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 … expand

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 [ PUBMED:8524259 PUBMED:1427040 ]. 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 [ PUBMED:11840327 ].

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) [ PUBMED:11840327 PUBMED:11162494 ]. All these Orange domain proteins have the bHLH domain 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 [ PUBMED:8524259 PUBMED:11840327 ].