[2] The first helix-loop-helix proteins identified were named E-proteins because they bind to Ephrussi-box (E-box) sequences.
The ID homologue gene in Drosophila is called extramacrochaetae (EMC) and encodes a transcription factor of the helix-loop-helix family that lacks a DNA binding domain.
[6] ID proteins are key regulators of development where they function to prevent premature differentiation of stem cells.
[13] Knockout mouse data show that ID genes are essential for heart development.
A recent publication in Cancer Research (August 2010) has shown that ID1 can be used to mark endothelial progenitor cells which are critical to tumour growth and angiogenesis.
[15] Perk, Iavarone, and Benezra, (2005), reviewed fifteen studies and compiled a list of the phenotypic effects of each ID gene when knocked out in mice.
Knockout of both ID1 and ID3 resulted in embryonic lethality due to brain hemorrhages and abnormalities in cardiac development.