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Gene Review

Hr46  -  Hormone receptor-like in 46

Drosophila melanogaster

Synonyms: 12.6, 2.4, CG11823, CG12208, CG33183, ...
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High impact information on Hr46

  • The oxidation state of the heme iron also determines whether E75 can interact with its heterodimer partner DHR3, suggesting an additional role as a redox sensor [1].
  • Messenger RNA molecules of 2.4, 2.55 and 3.05 kb code for the 68,000, 70,000 and 83,000 dalton heat shock proteins and hybridize to apparently uninterrupted DNA sequences of 2.1, 2.25 and 2.6 kb, respectively [2].
  • A 2.4 kb RNA corresponding to the ems transcript is expressed from cellular blastoderm throughout all embryonic and larval stages [3].
  • DHR3, an ecdysone-inducible early-late gene encoding a Drosophila nuclear receptor, is required for embryogenesis [4].
  • We used a reverse genetics approach to identify 11 DHR3 mutants from a pool of lethal mutations in the 46F region on the second chromosome [4].

Biological context of Hr46

  • Three DHR3 binding sites were identified downstream from the start site of betaFTZ-F1 transcription, further indicating that this gene is a direct target of DHR3 regulation [5].
  • Ectopic expression of DHR3 revealed that the polytene chromosome binding pattern is of functional significance [5].
  • Coordination of larval and prepupal gene expression by the DHR3 orphan receptor during Drosophila metamorphosis [5].
  • We find an unexpected close temporal relationship between DHR3, E75B, and betaFTZ-F1 expression after each major ecdysone pulse examined, reflecting the known cross-regulatory interactions of these genes in prepupae and suggesting that they act together at other stages in the life cycle [6].
  • The phenotypes associated with these lethal phases are consistent with the effects of DHR3 mutations on ecdysone-regulated gene expression [7].

Anatomical context of Hr46

  • Transcripts of 7.5-8 kilobases were present in most tissues, whereas a short mRNA of 2.4 kilobases was detected only in rat testis [8].
  • Compared with vector-transfected cells, COS-1 cells expressing hsBG had increased acyl-CoA synthetase activity with either long-chain fatty acid (2.4-fold) or VLCFA (2.6-fold) substrates [9].
  • Deletion of the PDZ-interacting domain also decreased the expression of TRPC4 in the plasma membrane by 2.4-fold, as assessed by cell surface biotinylation experiments [10].
  • In successive male germ-cell stages exposed to a low dose of 2.4 mM x h methyl methanesulfonate, efficient repair of premutational damage in spermatogonia and by the maternal repair system after fertilization was observed [11].
  • On Northern analysis, endothelial cells express two EG-1 RNA species (1.2 and 2.4 kb) [12].

Associations of Hr46 with chemical compounds

  • DHR3: a Drosophila steroid receptor homolog [13].
  • Finally, two recent reports have demonstrated: (i) lithium mediated regulation of Rev-erbalpha stability and (ii) E75 (the Drosophila orthologue of human Rev-erbalpha) is tightly bound by heme, and functions as a "gas sensor" through interaction with CO/NO and interferes with the repression of DHR3 (the Drosophila orthologue of human RORalpha) [14].
  • The catalytic centre activity for ethanol was 2.4 s-1 [15].
  • The CL/RL ratio of Tris-BP was 2.4, indicating that Tris-BP has cross-linking potential [16].
  • The wild-type enzyme exhibits a Km for xanthine of 2.4 X 10(-5) M, and for NAD+ of 4.0 X 10(-5) M [17].

Other interactions of Hr46

  • The structure of the DHR3 protein is strikingly similar to that of the MHR3 protein (e.g., 97% amino acid identity for the DNA binding domains), another orphan receptor encoded by an ecdysone-inducible early gene of another insect, Manduca sexta [13].
  • In this work, we examine the sequence, genomic organization, and developmental expression of the other gene, DHR3, which, like E75, encodes one of a growing number of "orphan" receptors for which ligands have not yet been identified [13].
  • DHR3 thus appears to function as a switch that defines the larval-prepupal transition by arresting the early regulatory response to ecdysone at puparium formation and facilitating the induction of the betaFTZ-F1 competence factor in mid-prepupae [5].
  • In contrast, DHR3 is required for maximal expression of the midprepupal regulatory genes, EcR, E74B, and betaFTZ-1 [7].
  • Developmental Northern blot analysis reveals that DHR39 is induced in mid third instar larvae and expressed throughout most of third instar larval and prepupal development, while DHR3 is briefly expressed in late third instar larvae and early prepupae [18].

Analytical, diagnostic and therapeutic context of Hr46


  1. The Drosophila nuclear receptor e75 contains heme and is gas responsive. Reinking, J., Lam, M.M., Pardee, K., Sampson, H.M., Liu, S., Yang, P., Williams, S., White, W., Lajoie, G., Edwards, A., Krause, H.M. Cell (2005) [Pubmed]
  2. Studies of cloned sequences from four Drosophila heat shock loci. Holmgren, R., Livak, K., Morimoto, R., Freund, R., Meselson, M. Cell (1979) [Pubmed]
  3. Empty spiracles, a gap gene containing a homeobox involved in Drosophila head development. Walldorf, U., Gehring, W.J. EMBO J. (1992) [Pubmed]
  4. DHR3, an ecdysone-inducible early-late gene encoding a Drosophila nuclear receptor, is required for embryogenesis. Carney, G.E., Wade, A.A., Sapra, R., Goldstein, E.S., Bender, M. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  5. Coordination of larval and prepupal gene expression by the DHR3 orphan receptor during Drosophila metamorphosis. Lam, G.T., Jiang, C., Thummel, C.S. Development (1997) [Pubmed]
  6. Temporal profiles of nuclear receptor gene expression reveal coordinate transcriptional responses during Drosophila development. Sullivan, A.A., Thummel, C.S. Mol. Endocrinol. (2003) [Pubmed]
  7. DHR3 is required for the prepupal-pupal transition and differentiation of adult structures during Drosophila metamorphosis. Lam, G., Hall, B.L., Bender, M., Thummel, C.S. Dev. Biol. (1999) [Pubmed]
  8. Myomegalin is a novel protein of the golgi/centrosome that interacts with a cyclic nucleotide phosphodiesterase. Verde, I., Pahlke, G., Salanova, M., Zhang, G., Wang, S., Coletti, D., Onuffer, J., Jin, S.L., Conti, M. J. Biol. Chem. (2001) [Pubmed]
  9. Very long-chain acyl-CoA synthetases. Human "bubblegum" represents a new family of proteins capable of activating very long-chain fatty acids. Steinberg, S.J., Morgenthaler, J., Heinzer, A.K., Smith, K.D., Watkins, P.A. J. Biol. Chem. (2000) [Pubmed]
  10. The PDZ-interacting domain of TRPC4 controls its localization and surface expression in HEK293 cells. Mery, L., Strauss, B., Dufour, J.F., Krause, K.H., Hoth, M. J. Cell. Sci. (2002) [Pubmed]
  11. The response of germ cells to ethylene oxide, propylene oxide, propylene imine and methyl methanesulfonate is a matter of cell stage-related DNA repair. Vogel, E.W., Nivard, M.J. Environ. Mol. Mutagen. (1997) [Pubmed]
  12. Identification of a novel endothelial-derived gene EG-1. Liu, C., Zhang, L., Shao, Z.M., Beatty, P., Sartippour, M., Lane, T.F., Barsky, S.H., Livingston, E., Nguyen, M. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  13. DHR3: a Drosophila steroid receptor homolog. Koelle, M.R., Segraves, W.A., Hogness, D.S. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  14. The orphan Rev-erb nuclear receptors: a link between metabolism, circadian rhythm and inflammation? Ramakrishnan, S.N., Muscat, G.E. Nuclear receptor signaling [electronic resource] : the e-journal of NURSA. (2006) [Pubmed]
  15. Biochemical properties of alcohol dehydrogenase from Drosophila lebanonensis. Winberg, J.O., Hovik, R., McKinley-McKee, J.S., Juan, E., Gonzalez-Duarte, R. Biochem. J. (1986) [Pubmed]
  16. Genotoxicity of the flame retardant tris(2,3-dibromopropyl)phosphate in the rat and Drosophila: effects of deuterium substitution. van Beerendonk, G.J., Nivard, M.J., Vogel, E.W., Nelson, S.D., Meerman, J.H. Carcinogenesis (1994) [Pubmed]
  17. Xanthine dehydrogenase from Drosophila melanogaster: a comparison of the kinetic parameters of the pure enzyme from two wild-type isoalleles differing at a putative regulatory site. Edwards, T.C., Candido, E.P., Chovnick, A. Mol. Gen. Genet. (1977) [Pubmed]
  18. Ecdysteroid regulation and DNA binding properties of Drosophila nuclear hormone receptor superfamily members. Horner, M.A., Chen, T., Thummel, C.S. Dev. Biol. (1995) [Pubmed]
  19. Temporal regulation of the mid-prepupal gene FTZ-F1: DHR3 early late gene product is one of the plural positive regulators. Kageyama, Y., Masuda, S., Hirose, S., Ueda, H. Genes Cells (1997) [Pubmed]
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