InterPro domain signatures (IPR000720, IPR008977, IPR000323, IPR036939, IPR014783, IPR014784, IPR020611) identify PAM as a copper type II ascorbate-dependent monooxygenase with catalytic, membrane-associated, and copper-binding properties.

EC 4.3.2.5 maps to GO:0004598 (peptidylamidoglycolate lyase activity), correctly identifying the PAL domain enzymatic activity.

UniProt subcellular location "Cytoplasmic vesicle, secretory vesicle membrane" maps to GO:0030658 (transport vesicle membrane).

ARBA rule ARBA00093736 identifies PAM as involved in peptide amidation (GO:0001519).

PANTHER family assignment (PTN000840922) supports extracellular region localization for PAM based on phylogenetic inference.

Combined evidence from EC:1.14.17.3 and PANTHER:PTN000840922 supports peptidylglycine monooxygenase activity (GO:0004504).

Crystal structure of the rat PHM catalytic core shows two copper sites and supports substrate activation by a copper-bound oxygen species.

The PAL catalytic core is a six-bladed beta-propeller with a three-histidine Zn(II) active site that catalyzes N-dealkylation of the peptidyl-alpha-hydroxyglycine.

PAM is the only known peptide-amidating enzyme, a type 1 membrane protein with PHM and PAL in its luminal domain. Splice forms PAM-1, PAM-2 (no linker between PHM and PAL) and PAM-3 (soluble) exist. Soluble PHM and PAL are co-secreted with peptides, and the cytosolic domain directs trafficking to the TGN and secretory granules.

The quail model lacks the 107-residue exon-16 linker (PAM-2-like) but keeps the transmembrane and cytosolic segments and every Cu, Zn and Ca ligand of human PAM.