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Information on EC 3.4.21.75 - Furin and Organism(s) Homo sapiens
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3.4.21.75 FurinSpecify your search results
Word Map
- 3.4.21.75
- proproteins
- sars-cov-2
- covid-19
- metalloproteinase
- ectodomain
- spike
- endoprotease
- coronavirus
- viruses
-
trans-golgi
-
disintegrin
- adam17
- ace2
- pandemic
- tmprss2
- neuropeptides
- endosomes
-
neuroendocrine
-
endoproteolytic
- propeptide
- proinsulin
- zymogen
- prodomain
- mt1-mmp
- virion
- anthrax
- subtilisins
- proglucagon
- proopiomelanocortin
-
exotoxin
-
uncleaved
- alpha1-antitrypsin
- prorenin
-
baffs
- portland
- betacoronavirus
- prostasin
-
secretogranin
-
alpha-amidating
-
juxtamembrane
- pharmacology
-
sds-stable
- medicine
-
corticotrophs
-
polybasic
- prosegment
-
monobasic
- drug development
- industry
- mers-cov
- pcsk9
- paramyxoviruses
-
membrane-type
-
subtilase
- analysis
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
furin, sheddase, prohormone convertase, furin a, furin protease, proconvertase, subtilisin-like proprotein convertase, furin-like protease, furin convertase, kpc-1, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
Dibasic processing enzyme
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furin
PACE
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Paired basic amino acid cleaving enzyme
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-
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Paired basic amino acid converting enzyme
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-
-
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Paired basic amino acid residue cleaving enzyme
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-
-
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PC1
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prohormone convertase
Proprotein convertase
Serine proteinase PACE
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SPC3
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Trans golgi network protease furin
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additional information
prohormone convertase
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-
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Proprotein convertase
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Proprotein convertase
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Proprotein convertase
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additional information
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furin is a crucial member of secretory mammalian subtilase, the proprotein convertase or proprotein convertase subtilisin/kexin, PCSK, superfamily
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
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-
-
-
CAS REGISTRY NUMBER
COMMENTARY
141760-45-4
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
(2-Aminobenzoyl)-Lys-Glu-Arg-Ser-Lys-Arg-Ser-Ala-Leu-Arg-Asp-(3-nitro)Tyr-Ala + H2O
(2-Aminobenzoyl)-Lys-Glu-Arg-Ser-Lys-Arg + Ser-Ala-Leu-Arg-Asp-(3-nitro)Tyr-Ala
-
-
-
?
2-amino benzoyl-AEQDRNTREVFAQ-T(3-nitro-tyrosine)-A + H2O
2-amino benzoyl-AEQDRNTR + EVFAQ-T(3-nitro-tyrosine)-A
-
furin-mediated cleavage of a fluorogenic peptide derived from hSARS-CoV spike protein
-
-
?
5-carboxyfluorescein-Gln-Arg-Val-Arg-Arg-Ala-Val-Gly-Ile-Asp-Lys(5-carboxytetramethylrhodamine)-OH + H2O
?
-
-
-
?
Abz-GIRRKRSVSHQ-N-(2,4-dinitrophenyl)ethylenediamine + H2O
Abz-GIRRKR + SVSHQ-N-(2,4-dinitrophenyl)ethylenediamine
-
FRET-peptide derived from Rous sarcoma viral envelope glycoprotein
-
-
?
Abz-GRRTRREAIVQ-N-(2,4-dinitrophenyl)ethylenediamine + H2O
Abz-GRRTRR + EAIVQ-N-(2,4-dinitrophenyl)ethylenediamine
-
FRET-peptide derived from Ebola Zaire viral envelope glycoprotein
-
-
?
Abz-HHRQRRSVSIQ-N-(2,4-dinitrophenyl)ethylenediamine + H2O
Abz-HHRQRR + SVSIQ-N-(2,4-dinitrophenyl)ethylenediamine
-
FRET-peptide derived from human A disintegrin and metalloproteinase with thrombospondin ADAM-TS 6
-
-
?
Abz-HKREKRQAKHQ-N-(2,4-dinitrophenyl)ethylenediamine + H2O
Abz-HKREKR + QAKHQ-N-(2,4-dinitrophenyl)ethylenediamine
-
FRET-peptide derived from human bone morphogenetic protein hBMP-2
-
-
?
Abz-HRREKRSVALQ-N-(2,4-dinitrophenyl)ethylenediamine + H2O
Abz-HRREKR + SVALQ-N-(2,4-dinitrophenyl)ethylenediamine
-
FRET-peptide derived from Dengue 2 viral envelope glycoprotein
-
-
?
Abz-HRRQKRSVALQ-N-(2,4-dinitrophenyl)ethylenediamine + H2O
Abz-HRRQKR + SVALQ-N-(2,4-dinitrophenyl)ethylenediamine
-
FRET-peptide derived from Dengue 3 viral envelope glycoprotein
-
-
?
Abz-KIRRRRDVVDQ-N-(2,4-dinitrophenyl)ethylenediamine + H2O
Abz-KIRRRR + DVVDQ-N-(2,4-dinitrophenyl)ethylenediamine
-
FRET-peptide derived from Herpes HHV-6A viral envelope glycoprotein
-
-
?
Abz-LKRRRRDTQQQ-N-(2,4-dinitrophenyl)ethylenediamine + H2O
Abz-LKRRRR + DTQQQ-N-(2,4-dinitrophenyl)ethylenediamine
-
FRET-peptide derived from Borna disease viral envelope glycoprotein
-
-
?
Abz-NLRRRRDLVDQ-N-(2,4-dinitrophenyl)ethylenediamine + H2O
Abz-NLRRRR + DLVDQ-N-(2,4-dinitrophenyl)ethylenediamine
-
FRET-peptide derived from Herpes HHV-6B viral envelope glycoprotein
-
-
?
Abz-RERRRKKRGLFGQ-N-(2,4-dinitrophenyl)ethylenediamine + H2O
Abz-RERRRKKR + GLFGQ-N-(2,4-dinitrophenyl)ethylenediamine
-
FRET-peptide derived from a mutation of the H5N1 influenza hemagglutinin processing site
-
-
?
Abz-RKRSRRQVNTQ-N-(2,4-dinitrophenyl)ethylenediamine + H2O
Abz-RKRSRR + QVNTQ-N-(2,4-dinitrophenyl)ethylenediamine
-
FRET-peptide derived from Ebola Sudan viral envelope glycoprotein
-
-
?
Abz-RRRAKRSPKHQ-N-(2,4-dinitrophenyl)ethylenediamine + H2O
Abz-RRRAKR + SPKHQ-N-(2,4-dinitrophenyl)ethylenediamine
-
FRET-peptide derived from human bone morphogenetic protein hBMP-4
-
-
?
Abz-RRRDKRSVALQ-N-(2,4-dinitrophenyl)ethylenediamine + H2O
Abz-RRRDKR + SVALQ-N-(2,4-dinitrophenyl)ethylenediamine
-
FRET-peptide derived from Dengue 4 viral envelope glycoprotein
-
-
?
Abz-RRRKKRGLFGQ-N-(2,4-dinitrophenyl)ethylenediamine + H2O
Abz-RRRKKR + GLfGQ-N-(2,4-dinitrophenyl)ethylenediamine
-
FRET-peptide derived from the H5N1 influenza hemagglutinin processing site
-
-
?
Abz-RRRKKRGLSGQ-N-(2,4-dinitrophenyl)ethylenediamine + H2O
Abz-RRRKKR + GLSGQ-N-(2,4-dinitrophenyl)ethylenediamine
-
FRET-peptide derived from a mutation of the H5N1 influenza hemagglutinin processing site
-
-
?
Abz-RRRKKRSLFGQ-N-(2,4-dinitrophenyl)ethylenediamine + H2O
Abz-RRRKKR + SLFGQ-N-(2,4-dinitrophenyl)ethylenediamine
-
FRET-peptide derived from a mutation of the H5N1 influenza hemagglutinin processing site
-
-
?
Abz-SKRSRRSVSVQ-N-(2,4-dinitrophenyl)ethylenediamine + H2O
Abz-SKRSRR + SVSVQVNTQ-N-(2,4-dinitrophenyl)ethylenediamine
-
FRET-peptide derived from Japan beta-encephalitis viral envelope glycoprotein
-
-
?
Abz-SRRHKRFAGVQ-N-(2,4-dinitrophenyl)ethylenediamine + H2O
Abz-SRRHKR + FAGVQ-N-(2,4-dinitrophenyl)ethylenediamine
-
FRET-peptide derived from measle virus Fo viral envelope glycoprotein
-
-
?
Abz-SRRKRRDVTPQ-N-(2,4-dinitrophenyl)ethylenediamine + H2O
Abz-SRRKRR + DVTPQ-N-(2,4-dinitrophenyl)ethylenediamine
-
FRET-peptide derived from Ebola Ivory Coast viral envelope glycoprotein
-
-
?
Abz-SRRKRRSASTQ-N-(2,4-dinitrophenyl)ethylenediamine + H2O
Abz-SRRKRR + SASTQ-N-(2,4-dinitrophenyl)ethylenediamine
-
FRET-peptide derived from Herpes HHV-8 viral envelope glycoprotein
-
-
?
Abz-SSRHRRALDTQ-N-(2,4-dinitrophenyl)ethylenediamine + H2O
Abz-SSRHRR + ALDTQ-N-(2,4-dinitrophenyl)ethylenediamine
-
FRET-peptide derived from human transforming growth factor TGF-beta3
-
-
?
Abz-TRRFRRSITEQ-N-(2,4-dinitrophenyl)ethylenediamine + H2O
Abz-TRRFRR + SITEQ-N-(2,4-dinitrophenyl)ethylenediamine
-
FRET-peptide derived from infectious bronchitis viral envelope glycoprotein
-
-
?
Ac-AAKYKR-4-methylcoumarin-7-amide + H2O
7-amino-4-methylcoumarin + Ac-AAKYKR
-
-
-
?
Ac-AARYKR-4-methylcoumarin-7-amide + H2O
7-amino-4-methylcoumarin + Ac-AARYKR
-
-
-
?
Ac-Arg-Val-Arg-Arg-4-nitroanilide + H2O
Ac-Arg-Val-Arg-Arg + 4-nitroaniline
-
-
-
-
?
Ac-KARYKR-4-methylcoumarin-7-amide + H2O
7-amino-4-methylcoumarin + Ac-KARYKR
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-
-
?
Ac-norleucine-YKR-4-methylcoumarin-7-amide
acetyl-norleucine-YKR + 7-amino-4-methylcoumarin
-
-
-
-
?
Ac-RA-norvaline-YKR-4-methylcoumarin-7-amide + H2O
7-amino-4-methylcoumarin + Ac-RA-norvaline-YKR
-
-
-
?
Ac-RAKYKR-4-methylcoumarin-7-amide + H2O
7-amino-4-methylcoumarin + Ac-RAKYKR
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-
-
?
Ac-RARYAR-4-methylcoumarin-7-amide + H2O
7-amino-4-methylcoumarin + Ac-RARYAR
-
-
-
?
Ac-RARYKR-4-methylcoumarin-7-amide + H2O
7-amino-4-methylcoumarin + Ac-RARYKR
-
-
-
?
Ac-RARYRR-4-methylcoumarin-7-amide + H2O
7-amino-4-methylcoumarin + Ac-RARYRR
-
-
-
?
Ac-RYKR-4-methylcoumarin-7-amide + H2O
7-amino-4-methylcoumarin + Ac-RYRR
-
-
-
?
Ac-RYRFKR-4-methylcoumarin-7-amide + H2O
7-amino-4-methylcoumarin + Ac-RYRFKR
-
-
-
?
acetyl-norleucine-YKR-7-amido-4-methylcoumarin + H2O
acetyl-norleucine-YKR + 7-amino-4-methylcoumarin
-
-
-
-
?
acetyl-RVRR-4-methylcoumarin 7-amide + H2O
acetyl-RVRR + 7-amino-4-methylcoumarin
-
-
-
-
?
acetyl-RVRR-aminoluciferin + H2O
acetyl-RVRR + D-aminoluciferin
-
the substrate consists of D-aminoluciferin coupled to the C-terminus of furin recognition peptide sequence, furin cleaves at the C-terminal to the last arginine residue. In the presence of furin, the probes are hydrolyzed to remove the peptide caging group and generate free D-aminoluciferin which subsequently produces light emission in the presence of firefly luciferase
-
-
?
acetyl-RYKR-4-methylcoumarin 7-amide + H2O
acetyl-RYKR + 7-amino-4-methylcoumarin
-
-
-
-
?
acetyl-RYKR-aminoluciferin + H2O
acetyl-RYKR + D-aminoluciferin
-
the substrate consists of D-aminoluciferin coupled to the C-terminus of furin recognition peptide sequence, furin cleaves at the C-terminal to the last arginine residue. In the presence of furin, the probes are hydrolyzed to remove the peptide caging group and generate free D-aminoluciferin which subsequently produces light emission in the presence of firefly luciferase
-
-
?
acetyl-Tyr-Glu-Lys-Glu-Arg-Ser-Lys-7-amido-4-methylcoumarin + H2O
acetyl-Tyr-Glu-Lys-Glu-Arg + Ser-Lys-7-amido-4-methylcoumarin
-
-
-
-
?
Acetyl-Tyr-Glu-Lys-Glu-Arg-Ser-Lys-Arg-4-methylcoumarin 7-amide + H2O
?
-
-
-
-
?
AcRARYKK-4-methylcoumarin-7-amide + H2O
7-amino-4-methylcoumarin + AcRARYKK
-
-
-
?
avian influenza virus A hemagglutinin + H2O
?
from strain vian influenza virus, A/chicken/Israel/810/2001 (H9N2), with R-S-K-R cleavage site
-
-
?
Boc-RVRR-4-methylcoumarin 7-amide + H2O
Boc-RVRR + 7-amino-4-methylcoumarin
-
-
-
-
?
Boc-RVRR-4-methylcoumarin-7-amide + H2O
7-amino-4-methylcoumarin + Boc-RVRR
-
-
-
?
epithelial Na+ channel + H2O
?
-
furin-dependent cleavage of the ectodomain at two sites in the alpha subunit and at a single site within the gamma subunit. Cleavage of the gamma subunit by furin and prostasin is required to release an inhibitory domain
-
-
?
full-length (pro)renin receptor + H2O
soluble (pro)renin receptor + 10 kDa fragment of (pro)renin receptor
Glu-Arg-Thr-Lys-Arg-(7-methylcoumarin-4-yl)acetate + H2O
Glu-Arg-Thr-Lys-Arg + (7-methylcoumarin-4-yl)acetate
-
-
-
-
?
gp40/15 + H2O
gp40 + gp15
-
cleaves recombinant Cryptosporidium parvum and Cryptosporidium hominis gp40/15. Putative furin cleavage site RSRR
-
-
?
gp40/15 subtype 1e + H2O
gp40 + gp15
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RSRR sequence is replaced by ISKR, has an alternative furin cleavage site at KSISKR2
-
-
?
hBMP-2 precursor protein + H2O
?
-
cleavage sites are HKREKR-/-QAKH and HVRISR-/-SLHQ
-
-
?
hBMP-4 precursor protein + H2O
?
-
cleavage sites are RRRAKR-/-SPKH and HVRISR-/-SLPQ
-
-
?
highly pathogenic Queretaro H5N2 hemagglutinin + H2O
?
-
only processed in the presence of heparin
-
-
?
histonin + H2O
?
-
furin releases intact histonin monomers from F4-multimeric histonin (12-mer). Histonin has an RLKR motif at the C-terminus after which furin cleaves specifically
-
-
?
HIV-1 gp160 + H2O
?
-
13mer and 19mer peptides digested equally well by furin at site1, showing complete processing at 5 h. 41mer and 51mer peptides are either barely or unprocessed, respectively. Product inhibition does not explain inability of furin to process the 41mer and 51mer peptides. Extended sequences require heparin for optimal processing
-
-
?
influenza variant Fujian-like H5N1 hemagglutinin + H2O
?
-
mutations at the furin-processing site of the hemagglutinin, is less cleaved (38%) by furin as compared to the parent Fujian-like strain derived peptides
-
-
?
membrane type-1 matrix metalloproteinase proenzyme + H2O
membrane type-1 matrix metalloproteinase + propeptide of membrane type-1 matrix metalloproteinase
N-benzyloxycarbonyl-RVRR-4-methylcoumarin 7-amide + H2O
N-benzyloxycarbonyl-RVRR + 7-amino-4-methylcoumarin
-
-
-
-
?
N-tert-butoxycarbonyl-Arg-Val-Arg-Arg-4-methylcoumarin 7-amide + H2O
?
-
-
-
-
?
PC1/3 C-terminal peptide + H2O
?
-
cleavage by furin into a peptide with an apparent molecular mass of 12.5 kDa. Cleavage of the C-terminal to the pair of Args occupying positions 627 and 628
-
-
?
PC2-S383A
?
-
furin fully processes the PC2 mutant at the secondary site in AtT-20 cells, site is accessible to in trans cleavage
-
-
?
PCSK9 + H2O
?
-
cleavage by furin at Arg218. Mutations R218S, F216L, and D374Y of PCSK9 associated with hypercholesterolemia result in total or partial loss of furin/PC5/6A processing at the motif RFHR21, mutant A443T shows enhanced susceptibility to furin cleavage
-
-
?
pGlu-Arg-Thr-Lys-4-methylcoumarin 7-amide + H2O
pGlu-Arg-Thr-Lys + 7-amino-4-methylcoumarin
-
-
-
-
?
pGlu-Arg-Thr-Lys-Arg-4-methylcoumarin 7-amide + H2O
pGlu-Arg-Thr-Lys-Arg + 7-amino-4-methylcoumarin
-
-
-
-
?
pGlu-Arg-Thr-Lys-Arg-4-methylcoumaryl-7-amide + H2O
pGlu-Arg-Thr-Lys-Arg + 7-amino-4-methylcoumarin
-
-
-
-
?
pGlu-Arg-Thr-Lys-Arg-7-amido-4-methylcoumarin + H2O
pGlu-Arg-Thr-Lys-Arg + 7-amino-4-methylcoumarin
-
-
-
?
phenylacetyl-Arg-Val-Arg-7-amido-4-methylcoumarin + H2O
phenylacetyl-Arg-Val-Arg + 7-amino-4-methylcoumarin
-
-
-
?
POMC prohormone precursor + H2O
ACTH + alpha-MSH + beta-endorphin
-
human pituitary may utilize the cathepsin L and prohormone convertase pathways for producing POMC-derived peptide hormones
-
-
?
pro-ADAMTS4 + H2O
?
-
furin plays an important role in the intracellular removal of ADAMTS4 prodomain. Multiple furin recognition sites: 206RPRR209, 209RAKR212, or 211KR212
-
-
?
pro-B-type natriuretic peptide + H2O
B-type natriuretic peptide + pro-peptide of B-type natriuretic peptide
pro-bone morphogenetic protein-4 + H2O
mature bone morphogenetic protein-4 + ?
-
-
-
?
pro-hepcidin + H2O
active mature hepcidin
-
furin processes the iron-regulatory peptide hepcidin to the bioactive mature hepcidin-25 form
-
-
?
pro-transforming growth factor-beta1 + H2O
transforming growth factor-beta1 + propeptide
-
-
-
?
procollagen V + H2O
?
-
proteolytic processing of the proalpha1(V) C-propeptide chain. Proteolytic C-propeptide removal by furin occurs between Arg1585 and Asn1586. Processing of the C-propeptide by furin is more efficient than processing by bone morphogenetic protein-1
-
-
?
proform tissue growth factor 1beta + H2O
tissue growth factor beta1 + propeptide
-
-
-
?
proPDGF-B + H2O
PDGF-B + PGDF-B propeptide
-
a growth factor proform of 31 kDa
mature form of 17 kDa
-
?
Protective antigen component of anthrax toxin + H2O
?
-
cleavage at the sequence Arg-Lys-Lys-Arg
-
-
?
Pyr-Arg-Thr-Lys-Arg-4-methylcoumaryl-7-amide + H2O
7-amino-4-methylcoumarin + Pyr-Arg-Thr-Lys-Arg
-
pERTKR-MCA
-
?
pyroglutamic acid-Arg-Thr-Lys-Arg-methylcoumaryl-7-amide + H2O
?
-
-
-
-
?
pyroglutamic acid-RTKR-4-methylcoumarin 7-amide + H2O
pyroglutamic acid-RTKR + 7-amino-4-methylcoumarin
-
-
-
-
?
RPTPkappa + H2O
?
-
furin is required for S1 processing of RPTPkappa in the secretory pathway. Purified furin cleaves RPTPkappa within the membrane-proximal fibronectin type III domain at the sequence RTKR
-
-
?
SARS coronavirus spike glycoprotein + H2O
?
-
introduction of a prototypic furin recognition motif at R667 allows for efficient cleavage of the mutant glycoprotein
-
-
?
Sema3B + H2O
?
cleavage at the furin recognition site is critical for the function of this tumor suppressor
-
-
?
Sema3C + H2O
?
cleavage at the furin recognition site 742RNRR745. The point mutation R745A at the basic domain at the hypothetical furin recognition site 742RNRR745 disables the processing of Sema3C at this specific location. The C-terminal arginine of the putative furin cleavage site at the basic domain of Sema3C protein is critical for its functions in angiogenesis process
-
-
?
t-butoxycarbonyl-Arg-Val-Arg-Arg-7-amido-4-methylcoumarin + H2O
?
-
-
-
?
tert-butoxycarbonyl-Arg-Val-Arg-Arg-4-methylcoumarin 7-amide + H2O
tert-butoxycarbonyl-Arg-Val-Arg-Arg + 7-amino-4-methylcoumarin
-
-
-
-
?
tert-butyloxycarbonyl-Arg-Val-Arg-Arg-4-methylcoumaryl-7-amide + H2O
tert-butyloxycarbonyl-Arg-Val-Arg-Arg + 7-amino-4-methylcoumarin
-
-
-
-
?
ADAMTS9 propeptide + H2O
?
-
the intact zymogen is secreted to the cell surface and is subsequently processed by furin before release into thge medium. ADAMTS9 processing is exclusively extracellular and occurs at the cell surface in cells that express high levels of furin
-
-
?
ADAMTS9 propeptide + H2O
?
-
ADAMTS is a disintegrin and metalloprotease domain with thrombospondin type 1 repeats
-
-
?
DSSARIRRNAKG + H2O
DSSARIRR + NAKG
-
peptide derived bone morphogenetic protein BMP10, cleavage occurs at residue R316
-
-
?
DSSARIRRNAKG + H2O
DSSARIRR + NAKG
-
peptide-derived bone morphogenetic protein BMP10, cleavage occurs at residue R316
-
-
?
full-length (pro)renin receptor + H2O
soluble (pro)renin receptor + 10 kDa fragment of (pro)renin receptor
-
i.e. (P)RR, cleavage site at Arg275-X-X-Arg278-/-, no activity with (P)RR mutant R275A/KT/R278A. The soluble form of the (pro)renin receptor generated through intracellular cleavage by furin is secreted in plasma
i.e. s(P)RR, a 28 kDa protein
-
?
full-length (pro)renin receptor + H2O
soluble (pro)renin receptor + 10 kDa fragment of (pro)renin receptor
-
i.e. (P)RR, a 35 kDa protein, cleavage site at Arg275-X-X-Arg278-/-, no activity with (P)RR mutant R275A/KT/R278A
i.e. s(P)RR, a 28 kDa protein
-
?
G-protein-coupled receptor GPR107 + H2O
?
cleavage by endoprotease furin, a disulfide bond connects the two resulting fragments, overview
-
-
?
G-protein-coupled receptor GPR107 + H2O
?
recombinant HA-tagged substrate expressed in HeLa cells. GPR107 contains an extended furin recognition site that includes KSKR, a variant of the classical furin cleavage motif (Arg-Xaa-(Lys/Arg)-Arg), although not common among furin substrates, in GPR107 the Lys residue replaces the first conserved Arg
-
-
?
human semaphorin 3F + H2O
?
-
furin processing of semaphorin 3F determines its anti-angiogenic activity by regulating direct binding and competition for neuropilin, overview
-
-
?
human semaphorin 3F + H2O
?
-
the substrate is produced as a C-terminal or an N-terminal human growth hormone fusion from the pLexM vector. Cleavage at the RXRR furin recognition site in the C-terminus, which is essential for the interaction of the C-terminus of Sema3F with the b1 domain of neuropilin
-
-
?
membrane type-1 matrix metalloproteinase proenzyme + H2O
membrane type-1 matrix metalloproteinase + propeptide of membrane type-1 matrix metalloproteinase
-
-
-
-
?
membrane type-1 matrix metalloproteinase proenzyme + H2O
membrane type-1 matrix metalloproteinase + propeptide of membrane type-1 matrix metalloproteinase
-
intracellular processing in breast carcinoma MCF-MT1-E240A-FLAG cells
-
-
?
membrane-tethered membrane type-1 matrix metallo-proteinase + H2O
?
-
furin regulates the intracellular activation and the uptake rate of cell surface-associated MT1-MMP at the surface of cancer cells. Furin and related PCs are the essential components of the specialized cellular machinery that controls the levels of the functionally active, mature, MT1-MMP enzyme on the cell surface to continually support the potency of pericellular proteolysis
-
-
?
membrane-tethered membrane type-1 matrix metallo-proteinase + H2O
?
-
there are two furin cleavage motifs, R89-R-P-R-C93 and R108-R-K-R-Y112
-
-
?
Moloney murine leukemia virus Env precursor protein + H2O
?
furin cleaves the Env precursor into the surface and transmembrane subunits in the cell and then the viral protease cleaves the R-peptide from TM in newvirus. Structure analysis of the open cage-like structure like that of the R-peptide precursor and of the mature protein, overview. Furin cleavage not only separates the subunits and liberates the fusion peptide at the end of TM but also allows the C-terminal domain to relocate into a peripheral position. This conformational change might explain how the C-terminal domain of surface subunit gains the potential to undergo disulfide isomerization, an event that facilitates membrane fusion
-
-
?
PA83 + H2O
PA63 + PA20
the protective antigen substrate is from Bacillus anthracis, commercial plant-produced deglycosylated PA83 (dPA83). Cleavage of the substrate generates two protein fragments with distinctly different molecular masses of 63 kDa (PA63) and 20 kDa (PA20). Plant-produced PA83 protein is almost fully cleaved by commercial furin, while plant-produced truncated enzymatically active furin displays about 75% relative activity compared to commercial human furin in vitro
-
-
?
pro-B-type natriuretic peptide + H2O
B-type natriuretic peptide + pro-peptide of B-type natriuretic peptide
-
activation by N-terminal fragment cleavage of proBNP in human plasma through furin
-
-
?
pro-B-type natriuretic peptide + H2O
B-type natriuretic peptide + pro-peptide of B-type natriuretic peptide
-
cleavage sequence is Arg73-Ala-Pro-Arg76-/-Ser77
-
-
?
pro-CD109 + H2O
CD109 + CD109 propeptide
-
CD109 is produced as a 205 kDa glycoprotein, which is then processed in the Golgi apparatus into 180 kDa and 25 kDa proteins by furin
-
-
?
pro-CD109 + H2O
CD109 + CD109 propeptide
-
CD109 is a glycosylphosphatidylinositol-anchored glycoprotein, cleavage motif comprises amino acids 1270-RRRR-1273
-
-
?
Protein precursor + H2O
?
-
cleavage of-Arg-Xaa-Yaa-Arg-+- bonds where Xaa can be any amino acid and Yaa is Arg or Lys
-
-
?
Protein precursor + H2O
?
-
pro-von Willebrand factor (both the P4 arginine and the P2 lysine play an important role in substrate recognition)
-
-
?
Protein precursor + H2O
?
-
the term -+- depicts the point of cleavage, e.g. stromelysin 3
-
-
?
Shiga toxin + H2O
?
-
not only the sequence known to be a minimal furin-recognition site, but also the structure around this site are important for furin processing of Shiga toxin and for rapid intoxication
-
-
?
additional information
?
-
-
no processing of: human lactase-phlorizin hydrolase
-
-
?
additional information
?
-
-
Preference for Arg-Glu-Lys-Arg-+-Ala vs. Lys-Ala-Lys-Arg-+-Arg
-
-
?
additional information
?
-
-
peptides patterned on the sequence 307-330 of the specific viral strains of the gp120 V3 loop
-
-
?
additional information
?
-
-
study of the specificity of human prohormone convertase PC1 and human furin
-
-
?
additional information
?
-
-
endoproteolytic cleavage at paired basic residues of proproteins of the eukaryotic secretory pathway
-
-
?
additional information
?
-
-
probably involved in the proteolysis resulting in secretion of rat endopeptidase 24.18 alpha-subunit
-
-
?
additional information
?
-
-
possible role in processing essential cellular factors
-
-
?
additional information
?
-
-
implicated in maturation of substrates involved in development, signaling, coagulation, and pathogenesis, constitutive secretory pathway
-
?
additional information
?
-
-
proteolytic processing of a variety of proteins in the exocytic and endocytic pathways
-
?
additional information
?
-
-
low pathogenic Mexico H5N2 hemagglutinin is not processed by furin
-
-
?
additional information
?
-
-
mutation in the RSRR cleavage site prevents processing of gp40/15
-
-
?
additional information
?
-
-
a three-step autocatalytic processing including the cleavage of the prodomain at the Arg-Leu-Gln-Arg89Q-Glu90 site, is required for the efficient activation of furin
-
-
?
additional information
?
-
-
furin possesses a strong preference for substrates containing the multibasic cleavage motif Arg-X-Arg/Lys-ArgV-X
-
-
?
additional information
?
-
-
the bioluminescence emission in the presence of firefly luciferase, recombinantly expressed as GFP-tagged enzyme in human MDA-MB-468 cells, breast adenocarcinoma cells, is furin-dependent and specific
-
-
?
additional information
?
-
-
furin cleavage sequence is RXXR-/-X, X is not Cys
-
-
?
additional information
?
-
-
furin is a proprotein convertase that requires the cleavage sequence R-X-K/R-R, clear interdependence of furin subsites, substrate specificity with synthetic peptide substrates, overview
-
-
?
additional information
?
-
-
furin performs a calcium-dependent proteolytic cleavage at the C-terminus of a consensus amino acid motif R-X-K/R-R, with X being any amino acid. This tetrapeptide motif provides sufficient specificity to bind the active furin
-
-
?
additional information
?
-
-
furin performs autocleaqvage to its soluble form
-
-
?
additional information
?
-
activation mechanism of avian influenza virus H9N2 by furin, overview. Israel810 HA can be cleaved in cells with high levels of furin expression, a mutation that eliminates a glycosylation site in HA1 allows the Israel810 hemagglutinin to gain universal cleavage in cell culture. Influenza virus HA is a complex protein, folded in a tertiary structure. In this situation, accessibility of the cleavage site to proteases becomes as important as the primary sequence itself
-
-
?
additional information
?
-
-
activation mechanism of avian influenza virus H9N2 by furin, overview. Israel810 HA can be cleaved in cells with high levels of furin expression, a mutation that eliminates a glycosylation site in HA1 allows the Israel810 hemagglutinin to gain universal cleavage in cell culture. Influenza virus HA is a complex protein, folded in a tertiary structure. In this situation, accessibility of the cleavage site to proteases becomes as important as the primary sequence itself
-
-
?
additional information
?
-
proprotein convertases represent highly selective serine proteases that activate their substrates upon proteolytic cleavage
-
-
?
additional information
?
-
-
proprotein convertases represent highly selective serine proteases that activate their substrates upon proteolytic cleavage
-
-
?
additional information
?
-
high substrate selectivity and enzymatic activity of furin
-
-
?
additional information
?
-
recombinant expression of Sema3 wild-type substrates and of mutant Sema3C (R745A, 85.2 kDa) in HEK-293FT cells
-
-
?
additional information
?
-
-
recombinant expression of Sema3 wild-type substrates and of mutant Sema3C (R745A, 85.2 kDa) in HEK-293FT cells
-
-
?
additional information
?
-
to transiently express the substrate factor IX (FIX, amino acids 29-461) in Nicotiana benthamiana plants, the signal peptide (amino acids 1-28) is removed from the FIX sequence (UniProt ID P00740) and replaced with a Nicotiana tabacum PR-1a signal peptide. a KDEL sequence and the His6 tag are added to the C-terminus. Enzyme substrate precursor polypeptide of factor IX (FIX) undergoes several post translational modifications (PTMs), including the removal of the signal peptide (aa 1-28), carboxylation of the first 12 glutamic acid residues downstream from the 18-amino acid propeptide sequence (aa 29-46) in the region rich in glutamic acid (aa 47-92, called the gamma-carboxyglutamic acid or Gla domain) at the N-terminus. Proper gamma-carboxylation of the Gla domain is required for binding to calcium and phospholipids that is critical for proper protease activity during coagulation. In vivo, vitamin K-dependent gamma-carboxylase binds to the 18-amino acid propeptide of FIX, which is then cleaved and is required for optimal binding of the Gla domain to Ca2+ and phospholipids
-
-
?
additional information
?
-
-
to transiently express the substrate factor IX (FIX, amino acids 29-461) in Nicotiana benthamiana plants, the signal peptide (amino acids 1-28) is removed from the FIX sequence (UniProt ID P00740) and replaced with a Nicotiana tabacum PR-1a signal peptide. a KDEL sequence and the His6 tag are added to the C-terminus. Enzyme substrate precursor polypeptide of factor IX (FIX) undergoes several post translational modifications (PTMs), including the removal of the signal peptide (aa 1-28), carboxylation of the first 12 glutamic acid residues downstream from the 18-amino acid propeptide sequence (aa 29-46) in the region rich in glutamic acid (aa 47-92, called the gamma-carboxyglutamic acid or Gla domain) at the N-terminus. Proper gamma-carboxylation of the Gla domain is required for binding to calcium and phospholipids that is critical for proper protease activity during coagulation. In vivo, vitamin K-dependent gamma-carboxylase binds to the 18-amino acid propeptide of FIX, which is then cleaved and is required for optimal binding of the Gla domain to Ca2+ and phospholipids
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ADAMTS9 propeptide + H2O
?
-
the intact zymogen is secreted to the cell surface and is subsequently processed by furin before release into thge medium. ADAMTS9 processing is exclusively extracellular and occurs at the cell surface in cells that express high levels of furin
-
-
?
DSSARIRRNAKG + H2O
DSSARIRR + NAKG
-
peptide derived bone morphogenetic protein BMP10, cleavage occurs at residue R316
-
-
?
full-length (pro)renin receptor + H2O
soluble (pro)renin receptor + 10 kDa fragment of (pro)renin receptor
-
i.e. (P)RR, cleavage site at Arg275-X-X-Arg278-/-, no activity with (P)RR mutant R275A/KT/R278A. The soluble form of the (pro)renin receptor generated through intracellular cleavage by furin is secreted in plasma
i.e. s(P)RR, a 28 kDa protein
-
?
G-protein-coupled receptor GPR107 + H2O
?
cleavage by endoprotease furin, a disulfide bond connects the two resulting fragments, overview
-
-
?
human semaphorin 3F + H2O
?
-
furin processing of semaphorin 3F determines its anti-angiogenic activity by regulating direct binding and competition for neuropilin, overview
-
-
?
membrane type-1 matrix metalloproteinase proenzyme + H2O
membrane type-1 matrix metalloproteinase + propeptide of membrane type-1 matrix metalloproteinase
-
intracellular processing in breast carcinoma MCF-MT1-E240A-FLAG cells
-
-
?
membrane-tethered membrane type-1 matrix metallo-proteinase + H2O
?
-
furin regulates the intracellular activation and the uptake rate of cell surface-associated MT1-MMP at the surface of cancer cells. Furin and related PCs are the essential components of the specialized cellular machinery that controls the levels of the functionally active, mature, MT1-MMP enzyme on the cell surface to continually support the potency of pericellular proteolysis
-
-
?
pro-ADAMTS4 + H2O
?
-
furin plays an important role in the intracellular removal of ADAMTS4 prodomain. Multiple furin recognition sites: 206RPRR209, 209RAKR212, or 211KR212
-
-
?
pro-B-type natriuretic peptide + H2O
B-type natriuretic peptide + pro-peptide of B-type natriuretic peptide
-
activation by N-terminal fragment cleavage of proBNP in human plasma through furin
-
-
?
pro-bone morphogenetic protein-4 + H2O
mature bone morphogenetic protein-4 + ?
-
-
-
?
pro-CD109 + H2O
CD109 + CD109 propeptide
-
CD109 is produced as a 205 kDa glycoprotein, which is then processed in the Golgi apparatus into 180 kDa and 25 kDa proteins by furin
-
-
?
pro-transforming growth factor-beta1 + H2O
transforming growth factor-beta1 + propeptide
-
-
-
?
proform tissue growth factor 1beta + H2O
tissue growth factor beta1 + propeptide
-
-
-
?
additional information
?
-
-
endoproteolytic cleavage at paired basic residues of proproteins of the eukaryotic secretory pathway
-
-
?
additional information
?
-
-
probably involved in the proteolysis resulting in secretion of rat endopeptidase 24.18 alpha-subunit
-
-
?
additional information
?
-
-
possible role in processing essential cellular factors
-
-
?
additional information
?
-
-
implicated in maturation of substrates involved in development, signaling, coagulation, and pathogenesis, constitutive secretory pathway
-
?
additional information
?
-
-
proteolytic processing of a variety of proteins in the exocytic and endocytic pathways
-
?
additional information
?
-
-
furin possesses a strong preference for substrates containing the multibasic cleavage motif Arg-X-Arg/Lys-ArgV-X
-
-
?
additional information
?
-
-
the bioluminescence emission in the presence of firefly luciferase, recombinantly expressed as GFP-tagged enzyme in human MDA-MB-468 cells, breast adenocarcinoma cells, is furin-dependent and specific
-
-
?
additional information
?
-
activation mechanism of avian influenza virus H9N2 by furin, overview. Israel810 HA can be cleaved in cells with high levels of furin expression, a mutation that eliminates a glycosylation site in HA1 allows the Israel810 hemagglutinin to gain universal cleavage in cell culture. Influenza virus HA is a complex protein, folded in a tertiary structure. In this situation, accessibility of the cleavage site to proteases becomes as important as the primary sequence itself
-
-
?
additional information
?
-
-
activation mechanism of avian influenza virus H9N2 by furin, overview. Israel810 HA can be cleaved in cells with high levels of furin expression, a mutation that eliminates a glycosylation site in HA1 allows the Israel810 hemagglutinin to gain universal cleavage in cell culture. Influenza virus HA is a complex protein, folded in a tertiary structure. In this situation, accessibility of the cleavage site to proteases becomes as important as the primary sequence itself
-
-
?
additional information
?
-
proprotein convertases represent highly selective serine proteases that activate their substrates upon proteolytic cleavage
-
-
?
additional information
?
-
-
proprotein convertases represent highly selective serine proteases that activate their substrates upon proteolytic cleavage
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
Mg2+
-
selective activation of furin by Mg2+ ions as a result of cooperativity between furin subsites. Furin hydrolysis of peptides from measles virus fusion protein Fo and from Asian avian influenza A, H5N1, is activated between 60- and 80-fold by MgCl2. Both the pH profile of furin and its intrinsic fluorescence are modified by Mg2+ ions, which bind to furin with a Kd value of 1.1 mM
Ca2+
strict Ca2+ dependence, calcium-dependent activity regulation of furin
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(1S,14S,17S,20S,23S,26S,33r)-26-amino-N-(4-carbamimidoylbenzyl)-20,23-bis(3-guanidinopropyl)-17-neopentyl-4,8,16,19,22,25,32-heptaoxo-3,9,15,18,21,24,31-heptaazabicyclo[31.2.2]heptatriacontane-14-carboxamide
-
(D-Arg)9-amide
-
protects RAW264.7 cells against anthrax toxemia with an IC50 of 0.0037 mM
(E)-N-((E)-5-(2-chloro-5-nitrobenzylidene)-4-oxothiazolidin-2-ylidene)-4-methylbenzenesulfonamide
-
competitive inhibitor
(N'Z,N''Z)-4,4'-oxybis(N'-(2-hydroxybenzylidene)benzenesulfonohydrazide)
-
competitive inhibitor
1,1'-((1R,3S,4S,6R)-4,6-bis(4-guanidinophenoxy)cyclohexane-1,3-diyl)diguanidine
meso compound
1,1'-((1R,3S,4S,6R)-4-((4-guanidinonaphthalen-1-yl)oxy)-6-(4-guanidinophenoxy)cyclohexane-1,3-diyl)diguanidine
racemate, blocks the S2 pocket
1,1'-((1S,3R,4R,6S)-4-((4-guanidinonaphthalen-1-yl)oxy)-6-(4-guanidinophenoxy)cyclohexane-1,3-diyl)diguanidine
blocks the S2 pocket
1,2,12,13-tetradehydro-3,4,10,11-tetrahydro-5,9-(azeno)-4,10-benzodiazacyclopentadecine
-
12% inhibition at 0.1 mM
1,2,12,13-tetradehydro-3,4,10,11-tetrahydro-5,9-(metheno)-4,10-benzodiazacyclopentadecine
-
10% inhibition at 0.1 mM
2-(11-hydroxy-3-oxo-3H-dibenzo[c,h]xanthen-7-yl)benzoic acid
-
noncompetitive inhibitor
3'-oxo-6a,14a-dihydro-3'H-spiro[dibenzo[c,h]xanthene-7,1'-isobenzofuran]-3,11-diyl diacetate
-
-
3,3',3'',3'''-(1,4-phenylenebis(methanetriyl))tetrakis(4-hydroxy-2H-chromen-2-one)
-
noncompetitive inhibitor
3,3'-((2,3-dihydro-1H-inden-5-yl)methylene)bis(4-hydroxy-2H-chromen-2-one)
-
noncompetitive inhibitor
3,3'-((2-bromophenyl)methylene)bis(4-hydroxy-2H-chromen-2-one)
-
noncompetitive inhibitor
3,3'-((2-chlorophenyl)methylene)bis(4-hydroxy-2H-chromen-2-one)
-
noncompetitive inhibitor
3,3'-((3,4,5-trimethoxyphenyl)methylene)bis(4-hydroxy-2H-chromen-2-one)
-
noncompetitive inhibitor
3,3'-((4-isopropoxyphenyl)methylene)bis(4-hydroxy-2H-chromen-2-one)
-
noncompetitive inhibitor
3,3'-(benzo[d][1,3]dioxol-5-ylmethylene)bis(4-hydroxy-2H-chromen-2-one)
-
noncompetitive inhibitor
3-guanidinomethyl-phenylacetyl-Arg-Val-Arg-(4-amidomethyl)-benzamidine
MI-52, a substrate-analogous, noncovalent inhibitor. The furin-MI-52 complex is highly stable
3-hydroxy-5-(4-methoxyphenyl)-2-(4-phenoxy-3-sulfophenyl)-3H-pyrazol-2-ium
-
competitive inhibitor
4,10-bis[(4-methylphenyl)sulfonyl]-1,2,12,13-tetradehydro-3,4,10,11-tetrahydro-5,9-(metheno)-4,10-benzodiazacyclopentadecine
-
-
4,6-bis(4-guanidinylphenoxy)-1-guanidinyl-3-(4-guanidinylphenylamino)cyclohexane
-
-
4,7-dibenzyl-1,2,9,10-tetradehydro-3,4,5,6,7,8-hexahydro-4,7-benzodiazacyclododecine
-
-
8,11,22,25-tetrabenzyl-5,6,13,14,19,20,27,28-octadehydro-7,8,9,10,11,12,21,22,23,24,25,26-dodecahydrodibenzo[h,t][1,4,13,16]tetraazacyclotetracosine
-
-
alpha1-Aantichymotrypsin
-
incorporation of furin recognition sequences within the reactive site loop of alpha1-antiprypsin leads to the production of furin inhibitors, construction of a series of alpha1-antichymotrypsin mutants by modifying the P7-P1 region of the reactive site loop
-
alpha1-antitrypsin M352R
i.e. alpha1-PDX. Engineering of alpha1-antitrypsin variants, containing Arg at the P1 site within the reactive site loop, with improved specificity for the proprotein convertase furin using site-directed random mutagenesis, screening, overview. The engineered a1-antitrypsin variant carrying the RXXR consensus motif for furin within its reactive site loop. Furin-mediated maturation of bone morphogenetic protein-4 is completely inhibited by ectopic expression of the AVNR variant
-
alpha1-antitrypsin Portland variant
-
i.e. alpha1-PDX, inhibits furin and the generation of soluble (pro)renin receptor
-
brefeldin A
-
blocks the tumor necrosis factor alpha-induced activation of furin and subsequent neutral sphingomyelinase activation, without altering the basal level of furin
Cu(2,2':6,2''-terpyridine)Cl2
-
IC50: 0.0077 mM, irreversible, competitive with substrate tert-butyloxycarbonyl-Arg-Val-Arg-Arg-4-methylcoumaryl-7-amide
Cu(4'-hydroxo-2,2':6',2''-terpyridine)Cl2
-
IC50: 0.0072 mM, irreversible, competitive with substrate tert-butyloxycarbonyl-Arg-Val-Arg-Arg-4-methylcoumaryl-7-amide
Cu(4'-[4-methoxyphenyl]-2,2':6',2''-terpyridine)Cl2
-
IC50: 0.0051 mM, irreversible, competitive with substrate tert-butyloxycarbonyl-Arg-Val-Arg-Arg-4-methylcoumaryl-7-amide
Cu(4,4''-dimethyl-4'-[p-tolyl]-2,2':6',2''-terpyridine)Cl2
-
IC50: 0.014 mM, irreversible, competitive with substrate tert-butyloxycarbonyl-Arg-Val-Arg-Arg-4-methylcoumaryl-7-amide
Cu(di-[2-picolyl]amine)Cl2
-
IC50: 0.038 mM, irreversible, competitive with substrate tert-butyloxycarbonyl-Arg-Val-Arg-Arg-4-methylcoumaryl-7-amide
cyclo[succinyl-Phe-2-Nal-Arg-Arg-Arg-Arg-Arg-Lys]-Arg 4-amidinobenzylamide
-
cyclo[succinyl-Phe-2-Nal-Arg-Arg-Arg-Arg-Arg-Lys]-Lys 4-amidinobenzylamide
-
furin-Eda peptide acyclic
-
synthesis, overview. Designed a potent furin inhibitor that contains a highly reactive beta-turn inducing and radical generating enediynyl amino acid moiety, which is inserted between P1 and P19 residues of hfurin98-112 peptide, derived from the primary cleavage site of furin's own prodomain. The inhibitor displays a predominantly beta-turn structure. The inhibitor protects furin protein from self degradation
hfurin25-107
-
i.e. furin prodomain protein, competitive inhibitor, blockade of furin activity and furin-induced tumor cells malignant phenotypes by the chemically synthesized human furin prodomain, overview. Secondary structure of furin prodomain protein, overview
-
histone H1
-
efficiently blocks furin-dependent pro-von Willebrand factor processing in a dose-dependent manner, interaction between histone H1 and furin mainly takes place on the cell surface. H1 may be involved in extracellular and/or intracellular furin regulation
-
inter-alpha-inhibitor protein IalphaIp
-
blocks furin activity in vitro and provides significant protection against cytotoxocity for murine peritoneal macrophages exposed to up to 500 ng/ml anthrax lethal toxin
-
Lys-Arg-Arg-Tle-Lys 4-amidinobenzylamide (Lys1-Lys5 4-[4-(2-amino-2-oxoethyl)piperazin-1-yl]butanamide bridged)
-
Lys-Arg-Arg-Tle-Lys 4-amidinobenzylamide (Lys1-Lys5 N1-[[4-(2-amino-2-oxoethyl)phenyl]methyl]butanediamide bridged)
-
Lys-Arg-Arg-Tle-Lys 4-amidinobenzylamide (Lys1-Lys5 N1-[[4-(2-amino-2-oxoethyl)phenyl]methyl]pentanediamide bridged)
-
m-guanidinomethyl-phenylacetyl-Arg-Val-Arg-(amidomethyl)-benzamidine
a competitive, noncovalent inhibitor, binding structure, overview
methyl 4-(bis(4-hydroxy-2-oxo-2H-chromen-3-yl)methyl)benzoate
-
noncompetitive inhibitor
monensin
-
blocks the tumor necrosis factor alpha-induced activation of furin and subsequent neutral sphingomyelinase activation, without altering the basal level of furin
N''-[(1E)-[2-[(4-chlorobenzyl)oxy]phenyl]methylidene]carbonohydrazonic diamide
-
competitive inhibitor
N,N'-[[(1R,3S,4S,6R)-4-carbamimidamido-6-(4-carbamimidamidoanilino)cyclohexane-1,3-diyl]bis(oxy-4,1-phenylene)]diguanidine
racemate, interferes directly with the catalytic competent conformation of the catalytic triad. Inhibition mechanism, overview
N,N'-[[(1S,3R,4R,6S)-4-carbamimidamido-6-(4-carbamimidamidoanilino)cyclohexane-1,3-diyl]bis(oxy-4,1-phenylene)]diguanidine
interferes directly with the catalytic competent conformation of the catalytic triad. Inhibition mechanism, overview
N-(benzo[d][1,3]dioxol-5-yl)-1,2,3,4-tetrahydroacridin-9-amine
-
competitive inhibitor
N-(thiazol-2-yl)-4-(5-((2,4,6-trioxotetrahydropyrimidin-5(6H)-ylidene)methyl)furan-2-yl)benzenesulfonamide
-
competitive inhibitor
N-[3,5-bis[(1E)-1-(2-carbamimidoylhydrazinylidene)ethyl]phenyl]-2-[3-[(1E)-1-(2-carbamimidoylhydrazinylidene)ethyl]-5-[(1Z)-1-(2-carbamimidoylhydrazinylidene)ethyl]phenoxy]acetamide
-
-
N-[3,5-bis[(1E)-1-(2-carbamimidoylhydrazinylidene)ethyl]phenyl]-4-carbamimidamidobutanamide
-
-
N-[3,5-bis[(1E)-1-(2-carbamimidoylhydrazinylidene)ethyl]phenyl]-5-carbamimidamidopentanamide
-
-
N-[3,5-bis[(1E)-1-(2-carbamimidoylhydrazinylidene)ethyl]phenyl]-N'-[3-[(1E)-1-(2-carbamimidoylhydrazinylidene)ethyl]-5-[(1Z)-1-(2-carbamimidoylhydrazinylidene)ethyl]phenyl]propanediamide
-
-
N2-(phenylacetyl)-L-arginyl-L-valyl-N-(3-carbamimidamidopropyl)-L-argininamide
-
-
N2-(phenylacetyl)-L-arginyl-L-valyl-N-(4-carbamimidamidobutyl)-L-argininamide
-
-
N2-(phenylacetyl)-L-arginyl-L-valyl-N-(4-carbamimidoylbenzyl)-L-argininamide
-
-
N2-(phenylacetyl)-L-arginyl-L-valyl-N-(5-carbamimidamidopentyl)-L-argininamide
-
-
N2-(phenylacetyl)-L-arginyl-L-valyl-N-[(1-carbamimidoylpiperidin-4-yl)methyl]-L-argininamide
-
-
N2-(phenylacetyl)-L-arginyl-L-valyl-N-[3-(aminomethyl)benzyl]-L-argininamide
-
-
N2-(phenylacetyl)-L-arginyl-L-valyl-N-[3-(carbamimidamidomethyl)benzyl]-L-argininamide
-
-
N2-(phenylacetyl)-L-arginyl-L-valyl-N-[4-(aminomethyl)benzyl]-L-argininamide
-
-
N2-(phenylacetyl)-L-arginyl-L-valyl-N-[4-(carbamimidamidomethyl)benzyl]-L-argininamide
-
-
phenylacetyl-Arg-Val-Arg-(amidomethyl)-benzamidine
a competitive, noncovalent inhibitor, binding structure, overview
proPC1/3 39-62 NHYLFKHKSHPRRSALAITKR
-
peptide derived from proprotein convertase 1/3
proPC1/3 39-62/A NAYLF KAKSAPRRSRRSALAITKR
-
peptide derived from proprotein convertase 1/3
proPC1/3 50-83 RRSRRSALHITKRLSDDDRVTWAEQQYEKERSKR
-
peptide derived from proprotein convertase 1/3
Zn(4'-[4-methoxyphenyl]-2,2':6',2''-terpyridine)Cl2
-
IC50: 0.009 mM, irreversible, competitive with substrate tert-butyloxycarbonyl-Arg-Val-Arg-Arg-4-methylcoumaryl-7-amide
Zn(4'-[p-tolyl]-2,2':6',2''-terpyridine)Cl2
-
IC50: 0.009 mM, irreversible, competitive with substrate tert-butyloxycarbonyl-Arg-Val-Arg-Arg-4-methylcoumaryl-7-amide
Zn(4,4''-dimethyl-4'-[p-tolyl]-2,2':6',2''-terpyridine)Cl2
-
0.014 mM, irreversible, competitive with substrate tert-butyloxycarbonyl-Arg-Val-Arg-Arg-4-methylcoumaryl-7-amide
[Cu(2,2':6,2''-terpyridine)Cl2] (OCl4)
-
IC50: 0.0069 mM, irreversible, competitive with substrate tert-butyloxycarbonyl-Arg-Val-Arg-Arg-4-methylcoumaryl-7-amide
alpha1-antitrypsin
-
incorporation of furin recognition sequences within the reactive site loop of alpha1-antiprypsin leads to the production of furin inhibitors, construction of a series of alpha1-antitrypsin mutants by modifying the P7-P1 region of the reactive site loop
-
alpha1-antitrypsin
-
in cells overexpressing alpha1-antitrypsin, mRNA level of furin is reduced
-
decanoyl-Arg-Val-Lys-Arg-chloromethylketone
-
significantly blocks the processing of ADAMTS4 in HEK-293 cells
decanoyl-Arg-Val-Lys-Arg-chloromethylketone
-
blocks cleavage of the first and second motifs in human hepatoma cells
decanoyl-Arg-Val-Lys-Arg-chloromethylketone
-
fully blocks the substrate cleavage by the wild-type enzyme
decanoyl-RVKR-chloromethyl ketone
-
inhibition of furin inhibits processing of pro-B-type natriuretic peptide
Zn2+
-
IC50: 0.021 mM, irreversible, competitive with substrate tert-butyloxycarbonyl-Arg-Val-Arg-Arg-4-methylcoumaryl-7-amide
additional information
-
a potent inhibitor containing a ketomethylene arginyl pseudopeptide bond; contains Cys near the active site His
-
additional information
-
Boc-RVRR-4-methylcoumarin-7-amide does not show any signs of substrate inhibition
-
additional information
-
the prodomain exhibits inhibitory action toward furin
-
additional information
-
siRNA-mediated depletion of endogenous c-Jun NH2-terminal kinase-interacting leucine zipper protein (JLP) or phosphoinositide kinase for position 5 containing a five finger domain (PIKfyve), profoundly delays microtubule-based transport of chimeric furin (Tac-furin) from endosomes to the trans-Golgi network in a CHO cell line, which is rescued upon ectopic expression of siRNA-resistant JLP or PIKfyve constructs
-
additional information
-
cell-permeable, small-molecule compound, which inhibits furin-mediated cleavage of pro-membrane type-1 matrix metalloproteinase, resulting in a 50% decrease in the invasiveness of the HT1080 cell
-
additional information
-
expression of furin in HaCaT cells declines with respect to time in response to UV radiation irrespective of the type or the dose used
-
additional information
-
O-glycosylation of substrate proBNP in the cleavage site region at Thr71 reduces furin cleaving activity, overview
-
additional information
-
EC values of furin inhibitors, overview. Inhibition of cell-surface PA83 processing in cell-based assays, overview
-
additional information
-
synthetic aromatic enediyne derivatives and their effects on protease activity of proprotein convertases furin, overview
-
additional information
peptidomimetic compounds based on a phenylacetyl-Arg-Val-Arg-4-(amidomethyl)benzamidine core structure belong to the strongest noncovalent enzyme inhibitors. Upon variation of the P5 position, dramatic changes of the Ki values are observed that cannot be explained by the known recognition motive. The Ki improves by approximately 2 orders of magnitude after addition of basic substituents, e.g., by modification of the Phac-moiety at P5 by a m- or p-guanidinomethyl group. Structure-guided drug design, overview
-
additional information
-
peptidomimetic compounds based on a phenylacetyl-Arg-Val-Arg-4-(amidomethyl)benzamidine core structure belong to the strongest noncovalent enzyme inhibitors. Upon variation of the P5 position, dramatic changes of the Ki values are observed that cannot be explained by the known recognition motive. The Ki improves by approximately 2 orders of magnitude after addition of basic substituents, e.g., by modification of the Phac-moiety at P5 by a m- or p-guanidinomethyl group. Structure-guided drug design, overview
-
additional information
active site distortions of human furin by a small molecule inhibitor N,N'-[[(1S,3R,4R,6S)-4-carbamimidamido-6-(4-carbamimidamidoanilino)cyclohexane-1,3-diyl]bis(oxy-4,1-phenylene)]diguanidine, analysis of binding structures of noncovalent 2,5-dideoxystreptamine-derived furin inhibitors, overview
-
additional information
-
active site distortions of human furin by a small molecule inhibitor N,N'-[[(1S,3R,4R,6S)-4-carbamimidamido-6-(4-carbamimidamidoanilino)cyclohexane-1,3-diyl]bis(oxy-4,1-phenylene)]diguanidine, analysis of binding structures of noncovalent 2,5-dideoxystreptamine-derived furin inhibitors, overview
-
additional information
analysis of the interactions of P4-P6 of furin with substrate-like peptide inhibitors using X-ray crystallography, substrate specificity is mediated at these binding sites, docking study, detailed overview
-
additional information
inhibitor constructuion, synthesis, and structure-function analysis, overview. Evaluation of inhibition of alphavirus propagation and inhibition of diphtheria toxin action
-
additional information
development of specific inhibitors of furin, synthesis of several truncated analogues of the bicyclic sunflower trypsin inhibitor (SFTI-1), or of compounds by various head-to-tail, head-to-side chain, and side-chain-to-tail cyclizations within multibasic octapeptides, or of several cationic cyclized peptides with cell-penetrating properties, overview. Inhibitory potency of these compounds is determined in enzyme kinetic assays with furin. Inhibitor docking study, crystal structure determination, and structure-function analysis. Modeling of furin in complex with inhibitors N2-(1,3-thiazol-2-yl)-L-arginyl-N-[(1S)-2-amino-2-oxo-1-(4-[[4-(trifluoromethyl)benzyl]oxy]phenyl)ethyl]-L-lysinamide, diphenyl (1-[[(benzyloxy)carbonyl]amino]-3-carbamimidamidopropyl)phosphonate, diphenyl (1-[[(benzyloxy)carbonyl]amino]-4-carbamimidamidobutyl)phosphonate, and diphenyl [2-(4-aminophenyl)-1-[[(benzyloxy)carbonyl]amino]ethyl]phosphonate. Inhibition of respiratory syncytial virus propagation in A549 cells
-
additional information
no inhibition of human furin by DFP, 4-(2-aminoethyl)benzensulfonylfluorid (AEBSF), and PMSF
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
heparin
-
optimizies furin processing of substrates containing multibasic residues at strategic P-positions within the cleavage site. Incubation of Fujian-like peptides with heparin results in ca. 2- to 3fold enhancement of processing. Heparin at a concentration of 0.02 mM dramatically enhances processing of the basic highly pathogenic Queretaro H5N2 peptide, albeit at neutral pH. It has no effect on processing of low pathogenic Mexico H5N2 peptide
additional information
-
heparin-peptide interaction may better expose site1, and hence allow more effective furin cleavage. Extended sequences require heparin for optimal processing by furin
-
additional information
-
His69 controls the pH-sensitive furin propeptide cleavage and enzyme activation in vitro. Protonated His69 disrupts the propeptide to expose the internal cleavage site and increases the efficiency of cleavage at Arg75 to yield the active enzyme
-
additional information
-
in the presence of trifluoroethanol, the N-terminal half of the prodomain is better structured and more compactly folded than the C-terminal half of the prodomain. N-terminal residues 1-46 of the prodomain in 50% trifluoroethanol populates backbone conformations containing a short helix, a beta-strand and a helix-loop-helix supersecondary structure with elements of tertiary interactions. The intervening segment (residues 47-65) is predominately unstructured with a long and highly flexible region surrounding the protease activation loop followed by a partially helical segment in the C-terminal end. A peptide fragment derived from residues Pro16-Arg49 can form the helix-loop-helix structure in aqueous solution in the absence of trifluoroethanol
-
additional information
-
L-Sox5 and Sox-6 act as negative regulators of Sox9-induced furin expression
-
additional information
-
expression of furin in irradiated Colo-16 cells remains constant for 48 h following exposure of the cells to either low dose UVA and/or UVB radiation, and high-dose UVA radiation. In cells irradiated with high-dose UVB radiation, significant increase in furin expression commencing at 12 h, which peaks at 24 h (5fold). Correlation between expression of pp38 and furin in Colo-16 cells, but not HaCaT cells, following UV exposure
-
additional information
structure of the unliganded form of the proprotein convertase furin suggests activation by a substrate-induced mechanism, complex activation mechanism, overview
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.03
(2-Aminobenzoyl)-Lys-Glu-Arg-Ser-Lys-Arg-Ser-Ala-Leu-Arg-Asp-(3-nitro)Tyr-Ala
-
-
0.00039
Abz-GIRRKRSVSHQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, absence of Mg2+
0.00042
Abz-GIRRKRSVSHQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, presence of Mg2+
0.00021
Abz-GRRTRREAIVQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, presence of Mg2+
0.0012
Abz-GRRTRREAIVQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, absence of Mg2+
0.0003
Abz-HHRQRRSVSIQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, absence of Mg2+
0.0032
Abz-HHRQRRSVSIQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, presence of Mg2+
0.00038
Abz-HKREKRQAKHQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, absence of Mg2+
0.0027
Abz-HKREKRQAKHQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, presence of Mg2+
0.0002
Abz-HRREKRSVALQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, presence of Mg2+
0.00022
Abz-HRREKRSVALQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, absence of Mg2+
0.00028
Abz-HRRQKRSVALQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, absence of Mg2+
0.00037
Abz-HRRQKRSVALQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, presence of Mg2+
0.00005
Abz-KIRRRRDVVDQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, presence of Mg2+
0.0001
Abz-KIRRRRDVVDQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, absence of Mg2+
0.00028
Abz-LKRRRRDTQQQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, absence of Mg2+
0.0052
Abz-LKRRRRDTQQQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, presence of Mg2+
0.00033
Abz-NLRRRRDLVDQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, presence of Mg2+
0.0014
Abz-NLRRRRDLVDQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, absence of Mg2+
0.0001
Abz-RERRRKKRGLFGQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, absence of Mg2+
0.0001
Abz-RERRRKKRGLFGQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, presence of Mg2+
0.0002
Abz-RKRSRRQVNTQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, presence of Mg2+
0.0065
Abz-RKRSRRQVNTQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, absence of Mg2+
0.0012
Abz-RRRAKRSPKHQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, presence of Mg2+
0.0122
Abz-RRRAKRSPKHQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, absence of Mg2+
0.00039
Abz-RRRDKRSVALQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, absence of Mg2+
0.00041
Abz-RRRDKRSVALQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, presence of Mg2+
0.0155
Abz-RRRKKRGLFGQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, absence of Mg2+
0.0155
Abz-RRRKKRGLFGQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, presence of Mg2+
0.00022
Abz-RRRKKRGLSGQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, absence of Mg2+
0.00022
Abz-RRRKKRGLSGQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, presence of Mg2+
0.00023
Abz-RRRKKRSLFGQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, absence of Mg2+
0.00023
Abz-RRRKKRSLFGQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, presence of Mg2+
0.00041
Abz-SKRSRRSVSVQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, absence of Mg2+
0.00049
Abz-SKRSRRSVSVQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, presence of Mg2+
0.00007
Abz-SRRHKRFAGVQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, absence of Mg2+
0.00007
Abz-SRRHKRFAGVQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, presence of Mg2+
0.00015
Abz-SRRKRRDVTPQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, presence of Mg2+
0.00045
Abz-SRRKRRDVTPQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, absence of Mg2+
0.00014
Abz-SRRKRRSASTQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, presence of Mg2+
0.005
Abz-SRRKRRSASTQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, absence of Mg2+
0.00086
Abz-SSRHRRALDTQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, absence of Mg2+
0.00416
Abz-SSRHRRALDTQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, presence of Mg2+
0.00053
Abz-TRRFRRSITEQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, absence of Mg2+
0.00053
Abz-TRRFRRSITEQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, presence of Mg2+
additional information
additional information
-
upon increase of the pH from 6.0 to 9.0, KM-decreases linearly up to pH 7.5 and then remains constant
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
5
Abz-RRRKKRGLFGQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, presence of Mg2+
29.6
Abz-GIRRKRSVSHQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, presence of Mg2+
30.3
Abz-GIRRKRSVSHQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, absence of Mg2+
3.6
Abz-GRRTRREAIVQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, absence of Mg2+
4.2
Abz-GRRTRREAIVQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, presence of Mg2+
28.9
Abz-HHRQRRSVSIQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, presence of Mg2+
39.5
Abz-HHRQRRSVSIQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, absence of Mg2+
6.3
Abz-HKREKRQAKHQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, presence of Mg2+
6.9
Abz-HKREKRQAKHQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, absence of Mg2+
7.6
Abz-HRREKRSVALQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, presence of Mg2+
12.2
Abz-HRREKRSVALQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, absence of Mg2+
9.2
Abz-HRRQKRSVALQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, absence of Mg2+
14.9
Abz-HRRQKRSVALQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, presence of Mg2+
0.6
Abz-KIRRRRDVVDQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, absence of Mg2+
3.1
Abz-KIRRRRDVVDQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, presence of Mg2+
0.61
Abz-LKRRRRDTQQQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, absence of Mg2+
6.7
Abz-LKRRRRDTQQQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, presence of Mg2+
2
Abz-NLRRRRDLVDQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, absence of Mg2+
3.5
Abz-NLRRRRDLVDQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, presence of Mg2+
2.6
Abz-RERRRKKRGLFGQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, absence of Mg2+
12.3
Abz-RERRRKKRGLFGQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, presence of Mg2+
8.4
Abz-RKRSRRQVNTQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, absence of Mg2+
11.3
Abz-RKRSRRQVNTQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, presence of Mg2+
5.3
Abz-RRRAKRSPKHQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, presence of Mg2+
8.7
Abz-RRRAKRSPKHQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, absence of Mg2+
12.2
Abz-RRRDKRSVALQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, presence of Mg2+
14.6
Abz-RRRDKRSVALQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, absence of Mg2+
2.4
Abz-RRRKKRGLSGQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, absence of Mg2+
6.7
Abz-RRRKKRGLSGQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, presence of Mg2+
1
Abz-RRRKKRSLFGQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, absence of Mg2+
7.6
Abz-RRRKKRSLFGQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, presence of Mg2+
10.5
Abz-SKRSRRSVSVQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, absence of Mg2+
18.3
Abz-SKRSRRSVSVQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, presence of Mg2+
0.21
Abz-SRRHKRFAGVQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, absence of Mg2+
2.4
Abz-SRRHKRFAGVQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, presence of Mg2+
9.2
Abz-SRRKRRDVTPQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, absence of Mg2+
9.9
Abz-SRRKRRDVTPQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, presence of Mg2+
10
Abz-SRRKRRSASTQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, absence of Mg2+
11.1
Abz-SRRKRRSASTQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, presence of Mg2+
5.6
Abz-SSRHRRALDTQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, absence of Mg2+
7.1
Abz-SSRHRRALDTQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, presence of Mg2+
16.4
Abz-TRRFRRSITEQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, absence of Mg2+
19.8
Abz-TRRFRRSITEQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, presence of Mg2+
additional information
additional information
-
over the pH intercal 6.0 to 9.0 kcat occurs as a bell-shaped form with a maximum at pH 7.0
-
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
322
Abz-RRRKKRGLFGQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, presence of Mg2+
70550
Abz-GIRRKRSVSHQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, presence of Mg2+
77100
Abz-GIRRKRSVSHQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, absence of Mg2+
3085
Abz-GRRTRREAIVQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, absence of Mg2+
20190
Abz-GRRTRREAIVQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, presence of Mg2+
9031
Abz-HHRQRRSVSIQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, presence of Mg2+
116100
Abz-HHRQRRSVSIQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, absence of Mg2+
2354
Abz-HKREKRQAKHQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, presence of Mg2+
17730
Abz-HKREKRQAKHQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, absence of Mg2+
38300
Abz-HRREKRSVALQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, presence of Mg2+
55640
Abz-HRREKRSVALQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, absence of Mg2+
32430
Abz-HRRQKRSVALQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, absence of Mg2+
40270
Abz-HRRQKRSVALQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, presence of Mg2+
6000
Abz-KIRRRRDVVDQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, absence of Mg2+
53450
Abz-KIRRRRDVVDQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, presence of Mg2+
1303
Abz-LKRRRRDTQQQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, presence of Mg2+
2184
Abz-LKRRRRDTQQQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, absence of Mg2+
1470
Abz-NLRRRRDLVDQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, absence of Mg2+
10610
Abz-NLRRRRDLVDQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, presence of Mg2+
1555
Abz-RERRRKKRGLFGQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, absence of Mg2+
123000
Abz-RERRRKKRGLFGQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, presence of Mg2+
1291
Abz-RKRSRRQVNTQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, absence of Mg2+
56300
Abz-RKRSRRQVNTQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, presence of Mg2+
710
Abz-RRRAKRSPKHQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, absence of Mg2+
4383
Abz-RRRAKRSPKHQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, presence of Mg2+
29660
Abz-RRRDKRSVALQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, presence of Mg2+
37510
Abz-RRRDKRSVALQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, absence of Mg2+
797
Abz-RRRKKRGLSGQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, absence of Mg2+
30500
Abz-RRRKKRGLSGQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, presence of Mg2+
606
Abz-RRRKKRSLFGQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, absence of Mg2+
33040
Abz-RRRKKRSLFGQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, presence of Mg2+
25360
Abz-SKRSRRSVSVQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, absence of Mg2+
37350
Abz-SKRSRRSVSVQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, presence of Mg2+
559
Abz-SRRHKRFAGVQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, absence of Mg2+
33860
Abz-SRRHKRFAGVQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, presence of Mg2+
20470
Abz-SRRKRRDVTPQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, absence of Mg2+
66000
Abz-SRRKRRDVTPQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, presence of Mg2+
1992
Abz-SRRKRRSASTQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, absence of Mg2+
76230
Abz-SRRKRRSASTQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, presence of Mg2+
1707
Abz-SSRHRRALDTQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, presence of Mg2+
6488
Abz-SSRHRRALDTQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, absence of Mg2+
28360
Abz-TRRFRRSITEQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, absence of Mg2+
37360
Abz-TRRFRRSITEQ-N-(2,4-dinitrophenyl)ethylenediamine
-
pH 7.0, 37°C, presence of Mg2+
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00000099
(1S,14S,17S,20S,23S,26S,33r)-26-amino-N-(4-carbamimidoylbenzyl)-20,23-bis(3-guanidinopropyl)-17-neopentyl-4,8,16,19,22,25,32-heptaoxo-3,9,15,18,21,24,31-heptaazabicyclo[31.2.2]heptatriacontane-14-carboxamide
pH and temperature not specified in the publication
0.012
2-(11-hydroxy-3-oxo-3H-dibenzo[c,h]xanthen-7-yl)benzoic acid
-
with CPA95 as substrate/with N-tert-butoxycarbonyl-Arg-Val-Arg-Arg-methylcoumarin amide as substrate
0.0033
3,3',3'',3'''-(1,4-phenylenebis(methanetriyl))tetrakis(4-hydroxy-2H-chromen-2-one)
-
with CPA95 as substrate
0.00104
3,3'-((2,3-dihydro-1H-inden-5-yl)methylene)bis(4-hydroxy-2H-chromen-2-one)
-
with CPA95 as substrate
0.1851
3,3'-((2-bromophenyl)methylene)bis(4-hydroxy-2H-chromen-2-one)
-
with Ac-Arg-Val-Arg-Arg-4-nitroanilide as substrate
0.0783
3,3'-((2-chlorophenyl)methylene)bis(4-hydroxy-2H-chromen-2-one)
-
with Ac-Arg-Val-Arg-Arg-4-nitroanilide as substrate
0.022
3,3'-((3,4,5-trimethoxyphenyl)methylene)bis(4-hydroxy-2H-chromen-2-one)
-
with Ac-Arg-Val-Arg-Arg-4-nitroanilide as substrate
0.0208
3,3'-((4-isopropoxyphenyl)methylene)bis(4-hydroxy-2H-chromen-2-one)
-
with Ac-Arg-Val-Arg-Arg-4-nitroanilide as substrate
0.00605
3,3'-(benzo[d][1,3]dioxol-5-ylmethylene)bis(4-hydroxy-2H-chromen-2-one)
-
with Ac-Arg-Val-Arg-Arg-4-nitroanilide as substrate
2
3-(alpha-acetonyl-benzyl)-4-(hydroxycoumarin)
-
with Ac-Arg-Val-Arg-Arg-4-nitroanilide as substrate
0.0000025
3-guanidinomethylphenylacetyl-Val-Arg 4-amidinobenzylamide
pH 7.0, 22°C
0.0000000000224
4-aminomethyl-phenylacetyl-Arg-Tle-Arg-4-aminomethyl-benzamidine
pH and temperature not specified in the publication
1.3
4-hydroxy-3-oxo-1-phenylbutylcoumarin
-
with Ac-Arg-Val-Arg-Arg-4-nitroanilide as substrate
0.000019
Ac-Ac-RQIKIWFQNRRMKWKKRVR 4-amidinobenzylamide
pH and temperature not specified in the publication
0.0000228
Ac-AGYLLGKINLKALAALAKKILRVR 4-amidinobenzylamide
pH and temperature not specified in the publication
0.0000107
Ac-RRRRRRRVR 4-amidinobenzylamide
pH and temperature not specified in the publication
0.000011
Ac-YGRKKRRQRRRVR 4-amidinobenzylamide
pH and temperature not specified in the publication
0.0024
acetyl-Val-Arg-4-aminomethyl-benzamidine
pH and temperature not specified in the publication
0.0000094
Arg-Arg-Arg-Arg-Arg-Arg
pH and temperature not specified in the publication
0.000006
Arg-Arg-Arg-Arg-Arg-Arg-Arg-Arg
pH and temperature not specified in the publication
0.0000093
Arg-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Arg
pH and temperature not specified in the publication
0.0000000337
Arg-Arg-Arg-Val-Arg-4-amidinobenzylamide
pH and temperature not specified in the publication
0.0000000000337
Arg-Arg-Arg-Val-Arg-4-aminomethyl-benzamidine
pH and temperature not specified in the publication
0.0000278
cyclo[(Arg)10]
pH and temperature not specified in the publication
0.0001104
cyclo[(Arg)6]
pH and temperature not specified in the publication
0.0000227
cyclo[(Arg)8]
pH and temperature not specified in the publication
0.00000068
cyclo[glutaryl-Arg-Arg-Arg-Lys]-Arg 4-amidinobenzylamide
pH and temperature not specified in the publication
0.000504
cyclo[glutaryl-Arg-Arg-Lys]-Arg 4-amidinobenzylamide
pH and temperature not specified in the publication
0.00000105
cyclo[glutaryl-Arg-Arg-Lys]-Lys 4-amidinobenzylamide
pH and temperature not specified in the publication
0.000000146
cyclo[succinyl-Phe-2-Nal-Arg-Arg-Arg-Arg-Arg-Lys]-Arg 4-amidinobenzylamide
pH and temperature not specified in the publication
0.000000154
cyclo[succinyl-Phe-2-Nal-Arg-Arg-Arg-Arg-Arg-Lys]-Lys 4-amidinobenzylamide
pH and temperature not specified in the publication
0.0000000538
cyclo[succinyl-Phe-2-Nal-Arg-Arg-Arg-Arg-Lys]-Arg 4-amidinobenzylamide
pH and temperature not specified in the publication
0.000000136
cyclo[succinyl-Phe-2-Nal-Arg-Arg-Arg-Arg-Lys]-Lys 4-amidinobenzylamide
pH and temperature not specified in the publication
0.000000378
cyclo[succinyl-Phe-2-Nal-Arg-Arg-Arg-Lys]-Arg 4-amidinobenzylamide
pH and temperature not specified in the publication
0.000000618
cyclo[succinyl-Phe-2-Nal-Arg-Arg-Arg-Lys]-Lys 4-amidinobenzylamide
pH and temperature not specified in the publication
0.00000011
D-Arg-D-Arg-D-Arg-Arg-Val-Arg 4-amidinobenzylamide
pH 7.0, 22°C
0.0000000378
D-Arg-D-Arg-D-Arg-D-Arg-Arg-Val-Arg 4-amidinobenzylamide
pH 7.0, 22°C
0.000156
hfurin25-107
-
pH 7.4, 37°C, versus N-benzyloxycarbonyl-RVRR-4-methylcoumarin 7-amide
-
0.000000491
Lys-Arg-Arg-Tle-Lys 4-amidinobenzylamide (Lys1-Lys5 4-[4-(2-amino-2-oxoethyl)piperazin-1-yl]butanamide bridged)
pH and temperature not specified in the publication
0.00000504
Lys-Arg-Arg-Tle-Lys 4-amidinobenzylamide (Lys1-Lys5 N1-[[4-(2-amino-2-oxoethyl)phenyl]methyl]butanediamide bridged)
pH and temperature not specified in the publication
0.00000117
Lys-Arg-Arg-Tle-Lys 4-amidinobenzylamide (Lys1-Lys5 N1-[[4-(2-amino-2-oxoethyl)phenyl]methyl]pentanediamide bridged)
pH and temperature not specified in the publication
0.1452
methyl 4-(bis(4-hydroxy-2-oxo-2H-chromen-3-yl)methyl)benzoate
-
with Ac-Arg-Val-Arg-Arg-4-nitroanilide as substrate
0.0118
N''-[(1E)-[2-[(4-chlorobenzyl)oxy]phenyl]methylidene]carbonohydrazonic diamide
-
with Ac-Arg-Val-Arg-Arg-4-nitroanilide as substrate
0.00058
N-[3,5-bis[(1E)-1-(2-carbamimidoylhydrazinylidene)ethyl]phenyl]-2-[3-[(1E)-1-(2-carbamimidoylhydrazinylidene)ethyl]-5-[(1Z)-1-(2-carbamimidoylhydrazinylidene)ethyl]phenoxy]acetamide
-
pH 7.0,22°C
0.00046
N-[3,5-bis[(1E)-1-(2-carbamimidoylhydrazinylidene)ethyl]phenyl]-4-carbamimidamidobutanamide
-
pH 7.0,22°C
0.00104
N-[3,5-bis[(1E)-1-(2-carbamimidoylhydrazinylidene)ethyl]phenyl]-5-carbamimidamidopentanamide
-
pH 7.0,22°C
0.00113
N-[3,5-bis[(1E)-1-(2-carbamimidoylhydrazinylidene)ethyl]phenyl]-N'-[3-[(1E)-1-(2-carbamimidoylhydrazinylidene)ethyl]-5-[(1Z)-1-(2-carbamimidoylhydrazinylidene)ethyl]phenyl]propanediamide
-
pH 7.0,22°C
0.000000193
N2(carbamidoyl)Arg-Ala-Arg-Val-Arg 4-amidinobenzylamide
pH 7.0, 22°C
0.000000449
N2(carbamidoyl)Arg-Arg-Arg-Val-Arg 4-amidinobenzylamide
pH 7.0, 22°C
0.0002693
N2-(3-aminomethyl-phenylacetyl)-Val-Arg 4-amidinobenzylamide
pH 7.0, 22°C
0.0000000459
N2-(5-(guanidino)valeroyl)-Val-Arg 4-amidinobenzylamide
pH 7.0, 22°C
0.0000267
N2-(5-guanidinopentanoly)-Val-Arg 4-amidinobenzylamide
pH 7.0, 22°C
0.00302
N2-(phenylacetyl)-L-arginyl-L-valyl-N-(3-aminopropyl)-L-argininamide
-
pH 7.0, temperature not specified in the publication
0.000063
N2-(phenylacetyl)-L-arginyl-L-valyl-N-(3-carbamimidamidopropyl)-L-argininamide
-
pH 7.0, temperature not specified in the publication
0.00749
N2-(phenylacetyl)-L-arginyl-L-valyl-N-(4-aminobutyl)-L-argininamide
-
pH 7.0, temperature not specified in the publication
0.000078
N2-(phenylacetyl)-L-arginyl-L-valyl-N-(4-carbamimidamidobutyl)-L-argininamide
-
pH 7.0, temperature not specified in the publication
0.00000081
N2-(phenylacetyl)-L-arginyl-L-valyl-N-(4-carbamimidoylbenzyl)-L-argininamide
-
pH 7.0, temperature not specified in the publication
0.000553
N2-(phenylacetyl)-L-arginyl-L-valyl-N-(5-aminopentyl)-L-argininamide
-
pH 7.0, temperature not specified in the publication
0.00107
N2-(phenylacetyl)-L-arginyl-L-valyl-N-(5-carbamimidamidopentyl)-L-argininamide
-
pH 7.0, temperature not specified in the publication
0.00971
N2-(phenylacetyl)-L-arginyl-L-valyl-N-(piperidin-4-ylmethyl)-L-argininamide
-
pH 7.0, temperature not specified in the publication
0.000053
N2-(phenylacetyl)-L-arginyl-L-valyl-N-[(1-carbamimidoylpiperidin-4-yl)methyl]-L-argininamide
-
pH 7.0, temperature not specified in the publication
0.00132
N2-(phenylacetyl)-L-arginyl-L-valyl-N-[3-(aminomethyl)benzyl]-L-argininamide
-
pH 7.0, temperature not specified in the publication
0.00273
N2-(phenylacetyl)-L-arginyl-L-valyl-N-[3-(carbamimidamidomethyl)benzyl]-L-argininamide
-
pH 7.0, temperature not specified in the publication
0.000627
N2-(phenylacetyl)-L-arginyl-L-valyl-N-[4-(aminomethyl)benzyl]-L-argininamide
-
pH 7.0, temperature not specified in the publication
0.00143
N2-(phenylacetyl)-L-arginyl-L-valyl-N-[4-(carbamimidamidomethyl)benzyl]-L-argininamide
-
pH 7.0, temperature not specified in the publication
0.0000000786
N2-acetyl-D-Leu-Leu-Leu-Leu-Arg-Val-Lys 4-amidinobenzylamide
pH 7.0, 22°C
0.000001
N2-acetyl-L-arginyl-L-valyl-N-(4-carbamimidoylbenzyl)-L-argininamide
-
pH 7.0, temperature not specified in the publication
0.000164
N2-acetyl-Leu-Leu-Leu-Leu-Arg-Tle-Arg 4-amidinobenzylamide
pH 7.0, 22°C
0.0000482
N2-acetyl-Leu-Leu-Leu-Leu-Arg-Tle-Lys 4-amidinobenzylamide
pH 7.0, 22°C
0.0000378
N2-acetyl-Leu-Leu-Leu-Leu-Arg-Val-Arg 4-amidinobenzylamide
pH 7.0, 22°C
0.000000164
N2-acetyl-Leu-Leu-Leu-Leu-Arg-Val-Lys 4-amidinobenzylamide
pH 7.0, 22°C
0.0000016
N2-decanoyl-L-arginyl-L-valyl-N-(4-carbamimidoylbenzyl)-L-argininamide
-
pH 7.0, temperature not specified in the publication
0.0000033
N2-decanoyl-L-arginyl-L-valyl-N-(4-carbamimidoylbenzyl)-L-lysinamide
-
pH 7.0, temperature not specified in the publication
0.000000051
N2-phenylacetyl-Ala-Arg-Arg-Val-Arg 4-amidinobenzylamide
pH 7.0, 22°C
0.0000000283
N2-phenylacetyl-Arg-Ala-Arg-Val-Arg 4-amidinobenzylamide
pH 7.0, 22°C
0.0000000337
N2-phenylacetyl-Arg-Arg-Arg-Val-Arg 4-amidinobenzylamide
pH 7.0, 22°C
0.0000000491
N2-phenylacetyl-Arg-Arg-Val-Arg 4-amidinobenzylamide
pH 7.0, 22°C
0.0000000563
N2-phenylacetyl-Arg-Val-Arg 4-amidinobenzylamide
pH 7.0, 22°C
0.0000000138
Nalpha(carbamidoyl)Arg-Arg-Val-Arg 4-amidinobenzylamide
pH 7.0, 22°C
0.00000081
phenylacetyl-Arg-Val-Arg-4-aminomethyl-benzamidine
pH and temperature not specified in the publication
0.000238
phenylacetyl-Cit-Arg-Val-Arg-4-aminomethyl-benzamidine
pH and temperature not specified in the publication
0.00000126
N2-(5-aminopentanoyl)-Val-Arg 4-amidinobenzylamide
pH 7.0, 22°C
0.0000385
N2-(5-aminopentanoyl)-Val-Arg 4-amidinobenzylamide
pH 7.0, 22°C
additional information
additional information
-
Ki-values of alpha1-antitrypsin and alpha1-antichymotrypsin mutants obtained by incorporation of furin recognition sequences within the reactive site loop of the molecule and modifying the P7-P1 region of the reactive site loop
-
additional information
additional information
Ki values of the inhibitors with inhibition constants above 0.1 nM are determined by fitting of the data to the equation for classical reversible competitive inhibition
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0037
(D-Arg)9-amide
Homo sapiens
-
protects RAW264.7 cells against anthrax toxemia with an IC50 of 0.0037 mM
0.102
(E)-N-((E)-5-(2-chloro-5-nitrobenzylidene)-4-oxothiazolidin-2-ylidene)-4-methylbenzenesulfonamide
Homo sapiens
-
with N-tert-butoxycarbonyl-Arg-Val-Arg-Arg-methylcoumarin amide as substrate
0.084
(N'Z,N''Z)-4,4'-oxybis(N'-(2-hydroxybenzylidene)benzenesulfonohydrazide)
Homo sapiens
-
with N-tert-butoxycarbonyl-Arg-Val-Arg-Arg-methylcoumarin amide as substrate
0.007
2-(11-hydroxy-3-oxo-3H-dibenzo[c,h]xanthen-7-yl)benzoic acid
Homo sapiens
-
with CPA95 as substrate/with N-tert-butoxycarbonyl-Arg-Val-Arg-Arg-methylcoumarin amide as substrate
0.025
3'-oxo-6a,14a-dihydro-3'H-spiro[dibenzo[c,h]xanthene-7,1'-isobenzofuran]-3,11-diyl diacetate
Homo sapiens
-
with CPA95 as substrate
0.055
3,3',3'',3'''-(1,4-phenylenebis(methanetriyl))tetrakis(4-hydroxy-2H-chromen-2-one)
Homo sapiens
-
with CPA95 as substrate
0.004
3,3'-((2,3-dihydro-1H-inden-5-yl)methylene)bis(4-hydroxy-2H-chromen-2-one)
Homo sapiens
-
with CPA95 as substrate
0.051
3-allyl-1-methyl-1,2,3,4-tetrahydroisoquinoline
Homo sapiens
-
with N-tert-butoxycarbonyl-Arg-Val-Arg-Arg-methylcoumarin amide as substrate
0.137
3-hydroxy-5-(4-methoxyphenyl)-2-(4-phenoxy-3-sulfophenyl)-3H-pyrazol-2-ium
Homo sapiens
-
with N-tert-butoxycarbonyl-Arg-Val-Arg-Arg-methylcoumarin amide as substrate
0.0000142
4,10-bis[(4-methylphenyl)sulfonyl]-1,2,12,13-tetradehydro-3,4,10,11-tetrahydro-5,9-(metheno)-4,10-benzodiazacyclopentadecine
Homo sapiens
-
-
0.0000105
4,7-dibenzyl-1,2,9,10-tetradehydro-3,4,5,6,7,8-hexahydro-4,7-benzodiazacyclododecine
Homo sapiens
-
-
0.028
6-oxo-6H-benzo[c]chromen-3-yl 2-chlorobenzoate
Homo sapiens
-
with N-tert-butoxycarbonyl-Arg-Val-Arg-Arg-methylcoumarin amide as substrate
0.00016 - 0.000192
8,11,22,25-tetrabenzyl-5,6,13,14,19,20,27,28-octadehydro-7,8,9,10,11,12,21,22,23,24,25,26-dodecahydrodibenzo[h,t][1,4,13,16]tetraazacyclotetracosine
0.0077
Cu(2,2':6,2''-terpyridine)Cl2
Homo sapiens
-
IC50: 0.0077 mM, irreversible, competitive with substrate tert-butyloxycarbonyl-Arg-Val-Arg-Arg-4-methylcoumaryl-7-amide
0.0072
Cu(4'-hydroxo-2,2':6',2''-terpyridine)Cl2
Homo sapiens
-
IC50: 0.0072 mM, irreversible, competitive with substrate tert-butyloxycarbonyl-Arg-Val-Arg-Arg-4-methylcoumaryl-7-amide
0.0051
Cu(4'-[4-methoxyphenyl]-2,2':6',2''-terpyridine)Cl2
Homo sapiens
-
IC50: 0.0051 mM, irreversible, competitive with substrate tert-butyloxycarbonyl-Arg-Val-Arg-Arg-4-methylcoumaryl-7-amide
0.014
Cu(4,4''-dimethyl-4'-[p-tolyl]-2,2':6',2''-terpyridine)Cl2
Homo sapiens
-
IC50: 0.014 mM, irreversible, competitive with substrate tert-butyloxycarbonyl-Arg-Val-Arg-Arg-4-methylcoumaryl-7-amide
0.038
Cu(di-[2-picolyl]amine)Cl2
Homo sapiens
-
IC50: 0.038 mM, irreversible, competitive with substrate tert-butyloxycarbonyl-Arg-Val-Arg-Arg-4-methylcoumaryl-7-amide
0.000193
furin-Eda peptide cyclic
Homo sapiens
-
versus substrate fluorogenic peptide derived from hSARS-CoV spike protein
0.159
N-(benzo[d][1,3]dioxol-5-yl)-1,2,3,4-tetrahydroacridin-9-amine
Homo sapiens
-
with N-tert-butoxycarbonyl-Arg-Val-Arg-Arg-methylcoumarin amide as substrate
0.011
N-(thiazol-2-yl)-4-(5-((2,4,6-trioxotetrahydropyrimidin-5(6H)-ylidene)methyl)furan-2-yl)benzenesulfonamide
Homo sapiens
-
with N-tert-butoxycarbonyl-Arg-Val-Arg-Arg-methylcoumarin amide as substrate
0.009
Zn(4'-[4-methoxyphenyl]-2,2':6',2''-terpyridine)Cl2
Homo sapiens
-
IC50: 0.009 mM, irreversible, competitive with substrate tert-butyloxycarbonyl-Arg-Val-Arg-Arg-4-methylcoumaryl-7-amide
0.009
Zn(4'-[p-tolyl]-2,2':6',2''-terpyridine)Cl2
Homo sapiens
-
IC50: 0.009 mM, irreversible, competitive with substrate tert-butyloxycarbonyl-Arg-Val-Arg-Arg-4-methylcoumaryl-7-amide
0.021
Zn2+
Homo sapiens
-
IC50: 0.021 mM, irreversible, competitive with substrate tert-butyloxycarbonyl-Arg-Val-Arg-Arg-4-methylcoumaryl-7-amide
0.0069
[Cu(2,2':6,2''-terpyridine)Cl2] (OCl4)
Homo sapiens
-
IC50: 0.0069 mM, irreversible, competitive with substrate tert-butyloxycarbonyl-Arg-Val-Arg-Arg-4-methylcoumaryl-7-amide
0.00016
8,11,22,25-tetrabenzyl-5,6,13,14,19,20,27,28-octadehydro-7,8,9,10,11,12,21,22,23,24,25,26-dodecahydrodibenzo[h,t][1,4,13,16]tetraazacyclotetracosine
Homo sapiens
-
-
0.000192
8,11,22,25-tetrabenzyl-5,6,13,14,19,20,27,28-octadehydro-7,8,9,10,11,12,21,22,23,24,25,26-dodecahydrodibenzo[h,t][1,4,13,16]tetraazacyclotetracosine
Homo sapiens
-
-
0.00004
furin-Eda peptide acyclic
Homo sapiens
-
versus substrate N-benzyloxy-RVRR-4-methylcoumarin 7-amide
0.00004
furin-Eda peptide acyclic
Homo sapiens
-
versus substrate N-benzyloxy-RVRR-4-methylcoumarin 7-amide, pH not specified in the publication, temperature not specified in the publication
0.000193
furin-Eda peptide acyclic
Homo sapiens
-
versus substrate fluorogenic peptide derived from hSARS-CoV spike protein, pH not specified in the publication, temperature not specified in the publication
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.5
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5 - 6.5
-
5: about 35% of activity maximum, 6.5: about 15% of activity maximum, mouse, acetyl-Arg-Ser-Lys-Arg-4-methylcoumarin 7-amide
6 - 7.5
-
influenza deltaK-Fujian-like H5N1 peptide is the best furin substrate between pH 6-7.5. At pH 6, all Fujian-like peptides are cleaved with lower kinetics as compared to pH 7.5. Low pathogenic Mexico H5N2 peptide and highly pathogenic Queretaro H5N2 peptide are not processed by furin at either pH 7.5 or 6
6 - 8
-
pH 6.0: about 70% of maximal activity, pH 8.0: about 65% of maximal activity
additional information
-
pH-profiles of furin activity in the presence and absence of salts, e.g. KCl. The pK1 values for the pH-profiles of hydrolysis of all four substrates in the presence of KCl are lower than those in its absence
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
25
37
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
29686, 29688, 29692, 29693, 29694, 29695, 29696, 29697, 29699, 29701, 668923, 669214, 669255, 669258, 669442, 670247, 670828, 677290, 677460, 677786, 677957, 677962, 678063, 678743, 678910, 679039, 679142, 679776, 679871, 680137, 680654, 680696, 680791, 680878, 681510, 681918, 682808, 682972, 693230, 697621, 698960, 699309, 699910, 700401, 700627, 700898, 707275, 707527, 707598, 708162, 708168, 708242, 708682, 708753, 709465, 710165, 710258, 710381, 717306, 717362, 717827, 717903, 717927, 718256, 718447
-
-
-
731038, 731605, 732149, 732423, 732499, 732774, 732833, 732859, 732972, 752361, 752405, 752785, 753128, 753199, 753279, 753282, 754359, 755027, 755183, 755251
SwissProt
rat somatomammotroph cell line, GH4C1 infected with vaccinia virus recombinants of human PC1
-
-
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
proprotein convertase furin is highly expressed in syncytial trophoblast in the first trimester human placentas, and expression of furin in the syncytiotrophoblast is significantly lower in the placentas from pre-eclamptic patients as compared with their gestational age-matched control placentas
additional information
-
furin is highly expressed in placental villi during early pregnancy, specifically in trophoblast column and trophoblast shell, regions where highly invasive cytotrophoblast cells invade the maternal decidua during human placentation
proprotein convertase furin is highly expressed in syncytial trophoblast in the first trimester human placentas, and expression of furin in the syncytiotrophoblast is significantly lower in the placentas from pre-eclamptic patients as compared with their gestational age-matched control placentas
additional information
-
preferentially expressed in T helper 1 cells in a Stat4-dependent manner
additional information
-
present in glucagon cells, absent from insulin cells, somatostatin cells and pancreatic polypeptide cells
additional information
-
colorectal carcinoma LoVo cell line is devoid of furin activity
additional information
cellular furin abundance in five human cell lines is shown to be strongly correlated with productive infectious bronchitis virus, IBV, infection, cells expressing furin, overview
additional information
-
cellular furin abundance in five human cell lines is shown to be strongly correlated with productive infectious bronchitis virus, IBV, infection, cells expressing furin, overview
additional information
the enzyme is constitutively expressed in all cell lines. No enzyme activity in LoVo colorectal carcinoma cells
additional information
ubiquitous expression, although furin is expressed universally, expression levels vary and can be quite low depending on tissue types
additional information
-
ubiquitous expression, although furin is expressed universally, expression levels vary and can be quite low depending on tissue types
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
furin-propeptide complex is restricted to the endoplasmic reticulum by a PACS-2- and COPI-dependent mechanism. His69 is a pH sensor that allows enzyme activation following transport of the furin-propeptide complex from the endoplasmic reticulum to the mildly acidic TGN/endosomal system
the enzyme contains a signal peptide (amino acids 1-25) and is secreted
-
-
cleavage of the furin propeptide occurs in the endoplasmic reticulum and is necessary but not sufficient for transport of furin out of this compartment
-
additional information
-
hypoxia triggers relocalization of furin from the trans-Golgi network to endosomomal compartments and the cell surface in cancer cells
-
hypoxia triggers relocalization of furin from the trans-Golgi network to endosomomal compartments and the cell surface in cancer cells
-
the membrane-bound enzyme undergoes post-translational processing to produce a soluble form of the enzyme that can be secreted
additional information
-
furin is present both in the intracellular secretory pathway and at the cell surface
-
additional information
furin is a protease localized in the trans-Golgi network and in late endocytic compartments
-
additional information
-
furin is a protease localized in the trans-Golgi network and in late endocytic compartments
-
additional information
complementary subcellular distribution of bioactive furin and proprotein convertase PC7. Furin activity in endosomes is 10fold less inhibited by decanoyl-RVKR-chloromethylketone and enriched over 3fold in endosomes compared to the trans-Golgi network. Development of targeted compartment-specific biosensors. Endogenous PC7, which resists the inhibitor, is active in distinct vesicles. The distribution of proprotein convertase activities at the tissue level are monitored by introduction of biosensor CLIP (cell-linked indicator of proteolysis). CLIP v.3 is suitable for ratiometric imaging without interference by FRET and can estimate PC activity in exocytic compartments, whereas CLIP v.4 can be used as a FRET-based biosensor to quantify PC activities in specific intracellular vesicles. Fusion to the cytosolic tail of PC7 directs CLIP v.4 to compartments that harbor furin activity, but not full-length PC7
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
malfunction
metabolism
physiological function
additional information
evolution
furin is a member of the pro-hormone/pro-protein convertase family of subtilisin-like endoproteinases
evolution
the enzyme belongs to the proprotein convertase family of proteases
evolution
the enzyme is a member of the subtilisin-like proprotein convertase family
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
evolution
furin belongs to the family of Ca2+-dependent proprotein convertases (PCs), all of which contain a subtilisin-like serine protease domain. Furin and the other six basic PCs, i.e. PC1, PC2, PC4, PACE4, PC5, and PC7, cleave their substrates at multibasic sequences mainly after arginine, whereas the nonbasic PC site-1 protease (S1P) cleaves preferentially after leucine, valine, or isoleucine
evolution
furin belongs to the proprotein convertase subtilisin/kexin (PCSK) family of enzymes play a crucial role in processing and trafficking of a wide variety of precursor proteins such as hormones, receptors, and enzymes
malfunction
-
blockade of furin activity and furin-induced tumor cells malignant phenotypes by the chemically synthesized human furin prodomain, overview
malfunction
-
furin is involved in many physiological and pathological processes
malfunction
-
furin is linked to cancer, tumorgenesis, and viral and bacterial pathogenesis
malfunction
-
inhibition of furin inhibits processing of pro-B-type natriuretic peptide
malfunction
ablation of productive infectious bronchitis virus, IBV, infection by knockdown of furin expression in H1299 cells
malfunction
furin siRNAs upregulate HIF-1alpha protein under normoxic condition to a level similar to that obtained by cobalt chloride treatment, eventually leading to activation of VEGF-A synthesis in two human head and neck squamous cell carcinoma cell lines. HIF-1alpha induction of the enzyme siRNAs and either cobalt chloride or the 26S ribosome inhibitor, MG-132, suggesting a post-transcriptional enzyme-mediated regulation, the induction by siRNAs is inhibited by a specific IGF-1R signaling inhibitor
malfunction
furin-specific siRNAs or inhibitors inhibit cell fusion in choriocarcinoma BeWo cells, as well as trophoblast syncytialization in human placental explants
malfunction
knockdown of the enzyme expression in C8161.9, MelJuSo, and HeLa cells by shRNA leads to reduced or complete loss of KISS1 processing
malfunction
an unbalanced activity of proprotein convertases is connected to pathologies like cancer, atherosclerosis, hypercholesterolaemia, and infectious diseases
malfunction
dysregulation of furin is implicated in numerous disease states, including cancer and fibrosis
malfunction
plant-produced human furin treated with PNGase F and Endo H does not exhibit cleavage activity. Similarly, when commercial human furin (NEB) is treated with commercial Endo H or PNGase F, no cleavage is observed for the substrate PA83
malfunction
Sema3B acts as a tumor suppressor in lung cancer and inhibits the formation of endothelial cells tubes in an in vitro angiogenesis. This function is abrogated upon mutation at the furin cleavage site. The C-terminal arginine of the putative furin cleavage site at the basic domain of Sema3C protein is critical for its functions in angiogenesis process
malfunction
the inhibition of furin in human Jurkat T cell lines also results in a decrease in interleukin-2 production, whereas the overexpression of wild-type furin is associated with elevated interleukin-2 levels
malfunction
the PLC motif in the cytosolic tail of proprotein convertase 7 (PC7) is dispensable for endosomal activity, but it is specifically required for trans-Golgi network (TGN) recycling and to rescue proactivin-A cleavage in furin-depleted B16-F1 melanoma cells. PC7 complements furin in cleaving Notch1 independently of PLC-mediated TGN access
metabolism
cellular furin content might be a potential factor determining the susceptibility of cultured human and animal cells to coronavirus infectious bronchitis virus infection
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
metabolism
furin promotes the activation of T cell receptor-induced transcription factors
physiological function
-
furin activation of the C-terminus of Sema3F produces a species that potently inhibits the binding of VEGF to neuropilin, the C-terminal neuropilin binding region of human Sema3F comprises residues 605-785. Furin processing of semaphorin 3F determines its anti-angiogenic activity by regulating direct binding and competition for neuropilin, mechanism, overview
physiological function
-
furin and related proprotein convertases cleave the multibasic motifs R-X-R/K/X-R in the precursor proteins and, as a result, transform the latent proproteins into biologically active proteins and peptides
physiological function
-
furin cleavage of CD109 is necessary for its biological activity, CD109 negatively regulates transforming growth factor-beta signaling in keratinocytes by directly modulating receptor activity. Processing of CD109 into 180 kDa and 25kDa proteins by furin, followed by complex formation with the type I TGF-beta receptor is required for the regulation of TGF-beta signaling in cancer cells and keratinocytes
physiological function
-
furin is involved in many physiological and pathological processes, it plays a role in human trophoblast invasion and migration
physiological function
-
furin is responsible for the shedding of the endogenous (pro)renin receptor, (P)RR, it generates the soluble form of (P)RR, in cultured cells
physiological function
-
the bioluminescence emission in the presence of firefly luciferase is furin-dependent and specific, furin activates the luciferase activity 7fold
physiological function
-
furin is involved in processing of bone morphogenetic protein BMP10. Processing occurs mostly intracellularly, but also at the cell surface
physiological function
-
hypoxia triggers relocalization of furin from the trans-Golgi network to endosomomal compartments and the cell surface in cancer cells. Exposing these cells back to normoxic conditions reverses furin redistribution, suggesting that the tumor microenvironment modulates furin trafficking in a highly regulated manner. Both Rab4GTPase-dependent recycling and interaction of furin with the cytoskeletal anchoring protein, filami A, are essential for the cell surface relocalization of furin. Interference with the association of furin with filamin A, prevents cell surface relocalization of furin and abolishes the ability of cancer cells to migrate in response to hypoxia
physiological function
furin cleavage of the Moloney murine leukemia virus Env precursor reorganizes the spike structure, overview
physiological function
furin is involved in the secretory pathway. It is the major proprotein convertase required for KISS1-to-kisspeptin processing. KISS1 is a broadly functional secreted proprotein that is then processed into small peptides, termed kisspeptins
physiological function
furin is the major processing protease of the secretory pathway. GPR107 localizes to the trans-Golgi network and is essential for retrograde transport. It is cleaved by the endoprotease furin
physiological function
furin mediates maturation of bone morphogenetic protein-4
physiological function
regulation of HIF-1 alpha, a major transcription factor involved in tumorigenesis by sensing intratumoral hypoxia, by the proprotein convertases furin and PC7 in human squamous carcinoma cells, overview. Furin is one of the numerous target genes regulated by HIF-1alpha transactivation and its distribution into endosomal compartments and onto the cell surface can be triggered by hypoxia via HIF-1alpha, overview
physiological function
the furin expression level is directly proportional to the efficiency of hemagglutinin cleavage, with implications for viral spread in the host, activation mechanism of avian influenza virus H9N2 by furin, overview
physiological function
the multinucleated syncytial trophoblast, which forms the outermost layer of the placenta and serves multiple functions, is differentiated from and maintained by cytotrophoblast cell fusion. Cytotrophoblast cell fusion and syncytialization are accompanied by furin expression. Processing of type 1 IGF receptor by furin is an essential mechanism for syncytialization. Furin function is required for the development of syncytiotrophoblast structure in the labyrinth layer, as well as for normal embryonic development
physiological function
activation of viral glycoproteins or bacterial toxins, furin and other PCs contribute to the propagation of certain pathogenic viruses and to the toxicity of some bacteria
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
furin is a calcium-dependent serine endoprotease that processes a wide variety of proproteins involved in cell function and homeostasis
physiological function
furin is a ubiquitous proprotein convertase that is involved in the processing (activation) of a wide variety of precursor proteins, including blood coagulation factors, cell surface receptors, hormones and growth factors, viral envelope glycoproteins, etc. and plays a critical regulatory role in a wide variety of cellular events
physiological function
proprotein convertase furin is a highly specific serine protease modifying and thereby activating proteins in the secretory pathway by proteolytic cleavage. Its substrates are involved in many diseases, including cancer and infections caused by bacteria and viruses
physiological function
proprotein convertase substilisin/kexin-type (PCSK) enzymes regulate proprotein maturation by catalyzing the proteolytic cleavage of their substrates. The prototype PCSK furin is induced upon T cell receptor (TCR) activation, and its expression in T cells is critical for the maintenance of peripheral immune tolerance. Proprotein convertase furin regulates T cell receptor-induced transactivation. TGF-beta1 and NOTCH1 are synthesized initially as inactive precursors and are proteolytically activated during T cell activation. In Jurkat cells, furin is dispensable for immediate T cell receptor (TCR) signaling steps, such as ERK, ZAP70, or LAT phosphorylation. Furin regulates the expression of interleukin-2 in human Jurkat T cell lines, specific TGF-beta1-independent role for furin in interleukin-2 regulation. Furin activates specifically and nonredundantly the anti-inflammatory cytokine pro-TGF-beta1 and thus, directly modulates the activity of CD4+ and CD8+ T cells. Importantly, Furin regulates its own activity by autocleavage, and its mRNA and protein levels are modulated dynamically during alterations in T cell physiology. Furin does not affect TCR-induced immediate phosphorylation events in Jurkat T cells
physiological function
proprotein convertases (PCs) are highly specific proteases required for the proteolytic modification of many secreted proteins. Calcium-dependent activity regulation of furin
physiological function
transforming growth factor beta (TGF-beta) is a signalling molecule that plays a key role in developmental and immunological processes in mammals. Pro-TGF-beta forms homodimers and is further processed in the trans-Golgi by a furin protease. Proteolytic cleavage by furin separates mature TGF-beta from latency-associated peptide (LAP). This dimeric complex is called the small latency complex (SLC) and keeps mature TGF-beta in an inactive form. Furin requires multiple processing steps and correct localization within the secretory pathway to become active
additional information
enzyme modeling by molecular dynamics calculations. Furin shows a complex activation mechanism and exists in at least four defined states: (i) the off state, incompatible with substrate binding as seen in the unliganded enzyme; (ii) the active on state seen in inhibitor-bound furin; and the respective (iii) calcium-free and (iv) calcium-bound forms. The transition from the off to the on state is triggered by ligand binding at subsites S1 to S4 and appears to underlie the preferential recognition of the four-residue sequence motif of furin. Ligation by calcium at the PC-specific binding site II influences the active-site geometry and determines the rotamer state of the oxyanion hole-forming Asn295, and adds a second level of the activity modulation of furin. Analysis of substrate induced structural rearrangements of furin, the spatial restrictions at and around the catalytic serine residue 368 of furin are structurally reminiscent of typical trypsin-like proteases, overview. Hotspots of conformational changes include the catalytic residues His194, Ser368, Asn295 of the oxyanion hole, the sodium binding site (Thr309 and Ser316), and residues in direct contact with the inhibitor peptide (e.g. the region Ser253-Pro256, the alignment template). Mapping of the Calpha displacement to the surface of the structure induced by inhibitor binding reveals a concerted local rearrangement at the substrate-binding cleft
additional information
X-ray structures of the proprotein convertase furin bound with substrate analogue inhibitors reveal substrate specificity determinants beyond the S4 pocket, overview. Substrate specificity is mediated at the P4-P6 binding sites of furin
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). FURIN_HUMAN
794
1
86678
Swiss-Prot
Secretory Pathway (Reliability: 1)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
homodimer
2 * 53446, recombinant prodomain-processed, nonglycosylated aa108-574-TEV-FLAG-His6 N387D/N440D mutant, mass spectrometry
additional information
-
secondary structure of furin prodomain protein, overview
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
glycoprotein
proteolytic modification
after autocleavage, proprotein convertases (PCs) exit the endoplasmatic reticulum. They remain bound to their inhibitory cleaved prosegments in latent form until arrival at the cell surface or, in the case of furin, in acidic endosomes, probably to avoid precocious activation or degradation of their substrates. Activated furin can then recycle from endosomes to the trans-Golgi network by binding to specific adaptors in the cytosol
glycoprotein
N-glycosylation is necessary for the proper folding and catalytic activity of plant produced or commercial human furin (NEB). Plant-produced human furin treated with PNGase F and Endo H does not exhibit cleavage activity. Similarly, when commercial human furin (NEB) is treated with commercial Endo H or PNGase F, no cleavage is observed for the substrate PA83
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
purified enzyme furin in complexes with inhibitors N2-phenylacetyl-L-Lys-L-Lys-L-Arg-aldehyde, N2-[(3,4-dichlorophenyl)acetyl]-L-lysyl-N-[(1S)-1-(1-carbamimidoylpiperidin-4-yl)-2-oxoethyl]-L-lysinamide, N2-[(3,4-dichlorophenyl)acetyl]-L-lysyl-N-[(1S)-1-(1-carbamimidoylpiperidin-4-yl)-2-oxoethyl]-L-lysinamide, N2-(1,3-thiazol-2-yl)-L-arginyl-N-[(1S)-2-amino-2-oxo-1-(4-[[4-(trifluoromethyl)benzyl]oxy]phenyl)ethyl]-L-lysinamide, diphenyl (1-[[(benzyloxy)carbonyl]amino]-3-carbamimidamidopropyl)phosphonate, diphenyl (1-[[(benzyloxy)carbonyl]amino]-4-carbamimidamidobutyl)phosphonate, and diphenyl [2-(4-aminophenyl)-1-[[(benzyloxy)carbonyl]amino]ethyl]phosphonate, vapor diffusion method, 9.0 mg/ml glycosylated human furin in 10 mm HEPES, pH 7.5, 100 mm NaCl, and 2 mm CaCl2 is mixed with an equal volume of crystallization solution containing 100 mm MES, 200 mm K/NaH2PO4, pH 5.5-6.0, and 2m NaCl, and equilibrated against reservoir solution with 3.0-3.6m NaCl, at 20°C, crystals are soaked for 16 h in soaking solution containing 3.13 M NaCl, 100 mM Mes/NaOH, pH 5.5, 200 mM NaH2PO4, 1 mM CaCl2, and 20% DMSO supplemented with inhibitor N2-phenylacetyl-L-Lys-L-Lys-L-Arg-aldehyde (5 mM), N2-[(3,4-dichlorophenyl)acetyl]-L-lysyl-N-[(1S)-1-(1-carbamimidoylpiperidin-4-yl)-2-oxoethyl]-L-lysinamide (5 mM), N2-(4-[(Z)-[3-(cyclohexylmethyl)-2,4-dioxo-1,3-thiazolidin-5-ylidene]methyl]benzoyl)-L-lysyl-N-[(1S)-2-amino-2-oxo-1-phenylethyl]-L-lysinamide (5 mM), N2-(1,3-thiazol-2-yl)-L-arginyl-N-[(1S)-2-amino-2-oxo-1-(4-[[4-(trifluoromethyl)benzyl]oxy]phenyl)ethyl]-L-lysinamide (5 mM), diphenyl (1-[[(benzyloxy)carbonyl]amino]-3-carbamimidamidopropyl)phosphonate (5 mM), diphenyl (1-[[(benzyloxy)carbonyl]amino]-4-carbamimidamidobutyl)phosphonate (1 mM), or diphenyl [2-(4-aminophenyl)-1-[[(benzyloxy)carbonyl]amino]ethyl]phosphonate (1 mM), X-ray diffraction structure determination and analysis
purified furin in complex with a non-substrate-like small molecule inhibitor N,N'-[[(1S,3R,4R,6S)-4-carbamimidamido-6-(4-carbamimidamidoanilino)cyclohexane-1,3-diyl]bis(oxy-4,1-phenylene)]diguanidine, hexagonal crystals of unliganded furin are soaked in a 5 mM solution of inhibitor in 100 mM MES, pH 5.5, 200 mM K/NaH2PO4, 1 mM CaCl2, 10% DMSO, and 3.4 mM NaCl for 16 h, X-ray diffraction structure determination and analysis at 1.9 A resolution
purified recombinant enzyme in complex with inhibitors m-guanidinomethyl-phenylacetyl-Arg-Val-Arg-(amidomethyl)-benzamidine or phenylacetyl-Arg-Val-Arg-(amidomethyl)-benzamidine, mixing of 7.5 mg/ml enzyme with 0.290 mM m-guanidinomethyl-phenylacetyl-Arg-Val-Arg-(amidomethyl)-benzamidine and 3 mM phenylacetyl-Arg-Val-Arg-(amidomethyl)-benzamidine, respectively, and 50 mM Tris, pH 8.5, 2.8 M sodium formate and 0.015 mM Cymal-7, at 30°C, displacement of the highly potent inhibitor m-guanidinomethyl-phenylacetyl-Arg-Val-Arg-(amidomethyl)-benzamidine by competitive soaking with excessive amounts of the less potent phenylacetyl-Arg-Val-Arg-(amidomethyl)-benzamidine, X-ray diffraction structure determination and analysis at 2.7 A resolution
purified recombinant furin mutant N387D/N440D in nonglycosylated apo-form, vapor diffusion method, 400 nl of 6 mg/ml of apo-furin (aa108-574-TEV-FLAG-His6 N387D/N440D) in 10 mM HEPES, pH 7.5, 150 mM NaCl, and 5 mM CaCl2, is mixed with 400 nl of crystallization solution containing 11-13% PEG 8000, 0.11-0.16 M potassium dihydrogen phosphate, and 0.1 M HEPES, pH 7.5, at 4°C, X-ray diffraction structure determination and analysis at 1.89 A resolution. The nonglycosylated furin protein reliably forms extremely durable apo crystals that diffract to high resolution, crystals are stable at 4°C for over one year. Digestion with TEV protease for the removal of the His6 and FLAG tags is not necessary for crystallization
purified recombinant His-tagged enzyme in complexes with three peptide-derived inhibitors, vapor diffusion method, mixing of 9 mg/ml protein in 10 mM HEPES, pH 7.5, 100 mM NaCl, and 2 mM CaCl2, with an equal volume of crystallization solution containing 100 mM MES, 200 mM K/NaH2PO4, pH 5.5-6.0, 3-4 M NaCl, and 3% dimethyl sulfoxide, and equilibration against reservoir solution containing 3-4 M NaCl, 20°C, crystals are soaked for about 16 h in a soaking solution conatining 3.16 M NaCl, 100 mM MES/NaOH, pH 5.5, 200 mM Na/KH2PO4, and 1 mM CaCl2 and supplemented with 2 mM Arg-Arg-Arg-Val-Arg-4-aminomethyl-benzamidine, or 1 mM phenylacetyl-Cit-Val-Arg-4-aminomethyl-benzamidine, or 1 mM 4-aminomethyl-phenylacetyl-Arg-Tle-Arg-4-aminomethyl-benzamidine, X-ray diffraction structure determination and analysis at 1.9-2.0 A resolution
purified unliganded furin in different functional states, different Ca2+- and inhibitor (3-guanidinomethyl-phenylacetyl-Arg-Val-Arg-(4-amidomethyl)-benzamidine)-bound forms of the enzyme, crystals of human furin are grown in sitting drops mixing equal volumes of 9 mg/ml protein solution and crystallization solution containing 100 mM MES, 200 mM K/NaH2PO4, pH 5.5-6.0, 3-4 M NaCl, and 3% v/v DMSO, the reservoir contains 3-4 M NaCl, for inhibitor binding studies the crystals are soaked with inhibitor and for calcium-studies the crystals are soaked with EDTA and Ca2+, X-ray diffraction structure determination and analysis at 1.8-2.0 A resolution
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D153N
-
is catalytically inert, is efficiently synthesized but inefficiently processed and secreted and therefore is difficult to be purified. Is incapable of self-activation, is less active than the wild-type
D4K
-
is readily isolated from the medium using metal-chelating chromatography, is less active than the wild-type
G
-
is readily isolated from the medium using metal-chelating chromatography, is less active than the wild-type
G5
-
is readily isolated from the medium using metal-chelating chromatography, is less active than the wild-type
G6
-
is readily isolated from the medium using metal-chelating chromatography, is less active than the wild-type
H6
-
is readily isolated from the medium using metal-chelating chromatography, is less active than the wild-type
H66L
-
profurin mutant, shows no measurable effect on propeptide excision relative to the control (65% mature furin). No effect on the pH-triggered activation and propeptide release or on the trypsin-mediated unmasking of furin
H69K
-
profurin mutant, 80% reduced efficiency of propeptide excision, fails to be activated by acidic pH or trypsinolysis
H69L
-
profurin mutant, 70% reduced efficiency of propeptide excision. Completely blocked ability of acid pH to trigger furin activation and propeptide cleavage but shows no effect on the trypsin-mediated activation step. Propeptide fails to dissociate from mature furin
K117P
-
mutation does not affect the efficiency of autocatalytic processing and the resulting secretory mutants are capable of prodomain processing at the primary cleavage site Arg-Thr-Lys-Arg107-Asp108. Is readily isolated from the medium using metal-chelating chromatography, is less active than the wild-type
K74G/R75G
-
secondary cleavage sites are inactivated, is incapable of self-activation
R1584A/R1585A
-
mutations efficiently protect the C-propeptide cleavage from furin activity. In absence of furin activity, bone morphogenetic protein-1 is capable of processing the C-propeptide even though less efficiently than furin
R75A
-
profurin mutant, substitution at the P1 position of the internal cleavage site, which blocks profurin activation but not propeptide excision or endoplasmic reticulum export of the furin-propeptide complex. No effect on the folding of the catalytic domain but blocked sensitivity of the furin-propeptide complex to acid pH
R89G
-
efficiency of self-activation of the mutant in which the tertiary cleavage site (Arg-Leu-Gln-Arg89Q-Glu90) is inactivated, is significantly reduced compared to that of wild-type furin
additional information
additional information
-
FD11 cell line, deficient in furin protease, processing of furin-site-containing glycoproteins is abrogated
additional information
-
furin cleavage-site mutant, neither trifluoperazine-induced nor basal shedding causes P-stalk accumulation
additional information
-
point mutations of sites A, B and C of furin P1A promoter. Mutations of site A and more importantly site B decreases Sox9-induced promoter activity, while mutations of both A and B sites result in only slight but nonsignificant additional inhibition. Mutation of site C does not reduce Sox9 activity
additional information
-
construction of an immunoproapoptotic molecule with antitumor activity: Her2-antigen e23sFv-TD-tBID with a 10-amino acid residue furin cleavage sequence. Purified e23sFv-TD-tBID protein recognized breast cancer cells from patients and preserved the ability to kill HER2-positive tumor cells after incubation in human serum
additional information
-
furin-deficient LoVo cells are uncapable to process pro-B-type natriuretic peptide, coexpression of human wild-type furin compensates and results in effective pro-B-type natriuretic peptide cleavage. Suppression of furin in HEK-293 cells by siRNA leads to the same result, overview
additional information
-
knockdown of furin expression by siRNA significantly inhibits invasion and migration of HTR8/SVneo cells, with corresponding decrease of matrix metalloproteinase-9, MMP-9, activities. In contrast, overexpression of furin markedly increases cell invasion and migration, accompanied by significant increase of MMP-9 activities. Furthermore, furin siRNA significantly increases the levels of both tissue inhibitors of MMPs, TIMP-1 and -2, overview. Proliferation of HTR8/SVneo cells is inhibited by furin siRNA
additional information
enhancement of productive IBV infection by knockin of furin in A-549 cells
additional information
-
enhancement of productive IBV infection by knockin of furin in A-549 cells
additional information
furin siRNA efficiently inhibits furin expression, expression of enzyme-specific siRNA in choriocarcinoma cells inhibits cell fusion
additional information
-
furin siRNA efficiently inhibits furin expression, expression of enzyme-specific siRNA in choriocarcinoma cells inhibits cell fusion
additional information
knockdown of the enzyme expression in C8161.9, MelJuSo, and HeLa cells by shRNA
additional information
engineering of the human furin gene for expression in plants, the production of a functional active recombinant truncated human furin in Nicotiana benthamiana plants. The signal peptide (amino acids 1-25) is removed from the furin sequence, and Nicotiana tabacum PR-1a signal peptide (MGFVLFSQLPSFLLVSTLLLFLVISHSCRA) is added to the N-terminus. The KDEL sequence (the endoplasmic reticulum retention signal) and the His6 tag (the affinity purification tag) are added to the C-terminus. A truncated form of furin (amino acids 26-595) is expressed with a PR-1a signal peptide at N-terminus and His6-KDEL at C-terminus
additional information
-
engineering of the human furin gene for expression in plants, the production of a functional active recombinant truncated human furin in Nicotiana benthamiana plants. The signal peptide (amino acids 1-25) is removed from the furin sequence, and Nicotiana tabacum PR-1a signal peptide (MGFVLFSQLPSFLLVSTLLLFLVISHSCRA) is added to the N-terminus. The KDEL sequence (the endoplasmic reticulum retention signal) and the His6 tag (the affinity purification tag) are added to the C-terminus. A truncated form of furin (amino acids 26-595) is expressed with a PR-1a signal peptide at N-terminus and His6-KDEL at C-terminus
additional information
expression and purification of nonglycosylated human furin using the BacMam technology and site-directed mutagenesis of the glycosylation sites. Recombinant nonglycosylated furin produced using this system retains full proteolytic activity indistinguishable from that of the glycosylated protein
additional information
-
expression and purification of nonglycosylated human furin using the BacMam technology and site-directed mutagenesis of the glycosylation sites. Recombinant nonglycosylated furin produced using this system retains full proteolytic activity indistinguishable from that of the glycosylated protein
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
a positively-charged Lys residue replacing His43 in the 16-49 fragment imparts stability to the super-secondary structure of the furin prodomain at both acidic and neutral pH
678743
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-70°C, 26% loss of activity of furin mutant hFUR713t, 21% loss of activity of soluble furin after 3 weeks, optimal conditions of conservation are at 50% glycerol
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant enzyme 300fold from HEK-293 cells by metal affinity chromatography, inhibitor based affinity chromatography, and gel filtration
recombinant FLAG/His6-tagged furin ectodomain from CHO cells or Spodoptera frugiperda Sf9 cells by nickel affinity chromatography, ultrafiltration, and gel filtration, to homogeneity
recombinant glycosylated His-tagged furin from HEK-293S cells by nickel affinity and inhibitor affinity chromatography, followed by gel filtration
recombinant His6-tagged enzyme from Nicotiana benthamiana leaves by nickel affinity chromatography, co-purification of the coexpressed proteins
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
CHO cell lines stably expressing Tac-furin chimeric protein (extracellular/transmembrane domain of the interleukin-2 receptor alpha-chain (Tac) and the cytoplasmic domain of furin)
-
expression in Spodoptera frugiperda Sf9 cells using the baculovirus transfection system
-
full-length epitope-tagged furin constructs or mutants expressed in A7 cells or BSC-40 cells
-
full-length furin prodomain overexpressed in Escherichia coli strain BL21 (DE3)
-
functional recombinant expression of His6-tagged human furin lacking its signal peptide in Nicotiana benthamiana plants. Plant-produced human furin is highly active both in vivo and in vitro and specifically cleaves the tested target proteins, factor IX (FIX) and protective antigen (PA83). Plants lack some of the important posttranslational modifications, including furin processing, but both, enzymatic deglycosylation and proteolytic processing of target proteins, can be achieved in vivo by coexpression of deglycosylating and furin cleavage enzymes in a single cell to produce deglycosylated and furin processed target proteins. Recombinant coexpression of engineered enzyme and substrate using the Agrobacterium tumefaciens strain AGL1 transfection method, expression in leaves. Coexpression of human furin with PA83 of Bacillus anthracis and deglycosylation enzymes Endo H or PNGase F in Nicotiana benthamiana. Deglycosylation efficiency of plant produced Endo H is greater than that of plant produced PNGase F. When full length furin is coexpressed with the PA83 protein in Nicotiana benthamina plants, there is little or no cleavage of PA83. Plant-produced human furin treated with PNGase F and Endo H does not exhibit cleavage activity
furin and pro-von Willebrand factor co-expressed in BHK21 cells. cDNA of furin subcloned into the pcDNA3/VSV expression vector between the EcoRI and XbaI sites. HeLa cells transiently transfected with pCMV-furin, pCDNA3-furin-VSV or pSVHVWF1.1
-
furin expression in CHO cells, COS-7 cells, furin-deficient FD11 cells, and furin-overexpressing cells
-
furin mutant and wild-type constructs transiently transfected into HEK-293 cells
-
furin precursor cDNA transferred to pcDNA3.1-. Co-expression of furin-site-containing spike glycoprotein with furin cDNA in FD11 cells or CHO cells
-
gene FURIN, recombinant expression of glycosylated aa108-574-TEV-FLAG-His6-furin and nonglycosylated aa108-574-TEV-FLAG-His6 N387D/N440D furin mutant (ectodomains with a TEV cleavage site) from plasmid termed furin aa1-574 in CHO cells and in Spodoptera frugiperda Sf9 cells via BacMam virus transfection, typically producing a highly glycosylated, heterogeneous protein
HEK-293 cells transiently cotransfected with cDNA encoding V5-tagged wild-type PCSK9 and furin
-
HepG2 cells transiently transfected with furin luciferase reporter constructs pGL2-P1, pGL2-P1A and pGL2-P1B
-
LoVo cells stably expressing furin. Furin cleavage-site mutant (LNTR) transfected into COS-7 cells
-
MDA-MB-231 breast cancer cells stably transfected with a vector containing furin prosegment
-
mutants expressed in Sf9 cells. Mutant constructs transiently transfected in LoVo cells
-
recombinant hfurin from the sectreted culture media of somatomammotroph GH4C1 cells following infection with respective cDNA encoding vaccinia viruses
-
the distribution of proprotein convertase activities at the tissue level are monitored by introduction of biosensor CLIP (cell-linked indicator of proteolysis). CLIP v.3 is suitable for ratiometric imaging without interference by FRET, whereas CLIP v.4 can be used as a FRET-based biosensor to quantify PC activities in specific intracellular vesicles, enzyme and CLIP expression in HEK-293T cells. Fusion to the cytosolic tail of PC7 directs CLIP v.4 to compartments that harbor furin activity, but not full-length proprotein convertase 7 (PC7)
transient co-expression of human furin and human TGF-beta1 in the presence of the latency-associated peptide (LAP) in Nicotiana benthamiana leaves processing of the latent complex by a furin-like protease does not occur in planta. The use of a chitinase signal peptide enhances the expression and secretion of LAP-TGF-beta1, and co-expression of human furin enables the proteolytic processing of latent TGF-beta1 into a biologically active protein. Mature TGF-beta1 can be expressed without LAP, but results in necrosis (due to improper signal peptide cleavage). The Fc portion of immunoglobulin alpha 1 (Fcalpha), a natural dimer, is used as a fusion partner allowing dimerization of TGF-beta1. Furin requires multiple processing steps and correct localization within the secretory pathway to become active. Biological activity of Fcalpha-TGF-beta1 in crude plant extracts is assessed in a cell-based assay using mink lung epithelial cells carrying a TGF-beta-responsive luciferase reporter gene that is activated upon binding to the TGF-beta receptor. Proteolytic processing of LAP-TGF-beta1 in plants requires co-expression of furin
transient expression of homogeneously glycosylated His-tagged furin in HEK-293S cells
transient expression of the enzyme in HEK-293 cells, co-expression of inhibitor mutant alpha1-antitrypsin M352R
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
cytokine transforming growth factor TGF-beta stimulates furin mRNA expression in HepG2 cells
-
furin expression is detected in all rhabdomyosarcoma cell lines tested at high levels, while myoblasts and fibroblasts show low levels of furin transcripts
-
furin expression is upregulated by the Th1 hallmark cytokine interleukin-12. T cell activation via T cell receptor induces furin expression
in heaptitis C virus-infected cells, furin expression is upregulated about 3fold
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
analysis
-
sensitive and specific assay for furin activity using an antibody capture step to immobilise furin from whole cell lysates. The assay has a minimum detection limit of 0.006 nM and is sensitive enough to determine the furin activity of many of the cell lines tested
drug development
industry
-
furin may be applied in mass production of a potent antimicrobial peptide histonin as a natural form, whereby overcoming its inherent toxicity and the low yield of production
medicine
pharmacology
-
development of an immunoproapoptotic molecule with antitumor activity: Her2-antigen e23sFv-TD-tBID with a 10-amino acid residue furin cleavage sequence. e23sFv-TD-tBID shows therapeutic value to humans by its cytotoxic effects on primary patient-derived breast tumor cells but not on endothelial cells. It also shows in vivo antitumor activity in female BALB/c athymic mice, overview
additional information
drug development
-
extensive clinical use, high bioavailability and relatively low toxicity of dicoumarols suggests that the dicoumarol structure will be a good starting point for development of drug-like inhibitors of furin and other proprotein convertases that can act both intracellularly and at the cell surface
drug development
-
furin is considered a major target for intervention of cancer, tumorgenesis, viral and bacterial pathogenesis
drug development
furin inhibitors are promising therapeutics for the treatment of cancer and numerous infections caused by bacteria and viruses, including the highly lethal Bacillus anthracis or the pandemic influenza virus
drug development
the activation of viral glycoproteins by the host protease furin is an essential step in the replipation of numerous pathogenic viruses. Thus, effective inhibitors of furin can serve as broad-spectrum antiviral drugs, rational design of various types of cyclic inhibitors
drug development
the deglycosylated active recombinant enzyme can be used for structure-guided drug discovery
medicine
-
potential therapeutic value of furin inhibitors, alpha1-PDX is able to block in vivo maturation of pro-gB, the cytomegalovirus envelope glycoprotein
medicine
-
copper and zinc complexes of terpyridine derivatives are stable under various conditions and are not expected to pose delivery problems, qualities vital for the development of a wide-scope anti-bioterror agent for civil and military uses
medicine
-
furin is predominantely expressed in tumors from patients surviving less than five years. Furin may constitute a marker for ovarian tumor progression and may contribute to predict the outcome of the disease
medicine
-
inhibiting furin-like proprotein convertases protects the host from the distinct furin-dependent infections and lay a foundation for novel, host cell-focused therapies against acute diseases
medicine
-
interleukin 12 induction of furin plays a role in interferon gamma protein regulation and control of T helper 1 cell differentiation
medicine
-
introduction of a prototypic furin recognition motif at R667 of the SARS coronavirus spike glycoprotein allows for efficient cleavage of the mutant glycoprotein and increases cell-cell fusion activity but shows no effect on virion infectivity
medicine
-
massive vaccination of host poultry results in an influenza variant Fujian-like H5N1 strain with two mutations at the furin-processing site of hemagglutinin, which is resistant to immunization
medicine
-
pivotal role for furin, MT1-MMP, and MMP2 in tumor necrosis factor alpha-induced sphingolipid signaling. This system may be a possible target to inhibit smooth muscle cell proliferation in vascular diseases
medicine
-
specific and opposing roles of furin and PACE4 in the regulation of MMP-9/TIMP-1 mediated cell motility and invasion. Furin prosegment inhibits cell migration and invasion as well as MMP-9 activity without affecting TIMP-1. It prevents adequate repair of scratch wounds
medicine
-
furin expression is detected in all rhabdomyosarcoma cell lines tested at high levels, while myoblasts and fibroblasts show low levels of furin transcripts. Peptide CMGTINTRTKKC has strong affinity for rhabdomyosarcoma cells in vitro and in vivo, by binding to furin
medicine
-
hypoxia triggers relocalization of furin from the trans-Golgi network to endosomomal compartments and the cell surface in cancer cells. Exposing these cells back to normoxic conditions reverses furin redistribution, suggesting that the tumor microenvironment modulates furin trafficking in a highly regulated manner. Both Rab4GTPase-dependent recycling and interaction of furin with the cytoskeletal anchoring protein, filamin-A, are essential for the cell surface relocalization of furin. Interference with the association of furin with filamin A, prevents cell surface relocalization of furin and abolishes the ability of cancer cells to migrate in response to hypoxia
medicine
-
increased replication of heaptitis C virus RNA in hepatitis C-infected cells is significantly reduced in the presence of transforming growth factor TGF-beta1 siRNA, thrombospondin-1 siRNA or furin siRNA
additional information
compartment-specific biosensors can be used to gain insight into the regulation of proprotein convertase trafficking and to map the tropism of PC-specific inhibitors
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Denault, J.B.; Leduc, R.
Furin/PACE/SPC1: a convertase involved in exocytic and endocytic processing of precursor proteins
FEBS Lett.
379
113-116
1996
Homo sapiens
Creemers, J.W.M.; Vey, M.; Schfer, W.; Ayoubi, T.A.Y.; Roebroek, A.J.M.; Klenk, H.D.; Garten, W.; van de Ven, W.J.M.
Endoproteolytic cleavage of its propeptide is a prerequisite for efficient transport of furin out of the endoplasmic reticulum
J. Biol. Chem.
270
2695-2702
1995
Bos taurus, Homo sapiens
Molloy, S.S.; Bresnahan, P.A.; Leppla, S.H.; Klimpel, K.R.; Thomas, G.
Human furin is a calcium-dependent serine endoprotease that recognizes the sequence Arg-X-X-Arg and efficiently cleaves anthrax toxin protective antigen
J. Biol. Chem.
267
16396-16402
1992
Homo sapiens
Wuthrich, M.; Creemers, J.W.M.; van de Ven, W.J.M.; Sterchi, E.E.
Human lactase-phlorizin hydrolase is not processed by furin, PC1/PC3, PC2, PACE4 and PC5/PC6A of the family of subtilisin-like proprotein processing proteases
Biochim. Biophys. Acta
1311
199-203
1996
Homo sapiens
Jean, F.; Boudreault, A.; Basak, A.; Seidah, N.G.; Lazure, C.
Fluorescent peptidyl substrates as an aid in studying the substrate specificity of human prohormone convertase PC1 and human furin and designing a potent irreversible inhibitor
J. Biol. Chem.
270
19225-19231
1995
Homo sapiens
Milhiet, P.E.; Chevallier, S.; Corbeil, D.; Seidah, N.G.; Boileau, G.
Proteolytic processing of the alpha-subunit of rat endopeptidase-24.18 by furin
Biochem. J.
309
683-688
1995
Homo sapiens
Vidricaire, G.; Denault, J.B.; Leduc, R.
Characterization of a secreted form of human furin endoprotease
Biochem. Biophys. Res. Commun.
195
1011-1018
1993
Homo sapiens
Brakch, N.; Dettin, M.; Scarinci, C.; Seidah, N.G.; di Bello, C.
Structural investigation and kinetic characterization of potential cleavage sites of HIV GP160 by human furin and PC1
Biochem. Biophys. Res. Commun.
213
356-361
1995
Homo sapiens
Rehemtulla, A.; Kaufman, R.J.
Preferred sequence requirements for cleavage of pro-von Willebrand factor by propeptide-processing enzymes
Blood
79
2349-2355
1992
Homo sapiens, Mammalia, Mus musculus
Jean, F.; Basak, A.; DiMaio, J.; Seidah, N.G.; Lazure, C.
An internally quenched fluorogenic substrate of prohormone convertase 1 and furin leads to a potent prohormone convertase inhibitor
Biochem. J.
307
689-695
1995
Homo sapiens
Jean, F.; Basak, A.; Rondeau, N.; Benjannet, S.; Hendy, G.N.; Seidah, N.G.
Enzymic characterization of murine and human prohormone convertase-1 (mPC1 and hPC1) expressed in mammalian GH4C1 cells
Biochem. J.
292
891-900
1993
Homo sapiens, Mus musculus
Garten, W.; Hallenberger, S.; Ortmann, D.; Schaefer, W.; Vey, M.; Angliker, H.; Shaw, E.; Klenk, H.D.
Processing of viral glycoproteins by the subtilisin-like endoprotease furin and its inhibition by specific peptidylchloroalkylketones
Biochimie
76
217-225
1994
aves, Homo sapiens
Basak, A.; Lazure, C.
Synthetic peptides derived from the prosegments of proprotein convertase 1/3 and furin are potent inhibitors of both enzymes
Biochem. J.
373
231-239
2003
Homo sapiens
Komiyama, T.; Fuller, R.S.
Engineered eglin c variants inhibit yeast and human proprotein processing proteases, Kex2 and furin
Biochemistry
39
15156-15165
2000
Saccharomyces cerevisiae, Homo sapiens
Dahlen, J.R.; Jean, F.; Thomas, G.; Foster, D.C.; Kisiel, W.
Inhibition of soluble recombinant furin by human proteinase inhibitor 8
J. Biol. Chem.
273
1851-1854
1998
Homo sapiens
Krysan, D.J.; Rockwell, N.C.; Fuller, R.S.
Quantitative characterization of furin specificity. Energetics of substrate discrimination using an internally consistent set of hexapeptidyl methylcoumarinamides
J. Biol. Chem.
274
23229-23234
1999
Homo sapiens
Cameron, A.; Appel, J.; Houghten, R.A.; Lindberg, I.
Polyarginines are potent furin inhibitors
J. Biol. Chem.
275
36741-36749
2000
Homo sapiens, Mus musculus
Basak, A.; Koch, P.; Dupelle, M.; Fricker, L.D.; Devi, L.A.; Chretien, M.; Seidah, N.G.
Inhibitory specificity and potency of proSAAS-derived peptides toward proprotein convertase 1
J. Biol. Chem.
276
32720-32728
2001
Homo sapiens
Bowler, R.P.; Nicks, M.; Olsen, D.A.; Thogersen, I.B.; Valnickova, Z.; Hojrup, P.; Franzusoff, A.; Enghild, J.J.; Crapo, J.D.
Furin proteolytically processes the heparin-binding region of extracellular superoxide dismutase
J. Biol. Chem.
277
16505-16511
2002
Homo sapiens, Mus musculus, Rattus norvegicus
Opal, S.M.; Artenstein, A.W.; Cristofaro, P.A.; Jhung, J.W.; Palardy, J.E.; Parejo, N.A.; Lim, Y.P.
Inter-alpha-inhibitor proteins are endogenous furin inhibitors and provide protection against experimental anthrax intoxication
Infect. Immun.
73
5101-5105
2005
Homo sapiens
Wang, P.; Tortorella, M.; England, K.; Malfait, A.M.; Thomas, G.; Arner, E.C.; Pei, D.
Proprotein convertase furin interacts with and cleaves pro-ADAMTS4 (aggrecanase-1) in the trans-Golgi network
J. Biol. Chem.
279
15434-15440
2004
Homo sapiens
Podsiadlo, P.; Komiyama, T.; Fuller, R.S.; Blum, O.
Furin inhibition by compounds of copper and zinc
J. Biol. Chem.
279
36219-36227
2004
Homo sapiens
Kacprzak, M.M.; Peinado, J.R.; Than, M.E.; Appel, J.; Henrich, S.; Lipkind, G.; Houghten, R.A.; Bode, W.; Lindberg, I.
Inhibition of furin by polyarginine-containing peptides: nanomolar inhibition by nona-D-arginine
J. Biol. Chem.
279
36788-36794
2004
Homo sapiens
Koo, B.H.; Longpre, J.M.; Somerville, R.P.; Alexander, J.P.; Leduc, R.; Apte, S.S.
Cell-surface processing of pro-ADAMTS9 by furin
J. Biol. Chem.
281
12485-12494
2006
Homo sapiens
Anders, L.; Mertins, P.; Lammich, S.; Murgia, M.; Hartmann, D.; Saftig, P.; Haass, C.; Ullrich, A.
Furin-, ADAM 10-, and gamma-secretase-mediated cleavage of a receptor tyrosine phosphatase and regulation of beta-catenins transcriptional activity
Mol. Cell. Biol.
26
3917-3934
2006
Homo sapiens, Mus musculus
Remacle, A.G.; Rozanov, D.V.; Fugere, M.; Day, R.; Strongin, A.Y.
Furin regulates the intracellular activation and the uptake rate of cell surface-associated MT1-MMP
Oncogene
25
5648-5655
2006
Homo sapiens
Dufour, E.K.; Desilets, A.; Longpre, J.M.; Leduc, R.
Stability of mutant serpin/furin complexes: dependence on pH and regulation at the deacylation step
Protein Sci.
14
303-315
2005
Homo sapiens
Han, J.; Gu, J.; Chi, C.
Possible role of histone H1 in the regulation of furin-dependent proprotein processing
Acta Biochim. Biophys. Sin.
39
173-180
2007
Homo sapiens
Guimont, P.; Grondin, F.; Dubois, C.M.
Sox9-dependent transcriptional regulation of the proprotein convertase furin
Am. J. Physiol. Cell Physiol.
293
C172-C183
2007
Homo sapiens, Mus musculus
Kim, J.M.; Jang, S.A.; Yu, B.J.; Sung, B.H.; Cho, J.H.; Kim, S.C.
High-level expression of an antimicrobial peptide histonin as a natural form by multimerization and furin-mediated cleavage
Appl. Microbiol. Biotechnol.
78
123-130
2008
Homo sapiens
Lee, S.N.; Kacprzak, M.M.; Day, R.; Lindberg, I.
Processing and trafficking of a prohormone convertase 2 active site mutant
Biochem. Biophys. Res. Commun.
355
825-829
2007
Homo sapiens
Kurmanova, A.; Llorente, A.; Polesskaya, A.; Garred, O.; Olsnes, S.; Kozlov, J.; Sandvig, K.
Structural requirements for furin-induced cleavage and activation of Shiga toxin
Biochem. Biophys. Res. Commun.
357
144-149
2007
Homo sapiens, Mus musculus
Bonod-Bidaud, C.; Beraud, M.; Vaganay, E.; Delacoux, F.; Font, B.; Hulmes, D.J.; Ruggiero, F.
Enzymatic cleavage specificity of the proalpha1(V) chain processing analysed by site-directed mutagenesis
Biochem. J.
405
299-306
2007
Homo sapiens
Bhattacharjya, S.; Xu, P.; Wang, P.; Osborne, M.J.; Ni, F.
Conformational analyses of a partially-folded bioactive prodomain of human furin
Biopolymers
86
329-344
2007
Homo sapiens
Pesu, M.; Muul, L.; Kanno, Y.; OShea, J.J.
Proprotein convertase furin is preferentially expressed in T helper 1 cells and regulates interferon gamma
Blood
108
983-985
2006
Homo sapiens, Mus musculus
Lapierre, M.; Siegfried, G.; Scamuffa, N.; Bontemps, Y.; Calvo, F.; Seidah, N.G.; Khatib, A.M.
Opposing function of the proprotein convertases furin and PACE4 on breast cancer cells malignant phenotypes: role of tissue inhibitors of metalloproteinase-1
Cancer Res.
67
9030-9034
2007
Homo sapiens
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
Rabah, N.; Gauthier, D.; Dikeakos, J.D.; Reudelhuber, T.L.; Lazure, C.
The C-terminal region of the proprotein convertase 1/3 (PC1/3) exerts a bimodal regulation of the enzyme activity in vitro
FEBS J.
274
3482-3491
2007
Homo sapiens
Pasquato, A.; Dettin, M.; Basak, A.; Gambaretto, R.; Tonin, L.; Seidah, N.G.; Di Bello, C.
Heparin enhances the furin cleavage of HIV-1 gp160 peptides
FEBS Lett.
581
5807-5813
2007
Homo sapiens
Wanyiri, J.W.; OConnor, R.; Allison, G.; Kim, K.; Kane, A.; Qiu, J.; Plaut, A.G.; Ward, H.D.
Proteolytic processing of the Cryptosporidium glycoprotein gp40/15 by human furin and by a parasite-derived furin-like protease activity
Infect. Immun.
75
184-192
2007
Cryptosporidium parvum, Homo sapiens
Feliciangeli, S.F.; Thomas, L.; Scott, G.K.; Subbian, E.; Hung, C.H.; Molloy, S.S.; Jean, F.; Shinde, U.; Thomas, G.
Identification of a pH sensor in the furin propeptide that regulates enzyme activation
J. Biol. Chem.
281
16108-16116
2006
Homo sapiens
Benjannet, S.; Rhainds, D.; Hamelin, J.; Nassoury, N.; Seidah, N.G.
The proprotein convertase (PC) PCSK9 is inactivated by furin and/or PC5/6A: functional consequences of natural mutations and post-translational modifications
J. Biol. Chem.
281
30561-30572
2006
Homo sapiens
Shiryaev, S.A.; Remacle, A.G.; Ratnikov, B.I.; Nelson, N.A.; Savinov, A.Y.; Wei, G.; Bottini, M.; Rega, M.F.; Parent, A.; Desjardins, R.; Fugere, M.; Day, R.; Sabet, M.; Pellecchia, M.; Liddington, R.C.; Smith, J.W.; Mustelin, T.; Guiney, D.G.; Lebl, M.; Strongin, A.Y.
Targeting host cell furin proprotein convertases as a therapeutic strategy against bacterial toxins and viral pathogens
J. Biol. Chem.
282
20847-20853
2007
Homo sapiens, Mus musculus, Mus musculus C57BL/6
Bruns, J.B.; Carattino, M.D.; Sheng, S.; Maarouf, A.B.; Weisz, O.A.; Pilewski, J.M.; Hughey, R.P.; Kleyman, T.R.
Epithelial Na+ channels are fully activated by furin- and prostasin-dependent release of an inhibitory peptide from the gamma-subunit
J. Biol. Chem.
282
6153-6160
2007
Homo sapiens, Mus musculus
Pasquato, A.; Seidah, N.G.
The H5N1 influenza variant Fujian-like hemagglutinin selected following vaccination exhibits a compromised furin cleavage: Neurological consequences of highly pathogenic Fujian H5N1 strains
J. Mol. Neurosci.
35
339-343
2008
Homo sapiens
Tellier, E.; Negre-Salvayre, A.; Bocquet, B.; Itohara, S.; Hannun, Y.A.; Salvayre, R.; Auge, N.
Role for furin in tumor necrosis factor alpha-induced activation of the matrix metalloproteinase/sphingolipid mitogenic pathway
Mol. Cell. Biol.
27
2997-3007
2007
Homo sapiens
Portela-Gomes, G.M.; Grimelius, L.; Stridsberg, M.
Prohormone convertases 1/3, 2, furin and protein 7B2 (Secretogranin V) in endocrine cells of the human pancreas
Regul. Pept.
146
117-124
2008
Homo sapiens
Follis, K.E.; York, J.; Nunberg, J.H.
Furin cleavage of the SARS coronavirus spike glycoprotein enhances cell-cell fusion but does not affect virion entry
Virology
350
358-369
2006
Homo sapiens
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
Homo sapiens
Hook, V.; Funkelstein, L.; Toneff, T.; Mosier, C.; Hwang, S.R.
Human pituitary contains dual cathepsin L and prohormone convertase processing pathway components involved in converting POMC into the peptide hormones ACTH, alpha-MSH, and beta-endorphin
Endocrine
35
429-437
2009
Homo sapiens
Ikonomov, O.C.; Fligger, J.; Sbrissa, D.; Dondapati, R.; Mlak, K.; Deeb, R.; Shisheva, A.
Kinesin adapter JLP links PIKfyve to microtubule-based endosome-to-trans-Golgi network traffic of furin
J. Biol. Chem.
284
3750-3761
2009
Homo sapiens
Gagliardo, B.; Kubat, N.; Faye, A.; Jaouen, M.; Durel, B.; Deschemin, J.C.; Canonne-Hergaux, F.; Sari, M.A.; Vaulont, S.
Pro-hepcidin is unable to degrade the iron exporter ferroportin unless maturated by a furin-dependent process
J. Hepatol.
50
394-401
2009
Homo sapiens, Mus musculus
Ito, K.; Kim, K.H.; Lok, A.S.; Tong, S.
Characterization of genotype-specific carboxyl-terminal cleavage sites of hepatitis B virus e antigen precursor and identification of furin as the candidate enzyme
J. Virol.
83
3507-3517
2009
Gallus gallus, Homo sapiens
Coppola, J.M.; Bhojani, M.S.; Ross, B.D.; Rehemtulla, A.
A small-molecule furin inhibitor inhibits cancer cell motility and invasiveness
Neoplasia
10
363-370
2008
Cricetulus griseus, Homo sapiens
Huynh, T.T.; Chan, K.S.; Piva, T.J.
Effect of ultraviolet radiation on the expression of pp38MAPK and furin in human keratinocyte-derived cell lines
Photodermatol. Photoimmunol. Photomed.
25
20-29
2009
Homo sapiens
Gawlik, K.; Shiryaev, S.A.; Zhu, W.; Motamedchaboki, K.; Desjardins, R.; Day, R.; Remacle, A.G.; Stec, B.; Strongin, A.Y.
Autocatalytic activation of the furin zymogen requires removal of the emerging enzymes N-terminus from the active site
PLoS ONE
4
e5031
2009
Homo sapiens
Izidoro, M.A.; Gouvea, I.E.; Santos, J.A.; Assis, D.M.; Oliveira, V.; Judice, W.A.; Juliano, M.A.; Lindberg, I.; Juliano, L.
A study of human furin specificity using synthetic peptides derived from natural substrates, and effects of potassium ions
Arch. Biochem. Biophys.
487
105-114
2009
Homo sapiens
Parker, M.W.; Hellman, L.M.; Xu, P.; Fried, M.G.; Vander Kooi, C.W.
Furin processing of semaphorin 3F determines its anti-angiogenic activity by regulating direct binding and competition for neuropilin
Biochemistry
49
4068-4075
2010
Homo sapiens
Dragulescu-Andrasi, A.; Liang, G.; Rao, J.
In vivo bioluminescence imaging of furin activity in breast cancer cells using bioluminogenic substrates
Bioconjug. Chem.
20
1660-1666
2009
Homo sapiens, Mus musculus
Wang, F.; Ren, J.; Qiu, X.C.; Wang, L.F.; Zhu, Q.; Zhang, Y.Q.; Huan, Y.; Meng, Y.L.; Yao, L.B.; Chen, S.Y.; Xu, Y.M.; Yang, A.G.
Selective cytotoxicity to HER2-positive tumor cells by a recombinant e23sFv-TD-tBID protein containing a furin cleavage sequence
Clin. Cancer Res.
16
2284-2294
2010
Homo sapiens
Semenov, A.G.; Postnikov, A.B.; Tamm, N.N.; Seferian, K.R.; Karpova, N.S.; Bloshchitsyna, M.N.; Koshkina, E.V.; Krasnoselsky, M.I.; Serebryanaya, D.V.; Katrukha, A.G.
Processing of pro-brain natriuretic peptide is suppressed by O-glycosylation in the region close to the cleavage site
Clin. Chem.
55
489-498
2009
Homo sapiens
Basak, A.; Chen, A.; Scamuffa, N.; Mohottalage, D.; Basak, S.; Khatib, A.M.
Blockade of furin activity and furin-induced tumor cells malignant phenotypes by the chemically synthesized human furin prodomain
Curr. Med. Chem.
17
2214-2221
2010
Homo sapiens
Cousin, C.; Bracquart, D.; Contrepas, A.; Corvol, P.; Muller, L.; Nguyen, G.
Soluble form of the (pro)renin receptor generated by intracellular cleavage by furin is secreted in plasma
Hypertension
53
1077-1082
2009
Homo sapiens, Mus musculus, Rattus norvegicus
Remacle, A.G.; Gawlik, K.; Golubkov, V.S.; Cadwell, G.W.; Liddington, R.C.; Cieplak, P.; Millis, S.Z.; Desjardins, R.; Routhier, S.; Yuan, X.W.; Neugebauer, W.A.; Day, R.; Strongin, A.Y.
Selective and potent furin inhibitors protect cells from anthrax without significant toxicity
Int. J. Biochem. Cell Biol.
42
987-995
2010
Homo sapiens
Becker, G.L.; Sielaff, F.; Than, M.E.; Lindberg, I.; Routhier, S.; Day, R.; Lu, Y.; Garten, W.; Steinmetzer, T.
Potent inhibitors of furin and furin-like proprotein convertases containing decarboxylated P1 arginine mimetics
J. Med. Chem.
53
1067-1075
2010
Homo sapiens
Hagiwara, S.; Murakumo, Y.; Mii, S.; Shigetomi, T.; Yamamoto, N.; Furue, H.; Ueda, M.; Takahashi, M.
Processing of CD109 by furin and its role in the regulation of TGF-beta signaling
Oncogene
29
2181-2191
2010
Homo sapiens
Zhou, Z.; Shen, T.; Zhang, B.H.; Lv, X.Y.; Lin, H.Y.; Zhu, C.; Xue, L.Q.; Wang, H.
The proprotein convertase furin in human trophoblast: Possible role in promoting trophoblast cell migration and invasion
Placenta
30
929-938
2009
Homo sapiens
Basak, A.; Khatib, A.M.; Mohottalage, D.; Basak, S.; Kolajova, M.; Bag, S.S.; Basak, A.
A novel enediynyl peptide inhibitor of furin that blocks processing of proPDGF-A, B and proVEGF-C
PLoS ONE
4
e7700
2009
Homo sapiens
Izidoro, M.A.; Assis, D.M.; Oliveira, V.; Santos, J.A.; Juliano, M.A.; Lindberg, I.; Juliano, L.
Effects of magnesium ions on recombinant human furin: selective activation of hydrolytic activity upon substrates derived from virus envelope glycoprotein
Biol. Chem.
391
1105-1112
2010
Homo sapiens
Sielaff, F.; Than, M.E.; Bevec, D.; Lindberg, I.; Steinmetzer, T.
New furin inhibitors based on weakly basic amidinohydrazones
Bioorg. Med. Chem. Lett.
21
836-840
2011
Homo sapiens
Susan-Resiga, D.; Essalmani, R.; Hamelin, J.; Asselin, M.C.; Benjannet, S.; Chamberland, A.; Day, R.; Szumska, D.; Constam, D.; Bhattacharya, S.; Prat, A.; Seidah, N.G.
Furin is the major processing enzyme of the cardiac-specific growth factor bone morphogenetic protein 10
J. Biol. Chem.
286
22785-22794
2011
Homo sapiens
Arsenault, D.; Lucien, F.; Dubois, C.M.
Hypoxia enhances cancer cell invasion through relocalization of the proprotein convertase furin from the trans-golgi network to the cell surface
J. Cell. Physiol.
227
789-800
2012
Homo sapiens
Bourne, G.L.; Grainger, D.J.
Development and characterisation of an assay for furin activity
J. Immunol. Methods
364
101-108
2011
Homo sapiens
Hajdin, K.; DAlessandro, V.; Niggli, F.K.; Schaefer, B.W.; Bernasconi, M.
Furin targeted drug delivery for treatment of rhabdomyosarcoma in a mouse model
PLoS ONE
5
e10445
2010
Homo sapiens, Mus musculus
Presser, L.D.; Haskett, A.; Waris, G.
Hepatitis C virus-induced furin and thrombospondin-1 activate TGF-beta1: role of TGF-beta1 in HCV replication
Virology
412
284-296
2011
Homo sapiens
Dahms, S.O.; Hardes, K.; Becker, G.L.; Steinmetzer, T.; Brandstetter, H.; Than, M.E.
X-ray structures of human furin in complex with competitive inhibitors
ACS Chem. Biol.
9
1113-1118
2014
Homo sapiens (P09958), Homo sapiens
Zhou, Z.; Zhang, Q.; Lu, X.; Wang, R.; Wang, H.; Wang, Y.L.; Zhu, C.; Lin, H.Y.; Wang, H.
The proprotein convertase furin is required for trophoblast syncytialization
Cell Death Dis.
4
e593-e602
2013
Mus musculus, Homo sapiens (P09958), Homo sapiens
Tafesse, F.G.; Guimaraes, C.P.; Maruyama, T.; Carette, J.E.; Lory, S.; Brummelkamp, T.R.; Ploegh, H.L.
GPR107, a G-protein-coupled receptor essential for intoxication by Pseudomonas aeruginosa exotoxin A, localizes to the Golgi and is cleaved by furin
J. Biol. Chem.
289
24005-24018
2014
Homo sapiens (P09958), Homo sapiens
Tse, L.V.; Hamilton, A.M.; Friling, T.; Whittaker, G.R.
A novel activation mechanism of avian influenza virus H9N2 by furin
J. Virol.
88
1673-1683
2014
Gallus gallus, Homo sapiens (P09958), Homo sapiens
Fu, J.; Zhang, J.; Gong, Y.; Testa, C.L.; Klein-Szanto, A.J.
Regulation of HIF-1 alpha by the proprotein convertases furin and PC7 in human squamous carcinoma cells
Mol. Carcinog.
54
698-706
2015
Homo sapiens (P09958), Homo sapiens
Harihar, S.; Pounds, K.M.; Iwakuma, T.; Seidah, N.G.; Welch, D.R.
Furin is the major proprotein convertase required for KISS1-to-Kisspeptin processing
PLoS ONE
9
e84958
2014
Homo sapiens (P09958)
Sjoeberg, M.; Wu, S.R.; Loeving, R.; Rantalainen, K.; Lindqvist, B.; Garoff, H.
Furin cleavage of the Moloney murine leukemia virus Env precursor reorganizes the spike structure
Proc. Natl. Acad. Sci. USA
111
6034-6039
2014
Homo sapiens (P09958)
Hada, K.; Isshiki, K.; Matsuda, S.; Yuasa, K.; Tsuji, A.
Engineering of alpha1-antitrypsin variants with improved specificity for the proprotein convertase furin using site-directed random mutagenesis
Protein Eng. Des. Sel.
26
123-131
2013
Homo sapiens (P09958)
Tay, F.P.; Huang, M.; Wang, L.; Yamada, Y.; Liu, D.X.
Characterization of cellular furin content as a potential factor determining the susceptibility of cultured human and animal cells to coronavirus infectious bronchitis virus infection
Virology
433
421-430
2012
Homo sapiens (P09958), Homo sapiens
Dahms, S.O.; Jiao, G.S.; Than, M.E.
Structural studies revealed active site distortions of human furin by a small molecule inhibitor
ACS Chem. Biol.
12
1211-1216
2017
Homo sapiens (P09958), Homo sapiens
Pearce, K.; Overton, L.; Gampe, R.; Barrett, G.; Taylor, J.; McKee, D.; Campobasso, N.; Nolte, R.; Reid, R.
BacMam production and crystal structure of nonglycosylated apo human furin at 1.89 A resolution
Acta Crystallogr. Sect. F
75
239-245
2019
Homo sapiens (P09958), Homo sapiens
Dahms, S.O.; Hardes, K.; Steinmetzer, T.; Than, M.E.
X-ray structures of the proprotein convertase furin bound with substrate analogue inhibitors reveal substrate specificity determinants beyond the S4 pocket
Biochemistry
57
925-934
2018
Homo sapiens (P09958)
Valiulyte, I.; Preitakaite, V.; Tamasauskas, A.; Kazlauskas, A.
Importance of the putative furin recognition site 742 RNRR 745 for antiangiogenic Sema3C activity in vitro
Braz. J. Med. Biol. Res.
51
e7786
2018
Homo sapiens (P09958), Homo sapiens
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 (P09958)
Hardes, K.; Ivanova, T.; Thaa, B.; McInerney, G.M.; Klokk, T.I.; Sandvig, K.; Kuenzel, S.; Lindberg, I.; Steinmetzer, T.
Elongated and shortened peptidomimetic inhibitors of the proprotein convertase furin
ChemMedChem
12
613-620
2017
Homo sapiens (P09958)
Van Lam van, T.; Ivanova, T.; Hardes, K.; Heindl, M.R.; Morty, R.E.; Boettcher-Friebertshaeuser, E.; Lindberg, I.; Than, M.E.; Dahms, S.O.; Steinmetzer, T.
Design, synthesis, and characterization of macrocyclic inhibitors of the proprotein convertase furin
ChemMedChem
14
673-685
2019
Homo sapiens (P09958)
Ortutay, Z.; Oksanen, A.; Aittomaeki, S.; Ortutay, C.; Pesu, M.
Proprotein convertase furin regulates T cell receptor-induced transactivation
J. Leukoc. Biol.
98
73-83
2015
Homo sapiens (P09958), Homo sapiens, Mus musculus (P23188), Mus musculus
Wilbers, R.H.; Westerhof, L.B.; van Raaij, D.R.; van Adrichem, M.; Prakasa, A.D.; Lozano-Torres, J.L.; Bakker, J.; Smant, G.; Schots, A.
Co-expression of the protease furin in Nicotiana benthamiana leads to efficient processing of latent transforming growth factor-beta1 into a biologically active protein
Plant Biotechnol. J.
14
1695-1704
2016
Homo sapiens (P09958), Homo sapiens
Mamedov, T.; Musayeva, I.; Acsora, R.; Gun, N.; Gulec, B.; Mammadova, G.; Cicek, K.; Hasanova, G.
Engineering, and production of functionally active human furin in N. benthamiana plant in vivo post-translational processing of target proteins by furin in plants
PLoS ONE
14
e0213438
2019
Homo sapiens (P09958), Homo sapiens
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