Peptidylglycine α‐amidating monooxygenase: A multifunctional protein with catalytic, processing, and routing domains

Abstract

Peptide α‐amidation is a widespread, often essential posttranslational modification shared by many bioactive peptides and accomplished by the products of a single gene encoding a multifunctional protein, peptidylglycine α‐amidating monooxygenase (PAM). PAM has two catalytic domains that work sequentially to produce the final α‐amidated product peptide. Tissue‐specific alternative splicing can generate forms of PAM retaining or lacking a domain required for the posttranslational separation of the two catalytic activities by endoproteases found in neuroendocrine tissue. Tissue‐specific alternative splicing also governs the presence of a transmembrane domain and generation of integral membrane or soluble forms of PAM. The COOH‐terminal domain of the integral membrane PAM proteins contains routing information essential for the retrieval of PAM from the surface of endocrine and nonendocrine cells. Tissue‐specific endoproteolytic processing can generate soluble PAM proteins from integral membrane precursors. Soluble PAM proteins are rapidly secreted from stably transfected nonneuroendo‐crine cells but are stored in the regulated secretory granules characteristic of neurons and endocrine cells. Copyright © 1993 The Protein Society