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Gene Review

Hr38  -  Hormone receptor-like in 38

Drosophila melanogaster

Synonyms: 38E.3, 38E.7, CG1864, DHR38, Dhr38, ...
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High impact information on Hr38

  • This response is unusual in that it does not involve direct binding of ecdysteroids to either DHR38 or USP [1].
  • X-ray crystallographic analysis of DHR38 reveals the absence of both a classic ligand binding pocket and coactivator binding site, features that seem to be common to all NGFI-B subfamily members [1].
  • Using this approach, we isolated three Drosophila genes, designated DHR38, DHR78, and DHR96 [2].
  • DHR38 is the Drosophila homolog of NGFI-B and binds specifically to an NGFI-B response element [2].
  • Moreover, transfection experiments in Schneider cells show that DHR38 can affect ecdysone-dependent transcription [3].

Biological context of Hr38

  • We characterized the molecular structure and expression of the Dhr38 gene and initiated an in vivo analysis of its function(s) in development [4].
  • The Dhr38 transcription unit spans more than 40 kb in length, includes four introns, and produces at least four mRNA isoforms differentially expressed in development; two of these are greatly enriched in the pupal stage and encode nested polypeptides [4].
  • Genomic organization of DHR38 gene in Drosophila: presence of Alu-like repeat in a translated exon and expression during embryonic development [5].
  • The DNA-binding domain with two zinc-fingers, and at least part of the ligand-binding peptide, is coded by the largest middle exon2 in DHR38 and exhibits up to 100% homology in short peptide motifs to its mammalian counterpart, where these domains are split into exons 3, 4, 5, and 6 [5].

Anatomical context of Hr38


Associations of Hr38 with chemical compounds

  • This suggests that DHR38 plays a role in the ecdysone response and that more generally NGFI-B type receptors may be able to function as heterodimers with retinoid X receptor type receptors in regulating transcription [3].
  • DHR38 is a member of the steroid receptor superfamily in Drosophila homologous to the vertebrate NGFI-B-type orphan receptors [4].

Physical interactions of Hr38

  • Although members of the NGFI-B family are thought to function exclusively as monomers, we show that DHR38 and BHR38 in fact interact strongly with USP and that this interaction is evolutionarily conserved [3].

Other interactions of Hr38

  • Conversely, none of the compounds tested had a significant effect on the activity of three Drosophila orphan nuclear receptors: DHR38, DHR78 or DHR96 [6].
  • Di-RXR-1 can bind in vitro to EcR and DHR38, both known insect USP partners [7].
  • Dhr38 alleles cause localized fragility and rupturing of the adult cuticle, demonstrating that Dhr38 plays an important role in late stages of epidermal metamorphosis [4].

Analytical, diagnostic and therapeutic context of Hr38

  • In situ hybridization to 0-24 h wholemount embryos showed strong expression of DHR38 in neurogenic regions and in the intestinal tract during embryogenesis, suggesting a spatial and temporal control of transcription, partially analogous to the central nervous system-specific expression of NGFI-B in mammals [5].


  1. The Drosophila orphan nuclear receptor DHR38 mediates an atypical ecdysteroid signaling pathway. Baker, K.D., Shewchuk, L.M., Kozlova, T., Makishima, M., Hassell, A., Wisely, B., Caravella, J.A., Lambert, M.H., Reinking, J.L., Krause, H., Thummel, C.S., Willson, T.M., Mangelsdorf, D.J. Cell (2003) [Pubmed]
  2. Isolation, regulation, and DNA-binding properties of three Drosophila nuclear hormone receptor superfamily members. Fisk, G.J., Thummel, C.S. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  3. Drosophila hormone receptor 38: a second partner for Drosophila USP suggests an unexpected role for nuclear receptors of the nerve growth factor-induced protein B type. Sutherland, J.D., Kozlova, T., Tzertzinis, G., Kafatos, F.C. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  4. Drosophila hormone receptor 38 functions in metamorphosis: a role in adult cuticle formation. Kozlova, T., Pokholkova, G.V., Tzertzinis, G., Sutherland, J.D., Zhimulev, I.F., Kafatos, F.C. Genetics (1998) [Pubmed]
  5. Genomic organization of DHR38 gene in Drosophila: presence of Alu-like repeat in a translated exon and expression during embryonic development. Komonyi, O., Mink, M., Csiha, J., Maróy, P. Arch. Insect Biochem. Physiol. (1998) [Pubmed]
  6. Transcriptional activation of the Drosophila ecdysone receptor by insect and plant ecdysteroids. Baker, K.D., Warren, J.T., Thummel, C.S., Gilbert, L.I., Mangelsdorf, D.J. Insect Biochem. Mol. Biol. (2000) [Pubmed]
  7. An rxr/usp homolog from the parasitic nematode, Dirofilaria immitis. Shea, C., Hough, D., Xiao, J., Tzertzinis, G., Maina, C.V. Gene (2004) [Pubmed]
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