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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
General
glycoprotein
hydroxylase; monooxygenase
membrane protein
phosphoprotein
Properties
SIZE: entity length = 973 aa
MW = 108 kD
COMPARTMENT: cellular membrane
MOTIF: Peptidylglycine alpha-hydroxylating monooxygenase {1-494}
MOTIF: signal sequence {1-20}
Intragranular {31-863}
MOTIF: cysteine residue {C42}
MODIFICATION: cysteine residue {C181}
cysteine residue {C76}
MODIFICATION: cysteine residue {C121}
copper [Cu]-binding site
SITE: 102-102
MOTIF: histidine residue (3)
copper [Cu]-binding site
SITE: 103-103
MOTIF: histidine residue (3)
cysteine residue {C109}
MODIFICATION: cysteine residue {C126}
cysteine residue {C121}
MODIFICATION: cysteine residue {C76}
cysteine residue {C126}
MODIFICATION: cysteine residue {C109}
copper [Cu]-binding site
SITE: 167-167
MOTIF: histidine residue (3)
cysteine residue {C181}
MODIFICATION: cysteine residue {C42}
cysteine residue {C222}
MODIFICATION: cysteine residue {C329}
copper [Cu]-binding site
SITE: 237-237
MOTIF: histidine residue (3)
copper [Cu]-binding site
SITE: 239-239
MOTIF: histidine residue (3)
cysteine residue {C288}
MODIFICATION: cysteine residue {C310}
copper [Cu]-binding site
SITE: 309-309
MOTIF: histidine residue (3)
cysteine residue {C310}
MODIFICATION: cysteine residue {C288}
cysteine residue {C329}
MODIFICATION: cysteine residue {C222}
Peptidyl-alpha-hydroxyglycine alpha- amidating lyase {495-817}
NHL repeat domain {498-541}
NHL repeat domain {567-608}
NHL repeat domain {617-662}
cysteine residue {C631}
MODIFICATION: cysteine residue {C652}
cysteine residue {C652}
MODIFICATION: cysteine residue {C631}
NHL repeat domain {670-714}
cysteine residue {C699}
MODIFICATION: cysteine residue {C710}
cysteine residue {C710}
MODIFICATION: cysteine residue {C699}
N-glycosylation site {N762}
NHL repeat domain {766-809}
transmembrane domain {864-887}
Ser phosphorylation site {S918}
RASSF9 interaction {925-942}
MOTIF: Ser phosphorylation site {S929}
Ser phosphorylation site {S942}
Ser phosphorylation site {S946}
Ser phosphorylation site {S955}
Ser phosphorylation site {S957}
Database Correlations
OMIM 170270
UniProt P19021
PFAM correlations
Entrez Gene 5066
Kegg hsa:5066
ENZYME correlations
References
UniProt :accession P19021