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Information on EC 3.4.21.B25 - PACE4 proprotein convertase and Organism(s) Rattus norvegicus and UniProt Accession Q78EH2

for references in articles please use BRENDA:EC3.4.21.B25
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EC Tree
     3 Hydrolases
         3.4 Acting on peptide bonds (peptidases)
             3.4.21 Serine endopeptidases
                3.4.21.B25 PACE4 proprotein convertase
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This record set is specific for:
Rattus norvegicus
UNIPROT: Q78EH2
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The taxonomic range for the selected organisms is: Rattus norvegicus
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
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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
pace4, pace-4, proprotein convertase pace4, paired basic amino acid-cleaving enzyme 4, xpace4, pace 4, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
PACE4
paired basic amino-acid-cleaving enzyme-4
-
proprotein convertase PACE4
-
-
subtilisin-like proprotein convertase 4
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of peptide bond
cleavage of C-N-linkage
CAS REGISTRY NUMBER
COMMENTARY hide
151662-24-7
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
benzyloxycarbonyl-REKR-7-amido-4-trifluoromethylcoumarin + H2O
?
show the reaction diagram
-
-
-
?
proADAMTS-4 + H2O
?
show the reaction diagram
recombinant PACE4 activates proADAMTS-4 by removal of the prodomain
-
-
?
proADAMTS-5 + H2O
?
show the reaction diagram
recombinant PACE4 activates proADAMTS-5 by removal of the prodomain
-
-
?
BMP2 proprotein + H2O
BMP2 + ?
show the reaction diagram
-
-
-
-
?
pro-branching morphogenesis protein 2 + H2O
?
show the reaction diagram
-
-
-
-
?
tert-butyloxycarbonyl-Arg-Val-Arg-Arg-4-methylcoumarin 7-amide + H2O
tert-butyloxycarbonyl-Arg-Val-Arg-Arg + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
?
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
pro-branching morphogenesis protein 2 + H2O
?
show the reaction diagram
-
-
-
-
?
additional information
?
-
PACE4 is identified as a proprotein convertase responsible for activation of aggrecanases in osteoarthritic and cytokine-stimulated cartilage
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Ca2+
-
dependent on
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2-(11-hydroxy-3-oxo-3H-dibenzo[c,h]xanthen-7-yl)benzoic acid
-
3,3',3'',3'''-(benzene-1,4-diyldimethanetriyl)tetrakis(4-hydroxy-2H-chromen-2-one)
-
3,3'-(1,3-benzodioxol-5-ylmethanediyl)bis(4-hydroxy-2H-chromen-2-one)
-
3,3'-(2,3-dihydro-1H-inden-5-ylmethanediyl)bis(4-hydroxy-2H-chromen-2-one)
-
decanoyl-RVKR-chloromethyl ketone
-
decanoyl-Arg-Val-Lys-Arg-chloromethylketone
-
100% inhibition at 0.01 mM
decanoyl-L-Arg-L-Val-L-Lys-chloromethylketone
-
potent inhibitor
decanoyl-L-Arg-L-Val-L-Lys-L-Arg-chloromethylketone
-
potent inhibitor
EDTA
-
78% inhibition at 10 mM
EGTA
-
71% inhibition at 10 mM
HgCl2
-
99% inhibition at 1 mM
L-Arg-L-Tyr-L-Lys-L-Arg-L-Thr
-
peptide inhibitor of PACE4
leupeptin
-
94% inhibition at 1 mM
ZnCl2
-
100% inhibition at 2 mM
additional information
-
not inhibited by leupeptin and soybean trypsin inhibitor
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.251
benzyloxycarbonyl-REKR-7-amido-4-trifluoromethylcoumarin
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.012
2-(11-hydroxy-3-oxo-3H-dibenzo[c,h]xanthen-7-yl)benzoic acid
-
0.0083
3,3',3'',3'''-(benzene-1,4-diyldimethanetriyl)tetrakis(4-hydroxy-2H-chromen-2-one)
-
0.014
3,3'-(1,3-benzodioxol-5-ylmethanediyl)bis(4-hydroxy-2H-chromen-2-one)
-
0.013
3,3'-(2,3-dihydro-1H-inden-5-ylmethanediyl)bis(4-hydroxy-2H-chromen-2-one)
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.002
L-Arg-L-Tyr-L-Lys-L-Arg-L-Thr
Rattus norvegicus
-
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
presence of PACE4 protein is restricted to chondrocytes of healthy cartilage, whereas the expression is increased in osteoarthritis cartilage
Manually annotated by BRENDA team
Purkinje cells, highest levels
Manually annotated by BRENDA team
lower levels
Manually annotated by BRENDA team
additional information
subcortical nucleus
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
-
silencing of PACE4 causes the suppression of branching morphogenesis and aquaporin 5 expression in rat embryonic submandibular gland rudiments culture system
physiological function
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
PCSK4_RAT
678
0
75740
Swiss-Prot
-
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
106000
-
SDS-PAGE, precursor protein
45000
SDS-PAGE, truncated form
97000
-
SDS-PAGE, mature protein
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
glycoprotein
3 potential N-glycosylation sites
proteolytic modification
-
cleavage activates the enzyme
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expressed in AtT-20 cells
expressed in HEK 293 cells
expressed in transgenic keratinocytes of K5.PACE4 mice
-
wild-type and deletion of the Cys-rich region
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
decanoyl-L-Arg-L-Val-L-Lys-L-Arg-chloromethylketone suppresses the expression of PACE4
-
the expression of PACE4 is not suppressed by furin
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
PACE4 represents a target for the development of osteoarthritis therapeutics
medicine
-
PACE4 overexpression results in enhanced susceptibility to carcinogenesis and tumor progression pointing to a new target for blocking tumor cell invasiveness, PACE4 enhances induced epidermal proliferation, activates matrix metalloproteinases in vivo, disrupts basement membrane structure, increases susceptibility to skin cancer and induces higher levels of matrix metalloproteinases and tumors of advanced malignant phenotype
additional information
the pattern of PACE4 expression in development suggests a role in the extracellular actions or activation of inductive signals
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Mains, R.E.; Berard, C.A.; Denault, J.B.; Zhou, A.; Johnson, R.C.; Leduc, R.
PACE4: a subtilisin-like endoprotease with unique properties
Biochem. J.
321
587-593
1997
Rattus norvegicus
-
Manually annotated by BRENDA team
Johnson, R.C.; Darlington, D.N.; Hand, T.A.; Bloomquist, B.T.; Mains, R.E.
PACE4: a subtilisin-like endoprotease prevalent in the anterior pituitary and regulated by thyroid status
Endocrinology
135
1178-1185
1994
Rattus norvegicus (Q63415), Rattus norvegicus
Manually annotated by BRENDA team
Bassi, D.E.; Lopez De Cicco, R.; Cenna, J.; Litwin, S.; Cukierman, E.; Klein-Szanto, A.J.
PACE4 expression in mouse basal keratinocytes results in basement membrane disruption and acceleration of tumor progression
Cancer Res.
65
7310-7319
2005
Rattus norvegicus
Manually annotated by BRENDA team
Mains, R.E.
Proprotein convertase PACE4
Handbook of Proteolytic Enzymes (Barrett, A. J. , Rawlings, N. D. , Woessner, J. F. , Eds. ) Academic Press
2
1871-1874
2004
Aplysia sp., Mus musculus, Homo sapiens (P29122), Rattus norvegicus (Q63415)
-
Manually annotated by BRENDA team
Akamatsu, T.; Purwanti, N.; Karabasil, M.R.; Li, X.; Yao, C.; Kanamori, N.; Hosoi, K.
Temporospatially regulated expression of subtilisin-like proprotein convertase PACE4 (SPC4) during development of the rat submandibular gland
Dev. Dyn.
236
314-320
2007
Rattus norvegicus (Q63415)
Manually annotated by BRENDA team
Malfait, A.M.; Arner, E.C.; Song, R.H.; Alston, J.T.; Markosyan, S.; Staten, N.; Yang, Z.; Griggs, D.W.; Tortorella, M.D.
Proprotein convertase activation of aggrecanases in cartilage in situ
Arch. Biochem. Biophys.
478
43-51
2008
Rattus norvegicus (Q78EH2)
Manually annotated by BRENDA team
Akamatsu, T.; Azlina, A.; Purwanti, N.; Karabasil, M.R.; Hasegawa, T.; Yao, C.; Hosoi, K.
Inhibition and transcriptional silencing of a subtilisin-like proprotein convertase, PACE4/SPC4, reduces the branching morphogenesis of and AQP5 expression in rat embryonic submandibular gland
Dev. Biol.
325
434-443
2009
Rattus norvegicus (Q78EH2)
Manually annotated by BRENDA team
Komiyama, T.; Coppola, J.M.; Larsen, M.J.; van Dort, M.E.; Ross, B.D.; Day, R.; Rehemtulla, A.; Fuller, R.S.
Inhibition of furin/PC-catalyzed surface and intracellular processing by small molecules
J. Biol. Chem.
284
15729-15738
2009
Rattus norvegicus (Q78EH2)
Manually annotated by BRENDA team
Byun, S.; Tortorella, M.D.; Malfait, A.M.; Fok, K.; Frank, E.H.; Grodzinsky, A.J.
Transport and equilibrium uptake of a peptide inhibitor of PACE4 into articular cartilage is dominated by electrostatic interactions
Arch. Biochem. Biophys.
499
32-39
2010
Rattus norvegicus
Manually annotated by BRENDA team
Akamatsu, T.; Azlina, A.; Javkhlan, P.; Hasegawa, T.; Yao, C.; Hosoi, K.
Salivary gland development: its mediation by a subtilisin-like proprotein convertase, PACE4
J. Med. Invest.
56
241-246
2009
Rattus norvegicus
Manually annotated by BRENDA team
Akamatsu, T.
Physiological role of a subtilisin - Like proprotein convertase, PACE4, in submandibular gland development
J. Oral Biosci.
52
81-93
2010
Rattus norvegicus
-
Manually annotated by BRENDA team