Top ▲
Target not currently curated in GtoImmuPdb
Target id: 611
Nomenclature: Retinoid X receptor-β
Systematic Nomenclature: NR2B2
Family: 2B. Retinoid X receptors
Gene and Protein Information  |
|||||
| Species | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
| Human | 533 | 6p21.32 | RXRB | retinoid X receptor beta | 2,19 |
| Mouse | 520 | 17 17.98 cM | Rxrb | retinoid X receptor beta | 12,15,18-19,21 |
| Rat | 458 | 20p12 | Rxrb | retinoid X receptor beta | 35 |
| Previous and Unofficial Names |
| RXRβ | nuclear receptor subfamily 2 group B member 2 | nuclear receptor co-regulator 1 | RCoR-1 | retinoid X receptor, beta |
| Database Links |
|
| Alphafold | P28702 (Hs), P28704 (Mm), P49743 (Rn) |
| CATH/Gene3D | 3.30.50.10 |
| ChEMBL Target | CHEMBL1870 (Hs), CHEMBL4047 (Mm), CHEMBL2805 (Rn) |
| DrugBank Target | P28702 (Hs) |
| Ensembl Gene | ENSG00000204231 (Hs), ENSMUSG00000039656 (Mm), ENSRNOG00000000464 (Rn) |
| Entrez Gene | 6257 (Hs), 20182 (Mm), 361801 (Rn) |
| Human Protein Atlas | ENSG00000204231 (Hs) |
| KEGG Gene | hsa:6257 (Hs), mmu:20182 (Mm), rno:361801 (Rn) |
| OMIM | 180246 (Hs) |
| Pharos | P28702 (Hs) |
| RefSeq Nucleotide | NM_021976 (Hs), NM_001205216 (Mm), NM_001205214 (Mm), NM_011306 (Mm), NM_001205215 (Mm), NM_206849 (Rn) |
| RefSeq Protein | NP_068811 (Hs), NP_035436 (Mm), NP_996731 (Rn) |
| UniProtKB | P28702 (Hs), P28704 (Mm), P49743 (Rn) |
| Wikipedia | RXRB (Hs) |
| Selected 3D Structures |
|||||||||||||
|
|
||||||||||||
| Natural/Endogenous Ligands |
| alitretinoin |
Download all structure-activity data for this target as a CSV file 
| Agonists |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| View species-specific agonist tables | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Antagonists |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DNA Binding |
|||||||
|
|||||||
| DNA Binding Comments | |||||||
| RXR can bind to several DR elements as common heterodimerization partners for members of the subfamily 1 of nuclear receptors. In direct repeats, RXR generally occupies the 5’-element. RXR can also form RXR-RXR homodimers that bind to DR1. | |||||||
| Name | Interaction | Effect | Reference |
| Co-binding Partners Comments | |||
| Binding partners are the same as RXRα | |||
| Main Co-regulators |
||||||
| Name | Activity | Specific | Ligand dependent | AF-2 dependent | Comments | References |
| NCOA1 | Co-activator | No | Yes | Yes | 17,25,28 | |
| NCOA2 | Co-activator | No | Yes | Yes | 17,32-33 | |
| NCOA3 | Co-activator | No | Yes | Yes | 9,17,25 | |
| Tissue Distribution
|
||||||||
|
||||||||
| Tissue Distribution Comments | ||||||||
| Similar expression patterns are observed in rodents and other mammals. | ||||||||
| Functional Assays
|
||||||||||
|
||||||||||
|
| Physiological Consequences of Altering Gene Expression
|
||||||||||
|
| Phenotypes, Alleles and Disease Models
|
Mouse data from MGI | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| General Comments |
| Through its heterodimeric interaction with many other nuclear receptors, RXRβ may play a role in a wide variety of diseases as well as in the control of multiple target genes. |
1. Allenby G, Bocquel MT, Saunders M, Kazmer S, Speck J, Rosenberger M, Lovey A, Kastner P, Grippo JF, Chambon P. (1993) Retinoic acid receptors and retinoid X receptors: interactions with endogenous retinoic acids. Proc Natl Acad Sci USA, 90 (1): 30-4. [PMID:8380496]
2. Almasan A, Mangelsdorf DJ, Ong ES, Wahl GM, Evans RM. (1994) Chromosomal localization of the human retinoid X receptors. Genomics, 20 (3): 397-403. [PMID:8034312]
3. Boehm MF, McClurg MR, Pathirana C, Mangelsdorf D, White SK, Hebert J, Winn D, Goldman ME, Heyman RA. (1994) Synthesis of high specific activity [3H]-9-cis-retinoic acid and its application for identifying retinoids with unusual binding properties. J Med Chem, 37 (3): 408-14. [PMID:8308867]
4. Boehm MF, Zhang L, Badea BA, White SK, Mais DE, Berger E, Suto CM, Goldman ME, Heyman RA. (1994) Synthesis and structure-activity relationships of novel retinoid X receptor-selective retinoids. J Med Chem, 37 (18): 2930-41. [PMID:8071941]
5. Canan Koch SS, Dardashti LJ, Cesario RM, Croston GE, Boehm MF, Heyman RA, Nadzan AM. (1999) Synthesis of retinoid X receptor-specific ligands that are potent inducers of adipogenesis in 3T3-L1 cells. J Med Chem, 42 (4): 742-50. [PMID:10052980]
6. Cesario RM, Klausing K, Razzaghi H, Crombie D, Rungta D, Heyman RA, Lala DS. (2001) The rexinoid LG100754 is a novel RXR:PPARgamma agonist and decreases glucose levels in vivo. Mol Endocrinol, 15 (8): 1360-9. [PMID:11463859]
7. Chawla A, Lazar MA. (1993) Induction of Rev-ErbA alpha, an orphan receptor encoded on the opposite strand of the alpha-thyroid hormone receptor gene, during adipocyte differentiation. J Biol Chem, 268 (22): 16265-9. [PMID:8344913]
8. Chawla A, Lazar MA. (1994) Peroxisome proliferator and retinoid signaling pathways co-regulate preadipocyte phenotype and survival. Proc Natl Acad Sci USA, 91 (5): 1786-90. [PMID:8127882]
9. 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]
10. Dollé P, Fraulob V, Kastner P, Chambon P. (1994) Developmental expression of murine retinoid X receptor (RXR) genes. Mech Dev, 45 (2): 91-104. [PMID:8199055]
11. Forman BM. (2002) The antidiabetic agent LG100754 sensitizes cells to low concentrations of peroxisome proliferator-activated receptor gamma ligands. J Biol Chem, 277 (15): 12503-6. [PMID:11877384]
12. Hamada K, Gleason SL, Levi BZ, Hirschfeld S, Appella E, Ozato K. (1989) H-2RIIBP, a member of the nuclear hormone receptor superfamily that binds to both the regulatory element of major histocompatibility class I genes and the estrogen response element. Proc Natl Acad Sci USA, 86 (21): 8289-93. [PMID:2554307]
13. Heitel P, Gellrich L, Kalinowsky L, Heering J, Kaiser A, Ohrndorf J, Proschak E, Merk D. (2019) Computer-Assisted Discovery and Structural Optimization of a Novel Retinoid X Receptor Agonist Chemotype. ACS Med Chem Lett, 10 (2): 203-208. DOI: 10.1021/acsmedchemlett.8b00551 [PMID:30783504]
14. Heyman RA, Mangelsdorf DJ, Dyck JA, Stein RB, Eichele G, Evans RM, Thaller C. (1992) 9-cis retinoic acid is a high affinity ligand for the retinoid X receptor. Cell, 68 (2): 397-406. [PMID:1310260]
15. Hoopes CW, Taketo M, Ozato K, Liu Q, Howard TA, Linney E, Seldin MF. (1992) Mapping of the mouse Rxr loci encoding nuclear retinoid X receptors RXR alpha, RXR beta, and RXR gamma. Genomics, 14 (3): 611-7. [PMID:1358808]
16. Lala DS, Mukherjee R, Schulman IG, Koch SS, Dardashti LJ, Nadzan AM, Croston GE, Evans RM, Heyman RA. (1996) Activation of specific RXR heterodimers by an antagonist of RXR homodimers. Nature, 383 (6599): 450-3. [PMID:8837780]
17. Laudet V, Gronemeyer H. (2002) The Nuclear Receptor Facts Book. In The Nuclear Receptor Facts Book. (Academic Press) .
18. Leid M, Kastner P, Chambon P. (1992) Multiplicity generates diversity in the retinoic acid signalling pathways. Trends Biochem Sci, 17 (10): 427-33. [PMID:1333659]
19. Leid M, Kastner P, Lyons R, Nakshatri H, Saunders M, Zacharewski T, Chen JY, Staub A, Garnier JM, Mader S. (1992) Purification, cloning, and RXR identity of the HeLa cell factor with which RAR or TR heterodimerizes to bind target sequences efficiently. Cell, 68 (2): 377-95. [PMID:1310259]
20. Levin AA, Sturzenbecker LJ, Kazmer S, Bosakowski T, Huselton C, Allenby G, Speck J, Kratzeisen C, Rosenberger M, Lovey A. (1992) 9-cis retinoic acid stereoisomer binds and activates the nuclear receptor RXR alpha. Nature, 355 (6358): 359-61. [PMID:1309942]
21. Mangelsdorf DJ, Borgmeyer U, Heyman RA, Zhou JY, Ong ES, Oro AE, Kakizuka A, Evans RM. (1992) Characterization of three RXR genes that mediate the action of 9-cis retinoic acid. Genes Dev, 6 (3): 329-44. [PMID:1312497]
22. 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.
23. 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]
24. Mascrez B, Ghyselinck NB, Watanabe M, Annicotte JS, Chambon P, Auwerx J, Mark M. (2004) Ligand-dependent contribution of RXRbeta to cholesterol homeostasis in Sertoli cells. EMBO Rep, 5 (3): 285-90. [PMID:14993927]
25. McKenna NJ, Lanz RB, O'Malley BW. (1999) Nuclear receptor coregulators: cellular and molecular biology. Endocr Rev, 20 (3): 321-44. [PMID:10368774]
26. Monczak Y, Trudel M, Lamph WW, Miller WH. (1997) Induction of apoptosis without differentiation by retinoic acid in PLB-985 cells requires the activation of both RAR and RXR. Blood, 90 (9): 3345-55. [PMID:9345016]
27. 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]
28. 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]
29. Pérez Santín E, Germain P, Quillard F, Khanwalkar H, Rodríguez-Barrios F, Gronemeyer H, de Lera AR, Bourguet W. (2009) Modulating retinoid X receptor with a series of (E)-3-[4-hydroxy-3-(3-alkoxy-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)phenyl]acrylic acids and their 4-alkoxy isomers. J Med Chem, 52 (10): 3150-8. [PMID:19408900]
30. Svensson S, Ostberg T, Jacobsson M, Norström C, Stefansson K, Hallén D, Johansson IC, Zachrisson K, Ogg D, Jendeberg L. (2003) Crystal structure of the heterodimeric complex of LXRalpha and RXRbeta ligand-binding domains in a fully agonistic conformation. EMBO J, 22 (18): 4625-33. [PMID:12970175]
31. Thacher SM, Vasudevan J, Chandraratna RA. (2000) Therapeutic applications for ligands of retinoid receptors. Curr Pharm Des, 6 (1): 25-58. [PMID:10637371]
32. Voegel JJ, Heine MJ, Tini M, Vivat V, Chambon P, Gronemeyer H. (1998) The coactivator TIF2 contains three nuclear receptor-binding motifs and mediates transactivation through CBP binding-dependent and -independent pathways. EMBO J, 17 (2): 507-19. [PMID:9430642]
33. Voegel JJ, Heine MJ, Zechel C, Chambon P, Gronemeyer H. (1996) TIF2, a 160 kDa transcriptional mediator for the ligand-dependent activation function AF-2 of nuclear receptors. EMBO J, 15 (14): 3667-75. [PMID:8670870]
34. Vuligonda V, Thacher SM, Chandraratna RA. (2001) Enantioselective syntheses of potent retinoid X receptor ligands: differential biological activities of individual antipodes. J Med Chem, 44 (14): 2298-303. [PMID:11428923]
35. Yu VC, Delsert C, Andersen B, Holloway JM, Devary OV, Näär AM, Kim SY, Boutin JM, Glass CK, Rosenfeld MG. (1991) RXR beta: a coregulator that enhances binding of retinoic acid, thyroid hormone, and vitamin D receptors to their cognate response elements. Cell, 67 (6): 1251-66. [PMID:1662118]
2B. Retinoid X receptors: Retinoid X receptor-β. Last modified on 16/01/2019. Accessed on 10/10/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=611.
