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Information on EC 3.4.24.82 - ADAMTS-4 endopeptidase and Organism(s) Mus musculus and UniProt Accession Q8BNJ2

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EC Tree
     3 Hydrolases
         3.4 Acting on peptide bonds (peptidases)
             3.4.24 Metalloendopeptidases
                3.4.24.82 ADAMTS-4 endopeptidase
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This record set is specific for:
Mus musculus
UNIPROT: Q8BNJ2 not found.
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The taxonomic range for the selected organisms is: Mus musculus
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
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Glutamyl endopeptidase; bonds cleaved include -Thr-Glu-Gly-Glu373-/-Ala-Arg-Gly-Ser- in the interglobular domain of mammalian aggrecan
Synonyms
adamts-4, adamts4, adamts-1, aggrecanase-1, aggrecanase 1, adamts 4, agg-1, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
a disintegrin and metalloproteinase with thrombospondin motifs 4
-
a disintegrin-like and metalloproteinase with thrombospondin motifs-4
-
aggrecanase-1
-
a disintegrin and metalloproteinase with thrombospondin motifs-4
-
-
ADAMTS 4
-
-
ADAMTS-4
-
-
ADAMTS4
-
-
aggrecanase 1
-
-
aggrecanase-1
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of peptide bond
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY hide
147172-61-0
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
amyloid beta 1-38 peptide + H2O
amyloid beta 4-38 fragment + amyloid beta 12-38 fragment + ?
show the reaction diagram
the enzyme cleaves after Glu4 and Glu12
-
-
?
amyloid beta 1-40 peptide + H2O
amyloid beta 4-40 fragment + amyloid beta 12-40 fragment
show the reaction diagram
the enzyme cleaves after Glu4 and Glu12
-
-
?
amyloid beta 1-42 peptide + H2O
amyloid beta 4-42 fragment + amyloid beta 12-42 fragment + ?
show the reaction diagram
the enzyme cleaves after Glu4 and Glu12
-
-
?
poly-ADP ribose polymerase-1 + H2O
?
show the reaction diagram
-
-
-
?
versican + H2O
?
show the reaction diagram
-
-
-
?
aggrecan + H2O
?
show the reaction diagram
-
40 microg
-
-
?
aggrecan + H2O
fragments of aggrecan
show the reaction diagram
hevin + H2O
?
show the reaction diagram
-
digestion of hevin by ADAMTS4 in vitro produces fragments similar to those present in brain lysates. The proteolysis liberates a hevin peptide, termed SPARC-like fragment, with significant homology to SPARC (secreted protein acidic and rich in cysteine)
-
-
?
K(6-(fluorescein-5-carboxamido)-hexanoic acid)-DVQEFRGVTAVIR-C(QSY9)-KGK + H2O
C(QSY9) + KGK + K(6-(fluorescein-5-carboxamido)-hexanoic acid)-DVQEFRGVTAVIR
show the reaction diagram
-
-
-
-
?
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
amyloid beta 1-38 peptide + H2O
amyloid beta 4-38 fragment + amyloid beta 12-38 fragment + ?
show the reaction diagram
the enzyme cleaves after Glu4 and Glu12
-
-
?
amyloid beta 1-40 peptide + H2O
amyloid beta 4-40 fragment + amyloid beta 12-40 fragment
show the reaction diagram
the enzyme cleaves after Glu4 and Glu12
-
-
?
amyloid beta 1-42 peptide + H2O
amyloid beta 4-42 fragment + amyloid beta 12-42 fragment + ?
show the reaction diagram
the enzyme cleaves after Glu4 and Glu12
-
-
?
poly-ADP ribose polymerase-1 + H2O
?
show the reaction diagram
-
-
-
?
versican + H2O
?
show the reaction diagram
-
-
-
?
aggrecan + H2O
fragments of aggrecan
show the reaction diagram
-
cleavage at the Glu373-Ala374 site
-
-
?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(R)-2-(3-fluoro-4'-((5-oxo-5,6,7,8-tetrahydronaphthalen-2-yloxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
-
(R)-2-(4'-((2,8-bis(trifluoromethyl)quinolin-4-yloxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
-
(R)-2-(4'-((3-(dimethylamino)phenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
-
(R)-2-(4'-((3-acetylphenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
-
(R)-2-(4'-((3-benzoylphenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
-
(R)-2-(4'-((3-fluorophenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
-
(R)-2-(4'-((3-hydroxyphenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
-
(R)-2-(4'-((3-methoxyphenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
-
(R)-2-(4'-((4-(4-fluorobenzoyl)phenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
-
(R)-2-(4'-((4-(cyclohexanecarbonyl)phenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
-
(R)-2-(4'-((4-(tert-butoxycarbonylamino)phenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
-
(R)-2-(4'-((4-acetylphenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
-
(R)-2-(4'-((4-fluorophenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
-
(R)-2-(4'-((4-isobutyrylphenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
-
(R)-2-(4'-((4-methoxyphenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
-
(R)-3-methyl-2-(4'-((3-methylquinolin-2-yloxy)methyl)biphenyl-4-ylsulfonamido)butanoic acid
-
(R)-3-methyl-2-(4'-((4-(6-methylpyridin-2-yloxy)phenoxy)methyl)biphenyl-4-ylsulfonamido)butanoic acid
-
(R)-3-methyl-2-(4'-((4-(morpholine-4-carbonyl)phenoxy)methyl)biphenyl-4-ylsulfonamido)butanoic acid
-
(R)-3-methyl-2-(4'-((4-(morpholinomethyl)phenoxy)methyl)biphenyl-4-ylsulfonamido)butanoic acid
-
(R)-3-methyl-2-(4'-((4-(pyridin-2-yloxy)phenoxy)methyl)biphenyl-4-ylsulfonamido)butanoic acid
-
(R)-3-methyl-2-(4'-((4-(pyrrolidine-1-carbonyl)phenoxy)methyl)biphenyl-4-ylsulfonamido)butanoic acid
-
(R)-3-methyl-2-(4'-((4-phenoxyphenoxy)methyl)biphenyl-4-ylsulfonamido)butanoic acid
-
(R)-3-methyl-2-(4'-((5-(trifluoromethyl)pyridin-2-yloxy)methyl)biphenyl-4-ylsulfonamido)butanoic acid
-
(R)-3-methyl-2-(4'-((5-oxo-5,6,7,8-tetrahydronaphthalen-2-yloxy)methyl)-3-(trifluoromethoxy)biphenyl-4-ylsulfonamido)butanoic acid
-
(R)-3-methyl-2-(4'-((5-oxo-5,6,7,8-tetrahydronaphthalen-2-yloxy)methyl)-3-(trifluoromethyl)biphenyl-4-ylsulfonamido)butanoic acid
-
(R)-3-methyl-2-(4'-((5-oxo-5,6,7,8-tetrahydronaphthalen-2-yloxy)methyl)biphenyl-4-ylsulfonamido)butanoic acid
-
(R)-3-methyl-2-(4'-((quinolin-2-yloxy)methyl)biphenyl-4-ylsulfonamido)butanoic acid
-
QEYKAHHSYKLMS
-
-
SC81956
-
demonstrates noncompetitive inhibition kinetics
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
interleukin-1
-
-
-
interleukin-1alpha
-
increase of ADAMTS-4 in wild-type mice
-
NFkappaB
-
-
-
oncostatin M
-
-
-
retinoic acid
-
-
transforming growth factor beta
-
-
-
Tumor necrosis factor alpha
-
-
-
additional information
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.026
QEYKAHHSYKLMS
-
at 37°C
0.0000228
SC81956
-
at 37°C
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00018
(R)-2-(3-fluoro-4'-((5-oxo-5,6,7,8-tetrahydronaphthalen-2-yloxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
Mus musculus
-
0.0002
(R)-2-(4'-((2,8-bis(trifluoromethyl)quinolin-4-yloxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
Mus musculus
-
0.0049
(R)-2-(4'-((3-(dimethylamino)phenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
Mus musculus
-
0.001
(R)-2-(4'-((3-acetylphenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
Mus musculus
-
0.00023
(R)-2-(4'-((3-benzoylphenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
Mus musculus
-
0.0012
(R)-2-(4'-((3-fluorophenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
Mus musculus
-
0.0011
(R)-2-(4'-((3-hydroxyphenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
Mus musculus
-
0.0018
(R)-2-(4'-((3-methoxyphenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
Mus musculus
-
0.00008
(R)-2-(4'-((4-(4-fluorobenzoyl)phenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
Mus musculus
-
0.00009
(R)-2-(4'-((4-(cyclohexanecarbonyl)phenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
Mus musculus
-
0.00059
(R)-2-(4'-((4-(tert-butoxycarbonylamino)phenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
Mus musculus
-
0.00043
(R)-2-(4'-((4-acetylphenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
Mus musculus
-
0.0017
(R)-2-(4'-((4-fluorophenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
Mus musculus
-
0.0001
(R)-2-(4'-((4-isobutyrylphenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
Mus musculus
-
0.0016
(R)-2-(4'-((4-methoxyphenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
Mus musculus
-
0.0002
(R)-3-methyl-2-(4'-((3-methylquinolin-2-yloxy)methyl)biphenyl-4-ylsulfonamido)butanoic acid
Mus musculus
-
0.00073
(R)-3-methyl-2-(4'-((4-(6-methylpyridin-2-yloxy)phenoxy)methyl)biphenyl-4-ylsulfonamido)butanoic acid
Mus musculus
-
0.0052
(R)-3-methyl-2-(4'-((4-(morpholine-4-carbonyl)phenoxy)methyl)biphenyl-4-ylsulfonamido)butanoic acid
Mus musculus
-
0.006
(R)-3-methyl-2-(4'-((4-(morpholinomethyl)phenoxy)methyl)biphenyl-4-ylsulfonamido)butanoic acid
Mus musculus
-
0.0009
(R)-3-methyl-2-(4'-((4-(pyridin-2-yloxy)phenoxy)methyl)biphenyl-4-ylsulfonamido)butanoic acid
Mus musculus
-
0.0019
(R)-3-methyl-2-(4'-((4-(pyrrolidine-1-carbonyl)phenoxy)methyl)biphenyl-4-ylsulfonamido)butanoic acid
Mus musculus
-
0.0004
(R)-3-methyl-2-(4'-((4-phenoxyphenoxy)methyl)biphenyl-4-ylsulfonamido)butanoic acid
Mus musculus
-
0.0008
(R)-3-methyl-2-(4'-((5-(trifluoromethyl)pyridin-2-yloxy)methyl)biphenyl-4-ylsulfonamido)butanoic acid
Mus musculus
-
0.02
(R)-3-methyl-2-(4'-((5-oxo-5,6,7,8-tetrahydronaphthalen-2-yloxy)methyl)-3-(trifluoromethoxy)biphenyl-4-ylsulfonamido)butanoic acid
Mus musculus
-
0.0032
(R)-3-methyl-2-(4'-((5-oxo-5,6,7,8-tetrahydronaphthalen-2-yloxy)methyl)-3-(trifluoromethyl)biphenyl-4-ylsulfonamido)butanoic acid
Mus musculus
-
0.00023
(R)-3-methyl-2-(4'-((5-oxo-5,6,7,8-tetrahydronaphthalen-2-yloxy)methyl)biphenyl-4-ylsulfonamido)butanoic acid
Mus musculus
-
0.0004
(R)-3-methyl-2-(4'-((quinolin-2-yloxy)methyl)biphenyl-4-ylsulfonamido)butanoic acid
Mus musculus
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
the enzyme translocates to the nucleus of apoptotic cells
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
aortas in enzyme-deficient mice show reduced elastic fibre destruction, versican degradation, macrophage infiltration, and apoptosis. Enzyme deficiency in mice partially prevents aortic destruction and proteoglycan degradation, decreases inflammatory cell infiltration in the aorta, and reduces aortic apoptosis
physiological function
malfunction
-
the lack of hevin cleavage, as seen in ADAMTS4-null mice results in altered Purkinje-cell morphology and a reactive gliosis phenotype in the brain of these adult animals
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
ATS4_MOUSE
833
0
90070
Swiss-Prot
Mitochondrion (Reliability: 2)
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
x * 68000, SDS-PAGE
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
E362A
catalytically inactive
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expressed in HEK-293 cells
expressed in Sf9 cells
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
enzyme expression is increased in mice with aortic aneurysm and dissection
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
degradation
-
degradation of cartilage in late-stage Lyme arthritis
medicine
-
therapeutic target in osteoarthritis
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Behera, A.K.; Hildebrand, E.; Szafranski, J.; Hung, H.H.; Grodzinsky, A.J.; Lafyatis, R.; Koch, A.E.; Kalish, R.; Perides, G.; Steere, A.C.; Hu, L.T.
Role of aggrecanase 1 in Lyme arthritis
Arthritis Rheum.
54
3319-3329
2006
Bos taurus, Homo sapiens, Mus musculus, Mus musculus C3H/HEN
Manually annotated by BRENDA team
Wittwer, A.J.; Hills, R.L.; Keith, R.H.; Munie, G.E.; Arner, E.C.; Anglin, C.P.; Malfait, A.M.; Tortorella, M.D.
Substrate-dependent inhibition kinetics of an active site-directed inhibitor of ADAMTS-4 (aggrecanase 1)
Biochemistry
46
6393-6401
2007
Mus musculus
Manually annotated by BRENDA team
Bondeson, J.; Wainwright, S.; Hughes, C.; Caterson, B.
The regulation of the ADAMTS4 and ADAMTS5 aggrecanases in osteoarthritis: a review
Clin. Exp. Rheumatol.
26
139-145
2008
Bos taurus, Homo sapiens, Mus musculus, Sus scrofa
Manually annotated by BRENDA team
Rogerson, F.M.; Stanton, H.; East, C.J.; Golub, S.B.; Tutolo, L.; Farmer, P.J.; Fosang, A.J.
Evidence of a novel aggrecan-degrading activity in cartilage: Studies of mice deficient in both ADAMTS-4 and ADAMTS-5
Arthritis Rheum.
58
1664-1673
2008
Mus musculus
Manually annotated by BRENDA team
Hopper, D.W.; Vera, M.D.; How, D.; Sabatini, J.; Xiang, J.S.; Ipek, M.; Thomason, J.; Hu, Y.; Feyfant, E.; Wang, Q.; Georgiadis, K.E.; Reifenberg, E.; Sheldon, R.T.; Keohan, C.C.; Majumdar, M.K.; Morris, E.A.; Skotnicki, J.; Sum, P.E.
Synthesis and biological evaluation of ((4-keto)-phenoxy)methyl biphenyl-4-sulfonamides: a class of potent aggrecanase-1 inhibitors
Bioorg. Med. Chem. Lett.
19
2487-2491
2009
Mus musculus (Q8BNJ2)
Manually annotated by BRENDA team
Weaver, M.S.; Workman, G.; Cardo-Vila, M.; Arap, W.; Pasqualini, R.; Sage, E.H.
Processing of the matricellular protein hevin in mouse brain is dependent on ADAMTS4
J. Biol. Chem.
285
5868-5877
2010
Mus musculus
Manually annotated by BRENDA team
Rao, N.; Ke, Z.; Liu, H.; Ho, C.; Kumar, S.; Xiang, W.; Zhu, Y.; Ge, R.
ADAMTS4 and its proteolytic fragments differentially affect melanoma growth and angiogenesis in mice
Int. J. Cancer
133
294-306
2013
Mus musculus (Q8BNJ2)
Manually annotated by BRENDA team
Walter, S.; Jumpertz, T.; Huettenrauch, M.; Ogorek, I.; Gerber, H.; Storck, S.E.; Zampar, S.; Dimitrov, M.; Lehmann, S.; Lepka, K.; Berndt, C.; Wiltfang, J.; Becker-Pauly, C.; Beher, D.; Pietrzik, C.U.; Fraering, P.C.; Wirths, O.; Weggen, S.
The metalloprotease ADAMTS4 generates N-truncated A?4-x species and marks oligodendrocytes as a source of amyloidogenic peptides in Alzheimers disease
Acta Neuropathol.
137
239-257
2019
Mus musculus (Q8BNJ2), Mus musculus
Manually annotated by BRENDA team
Ren, P.; Hughes, M.; Krishnamoorthy, S.; Zou, S.; Zhang, L.; Wu, D.; Zhang, C.; Curci, J.A.; Coselli, J.S.; Milewicz, D.M.; LeMaire, S.A.; Shen, Y.H.
Critical role of ADAMTS-4 in the development of sporadic aortic aneurysm and dissection in mice
Sci. Rep.
7
12351
2017
Mus musculus (Q8BNJ2), Mus musculus
Manually annotated by BRENDA team