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NR1H2  -  nuclear receptor subfamily 1, group H,...

Homo sapiens

Synonyms: LXR-b, LXRB, Liver X receptor beta, NER, NER-I, ...
 
 
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Disease relevance of NR1H2

  • NER, a new member of the steroid hormone nuclear receptor (NR)-encoding gene family, was isolated from a human osteosarcoma SAOS/B10 cell line cDNA library [1].
  • The nominal associations of LXRA and LXRB alleles with obesity are interesting and should be further investigated in independent data sets [2].
  • The aims of this study were to determine: (i) whether oxysterols applied topically to the skin of mice induce differentiation in normal epidermis; (ii) whether this effect is mediated via liver X receptor-alpha and/or liver X receptor-beta; and (iii) whether oxysterols normalize epidermal morphology in an animal model of epidermal hyperplasia [3].
  • Our previous experiments have suggested that a major autosomal recessive gene and several minor genes regulate the inheritance of tonic-clonic seizures in NER [4].
  • RESULTS: After the F9 generation, 94%-98% of NER exhibited spontaneous tonic-clonic convulsions, beginning with neck and forelimb clonus, wild jumping/running, opisthotonic posturing, and evolving to tonic, then clonic convulsion, followed by postictal flaccidity [5].
 

Psychiatry related information on NR1H2

 

High impact information on NR1H2

 

Chemical compound and disease context of NR1H2

  • Biopsies from 131 women with squamous cell carcinoma of the cervix diagnosed between May 1983 and July 1986 were assayed for nuclear and "cytoplasmic" estrogen receptors (NER and CER) [11].
  • These experiments examined the effects of a high and a low dose of estradiol benzoate (EB) in enhancing lordosis behavior and correlated these effects with the retention of hypothalamic nuclear estrogen receptors (NER) in female hamsters [12].
  • Nuclear estradiol receptors (NER) were measured in human breast carcinomas by extracting nuclei with 0.6 mol/l KCl and adsorption to hydroxylapatite [13].
 

Biological context of NR1H2

  • As part of this analysis, we have assessed the NR1H2 gene on chromosome 19 and report here a modest association with the locus in sibpairs with late onset disease [6].
  • NER codes for a polypeptide of 461 amino acids which contains the conserved sequences of the DNA-binding and ligand-binding domains of typical steroid hormone NR [1].
  • The LXRA and LXRB genes were screened for polymorphisms and common single nucleotide polymorphisms genotyped in obese and nonobese women [2].
  • OBJECTIVE: LXRA and LXRB genes regulate adiposity, energy dissipation, as well as glucose and lipid homeostasis in mice [2].
  • Mitosis (NEB to NER) is twice as long in Colcemid-treated eggs as in the untreated controls [14].
 

Anatomical context of NR1H2

 

Associations of NR1H2 with chemical compounds

  • In this study, we identified the first nonoxysterol natural product that functions as a ligand for the liver X receptor (LXRalpha and LXRbeta; NR1H3, NR1H2), a NHR that acts as the receptor for oxysterols and plays a key role in regulation of cholesterol metabolism and transport as well as glucose metabolism [17].
  • The x-ray crystal structures of the human liver X receptor beta ligand binding domain complexed to sterol and nonsterol agonists revealed a perpendicular histidinetryptophan switch that holds the receptor in its active conformation [18].
  • Although no ligand was identified for NER-I, its wide distribution may indicate that this novel steroid hormone NR may play a basic role in cell function [1].
  • We have detected frequent alternative splicing of a gene that encodes NER, a protein homologous to the retinoic acid receptors, in cancer cells [19].
  • Relative mutation frequencies increased with the adduct level, with 1.3-3.6-fold higher numbers of mutations in the XP cells compared to the GM00637 cells, indicating that NER plays a significant role in the removal of these particular tamoxifen DNA adducts [20].
 

Other interactions of NR1H2

  • The present work shows that the acetyl-podocarpic dimer (APD) is a potent, selective agonist for both LXRalpha (NR1H3) and LXRbeta (NR1H2) [21].
  • Plausible positional candidate genes include NR1H2 and TULP2 [22].
  • A reciprocal analysis showed that each human receptor had one or more Fugu orthologs, excepting CAR (NR1I3) and LXRbeta (NR1H2) [23].
  • We characterize the ability of the liver X receptor (LXRalpha [NR1H3] and LXRbeta [NR1H2]) agonist, T0901317, to activate the farnesoid X receptor (FXR [NR4H4]) [24].
 

Analytical, diagnostic and therapeutic context of NR1H2

  • Recent data suggest that the nuclear transcription factors liver X receptor-alpha and liver X receptor-beta (LXRalpha and LXRbeta) limit plaque formation in animal models by modulating macrophage function [25].
  • Assignment of the human ubiquitous receptor gene (UNR) to 19q13.3 using fluorescence in situ hybridization [26].
  • When tumors were assayed for CER, nuclear estrogen receptor (NER), and cytoplasmic progesterone receptor (CPR), there were no racial differences in the proportions of tumors containing all 3 receptors, but significant variations were found in neoplasms with no receptors and in those with apparently defective receptors [27].
  • Furthermore, there was evidence of interaction between LXRA and LXRB alleles in determining body mass index [2].
  • Northern blot analysis indicates that RIP14 is expressed specifically in liver and kidney, while RIP15 is expressed in every tissue tested [28].

References

  1. NER, a new member of the gene family encoding the human steroid hormone nuclear receptor. Shinar, D.M., Endo, N., Rutledge, S.J., Vogel, R., Rodan, G.A., Schmidt, A. Gene (1994) [Pubmed]
  2. Liver X receptor gene polymorphisms and adipose tissue expression levels in obesity. Dahlman, I., Nilsson, M., Jiao, H., Hoffstedt, J., Lindgren, C.M., Humphreys, K., Kere, J., Gustafsson, J.A., Arner, P., Dahlman-Wright, K. Pharmacogenet. Genomics (2006) [Pubmed]
  3. Oxysterol stimulation of epidermal differentiation is mediated by liver X receptor-beta in murine epidermis. Kömüves, L.G., Schmuth, M., Fowler, A.J., Elias, P.M., Hanley, K., Man, M.Q., Moser, A.H., Lobaccaro, J.M., Williams, M.L., Mangelsdorf, D.J., Feingold, K.R. J. Invest. Dermatol. (2002) [Pubmed]
  4. Chromosomal mapping of genes for epilepsy in NER: a rat strain with tonic-clonic seizures. Maihara, T., Noda, A., Yamazoe, H., Voigt, B., Kitada, K., Serikawa, T. Epilepsia (2000) [Pubmed]
  5. NER rat strain: a new type of genetic model in epilepsy research. Noda, A., Hashizume, R., Maihara, T., Tomizawa, Y., Ito, Y., Inoue, M., Kobayashi, K., Asano, Y., Sasa, M., Serikawa, T. Epilepsia (1998) [Pubmed]
  6. Genetic variability at the LXR gene (NR1H2) may contribute to the risk of Alzheimer's disease. Adighibe, O., Arepalli, S., Duckworth, J., Hardy, J., Wavrant-De Vrièze, F. Neurobiol. Aging (2006) [Pubmed]
  7. International Union of Pharmacology. LXII. The NR1H and NR1I Receptors: Constitutive Androstane Receptor, Pregnene X Receptor, Farnesoid X Receptor {alpha}, Farnesoid X Receptor beta, Liver X Receptor {alpha}, Liver X Receptor beta, and Vitamin D Receptor. Moore, D.D., Kato, S., Xie, W., Mangelsdorf, D.J., Schmidt, D.R., Xiao, R., Kliewer, S.A. Pharmacol. Rev. (2006) [Pubmed]
  8. A novel regulation mechanism of DNA repair by damage-induced and RAD23-dependent stabilization of xeroderma pigmentosum group C protein. Ng, J.M., Vermeulen, W., van der Horst, G.T., Bergink, S., Sugasawa, K., Vrieling, H., Hoeijmakers, J.H. Genes Dev. (2003) [Pubmed]
  9. Nucleotide excision repair of DNA with recombinant human proteins: definition of the minimal set of factors, active forms of TFIIH, and modulation by CAK. Araújo, S.J., Tirode, F., Coin, F., Pospiech, H., Syväoja, J.E., Stucki, M., Hübscher, U., Egly, J.M., Wood, R.D. Genes Dev. (2000) [Pubmed]
  10. A role for hnRNP C1/C2 and Unr in internal initiation of translation during mitosis. Schepens, B., Tinton, S.A., Bruynooghe, Y., Parthoens, E., Haegman, M., Beyaert, R., Cornelis, S. EMBO J. (2007) [Pubmed]
  11. Nuclear and "cytoplasmic" estrogen and progesterone receptors in squamous cell carcinoma of the cervix. Darne, J., Soutter, W.P., Ginsberg, R., Sharp, F. Gynecol. Oncol. (1990) [Pubmed]
  12. Hypothalamic nuclear estrogen receptors and lordosis behavior in hamsters. Ahdieh, H.B., Siegel, H.I. Physiol. Behav. (1986) [Pubmed]
  13. Studies on nuclear estradiol receptors in human mammary carcinomas. O'Connell, M., McDonnell, L., Duffy, M.J. Clin. Chim. Acta (1982) [Pubmed]
  14. Role of spindle microtubules in the control of cell cycle timing. Sluder, G. J. Cell Biol. (1979) [Pubmed]
  15. DNA repair characteristics and mutations in the ERCC2 DNA repair and transcription gene in a trichothiodystrophy patient. Takayama, K., Danks, D.M., Salazar, E.P., Cleaver, J.E., Weber, C.A. Hum. Mutat. (1997) [Pubmed]
  16. Alteration in the choice of DNA repair pathway with increasing sequence selective DNA alkylation in the minor groove. Brooks, N., McHugh, P.J., Lee, M., Hartley, J.A. Chem. Biol. (2000) [Pubmed]
  17. A natural product ligand of the oxysterol receptor, liver X receptor. Bramlett, K.S., Houck, K.A., Borchert, K.M., Dowless, M.S., Kulanthaivel, P., Zhang, Y., Beyer, T.P., Schmidt, R., Thomas, J.S., Michael, L.F., Barr, R., Montrose, C., Eacho, P.I., Cao, G., Burris, T.P. J. Pharmacol. Exp. Ther. (2003) [Pubmed]
  18. X-ray crystal structure of the liver X receptor beta ligand binding domain: regulation by a histidine-tryptophan switch. Williams, S., Bledsoe, R.K., Collins, J.L., Boggs, S., Lambert, M.H., Miller, A.B., Moore, J., McKee, D.D., Moore, L., Nichols, J., Parks, D., Watson, M., Wisely, B., Willson, T.M. J. Biol. Chem. (2003) [Pubmed]
  19. Frequent association of alternative splicing of NER, a nuclear hormone receptor gene in cancer tissues. Saito, H., Nakatsuru, S., Inazawa, J., Nishihira, T., Park, J.G., Nakamura, Y. Oncogene (1997) [Pubmed]
  20. Mutation spectra induced by alpha-acetoxytamoxifen-DNA adducts in human DNA repair proficient and deficient (xeroderma pigmentosum complementation group A) cells. McLuckie, K.I., Crookston, R.J., Gaskell, M., Farmer, P.B., Routledge, M.N., Martin, E.A., Brown, K. Biochemistry (2005) [Pubmed]
  21. A potent synthetic LXR agonist is more effective than cholesterol loading at inducing ABCA1 mRNA and stimulating cholesterol efflux. Sparrow, C.P., Baffic, J., Lam, M.H., Lund, E.G., Adams, A.D., Fu, X., Hayes, N., Jones, A.B., Macnaul, K.L., Ondeyka, J., Singh, S., Wang, J., Zhou, G., Moller, D.E., Wright, S.D., Menke, J.G. J. Biol. Chem. (2002) [Pubmed]
  22. Genome-wide linkage analysis for severe obesity in french caucasians finds significant susceptibility locus on chromosome 19q. Bell, C.G., Benzinou, M., Siddiq, A., Lecoeur, C., Dina, C., Lemainque, A., Clément, K., Basdevant, A., Guy-Grand, B., Mein, C.A., Meyre, D., Froguel, P. Diabetes (2004) [Pubmed]
  23. The first completed genome sequence from a teleost fish (Fugu rubripes) adds significant diversity to the nuclear receptor superfamily. Maglich, J.M., Caravella, J.A., Lambert, M.H., Willson, T.M., Moore, J.T., Ramamurthy, L. Nucleic Acids Res. (2003) [Pubmed]
  24. T0901317 is a dual LXR/FXR agonist. Houck, K.A., Borchert, K.M., Hepler, C.D., Thomas, J.S., Bramlett, K.S., Michael, L.F., Burris, T.P. Mol. Genet. Metab. (2004) [Pubmed]
  25. LXR activation reduces proinflammatory cytokine expression in human CD4-positive lymphocytes. Walcher, D., Kümmel, A., Kehrle, B., Bach, H., Grüb, M., Durst, R., Hombach, V., Marx, N. Arterioscler. Thromb. Vasc. Biol. (2006) [Pubmed]
  26. Assignment of the human ubiquitous receptor gene (UNR) to 19q13.3 using fluorescence in situ hybridization. Le Beau, M.M., Song, C., Davis, E.M., Hiipakka, R.A., Kokontis, J.M., Liao, S. Genomics (1995) [Pubmed]
  27. Breast cancer prognosis in three different racial groups in relation to steroid hormone receptor status. Pegoraro, R.J., Nirmul, D., Reinach, S.G., Jordaan, J.P., Joubert, S.M. Breast Cancer Res. Treat. (1986) [Pubmed]
  28. Isolation of proteins that interact specifically with the retinoid X receptor: two novel orphan receptors. Seol, W., Choi, H.S., Moore, D.D. Mol. Endocrinol. (1995) [Pubmed]
 
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