Information on EC 3.4.21.B27 - proprotein convertase 7

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The enzyme appears in viruses and cellular organisms

EC NUMBER
COMMENTARY hide
3.4.21.B27
preliminary BRENDA-supplied EC number
RECOMMENDED NAME
GeneOntology No.
proprotein convertase 7
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REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
cleaves proteins typically at sites marked by the consensus Arg-Xaa-(Lys/Arg)-Arg sequence
show the reaction diagram
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-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
cleavage of C-N-linkage
hydrolysis of peptide bond
CAS REGISTRY NUMBER
COMMENTARY hide
99676-46-7
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
gene pcsk7
UniProt
Manually annotated by BRENDA team
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-
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Manually annotated by BRENDA team
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-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
the enzyme is a member of the subtilisin/kexin family of pro-protein convertases
malfunction
metabolism
-
when iron is limiting, human transferrin receptor TfR1 levels increase at least in part by way of the down-regulation of PC7 enzyme expression
physiological function
additional information
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
2-aminobenzoyl-GGRRTRREAI-(3-nitro)-Tyr-A + H2O
?
show the reaction diagram
-
fluorogenic substrate encompassing the processing site of envelope glycoproteins of ebola virus
-
?
2-aminobenzoyl-RNTPRERKKRGL-(3-nitro)-Tyr-A + H2O
?
show the reaction diagram
-
-
-
?
2-aminobenzoyl-RNTPRERRRKKRGL-(3-nitro)-Tyr-A + H2O
?
show the reaction diagram
-
fluorogenic substrate encompassing the processing site of envelope glycoproteins of Hong Kong virus
-
?
2-aminobenzoyl-RNTPRKKRGL-(3-nitro)-Tyr-A + H2O
?
show the reaction diagram
-
-
-
?
2-aminobenzoyl-RNTPRRRKKRGL-(3-nitro)-Tyr-A + H2O
?
show the reaction diagram
-
-
-
?
2-aminobenzoyl-SKKRKRRFLG-(3-nitro)-Tyr-A + H2O
?
show the reaction diagram
-
fluorogenic substrate encompassing the processing site of envelope glycoproteins of respiratory syncytial virus
-
?
HIV-1 gp160 + H2O
HIV1 gp120 + gp41
show the reaction diagram
-
-
-
-
?
human immunodeficiency virus envelope glycoprotein pg160 + H2O
?
show the reaction diagram
-
-
-
?
human transferrin receptor 1 + H2O
?
show the reaction diagram
KEKR-4-methylcoumarin 7-amide + H2O
KEKR + 4-methylcoumarin 7-amine
show the reaction diagram
-
weak substrate
-
?
L-pyroglutamyl-Arg-Thr-Lys-Arg-4-methylcoumarin 7-amide + H2O
L-pyroglutamyl-Arg-Thr-Lys-Arg + 4-methylcoumarin 7-amine
show the reaction diagram
-
-
-
?
Lys-Ser-Val-Lys-Lys-Arg-Ser-Val-Ser-Glu-Ile-Gln-Leu + H2O
Lys-Ser-Val-Lys-Lys-Arg + Ser-Val-Ser-Glu-Ile-Gln-Leu
show the reaction diagram
-
-
-
-
?
membrane-bound leptin receptor + H2O
soluble leptin receptor
show the reaction diagram
-
-
-
-
?
pERTKR-4-methylcoumarin 7-amide + H2O
pERTKR + 4-methylcoumarin 7-amine
show the reaction diagram
pGlu-Arg-Thr-Lys-Arg-4-methylcoumarin 7-amide + H2O
pGlu-Arg-Thr-Lys-Arg + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
?
preprohepcidin + H2O
?
show the reaction diagram
pro-bone morphogenetic protein 4 + H2O
bone morphogenetic protein 4 + ?
show the reaction diagram
-
PC7, or a convertase with similar substrate specificity, functions to selectively cleave the S1 site of pro-BMP4 in a developmentally regulated fashion
-
-
?
pro-parathyroid hormone tridecapeptide + H2O
?
show the reaction diagram
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-
-
?
pro-PC4 heptadecapeptide + H2O
?
show the reaction diagram
-
-
-
?
pro-VEGF-C + H2O
VEGF-C + ?
show the reaction diagram
proneuroendocrine protein 7B2 + H2O
neuroendocrine protein 7B2
show the reaction diagram
-
-
-
-
?
pyro-ERTKR-7-amido-4-methylcoumarin + H2O
pyro-ERTKR + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
-
?
Q-VEGF-C + H2O
VEGF-C + ?
show the reaction diagram
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intramolecularly quenched fluorogenic peptide
-
?
Q-VHSIIRRSLP + H2O
Q-VHSIIRR + SLP
show the reaction diagram
-
synthetic fluorigenic peptide mimicking the cleavage site of pro-VEGF-C
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?
RFAR-4-methylcoumarin 7-amide + H2O
RFAR + 4-methylcoumarin 7-amine
show the reaction diagram
-
weak substrate
-
?
RKKR-4-methylcoumarin 7-amide + H2O
RKKR + 4-methylcoumarin 7-amine
show the reaction diagram
-
-
-
?
RSKR-4-methylcoumarin 7-amide + H2O
RSKR + 4-methylcoumarin 7-amine
show the reaction diagram
RVRR-4-methylcoumarin 7-amide + H2O
RVRR + 4-methylcoumarin 7-amine
show the reaction diagram
-
weak substrate
-
?
Tyr-Glu-Thr-Leu-Arg-Arg-Arg-Val-Lys-Arg-Ser-Leu-Val-Val-Pro-Thr-Asp + H2O
Tyr-Glu-Thr-Leu-Arg-Arg-Arg-Val-Lys-Arg + Ser-Leu-Val-Val-Pro-Thr-Asp
show the reaction diagram
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-
-
-
?
YEKERSKR-4-methylcoumarin 7-amide + H2O
YEKERSKR + 4-methylcoumarin 7-amine
show the reaction diagram
-
-
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?
additional information
?
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NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
human transferrin receptor 1 + H2O
?
show the reaction diagram
preprohepcidin + H2O
?
show the reaction diagram
-
key role of the convertases furin, PACE4, PC5 and/or PC7 in the generation and secretion of active hepcidin
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-
?
pro-VEGF-C + H2O
VEGF-C + ?
show the reaction diagram
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pro-VEGF-C processing is required for VEGF-C induced tumor antiogenesis and lymphangiogenesis
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?
additional information
?
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
14-dehydroandrographolide 3,19-O-disuccinoyl monoester
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14-dehydroandrographolide succinoyl monoester
alpha1-PDX
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andrographolide 3alpha,14alpha,19-O-trisuccinate
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andrographolide 3alpha,14beta,19-O-trisuccinate
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CuSO4
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97% inhibition at 1 mM
D-Arg-Arg-Arg-Arg-Arg-Arg
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D-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Arg
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decanoyl-RVKR-chloromethylketone
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EAVLAKHEAVRWHSEQRLLKRAKR
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C-terminal region of the PC7 prosegment, strong inhibition, competitive
EDTA
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95% inhibition at 10 mM
histatin-3
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competitive, reversible, strong inhibitor
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histatin-5
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L-Arg-Arg-Arg-Arg
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L-Arg-Arg-Arg-Arg-Arg
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L-Arg-Arg-Arg-Arg-Arg-Arg
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L-Arg-Arg-Arg-Arg-Arg-Arg-Arg
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L-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Arg
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L-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Arg
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monopyridinium andrographolide 3alpha,14alpha/beta,19-O-trisuccinate
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N-terminal pro-segment of PC7
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inhibits its parent enzyme, 50% inhibition at 0.0000004 mM
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neoandrographolide
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syn: 14-deoxyandrographiside, weak inhibitor, 50% inhibition between 0.5 mM and 2 mM
ZnSO4
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94% inhibition at 1 mM
additional information
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the enzyme displays resistance to alpha1-PDX
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0031
2-aminobenzoyl-GGRRTRREAI-(3-nitro)-Tyr-A
-
pH 7, 37C
0.0021
2-aminobenzoyl-RNTPRERKKRGL-(3-nitro)-Tyr-A
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pH 7, 37C
0.0051
2-aminobenzoyl-RNTPRERRRKKRGL-(3-nitro)-Tyr-A
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pH 7, 37C
0.0042
2-aminobenzoyl-RNTPRKKRGL-(3-nitro)-Tyr-A
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pH 7, 37C
0.0033
2-aminobenzoyl-RNTPRRRKKRGL-(3-nitro)-Tyr-A
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pH 7, 37C
0.0031
2-aminobenzoyl-SKKRKRRFLG-(3-nitro)-Tyr-A
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pH 7, 37C
0.164
pERTKR-4-methylcoumarin 7-amide
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pH 6.5
0.113
Q-VEGF-C
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pH 7.3, 37C
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0304
14-dehydroandrographolide 3,19-O-disuccinoyl monoester
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-
0.036
andrographolide 3alpha,14beta,19-O-trisuccinate
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0.001875
D-Arg-Arg-Arg-Arg-Arg-Arg
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in 20 mM Bis-Tris, pH 6.5, 1 mM CaCl2, at 37C
0.000081
D-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Arg
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in 20 mM Bis-Tris, pH 6.5, 1 mM CaCl2, at 37C
0.000007
EAVLAKHEAVRWHSEQRLLKRAKR
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pH 7
0.0024
histatin-3
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pH 6.5
-
0.0123
histatin-5
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pH 6.5
-
0.006
L-Arg-Arg-Arg-Arg
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in 20 mM Bis-Tris, pH 6.5, 1 mM CaCl2, at 37C
0.0011
L-Arg-Arg-Arg-Arg-Arg
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in 20 mM Bis-Tris, pH 6.5, 1 mM CaCl2, at 37C
0.00105
L-Arg-Arg-Arg-Arg-Arg-Arg
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in 20 mM Bis-Tris, pH 6.5, 1 mM CaCl2, at 37C
0.000312
L-Arg-Arg-Arg-Arg-Arg-Arg-Arg
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in 20 mM Bis-Tris, pH 6.5, 1 mM CaCl2, at 37C
0.0002
L-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Arg
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in 20 mM Bis-Tris, pH 6.5, 1 mM CaCl2, at 37C
0.00012
L-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Arg
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in 20 mM Bis-Tris, pH 6.5, 1 mM CaCl2, at 37C
0.026
monopyridinium andrographolide 3alpha,14alpha/beta,19-O-trisuccinate
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.4
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assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
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assay at
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
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correlation between plasma levels of the soluble human transferrin receptor 1 and the PCSK7 gene
Manually annotated by BRENDA team
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primary
Manually annotated by BRENDA team
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expression is restricted to non-cancerous HOSE cell lines
Manually annotated by BRENDA team
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T-lymphocyte including CD4+ cells
Manually annotated by BRENDA team
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the cleaved form of PC7 is present in both embryos and oocytes, PC7-like activity is not detected in oocytes
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
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trans-Golgi network
Manually annotated by BRENDA team
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truncated enzyme
-
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
12350
-
MALDI-TOF mass spectroscopy
65000
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SDS-PAGE, truncated enzyme
67000
calculated from nucleic acid sequence
101000
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
glycoprotein
lipoprotein
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the enzyme has palmitoylated cysteines, Cys699 and Cys704 within its C-terminus, these posttranslational modifications are not required for transferrin receptor 1 shedding
proteolytic modification
side-chain modification
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Cys699 and Cys704 are palmitoylated
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
Mono Q HR column chromatography, HIC 6FF column chromatography, and Superdex 200 gel filtration
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expressed in HEK-293 and COS-1 cells
expressed in HEK-293 cells, COS-1 cells, and Neuro2A cells
-
expressed in Schneider 2 cells
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gene pcsk7, DNA and amino acid sequence determination and analysis, sequence comparison,expression analysis
gene SPC7, DNA and amino acid sequence determination and analysis
isoform PC7A; isoform PC7B, lacking a 39bp segment compared to PC7A
recombinant enzyme expression of wild-type enzyme mutant enzymes in HuH-7 cells, also expression of the wild-type enzyme in Hep-G2 cells, HEK-293 cells, K-562 cells, CHO cells, and COS-1 cells, functional co-expression with the human transferrin receptor 1 substrate
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wild-type and truncated form
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
depletion of iron in the medium of hepatoma cell lines incubated with the iron chelator desferrioxamine results in the enzyme downregulation
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high mRNA levels of PC7 in the visual cortex are seen at postnatal week 1
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PC7 expression levels in the visual cortex are sharply reduced at postnatal week 5 compared to postnatal week 3
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
C699A
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site-directed mutagenesis, the mutant activity with substrate transferrin receptor 1 is unaltered compared to the wild-type enzyme
C704A
-
site-directed mutagenesis, the mutant activity with substrate transferrin receptor 1 is unaltered compared to the wild-type enzyme
D188G
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site-directed mutagenesis, the autocatalytic processing of the PC7 zymogen is severely impaired leading to accumulation of the inactive pro-enzyme
R316C
-
site-directed mutagenesis, the autocatalytic processing of the PC7 zymogen is severely impaired leading to accumulation of the inactive pro-enzyme
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine