{PDOC51054}
{PS51054; ORANGE}
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* Orange domain profile *
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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.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Last update: January 2005 / First entry.

[ 1] Dawson S.R., Turner D.L., Weintraub H., Parkhurst S.M.
     "Specificity 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."
     Mol. Cell. Biol. 15:6923-6931(1995).
     PubMed=8524259
[ 2] Knust E., Schrons H., Grawe F., Campos-Ortega J.A.
     "Seven genes of the Enhancer of split complex of Drosophila
     melanogaster encode helix-loop-helix proteins."
     Genetics 132:505-518(1992).
     PubMed=1427040
[ 3] Davis R.L., Turner D.L.
     "Vertebrate hairy and Enhancer of split related proteins:
     transcriptional repressors regulating cellular differentiation and
     embryonic patterning."
     Oncogene 20:8342-8357(2001).
     PubMed=11840327; DOI=10.1038/sj/onc/1205094
[ 4] Fujimoto K., Shen M., Noshiro M., Matsubara K., Shingu S., Honda K.,
     Yoshida E., Suardita K., Matsuda Y., Kato Y.
     "Molecular cloning and characterization of DEC2, a new member of basic
     helix-loop-helix proteins."
     Biochem. Biophys. Res. Commun. 280:164-171(2001).
     PubMed=11162494; DOI=10.1006/bbrc.2000.4133

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