Mammalian neural and endocrine pro-protein and pro-hormone convertases belonging to the subtilisin family of serine proteinases.
Conversion of pro-hormones and precursor proteins into biologically active peptides and proteins involves the concerted action of a number of convertases and post-translation modification enzymes. The identification of the yeast convertase kexin as a prototype processing enzyme led to the discovery of the mammalian convertase designated furin, PC1 and PC2. Whereas furin is ubiquitously expressed, PC1 and PC2 are found only in endocrine and neural tissues and cell lines. In man and mouse, the genes coding for furin, PC1 and PC2 reside on three different chromosomes. The analysis of the intracellular processing of PC1 and PC2 and the removal of their pro-segment is presented, together with a summary of the cleavage specificity of these enzymes for precursors such as pro-opiomelanocortin (POMC) and human pro-renin. The distinct tissue distribution of PC1 and PC2 and their coregulation with POMC in the pituitary neurointermediate lobe adds credence to their physiological role as convertases involved in the tissue-specific processing of precursor proteins.
Seidah
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NG
J.A. DeSève Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montréal, Que., Canada.
Day
R
R
Marcinkiewicz
M
M
Benjannet
S
S
Chrétien
M
M
D000595:Amino Acid Sequence; D000818:Animals; D001971:Bromocriptine / Q000494:pharmacology; D002874:Chromosome Mapping; D004702:Endocrine Glands / Q000378:metabolism; D006220:Haloperidol / Q000494:pharmacology; D006728:Hormones / Q000378:metabolism; D008969:Molecular Sequence Data; D009417:Nerve Tissue / Q000378:metabolism; D011333:Pro-Opiomelanocortin / Q000378:metabolism; D045706:Proprotein Convertase 2; D043484:Proprotein Convertases; D011487:Protein Conformation; D011498:Protein Precursors / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000032:analysis; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism; D013379:Substrate Specificity; D013381:Subtilisins / Q000235:genetics / Q000378:metabolism*; D014018:Tissue Distribution; D014158:Transcription, Genetic / Q000187:drug effects
D006728:Hormones; D011498:Protein Precursors; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; D001971:Bromocriptine; D011333:Pro-Opiomelanocortin; C489716:PCSK4 protein, human; C489717:Pcsk4 protein, mouse; D043484:Proprotein Convertases; D012697:Serine Endopeptidases; D013381:Subtilisins; C058751:KEX2 protein, S cerevisiae; D045706:Proprotein Convertase 2; D006220:Haloperidol