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Retinoid X receptor-γ

Systematic Nomenclature: NR2B3

Family: 2B. Retinoid X receptors

Contents:
Gene and Protein Information
Previous and Unofficial Names
Database Links
Selected 3D Structures
Agonists
Antagonists
DNA Binding
Co-binding Partners
Main Co-regulators
Tissue Distribution
Physiological Consequences of Altering Gene Expression
Phenotypes, Alleles and Disease Models
References
Gene and Protein Information
Species AA Chromosomal Location Gene Symbol Gene Name Reference
Human 463 1q22-q23 RXRG retinoid X receptor, gamma 2,24
Mouse 463 1 88.1 cM Rxrg retinoid X receptor gamma 15,20-21,24
Rat 463 13q24 Rxrg retinoid X receptor gamma 3
Previous and Unofficial Names
RXRγ
NR2B3
nuclear receptor subfamily 2 group B member 3
MGC109416
RXR gamma-1
retinoic X receptor gamma-1
retinoic acid receptor RXR-gamma
retinoid X receptor gamma
Database Links
ChEMBL Target 266 (Hs), 12793 (Mm), 12391 (Rn)
DrugBank Target 780 (Hs)
Ensembl ENSG00000143171 (Hs), ENSMUSG00000015843 (Mm), ENSRNOG00000004537 (Rn)
Entrez Gene 6258 (Hs), 20183 (Mm), 83574 (Rn)
GeneCards RXRG (Hs)
GenitoUrinary Development Molecular Anatomy Project Rxrg (Mm)
HomoloGene 21373 (Hs)
Human Protein Reference Database 01579 (Hs)
InterPro P48443 (Hs), P28705 (Mm), Q5BJR8 (Rn)
KEGG Gene hsa:6258 (Hs), mmu:20183 (Mm), rno:83574 (Rn)
NURSA Receptor 2B3
OMIM 180247 (Hs)
PharmGKB Gene PA34892 (Hs)
PhosphoSitePlus P48443 (Hs), P28705 (Mm), Q5BJR8 (Rn)
RefSeq Nucleotide NM_006917 (Hs), NM_009107 (Mm), NM_001159731 (Mm), NM_031765 (Rn)
RefSeq Protein NP_008848 (Hs), NP_033133 (Mm), NP_113953 (Rn)
TreeFam ENSG00000143171 (Hs), ENSMUSG00000015843 (Mm), ENSRNOG00000004537 (Rn)
UniProt P48443 (Hs), P28705 (Mm), Q5BJR8 (Rn)
Retinoic acid, retinoid X and retinoic acid-related orphan
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  RXR-gamma - ligand-binding domain (Apostructure)
PDB Id:  2GL8
Resolution:  2.4Å
Species:  Human
References: 
Search for other structures on the PDB
Search by keyword: Retinoid X receptor-γ Search by accession number: P48443, Q5BJR8, P28705
Natural/Endogenous Ligand(s)
9-cis-retinoic acid
Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
AGN194204 ? Agonist 8.4 pKd 33
LG100268 ? Agonist 8.0 – 8.52 pIC50 4,18,30
bexarotene Hs Agonist 7.54 pIC50 5,7,30
9-cis-retinoic acid Hs Agonist 7.0 – 8.0 pIC50 1,14,18,22,24,28
View species-specific agonist tables
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
LG100754 ? Antagonist 0.79 pIC50 8,12,18
DNA Binding
Structure:  Homodimer, Heterodimer, RXR partner
HRE core sequence:  5’-AGGTCA
Response element:  DR1, DR2, DR3, DR4, DR5
DNA Binding Comments
RXR can bind to several DR elements as common heterodimerization patners 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 19,27,29
NCOA2 Co-activator No Yes Yes 19,31-32
NCOA3 Co-activator No Yes Yes 9,19,27
Tissue Distribution
muscle, brain
Species:  Mouse
Technique:  Northern, In situ, Western, Other
References:  10-11,13,23-24
Tissue Distribution Comments
RXRg displays the highest restricted expression pattern of the three RXRs.The RXRg1 isoform is expressed in brain and muscle, whereas RXRg2 is highly expressed in both cardiac and skeletal muscles. Similar expression pattern observed in the rat.
Physiological Consequences of Altering Gene Expression
Knockout mice:- are viable and fertile but show metabolic and behavorial defects.
Species:  Mouse
Tissue: 
Technique:  Knock-out by homologous recombination in embryonic stem cells
References:  6,16-17,25-26
Phenotypes, Alleles and Disease Models Mouse data from MGI

Click here to show/hide data

Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Rxrgtm1Ysa Rxrgtm1Ysa/Rxrgtm1Ysa
either: (involves: 129S2/SvPas * C57BL/6) or (involves: 129S2/SvPas * C57BL/6 * ICR)		 MGI:98216  MP:0004077 abnormal striatum morphology PMID: 10336693 
Rxrgtm2Ysa Rxrgtm2Ysa/Rxrgtm2Ysa
involves: C57BL/6 * CBA		 MGI:98216  MP:0004077 abnormal striatum morphology PMID: 10336693 
Rxrgtm1Ysa Rxrgtm1Ysa/Rxrgtm1Ysa
either: (involves: 129S2/SvPas * C57BL/6) or (involves: 129S2/SvPas * C57BL/6 * ICR)		 MGI:98216  MP:0002822 catalepsy PMID: 10336693 
Rxrgtm1Ysa Rxrgtm1Ysa/Rxrgtm1Ysa
B6.129S2-Rxrg		 MGI:98216  MP:0004037 increased muscle relaxation PMID: 10336693 
Rxrgtm1Ipc Rxrgtm1Ipc/Rxrgtm1Ipc
involves: 129S2/SvPas		 MGI:98216  MP:0002169 no abnormal phenotype detected PMID: 8799145 
Rxrgtm1Ysa Rxrgtm1Ysa/Rxrgtm1Ysa
either: (involves: 129S2/SvPas * C57BL/6) or (involves: 129S2/SvPas * C57BL/6 * ICR)		 MGI:98216  MP:0002083 premature death PMID: 10336693 

REFERENCES

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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. U.S.A., 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. Belanger, AJ; Luo, Z; Vincent, KA; Akita, GY; Cheng, SH; Gregory, RJ; Jiang, C. (2007) Hypoxia-inducible factor 1 mediates hypoxia-induced cardiomyocyte lipid accumulation by reducing the DNA binding activity of peroxisome proliferator-activated receptor alpha/retinoid X receptor. Biochem. Biophys. Res. Commun., 364 (3): 567-72. [PMID:17963722]

4. 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]

5. 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]

6. Brown, NS; Smart, A; Sharma, V; Brinkmeier, ML; Greenlee, L; Camper, SA; Jensen, DR; Eckel, RH; Krezel, W; Chambon, P; Haugen, BR. (2000) Thyroid hormone resistance and increased metabolic rate in the RXR-gamma-deficient mouse. J. Clin. Invest., 106 (1): 73-9. [PMID:10880050]

7. 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]

8. 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]

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. Chiang, MY; Misner, D; Kempermann, G; Schikorski, T; Giguère, V; Sucov, HM; Gage, FH; Stevens, CF; Evans, RM. (1998) An essential role for retinoid receptors RARbeta and RXRgamma in long-term potentiation and depression. Neuron, 21 (6): 1353-61. [PMID:9883728]

11. 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]

12. 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]

13. Haugen, BR; Brown, NS; Wood, WM; Gordon, DF; Ridgway, EC. (1997) The thyrotrope-restricted isoform of the retinoid-X receptor-gamma1 mediates 9-cis-retinoic acid suppression of thyrotropin-beta promoter activity. Mol. Endocrinol., 11 (4): 481-9. [PMID:9092800]

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. Krezel, W; Dupé, V; Mark, M; Dierich, A; Kastner, P; Chambon, P. (1996) RXR gamma null mice are apparently normal and compound RXR alpha +/-/RXR beta -/-/RXR gamma -/- mutant mice are viable. Proc. Natl. Acad. Sci. U.S.A., 93 (17): 9010-4. [PMID:8799145]

17. 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]

18. 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]

19. Laudet, V. and Gronemeyer, H. (2002) The Nuclear Receptor Facts Book. in The Nuclear Receptor Facts Book Academic Press.

20. 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]

21. 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]

22. 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]

23. Liu, Q; Linney, E. (1993) The mouse retinoid-X receptor-gamma gene: genomic organization and evidence for functional isoforms. Mol. Endocrinol., 7 (5): 651-8. [PMID:8391126]

24. 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]

25. Mark, M. and Chambon, P. (2003) Functions of RARs and RXRs in vivo: genetic dissection of the retinoid signaling pathway. Pure Appl Chem, 75: 1709-1732.

26. 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]

27. McKenna, NJ; Lanz, RB; O'Malley, BW. (1999) Nuclear receptor coregulators: cellular and molecular biology. Endocr. Rev., 20 (3): 321-44. [PMID:10368774]

28. 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]

29. 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]

30. Thacher, SM; Vasudevan, J; Chandraratna, RA. (2000) Therapeutic applications for ligands of retinoid receptors. Curr. Pharm. Des., 6 (1): 25-58. [PMID:10637371]

31. 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]

32. 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]

33. 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]

To cite this database page, please use the following:

2B. Retinoid X receptors: Retinoid X receptor-γ. Last modified on 26/03/2012. Accessed on 18/05/2013. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=612.


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