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Information on EC 3.4.21.61 - Kexin and Organism(s) Homo sapiens and UniProt Accession Q8NBP7

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EC Tree
     3 Hydrolases
         3.4 Acting on peptide bonds (peptidases)
             3.4.21 Serine endopeptidases
                3.4.21.61 Kexin
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UNIPROT: Q8NBP7 not found.
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The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Synonyms
pcsk9, proprotein convertase subtilisin/kexin type 9, proprotein convertase, pc1/3, kexin, kex2p, pcsk6, prohormone convertase 1, proprotein convertase subtilisin kexin type 9, prohormone convertase 2, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
PCSK type 9
-
plasma proprotein convertase subtilisin-kexin type 9
-
pro-protein convertase subtilisin/kexin type 9
-
proprotein convertase subtilisin kexin type 9
-
proprotein convertase subtilisin kexin-9
-
proprotein convertase subtilisin-like/kexin type 9
-
proprotein convertase subtilisin/kexin type 9
-
adrenorphin-Gly-generating enzyme
-
-
-
-
corin activating enzyme
-
-
endoproteinase Kex2p
-
-
-
-
Gene KEX2 dibasic proteinase
-
-
-
-
Kex 2p proteinase
-
-
-
-
Kex2 endopeptidase
-
-
-
-
Kex2 endoprotease
-
-
-
-
Kex2 endoproteinase
-
-
-
-
Kex2 protease
-
-
-
-
Kex2 proteinase
-
-
-
-
Kex2-like endoproteinase
-
-
-
-
Kex2-like precursor protein processing endoprotease
-
-
-
-
Paired-basic endopeptidase
-
-
-
-
PCSK6
Prohormone-processing endoprotease
-
-
-
-
Prohormone-processing KEX2 proteinase
-
-
-
-
Prohormone-processing proteinase
-
-
-
-
Proprotein convertase
-
-
-
-
proprotein convertase subtilisin kexin type 9
-
-
proprotein convertase subtilisin/kexin 6
-
-
proprotein convertase subtilisin/kexin type 6
-
proprotein convertase subtilisin/kexin type 9
-
-
proprotein convertase subtilisin/kexin type 9 (PCSK9)Proprotein convertase subtilisin/kexin type 9
-
-
Protease KEX2
-
-
-
-
Proteinase Kex2p
-
-
-
-
Proteinase yscF
-
-
-
-
Proteinase, prohormone-processing
-
-
-
-
Yeast KEX2 protease
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of peptide bond
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY hide
99676-46-7
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
low density lipoprotein receptor
?
show the reaction diagram
-
-
-
?
low density lipoprotein receptor + H2O
?
show the reaction diagram
low density lipoprotein receptor-related protein 1 + H2O
?
show the reaction diagram
degradation
-
-
?
low-density lipoprotein receptor
?
show the reaction diagram
PCSK9 posttranslationally promotes the degradation of the low-density lipoprotein receptor
-
-
?
corin + H2O
?
show the reaction diagram
-
activating processing of corin by enzyme PCSK6
-
-
?
low density lipoprotein receptor + H2O
?
show the reaction diagram
low density lipoprotein receptor-related protein 1 + H2O
?
show the reaction diagram
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
low density lipoprotein receptor + H2O
?
show the reaction diagram
low density lipoprotein receptor-related protein 1 + H2O
?
show the reaction diagram
degradation
-
-
?
corin + H2O
?
show the reaction diagram
-
activating processing of corin by enzyme PCSK6
-
-
?
low density lipoprotein receptor-related protein 1 + H2O
?
show the reaction diagram
-
degradation
-
-
?
additional information
?
-
both furinand hepsin-cleaved enzymes are able to degrade LDL receptor on HepG2 cells resulting in elevated serum cholesterol levels
-
-
?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
5alpha,6alpha-epoxy-(22E,24R)-ergosta-8(14),22-diene-3beta,7beta-diol
isolated from fruiting bodies of Sparassis crispa
adenosine
-
Berberine
-
hanabiratakelide A
isolated from fruiting bodies of Sparassis crispa
sparoside A
isolated from fruiting bodies of Sparassis crispa
sterol
-
completely blocks increase in PCSK9 mRNA by lovastatin
TIMP-3
-
completely abolishes the production of the 34-kDa PCSK9 product
-
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
atorvastatin
-
significantly increases circulating PCSK9 levels by 34% compared with baseline and placebo and decreases low density lipoprotein cholesterol levels by 42%
lovastatin
-
suppresses endogenous synthesis of sterols, increases both the proteins and mRNAs for PCSK9. 10 mM can reverse the increase of PCSK9 expression by lovastatin
sodium mevalonate
-
suppresses endogenous synthesis of sterols, PCSK9 is further increased
sterol-regulatory element binding protein-1
-
dramatically increases the promoter activity of PCSK9
-
sterol-regulatory element binding protein-2
-
dramatically increases the promoter activity of PCSK9
-
additional information
-
depletion of sterols induces PCSK9 in a time-dependent manner
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
additional information
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00823
5alpha,6alpha-epoxy-(22E,24R)-ergosta-8(14),22-diene-3beta,7beta-diol
Homo sapiens
pH and temperature not specified in the publication
0.01846
adenosine
Homo sapiens
pH and temperature not specified in the publication
0.00804
Berberine
Homo sapiens
pH and temperature not specified in the publication
0.00718
hanabiratakelide A
Homo sapiens
pH and temperature not specified in the publication
0.0201
sparoside A
Homo sapiens
pH and temperature not specified in the publication
additional information
additional information
Homo sapiens
at 20°C in 0.05 ml of buffer containing 10 mM Hepes, pH 7.4, 150 mM NaCl, 0.1 mM CaCl2, and 0.05% (w/v) bovine serum albumin: 0.0000048 mM with 1G08 fragment antigen binding, when wild-type expressed in HEK-293 cells, 0.0000150 mM with 1G08 fragment antigen binding, when wild-type expressed in Hep-G2 cells, 0.001 mM with 1G08 fragment antigen binding, when mutant R549A , mutant R580A/R582A and mutant E607A/K609A/E612N expressed in HEK-293 cells
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
20
assay at
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
highest level of expression
Manually annotated by BRENDA team
additional information
Caco-2/15 cell
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
epithelial cells, accumulates at the apical and basolateral sides of the cells
Manually annotated by BRENDA team
on its way through the Golgi and trans-Golgi complex, the enzyme co-localizes with the protein sortilin, the protein-protein interaction is probably required for cellular secretion
Manually annotated by BRENDA team
additional information
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
physiological function
malfunction
-
lack of PCSK6-dependent corin activation leads to hypertension. PCSK6-mediated processing of corin is reduced in the presence of corin variants T555I and Q568P previously associated to hypertension and to heart disease
metabolism
physiological function
additional information
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
PCSK9_HUMAN
692
0
74286
Swiss-Prot
-
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
75979
1 * 75979, purified PCSK9, gel filtration. 1* 45708, purified PCSK9DELTAC, gel filtration
64000
-
mature form of wild-type PCSK9, Western blot analysis
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
monomer
1 * 75979, purified PCSK9, gel filtration. 1* 45708, purified PCSK9DELTAC, gel filtration
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
proteolytic modification
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
A433T
is associated with a plasma PCSK9 concentration of 222 ng/ml
C678X
a loss-of-function mutation that abolishes the release of the enzyme from the endoplasmic reticulum
D374Y
E569K
site-directed mutagenesis, the mutant shows slightly decreased ability to block LDL uptake into HepG2 cells compared to the wild-type enzyme
E607A/K609A/E612N
mutation does not affect the overall integrity of the PCSK9 protein, shows similar cellular uptake potencies as the wild-type, impairs 1G08-PCSK9 binding
F216L
G365R
is associated with a plasma PCSK9 concentration of 205 ng/ml
G517R
site-directed mutagenesis, the mutant shows highly decreased ability to block LDL uptake into HepG2 cells compared to the wild-type enzyme
Q152H
a dominant negative mutation that restricts enzyme proteolysis and secretion independently
Q152I
te mutation completely abrogates proteolysis in both intra- and intermolecular systems but has only a limited impact on secretion
Q152R
the mutation completely abolished both proteolysis and secretion
Q152X
four phenotypes of Q152X mutants, overview
Q190R
is associated with a plasma PCSK9 concentration of 55 ng/ml
R215H
a naturally occurring gain-of-function mutation associated with hypercholesterolemia, the mutation impairs furin-mediated enzyme cleavage
R218S
a naturally occurring gain-of-function mutation associated with hypercholesterolemia, the mutation impairs furin-mediated enzyme cleavage
R434W
is associated with a plasma PCSK9 concentration of 51 ng/ml
R46L
is associated with a plasma PCSK9 concentration of 51-59 ng/ml
R53V
is associated with a plasma PCSK9 concentration of 39 ng/ml
R549A
mutation does not affect the overall integrity of the PCSK9 protein, shows similar cellular uptake potencies as the wild-type, impairs 1G08-PCSK9 binding
R580A/R582A
mutation does not affect the overall integrity of the PCSK9 protein, shows similar cellular uptake potencies as the wild-type, impairs 1G08-PCSK9 binding
R659A
site-directed mutagenesis, the mutant shows slightly decreased ability to block LDL uptake into HepG2 cells compared to the wild-type enzyme
R659E
site-directed mutagenesis, the mutant shows slightly decreased ability to block LDL uptake into HepG2 cells compared to the wild-type enzyme
S127R
naturally occurring gain-of-function mutation, associated to hypercholesterolemia and premature atherosclerosisias. Strongly diminishes processing (21% maturation)
S386A
S462P
a loss-of-function mutation that abolishes the release of the enzyme from the endoplasmic reticulum
S636R
site-directed mutagenesis, the mutant shows slightly decreased ability to block LDL uptake into HepG2 cells compared to the wild-type enzyme
V149A
the mutant shows intolerance for intermolecular cleavage of the enzyme, residue Val149 is critical for secretion
V610R
site-directed mutagenesis, the mutant shows highly decreased ability to block LDL uptake into HepG2 cells compared to the wild-type enzyme
V644R
site-directed mutagenesis, the mutant shows highly decreased ability to block LDL uptake into HepG2 cells compared to the wild-type enzyme
A443T
-
is expressed, processed, and secreted normally, and reduces cellular LDL uptake in a concentration-dependent like the wild-type
D374Y
DeltaN218
-
in COS-1 cells only apparent upon co-expression of PC5A. Untreated Y1 cells secrete PCSK9-DeltaN218, stimulation with 8-Br-cAMP increases the level and especially that of the 34-kDa PCSK9 product
N425S
-
is expressed, processed, and secreted normally, and reduces cellular LDL uptake in a concentration-dependent like the wild-type
R218S
-
noncleavable mutant
R469W
-
natural mutation, cannot modify the ability of PC5A to produce the 34-kDa PCSK9 product in HEK293 cells
R496W
-
natural mutation, cannot modify the ability of PC5A to produce the 34-kDa PCSK9 product in HEK293 cells
S127R
-
naturally occurring gain-of-function mutant causes severe hypercholesterolemia
additional information
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-70°C
-
-80°C
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
at 4°C by binding to anti-FLAG M2 affinity gel
gel filtration
recombinant His-tagged enzyme from HEK-293T cell medium by nickel affinity chromatography
by Ni-nitriloacetic acid and size-exclusion chromatography, more than 95% pure
-
on Ni-NTA resin
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
full-length and mutant PCSK9-V5-His proteins expressed in HEK-293 cells. Truncated PCSK9DELTAC (Gln-31-Ala-451) proteins with a C-terminal His tag expressed in Escherichia coli BL21 cells
recombinant expression of enzyme mutants in Hep-G2 cells
recombinant His-tagged enzyme catalytic domain expression in HEK-293T cells and secretion to the medium
recombinant overexpression of the human enzyme in mouse LDL-receptor null mutant cells, expression and protein profiles, overview. Overexpression of PCSK9 increases plasma ApoB levels in an LDLR-independent fashion
wild type and mutant D374Y-FLAG expressed in Hep-G2 cells
wild-type PCSK9 with a V5 epitope flag inserted into pcDNA3.1. PCSK9 mutants expressed in primary hepatocytes derived from PCSK9-/- mice
cDNAs encoding full-length PCSK9 splicing variant or mutants inserted into a modified pJB02 vector with a C-terminal Flag-HIS6 or HIS6 tag, respectively. The resulting constructs used for transient transfection of HEK-293 cells
-
expressed in HEK-293 cells, COS-1 cells or Y1 cells
-
expression in HEK293 cell
-
expression in HEK293T and HepG2 cells
-
into vector pET-21a(+)
-
overexpressed in HEK-293 cells
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
amounts of PCSK9 mRNA and protein in Caco-2/15 cells are associated to the regulation of 3-hydroxy-3-methylglutaryl-CoA reductase and sterol regulatory element binding protein-2 that can transcriptionally activate PCSK9 via sterol-regulatory elements located in its proximal promoter region. Depletion of cholesterol content by hydroxypropyl-beta-cyclodextrin upregulates PCSK9 transcripts (20%) and protein mass (540%), in parallel with sterol regulatory element binding protein-2 protein levels
cholesterol (0.1 mM) solubilized in albumin or micelles significantly downregulates PCSK9 gene (30%) and protein expression (50%) in Caco-2/15 cells. Cells treated with 25-hydroxycholesterol (0.05 mM) also display significant reduction in PCSK9 gene (37%) and protein (75%) expression. Addition of bile acids taurocholate and deoxycholate to the apical culture medium lowers PCSK9 gene expression (25%) and raises PCSK9 protein expression (30%), respectively, probably via the modulation of farnesoid X receptor
cholesteryl ester transfer protein inhibitors downregulate PCSK9 and LDLR expression through decreases in SREBP2 expression in hepatocytes. Glitazones, rapamycine, berberine, and resistin cause a reduction of enzyme expression via HNF1alpha reduction. Reduction of enzyme expression can be achieved by peroxisome proliferator-activated receptor alpha and activation of sterolresponse element binding protein 2. In HepG2 cells, hyperinsulinemia decreases the enzyme expression, an effect which is also observed in post-menopausal obese women
in healthy men 24 h hyperinsulinemia does not alter plasma the enzyme concentrations, and the enzyme expression is similar in normal, pre- and Typ2-diabetic patients
knockdown of PCSK9 expression in immortalized human hepatocytes using specific siRNA which results in a 38% and 53% decrease in PCSK9 protein quantity, respectively in cell lysates and culture media compared with controls
PCSK9 is expressed throughout the entire small intestine and in enterocytes. PCSK9 is expressed almost exclusively in the epithelial barrier of the duodenum and ileum, both in enterocytes and goblet cells. PCSK9 is 160% upregulated by 0.01 mM pravastatin in CaCo-2 cells after exposure for 48 h
PCSK9 levels correlate with plasma cholesterol, LDL-C, triglycerides, fasting glucose, age and body mass index. In hypercholesterolemic patients, circulating PCSK9 is higher than in healthy volunteers, and increases with increasing statin dose, and further increased when ezetimibe is added. Ezetimibe treatment of Hep-G2 (hepatocytes) and Caco-2 (enterocytes) cells causes a slight increase in PCSK9 mRNA, but no significant rise in PCSK9 protein secretion, suggesting that these transformed cells are not ideal model cell lines
the enzyme is up-regulated during apoptosis of neurons. Statins and increase the transcription factor SREBP2, statins also the HNF1alpha expression, and fibrates increase PPAralpha, all leading to increased enzyme PCSK9 expression. Activation of enzyme expression can be mediated by activation of insulin receptors and subsequent activation of the sterolresponse element binding protein 1 and mammalian target of rapamycin pathways
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
diagnostics
plasma enzyme concentrations are predictive for 4-5 year major cardiovascular event rate, and enzyme serum concentrations correlate with cardiovascular risk
drug development
medicine
drug development
-
PCSK6 may become a reasonable target for the development of drugs able to control high blood pressure by directly modulating pro-ANP cleavage
medicine
additional information
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Mayer, G.; Hamelin, J.; Asselin, M.; Pasquato, A.; Marcinkiewicz, E.; Tang, M.; Tabibzadeh, S.; Seidah, N.G.
The regulated cell surface zymogen activation of the proprotein convertase PC5A directs the processing of its secretory substrates
J. Biol. Chem.
283
2373-2384
2008
Homo sapiens
Manually annotated by BRENDA team
Alborn, W.E.; Cao, G.; Careskey, H.E.; Qian, Y.W.; Subramaniam, D.R.; Davies, J.; Conner, E.M.; Konrad, R.J.
Serum proprotein convertase subtilisin kexin type 9 is correlated directly with serum LDL cholesterol
Clin. Chem.
53
1814-1819
2007
Homo sapiens
Manually annotated by BRENDA team
Schmidt, R.J.; Zhang, Y.; Zhao, Y.; Qian, Y.W.; Wang, H.; Lin, A.; Ehsani, M.E.; Yu, X.; Wang, G.; Singh, J.; Su, E.W.; Li, S.; Konrad, R.J.; Cao, G.
A novel splicing variant of proprotein convertase subtilisin/kexin type 9
DNA Cell Biol.
27
183-189
2008
Homo sapiens
Manually annotated by BRENDA team
Careskey, H.E.; Davis, R.A.; Alborn, W.E.; Troutt, J.S.; Cao, G.; Konrad, R.J.
Atorvastatin increases human serum levels of proprotein convertase subtilisin/kexin type 9
J. Lipid Res.
49
394-398
2008
Homo sapiens
Manually annotated by BRENDA team
Jeong, H.J.; Lee, H.S.; Kim, K.S.; Kim, Y.K.; Yoon, D.; Park, S.W.
Sterol-dependent regulation of proprotein convertase subtilisin/kexin type 9 expression by sterol-regulatory element binding protein-2
J. Lipid Res.
49
399-409
2008
Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Leblond, F.; Seidah, N.G.; Precourt, L.P.; Delvin, E.; Dominguez, M.; Levy, E.
Regulation of the proprotein convertase subtilisin/kexin type 9 in intestinal epithelial cells
Am. J. Physiol. Gastrointest. Liver Physiol.
296
G805-G815
2009
Homo sapiens (Q8NBP7)
Manually annotated by BRENDA team
Le May, C.; Kourimate, S.; Langhi, C.; Chetiveaux, M.; Jarry, A.; Comera, C.; Collet, X.; Kuipers, F.; Krempf, M.; Cariou, B.; Costet, P.
Proprotein convertase subtilisin kexin type 9 null mice are protected from postprandial triglyceridemia
Arterioscler. Thromb. Vasc. Biol.
29
684-690
2009
Mus musculus, Homo sapiens (Q8NBP7), Homo sapiens
Manually annotated by BRENDA team
Kourimate, S.; Chetiveaux, M.; Jarnoux, A.L.; Lalanne, F.; Costet, P.
Cellular and secreted pro-protein convertase subtilisin/kexin type 9 catalytic activity in hepatocytes
Atherosclerosis
206
134-140
2009
Homo sapiens (Q8NBP7), Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Ni, Y.G.; Condra, J.H.; Orsatti, L.; Shen, X.; Di Marco, S.; Pandit, S.; Bottomley, M.J.; Ruggeri, L.; Cummings, R.T.; Cubbon, R.M.; Santoro, J.C.; Ehrhardt, A.; Lewis, D.; Fisher, T.S.; Ha, S.; Njimoluh, L.; Wood, D.D.; Hammond, H.A.; Wisniewski, D.; Volpari, C.; Noto, A.; Lo Surdo, P.; Hubbard, B.; Carfi, A.
A proprotein convertase subtilisin-like/kexin type 9 (PCSK9) C-terminal domain antibody antigen-binding fragment inhibits PCSK9 internalization and restores low density lipoprotein uptake
J. Biol. Chem.
285
12882-12891
2010
Homo sapiens (Q8NBP7)
Manually annotated by BRENDA team
Lan, H.; Pang, L.; Smith, M.M.; Levitan, D.; Ding, W.; Liu, L.; Shan, L.; Shah, V.V.; Laverty, M.; Arreaza, G.; Zhang, Q.; Murgolo, N.J.; Hernandez, M.; Greene, J.R.; Gustafson, E.L.; Bayne, M.L.; Davis, H.R.; Hedrick, J.A.
Proprotein convertase subtilisin/kexin type 9 (PCSK9) affects gene expression pathways beyond cholesterol metabolism in liver cells
J. Cell. Physiol.
224
273-281
2010
Homo sapiens (Q8NBP7)
Manually annotated by BRENDA team
Chan, J.C.; Piper, D.E.; Cao, Q.; Liu, D.; King, C.; Wang, W.; Tang, J.; Liu, Q.; Higbee, J.; Xia, Z.; Di, Y.; Shetterly, S.; Arimura, Z.; Salomonis, H.; Romanow, W.G.; Thibault, S.T.; Zhang, R.; Cao, P.; Yang, X.P.; Yu, T.; Lu, M.; Retter, M.W.; Kwon, G.; Henne, K.; Pan, O.; Tsai, M.M.; Fuchslocher, B.; Yang, E.; Z, Z.h.
A proprotein convertase subtilisin/kexin type 9 neutralizing antibody reduces serum cholesterol in mice and nonhuman primates
Proc. Natl. Acad. Sci. USA
106
9820-9825
2009
Macaca fascicularis, Mus musculus, Homo sapiens (Q8NBP7)
Manually annotated by BRENDA team
Davignon, J.; Dubuc, G.
Statins and ezetimibe modulate plasma proprotein convertase subtilisin kexin-9 (PCSK9) levels
Trans. Am. Clin. Climatol. Assoc.
120
163-173
2009
Homo sapiens (Q8NBP7), Homo sapiens
Manually annotated by BRENDA team
Mousavi, S.A.; Berge, K.E.; Berg, T.; Leren, T.P.
Affinity and kinetics of proprotein convertase subtilisin/kexin type 9 binding to low-density lipoprotein receptors on HepG2 cells
FEBS J.
278
2938-2950
2011
Homo sapiens
Manually annotated by BRENDA team
Du, F.; Hui, Y.; Zhang, M.; Linton, M.; Fazio, S.; Fan, D.
A novel domain interaction regulates secretion of proprotein convertase subtilisin/kexin type 9
J. Biol. Chem.
286
43054-43061
2011
Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Pearlstein, R.; Hu, Q.; Zhou, J.; Yowe, D.; Levell, J.; Dale, B.; Kaushik, V.; Daniels, D.; Hanrahan, S.; Sherman, W.; Abel, R.
New hypotheses about the structure-function of proprotein convertase subtilisin/kexin type 9: Analysis of the epidermal growth factor-like repeat A docking site using WaterMap
Proteins
78
2571-2586
2010
Homo sapiens
Manually annotated by BRENDA team
Sun, H.; Samarghandi, A.; Zhang, N.; Yao, Z.; Xiong, M.; Teng, B.B.
Proprotein convertase subtilisin/kexin type 9 interacts with apolipoprotein B and prevents its intracellular degradation, irrespective of the low-density lipoprotein receptor
Arterioscler. Thromb. Vasc. Biol.
32
1585-1595
2012
Homo sapiens (Q8NBP7), Mus musculus (Q80W65), Mus musculus C57BL/6 (Q80W65)
Manually annotated by BRENDA team
Schulz, R.; Schlueter, K.D.; Laufs, U.
Molecular and cellular function of the proprotein convertase subtilisin/kexin type 9 (PCSK9)
Basic Res. Cardiol.
110
4
2015
Mus musculus (Q80W65), Homo sapiens (Q8NBP7)
Manually annotated by BRENDA team
Kwakernaak, A.J.; Lambert, G.; Dullaart, R.P.
Plasma proprotein convertase subtilisin-kexin type 9 is predominantly related to intermediate density lipoproteins
Clin. Biochem.
47
679-682
2014
Homo sapiens (Q8NBP7)
Manually annotated by BRENDA team
Lipari, M.T.; Li, W.; Moran, P.; Kong-Beltran, M.; Sai, T.; Lai, J.; Lin, S.J.; Kolumam, G.; Zavala-Solorio, J.; Izrael-Tomasevic, A.; Arnott, D.; Wang, J.; Peterson, A.S.; Kirchhofer, D.
Furin-cleaved proprotein convertase subtilisin/kexin type 9 (PCSK9) is active and modulates low density lipoprotein receptor and serum cholesterol levels
J. Biol. Chem.
287
43482-43491
2012
Homo sapiens (Q8NBP7)
Manually annotated by BRENDA team
Chorba, J.S.; Shokat, K.M.
The proprotein convertase subtilisin/kexin type 9 (PCSK9) active site and cleavage sequence differentially regulate protein secretion from proteolysis
J. Biol. Chem.
289
29030-29043
2014
Homo sapiens (Q8NBP7)
Manually annotated by BRENDA team
Canuel, M.; Sun, X.; Asselin, M.C.; Paramithiotis, E.; Prat, A.; Seidah, N.G.
Proprotein convertase subtilisin/kexin type 9 (PCSK9) can mediate degradation of the low density lipoprotein receptor-related protein 1 (LRP-1)
PLoS ONE
8
e64145
2013
Cricetulus griseus, Homo sapiens, Mus musculus (Q80W65), Mus musculus
Manually annotated by BRENDA team
Geschwindner, S.; Andersson, G.M.; Beisel, H.G.; Breuer, S.; Hallberg, C.; Kihlberg, B.M.; Lindqvist, A.M.; OMahony, G.; Plowright, A.T.; Raubacher, F.; Knecht, W.
Characterisation of de novo mutations in the C-terminal domain of proprotein convertase subtilisin/kexin type 9
Protein Eng. Des. Sel.
2015
1-9
2015
Homo sapiens (Q8NBP7), Homo sapiens
Manually annotated by BRENDA team
Volpe, M.; Rubattu, S.
Novel insights into the mechanisms regulating pro-atrial natriuretic peptide cleavage in the heart and blood pressure regulation proprotein convertase subtilisin/kexin 6 is the corin activating enzyme
Circ. Res.
118
196-198
2016
Homo sapiens
Manually annotated by BRENDA team
Bang, S.; Chae, H.S.; Lee, C.; Choi, H.G.; Ryu, J.; Li, W.; Lee, H.; Jeong, G.S.; Chin, Y.W.; Shim, S.H.
New aromatic compounds from the fruiting body of Sparassis crispa (Wulf.) and their inhibitory activities on proprotein convertase subtilisin/kexin type 9 mRNA expression
J. Agric. Food Chem.
65
6152-6157
2017
Homo sapiens (Q8NBP7)
Manually annotated by BRENDA team
Jiang, H.; Wang, L.; Wang, F.; Pan, J.
Proprotein convertase subtilisin/kexin type 6 promotes in vitro proliferation, migration and inflammatory cytokine secretion of synovial fibroblast-like cells from rheumatoid arthritis via nuclear-kappaB, signal transducer and activator of transcription 3 and activator of transcription 3 and extracellular signal regulated 1/2 pathways
Mol. Med. Rep.
16
8477-8484
2017
Homo sapiens (P29122), Homo sapiens
Manually annotated by BRENDA team
Wang, P.; Wang, F.; Wang, L.; Pan, J.
Proprotein convertase subtilisin/kexin type 6 activates the extracellular signal-regulated kinase 1/2 and Wnt family member 3A pathways and promotes in vitro proliferation, migration and invasion of breast cancer MDA-MB-231 cells
Oncol. Lett.
16
145-150
2018
Homo sapiens (P29122), Homo sapiens
Manually annotated by BRENDA team