endothelin converting enzyme-1; ECE-1 (ECE1)

Function

• converts big endothelin-1 to endothelin-1
• inhibited by phosphoramidon
• hydrolysis of 21-Trp-|-Val-22 bond in big endothelin to form endothelin 1
• substrates:
  • big endothelins
  • bradykinin
  • substance P
  • oxidized insulin B chain
  • amyloid A4 peptide
• inhibitors: phosphoramidon

Cofactor: binds 1 Zn+2 per subunit (putative)

Structure

• homodimer
• belongs to the peptidase M13 family

Compartment

membrane, plasma membrane, internal membranes

Alternative splicing

named isoforms=4, A-D

Expression

• all isoforms are expressed in umbilical vein endothelial cells, polynuclear neutrophils, fibroblasts, atrium cardiomyocytes & ventricles
• isoforms A, B & C are also expressed in placenta, lung, heart, adrenal gland & pheochromocytoma
• isoforms A & C in liver, testis & small intestine
• isoform B, C & D in endothelial cells & umbilical vein smooth muscle cells
• isoforms C & D in saphenous vein cells, & isoform C in kidney

Pathology

• defects in ECE1 are a cause of Hirschsprung disease, cardiac defects & autonomic dysfunction

More general terms

• endothelin-converting enzyme
• glycoprotein
• phosphoprotein

Database

• UniProt: http://www.uniprot.org/uniprot/P42892.html
• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=1889
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:1889
• OMIM: https://mirror.omim.org/entry/142623
• OMIM: https://mirror.omim.org/entry/600423