Target General Infomation
Target ID
T94085
Former ID
TTDS00073
Target Name
Retinoic acid receptor alpha
Gene Name
RARA
Synonyms
RAR alpha; RAR-alpha; RARA
Target Type
Clinical Trial
Disease Alzheimer disease [ICD9: 331; ICD10: G30]
Acquired immune deficiency syndrome [ICD9: 42; ICD10: B20]
Colorectal cancer [ICD9: 153, 154; ICD10: C18-C21]
Solid tumours [ICD9: 140-199, 210-229; ICD10: C00-D48]
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 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 associatewith 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. RARA plays an essential role in the regulation of retinoic acid-induced germ cell development during spermatogenesis. Has a role in the survival of early spermatocytes at the beginning prophase of meiosis. In Sertoli cells, may promote the survival and development of early meiotic prophase spermatocytes. In concert with RARG, required for skeletal growth, matrix homeostasis and growth plate function (By similarity). Regulates expression of target genes in a ligand- dependent manner by recruiting chromatin complexes containing KMT2E/MLL5. Mediates retinoic acid-induced granulopoiesis.
BioChemical Class
Nuclear hormone receptor
Target Validation
T94085
UniProt ID
Sequence
MASNSSSCPTPGGGHLNGYPVPPYAFFFPPMLGGLSPPGALTTLQHQLPVSGYSTPSPAT
IETQSSSSEEIVPSPPSPPPLPRIYKPCFVCQDKSSGYHYGVSACEGCKGFFRRSIQKNM
VYTCHRDKNCIINKVTRNRCQYCRLQKCFEVGMSKESVRNDRNKKKKEVPKPECSESYTL
TPEVGELIEKVRKAHQETFPALCQLGKYTTNNSSEQRVSLDIDLWDKFSELSTKCIIKTV
EFAKQLPGFTTLTIADQITLLKAACLDILILRICTRYTPEQDTMTFSDGLTLNRTQMHNA
GFGPLTDLVFAFANQLLPLEMDDAETGLLSAICLICGDRQDLEQPDRVDMLQEPLLEALK
VYVRKRRPSRPHMFPKMLMKITDLRSISAKGAERVITLKMEIPGSMPPLIQEMLENSEGL
DTLSGQPGGGGRDGGGLAPPPGSCSPSLSPSSNRSSPATHSP
Drugs and Mode of Action
Drug(s) Tamibarotene Drug Info Phase 2/3 Alzheimer disease [529087], [539714]
IRX-5183 Drug Info Discontinued in Phase 2 Solid tumours [547464]
LG100268 Drug Info Discontinued in Phase 1 Acquired immune deficiency syndrome [539849], [546896]
Antagonist AGN193109 Drug Info [525680]
BMS614 Drug Info [526251]
Ro 41-5253 Drug Info [526743]
Agonist AGN193836 Drug Info [526437]
BMS753 Drug Info [525545]
CD666 Drug Info [526744]
IRX-5183 Drug Info [526923], [529087]
LG100268 Drug Info [537277]
Ro 40-6055 Drug Info [528094]
Ro-40-0655 Drug Info [529087]
[3H]9-cis-retinoic acid Drug Info [534000]
Modulator Tamibarotene Drug Info [531992]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
DRM DRM Info
Pathways
KEGG Pathway Pathways in cancer
Transcriptional misregulation in cancer
Acute myeloid leukemia
Pathway Interaction Database Retinoic acid receptors-mediated signaling
Reactome Nuclear Receptor transcription pathway
WikiPathways Vitamin A and Carotenoid Metabolism
Nuclear Receptors in Lipid Metabolism and Toxicity
Integrated Pancreatic Cancer Pathway
Adipogenesis
Nuclear Receptors
References
Ref 529087Tamibarotene. Drugs Today (Barc). 2007 Aug;43(8):563-8.
Ref 539714(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: 2648).
Ref 539849(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: 2808).
Ref 546896Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800010920)
Ref 547464Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800016603)
Ref 525545Structural basis for engineering of retinoic acid receptor isotype-selective agonists and antagonists. Chem Biol. 1999 Aug;6(8):519-29.
Ref 525680Therapeutic applications for ligands of retinoid receptors. Curr Pharm Des. 2000 Jan;6(1):25-58.
Ref 526251Co-regulator recruitment and the mechanism of retinoic acid receptor synergy. Nature. 2002 Jan 10;415(6868):187-92.
Ref 526437Bioorg Med Chem Lett. 2002 Nov 4;12(21):3145-8.Synthesis and biological activity of retinoic acid receptor-alpha specific amides.
Ref 526743A retinoic acid receptor alpha antagonist selectively counteracts retinoic acid effects. Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):7129-33.
Ref 526744Identification of synthetic retinoids with selectivity for human nuclear retinoic acid receptor gamma. Biochem Biophys Res Commun. 1992 Jul 31;186(2):977-83.
Ref 526923Retinoic acid receptor alpha and retinoid X receptor specific agonists reduce renal injury in established chronic glomerulonephritis of the rat. J Mol Med (Berl). 2004 Feb;82(2):116-25. Epub 2004 Jan 8.
Ref 528094Selective high affinity retinoic acid receptor alpha or beta-gamma ligands. Mol Pharmacol. 1991 Oct;40(4):556-62.
Ref 529087Tamibarotene. Drugs Today (Barc). 2007 Aug;43(8):563-8.
Ref 531992Tamibarotene: a candidate retinoid drug for Alzheimer's disease. Biol Pharm Bull. 2012;35(8):1206-12.
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 537277Placental steroidogenesis in rats is independent of signaling pathways induced by retinoic acids. Gen Comp Endocrinol. 2009 Sep 15;163(3):285-91. Epub 2009 May 3.

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