endothelin-converting enzyme 2; ECE-2 (ECE2, KIAA0604)

Function

• converts big endothelin-1 to endothelin-1
• role in processing of various neuroendocrine peptides, including: neurotensin, angiotensin I, substance P, proenkephalin-derived peptides, & prodynorphin-derived peptides
• may limit beta-amyloid peptide accumulation in brain
• may also have methyltransferase activity
• hydrolysis of 21-Trp-|-Val-22 bond in big endothelin to form endothelin 1

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

Kinetic parameters:

• KM=0.4 uM for big ET-1
• KM=1.4 uM for peptide E
• KM=27.4 uM for bradykinin
• KM=48.4 uM for dynorphin B
• optimum pH is 5.0-5.5; inactive at neutral pH

Structure

• in the N-terminal section; belongs to the methyltransferase superfamily M13 family
• in the C-terminal section; belongs to the peptidase

Compartment

• Golgi membrane
• cytoplasmic granule membrane

Alternative splicing

named isoforms=4; A-D

Expression

• expressed in brain

Pathology

• strongly down-regulated in inferior parietal lobe of patients with Alzheimer disease (at protein level)

More general terms

• endothelin-converting enzyme
• glycoprotein
• phosphoprotein

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=9718
• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=110599
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:110599
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:9718
• OMIM: https://mirror.omim.org/entry/610145
• UniProt: http://www.uniprot.org/uniprot/P0DPD6.html