Information on EC 3.4.24.79 - pappalysin-1

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The expected taxonomic range for this enzyme is: Bilateria

EC NUMBER
COMMENTARY hide
3.4.24.79
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RECOMMENDED NAME
GeneOntology No.
pappalysin-1
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REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
Cleavage of the Met135-/-Lys bond in insulin-like growth factor binding protein (IGFBP)-4, and the Ser143-/-Lys bond in IGFBP-5
show the reaction diagram
CAS REGISTRY NUMBER
COMMENTARY hide
151662-33-8
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
-
-
Manually annotated by BRENDA team
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-
-
Manually annotated by BRENDA team
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-
-
Manually annotated by BRENDA team
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-
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Manually annotated by BRENDA team
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-
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Manually annotated by BRENDA team
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-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
physiological function
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
IGF-binding protein-2 + H2O
?
show the reaction diagram
IGF-binding protein-4 + H2O
?
show the reaction diagram
IGF-binding protein-5 + H2O
?
show the reaction diagram
inhibitory insulin-like growth factor binding protein-4 + H2O
?
show the reaction diagram
-
-
-
-
?
insulin-like growth factor binding protein + H2O
?
show the reaction diagram
-
-
-
-
?
insulin-like growth factor binding protein-4 + H2O
?
show the reaction diagram
insulin-like growth factor binding protein-5 + H2O
?
show the reaction diagram
insulin-like growth factor-binding protein-2 + H2O
?
show the reaction diagram
-
-
-
-
?
insulin-like growth factor-binding protein-4 + H2O
?
show the reaction diagram
-
-
-
-
?
insulin-like growth factor-binding protein-5 + H2O
?
show the reaction diagram
-
-
-
-
?
additional information
?
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NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
IGF-binding protein-2 + H2O
?
show the reaction diagram
-
-
-
-
?
IGF-binding protein-4 + H2O
?
show the reaction diagram
IGF-binding protein-5 + H2O
?
show the reaction diagram
inhibitory insulin-like growth factor binding protein-4 + H2O
?
show the reaction diagram
-
-
-
-
?
insulin-like growth factor binding protein + H2O
?
show the reaction diagram
-
-
-
-
?
insulin-like growth factor binding protein-4 + H2O
?
show the reaction diagram
insulin-like growth factor-binding protein-2 + H2O
?
show the reaction diagram
-
-
-
-
?
insulin-like growth factor-binding protein-4 + H2O
?
show the reaction diagram
-
-
-
-
?
insulin-like growth factor-binding protein-5 + H2O
?
show the reaction diagram
-
-
-
-
?
additional information
?
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1,10-phenanthroline
3,4-dichloroisocoumarin
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alpha1-Antichymotrypsin
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potent inhibitor
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beta-mercaptoethanol
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beta-phorbol-12,13-didecanoate
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100 nM, time-dependent inhibition, possibly through induction of pro-eosinophil major basic protein
EGTA
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5 mM
heparin
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up to 60% inhibition
IGF-I
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the rate of IGFBP-4 proteolysis is dramatically increased upon addition of IGF-I or -II with IGF-II being more potent than IGF-I, while IGFBP-5 cleavage is slightly inhibited, overview
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IGF-II
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the rate of IGFBP-4 proteolysis is dramatically increased upon addition of IGF-I or -II with IGF-II being more potent than IGF-I, while IGFBP-5 cleavage is slightly inhibited, overview
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PAC1
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specific monoclonal antibody inhibiting PAPP-A activity against IGFBP-4, only slight inhibition of IGFBP-5 proteolysis
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pro-eosinophil major basic protein
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physiological inhibitor
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proform of eosinophil major basic protein
additional information
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
IGF-I
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the rate of IGFBP-4 proteolysis is dramatically increased upon addition of IGF-I or -II with IGF-II being more potent than IGF-I, while IGFBP-5 cleavage is slightly inhibited, the mechanism of IGF-modulated proteolysis of IGFBP-4 and -5 involves changes in both the recognition of substrate and the turnover rate, overview
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IGF-II
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the rate of IGFBP-4 proteolysis is dramatically increased upon addition of IGF-I or -II with IGF-II being more potent than IGF-I, while IGFBP-5 cleavage is slightly inhibited, the mechanism of IGF-modulated proteolysis of IGFBP-4 and -5 involves changes in both the recognition of substrate and the turnover rate, overview
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additional information
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00045 - 0.00163
IGFBP-4
0.00031 - 0.00064
IGFBP-5
additional information
additional information
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.64 - 0.89
IGFBP-4
0.31 - 0.75
IGFBP-5
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0000012
PAC1 antibody
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pH 7.5, 37C, inhibition of PAPP-A
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.4
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assay at
7.5
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assay at
7.6
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assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
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the enzyme is extracted from plaque tissue samples of endarterectomy and aneurysm patients
Manually annotated by BRENDA team
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Manually annotated by BRENDA team
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of bone fracture in the mid-shaft
Manually annotated by BRENDA team
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enzyme expression during follicular development and in cell culture
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
additional information
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the PAPP-A-proMBP complex is formed at the cell surface in vivo rather than in the circulation, the redox potential of the tissue microenvironment controls the process, chondroitin or dermatan sulfate do not have any effect on complex formation
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Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
400000
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
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x * 400000, SDS-PAGE
additional information
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primary sequence, structure motifs, and domain structure and function, the first 350 amino acid residues comprise the proteolytic domain, overview
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
glycoprotein
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proteolytic modification
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the enzyme performs autocatalytic cleavage
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
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10 min, no loss of activity
55
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10 min, no loss of activity
70 - 95
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10 min, complete inactivation
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
half-life of circulating PAPP-A and proMBP in complex is severalfold higher than both of the uncomplexed proteins
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high salt condition, SDS, or beta-mercaptoethanol inhibit
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Triton X-100, Tween-20, NP-40, sodium azide, glycerol do not affect enzyme activity
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-30C, 1 year, no loss of activity
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4C, 3 days, no loss of activity
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
recombinant His-tagged wild-type and mutant chimeric PAPP-A and PAPP-A2 from HEK-293T cells
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recombinant His6-tagged PAPP-A laminin G domain from Escherichia coli by nickel affinity chromatography
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recombinant PAPP-A wild-type and mutant E483A from HEK-293T cells by immunoaffinity chromatography
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
DNA and amino acid sequence determination and anaylsis, sequence comparisons
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expressed in mouse arterial smooth muscle cells
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expressed in SKOV-3 cells
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expression of His-tagged wild-type and mutant chimeric PAPP-A and PAPP-A2 in HEK-293T cells
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expression of PAPP-A wild-type and mutant E483A in HEK-293T cells, co-expression with inhibitor proMBP
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expression of the enzyme in transgenic mice, expression of FLAG-tagged enzyme in primary mouse osteoblasts
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expression of the His6-tagged PAPP-A laminin G domain in Escherichia coli, expression of wild-type andtruncation mutant enzymes, comparising residues 1-310, in HEK293T cells
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overexpression in transgenic mice heart, brain, liver, kidney, forearm, and spleen, expression analysis, overview
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
after intravenous unfractionated heparin and low molecular weight heparin free PAPP-A increases significantly (85 to 310fold from baseline)
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enzyme concentrations are reduced in the first trimester of pregnancies affected by fetal Down's syndrome. interferon-gamma decreases enzyme expression in human fibroblasts
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enzyme expression in cultured human dermal fibroblasts, human coronary artery endothelial, osteoblasts, and smooth muscle cells is stimulated by tumor necrosis factor-alpha, interleukin-1beta, interleukin-4, and transforming growth factor-beta. Enzyme expression is upregulated in response to acute injury. Gene expression is induced by forskolin and prostaglandin E2 in human osteoblasts, by bone morphogenic protein-2 in human mesenchymal stem cells, and by follicle-stimulating hormone in bovine granulosa cells in culture
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injection of heparin (5000 IU) elicits increase in enzyme concentrations
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
E483A
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a proteolytically inactive PAPP-A mutant
additional information
Renatured/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
microdialysis against water reverses high salt inhibition
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readdition of 5 mM Ca2+, but not of 0.1 mM Zn2+, restores EDTA-treated enzyme
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
diagnostics
medicine
molecular biology