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Gene Review

Hr39  -  Hormone receptor-like in 39

Drosophila melanogaster

Synonyms: CG8676, DHR30, DHR39, DHR39/Ftz-F1beta, Dmel\CG8676, ...
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High impact information on Hr39

  • Bon binds via an LxxLL motif to the AF-2 activation domain present in the ligand binding domain of betaFTZ-F1 and behaves as a transcriptional inhibitor in vivo [1].
  • Here we show that FTZ-F1 does have an AF2 motif and that it is required to bind a coactivator, the homeodomain-containing protein Fushi tarazu (FTZ) [2].
  • In Drosophila cultured cells, FTZ is required for FTZ-F1 activation of a FTZ-F1 reporter gene [3].
  • Base substitutions in the FTZ-F1 binding site within the 0.8-kb promoter abolished expression of lacZ [4].
  • FTF recognizes the DNA sequence 5'-TCAAGGTCA-3', the canonical recognition motif for FTZ-F1 receptors. cDNA sequence homologies indicate that rat FTF is the ortholog of mouse LRH-1 and Xenopus xFF1rA [5].

Biological context of Hr39

  • By electrophoretic mobility shift analysis we show that a DHR39 fusion protein binds specifically to two FTZ-F1 binding sites [6].
  • Over expression of an alternative DHR39 open reading frame that lacks part of the putative ligand binding domain does not alter Adh expression [6].
  • Temporal and spatial expression patterns of the FTZ-F1 beta gene suggest that it may have multiple roles in early embryogenesis, neurogenesis, and in the adult [7].
  • Northern blot analysis detected FTZ-F1 beta expression at all stages of the Drosophila life cycle including a possible maternal component [7].
  • These results suggest that betaFTZ-F1 regulates genes associated with ecdysis and metamorphosis, and that the exact timing of its action in the ecdysone-induced gene cascade is important for proper development [8].

Anatomical context of Hr39

  • In situ hybridization to embryos has shown that DHR39 RNA is found primarily in the central nervous system, and not in embryonic tissues that express ADH [6].
  • A PCR approach has been used to isolate, from Bombyx mori, a cDNA encoding a novel orphan receptor (GRF) that is most closely related to Bombyx betaFTZ-F1 and to the vertebrate germ cell nuclear factor [9].
  • FTZ-F1 is a member of the orphan nuclear receptors, which belongs to the steroid hormone receptor superfamily, and plays a role in the blastoderm and nervous system development in Drosophila [10].
  • However, OR2.0 consists of 2945 bp, is expressed in the livers and the adrenal glands, and is considered to be the chicken counterpart of mouse LRH-1, which is a member of the FTZ-F1 family in mammals [10].
  • Both MHR4 and betaFTZ-F1 mRNAs were found in the testis during the onset of spermatogenesis in the prepupal period [11].

Associations of Hr39 with chemical compounds

  • We previously reported that the steroid receptor superfamily member FTZ-F1 binds to this site [6].

Regulatory relationships of Hr39

  • In contrast, over expression of FTZ-F1 specifically activates distal Adh expression [6].

Other interactions of Hr39

  • These data suggest that FTZ-F1 alpha and FTZ-F1 beta likely coregulate common target genes by competition for binding to a 9-bp recognition element [12].
  • Using wild-type and N-terminally truncated receptors, we have determined that FTZ-F1 alpha and FTZ-F1 beta both bind as monomers to the 9-bp F1RE in the zebra element, as well as to an imperfect inverted F1RE repeat present in the Drosophila alcohol dehydrogenase gene [12].
  • 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 [13].
  • A putative pupal cuticle gene, EDG84A, is expressed slightly following FTZ-F1 expression during the prepupal period and carries a strong FTZ-F1 binding site between bases 100 and 92 upstream of its transcription start site [4].

Analytical, diagnostic and therapeutic context of Hr39


  1. Bonus, a Drosophila homolog of TIF1 proteins, interacts with nuclear receptors and can inhibit betaFTZ-F1-dependent transcription. Beckstead, R., Ortiz, J.A., Sanchez, C., Prokopenko, S.N., Chambon, P., Losson, R., Bellen, H.J. Mol. Cell (2001) [Pubmed]
  2. FTZ-Factor1 and Fushi tarazu interact via conserved nuclear receptor and coactivator motifs. Schwartz, C.J., Sampson, H.M., Hlousek, D., Percival-Smith, A., Copeland, J.W., Simmonds, A.J., Krause, H.M. EMBO J. (2001) [Pubmed]
  3. Segmentation gene product Fushi tarazu is an LXXLL motif-dependent coactivator for orphan receptor FTZ-F1. Suzuki, T., Kawasaki, H., Yu, R.T., Ueda, H., Umesono, K. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  4. Regulation of the EDG84A gene by FTZ-F1 during metamorphosis in Drosophila melanogaster. Murata, T., Kageyama, Y., Hirose, S., Ueda, H. Mol. Cell. Biol. (1996) [Pubmed]
  5. The alpha1-fetoprotein locus is activated by a nuclear receptor of the Drosophila FTZ-F1 family. Galarneau, L., Paré, J.F., Allard, D., Hamel, D., Levesque, L., Tugwood, J.D., Green, S., Bélanger, L. Mol. Cell. Biol. (1996) [Pubmed]
  6. Activation and repression of Drosophila alcohol dehydrogenase distal transcription by two steroid hormone receptor superfamily members binding to a common response element. Ayer, S., Walker, N., Mosammaparast, M., Nelson, J.P., Shilo, B.Z., Benyajati, C. Nucleic Acids Res. (1993) [Pubmed]
  7. FTZ-F1 beta, a novel member of the Drosophila nuclear receptor family. Ohno, C.K., Petkovich, M. Mech. Dev. (1993) [Pubmed]
  8. Temporally restricted expression of transcription factor betaFTZ-F1: significance for embryogenesis, molting and metamorphosis in Drosophila melanogaster. Yamada, M., Murata, T., Hirose, S., Lavorgna, G., Suzuki, E., Ueda, H. Development (2000) [Pubmed]
  9. Characterization and DNA-binding properties of GRF, a novel monomeric binding orphan receptor related to GCNF and betaFTZ-F1. Charles, J.P., Shinoda, T., Chinzei, Y. Eur. J. Biochem. (1999) [Pubmed]
  10. Molecular cloning of chicken FTZ-F1-related orphan receptors. Kudo, T., Sutou, S. Gene (1997) [Pubmed]
  11. Isolation and developmental expression of two nuclear receptors, MHR4 and betaFTZ-F1, in the tobacco hornworm, Manduca sexta. Weller, J., Sun, G.C., Zhou, B., Lan, Q., Hiruma, K., Riddiford, L.M. Insect Biochem. Mol. Biol. (2001) [Pubmed]
  12. The Drosophila nuclear receptors FTZ-F1 alpha and FTZ-F1 beta compete as monomers for binding to a site in the fushi tarazu gene. Ohno, C.K., Ueda, H., Petkovich, M. Mol. Cell. Biol. (1994) [Pubmed]
  13. 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]
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