Family

Peptidylglycine alpha-hydroxylating monooxygenase/peptidyl-hydroxyglycine alpha-amidating lyase (IPR000720)

Short name: PHM/PAL

Family relationships

None.

Description

In vertebrates, peptidylglycine alpha-amidating monooxygenase (PAM) is a multifunctional protein found in secretory granules. The protein contains two enzymes, peptidylglycine alpha-hydroxylating monooxygenase (PHM) and peptidyl-alpha-hydroxyglycine alpha-amidating lyase (PAL), that act sequentially to catalyse the alpha-amidation of neuroendocrine peptides [PMID: 1988445, PMID: 1448112]:

peptidylglycine + ascorbate + O2 = peptidyl-(2-hydroxyglycine) + dehydroascorbate + H2O

The product is unstable and dismutates to glyoxylate and the corresponding desglycine peptide amide. The first step of the reaction is catalysed by peptidylglycine alpha-hydroxylating monooxygenase (PHM), and is dependent on copper, ascorbate and molecular oxygen; peptidyl-alpha-hydroxyglycine alpha-amidating lyase (PAL) catalyses the second step of the reaction [PMID: 1448112].

PHM share protein sequence similarity with dopamine-beta-monooxygenases (DBH), a class of ascorbate-dependent enzymes that requires copper as a cofactor and uses ascorbate as an electron donor. PHM and DBH share a few regions of sequence similarity, some of which contain clusters of conserved histidine residues that may be involved in copper binding [PMID: 11028916, PMID: 16301310].

Interestingly, in Drosophila, the PHM and PAL enzyme are not fused. The Drosophila genome predicts expression of one monofunctional PHM gene and two monofunctional PAL genes [PMID: 15198673]. Drosophila PHM encodes an active enzyme that is required for peptide amidation in vivo [PMID: 10993678], while both PAL proteins display PAL enzymatic activity and are involved in neuroendocrine biosynthesis [PMID: 15198673].

GO terms

Biological Process

GO:0006518 peptide metabolic process

Molecular Function

GO:0003824 catalytic activity

Cellular Component

GO:0016020 membrane

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
PRINTS