty liver disease (NAFLD)
Bile secretion
Hepatitis C
Pathways in cancer
Transcriptional misregulation in cancer
Thyroid cancer
Small cell lung cancer
Non-small cell lung cancer
PANTHER Pathway Vitamin D metabolism and pathway
Pathway Interaction Database Regulation of Androgen receptor activity
RXR and RAR heterodimerization with other nuclear receptor
Retinoic acid receptors-mediated signaling
a6b1 and a6b4 Integrin signaling
Reactome RORA activates gene expression
CLOCK,NPAS2 activates circadian gene expression
Recycling of bile acids and salts
PPARA activates gene expression
Import of palmitoyl-CoA into the mitochondrial matrix
YAP1- and WWTR1 (TAZ)-stimulated gene expression
Regulation of pyruvate dehydrogenase (PDH) complex
Endogenous sterols
Transcriptional activation of mitochondrial biogenesis
Activation of gene expression by SREBF (SREBP)
Transcriptional regulation of white adipocyte differentiation
Nuclear Receptor transcription pathway
Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha)
Circadian Clock
WikiPathways Vitamin A and Carotenoid Metabolism
NRF2 pathway
Nuclear Receptors Meta-Pathway
Farnesoid X Receptor Pathway
PPAR Alpha Pathway
Vitamin D Receptor Pathway
Pregnane X Receptor pathway
Constitutive Androstane Receptor Pathway
Liver X Receptor Pathway
Regulation of Lipid Metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha)
Transcriptional Regulation of White Adipocyte Differentiation
YAP1- and WWTR1 (TAZ)-stimulated gene expression
Activation of Gene Expression by SREBP (SREBF)
Integrated Pancreatic Cancer Pathway
Adipogenesis
Circadian Clock
Nuclear Receptors
Vitamin D Metabolism
References
Ref 536739Emerging drugs in cutaneous T cell lymphoma. Expert Opin Emerg Drugs. 2008 Jun;13(2):345-61.
Ref 539848(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 2807).
Ref 526108The rexinoid LG100754 is a novel RXR:PPARgamma agonist and decreases glucose levels in vivo. Mol Endocrinol. 2001 Aug;15(8):1360-9.
Ref 526251Co-regulator recruitment and the mechanism of retinoic acid receptor synergy. Nature. 2002 Jan 10;415(6868):187-92.
Ref 526387Novel retinoid X receptor antagonists: specific inhibition of retinoid synergism in RXR-RAR heterodimer actions. J Med Chem. 2002 Aug 1;45(16):3327-30.
Ref 527278Characterization of the interaction between retinoic acid receptor/retinoid X receptor (RAR/RXR) heterodimers and transcriptional coactivators through structural and fluorescence anisotropy studies. J Biol Chem. 2005 Jan 14;280(2):1625-33. Epub 2004 Nov 4.
Ref 527690J Med Chem. 2005 Aug 25;48(17):5383-403.Farnesoid X receptor: from structure to potential clinical applications.
Ref 533651Activation of mammalian retinoid X receptors by the insect growth regulator methoprene. Proc Natl Acad Sci U S A. 1995 Jun 20;92(13):6157-60.
Ref 534000Retinoic acid receptors and retinoid X receptors: interactions with endogenous retinoic acids. Proc Natl Acad Sci U S A. 1993 Jan 1;90(1):30-4.
Ref 534113Phytanic acid is a retinoid X receptor ligand. Eur J Biochem. 1996 Feb 15;236(1):328-33.
Ref 551374The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
Ref 556264Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.

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