Endoglin also known as ENG, is a type of membrane glycoprotein which is located on the surface of cells and is part of the TGF beta receptor complex. It is also known as CD105, END, FLJ41744, HHT1, ORW, OR ORW1. Endoglin plays a vital role in angiogenesis, which means that it is an important protein for the growth of tumors and survival and metastasis of cancer cells in various areas of the body.
Located on chromosome 9, with the cytogenetic band being at 9q34, this protein is encoded by 39,757 bp and is made up of over 600 amino acids. Endoglin expression is usually low in resting cells. However, one the process of neoangiogenesis begins and the endothelial cells are active, this changes - cells become active in areas like inflamed tissues, tumor vessels, psoriasis, and during the process of embryogenesis.
The glycoprotein of Endoglin is made up of a homodimer of 180 KDA which has disulfide links; it is the 350 and 582 cysteines that are connected to the disulfide linking of these different homodimers. With a large extracellular domain made up of 561 amino acids, a hydrophobic transmembrane and a shorter than normal cytoplasmic tail made up of 45 amino acids. The cellular region with 260 amino acids, which is closest to the extracellular membrane is known as the ZP domain. Whereas the outer section is known as the orphan domain, and it is the section that binds ligands together, like BMP-9. There are two types of Endoglin which can be created by alternative splicing; these are the longer isoform and the shorter isoform. However, the large isoform tends to have greater use than the shorter isoform. A soluble type of Endoglin can be made by the proteolytic cleaving action of metalloproteinase occurring in the extracellular domain close to the membrane.
It has been discovered that Endoglin can work as an auxiliary receptor for the TGF-beta complex. This means that it can be used to modulate a response to the binding of TGF-beta 1, TGF-beta 3, activin-A, BMP-2, and BMP-7. As well as TGF-beta signalling, it is also thought that Endoglin may also have other functions. It has been suggested that Endoglin is involved in the cytoskeletal organization, which means that it affects morphology and migration of cells. It also has a role in the development of the cardiovascular system, as well as on vascular remodelling. The expression of Endoglin is regulated when the heart is developing. Studies have shown that mice without the Endoglin gene, die because they have cardiovascular abnormalities.
In human medicine, Endoglin could potentially be used in the autosomal dominant disorder called hereditary hemorrhagic telangiectasia (HHT) type 1. This is the first human disease that is linked to the TGF beta receptor complex. Leading to constant nose bleeds, skin problems, and mucosa, as well as potentially causing arteriovenous malformations in various organs, from the brain to the liver.
Studies have shown that certain mutations lead to this disorder, these include a cytosine to guanine substitution, converting a tyrosine to prevent codon, a 39 base pair deletion, and a two base pair deletion which causes an early stop codon. Research has shown that elevated Endoglin levels have been found in pregnant women who have, or go onto have, preeclampsia.