ENG gene

The ENG gene (ENG stands for endoglin), also known as the HHT1 gene, is a protein-coding gene located on chromosome 9q34.11. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. An important paralog of this gene is TGFBR3.

The ENG gene encodes a homodimeric transmembrane protein, which is an important glycoprotein of the vascular endothelium. This protein is a component of the receptor complex for the transforming growth factor beta and binds with high affinity to the peptides beta1 and beta3.

Mutations in this gene cause hereditary hemorrhagic telangiectasia, also known as Osler-Rendu-Weber syndrome 1, an autosomal dominant multisystemic vascular dysplasia. This gene may also be involved in pre-eclampsia and various cancers. Related pathways include TGF-beta receptor signaling in skeletal dysplasia and angiogenesis (CST).

Vascular endothelial glycoprotein that plays an important role in the regulation of angiogenesis (PubMed: Castonguay R et al. 2011; Nolan-Stevaux O et al. 2012).23300529). Required for the normal structure and integrity of the adult vascular system (McAllister KA et al. 1994). Endoglin regulates the migration of vascular endothelial cells (McAllister KA et al. 1994). The protein is required for normal extraembryonic angiogenesis and embryonic heart development. May regulate endothelial cell shape changes in response to blood flow that drive vascular remodeling and the establishment of normal vascular morphology during angiogenesis. Endoglin may play a critical role in the binding of endothelial cells to integrins and/or other RGD receptors. Acts as a TGF-beta co-receptor and is involved in the TGF-beta/BMP signaling cascade that ultimately leads to activation of SMAD transcription factors (Castonguay R et al. 2011; Nolan-Stevaux O et al. 201). Required for GDF2/BMP9 signaling through SMAD1 in endothelial cells and modulates TGFB1 signaling through SMAD3 (Castonguay R et al. 2011; Nolan-Stevaux O et al. 2012).

1. Castonguay R et al. (2011) Soluble endoglin specifically binds bone morphogenetic proteins 9 and 10 via its orphan domain, inhibits blood vessel formation, and suppresses tumor growth. J Biol Chem 286:30034-30046.
2. Lee NY et al. (2007) The interaction of endoglin with beta-arrestin2 regulates transforming growth factor-beta-mediated ERK activation and migration in endothelial cells. J Biol Chem 282:21507-21517.
3. McAllister KA et al. (1994) Endoglin, a TGF-beta binding protein of endothelial cells, is the gene for hereditary haemorrhagic telangiectasia type 1. Nat Genet 8:345-351.
4. Nolan-Stevaux O et al. (2012) Endoglin requirement for BMP9 signaling in endothelial cells reveals new mechanism of action for selective anti-endoglin antibodies. PLoS One 7:e50920.