PAM

This gene encodes a multifunctional protein. The encoded preproprotein is proteolytically processed to generate the mature enzyme. This enzyme includes two domains with distinct catalytic activities, a peptidylglycine alpha-hydroxylating monooxygenase (PHM) domain and a peptidyl-alpha-hydroxyglycine alpha-amidating lyase (PAL) domain. These catalytic domains work sequentially to catalyze the conversion of neuroendocrine peptides to active alpha-amidated products. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Jan 2016]

Full Name

Peptidylglycine Alpha-Amidating Monooxygenase

Function

Bifunctional enzyme that catalyzes the post-translational modification of inactive peptidylglycine precursors to the corresponding bioactive alpha-amidated peptides, a terminal modification in biosynthesis of many neural and endocrine peptides (PubMed:12699694).
Alpha-amidation involves two sequential reactions, both of which are catalyzed by separate catalytic domains of the enzyme. The first step, catalyzed by peptidyl alpha-hydroxylating monooxygenase (PHM) domain, is the copper-, ascorbate-, and O2- dependent stereospecific hydroxylation (with S stereochemistry) at the alpha-carbon (C-alpha) of the C-terminal glycine of the peptidylglycine substrate (PubMed:12699694).
The second step, catalyzed by the peptidylglycine amidoglycolate lyase (PAL) domain, is the zinc-dependent cleavage of the N-C-alpha bond, producing the alpha-amidated peptide and glyoxylate (PubMed:12699694).
Similarly, catalyzes the two-step conversion of an N-fatty acylglycine to a primary fatty acid amide and glyoxylate (By similarity).

Biological Process

Central nervous system developmentIEA:Ensembl
Fatty acid primary amide biosynthetic processISS:UniProtKB
Heart developmentIEA:Ensembl
LactationIEA:Ensembl
Limb developmentIEA:Ensembl
Long-chain fatty acid metabolic processIEA:Ensembl
Maternal process involved in female pregnancyIEA:Ensembl
OdontogenesisIEA:Ensembl
Ovulation cycle processIEA:Ensembl
Peptide amidationManual Assertion Based On ExperimentIDA:UniProtKB
Protein amidationIEA:Ensembl
Regulation of actin cytoskeleton organizationIEA:Ensembl
Regulation of protein secretionIEA:Ensembl
Regulation of transcription by RNA polymerase IIIEA:Ensembl
Response to copper ionIEA:Ensembl
Response to estradiolIEA:Ensembl
Response to glucocorticoidIEA:Ensembl
Response to hypoxiaIEA:Ensembl
Response to pHIEA:Ensembl
Response to xenobiotic stimulusIEA:Ensembl
Response to zinc ionManual Assertion Based On ExperimentIDA:UniProtKB
Toxin metabolic processIEA:Ensembl

Cellular Location

Cytoplasmic vesicle, secretory vesicle membrane
Secretory granules.
Isoform 1
Membrane
Isoform 2
Membrane
Isoform 3
Secreted
Secreted from secretory granules.
Isoform 4
Secreted
Secreted from secretory granules.

Topology

Intragranular: 31-863
Helical: 864-887
Cytoplasmic: 888-973