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2-aminobenzoyl-GGRRTRREAI-(3-nitro)-Tyr-A + H2O
?
-
fluorogenic substrate encompassing the processing site of envelope glycoproteins of ebola virus
-
?
2-aminobenzoyl-RNTPRERKKRGL-(3-nitro)-Tyr-A + H2O
?
-
-
-
?
2-aminobenzoyl-RNTPRERRRKKRGL-(3-nitro)-Tyr-A + H2O
?
-
fluorogenic substrate encompassing the processing site of envelope glycoproteins of Hong Kong virus
-
?
2-aminobenzoyl-RNTPRKKRGL-(3-nitro)-Tyr-A + H2O
?
-
-
-
?
2-aminobenzoyl-RNTPRRRKKRGL-(3-nitro)-Tyr-A + H2O
?
-
-
-
?
2-aminobenzoyl-SKKRKRRFLG-(3-nitro)-Tyr-A + H2O
?
-
fluorogenic substrate encompassing the processing site of envelope glycoproteins of respiratory syncytial virus
-
?
HIV-1 gp160 + H2O
HIV1 gp120 + gp41
-
-
-
-
?
human immunodeficiency virus envelope glycoprotein pg160 + H2O
?
-
-
-
?
human transferrin receptor 1 + H2O
?
KEKR-4-methylcoumarin 7-amide + H2O
KEKR + 7-amino-4-methylcoumarin
-
weak substrate
-
?
L-pyroglutamyl-Arg-Thr-Lys-Arg-4-methylcoumarin 7-amide + H2O
L-pyroglutamyl-Arg-Thr-Lys-Arg + 7-amino-4-methylcoumarin
-
-
-
?
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
-
-
-
-
?
membrane-bound leptin receptor + H2O
soluble leptin receptor
-
-
-
-
?
Notch 1 + H2O
?
PC7 complements furin (EC 3.4.21.75) in cleaving Notch1 independently of PLC motif-mediated trans-Golgi network access
-
-
?
pERTKR-4-methylcoumarin 7-amide + H2O
pERTKR + 7-amino-4-methylcoumarin
pGlu-Arg-Thr-Lys-Arg-4-methylcoumarin 7-amide + H2O
pGlu-Arg-Thr-Lys-Arg + 7-amino-4-methylcoumarin
-
-
-
?
pro-bone morphogenetic protein 4 + H2O
bone morphogenetic protein 4 + ?
-
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
?
-
-
-
?
pro-PC4 heptadecapeptide + H2O
?
-
-
-
?
pro-VEGF-C + H2O
VEGF-C + ?
proactivin A + H2O
activin A + ?
-
-
-
?
proneuroendocrine protein 7B2 + H2O
neuroendocrine protein 7B2
-
-
-
-
?
pyro-ERTKR-7-amido-4-methylcoumarin + H2O
pyro-ERTKR + 7-amino-4-methylcoumarin
-
-
-
-
?
Q-VEGF-C + H2O
VEGF-C + ?
-
intramolecularly quenched fluorogenic peptide
-
?
Q-VHSIIRRSLP + H2O
Q-VHSIIRR + SLP
-
synthetic fluorigenic peptide mimicking the cleavage site of pro-VEGF-C
-
?
RFAR-4-methylcoumarin 7-amide + H2O
RFAR + 7-amino-4-methylcoumarin
-
weak substrate
-
?
RKKR-4-methylcoumarin 7-amide + H2O
RKKR + 7-amino-4-methylcoumarin
-
-
-
?
RSKR-4-methylcoumarin 7-amide + H2O
RSKR + 7-amino-4-methylcoumarin
RVRR-4-methylcoumarin 7-amide + H2O
RVRR + 7-amino-4-methylcoumarin
-
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
-
-
-
-
?
YEKERSKR-4-methylcoumarin 7-amide + H2O
YEKERSKR + 7-amino-4-methylcoumarin
-
-
-
?
additional information
?
-
human transferrin receptor 1 + H2O
?
cleavage at an atypical site KTECER-/-LA
-
-
?
human transferrin receptor 1 + H2O
?
cleavage at an atypical site KTECER-/-LA, in which the P1 Arg100 and P6 Lys95 are critical,.cleavage at Arg100
-
-
?
human transferrin receptor 1 + H2O
?
cleavage at an atypical site KTECER-/-LA, in which the P1 Arg100 and P6 Lys95 are critical, cleavage at Arg100. Identification of the KTECER100;LA cleavage site by site-directed mutagenesis using substrate mutants, overview
-
-
?
pERTKR-4-methylcoumarin 7-amide + H2O
pERTKR + 7-amino-4-methylcoumarin
-
-
-
?
pERTKR-4-methylcoumarin 7-amide + H2O
pERTKR + 7-amino-4-methylcoumarin
-
-
-
?
pERTKR-4-methylcoumarin 7-amide + H2O
pERTKR + 7-amino-4-methylcoumarin
-
-
-
?
preprohepcidin + H2O
?
-
key role of the convertases furin, PACE4, PC5 and/or PC7 in the generation and secretion of active hepcidin
-
-
?
preprohepcidin + H2O
?
-
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
-
-
?
pro-VEGF-C + H2O
VEGF-C + ?
-
cleaves at the physiological HSIIRRSL site after R227
-
?
pro-VEGF-C + H2O
VEGF-C + ?
-
pro-VEGF-C processing is required for VEGF-C induced tumor antiogenesis and lymphangiogenesis
-
?
RSKR-4-methylcoumarin 7-amide + H2O
RSKR + 7-amino-4-methylcoumarin
-
-
-
?
RSKR-4-methylcoumarin 7-amide + H2O
RSKR + 7-amino-4-methylcoumarin
-
weak substrate
-
?
additional information
?
-
-
no cleavage of HIV-1 gp120 into gp77 + gp53
-
-
?
additional information
?
-
-
soluble proprotein convertase PC7 cannot process wild type epidermal growth factor precursor
-
-
?
additional information
?
-
-
the enzyme indirectly induces the processing of membrane-bound and soluble epidermal growth factor precursor into an about 115 kDa transmembrane form (EGF-115) at the VHPR290 motif. The production of EGF-115 is most probably achieved via the activation by PC7 of a latent serine and/or cysteine protease(s)
-
-
?
additional information
?
-
hemojuvelin is not directly cleaved by the enzyme despite the presence of a RNRR motif. No activity on hepcidin
-
-
?
additional information
?
-
no activity with hepcidin
-
-
?
additional information
?
-
-
soluble proprotein convertase PC7 cannot process wild type epidermal growth factor precursor
-
-
?
additional information
?
-
-
the enzyme indirectly induces the processing of membrane-bound and soluble epidermal growth factor precursor into an about 115 kDa transmembrane form (EGF-115) at the VHPR290 motif. The production of EGF-115 is most probably achieved via the activation by PC7 of a latent serine and/or cysteine protease(s)
-
-
?
additional information
?
-
-
general recognition sequence of either Arg/Lys-Arg- or Arg/Lys-(Xaa)n-Arg-
-
-
?
additional information
?
-
-
the PC7 precursor protein undergoes efficient autocatalytic activation in both oocytes and embryos. PC7 requires a P2 basic residue to cleave a substrate
-
-
?
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evolution
the enzyme is a member of the subtilisin/kexin family of pro-protein convertases
evolution
four of nine conserved proprotein convertases (PCs), including furin, Pace4, PC5A/B, and PC7, cleave substrates after the minimal dibasic recognition motif (K/R)-(X)n-(K/R)Y, where n is 0, 2, 4, or 6 and X can be any amino acid. In 152 PC sequences examined across species, the catalytic sites are 95% identical
malfunction
-
cells silenced for proprotein convertase 7 have substantially reduced MHC class I surface levels caused by high instability and significantly delayed surface accumulation of these molecules
malfunction
an enzyme PC7 chimera, in which the transmembrane domain and the cytosolic tail are replaced by that of the convertase furin, loses its ability to cleave the transferrin receptor
malfunction
enzyme loss of function suppresses markers for anterior patterning of neural tissues and early eye development
malfunction
inhibiting the enzyme in zebrafish results in various developmental defects and dysregulation of gene expressions, phenotypes, overview
malfunction
the PLC motif in the cytosolic tail of proprotein convertase 7 (PC7) is dispensable for endosomal activity, but is specifically required for trans-Golgi network (TGN) recycling and to rescue proactivin-A cleavage in furin-depleted B16-F1 melanoma cells. In sharp contrast, PC7 complements furin in cleaving Notch1 independently of PLC-mediated TGN access
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
metabolism
all proprotein convertase (PC) activity detected in the trans-Golgi network/endosomal system of B16-F1 cells is mediated by furin, but not by endogenous PC7. Enzyme PC7 can rescue proActivin-A cleavage in furin-depleted B16-F1 melanoma cells
physiological function
-
proprotein convertase 7 is required for normal MHC class I surface levels in the context of a defective peptide-loading complex
physiological function
-
proprotein convertase PC7 enhances the activation of the epidermal growth factor receptor pathway through processing of the epidermal growth factor precursor
physiological function
-
proprotein convertase PC7 enhances the activation of the epidermal growth factor receptor pathway through processing of the epidermal growth factor precursor
physiological function
the enzyme cleaves many pro-proteins to release their active proteins, including members of the bone morphogenetic protein (BMP) family of signaling molecules. The enzyme is required during embryonic development of eyes and brain, overview
physiological function
the enzyme is essential for zebrafish development and regulates the expression and proteolytic cleavage of transforming growth factor beta1a
physiological function
the enzyme is involved in the regulation of systemic iron homeostasis via shedding of human transferrin receptor 1, TfR1, as its unique mechanism. Shedding of hTfR1 by the enzyme requires endocytosis into acidic clathrin-coated vesicles, enzyme transmembrane domain and cytosolic tail are critical for hTfR1 shedding in the endosomes
physiological function
the enzyme is involved in the regulation of systemic iron homeostasis via shedding of soluble human transferrin receptor 1, TfR1, as its unique mechanism. But the enzyme is not involved in hepcidin regulation by influencing solube hemojuvelin level
physiological function
CRISPR editing reveals that both furin and PC7 are functional in B16-F1 cells and able to substitute for each other during Notch1 and ADAM10 precursor processing
physiological function
morula compaction and inner cell mass formation depend on PC7 and the related proteases Furin and Pace4. These proteases jointly regulate cell-cell adhesion mediated by E-cadherin processing during blastocyst formation
additional information
homology structure modeling, overview
additional information
-
homology structure modeling, overview
additional information
a PLC motif in the cytosolic tail of PC7 is dispensable for endosomal activity, but it is specifically required for trans-Golgi network recycling and to rescue proActivin-A cleavage in furin-depleted B16-F1 melanoma cells
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Tsuji, A.; Hine, C.; Mori, K.; Tamai, Y.; Higashine, K.; Nagamune, H.; Matsuda, Y.
A novel member, PC7, of the mammalian kexin-like protease family: homology to PACE4A, its brain-specific expression and identification of isoforms
Biochem. Biophys. Res. Commun.
202
1452-1459
1994
Rattus norvegicus (Q63793)
brenda
Nakayama, K.
Furin: a mammalian subtilisin/Kex2p-like endoprotease involved in processing of a wide variety of precursor proteins
Biochem. J.
327
625-635
1997
Mammalia
-
brenda
Basak, A.; Cooper, S.; Roberge, A.G.; Banik, U.K.; Chretien, M.; Seidah, N.G.
Inhibition of proprotein convertases-1, -7 and furin by diterpines of Andrographis paniculata and their succinoyl esters
Biochem. J.
338
107-113
1999
Homo sapiens
-
brenda
Basak, A.; Zhong, M.; Munzer, J.S.; Chretien, M.; Seidah, N.G.
Implication of the proprotein convertases furin, PC5 and PC7 in the cleavage of surface glycoproteins of Hong Kong, Ebola and respiratory syncytial viruses: a comparative analysis with fluorogenic peptides
Biochem. J.
353
537-545
2001
Rattus norvegicus
brenda
Bhattacharjya, S.; Xu, P.; Zhong, M.; Chretien, M.; Seidah, N.G.; Ni, F.
Inhibitory activity and structural characterization of a C-terminal peptide fragment derived from the prosegment of the proprotein convertase PC7
Biochemistry
39
2868-2877
2000
Rattus norvegicus
brenda
Munzer, J.S.; Basak, A.; Zhong, M.; Mamarbachi, A.; Hamelin, J.; Savaria, D.; Lazure, C.; Hendy, G.N.; Benjannet, S.; Chretien, M.; Seidah, N.G.
In vitro characterization of the novel proprotein convertase PC7
J. Biol. Chem.
272
19672-19681
1997
Rattus norvegicus
brenda
Zhong, M.; Munzer, J.S.; Basak, A.; Benjannet, S.; Mowla, S.J.; Decroly, E.; Chretien, M.; Seidah, N.G.
The prosegments of furin and PC7 as potent inhibitors of proprotein convertases. In vitro and ex vivo assessment of their efficacy and selectivity
J. Biol. Chem.
274
33913-33920
1999
Rattus norvegicus
brenda
Siegfried, G.; Basak, A.; Cromlish, J.A.; Benjannet, S.; Marcinkiewicz, J.; Chretien, M.; Seidah, N.G.; Khatib, A.M.
The secretory proprotein convertases furin, PC5, and PC7 activate VEGF-C to induce tumorigenesis
J. Clin. Invest.
111
1723-1732
2003
Rattus norvegicus
brenda
Basak, A.; Ernst, B.; Brewer, D.; Seidah, N.G.; Munzer, J.S.; Lazure, C.; Lajoie, G.A.
Histidine-rich human salivary peptides are inhibitors of proprotein convertases furin and PC7 but act as substrates for PC1
J. Pept. Res.
49
596-603
1997
Rattus norvegicus
brenda
Cammisotto, P.G.; Gingras, D.; Renaud, C.; Levy, E.; Bendayan, M.
Secretion of soluble leptin receptors by exocrine and endocrine cells of the gastric mucosa
Am. J. Physiol. Gastrointest. Liver Physiol.
290
G242-G249
2006
Rattus norvegicus
brenda
Seidah, N.G.; Chretien, M.
Proprotein convertase 7
Handbook of Proteolytic Enzymes (Barrett, A. J. , Rawlings, N. D. , Woessner, J. F. , Eds. ) Academic Press
2
1877-1880
2004
Gallus gallus, Homo sapiens, Mus musculus, Rattus norvegicus
-
brenda
Page, R.E.; Klein-Szanto, A.J.; Litwin, S.; Nicolas, E.; Al-Jumaily, R.; Alexander, P.; Godwin, A.K.; Ross, E.A.; Schilder, R.J.; Bassi, D.E.
Increased expression of the pro-protein convertase furin predicts decreased survival in ovarian cancer
Cell. Oncol.
29
289-299
2007
Homo sapiens
brenda
Fugere, M.; Appel, J.; Houghten, R.A.; Lindberg, I.; Day, R.
Short polybasic peptide sequences are potent inhibitors of PC5/6 and PC7: use of positional scanning-synthetic peptide combinatorial libraries as a tool for the optimization of inhibitory sequences
Mol. Pharmacol.
71
323-332
2007
Homo sapiens
brenda
Freyer, C.; Kilpatrick, L.M.; Salamonsen, L.A.; Nie, G.
Pro-protein convertases (PCs) other than PC6 are not tightly regulated for implantation in the human endometrium
Reproduction
133
1189-1197
2007
Homo sapiens (Q16549)
brenda
Padua, M.B.; Hansen, P.J.
Regulation of DNA synthesis and the cell cycle in human prostate cancer cells and lymphocytes by ovine uterine serpin
BMC Cell Biol.
9
5
2008
Mus musculus
brenda
Jarvinen, M.; Chinnaswamy, K.; Sturtevant, A.; Hatley, N.; Sucic, J.
Effects of age and retinal degeneration on the expression of proprotein convertases in the visual cortex
Brain Res.
1317
1-12
2010
Mus musculus
brenda
Nelsen, S.M.; Christian, J.L.
Site-specific cleavage of BMP4 by furin, PC6, and PC7
J. Biol. Chem.
284
27157-27166
2009
Xenopus laevis
brenda
Rousselet, E.; Benjannet, S.; Hamelin, J.; Canuel, M.; Seidah, N.
The proprotein convertase PC7: Unique zymogen activation and trafficking pathways
J. Biol. Chem.
286
2728-2738
2011
Homo sapiens, Rattus norvegicus
brenda
Rousselet, E.; Benjannet, S.; Marcinkiewicz, E.; Asselin, M.; Lazure, C.; Seidah, N.
Proprotein convertase PC7 enhances the activation of the EGF receptor pathway through processing of the EGF precursor
J. Biol. Chem.
286
9185-9195
2011
Homo sapiens, Mus musculus
brenda
Leonhardt, R.; Fiegl, D.; Rufer, E.; Karger, A.; Bettin, B.; Knittler, M.
Post-endoplasmic reticulum rescue of unstable MHC class I requires proprotein convertase PC7
J. Immunol.
184
2985-2998
2010
Homo sapiens
brenda
Guillemot, J.; Canuel, M.; Essalmani, R.; Prat, A.; Seidah, N.G.
Implication of the proprotein convertases in iron homeostasis: proprotein convertase 7 sheds human transferrin receptor 1 and furin activates hepcidin
Hepatology
57
2514-2524
2013
Homo sapiens (Q16549)
brenda
Schwienbacher, C.; Serafin, A.; Zanon, A.; Pramstaller, P.; Pichler, I.; Hicks, A.
Involvement of proprotein convertase PCSK7 in the regulation of systemic iron homeostasis
Hepatology
58
1860-1861
2013
Homo sapiens (Q16549)
brenda
Turpeinen, H.; Oksanen, A.; Kivinen, V.; Kukkurainen, S.; Uusimaeki, A.; Raemet, M.; Parikka, M.; Hytoenen, V.P.; Nykter, M.; Pesu, M.
Proprotein convertase subtilisin/kexin type 7 (PCSK7) is essential for the zebrafish development and bioavailability of transforming growth factor beta1a (TGFbeta1a)
J. Biol. Chem.
288
36610-36623
2013
Danio rerio (F1R440), Danio rerio
brenda
Senturker, S.; Thomas, J.T.; Mateshaytis, J.; Moos, M.
A homolog of subtilisin-like proprotein convertase 7 is essential to anterior neural development in Xenopus
PLoS ONE
7
e39380
2012
Xenopus laevis (E1U2Y7)
brenda
Ginefra, P.; Filippi, B.G.H.; Donovan, P.; Bessonnard, S.; Constam, D.B.
Compartment-specific biosensors reveal a complementary subcellular distribution of bioactive furin and PC7
Cell Rep.
22
2176-2189
2018
Homo sapiens (Q16549), Mus musculus (Q61139)
brenda
Declercq, J.; Ramos-Molina, B.; Sannerud, R.; Brouwers, B.; Pruniau, V.P.E.G.; Meulemans, S.; Plets, E.; Annaert, W.; Creemers, J.W.M.
Endosome to trans-Golgi network transport of Proprotein Convertase 7 is mediated by a cluster of basic amino acids and palmitoylated cysteines
Eur. J. Cell Biol.
96
432-439
2017
Rattus norvegicus (Q62849)
brenda
Bessonnard, S.; Mesnard, D.; Constam, D.
PC7 and the related proteases Furin and Pace4 regulate E-cadherin function during blastocyst formation
J. Cell Biol.
210
1185-1197
2015
Mus musculus (Q61139)
brenda
Pelucchi, S.; Galimberti, S.; Greni, F.; Rametta, R.; Mariani, R.; Pelloni, I.; Girelli, D.; Busti, F.; Ravasi, G.; Valsecchi, M.G.; Valenti, L.; Piperno, A.
Proprotein convertase 7 rs236918 associated with liver fibrosis in Italian patients with HFE-related hemochromatosis
J. Gastroenterol. Hepatol.
31
1342-1348
2016
Homo sapiens (Q16549), Homo sapiens
brenda