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Information on EC 3.4.21.B1 - hyaluronan-binding serine protease
for references in articles please use BRENDA:EC3.4.21.B1preliminary BRENDA-supplied EC number
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EC Tree
3.4.21.B1 hyaluronan-binding serine proteaseSpecify your search results
Word Map
- 3.4.21.B1
-
marburg
-
fibrinolysis
-
haemostasis
-
nonmedullary
-
autoactivation
- pro-urokinase
-
fnmtc
- medicine
-
srgap1
- analysis
The enzyme appears in viruses and cellular organisms
Synonyms
habp2, phbsp, factor vii-activating protease, factor vii activating protease, plasma hyaluronan-binding protein, factor seven activating protease, hyaluronan binding protein 2, hyaluronan-binding protease, gelatinolytic serine proteinase, 
more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
factor VII activating protease
factor VII-activating protease
FSAP
HABP2
PHBP
plasma hyaluronan-binding protein
factor VII-activating protease
-
-
FSAP
-
-
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
endopeptidase activity. Cleaves C-terminal site of Lys and Arg
-
-
-
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
cleavage of C-N-linkage
hydrolysis of peptide bond
cleavage of C-N-linkage
-
-
hydrolysis of peptide bond
-
-
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CAS REGISTRY NUMBER
COMMENTARY
246521-08-4
-
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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
Ala-Lys-Nle-Arg-7-amido-4-methylcoumarin + H2O
Ala-Lys-Nle-Arg + 7-amino-4-methylcoumarin
-
-
-
?
benzoyl-Ile-Glu(gamma-OR)-Gly-Arg-4-nitroanilide + H2O
benzoyl-Ile-Glu(gamma-OR)-Gly-Arg + 4-nitroaniline
i.e. A-2222, weak chromogenic substrate
-
?
CH2SO2-D-cyclohexylalanine-butanoyl-Arg-4-nitroanilide + H2O
CH2SO2-D-cyclohexylalanine-butanoyl-Arg + 4-nitroaniline
i.e. Pefa-5979, chromogenic substrate
-
?
CH2SO2-D-cyclohexylglycine-Gly-Arg-4-nitroanilide
CH2SO2-D-cyclohexylglycine-Gly-Arg + 4-nitroaniline
i.e. Pefa-3107, chromogenic substrate
-
?
CH3-OCO-D-cyclohexylalanine-Gly-Arg-4-nitroanilide + H2O
CH3-OCO-D-cyclohexylalanine-Gly-Arg + 4-nitroaniline
i.e. Pefa-5523, chromogenic substrate
-
?
D-Ala-cyclohexyltyrosine-Lys-4-nitroanilide + H2O
D-Ala-cyclohexyltyrosine-Lys + 4-nitroaniline
i.e. Pefa-5329, weak chromogenic substrate
-
?
D-cyclohexylglycine-Ala-Arg-4-nitroanilide + H2O
D-cyclohexylglycine-Ala-Arg + 4-nitroaniline
i.e. Pefa-5114, good chromogenic substrate
-
?
D-Lys(benzyloxycarbonyl)-Pro-Arg-4-nitroanilide + H2O
D-Lys(benzyloxycarbonyl)-Pro-Arg + 4-nitroaniline
i.e. Pefa-5773, chromogenic substrate
-
?
D-Phe-Pip-Arg-4-nitroanilide + H2O
D-Phe-Pip-Arg + 4-nitroaniline
i.e. S-2238, chromogenic substrate
-
?
DL-pyroglutamic acid-cyclohexylglycine-Arg-4-nitroanilide + H2O
DL-pyroglutamic acid-cyclohexylglycine-Arg + 4-nitroaniline
i.e. Pefa-3297, good chromogenic substrate
-
?
fibrinogen + ?
?
-
cleaves the alpha-chain at multiple sites and the beta-chain between lysine53 and lysine54 but not the gamma-chain
-
?
fibroblast growth factor receptor 1 + H2O
?
-
HABP activates the p44/42-dependent MAPK (ERK1/2) signalling cascade independent of the B2-receptor, involving the fibroblast growth factor receptor-1 and basic fibroblast growth factor. This signalling pathway leads to phosphorylation of the kinases Raf, MEK1/2 and ERK1/2
-
-
?
high molecular weight kininogen + H2O
activated cofactor kininogen + bradykinin
-
activates kininogen
-
?
L-pyroglutamic acid-cyclo-hexylglycine-Arg-para-nitroanilide + H2O
?
-
P-3342, fluorogenic substrate
-
?
L-pyroglutamic acid-Pro-Arg-4-nitroanilide + H2O
L-pyroglutamic acid-Pro-Arg + 4-nitroaniline
i.e. S-2366, chromogenic substrate
-
?
L-pyroglutamylglycyl-L-arginine-p-nitroanilide + H2O
L-pyroglutamylglycyl-L-arginine + p-nitroaniline
-
-
-
?
N-tert-butoxycarbonyl-Phe-Ser-Arg-7-amido-4-methylcoumarin + H2O
N-tert-butoxycarbonyl-Phe-Ser-Arg + 7-amino-4-methylcoumarin
-
synthetic substrate
-
?
single chain urokinase type plasminogen activator + H2O
two chain urokinase type plasminogen activator
-
-
-
-
?
tissue factor pathway inhibitor + H2O
?
-
the enzyme inhibits tissue factor pathway inhibitor, cleavage occurs between kringle domains K1 and K2 (Lys86-Thr87), as well as in the active site of K2 (Arg107-Gly108) and K3 (Arg199-Ala200) domains
-
-
?
urinary plasminogen activator + ?
?
-
converts the inactive single chain urinary plasminogen activator to the active two chain form
-
?
Z-D-Arg-Gly-Arg-4-nitroanilide + H2O
Z-D-Arg-Gly-Arg + 4-nitroaniline
i.e. S-2765, good chromogenic substrate
-
?
basic fibroblast growth factor + H2O
?
-
HABP activates the p44/42-dependent MAPK (ERK1/2) signalling cascade independent of the B2-receptor, involving the fibroblast growth factor receptor-1 and basic fibroblast growth factor. This signalling pathway leads to phosphorylation of the kinases Raf, MEK1/2 and ERK1/2
-
-
?
CTCF + H2O
?
-
essential factor for optimal transcription from the amyloid beta-protein precursor promoter, enzyme cleaves CTCF at three major sites
-
?
CTCF + H2O
?
-
essential factor for optimal transcription from the amyloid beta-protein precursor promoter, enzyme cleaves CTCF at three major sites
-
?
CTCF + H2O
?
-
essential factor for optimal transcription from the amyloid beta-protein precursor promoter, enzyme cleaves CTCF at three major sites
-
?
CTCF + H2O
?
-
essential factor for optimal transcription from the amyloid beta-protein precursor promoter, enzyme cleaves CTCF at three major sites
-
?
Fibrinogen + H2O
?
-
cleaves the alpha-chain at multiple sites and the beta-chain between lysine53 and lysine54 but not the gamma-chain
-
-
?
high molecular weight kininogen + H2O
low molecular weight kininogen + bradykinin
-
-
-
-
?
high molecular weight kininogen + H2O
low molecular weight kininogen + bradykinin
-
HABP triggers Ca2+ release in HUVEC cells via the bradykinin B2 receptor
-
-
?
high molecular weight kininogen profactor + H2O
activated kininogen + bradykinin
-
-
-
-
?
high molecular weight kininogen profactor + H2O
activated kininogen + bradykinin
-
activates kininogen, cleaves between Arg419 and Lys 420
-
?
platelet-derived growth factor-BB + H2O
?
-
the enzyme inhibits platelet-derived growth factor-BB
-
-
?
Protein + H2O
?
-
cleaves C-terminal side of Arg effectively and that of Lys weakly
-
?
additional information
?
-
-
enzyme displays pro-urokinase-activating properties as well as factor VII-activating protease activity
-
?
additional information
?
-
-
extracellular activity of HABP affects gene expression level through phosphorylation of two transcription factors, the cAMP responsive element binding protein CREB and the protooncogene c-Myc
-
-
?
additional information
?
-
-
FSAP circulates as single-chain zymogen in plasma, which is autoactivated to an enzymatically active two-chain form
-
-
?
additional information
?
-
-
single-chain inactive zymogen is autoactivated to the two-chain active enzyme
-
-
?
additional information
?
-
regulation of FSAP activity is dependent on its EGF-3 domain and over-expression of active variants induces cell death
-
-
?
additional information
?
-
-
pro-plasma hyaluronan-binding protein autoproteolytically converts to an active two-chain form with the aid of an effector such as spermidine and heparin. Tannic acid, delphinidin, hamamelitannin, (-)-epicatechin gallate, and 3,5-di-O-caffeoylquinic inhibit spermidine-induced pro-plasma hyaluronan-binding protein autoactivation
-
-
?
additional information
?
-
substrate Ala-Lys-Nle-Arg-7-amido-4-methylcoumarin is based on a representive FSAP-cleaved sequence obtained from positional scanning substrate combinatorial library method. The results show a predilection for cleavage at a cluster of basic amino acids on the nonprime side. Molecular modelling studies show a preference for Arg over Lys at the P1 site
-
-
?
additional information
?
-
-
histone-mediated pro-plasma hyaluronan-binding protein activation in plasma leads to the formations of bradykinin and plasma hyaluronan-binding protein-alpha2-antiplasmin complex as well as histone degradation
-
-
?
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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
fibrinogen + ?
?
-
cleaves the alpha-chain at multiple sites and the beta-chain between lysine53 and lysine54 but not the gamma-chain
-
?
platelet-derived growth factor-BB + H2O
?
-
the enzyme inhibits platelet-derived growth factor-BB
-
-
?
tissue factor pathway inhibitor + H2O
?
-
the enzyme inhibits tissue factor pathway inhibitor, cleavage occurs between kringle domains K1 and K2 (Lys86-Thr87), as well as in the active site of K2 (Arg107-Gly108) and K3 (Arg199-Ala200) domains
-
-
?
Fibrinogen + H2O
?
-
cleaves the alpha-chain at multiple sites and the beta-chain between lysine53 and lysine54 but not the gamma-chain
-
-
?
high molecular weight kininogen profactor + H2O
activated kininogen + bradykinin
-
-
-
-
?
high molecular weight kininogen profactor + H2O
activated kininogen + bradykinin
-
activates kininogen, cleaves between Arg419 and Lys 420
-
?
Protein + H2O
?
-
cleaves C-terminal side of Arg effectively and that of Lys weakly
-
?
additional information
?
-
regulation of FSAP activity is dependent on its EGF-3 domain and over-expression of active variants induces cell death
-
-
?
additional information
?
-
-
histone-mediated pro-plasma hyaluronan-binding protein activation in plasma leads to the formations of bradykinin and plasma hyaluronan-binding protein-alpha2-antiplasmin complex as well as histone degradation
-
-
?
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
C1 esterase inhibitor
-
inhibits autoactivation at physiological concentrations
-
inhibitor C1
-
C1 inhibitor of the serpin family, forms a complex with the enzyme, 50% inhibition at 0.001 mg/ml
-
PPACK
-
potent serine protease inhibitor, inhibits autoactivation at physiological concentrations
alpha2-antiplasmin
-
potently inhibits amidolytic activity of FSAP, but no complex formation can be observed
-
Aprotinin
-
potent serine protease inhibitor, inhibits autoactivation at physiological concentrations
C1 inhibitor
-
potently inhibits amidolytic activity of FSAP, but no complex formation can be observed
-
KPI domain of amyloid-beta precursor protein
-
complete inhibition at 0.012 mg/ml
-
KPI domain of amyloid-beta precursor protein
-
complete inhibition at 0.012 mg/ml
-
KPI domain of amyloid-beta precursor protein
-
complete inhibition at 0.012 mg/ml
-
KPI domain of amyloid-beta precursor protein
-
complete inhibition at 0.012 mg/ml
-
plasminogen activator inhibitor-1
-
potently inhibits amidolytic activity of FSAP, FSAP-plasminogen activator inhibitor-1 complex formation. Residue Arg346 is a critical recognition element on plasminogen activator inhibitor-1 for interaction with FSAP. RNA, but not DNA, fragments (more than 400 nucleotides in length) dramatically enhance reactivity of plasminogen activator inhibitor-1 with FSAP. Reactivity can be also enhanced by vitronectin. Also antagonizes FSAP-driven inhibition of vascular smooth muscle cell proliferation
Protease nexin-1
-
inhibits FSAP enzymatic activity, which leads to the loss of the inhibitory effect of FSAP on platelet-derived growth factor-BB-mediated DNA synthesis and mitogen-activated protein kinase phosphorylation in vascular smooth-muscle cells. The FSAP-protease nexin-1 complex binds to the low-density lipoprotein receptor-related protein and is subsequently internalized. This binding is inhibited by receptor associated protein as well as heparin. The FSAP-inhibitor complexes are internalized via low-density lipoprotein receptor-related protein without influencing the platelet-derived growth factor-BB signal transduction pathway
-
additional information
-
alpha1-proteinase inhibitor and antithrombin III have no effect, no complex formation is observed
-
additional information
-
complex formation of FSAP with inhibitors results in rapid internalization of the complexes by low-density lipoprotein receptor-related protein via receptor-mediated endocytosis
-
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
histone
-
histones H1, H2A, H2B, H3, and H4 promote pro-plasma hyaluronan-binding protein autoactivation in vivo. Histones do not affect enzymatic activity of the active form of plasma hyaluronan-binding protein
hyaluronic acid
-
activates single-chain inactivate zymogen to the two-chain active enzyme
IL-8
-
can stimulate the expression of HABP mRNA in lung microvascular endothelial cells and in bronchial epithelial cells
-
LPS
-
stimulates FSAP mRNA expression 6fold after 1 h, reaching a plateau at 2 h (7fold stimulation) and gradually decreases until returning to the base level at 24 h
-
phosphatidylethanolamine
-
enhances autofragmentation and serine protease activity at 0.001 mg/ml and 0.00001 mg/ml
polyethylenimine
FSAP is exclusively activated by the positively charged surfaces polyethylenimine and poly-L-lysine
-
Dextran sulfate
-
strongly accelerates autoactivation, strongest acceleration at 0.02 mg/ml of 5-kDa-dextran sulfate
-
heparin
-
strongly accelerates autoactivation, optimum concentration: 5-10 U/ml, presence of 7.5 U/ml reduces the half-life of the proenzyme from 12 min to 3.5 min
heparin
-
activates single-chain inactivate zymogen to the two-chain active enzyme
poly-L-lysine
FSAP is exclusively activated by the positively charged surfaces polyethylenimine and poly-L-lysine
RNA
-
natural or artificial RNA is an effective cofactor for FSAP mediated platelet-derived growth factor-BB degradation, whereas the effect of DNA is weak
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.56
DL-pyroglutamic acid-cyclohexylglycine-Arg 4-nitroanilide
pH 8.2, 37°C
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
4.9
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
-
-
brenda
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
additional information
-
abundant in neointima and in arteriosclerotic carotid arteries, but not in normal arteries. Accumulation in unstable coronary atherosclerotic plaques with elevated RNA expression in patients with acute coronary syndromes
brenda
-
FSAP expression in stable and especially unstable coronary atherosclerotic lesions. FSAP mainly in inflammatory regions within the shoulders of the plaque surounding or located within the lipid core that is infiltrated by macrophages. Some FSAP present within fibrotic regions in the cap of the plaque. Tight colocalization of FSAP and uPA-presenting cells in all plaques. Colocalization also with CD11b/CD68. Also present in hypocellular- and lipid rich areas of atherosclerotic plaques in internal mammary arteries, absent from normal non-atherosclerotic arteries
brenda
-
IL-8 can stimulate the expression of HABP mRNA in lung microvascular endothelial cells and in bronchial epithelial cells
brenda
-
-
brenda
-
elevated protein and activity levels of HABP in the plasma and in the broncheoalveolar fluid of patients with acquired respiratory distress syndrome
brenda
additional information
-
absent from normal vessels, but abundant in unstable atherosclerotic plaques
brenda
additional information
-
plasminogen activator inhibitor-1-FSAP complexes in addition to high levels of extracellular RNA in bronchoalveolar lavage fluids from patients with acute respiratory distress syndrome
brenda
additional information
-
weak expression in dentritic cells, absent from vascular smooth muscle cells and HUVEC cells
brenda
additional information
analysis of the tissue distribution of enzyme mRNA, the enzyme is synthesized in hepatopancreas and carried to the muscle, kidney, heart and ovary via the bloodstream in the red sea bream
brenda
additional information
-
analysis of the tissue distribution of enzyme mRNA, the enzyme is synthesized in hepatopancreas and carried to the muscle, kidney, heart and ovary via the bloodstream in the red sea bream
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
additional information
additional information
the enzyme has a secretory signal sequence at the N-terminus
-
brenda
additional information
-
the enzyme has a secretory signal sequence at the N-terminus
-
brenda
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
the active site residues of a serine proteinase are conserved in the serine protease domain of the enzyme. The enzyme has a similar domain structure and tissue distribution to those of human hyaluronan binding protein 2 (HABP2), putative phylogenetic tree
malfunction
-
the variant Marburg I polymorphism results in low enzymatic activity and is associated with an enhanced risk of carotid stenosis and stroke
metabolism
FSAP is exclusively activated by the positively charged surfaces polyethylenimine and poly-L-lysine, not by the negatively charged glass or self-assembled monolayer with carboxyl group termination or uncharged (Teflon AF) surfaces. Activation is concomitant with coagulation. A contact phase inhibitor diminishes coagulation to background levels for all surfaces except polyethylenimine
physiological function
physiological function
-
factor VII-activating protease has potential effects on hemostasis
physiological function
-
the enzyme plays roles in regulating inflammation, vascular function, fibrosis and atherosclerosis
physiological function
-
the enzyme regulates hemostasis- and remodeling-associated processes in the vasculature
physiological function
the serine protease is possibly involved in the extracellular matrix turnover. It might be involved in the post-mortem fish muscle softening
physiological function
FSAP alters fibrin clot properties by fibrinogenolysis. Treatment of human fibrinogen with FSAP releases truncated fibrinogen which shows a delayed thrombin-catalyzed polymerization and forms fibrin clots of reduced turbidity. The clots reveal a less coarse fibrin network with thinner fibers and a smaller pore size. FSAP-treated fibrinogen or plasma exhibits a significantly faster tissue plasminogen activator-driven lysis, which correlates exclusively with cleavage of fibrinogen and not with activation of plasminogen activators
physiological function
HABP2 overexpression increases LMW-HA-induced urokinase plasminogen activator activation, migration, and extravasation in human lung adenocarcinoma cells. In vivo, overexpression of HABP2 in human lung adenocarcinoma cells increases primary tumor growth rates in nude mice by about 2fold and lung metastasis by about 10fold compared to vector control cells
physiological function
phorbol ester-mediated neutrophil extracellular trap (NET) formation is marginally stimulated by FSAP. Plasma-derived FSAP as well as exogenous FSAP binds to NET, and FSAP and NETs colocalize in coronary thrombi from patients with acute myocardial infarction. No activation of pro-FSAP by NETs is evident, but after disintegration of NETs with DNase, a robust activation of pro-FSAP, due to release of histones from nucleosomes, is detected. The released histones are in turn degraded by FSAP. Histone cytotoxicity towards endothelial cells is neutralized by FSAP more potently than by activated protein C
physiological function
upon stimulation of vascular smooth muscle cells (VSMC) and endothelial cells (EC) with FSAP, pathways significantly activated by FSAP include those related to inflammation, apoptosis and cell growth in VSMC and inflammation in EC. The key upregulated genes in VSMC are AREG, PTGS2 and IL6, and in EC these are SELE, VCAM1, and IL8. Secretion of IL6 in VSMC and IL8 in EC is also stimulated by FSAP. Recombinant wild type protease domain of FSAP, but not the Marburg I-isoform, can recapitulate most of these effects. In VSMC, but not EC, gene expression by FSAP is impaired by PAR1 (protease-activated receptor1) receptor antagonists
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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). Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
27000
30000
44000
50000
64000
70000
27000
-
1 * 50000 + 1 * 27000, active form after cleavage at Arg290 by autocatalytic action, subunits are linked by a disulfide bond
50000
-
1 * 50000 + 1 * 27000, active form after cleavage at Arg290 by autocatalytic action, subunits are linked by a disulfide bond
64000
-
metabolic labelling and immunoprecipitation under non reducing conditions
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
heterodimer
-
1 * 50000 + 1 * 27000, active form after cleavage at Arg290 by autocatalytic action, subunits are linked by a disulfide bond
additional information
additional information
the enzyme has a secretory signal sequence at the N-terminus, three epidermal growth factor-like domains, a kringle domain, and a trypsin-like serine protease domain
additional information
-
the enzyme has a secretory signal sequence at the N-terminus, three epidermal growth factor-like domains, a kringle domain, and a trypsin-like serine protease domain
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POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
glycoprotein
proteolytic modification
glycoprotein
-
only N-terminal portion is glycosylated, 3.5% carbohydrate content represented by N-glucosamine, N-galactosamine, galactose, mannose, glucose and fucose
proteolytic modification
-
autoactivation leads to the typical protease two-chain pattern and subsequent degradation products
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
E393Q
-
Marburg II single nucleotide polymorphism. Is not associated with altered enzymatic activity or any other changes in FSAP function
G511E
-
Marburg I mutant, underlies a polymorphism in the HABP2 gene, is found in 5-10% of the population. Is associated with an impaired pro-urikinase activation, and increased neointima formation correlated with reduced proteolysis of platlet derived growth factor-BB. The polymorphism is correlated with carotid stenosis and may contribute to the risk of venous thrombosis
G534E
additional information
G534E
-
Marburg I single nucleotide polymorphism. Has a 5fold lower enzymatic activity. Is a weak activator of pro-uPA, ability to activate factor VII is unchanged. Is strongly linked to late complications of carotid stenosis, direct role in atherosclerosis, risk factor for cardiovascular disease in general, may be also associated with venous thromboembolism
G534E
the naturally occurring G534E-variant exhibits reduced proteolytic activity
additional information
the DEGF-3 mutant shows diminished binding to and activation by heparin
additional information
-
the 1601GA genotype of the 1601 G/A polymorphism in the factor VII-activating protease gene expresses reduced levels of an alloenzyme with reduced pro-fibrinolytic activity. The relative increase in FSAP activity is significantly higher in women carrying the 1601GG genotype (63%) than in women carrying 1601GA genotype (50%) and is associated with an increased activation of factor VII
additional information
fusion of a modified TSG-6 Link module with mutationally inactivated heparin-binding sequence and the Fc portion of human IgG1 (TSG-6-DELTAHep-Fc)
additional information
-
fusion of a modified TSG-6 Link module with mutationally inactivated heparin-binding sequence and the Fc portion of human IgG1 (TSG-6-DELTAHep-Fc)
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TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
homogeneity
purification with 6M urea yields the single-chain zymogen, whereas native conditions yield the activated two-chain form
-
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
gene HABP2, from hepatopancreas, DNA and amino acid sequence determination and analysis, phylogenetic analysis
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
in late pregnancy the plasma FSAP antigen and activity is significantly higher compared with levels in non-pregnant women and remains elevated after delivery, plasma FSAP levels in women using oral contraceptives are also significantly elevated compared to the control group. FSAP mRNA levels are strongly induced by estradiol in monocytes but not in hepatocytes
-
oral contraceptive use with preparartions containing ethinylestradiol, levonorgestrel, desogestrel, gestodene, and norgestimate increases the plasma measures of factor VII-activating protease
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RENATURED/Commentary
ORGANISM
UNIPROT
LITERATURE
complete recovery of enzyme activity within 2 min of incubation at 1 M urea after denaturation in 6M urea
-
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
analysis
substrate Ala-Lys-Nle-Arg-7-amido-4-methylcoumarin can be used to measure FSAP activity in plasma
medicine
additional information
-
nucleic acids are cofactors for FSAP-mediated inhibition of platelet-derived growth factor-BB-induced cell proliferation and mitogen-activated protein kinase 44/42 phosphorylation in vascular smooth muscle cells. FSAP protects RNA from the actions of RNase
medicine
-
FSAP accumulation in coronary atherosclerotic lesions, is due to either local synthesis by monocytes/macrophages, or uptake from the plasma due to plaque hemorrhage. Higher expression of FSAP in unstable plaques may destabilize plaque through reducing vascular smooth muscle cell proliferation/migration and altering the hemostatic balance
medicine
-
plays a role in physiologic function of the pericellular environment of the vasculature. Proteolytically inactivates growth factors. May regulate angiogenic processes, like neovascularisation during tissue remodelling, wound repair or tumor progression. May contribute to extravascular fibrin deposition and inflammatory processes in the injured lung
medicine
-
proangiogenic potential of HABP, which, in combination with a profibrinolytic activity, directs the physiological function of this plasma protease to processes in which clot lysis, cell motility and neovascularisation are pivotal processes, e.g., in wound healing, tissue repair and tumour progession
medicine
-
role in atherosclerosis, contributes to vascular fibroproliferative inflammatory diseases in the context of pericellular proteolysis of the extracellular matrix, growth factor activity and haemostasis
medicine
the G534E variant of FSAP is a risk locus for chronic hepatitis C virus(HCV)-induced liver fibrosis and cirrhosis by determining platelet-derived growth factor BB (PDGF-BB)mediated hepatic stellate cell proliferation through a single amino acid substitution in FSAP. FSAP G534E might be useful for risk stratification in patients with HCV infection
medicine
FSAP measures are higher in women compared with age-matched men. The extent of coronary artery calcification in women is positively associated with total FSAP, but negatively associated with the specific activity of FSAP. No difference in FSAP measures is observed in men
medicine
FSAP-alpha2-antiplasmin complex levels are markedly elevated in patients with Gram-negative sepsis as compared with controls. The FSAP level increases by 16.82 AU/ml in patients with melioidosis after adjustment for the effect of diabetes melitus in the regression model. FSAP activation is correlated with nucleosome release. No difference in FSAP activation on admission is seen between survivors and non-survivors, but the extent of FSAP activation correlates with stage of the disease
medicine
HABP2 is an important regulator of lung cancer progression. HABP2 expression is increased in several subtypes of patient non-small cell lung cancer samples. HABP2 overexpression increases LMW-HA-induced urokinase plasminogen activator activation, migration, and extravasation in human lung adenocarcinoma cells. In vivo, overexpression of HABP2 in human lung adenocarcinoma cells increases primary tumor growth rates in nude mice by about 2fold and lung metastasis by about 10fold compared to vector control cells
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Etscheid, M.; Hunfeld, A.; Konig, H.; Seitz, R.; Dodt, J.
Activation of proPHBSP, the zymogen of a plasma hyaluronan binding serine protease, by an intermolecular autocatalytic mechanism
Biol. Chem.
381
1223-1231
2000
Homo sapiens
brenda
Romisch, J.
Factor VII activating protease (FSAP): a novel protease in hemostasis
Biol. Chem.
383
1119-1124
2002
Homo sapiens
brenda
Etscheid, M.; Beer, N.; Fink, E.; Seitz, R.; Johannes, D.
The hyaluronan-binding serine protease from human plasma cleaves HMW and LMW kininogen and releases bradykinin
Biol. Chem.
383
1633-1643
2002
Homo sapiens
brenda
Choi-Miura, N.H.; Yoda, M.; Saito, K.; Takahashi, K.; Tomita, M.
Identification of the substrates for plasma hyaluronan binding protein
Biol. Pharm. Bull.
24
140-143
2001
Homo sapiens
brenda
Choi-Miura, N.H.; Saito, K.; Takahashi, K.; Yoda, M.; Tomita, M.
Regulation mechanism of the serine protease activity of plasma hyaluronan binding protein
Biol. Pharm. Bull.
24
221-225
2001
Homo sapiens
brenda
Choi-Miura, N.H.; Takahashi, K.; Yoda, M.; Saito, K.; Mazda, T.; Tomita, M.
Proteolytic activation and inactivation of the serine protease activity of plasma hyaluronan binding protein
Biol. Pharm. Bull.
24
448-452
2001
Homo sapiens
brenda
Kannemeier, C.; Feussner, A.; Stohr, H.A.; Weisse, J.; Preissner, K.T.; Romisch, J.
Factor VII and single-chain plasminogen activator-activating protease: activation and autoactivation of the proenzyme
Eur. J. Biochem.
268
3789-3796
2001
Homo sapiens
brenda
Hunfeld, A.; Etscheid, M.; Konig, H.; Seitz, R.; Dodt, J.
Detection of a novel plasma serine protease during purification of vitamin K-dependent coagulation factors
FEBS Lett.
456
290-294
1999
Homo sapiens (Q14520), Homo sapiens
brenda
Vostrov, A.A.; Quitschke, W.W.
Plasma hyaluronan-binding protein is a serine protease
J. Biol. Chem.
275
22978-22985
2000
Bos taurus, Oryctolagus cuniculus, Equus sp., Homo sapiens
brenda
Etscheid, M.; Beer, N.; Dodt, J.
The hyaluronan-binding protease upregulates ERK1/2 and PI3K/Akt signalling pathways in fibroblasts and stimulates cell proliferation and migration
Cell. Signal.
17
1486-1494
2005
Homo sapiens
brenda
Choi-Miura, N.H.
Novel human plasma proteins, IHRP (acute phase protein) and PHBP (serine protease), which bind to glycosaminoglycans
Curr. Med. Chem. Cardiovasc. Hematol. Agents
2
239-248
2004
Homo sapiens
brenda
Parahuleva, M.S.; Kanse, S.M.; Parviz, B.; Barth, A.; Tillmanns, H.; Bohle, R.M.; Sedding, D.G.; Hoelschermann, H.
Factor Seven Activating Protease (FSAP) expression in human monocytes and accumulation in unstable coronary atherosclerotic plaques
Atherosclerosis
196
164-171
2008
Homo sapiens
brenda
Muhl, L.; Nykjaer, A.; Wygrecka, M.; Monard, D.; Preissner, K.T.; Kanse, S.M.
Inhibition of PDGF-BB by Factor VII-activating protease (FSAP) is neutralized by protease nexin-1, and the FSAP-inhibitor complexes are internalized via LRP
Biochem. J.
404
191-196
2007
Homo sapiens
brenda
Shibamiya, A.; Muhl, L.; Tannert-Otto, S.; Preissner, K.T.; Kanse, S.M.
Nucleic acids potentiate Factor VII-activating protease (FSAP)-mediated cleavage of platelet-derived growth factor-BB and inhibition of vascular smooth muscle cell proliferation
Biochem. J.
404
45-50
2007
Homo sapiens
brenda
Kress, J.A.; Seitz, R.; Dodt, J.; Etscheid, M.
Induction of intracellular signalling in human endothelial cells by the hyaluronan-binding protease involves two distinct pathways
Biol. Chem.
387
1275-1283
2006
Homo sapiens
brenda
Etscheid, M.; Kress, J.; Seitz, R.; Dodt, J.
The hyaluronic acid-binding protease: a novel vascular and inflammatory mediator?
Int. Immunopharmacol.
8
166-170
2008
Homo sapiens
brenda
Wygrecka, M.; Morty, R.E.; Markart, P.; Kanse, S.M.; Andreasen, P.A.; Wind, T.; Guenther, A.; Preissner, K.T.
Plasminogen activator inhibitor-1 is an inhibitor of factor VII-activating protease in patients with acute respiratory distress syndrome
J. Biol. Chem.
282
21671-21682
2007
Homo sapiens
brenda
Kanse, S.M.; Parahuleva, M.; Muhl, L.; Kemkes-Matthes, B.; Sedding, D.; Preissner, K.T.
Factor VII-activating protease (FSAP): vascular functions and role in atherosclerosis
Thromb. Haemost.
99
286-289
2008
Homo sapiens
brenda
Stephan, S.; Schwarz, H.; Borchert, A.; Bussfeld, D.; Quak, E.; Simshaeuser-Knaub, B.; Teigelkamp, S.; Behrens, F.; Vitzthum, F.
Tests for the measurement of factor VII-activating protease (FSAP) activity and antigen levels in citrated plasma, their correlation to PCR testing, and utility for the detection of the Marburg I-polymorphism of FSAP
Clin. Chem. Lab. Med.
46
1109-1116
2008
Homo sapiens (Q14520)
brenda
Muhl, L.; Hersemeyer, K.; Preissner, K.T.; Weimer, T.; Kanse, S.M.
Structure-function analysis of factor VII activating protease (FSAP): sequence determinants for heparin binding and cellular functions
FEBS Lett.
583
1994-1998
2009
Homo sapiens (Q14520)
brenda
Wasmuth, H.E.; Tag, C.G.; Van de Leur, E.; Hellerbrand, C.; Mueller, T.; Berg, T.; Puhl, G.; Neuhaus, P.; Samuel, D.; Trautwein, C.; Kanse, S.M.; Weiskirchen, R.
The Marburg I variant (G534E) of the factor VII-activating protease determines liver fibrosis in hepatitis C infection by reduced proteolysis of platelet-derived growth factor BB
Hepatology
49
775-780
2009
Homo sapiens (Q14520), Homo sapiens
brenda
Parahuleva, M.S.; Hoelschermann, H.; Erdogan, A.; Langanke, E.; Prickartz, I.; Parviz, B.; Weiskirchen, R.; Tillmanns, H.; Kanse, S.M.
Factor Seven Activating Protease (FSAP) levels during normal pregnancy and in women using oral contraceptives
Thromb. Res.
126
e36-e40
2010
Homo sapiens
brenda
Kanse, S.M.; Declerck, P.J.; Ruf, W.; Broze, G.; Etscheid, M.
Factor VII-activating protease promotes the proteolysis and inhibition of tissue factor pathway inhibitor
Arterioscler. Thromb. Vasc. Biol.
32
427-433
2012
Homo sapiens
brenda
Yamamichi, S.; Fujiwara, Y.; Kikuchi, T.; Nishitani, M.; Matsushita, Y.; Hasumi, K.
Extracellular histone induces plasma hyaluronan-binding protein (factor VII activating protease) activation in vivo
Biochem. Biophys. Res. Commun.
409
483-488
2011
Mus musculus
brenda
Yamamoto, E.; Nishimura, N.; Okada, K.; Sekido, C.; Yamamichi, S.; Hasumi, K.
Inhibitors of autoactivation of plasma hyaluronan-binding protein (factor VII activating protease)
Biol. Pharm. Bull.
34
462-470
2011
Homo sapiens
brenda
Sidelmann, J.J.; Skouby, S.O.; Kluft, C.; Winkler, U.; Vitzthum, F.; Schwarz, H.; Gram, J.; Jespersen, J.
Plasma factor VII-activating protease is increased by oral contraceptives and induces factor VII activation in-vivo
Thromb. Res.
128
e67-e72
2011
Homo sapiens
brenda
Yoshida, A.; Wang, Y.; Bae, I.; Cao, M.J.; Osatomi, K.; Hara, K.
Molecular cloning and tissue distribution of hyaluronan binding protein 2 (HABP2) in red sea bream Pagrus major
Comp. Biochem. Physiol. B
165
271-276
2013
Pagrus major (S6B5D3), Pagrus major
brenda
Sperling, C.; Maitz, M.F.; Grasso, S.; Werner, C.; Kanse, S.M.
A positively charged surface triggers coagulation activation through factor VII activating protease (FSAP)
ACS Appl. Mater. Interfaces
9
40107-40116
2017
Homo sapiens (Q14520)
brenda
Byskov, K.; Boettger, T.; Ruehle, P.F.; Nielsen, N.V.; Etscheid, M.; Kanse, S.M.
Factor VII activating protease (FSAP) regulates the expression of inflammatory genes in vascular smooth muscle and endothelial cells
Atherosclerosis
265
133-139
2017
Homo sapiens (Q14520), Homo sapiens
brenda
Etscheid, M.; Subramaniam, S.; Lochnit, G.; Zabczyk, M.; Undas, A.; Lang, I.M.; Hanschmann, K.M.; Kanse, S.M.
Altered structure and function of fibrinogen after cleavage by Factor VII Activating Protease (FSAP)
Biochim. Biophys. Acta Mol. Basis Dis.
1864
3397-3406
2018
Homo sapiens (Q14520), Homo sapiens
brenda
Ramanathan, R.; Gram, J.B.; Sand, N.P.R.; Norgaard, B.L.; Diederichsen, A.C.P.; Vitzthum, F.; Schwarz, H.; Sidelmann, J.J.
Factor VII-activating protease sex-related association with coronary artery calcification
Blood Coagul. Fibrinolysis
28
558-563
2017
Homo sapiens (Q14520), Homo sapiens
brenda
Mirzapoiazova, T.; Mambetsariev, N.; Lennon, F.E.; Mambetsariev, B.; Berlind, J.E.; Salgia, R.; Singleton, P.A.
HABP2 is a novel regulator of hyaluronan-mediated human lung cancer progression
Front. Oncol.
5
164
2015
Homo sapiens (Q14520), Homo sapiens
brenda
de Jong, H.K.; Koh, G.C.; Bulder, I.; Stephan, F.; Wiersinga, W.J.; Zeerleder, S.S.
Diabetes-independent increase of factor VII-activating protease activation in patients with Gram-negative sepsis (melioidosis)
J. Thromb. Haemost.
13
41-6
2015
Homo sapiens (Q14520)
brenda
Kara, E.; Manna, D.; Loeset, G..; Schneider, E.L.; Craik, C.S; Kanse, S.
Analysis of the substrate specificity of Factor VII activating protease (FSAP) and design of specific and sensitive peptide substrates
Thromb. Haemost.
117
1750-1760
2017
Homo sapiens (Q14520)
brenda
Grasso, S.; Neumann, A.; Lang, I.M.; Etscheid, M.; von Kckritz-Blickwede, M.; Kanse, S.M.
Interaction of factor VII activating protease (FSAP) with neutrophil extracellular traps (NETs)
Thromb. Res.
161
36-42
2018
Homo sapiens (Q14520), Homo sapiens
brenda
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