Primary structure of endoglin, an RGD-containing glycoprotein of human endothelial cells.

Abstract

Endoglin is a major glycoprotein of human vascular endothelium. As observed with monoclonal antibody 44G4, the distribution of endoglin is restricted to endothelial cells in all tissues except bone marrow. cDNA clones were isolated from an endothelial cell lambda gt11 cDNA library using a rabbit antibody prepared against endoglin purified from placenta. Eleven antibody-positive and cross-hybridizing clones were obtained; reactivity with endothelial cell 3.4-kilobase mRNA transcript was observed. The N-terminal sequence of placental endoglin was determined and found within the deduced protein sequence, thus confirming the identity of the cDNA and revealing a partial signal peptide. Endoglin is a type I integral membrane protein of Mr = 68,051 with an extracellular region of 561 amino acids, a hydrophobic transmembrane domain, and a 47-residue cytoplasmic tail. There are four potential N-linked glycosylation sites in the N-terminal domain and a probable O-glycan domain rich in Ser and Thr residues proximal to the membrane-spanning domain. Data base searches revealed that endoglin is a novel protein. The sequence contains an RGD tripeptide (374-376), the first identified on a surface protein of endothelium. The presence of RGD, a key recognition structure in cellular adhesion, suggests a critical role for endoglin in the binding of endothelial cells to integrins and/or other RGD receptors.