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2-Aminobenzoyl-Ala-Gly-Leu-Ala 4-nitrobenzyl amide + H2O
?
-
-
-
-
?
acetyl-Ala-Ala-Leu-Gly-Ala + H2O
?
-
-
-
-
?
acetyl-Glu-Ala-Leu-Gly-Ala + H2O
?
-
-
-
-
?
Acetyl-Val-Ala-Ala-Leu-Gly-Ala + H2O
?
-
-
-
-
?
acetyl-Val-Ala-Leu-Gly-Gly + H2O
?
-
-
-
-
?
Acetyl-Val-Ala-Leu-Leu-Ala + H2O
?
-
best substrate of synthetic acetylated pentapeptides
-
-
?
acetyl-Val-Ala-Phe-Gly-Ala + H2O
?
-
-
-
-
?
acetyl-Val-Gly-Leu-Gly-Ala + H2O
?
-
-
-
-
?
angiotensin I + H2O
Asp-Arg-Val-Tyr-Ile-His + Pro + Phe-His-Leu
-
i.e. Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu, cleaved at His-Pro and Pro-Phe
-
?
Basement membrane preparation + H2O
Soluble peptides
Basement membranes surrounding capillaries + H2O
?
bovine aggrecan monomer + H2O
?
cartilage aggrecan + H2O
?
-
-
-
?
Collagen type IV + H2O
Hydrolyzed collagen type IV
Fibrinogen + H2O
?
-
-
-
-
?
Fibrinogen + H2O
Hydrolyzed fibrinogen
-
-
-
-
?
Fibronectin + H2O
?
-
-
-
-
?
FSFRLT + H2O
?
-
good substrate
-
-
?
Gelatin of collagen type I + H2O
Hydrolyzed gelatin of collagen type I
Gelatin of collagen type III + H2O
?
-
i.e. denatured collagen
-
-
?
Gelatin of collagen type V + H2O
Hydrolyzed gelatin of collagen type V
-
i.e. denatured collagen, hydrolysis at 38øC and above, not below
MW 130000, MW 118000, MW 93000 and MW 85000 fragments
?
Glu-Ala-Leu-Tyr-Leu + H2O
?
-
peptide derived from insulin B-chain
-
-
?
hide powder azure + H2O
?
HTLRKA + H2O
?
-
good substrate
-
-
?
Human alpha2-macroglobulin + H2O
?
-
cleavage at Arg696-Leu697
-
-
?
IAQLNR + H2O
?
-
good substrate
-
-
?
IPLRTV + H2O
?
-
good substrate
-
-
?
Leu-Val-Glu-Ala-Leu-Tyr-Leu + H2O
Leu-Val-Glu-Ala + Leu-Tyr-Leu
Luteinizing hormone-releasing hormone + H2O
?
-
cleavage sites: Trp3-Ser4, Gly6-Leu7
-
-
?
Met-enkephalin + H2O
Tyr-Gly-Gly + Phe-Met
-
i.e. Tyr-Gly-Gly-Phe-Met, cleavage site: Gly3-Phe4
-
-
?
Nidogen + H2O
?
-
basement membrane component
-
-
?
Oxidized insulin B-chain + H2O
?
SFMRLS + H2O
?
-
good substrate
-
-
?
TQRKRS + H2O
?
-
good substrate
-
-
?
Val-Glu-Ala-Leu-Tyr-Leu + H2O
?
-
peptide derived from insulin B-chain
-
-
?
von Willebrand factor + H2O
?
additional information
?
-
Basement membrane preparation + H2O
Soluble peptides
-
-
-
-
?
Basement membrane preparation + H2O
Soluble peptides
-
poor substrate: component band a
-
?
Basement membranes surrounding capillaries + H2O
?
-
involved in disruption of capillary membranes causing hemorrhage in surrounding tissue
-
-
?
Basement membranes surrounding capillaries + H2O
?
-
together with hemorrhagic toxins a, b, e and f responsible for hemorrhage
-
-
?
Basement membranes surrounding capillaries + H2O
?
-
together with atrolysins B and E member of the class P-I hemorrhagic toxins
-
-
?
Basement membranes surrounding capillaries + H2O
?
-
less potent hemorrhagic toxins of Crotalus atrox venom
-
-
?
bovine aggrecan monomer + H2O
?
-
-
-
?
bovine aggrecan monomer + H2O
?
-
purified atrolysin C can cleave at the cleavage sites VIPEN + FFBVG and ITEGE + ARGSV independently
-
-
?
Collagen type IV + H2O
Hydrolyzed collagen type IV
-
basement membrane component, alpha1 (MW 185000) and alpha2 (MW 170000) chain
-
-
?
Collagen type IV + H2O
Hydrolyzed collagen type IV
-
basement membrane component, alpha1 (MW 185000) and alpha2 (MW 170000) chain
MW 170000, MW 164000, MW 125000, MW 110000, MW 940000 and MW 64000 fragments
?
Dimethylcasein + H2O
?
-
-
-
-
?
Dimethylcasein + H2O
?
-
-
-
-
?
Gelatin of collagen type I + H2O
Hydrolyzed gelatin of collagen type I
-
i.e. denatured collagen
-
-
?
Gelatin of collagen type I + H2O
Hydrolyzed gelatin of collagen type I
-
i.e. denatured collagen
MW 60000 and MW 50000 fragments
?
hide powder azure + H2O
?
-
-
-
-
?
hide powder azure + H2O
?
-
-
-
-
?
Laminin + H2O
?
-
-
-
-
?
Laminin + H2O
?
-
basement membrane component, poor substrate
-
-
?
Leu-Val-Glu-Ala-Leu-Tyr-Leu + H2O
Leu-Val-Glu-Ala + Leu-Tyr-Leu
-
cleavage at Ala-Leu
-
-
?
Leu-Val-Glu-Ala-Leu-Tyr-Leu + H2O
Leu-Val-Glu-Ala + Leu-Tyr-Leu
-
peptide derived from insulin B-chain, best substrate
-
-
?
Oxidized insulin B-chain + H2O
?
-
-
-
-
?
Oxidized insulin B-chain + H2O
?
-
cleavage at Gly23-Phe24
-
-
?
Oxidized insulin B-chain + H2O
?
-
cleavage at His5-Leu6, His10-Leu11, Ala14-Leu15 (most rapidly cleaved bond)
-
-
?
Oxidized insulin B-chain + H2O
?
-
cleaves the same bonds as atrolysin B and A (the latter except Gly23-Phe24)
-
-
?
Oxidized insulin B-chain + H2O
?
-
cleavage at Tyr16-Leu17 (slightly less rapidly cleaved bond)
-
-
?
Oxidized insulin B-chain + H2O
?
-
cleavage at Gly23-Phe24
-
-
?
Oxidized insulin B-chain + H2O
?
-
Crotalus ruber ruber toxin HT-3 does not cleave the His5-Leu6 bond which is cleaved by HT-2
-
-
?
von Willebrand factor + H2O
?
-
VWF is a large, multidomain glycoprotein present in human blood and in the secretory granules of endothelial cells and platelets
-
-
?
von Willebrand factor + H2O
?
-
i.e. VWF, is a large, multidomain glycoprotein, atrolysin C does not require specific interaction with the VWA1 domain and likely cleaves VWF in a nonlocalized manner, cleavage in sequences MSMG-/-VSG, MSMG(C)V-/-G, LVPDS-/-H, and MSMG(C)VSG, after the D domain and the cystine knot-like domain, atrolysin C cleaves VWF at widely distributed sites identified next to VWD3 and VWD4 domains, overview
-
-
?
additional information
?
-
-
no hydrolysis of fibrin
-
-
?
additional information
?
-
-
no hydrolysis of interstitial collagen, native type I collagen
-
-
?
additional information
?
-
-
no hydrolysis of peptide Ala-Leu-Tyr-Leu
-
-
?
additional information
?
-
-
cleavage specificity, compared to hemorrhagic toxins a and b
-
-
?
additional information
?
-
-
substrate requirements: small aliphatic residues at P1 (Ala or Gly) and Leu at P2
-
-
?
additional information
?
-
-
substrate digestion patterns differ from those of atrolysins A and E
-
-
?
additional information
?
-
-
peptides of four residues or less are not hydrolyzed, no significant degradation of fibrin
-
-
?
additional information
?
-
-
hemorrhagic and myonecrotic activity
-
-
?
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Arthritis
ADAMTS5 is the major aggrecanase in mouse cartilage in vivo and in vitro.
Arthritis
Aggrecan is degraded by matrix metalloproteinases in human arthritis. Evidence that matrix metalloproteinase and aggrecanase activities can be independent.
Arthritis
Aggrecanase and metalloproteinase-specific aggrecan neo-epitopes are induced in the articular cartilage of mice with collagen II-induced arthritis.
Arthritis
Aggrecanase cleavage in juvenile idiopathic arthritis patients is minimally detected in the aggrecan interglobular domain but robust at the aggrecan C-terminus.
Arthritis
Aggrecanase-mediated cartilage degradation.
Arthritis
Aggrecanase. A target for the design of inhibitors of cartilage degradation.
Arthritis
Association between synovial fluid levels of aggrecan ARGS fragments and radiographic progression in knee osteoarthritis.
Arthritis
Current and emerging therapeutic strategies for preventing inflammation and aggrecanase-mediated cartilage destruction in arthritis.
Arthritis
Degradation of cartilage aggrecan by collagenase-3 (MMP-13).
Arthritis
Experimental arthritis: Oral aggrecanase inhibitor may slow postinjury cartilage breakdown.
Arthritis
Expression and regulation of aggrecanase in arthritis: the role of TGF-beta.
Arthritis
Interleukin-1 Induction of Aggrecanase Gene Expression in Human Articular Chondrocytes is Mediated by Mitogen-Activated Protein Kinases.
Arthritis
Mannosamine inhibits aggrecanase-mediated changes in the physical properties and biochemical composition of articular cartilage.
Arthritis
Mechanisms of proteoglycan metabolism that lead to cartilage destruction in the pathogenesis of arthritis.
Arthritis
Sites of aggrecan cleavage by recombinant human aggrecanase-1 (ADAMTS-4).
Arthritis
Synovial fluid level of aggrecan ARGS fragments is a more sensitive marker of joint disease than glycosaminoglycan or aggrecan levels: a cross-sectional study.
Arthritis
TGF-beta-induced expression of tissue inhibitor of metalloproteinases-3 gene in chondrocytes is mediated by extracellular signal-regulated kinase pathway and Sp1 transcription factor.
Arthritis
TIMP-3 is a potent inhibitor of aggrecanase 1 (ADAM-TS4) and aggrecanase 2 (ADAM-TS5).
Arthritis, Juvenile
Aggrecanase cleavage in juvenile idiopathic arthritis patients is minimally detected in the aggrecan interglobular domain but robust at the aggrecan C-terminus.
Arthritis, Rheumatoid
A microplate assay for the screening of ADAMTS-4 inhibitors.
Arthritis, Rheumatoid
Expression of a wide range of extracellular matrix molecules in the tendon and trochlea of the human superior oblique muscle.
Carcinoma
Expression and distribution of aggrecanases in human larynx: ADAMTS-5/aggrecanase-2 is the main aggrecanase in laryngeal carcinoma.
Chondrosarcoma
The intermediates of aggrecanase-dependent cleavage of aggrecan in rat chondrosarcoma cells treated with interleukin-1.
Chondrosarcoma
Truncation of the amino-terminus of the recombinant aggrecan rAgg1mut leads to reduced cleavage at the aggrecanase site. Efficient aggrecanase catabolism may depend on multiple substrate interactions.
Chondrosarcoma
Utilization of a recombinant substrate rAgg1 to study the biochemical properties of aggrecanase in cell culture systems.
Endometrial Neoplasms
The investigation of serum levels of ADAMTS 5 and 8 (the A disintegrin and metalloproteinase with thrombospondin motifs) in the etiology of endometrial cancer.
Infections
Borrelia burgdorferi aggrecanase activity: more evidence for persistent infection in Lyme disease.
Intervertebral Disc Degeneration
Matrix metalloproteinases and aggrecanase: their role in disorders of the human intervertebral disc.
Intervertebral Disc Degeneration
Region-Dependent Aggrecan Degradation Patterns in the Rat Intervertebral Disc Are Affected by Mechanical Loading In Vivo.
Intervertebral Disc Displacement
Matrix metalloproteinases and aggrecanase: their role in disorders of the human intervertebral disc.
Joint Diseases
Association of serum levels of aggrecan ARGS, NITEGE fragments and radiologic knee osteoarthritis in Tunisian patients.
Joint Diseases
Development and characterization of a highly specific and sensitive sandwich ELISA for detection of aggrecanase-generated aggrecan fragments.
Joint Diseases
Release of hyaluronan and hyaladherins (aggrecan G1 domain and link proteins) from articular cartilage exposed to ADAMTS-4 (aggrecanase 1) or ADAMTS-5 (aggrecanase 2).
Joint Diseases
Synovial fluid level of aggrecan ARGS fragments is a more sensitive marker of joint disease than glycosaminoglycan or aggrecan levels: a cross-sectional study.
Joint Diseases
The structure of aggrecan fragments in human synovial fluid. Evidence that aggrecanase mediates cartilage degradation in inflammatory joint disease, joint injury, and osteoarthritis.
Leukemia
Interleukin 17 induced nitric oxide suppresses matrix synthesis and protects cartilage from matrix breakdown.
Lyme Disease
Borrelia burgdorferi aggrecanase activity: more evidence for persistent infection in Lyme disease.
Lyme Disease
Lyme disease spirochaetes possess an aggrecan-binding protease with aggrecanase activity.
Melanoma
Application of topologically constrained mini-proteins as ligands, substrates, and inhibitors.
Neoplasms
"Aggrecanase" activity is implicated in tumour necrosis factor alpha mediated cartilage aggrecan breakdown but is not detected by an in vitro assay.
Neoplasms
ADAMTS-9 is synergistically induced by interleukin-1beta and tumor necrosis factor alpha in OUMS-27 chondrosarcoma cells and in human chondrocytes.
Neoplasms
Effect of intra-articular administration of interleukin 1 receptor antagonist on cartilage repair in temporomandibular joint.
Neoplasms
Effect of low molecular weight heparin and different heparin molecular weight fractions on the activity of the matrix-degrading enzyme aggrecanase: structure-function relationship.
Neoplasms
Elevated expression of hypoxia-inducible factor-2alpha regulated catabolic factors during intervertebral disc degeneration.
Neoplasms
Expression and distribution of aggrecanases in human larynx: ADAMTS-5/aggrecanase-2 is the main aggrecanase in laryngeal carcinoma.
Neoplasms
Increased type II collagen degradation and very early focal cartilage degeneration is associated with upregulation of chondrocyte differentiation related genes in early human articular cartilage lesions.
Neoplasms
Interleukin 17 induced nitric oxide suppresses matrix synthesis and protects cartilage from matrix breakdown.
Neoplasms
Oncostatin M in combination with tumour necrosis factor {alpha} induces a chondrocyte membrane associated aggrecanase that is distinct from ADAMTS aggrecanase-1 or -2.
Neoplasms
The intermediates of aggrecanase-dependent cleavage of aggrecan in rat chondrosarcoma cells treated with interleukin-1.
Neoplasms
The investigation of serum levels of ADAMTS 5 and 8 (the A disintegrin and metalloproteinase with thrombospondin motifs) in the etiology of endometrial cancer.
Neoplasms
Tumor necrosis factor alpha-dependent aggrecan cleavage and release of glycosaminoglycans in the meniscus is mediated by nitrous oxide-independent aggrecanase activity in vitro.
Oligodendroglioma
Microvesicles shed by oligodendroglioma cells and rheumatoid synovial fibroblasts contain aggrecanase activity.
Osteoarthritis
10mM glucosamine prevents activation of proADAMTS5 (aggrecanase-2) in transfected cells by interference with post-translational modification of furin.
Osteoarthritis
A microplate assay for the screening of ADAMTS-4 inhibitors.
Osteoarthritis
A short-term pharmacodynamic model for monitoring aggrecanase activity: injection of monosodium iodoacetate (MIA) in rats and assessment of aggrecan neoepitope release in synovial fluid using novel ELISAs.
Osteoarthritis
Advances in the development of novel aggrecanase inhibitors.
Osteoarthritis
Aggrecanase and aggrecan degradation in osteoarthritis: a review.
Osteoarthritis
An aggrecanase and osteoarthritis.
Osteoarthritis
Animal models of osteoarthritis: lessons learned while seeking the 'Holy Grail'.
Osteoarthritis
Anti-ADAMTS5 monoclonal antibodies: implications for aggrecanase inhibition in osteoarthritis.
Osteoarthritis
Arylsulfonamide inhibitors of aggrecanases as potential therapeutic agents for osteoarthritis: Synthesis and biological evaluation.
Osteoarthritis
CXCL12/CXCR4 Axis Regulates Aggrecanase Activation and Cartilage Degradation in a Post-Traumatic Osteoarthritis Rat Model.
Osteoarthritis
Development of human neutralizing antibody to ADAMTS4 (aggrecanase-1) and ADAMTS5 (aggrecanase-2).
Osteoarthritis
Effect of dehydroepiandrosterone on aggrecanase expression in articular cartilage in a rabbit model of osteoarthritis.
Osteoarthritis
Effects of hexosamines and omega-3/omega-6 fatty acids on pH regulation by interleukin 1-treated isolated bovine articular chondrocytes.
Osteoarthritis
Exosite inhibition of ADAMTS-5 by a glycoconjugated arylsulfonamide.
Osteoarthritis
Genetic variation including nonsynonymous polymorphisms of a major aggrecanase, ADAMTS-5, in susceptibility to osteoarthritis.
Osteoarthritis
Inhibition of ADAM-TS4 and ADAM-TS5 prevents aggrecan degradation in osteoarthritic cartilage.
Osteoarthritis
Knockout of ADAMTS5 does not eliminate cartilage aggrecanase activity but abrogates joint fibrosis and promotes cartilage aggrecan deposition in murine osteoarthritis models.
Osteoarthritis
Release of hyaluronan and hyaladherins (aggrecan G1 domain and link proteins) from articular cartilage exposed to ADAMTS-4 (aggrecanase 1) or ADAMTS-5 (aggrecanase 2).
Osteoarthritis
Synthesis and biological evaluation of biphenylsulfonamide carboxylate aggrecanase-1 inhibitors.
Osteoarthritis
The regulation of the ADAMTS4 and ADAMTS5 aggrecanases in osteoarthritis: a review.
Osteoarthritis
The structure of aggrecan fragments in human synovial fluid. Evidence that aggrecanase mediates cartilage degradation in inflammatory joint disease, joint injury, and osteoarthritis.
Osteoarthritis
Translational development of an ADAMTS-5 antibody for osteoarthritis disease modification.
Osteoarthritis
Will the real aggrecanase(s) step up: evaluating the criteria that define aggrecanase activity in osteoarthritis.
Osteoarthritis, Knee
The association between changes in synovial fluid levels of ARGS-aggrecan fragments, progression of radiographic osteoarthritis and self-reported outcomes: a cohort study.
Persistent Infection
Borrelia burgdorferi aggrecanase activity: more evidence for persistent infection in Lyme disease.
Post-Lyme Disease Syndrome
Borrelia burgdorferi aggrecanase activity: more evidence for persistent infection in Lyme disease.
Rheumatic Diseases
A microplate assay for the screening of ADAMTS-4 inhibitors.
Spondylolisthesis
Matrix metalloproteinases and aggrecanase: their role in disorders of the human intervertebral disc.
Temporomandibular Joint Disorders
Aggrecanase analysis of synovial fluid of temporomandibular joint disorders.
Temporomandibular Joint Disorders
Expression of matrix metalloproteinases and aggrecanase in the synovial fluids of patients with symptomatic temporomandibular disorders.
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Fox, J.W.; Bjarnason, J.B.
Atrolysins: metalloproteinases from Crotalus atrox venom
Methods Enzymol.
248
368-387
1995
Crotalus atrox
brenda
Bjarnason, J.B.; Hamilton, D.; Fox, J.W.
Studies on the mechanism of hemorrhage production by five proteolytic hemorrhagic toxins from Crotalus atrox venom
Biol. Chem. Hoppe-Seyler
369
121-129
1988
Crotalus atrox
brenda
Bjarnason, J.B.; Tu, A.T.
Hemorrhagic toxins from Western diamondback rattlesnake (Crotalus atrox) venom: isolation and characterization of five toxins and the role of zinc in hemorrhagic toxin e
Biochemistry
17
3395-3404
1978
Crotalus atrox
brenda
Fox, J.W.; Campbell, R.; Beggerly, L.; Bjarnason, J.B.
Substrate specificities and inhibition of two hemorrhagic zinc proteases Ht-c and Ht-d from Crotalus atrox venom
Eur. J. Biochem.
156
65-72
1986
Crotalus atrox
brenda
Bjarnason, J.B.; Fox, J.W.
Characterization of two hemorrhagic zinc proteinases, toxin c and toxin d, from western diamondback rattlesnake (Crotalus atrox) venom
Biochim. Biophys. Acta
911
356-363
1987
Crotalus atrox
brenda
Shannon, J.D.; Baramova, E.N.; Bjarnason, J.B.; Fox, J.W.
Amino acid sequence of a Crotalus atrox venom metalloproteinase which cleaves type IV collagen and gelatin
J. Biol. Chem.
264
11575-11583
1989
Crotalus atrox
brenda
Zhang, D.; Botos, I.; Gomis-Ruth, F.X.; Doll, R.; Blood, C.; Njoroge, F.G.; Fox, J.W.; Bode, W.; Meyer, E.F.
Structural interaction of natural and synthetic inhibitors with the venom metalloproteinase, atrolysin C (form d)
Proc. Natl. Acad. Sci. USA
91
8447-8451
1994
Crotalus atrox
brenda
Takeya, H.; Onikura, A.; Nikai, T.; Sugihara, H.; Iwanaga, S.
Primary structure of a hemorrhagic metalloproteinase, HT-2, isolated from the venom of Crotalus ruber ruber
J. Biochem.
108
711-719
1990
Crotalus ruber ruber
brenda
Mori, N.; Nikali, T.; Sugihara, H.; Tu, A.T.
Biochemical characterization of hemorrhagic toxins with fibrinogenase activity isolated from Crotalus ruber ruber venom
Arch. Biochem. Biophys.
253
108-121
1987
Crotalus ruber ruber
brenda
Tortorella, M.D.; Pratta, M.A.; Fox, J.W.; Arner, E.C.
The interglobular domain of cartilage aggrecan is cleaved by hemorrhagic metalloproteinase HT-d (atrolysin C) at the matrix metalloproteinase and aggrecanase sites
J. Biol. Chem.
273
5846-5850
1998
Crotalus atrox
brenda
Pinto, A.F.; Terra, R.M.; Guimaraes, J.A.; Kashiwagi, M.; Nagase, H.; Serrano, S.M.; Fox, J.W.
Structural features of the reprolysin atrolysin C and tissue inhibitors of metalloproteinases (TIMPs) interaction
Biochem. Biophys. Res. Commun.
347
641-648
2006
Crotalus atrox
brenda
Fox, J.W.
Atrolysin C
Handbook Of Proteolytic Enzymes(Barrett,A. J. ,Rawlings,N. D. ,Woessner,J. F. ,Eds. )Academic Press
1
671-673
2004
Crotalus atrox
-
brenda
Ramos, O.H.; Selistre-de-Araujo, H.S.
Comparative analysis of the catalytic domain of hemorrhagic and non-hemorrhagic snake venom metallopeptidases using bioinformatic tools
Toxicon
44
529-538
2004
Crotalus atrox (P15167)
brenda
Serrano, S.M.; Wang, D.; Shannon, J.D.; Pinto, A.F.; Polanowska-Grabowska, R.K.; Fox, J.W.
Interaction of the cysteine-rich domain of snake venom metalloproteinases with the A1 domain of von Willebrand factor promotes site-specific proteolysis of von Willebrand factor and inhibition of von Willebrand factor-mediated platelet aggregation
FEBS J.
274
3611-3621
2007
Crotalus atrox
brenda
Dagda, R.K.; Gasanov, S.E.; Zhang, B.; Welch, W.; Rael, E.D.
Molecular models of the Mojave rattlesnake (Crotalus scutulatus scutulatus) venom metalloproteinases reveal a structural basis for differences in hemorrhagic activities
J. Biol. Phys.
40
193-216
2014
Crotalus atrox (Q90392), Crotalus atrox, Crotalus scutulatus scutulatus
brenda