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Target not currently curated in GtoImmuPdb
Target id: 591
Nomenclature: Retinoic acid receptor-β
Systematic Nomenclature: NR1B2
Family: 1B. Retinoic acid receptors
Gene and Protein Information  |
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| Species | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
| Human | 455 | 3p24.2 | RARB | retinoic acid receptor beta | 3,32 |
| Mouse | 482 | 14 7.08 cM | Rarb | retinoic acid receptor, beta | 32,34,53-54 |
| Rat | 291 | 15p16 | Rarb | retinoic acid receptor, beta | 32 |
| Gene and Protein Information Comments | |||||
| The 448 aa human isoform (1, a.k.a. β2) is the predominant transcript. Other alternatively spliced transcripts are described, including the 455 aa isoform 3 (a.k.a. β1; NP_001277145). | |||||
| Previous and Unofficial Names |
| HAP | HBV-activated protein | RAR beta 2 | retinoic acid receptor |
| Database Links |
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| Alphafold | P10826 (Hs), P22605 (Mm), D3ZFD9 (Rn) |
| CATH/Gene3D | 3.30.50.10 |
| ChEMBL Target | CHEMBL2008 (Hs), CHEMBL3266 (Mm) |
| DrugBank Target | P10826 (Hs) |
| Ensembl Gene | ENSG00000077092 (Hs), ENSMUSG00000017491 (Mm), ENSRNOG00000024061 (Rn) |
| Entrez Gene | 5915 (Hs), 218772 (Mm), 24706 (Rn) |
| Human Protein Atlas | ENSG00000077092 (Hs) |
| KEGG Gene | hsa:5915 (Hs), mmu:218772 (Mm), rno:24706 (Rn) |
| OMIM | 180220 (Hs) |
| Orphanet | ORPHA368114 (Hs) |
| Pharos | P10826 (Hs) |
| RefSeq Nucleotide | NM_016152 (Hs), NM_011243 (Mm), NM_031529 (Rn) |
| RefSeq Protein | NP_000956 (Hs), NP_057236 (Hs), NP_035373 (Mm), NP_113717 (Rn) |
| SynPHARM |
79006 (in complex with tretinoin) 6287 (in complex with tretinoin) 6285 (in complex with TTNPB) |
| UniProtKB | P10826 (Hs), P22605 (Mm), D3ZFD9 (Rn) |
| Wikipedia | RARB (Hs) |
| Selected 3D Structures |
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| Natural/Endogenous Ligands |
| tretinoin |
Download all structure-activity data for this target as a CSV file 
| Agonists |
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| Agonist Comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| All-trans-retinoic acid is the most potent endogenous retinoid. The existence of 9-cis retinoic acid as a natural bioactive retinoid remains to be established. Synthetic compounds (reported above) are not metabolized by CYP26. BMS641 is a partial RARβ-selective agonist. However no fully RARβ-selective agonist has been reported so far. Although tazarotene has high affinity for all retinoic acid receptor isoforms, it has roughly 5-8 times higher affinity for the β isoform [6]. Adapalene is selective for the β and γ RARs over the α isoform [5]. |
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| Antagonists |
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| To date, no pure RARβ-selective antagonist has been reported. Both AGN193109 and BMS493 inverse agonists can induce corepressor association with RARβ instead of RARα. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DNA Binding |
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| DNA Binding Comments | |||||||
| Transient transfection using a reporter gene and EMSA have shown that RXR-RARβ heterodimers bind to a DR5 element. | |||||||
| Co-binding Partners |
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| Name | Interaction | Effect | Reference |
| AP1 | Functional | RARb inhibits AP-1 driven transactivation | 36 |
| Main Co-regulators |
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| Name | Activity | Specific | Ligand dependent | AF-2 dependent | Comments | References |
| NCOA1 | Co-activator | No | Yes | Yes | A member of the p160 family | 11,37 |
| MED1 | Co-activator | No | Yes | Yes | A member of the DRIP/TRAP/SMCC complex | 25,33,39,52 |
| NCOA3 | Co-activator | No | Yes | Yes | A member of the p160 family | 7,11,26 |
| NCOA2 | Co-activator | No | Yes | Yes | A member of the p160 family | 12,24,46 |
| Tissue Distribution
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| Tissue Distribution Comments | ||||||||||
| Similar distribution patterns are seen in the mouse and rat. | ||||||||||
| Physiological Consequences of Altering Gene Expression
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| Physiological Consequences of Altering Gene Expression Comments | ||||||||||
| Note that the specific RARβ1/β3 null mutants are apparently normal, and the specific RARβ2/β4 null mutants exhibited persistence and hyperplasia of the primary vitreous body. | ||||||||||
| Phenotypes, Alleles and Disease Models
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Mouse data from MGI | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Clinically-Relevant Mutations and Pathophysiology
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| Biologically Significant Variants
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| General Comments |
| Using F9 RARβ2 null cells, some genes have been identified that require RARβ2 for their regulation by ATRA in F9 cells [27,55]. In contrast to RARα, unliganded RARβ poorly interacts with both NCoR and SMRT corepressors. |
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2. Bernard BA, Bernardon JM, Delescluse C, Martin B, Lenoir MC, Maignan J, Charpentier B, Pilgrim WR, Reichert U, Shroot B. (1992) Identification of synthetic retinoids with selectivity for human nuclear retinoic acid receptor gamma. Biochem Biophys Res Commun, 186 (2): 977-83. [PMID:1323296]
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4. Castillo L, Milano G, Santini J, Demard F, Pierrefite V. (1997) Analysis of retinoic acid receptor beta expression in normal and malignant laryngeal mucosa by a sensitive and routine applicable reverse transcription-polymerase chain reaction enzyme-linked immunosorbent assay method. Clin Cancer Res, 3 (11): 2137-42. [PMID:9815607]
5. Charpentier B, Bernardon JM, Eustache J, Millois C, Martin B, Michel S, Shroot B. (1995) Synthesis, structure-affinity relationships, and biological activities of ligands binding to retinoic acid receptor subtypes. J Med Chem, 38 (26): 4993-5006. [PMID:8544175]
6. Charton J, Deprez-Poulain R, Hennuyer N, Tailleux A, Staels B, Deprez B. (2009) Novel non-carboxylic acid retinoids: 1,2,4-oxadiazol-5-one derivatives. Bioorg Med Chem Lett, 19 (2): 489-92. [PMID:19058965]
7. Chen H, Lin RJ, Schiltz RL, Chakravarti D, Nash A, Nagy L, Privalsky ML, Nakatani Y, Evans RM. (1997) Nuclear receptor coactivator ACTR is a novel histone acetyltransferase and forms a multimeric activation complex with P/CAF and CBP/p300. Cell, 90 (3): 569-80. [PMID:9267036]
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9. Dollé P, Ruberte E, Kastner P, Petkovich M, Stoner CM, Gudas LJ, Chambon P. (1989) Differential expression of genes encoding alpha, beta and gamma retinoic acid receptors and CRABP in the developing limbs of the mouse. Nature, 342 (6250): 702-5. [PMID:2556642]
10. Dollé P, Ruberte E, Leroy P, Morriss-Kay G, Chambon P. (1990) Retinoic acid receptors and cellular retinoid binding proteins. I. A systematic study of their differential pattern of transcription during mouse organogenesis. Development, 110 (4): 1133-51. [PMID:1966045]
11. Farboud B, Hauksdottir H, Wu Y, Privalsky ML. (2003) Isotype-restricted corepressor recruitment: a constitutively closed helix 12 conformation in retinoic acid receptors beta and gamma interferes with corepressor recruitment and prevents transcriptional repression. Mol Cell Biol, 23 (8): 2844-58. [PMID:12665583]
12. Germain P, Iyer J, Zechel C, Gronemeyer H. (2002) Co-regulator recruitment and the mechanism of retinoic acid receptor synergy. Nature, 415 (6868): 187-92. [PMID:11805839]
13. Germain P, Kammerer S, Pérez E, Peluso-Iltis C, Tortolani D, Zusi FC, Starrett J, Lapointe P, Daris JP, Marinier A, de Lera AR, Rochel N, Gronemeyer H. (2004) Rational design of RAR-selective ligands revealed by RARbeta crystal stucture. EMBO Rep, 5 (9): 877-82. [PMID:15319780]
14. Ghyselinck NB, Dupé V, Dierich A, Messaddeq N, Garnier JM, Rochette-Egly C, Chambon P, Mark M. (1997) Role of the retinoic acid receptor beta (RARbeta) during mouse development. Int J Dev Biol, 41 (3): 425-47. [PMID:9240560]
15. Goncalves MB, Clarke E, Jarvis CI, Barret Kalindjian S, Pitcher T, Grist J, Hobbs C, Carlstedt T, Jack J, Brown JT et al.. (2019) Discovery and lead optimisation of a potent, selective and orally bioavailable RARβ agonist for the potential treatment of nerve injury. Bioorg Med Chem Lett, 29 (8): 995-1000. [PMID:30792038]
16. Grondona JM, Kastner P, Gansmuller A, Décimo D, Chambon P, Mark M. (1996) Retinal dysplasia and degeneration in RARbeta2/RARgamma2 compound mutant mice. Development, 122 (7): 2173-88. [PMID:8681798]
17. Haq R, Pfahl M, Chytil F. (1991) Retinoic acid affects the expression of nuclear retinoic acid receptors in tissues of retinol-deficient rats. Proc Natl Acad Sci USA, 88 (18): 8272-6. [PMID:1654565]
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19. Klaholz BP, Mitschler A, Moras D. (2000) Structural basis for isotype selectivity of the human retinoic acid nuclear receptor. J Mol Biol, 302 (1): 155-70. [PMID:10964567]
20. Klein ES, Pino ME, Johnson AT, Davies PJ, Nagpal S, Thacher SM, Krasinski G, Chandraratna RA. (1996) Identification and functional separation of retinoic acid receptor neutral antagonists and inverse agonists. J Biol Chem, 271 (37): 22692-6. [PMID:8798442]
21. Klein ES, Wang JW, Khalifa B, Gavigan SA, Chandraratna RA. (2000) Recruitment of nuclear receptor corepressor and coactivator to the retinoic acid receptor by retinoid ligands. Influence of DNA-heterodimer interactions. J Biol Chem, 275 (25): 19401-8. [PMID:10777502]
22. Krezel W, Ghyselinck N, Samad TA, Dupé V, Kastner P, Borrelli E, Chambon P. (1998) Impaired locomotion and dopamine signaling in retinoid receptor mutant mice. Science, 279 (5352): 863-7. [PMID:9452386]
23. Krust A, Kastner P, Petkovich M, Zelent A, Chambon P. (1989) A third human retinoic acid receptor, hRAR-gamma. Proc Natl Acad Sci USA, 86 (14): 5310-4. [PMID:2546152]
24. Laudet V, Gronemeyer H. (2002) The Nuclear Receptor Facts Book. In The Nuclear Receptor Facts Book. (Academic Press) .
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27. Li R, Faria TN, Boehm M, Nabel EG, Gudas LJ. (2004) Retinoic acid causes cell growth arrest and an increase in p27 in F9 wild type but not in F9 retinoic acid receptor beta2 knockout cells. Exp Cell Res, 294 (1): 290-300. [PMID:14980522]
28. Lund BW, Knapp AE, Piu F, Gauthier NK, Begtrup M, Hacksell U, Olsson R. (2009) Design, synthesis, and structure-activity analysis of isoform-selective retinoic acid receptor beta ligands. J Med Chem, 52 (6): 1540-5. [PMID:19239230]
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30. Mark M, Chambon P. (2003) Functions of RARs and RXRs in vivo: genetic dissection of the retinoid signaling pathway. Pure Appl Chem, 75: 1709-1732.
31. Mark M, Ghyselinck NB, Chambon P. (2006) Function of retinoid nuclear receptors: lessons from genetic and pharmacological dissections of the retinoic acid signaling pathway during mouse embryogenesis. Annu Rev Pharmacol Toxicol, 46: 451-80. [PMID:16402912]
32. Mattei MG, Rivière M, Krust A, Ingvarsson S, Vennström B, Islam MQ, Levan G, Kautner P, Zelent A, Chambon P. (1991) Chromosomal assignment of retinoic acid receptor (RAR) genes in the human, mouse, and rat genomes. Genomics, 10 (4): 1061-9. [PMID:1655630]
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34. Nagpal S, Zelent A, Chambon P. (1992) RAR-beta 4, a retinoic acid receptor isoform is generated from RAR-beta 2 by alternative splicing and usage of a CUG initiator codon. Proc Natl Acad Sci USA, 89 (7): 2718-22. [PMID:1313565]
35. Nagy L, Thomázy VA, Shipley GL, Fésüs L, Lamph W, Heyman RA, Chandraratna RA, Davies PJ. (1995) Activation of retinoid X receptors induces apoptosis in HL-60 cell lines. Mol Cell Biol, 15 (7): 3540-51. [PMID:7791761]
36. Nicholson RC, Mader S, Nagpal S, Leid M, Rochette-Egly C, Chambon P. (1990) Negative regulation of the rat stromelysin gene promoter by retinoic acid is mediated by an AP1 binding site. EMBO J, 9 (13): 4443-54. [PMID:2176152]
37. Oñate SA, Tsai SY, Tsai MJ, O'Malley BW. (1995) Sequence and characterization of a coactivator for the steroid hormone receptor superfamily. Science, 270 (5240): 1354-7. [PMID:7481822]
38. Picard E, Seguin C, Monhoven N, Rochette-Egly C, Siat J, Borrelly J, Martinet Y, Martinet N, Vignaud JM. (1999) Expression of retinoid receptor genes and proteins in non-small-cell lung cancer. J Natl Cancer Inst, 91 (12): 1059-66. [PMID:10379969]
39. Pogenberg V, Guichou JF, Vivat-Hannah V, Kammerer S, Pérez E, Germain P, de Lera AR, Gronemeyer H, Royer CA, Bourguet W. (2005) Characterization 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, 280 (2): 1625-33. [PMID:15528208]
40. Qiu H, Zhang W, El-Naggar AK, Lippman SM, Lin P, Lotan R, Xu XC. (1999) Loss of retinoic acid receptor-beta expression is an early event during esophageal carcinogenesis. Am J Pathol, 155 (5): 1519-23. [PMID:10550308]
41. Ruberte E, Dolle P, Chambon P, Morriss-Kay G. (1991) Retinoic acid receptors and cellular retinoid binding proteins. II. Their differential pattern of transcription during early morphogenesis in mouse embryos. Development, 111 (1): 45-60. [PMID:1849812]
42. Ruberte E, Dolle P, Krust A, Zelent A, Morriss-Kay G, Chambon P. (1990) Specific spatial and temporal distribution of retinoic acid receptor gamma transcripts during mouse embryogenesis. Development, 108 (2): 213-22. [PMID:2161730]
43. Thacher SM, Vasudevan J, Chandraratna RA. (2000) Therapeutic applications for ligands of retinoid receptors. Curr Pharm Des, 6 (1): 25-58. [PMID:10637371]
44. Thoreau E, Arlabosse JM, Bouix-Peter C, Chambon S, Chantalat L, Daver S, Dumais L, Duvert G, Feret A, Ouvry G et al.. (2018) Structure-based design of Trifarotene (CD5789), a potent and selective RARγ agonist for the treatment of acne. Bioorg Med Chem Lett, 28 (10): 1736-1741. [PMID:29706423]
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1B. Retinoic acid receptors: Retinoic acid receptor-β. Last modified on 10/07/2023. Accessed on 18/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=591.
