PROSITE documentation PDOC51054
Orange domain profile


The Orange domain is a motif of ~35 amino acids present in eukaryotic DNA-binding transcription repressors, which regulate cell differentiation, embryonic patterning and other biological processes in both vertebrates and invertebrates. The Orange domain is located just C-terminal to a basic helix-loop-helix (bHLH) domain in the bHLH-Orange (bHLH-O) proteins. This family of bHLH repressors is related to the Drosophila hairy and Enhancer-of-split proteins, wherein the Orange domain was first described and also named helix III/IV region [1,2]. The transcription of many vertebrate bHLH-O genes is regulated by the Notch signaling pathway, which controls fate decisions and other developmental processes. Orange domain proteins function as transcription repressors involved in the regulation of differentiation, anteroposterior segmentation and sex determination in flies [3].

Four subfamilies of bHLH-Orange proteins have been identified, i.e. hairy, Enhancer of split, Hey (also named HRT or Hesr) and Stra13 (also named SHARP, DEC, CLAST or BHLHB2) [3,4]. All these Orange domain proteins have the bHLH domain (see <PDOC00038>) and except for the Stra13 subfamily, the other subfamily members have a conserved tetrapeptide motif in the C-terminal extremity. The C-terminal motif of the hairy and Enhancer of split proteins is WRPW and this binds the transcriptional corepressor groucho/TLE. For the Hey subfamily members the C-terminal motif is YXXW. The Orange domain may confer specificity of function to different family members and/or it may be involved in dimerization [1,3].

Some proteins known to contain an Orange domain:

  • Fruit fly hairy protein, a transcription repressor which regulates the embryonic segmentation and adult bristle patterning.
  • Fruit fly enhancer of split proteins E(spl), transcription repressors that are active during neurogenesis.
  • Fruit fly deadpan, a hairy-like protein involved in the functional differentiation of neurons.
  • Mammalian HES1 and HES5 proteins, regulators involved in neuronal differentiation.
  • Vertebrate Hey proteins, involved in blood vessel development.

The profile we developed covers the entire Orange domain.

Last update:

January 2005 / First entry.


Technical section

PROSITE method (with tools and information) covered by this documentation:

ORANGE, PS51054; Orange domain profile  (MATRIX)


1AuthorsDawson S.R. Turner D.L. Weintraub H. Parkhurst S.M.
TitleSpecificity for the hairy/enhancer of split basic helix-loop-helix (bHLH) proteins maps outside the bHLH domain and suggests two separable modes of transcriptional repression.
SourceMol. Cell. Biol. 15:6923-6931(1995).
PubMed ID8524259

2AuthorsKnust E. Schrons H. Grawe F. Campos-Ortega J.A.
TitleSeven genes of the Enhancer of split complex of Drosophila melanogaster encode helix-loop-helix proteins.
SourceGenetics 132:505-518(1992).
PubMed ID1427040

3AuthorsDavis R.L. Turner D.L.
TitleVertebrate hairy and Enhancer of split related proteins: transcriptional repressors regulating cellular differentiation and embryonic patterning.
SourceOncogene 20:8342-8357(2001).
PubMed ID11840327

4AuthorsFujimoto K. Shen M. Noshiro M. Matsubara K. Shingu S. Honda K. Yoshida E. Suardita K. Matsuda Y. Kato Y.
TitleMolecular cloning and characterization of DEC2, a new member of basic helix-loop-helix proteins.
SourceBiochem. Biophys. Res. Commun. 280:164-171(2001).
PubMed ID11162494

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