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Information on EC 3.4.24.B12 - ADAMTS5 endopeptidase and Organism(s) Mus musculus and UniProt Accession Q9R001
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3.4.24.B12 ADAMTS5 endopeptidaseSpecify your search results
Word Map
- 3.4.24.B12
- cartilage
- osteoarthritis
- chondrocytes
-
articular
- metalloproteinase
- collagen
- joint
-
disintegrin
- degeneration
- adamts-4
- tnf
- proteoglycans
- knee
-
intervertebral
-
degener
- synovial
- cox-2
- mmp-1
-
col2a1
- pulposus
- meniscus
- interleukin-1
-
intra-articular
- versican
-
disintegrin-like
- timp-3
-
temporomandibular
-
subchondral
-
safranin
-
cruciate
-
matrix-degrading
-
neoepitope
-
chondroprotective
-
chondrogenic
- brevican
- medicine
-
mankin
-
surgically-induced
-
oa-like
-
collagen-ii
-
meniscectomy
-
anti-catabolic
-
cartilage-degrading
-
interglobular
-
dmm-induced
-
condylar
-
oa-related
-
oa-associated
- osteophyte
-
motifs-4
-
osteoarthritis-like
The taxonomic range for the selected organisms is: Mus musculus
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
adamts-5, adamts5, aggrecanase-2, adam-ts5, aggrecanase 2, aggrecanase-, adamts11, agg-2, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
a disintegrin and metalloproteinase with thrombospondin type 1 motifs, member 5
-
a disintegrin-like and metalloproteinase with thrombospondin-1 motifs 5
-
ADAMTS5
aggrecanase-2
CAS REGISTRY NUMBER
COMMENTARY
405150-12-1
-
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
versican + H2O
?
expression of Adamts5 during neuromuscular development and in smooth muscle cells coincides with the broadly distributed proteoglycan versican, an ADAMTS5 substrate
-
-
?
versican + H2O
?
-
cleaves versican at Glu441-Ala442 within the glycosaminoglycan beta region of versican V1
-
-
?
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
versican + H2O
?
expression of Adamts5 during neuromuscular development and in smooth muscle cells coincides with the broadly distributed proteoglycan versican, an ADAMTS5 substrate
-
-
?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(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-isobutyrylphenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
-
-
(R)-3-methyl-2-(4'-((5-oxo-5,6,7,8-tetrahydronaphthalen-2-yloxy)methyl)biphenyl-4-ylsulfonamido)butanoic acid
-
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
interleukin-1alpha
-
increased transcription in the presence of interleukin-1alpha
-
additional information
-
ADAMTS5 expression is not stimulated by interleukin-1, tumor necrosis factor alpha, oncostatin M or transforming growth factor beta
-
additional information
-
little effect from interleukin-1alpha and retinoate on aggrecanase activity
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0026
(R)-2-(4'-((4-(cyclohexanecarbonyl)phenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
Mus musculus
-
-
0.0084
(R)-2-(4'-((4-isobutyrylphenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid
Mus musculus
-
-
0.0066
(R)-3-methyl-2-(4'-((5-oxo-5,6,7,8-tetrahydronaphthalen-2-yloxy)methyl)biphenyl-4-ylsulfonamido)butanoic acid
Mus musculus
-
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
constitutive Adamts5 expression in adult tissue
embryonic expression is scarce prior to 11.5 days of gestation (E11.5) and noted only in the floor plate of the developing brain at E9.5. After E11.5 there is continued expression in brain, especially in the choroid plexus, peripheral nerves, dorsal root ganglia, cranial nerve ganglia, spinal and cranial nerves, and neural plexuses of the gut. In addition to nerves, developing limbs have Adamts5 expression in skeletal muscle (from E13.5), tendons (from E16.5), and inter-digital mesenchyme of the developing autopod (E13.515.5)
in the kidney, constitutive Adamts5 expression in adult tissue
lining the peritoneal, pericardial and pleural cavities, constitutive Adamts5 expression in adult tissue
of the peripheral and autonomic nervous system, constitutive Adamts5 expression in adult tissue
in bronchi and pancreatic ducts, constitutive Adamts5 expression in adult tissue. Expression of Adamts5 during neuromuscular development and in smooth muscle cells coincides with the broadly distributed proteoglycan versican, an ADAMTS5 substrate
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
physiological function
malfunction
-
ADAMTS-5 deficient mice do not develop mechanical allodynia associated with osteoarthritis following medial meniscal destabilization
malfunction
-
ADAMTS5-/- mice have significantly less cartilage damage than wild-type after induction of osteoarthritis through surgical instability
malfunction
-
ADAMTS5 deficient mice have reduced versican proteolysis, increased pericellular matrix, altered cell shape, enhanced alpha-smooth muscle actin expression and increased contractility within three dimensional collagen gels
malfunction
enzyme-deficient mice develop less subcutaneous and gonadal white adipose tissue as compared to their wild type littermates. Enhanced browning of white adipose tissue and improved insulin sensitivity are seen in enzyme-knockout mice upon cold exposure
malfunction
influenza virus infection of enzyme-deficient mice results in delayed virus clearance, compromised T cell migration and immunity and accumulation of versican. Enzyme-deficient mice exhibit increased weight loss and delayed influenza virus clearance following infection
physiological function
-
ADAMTS5 maintains optimal versican content and pericellular matrix volume by continually trimming versican in hyaluronan-versican aggregates
physiological function
-
in the growth plate ADAMTS-5 has a physiological function in the intracellular processing of matrilins and potentially of other extracellular matrix proteins
physiological function
-
ADAMTS-5 is markedly reduced in atherosclerotic aortas of apolipoprotein E-null mice. The reduction of ADAMTS-5 is accompanied by accumulation of biglycan and versican, the major lipoprotein-binding proteoglycans, in atherosclerosis. ADAMTS-5 activity induced the release of ADAMTS-specific versican and aggrecan fragments as well as biglycan and link protein from the aortic wall. Fibroblast growth factor 2 inhibits ADAMTS-5 expression in isolated aortic smooth muscle cells and blocked the spontaneous release of ADAMTS-generated versican and aggrecan fragments from aortic explants. In aortas of ADAMTS-5-deficient mice, ADAMTS-specific versican neoepitopes are not detectable. Biglycan levels are increased. ADAMTS-5 proteolytic activity reduces the low density lipoprotein binding ability of biglycan and releases low density lipoprotein from human aortic lesions
physiological function
the enzyme is a critical regulator of virus-specific T cell immunity. Its enzymatic activity plays a key role in the development of influenza-specific immunity. The enzyme cleaves large proteoglycans such as aggrecan, leading to the destruction of cartilage and osteoarthritis
physiological function
the enzyme is a principal mediator of aggrecan loss in osteoarthritis
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). PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
Adamts5 mRNA is superinduced in Fgf2/ mice compared with Fgf2+/+ (fibroblast growth factor 2) mice 2 weeks following surgical destabilization of the medial meniscus
-
fibroblast growth factor 2 inhibits ADAMTS-5 expression in isolated aortic smooth muscle cells and blocks the spontaneous release of ADAMTS-generated versican and aggrecan fragments from aortic explants
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
medicine
-
stop progression of cartilage degradation in osteoarthritis by prevention of aggrecan cleavage via inhibition of aggrecanase
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Boeckmann, B.; Bairoch, A.; Apweiler, R.; Blatter, M.C.; Estreicher, A.; Gasteiger, E.; Martin M.J.; Michoud, K.; O'Donovan, C.; Phan, I.; Pilbout, S.; Schneider, M.
The SWISS-PROT protein knowledgebase and its supplement TrEMBL
Nucleic Acids Res.
31
365-370
2003
Bos taurus (Q9TT92), Homo sapiens (Q9UNA0), Mus musculus (Q9R001)
Stanton, H.; Rogerson, F.M.; East, C.J.; Golub, S.B.; Lawlor, K.E.; Meeker, C.T.; Little, C.B.; Last, K.; Farmer, P.J.; Campbell, I.K.; Fourie, A.M.; Fosang, A.J.
ADAMTS5 is the major aggrecanase in mouse cartilage in vivo and in vitro
Nature
434
648-652
2005
Mus musculus
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
Homo sapiens, Mus musculus
Fosang, A.J.; Rogerson, F.M.; East, C.J.; Stanton, H.
ADAMTS-5: the story so far
Eur. Cell Mater.
15
11-26
2008
Bos taurus, Homo sapiens, Mus musculus
Ilic, M.Z.; East, C.J.; Rogerson, F.M.; Fosang, A.J.; Handley, C.J.
Distinguishing aggrecan loss from aggrecan proteolysis in ADAMTS-4 and ADAMTS-5 single and double deficient mice
J. Biol. Chem.
282
37420-37428
2007
Mus musculus
McCulloch, D.R.; Goff, C.L.; Bhatt, S.; Dixon, L.J.; Sandy, J.D.; Apte, S.S.
Adamts5, the gene encoding a proteoglycan-degrading metalloprotease, is expressed by specific cell lineages during mouse embryonic development and in adult tissues
Gene Expr. Patterns
9
314-323
2009
Mus musculus (Q9R001), Mus musculus
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 (Q9R001), Mus musculus
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
Chia, S.L.; Sawaji, Y.; Burleigh, A.; McLean, C.; Inglis, J.; Saklatvala, J.; Vincent, T.
Fibroblast growth factor 2 is an intrinsic chondroprotective agent that suppresses ADAMTS-5 and delays cartilage degradation in murine osteoarthritis
Arthritis Rheum.
60
2019-2027
2009
Mus musculus
Botter, S.; Glasson, S.; Hopkins, B.; Clockaerts, S.; Weinans, H.; van Leeuwen, J.; van Osch, G.
ADAMTS5-/- mice have less subchondral bone changes after induction of osteoarthritis through surgical instability: implications for a link between cartilage and subchondral bone changes
Osteoarthritis Cartilage
17
636-645
2009
Mus musculus
Malfait, A.M.; Ritchie, J.; Gil, A.S.; Austin, J.S.; Hartke, J.; Qin, W.; Tortorella, M.D.; Mogil, J.S.
ADAMTS-5 deficient mice do not develop mechanical allodynia associated with osteoarthritis following medial meniscal destabilization
Osteoarthritis Cartilage
18
572-580
2010
Mus musculus
Hattori, N.; Carrino, D.A.; Lauer, M.E.; Vasanji, A.; Wylie, J.D.; Nelson, C.M.; Apte, S.S.
Pericellular versican regulates the fibroblast-myofibroblast transition: a role for ADAMTS5 protease-mediated proteolysis
J. Biol. Chem.
286
34298-34310
2011
Mus musculus
Groma, G.; Grskovic, I.; Schael, S.; Ehlen, H.W.; Wagener, R.; Fosang, A.; Aszodi, A.; Paulsson, M.; Brachvogel, B.; Zaucke, F.
Matrilin-4 is processed by ADAMTS-5 in late Golgi vesicles present in growth plate chondrocytes of defined differentiation state
Matrix Biol.
30
275-280
2011
Mus musculus
Didangelos, A.; Mayr, U.; Monaco, C.; Mayr, M.
Novel role of ADAMTS-5 protein in proteoglycan turnover and lipoprotein retention in atherosclerosis
J. Biol. Chem.
287
19341-19345
2012
Mus musculus
Apte, S.S.
Anti-ADAMTS5 monoclonal antibodies implications for aggrecanase inhibition in osteoarthritis
Biochem. J.
473
e1-e4
2016
Mus musculus (P59384), Mus musculus
McMahon, M.; Ye, S.; Izzard, L.; Dlugolenski, D.; Tripp, R.A.; Bean, A.G.; McCulloch, D.R.; Stambas, J.
ADAMTS5 is a critical regulator of virus-specific T cell immunity
PLoS Biol.
14
e1002580
2016
Mus musculus (P59384)
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