3.4.21.B25: PACE4 proprotein convertase
This is an abbreviated version!
For detailed information about PACE4 proprotein convertase, go to the full flat file.
Word Map on EC 3.4.21.B25
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3.4.21.B25
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convertases
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furin
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prohormone
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endoproteases
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furin-deficient
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furin-like
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alpha1-pdx
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dibasic
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pro-proteins
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alpha1-antitrypsin
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portland
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endoproteolysis
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diagnostics
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kexin
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kexin-like
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ski-1
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cys-rich
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medicine
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subtilisin-related
- 3.4.21.B25
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convertases
- furin
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prohormone
- endoproteases
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furin-deficient
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furin-like
- alpha1-pdx
-
dibasic
-
pro-proteins
- alpha1-antitrypsin
- portland
-
endoproteolysis
- diagnostics
- kexin
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kexin-like
- ski-1
-
cys-rich
- medicine
-
subtilisin-related
Reaction
releases mature proteins from their proproteins by cleavage of Arg-Xaa-Yaa-Arg-Zaa bonds, where Xaa can be any amino acid and Yaa is Arg or Lys =
Synonyms
PACE 4, PACE-4, PACE4, PACE4/SPC4, paired basic amino acid cleaving enzyme 4, paired basic amino acid-cleaving enzyme 4, paired basic amino-acid-cleaving enzyme-4, PC7, proprotein convertase PACE4, S08.075, SPC4, subtilisin-like proprotein convertase, subtilisin-like proprotein convertase 4, subtilisin-like proprotein convertase PACE4, XPACE4
ECTree
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Substrates Products
Substrates Products on EC 3.4.21.B25 - PACE4 proprotein convertase
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REACTION DIAGRAM
anthrax toxin PA + H2O
?
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contains the sequence RKKR at the cleavage site
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?
benzyloxycarbonyl-REKR-7-amido-4-trifluoromethylcoumarin + H2O
?
-
-
-
?
human immunodeficiency virus type 1 Vpr + H2O
?
undergoes proteolytic processing at a very well conserved proprotein convertase cleavage site, R85QRR88-/-, proprotein convertases PC5 and PACE4 can efficiently process extracellular Vpr
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-
?
pGlu-Arg-Thr-Lys-Arg-7-amido-4-methylcoumarin + H2O
pGlu-Arg-Thr-Lys-Arg + 7-amino-4-methylcoumarin
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-
-
?
pro-beta site APP cleaving enzyme + H2O
beta site APP cleaving enzyme + ?
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i.e. BACE, weak substrate
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?
proADAMTS-4 + H2O
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recombinant PACE4 activates proADAMTS-4 by removal of the prodomain
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-
?
proADAMTS-5 + H2O
?
recombinant PACE4 activates proADAMTS-5 by removal of the prodomain
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-
?
prosomatostatin + H2O
somatostatin-14 + somatostatin-28
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enzyme cleaves at a dibasic Arg-Lys site
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?
Pyr-Arg-Thr-Lys-Arg-4-methylcoumarin-7-amide + H2O
Pyr-Arg-Thr-Lys-Arg + 7-amino-4-methylcoumarin
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-
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ir
tert-butyloxycarbonyl-Arg-Val-Arg-Arg-4-methylcoumarin 7-amide + H2O
tert-butyloxycarbonyl-Arg-Val-Arg-Arg + 7-amino-4-methylcoumarin
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-
-
?
Vg1 + H2O
?
Vg1 in a TgF beta-related growth factor localized to vegetal blastomers in Xenopus embryos
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-
?
mature insulin receptor isoform B + ?
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-
-
?
insulin receptor isoform B zymogen + H2O
mature insulin receptor isoform B + ?
maturation
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-
?
?
key role of the convertases furin, PACE4, PC5 and/or PC7 in the generation and secretion of active hepcidin
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-
?
preprohepcidin + H2O
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key role of the convertases furin, PACE4, PC5 and/or PC7 in the generation and secretion of active hepcidin. PC7 processes this peptide at the cleavage site of preprohepcidin PMFQRRRRR-/-, resulting in a major 1305 Da N-terminal product. Two minor products with masses of 149 Da and 993 Da are also detected which correspond to the loss of one (PMFQRRRR) or two (PMFQRRR) C-terminal Arg, respectively
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-
?
mature bone morphogenetic protein 6 + ?
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BMP6, the substrate is exclusively found in hypertrophic chondrocytes
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-
?
proform bone morphogenetic protein 6 + H2O
mature bone morphogenetic protein 6 + ?
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BMP6, recombinantly expressed FLAG-tagged human substrate protein. The enzyme recognizes the sequence RTTR(371-374) of human BMP6 and cleaves proBMP6 at its C-terminus
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-
?
mature von Willebrand factor + ?
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-
-
?
von Willebrand factor precursor + H2O
mature von Willebrand factor + ?
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-
-
?
von Willebrand factor precursor + H2O
mature von Willebrand factor + ?
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-
?
von Willebrand factor precursor + H2O
mature von Willebrand factor + ?
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cleavage requires both the P4 arginine and the P2 lysine
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?
?
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enzyme cleaves at sites with paired basic amino acid residues
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?
additional information
?
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PACE4-CS recognizes the motifs X-Ala and X-Pro
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?
additional information
?
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enzyme binds tightly to heparin and anchors heparan sulfate proteoglycans at the extracellular matrix, role in spatiotemporal regulation of TGFbeta-related factors' biological activity
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?
additional information
?
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no activity with insulin receptor isoform A zymogen
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-
?
additional information
?
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enzyme requires basic residues in the -1, -2 and -4 position of the substrate sequence, can recognize RAAR and, to a much lesser extent, KR and RR
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?
additional information
?
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role in proteolytic activation of anthrax toxin PA
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?
additional information
?
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does not cleave proopiomelanocortin, proglucagon, prosomatostatin and secretogranin in neuroendocrine cells
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-
?
additional information
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the main substrates for PACE4 are membrane type matrix metalloproteinases
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-
?
additional information
?
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PACE4 is identified as a proprotein convertase responsible for activation of aggrecanases in osteoarthritic and cytokine-stimulated cartilage
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-
?
additional information
?
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PACE4 regulates the submandibular gland development via the activation of some growth/differentiation factors
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-
?
additional information
?
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no cleavage of Xnr5, Derrière or ActivinB pro-proteins
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-
?
additional information
?
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no cleavage of Xnr5, Derrière or ActivinB pro-proteins
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-
?