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Gene Review

NR1D2  -  nuclear receptor subfamily 1, group D,...

Homo sapiens

Synonyms: BD73, EAR-1R, EAR-1r, HZF2, Hs.37288, ...
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Disease relevance of NR1D2

  • Cardiac ischemia (RR= 1.8; 95% CI=1.0 to 3.4) and an increased RVR (RR=1.7; 95% CI=0.9 to 3.4) tended to increase the risk of weaning failure [1].
  • Unilateral renal injury, whether caused by ureteral obstruction or ischemia, is followed by an increase in RVR, a decrease in RBF, and eventual tubular atrophy [2].

High impact information on NR1D2

  • Peripheral alpha antagonists not only preserve renal hemodynamics, but decrease RVR and maintain renal perfusion autoregulation in the face of decreased systemic perfusion pressures [3].
  • ROR alpha1 and RVR are orphan members of the superfamily of nuclear hormone receptors which constitutively activate and repress, respectively, gene transcription by binding to a common DNA sequence [4].
  • Moreover, Northern blot analysis demonstrated a direct modulation of an exogenously introduced N-myc gene by ROR alpha1 and RVR in COS-1 cells [4].
  • Yet for each picomolar increment in plasma ANP during immersion, the corresponding increases in urinary excretion of cyclic guanosine monophosphate (26 vs. 279 pmol/min) and sodium (9 vs. 47 mumol/min) and the reciprocal lowering of RVR (0.7 vs. 1.9 U) were blunted in the diabetic versus control group [5].
  • With liberal sodium, no differences in blood pressure were detected, whereas angiotensin I induced a higher response of ERPF ( DD 40+/-5% vs II 35+/-4%, p<0.05) and RVR ( DD 105+/-20% and II 89+/-16% p<0.05) in DD-homozygotes [6].

Biological context of NR1D2

  • This investigation utilised the mammalian two hybrid system and transfection analysis to demonstrate that Rev-erbA alpha and RVR will not efficiently interact with either ID-I or ID-II separately from RIP13a or RIP13delta1 [7].
  • Like Rev-Erb, BD73 binds as a monomer to a DNA sequence which consists of a specific A/T-rich sequence upstream of the consensus hexameric half-site specified by the P box of the DNA-binding domain [8].
  • Under the conditions examined, neither BD73 nor Rev-Erb activated reporters containing multiple copies of their common binding site [8].
  • Amino acid sequence comparisons suggest that the A box sequence, which has been suggested to mediate monomer binding by other superfamily members, lies closer to the DNA-binding domain in BD73 and Rev-Erb than in other receptors [8].
  • Unlike Rev-Erb, in which the opposite strand of the C-terminal coding region encodes the C-terminal portion of a variant thyroid hormone receptor isoform, the opposite strand of the C-terminal coding region of BD73 does not have any extensive open reading frames [8].

Anatomical context of NR1D2


Associations of NR1D2 with chemical compounds


Other interactions of NR1D2

  • Rev-erbA alpha and RVR are orphan nuclear receptors that function as dominant transcriptional silencers [11].
  • Two receptor interaction domains in the corepressor, N-CoR/RIP13, are required for an efficient interaction with Rev-erbA alpha and RVR: physical association is dependent on the E region of the orphan receptors [7].
  • In conclusion, our study has identified a new corepressor interaction region, CIR-1, in the N terminus of helix 3 in the E region of RVR and Rev-erbA alpha, that is required for transcriptional silencing [11].
  • RV14 upregulated the expression of the mRNA and protein of intercellular adhesion molecule-1 (ICAM-1), the major RV receptor, and it increased the cytokine production [14].
  • The results obtained point to the involvement of a carboxyl-terminal sequence adjacent to the second zinc finger of the Rev-erb beta DBD in protein-DNA interaction as a monomer or in protein-DNA and protein-protein interactions as a homodimer [15].

Analytical, diagnostic and therapeutic context of NR1D2


  1. Cardiac ischemia during weaning from mechanical ventilation. Chatila, W., Ani, S., Guaglianone, D., Jacob, B., Amoateng-Adjepong, Y., Manthous, C.A. Chest (1996) [Pubmed]
  2. Renal counterbalance. Finn, W.F. J. Lab. Clin. Med. (1985) [Pubmed]
  3. Antiadrenergic antihypertensive drugs: their effect on renal function. Bernstein, K.N., O'Connor, D.T. Annu. Rev. Pharmacol. Toxicol. (1984) [Pubmed]
  4. Differential regulation of the N-myc proto-oncogene by ROR alpha and RVR, two orphan members of the superfamily of nuclear hormone receptors. Dussault, I., Giguère, V. Mol. Cell. Biol. (1997) [Pubmed]
  5. Atrial natriuretic peptide and response to changing plasma volume in diabetic nephropathy. Lieberman, J.S., Parra, L., Newton, L., Scandling, J.D., Loon, N., Myers, B.D. Diabetes (1991) [Pubmed]
  6. The influence of the ACE ( I/D) polymorphism on systemic and renal vascular responses to angiotensins in normotensive, normoalbuminuric Type 1 diabetes mellitus. Luik, P.T., Hoogenberg, K., Kerstens, M.N., Beusekamp, B.J., De Jong, P.E., Dullaart, R.P., Navis, G.J. Diabetologia (2003) [Pubmed]
  7. Two receptor interaction domains in the corepressor, N-CoR/RIP13, are required for an efficient interaction with Rev-erbA alpha and RVR: physical association is dependent on the E region of the orphan receptors. Downes, M., Burke, L.J., Bailey, P.J., Muscat, G.E. Nucleic Acids Res. (1996) [Pubmed]
  8. A new orphan member of the nuclear hormone receptor superfamily closely related to Rev-Erb. Dumas, B., Harding, H.P., Choi, H.S., Lehmann, K.A., Chung, M., Lazar, M.A., Moore, D.D. Mol. Endocrinol. (1994) [Pubmed]
  9. Rev-erb beta, a new member of the nuclear receptor superfamily, is expressed in the nervous system during chicken development. Bonnelye, E., Vanacker, J.M., Desbiens, X., Begue, A., Stehelin, D., Laudet, V. Cell Growth Differ. (1994) [Pubmed]
  10. Radiologic diagnosis of renovascular hypertension and percutaneous transluminal renal angioplasty. Tack, C., Sos, T.A. Seminars in nuclear medicine. (1989) [Pubmed]
  11. Identification and characterization of a novel corepressor interaction region in RVR and Rev-erbA alpha. Burke, L.J., Downes, M., Laudet, V., Muscat, G.E. Mol. Endocrinol. (1998) [Pubmed]
  12. Transcriptional repression by the orphan steroid receptor RVR/Rev-erb beta is dependent on the signature motif and helix 5 in the E region: functional evidence for a biological role of RVR in myogenesis. Burke, L., Downes, M., Carozzi, A., Giguère, V., Muscat, G.E. Nucleic Acids Res. (1996) [Pubmed]
  13. Renal effects of acute calcium blockade with nifedipine in hypertensive patients receiving beta-adrenoceptor-blocking drugs. Christensen, C.K., Lederballe Pedersen, O., Mikkelsen, E. Clin. Pharmacol. Ther. (1982) [Pubmed]
  14. Erythromycin inhibits rhinovirus infection in cultured human tracheal epithelial cells. Suzuki, T., Yamaya, M., Sekizawa, K., Hosoda, M., Yamada, N., Ishizuka, S., Yoshino, A., Yasuda, H., Takahashi, H., Nishimura, H., Sasaki, H. Am. J. Respir. Crit. Care Med. (2002) [Pubmed]
  15. Structural features involved in the formation of a complex between the monomeric or the dimeric form of the rev-erb beta DNA-binding domain and its DNA reactive sites. Terenzi, H., Alzari, P.M., Zakin, M.M. Biochemistry (1998) [Pubmed]
  16. The unassisted respiratory rate-tidal volume ratio accurately predicts weaning outcome. Chatila, W., Jacob, B., Guaglionone, D., Manthous, C.A. Am. J. Med. (1996) [Pubmed]
  17. Divergent effects of calcium channel and angiotensin converting enzyme blockade on glomerulotubular function in cyclosporine-treated renal allograft recipients. Sennesael, J.J., Lamote, J.G., Violet, I., Tasse, S., Verbeelen, D.L. Am. J. Kidney Dis. (1996) [Pubmed]
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