110 - Endothelin-converting enzyme 1

Abstract

This chapter focuses on the structural chemistry of Endothelin-Converting Enzyme 1 (ECE-1). The ECE-1 is a type II integral membrane protein with a short N-terminal cytoplasmic tail, a transmembrane hydrophobic domain and a large extracellular domain containing the catalytic site and a zinc-binding motif (HEXXH). Four isoforms of human ECE-1 (1a, 1b, 1c, and 1d), generated from alternative splicing of a single gene, have been identified. These four isoforms have identical extracellular domains, differing only in their cytoplasmic tails. Amino acid sequences within the cytoplasmic tails determine whether the isoforms are targeted to the cell surface or to intracellular compartments such as the trans-Golgi network. ECE-1 has 10 sites predicted to be N-glycosylated in the extracellular domain and a high glycosylation level is evident from the apparent molecular mass of 120–130 kDa estimated from SDS-PAGE. Immunohistochemical studies indicate that ECE-1 expression is highest in the cardiovascular endothelium, but is also present in endocrine tissues such as testis, ovary and adrenal gland.