peptidyl-glycine alpha-amidating monooxygenase; includes: peptidylglycine alpha-hydroxylating monooxygenase; PHM; peptidyl-alpha-hydroxyglycine alpha-amidating lyase; peptidylamidoglycolate lyase; PAL (PAM)

Function

• bifunctional enzyme
• catalyzes 2 sequential steps in C-terminal alpha-amidation of peptides
• the monooxygenase part produces an unstable peptidyl- (2-hydroxyglycine) intermediate that is dismutated to glyoxylate & the corresponding desglycine peptide amide by the lyase part
• C-terminal amidation of peptides such as neuropeptides is essential for full biological activity
• interacts with RASSF9 (putative)

peptidylglycine + ascorbate + O2 = peptidyl(2-hydroxyglycine) +

dehydroascorbate + H2O

peptidylamidoglycolate = peptidyl amide + glyoxylate

Cofactor:

• Zn+2; for the lyase reaction
• binds 2 copper ions per subunit; for the monoxygenase reaction

Inhibition:

• inhibited by EDTA, phenylglyoxal & diethyl pyrocarbonate

Structure

• monomer
• in the C-terminal section; belongs to the peptidyl- alpha-hydroxyglycine alpha-amidating lyase family
• in the N-terminal section; belongs to the copper type II ascorbate-dependent monooxygenase family
• contains 5 NHL repeats

Compartment

• isoform 1: membrane; single-pass type 1 membrane protein
• isoform 2: membrane; single-pass type 1 membrane protein
• isoform 3: secreted; secreted from secretory granules
• isoform 4: secreted; secreted from secretory granules

Alternative splicing

• named isoforms=5
• additional isoforms seem to exist

More general terms

• hydroxylase; monooxygenase
• glycoprotein
• membrane protein
• phosphoprotein

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=5066
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:5066
• OMIM: https://mirror.omim.org/entry/170270
• UniProt: http://www.uniprot.org/uniprot/P19021.html