Information on EC 3.4.24.B11 - ADAMTS1 endopeptidase

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The expected taxonomic range for this enzyme is: Tetrapoda

EC NUMBER
COMMENTARY hide
3.4.24.B11
preliminary BRENDA-supplied EC number
RECOMMENDED NAME
GeneOntology No.
ADAMTS1 endopeptidase
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REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
proteolytic degradation of proteins
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of peptide bond
CAS REGISTRY NUMBER
COMMENTARY hide
241475-68-3
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
UniProt
Manually annotated by BRENDA team
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-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
-
silencing of Adamts1 blocks the adverse effects of ethanol on collagen and elastin levels
metabolism
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the enzyme is controlled by the FoxO1-sestrin 3-AMP-activated protein kinase signaling cascade and regulates ethanol-induced changes in collagen I and elastin levels
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
aggrecan + H2O
11 aggrecan fragment
show the reaction diagram
several cleavage sites are determined
product determination, overview
?
aggrecan + H2O
2 aggrecan fragment
show the reaction diagram
-
cleavage site is Glu373-Ala374
-
?
aggrecan + H2O
?
show the reaction diagram
alpha2-macroglobulin + H2O
?
show the reaction diagram
-
cleavage of the bait region of alpha2-macroglobulin, complex formation with alpha2-macroglobulin is dependent on the proteolytic activity
-
?
brevican + H2O
?
show the reaction diagram
Collagen type I + H2O
?
show the reaction diagram
-
-
-
-
?
desmocollin-3 + H2O
?
show the reaction diagram
-
-
-
-
?
dystroglycan 1 + H2O
?
show the reaction diagram
-
-
-
-
?
Mac-2-binding protein + H2O
?
show the reaction diagram
-
-
-
-
?
nidogen-1 + H2O
?
show the reaction diagram
-
-
-
-
?
nidogen-2 + H2O
?
show the reaction diagram
-
-
-
-
?
peptide fragments of aggrecan + H2O
?
show the reaction diagram
-
peptide sequences contain the cleavage site of aggrecan at E373-A374
-
?
proteins + H2O
peptides
show the reaction diagram
syndecan-4 + H2O
?
show the reaction diagram
thrombospondin 1 + H2O
?
show the reaction diagram
-
cleavage site...TEENRELVSE/LKRPPL...
-
-
?
thrombospondin-1 + H2O
36000 Da fragment + 110000 Da fragment
show the reaction diagram
-
-
-
-
?
thrombospondin-2 + H2O
42000 Da fragment + 30000 Da fragment
show the reaction diagram
-
-
-
-
?
tissue factor pathway inhibitor-2 + H2O
?
show the reaction diagram
-
-
-
-
?
Type I collagen + H2O
?
show the reaction diagram
-
-
-
-
?
versican + H2O
?
show the reaction diagram
versican + H2O
DPEAAE + ?
show the reaction diagram
-
ADAMTS-1 cleaves versican at the Glu441-Ala442 bond to generate a 70000 Da fragment termed DPEAAE
-
-
?
versican isoform V0 + H2O
2 peptides
show the reaction diagram
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a second cleavage site might be Glu405-Gln406, cleavage site is Glu1428-Ala1429 in the V0 isoform, activity with recombinant and native human substrate protein
product identification
?
versican isoform V1 + H2O
2 peptides
show the reaction diagram
-
a second cleavage site might be Glu405-Gln406, cleavage site is Glu441-Ala442 in the V1 isoform, activity with recombinant and native human substrate protein
product identification
?
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
aggrecan + H2O
?
show the reaction diagram
Collagen type I + H2O
?
show the reaction diagram
-
-
-
-
?
proteins + H2O
peptides
show the reaction diagram
syndecan-4 + H2O
?
show the reaction diagram
-
ADAMTS1 cleaves the ectodomain of syndecan-4. The shedding of syndecan-4 by ADAMTS1 disrupts cell adhesion and promotes cell migration
-
-
?
versican + H2O
DPEAAE + ?
show the reaction diagram
-
ADAMTS-1 cleaves versican at the Glu441-Ala442 bond to generate a 70000 Da fragment termed DPEAAE
-
-
?
additional information
?
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Ca2+
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contains a Ca2+-binding site
additional information
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1,10-phenanthroline
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complete inhibition
Brg1 protein
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repressess ADAMTS1 expression
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catechin gallate esters
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from green tea Camellia sinensis, strong inhibition, independent of Zn2+, reversible
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doxycycline
-
partial inhibition
GM6001
-
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heparin
Interleukin-1beta
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0.1-10 ng/ml, transcriptional downregulation
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marimastat
-
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matrix metalloprotease inhibitor BB94
-
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matrix metalloprotease inhibitor I
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partial inhibition
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matrix metalloprotease inhibitor TIMP2
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slight inhibition
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matrix metalloprotease inhibitor TIMP3
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slight inhibition
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Phenanthroline
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inhibition of complex formation with alpha2-macroglobulin
TIMP3
-
-
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tissue inhibitor of metalloproteinases-3
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additional information
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
cytokine
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stimulation of gene expression in colon carcinoma cell line
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fibronectin
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2fold enhancement of activity
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fibulin-1
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4fold enhancement of activity with 0.001 mg at 1:1, 1:2, and 1:3 molar ratio in 50 mM Tris, pH 7.4, 10 mM CaCl2, 80 mM NaCl overnight at 37 °C
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interleukin-1
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stimulation of gene expression in colon carcinoma cell line
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MMP-15
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activates ADAMTS-1
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additional information
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
140
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partially purified recombinant enzyme
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.5
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assay at
8
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assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
-
Manually annotated by BRENDA team
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humans with osteoarthritis
Manually annotated by BRENDA team
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embryonic presumptive ectoderm, Spemann organizer region, trunk organizer region and posterior ectoderm
Manually annotated by BRENDA team
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basal lamina of epithelium of intestine, nasal cavity, choroids plexus, skin and intracellular storage vesicles
Manually annotated by BRENDA team
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tissue containing a 62 kDa fragment of ADAMTS-1
Manually annotated by BRENDA team
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tissue containing a 62 kDa fragment of ADAMTS-1
Manually annotated by BRENDA team
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metastatic lymph node
Manually annotated by BRENDA team
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prostate stromal cell
Manually annotated by BRENDA team
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low expression level
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
associated
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
62000
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SDS-PAGE, fragment of ADAMTS-1
65000
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major mature enzyme, SDS-PAGE
67000
x * 67000, recombinant processed form 2, SDS-PAGE, x * 85000, recombinant processed form 1, SDS-PAGE, x * 110000, recombinant unprocessed enzyme, SDS-PAGE
85000
x * 67000, recombinant processed form 2, SDS-PAGE, x * 85000, recombinant processed form 1, SDS-PAGE, x * 110000, recombinant unprocessed enzyme, SDS-PAGE
89000
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x * 89000, recombinant mature enzyme, SDS-PAGE
95000
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SDS-PAGE
110000
115000
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
proteolytic modification
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
in complex with marimastat, sitting drop vapour diffusion method with 0.2-0.6 M sodium acetate, 0.05 M cadmium sulfate, 0.1 M HEPES (pH 7.0), and 12-22% glycerol
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
CNBr-activated CL-4B-Sepharose affinity chromatography
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Hi-trap heparin-sepharose column chromatography and Nickel-chelating chromatography
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Ni-NTA Superflow column chromatography, Ni-NTA resin column chromatography, and Superdex 75 gel filtration
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Ni2+-probond and anti-v5 antibody-conjugated affinity column chromatography
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partially, recombinant His-tagged enzyme from insect cells, 200fold
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recombinant enzyme from cell line 293T
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recombinant His-tagged enzyme from Escherichia coli strain BL21
recombinant His-tagged wild-type and mutants
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recombinant Myc-His-tagged enzyme from cell line 293T
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
3'-untranslated region
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adamts-1 gene maps to chromosome 16, region C3-C5, transient expression in COS-7 cells of FLAG-tagged wild-type and deletion mutants and mutant E386Q
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DNA and amino acid sequence determination and analysis, in itro translation, expression as His-tagged protein in Escherichia coli strain BL21
expressed in 293-T cells
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expressed in High-FiveTM insect cells with pIB/V5-His insect cell expression vector
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expressed in HUVEC cells
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expressed in MCF7TetOff neo cells
expressed in Saccharomyces cerevisiae
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expressed in Saccharomyces cerevisiae strain CG-1945
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expressed in SaOS-2 cells
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expressed in Sf21 insect cells
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expression as Myc-His-tagged wild-type and truncated mutant in 293T cell line
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expression in CHO cells
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expression of full-length wild-type enzyme in human embryonic kidney cell line 293T, expression of C-terminal region of the enzyme, corresponding to amino acid residues 549-951, in breast tumor derived cell line T47D
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expression of His-Myc-tagged wild-type enzyme and tagged mutant E385A, as well as truncated construct comprising the amino acid residues 549-951, in the carcinoma cell line T47D
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expression of His-tagged enzyme in insect cells via baculovirus infection
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for overexpression experiments
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transient expression in HEK293 cells of FLAG- and His-tagged wild-type and deletion mutants, the majority of the recombinant protein is expressed in an active form without the proprotein domain
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
ADAMTS-1 mRNA expression is strongly, indirectly and progressively upregulated over the period of 30 min to 16 h by vascular endothelial growth factor A
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elevated ADAMTS1 expression in endometrial adenocarcinoma, PGF2alpha-FP signalling upregulates ADAMTS1 expression via a calmodulin-NFAT-dependent pathway
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in aggressive and highly plastic melanoma and Ewing sarcoma cells
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incubation of myocytes with ethanol increases Adamt1 mRNA without changing the overall level of Adamts1 protein
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luteinizing hormone/human chorionic gonadotropin (LH/hCG)-induced gene, follicle-size dependent; luteinizing hormone/human chorionic gonadotropin (LH/hCG)-induced gene, follicle-size dependent
mRNA expression is increased by forskolin and overexpression of the catalytic subunit of protein kinase A,. Furthermore, treatment with a soluble epidermal growth factor induces mRNA expression in granulosa cells. The enzyme expression is increased at 6 to 24 hours after human chorionic gonadotropin in granulosa cells
overexpression promotes bone metastasis
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transiently expressed in the infarcted heart, when stimulated with tissue necrosis factor, the expression level of mRNA rapidly increases
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upregulated in endothelial cells by shear stress
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine