 Abstract
The members of this family are proprotein convertases that process latent precursor proteins into their biologically active products.
The prohormone-processing yeast KEX2 protease can act as an intracellular membrane protein or a soluble, secreted endopeptidase. The protein is required for processing of precursors of alpha-factor and killer toxin.
PCSK1 (proprotein convertase 1, NEC1) and PCSK2 (proprotein convertase 2, NEC2) are type I proinsulin-processing enzymes that play a key role in regulating insulin biosynthesis. They are also known to cleave proopiomelanocortin, prorenin, proenkephalin, prodynorphin, prosomatostatin and progastrin.
PACE4 (paired basic amino acid cleaving system 4, SPC4) is a calcium-dependent serine endoprotease that can cleave precursor
protein at their paired basic amino acid processing sites. Some of its substrates are - transforming growth factor beta related proteins, proalbumin, and von Willebrand factor.
Furin (PACE, paired basic amino acid cleaving enzyme, membrane associated receptor protein) is serine endoprotease responsible for
processing variety of substrates (proparathyroid hormone, transforming growth factor beta 1 precursor, proalbumin, pro-beta-secretase, membrane type-1 matrix metalloproteinase, beta subunit of pro-nerve growth factor and von Willebrand factor).
PC7 (proprotein convertase subtilisin/kexin type 7) is a closely related to PACE and PACE4. This calcium-dependent serine endoprotease is concentrated in the trans-Golgi network, associated with the membranes, and is not secreted. It can process proalbumin. PC7 and furin are also thought to be one of the proteases responsible for the activation of HIV envelope glycoproteins gp160 and gp140.
Selected references
| Seidah NG, Mowla SJ, Hamelin J, Mamarbachi AM, Benjannet S, Toure BB, Basak A, Munzer JS, Marcinkiewicz J, Zhong M, Barale JC, Lazure C, Murphy RA, Chretien M, Marcinkiewicz M | | Mammalian subtilisin/kexin isozyme SKI-1: A widely expressed proprotein
convertase with a unique cleavage specificity and cellular localization. | | Proc Natl Acad Sci U S A 1999 Feb 16;96(4) : 1321-6. | | PMID: 99145548 |
This ELM has been assigned the following Gene Ontology (GO) terms for biological process, cellular component and molecular function.
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Biological Process |
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proteolysis and peptidolysis
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Cellular Component |
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endoplasmic reticulum lumen |
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endoplasmic reticulum |
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Golgi apparatus |
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Molecular Function |
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subtilase |
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peptidase |
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