CLV_PCSK_PC1ET2_1
ELM server details
ELM
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Functional site class:
PCSK cleavage site
Functional site description:
The subtilisin-like proprotein convertases are expressed extensively in mammalian neural and endocrine cells and play a major role in the proteolytic processing of both neuropeptide and peptide hormone precursors.
ELM(s): CLV_PCSK_PC1ET2_1, CLV_PCSK_SKI1_1, CLV_PCSK_KEX2_1, CLV_PCSK_FUR_1, CLV_PCSK_PC7_1
CLV_PCSK_PC1ET2_1 description: NEC1/NEC2 cleavage site (Lys-Arg-|-Xaa)
Pattern: KR.
Present in taxon(s): Vertebrata  
Not represented in taxon(s):

o 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.

o Selected references

Johanning K, Juliano MA, Juliano L, Lazure C, Lamango NS, Steiner DF, Lindberg I
Specificity of prohormone convertase 2 on proenkephalin and proenkephalin-related substrates.
J Biol Chem 1998 Aug 28;273(35) : 22672-80.
PMID: 9712897

Lindberg I, van den Hurk WH, Bui C, Batie CJ
Enzymatic characterization of immunopurified prohormone convertase 2: potent inhibition by a 7B2 peptide fragment.
Biochemistry 1995 Apr 25;34(16) : 5486-93.
PMID: 7727407

Seidah NG, Chretien M, Day R
The family of subtilisin/kexin like pro-protein and pro-hormone convertases: divergent or shared functions.
Biochimie 1994;76(3) : 197-209.
PMID: 7819324

Seidah NG, Hamelin J, Gaspar AM, Day R, Chretien M
The cDNA sequence of the human pro-hormone and pro-protein convertase PC1.
DNA Cell Biol 1992 May;11(4) : 283-9.
PMID: 1605851

o This ELM has been assigned the following Gene Ontology (GO) terms for biological process, cellular component and molecular function.

Biological Process
  proteolysis and peptidolysis
Cellular Component
  extracellular
  Golgi apparatus
  Golgi membrane
Molecular Function
  proprotein convertase 1
  proprotein convertase 2

 

o Instances for CLV_PCSK_PC1ET2_1

No instances annotated