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Information on EC 3.4.24.86 - ADAM 17 endopeptidase and Organism(s) Rattus norvegicus and UniProt Accession Q9Z1K9
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3.4.24.86 ADAM 17 endopeptidaseSpecify your search results
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- 3.4.24.86
- adam10
- ectodomains
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secretase
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membrane-proximal
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non-amyloidogenic
- cxcl16
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membrane-tethered
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egfr-dependent
The taxonomic range for the selected organisms is: Rattus norvegicus
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
adam17, adam-17, tnf-alpha converting enzyme, tace/adam17, a disintegrin and metalloproteinase 17, tumor necrosis factor-alpha converting enzyme, a disintegrin and metalloprotease 17, tumor necrosis factor-alpha-converting enzyme, metalloproteinase adam17, tumor necrosis factor alpha-converting enzyme, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
ADAM17 proteinase
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metalloprotease TACE
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metalloproteinase ADAM17
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pro tumor necrosis factor cleavage enzyme
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pro-tumor necrosis factor-alpha-processing enzyme
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proteinase, pro-tumor necrosis factor (9CI)
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TACE
TACE proteinase
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TNF-alpha convertase
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TNF-alpha converting enzyme
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TNF-alpha processing protease
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tumor necrosis factor alpha convertase
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tumor necrosis factor alpha-converting enzyme
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tumor necrosis factor-alpha converting enzyme
TACE
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tumor necrosis factor-alpha converting enzyme
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CAS REGISTRY NUMBER
COMMENTARY
151769-16-3
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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
TNF-alpha + H2O
?
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ranitidine enhances TNF-alpha production after lipopolysaccharide treatment through augmented p38 activation, and this seems to occur through TACE
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?
additional information
?
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TACE-mediated ectodomain shedding of erbB ligands, epitomized by TGFalpha is a key component of the neuron-to-glia signaling mechanism used by excitatory amino acids to facilitate the advent of female puberty
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-
?
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
TNF-alpha + H2O
?
-
ranitidine enhances TNF-alpha production after lipopolysaccharide treatment through augmented p38 activation, and this seems to occur through TACE
-
-
?
additional information
?
-
-
TACE-mediated ectodomain shedding of erbB ligands, epitomized by TGFalpha is a key component of the neuron-to-glia signaling mechanism used by excitatory amino acids to facilitate the advent of female puberty
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-
?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1,25-dihydroxyvitamin D
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1,25-dihydroxyvitamin D inhibition of TACE is a potential common mechanism underlying the efficacy of therapy with 1,25-dihydroxyvitamin D or its analogs to improve outcomes in chronic kidney disease. 1,25-dihydroxyvitamin D prevents/moderates not only the onset and progression of parathyroid TACE/TGFalpha-driven secondary hyperparathyroidism, but renal TACE/TGFalpha-driven fibrotic and inflammatory lesions to the renal parenchyma, and TACE/TNFalpha-driven systemic inflammation
BMS-561392
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TACE inhibitor also named DPC-333 is administered 15 min before ranitidine or its vehicle. Serum TNF-alpha concentration are measured 1 h afterwards. lipopolysaccharide/ranitidine treatment causes a significant increase in serum TNF-alpha concentration compared with lipopolysaccharide/vehicle treatment. Inhibitor does not affect serum TNF-alpha concentration after lipopolysaccharide/vehicle treatment. By contrast, it decreases serum TNF-alpha concentration after lipopolysaccharide/ranitidine treatment to the same level as lipopolysaccharide/vehicle treatment at both 1 h. In addition, TACE inhibitor decreases plasma active plasminogen activator inhibitor-1 concentration after lipopolysaccharide/ranitidine treatment to almost the same level as lipopolysaccharide/vehicle treatment
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
four and half LIM domain 2 protein
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four and half LIM domain 2 protein binds both ADAM-17 and the actin-based cytoskeletonand is involved in the regulation of ADAM-17 cellular localization and activity
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lipopolysaccharide
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lipopolysaccharide-vehicle or lipopolysaccharide-ranitidine treatments of rats causes a significant increase in hepatic TACE activity
oxygen
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low oxygen concentrations enhance TACE mRNA levels in synovial cells through direct binding of hypoxia-inducible factor-1 to the 5' promoter region
Tumor necrosis factor alpha
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20 ng/ml tumor necrosis factor alpha enhances TACE mRNA levels in synovial cells through direct binding of hypoxia-inducible factor-1 to the 5' promoter region
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
both ADAM10, EC 3.4.24.81, and ADAM17 are present during all stages of spermatogenesis
both ADAM10, EC 3.4.24.81, and ADAM17 are present during all stages of spermatogenesis
both ADAM10, EC 3.4.24.81, and ADAM17 are present during all stages of spermatogenesis. Protein level and cell surface localization strongly dropp in Dark segments as compared with the rest of the segments
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marrow stromal cell-brain microvascular endothelial cell contact coculture and indirect co-culture of marrow stromal cell and brain microvascular endothelial cell
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within the hypothalamus, TACE is most abundantly expressed in astrocytes of the median eminence, specific changes in TACE activity are required for the normal timimg of puberty. TACE is a component of the neuron-to-glia signaling process used by glutamatergic neurons to control female sexual development
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TACE protein is localized to mononuclear cells (MNC), which infiltrate the liver from the spleen after hepatectomy. The kinetics of TACE expression is in accordance with the number of TACE-staining mononuclear cells and synchronizes with those of transforming growth factor-alpha. TACE-staining mononuclear cells partially overlapp with CD3+ T lymphocytes
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marrow stromal cell-brain microvascular endothelial cell contact coculture and indirect co-culture of marrow stromal cell and brain microvascular endothelial cell
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primary cellular source of ADAM-17 in inflamed peripheral nervous system (experimental autoimmune neuritis). Not all T lymphocytes within the inflamed peripheral nervous system express ADAM-17. No ADAM-17 expressing cells are found in nerves from control animals
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the expression of TACE is increased in intermittent and prolonged hyperoxia
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expression of TACE in liver and spleen tissues after 70% partial hepatectomy is a time-dependent alteration, reaching a maximal level between 24 and 48 h and remaining elevated for more than 168 h
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
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only the mature form of ADAM-17 associates with the cytoskeleton
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
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inhibition of TACE with TAPI-2 or inhibition of TNF-alpha with Etanercept attenuates endothelial differentiation of marrow stromal cells in the direct co-culture condition with rain microvascular endothelial cells
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). ADA17_RAT
827
1
93017
Swiss-Prot
Secretory Pathway (Reliability: 2)
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
transcript levels of TACE and TNF-alpha as well as TACE protein expression are significantly upregulated in direct, but not in indirect coculture condition of marrow stromal cell and brain microvascular endothelial cell
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
molecular biology
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TACE may be involved in liver regeneration by pathway mediated with transforming growth factor-alpha-epidermal growth factor recptor in the cell-cycle progressive phase in vivo. TACE production and effect by paracrine may be a pathway of involvement in liver regeneration for the activated CD3+ T lymphocytes
medicine
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TACE inhibitors prevent TNFalpha release and protect against TNFalpha-mediated disease
medicine
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ADAM-17 is a putative target for treatment of neuroinflammatory diseases
medicine
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inhibition of TACE might be a potential therapeutic strategy for neuroprotection after focal ischemic stroke
medicine
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TACE proteolysis is a promoter of stroke-induced SVZ progenitor cell neurogenesis, and suggest this protease activity may represent an attractive therapeutic target for stroke recovery
medicine
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in order to explore the role of TACE and NF-kappa B in hyperoxia-induced brain-ischemic tolerance, rodents are exposed to 95% inspired hyperoxia 4 h/day for six consecutive days or for 24 continous hours (prolonged hyperoxia). 24 h after the treatment. TACE, serum TNF-alpha and phosphor-kappaBalpha expression is up-regulated. Brain ischemic tolerance, inspired hyperoxia and prolonged hyperoxia may partly exert their effects via triggering TACE/TNF-alpha /NF-kappaB
medicine
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1,25-dihydroxyvitamin D inhibition of TACE is a potential common mechanism underlying the efficacy of therapy with 1,25-dihydroxyvitamin D or its analogs to improve outcomes in chronic kidney disease. 1,25-dihydroxyvitamin D prevents/moderates not only the onset and progression of parathyroid TACE/TGFalpha-driven secondary hyperparathyroidism, but renal TACE/TGFalpha-driven fibrotic and inflammatory lesions to the renal parenchyma, and TACE/TNFalpha-driven systemic inflammation
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
Cricetulus griseus (Q923X3), Rattus norvegicus (Q9Z1K9)
Fiorucci, S.; Antonelli, E.; Migliorati, G.; Santucci, L.; Morelli, O.; Federici, B.; Morelli, A.
TNFalpha processing enzyme inhibitors prevent aspirin-induced TNFalpha release and protect against gastric mucosal injury in rats
Aliment. Pharmacol. Ther.
12
1139-1153
1998
Mus musculus, Rattus norvegicus
Rabinowitz, M.H.; Andrews, R.C.; Becherer, J.D.; Bickett, D.M.; Bubacz, D.G.; Conway, J.G.; Cowan, D.J.; Gaul, M.; Glennon, K.; Lambert, M.H.; Leesnitzer, M.A.; McDougald, D.L.; Moss, M.L.; Musso, D.L.; Rizzolio, M.C.
Design of selective and soluble inhibitors of tumor necrosis factor-alpha converting enzyme (TACE)
J. Med. Chem.
44
4252-4267
2001
Homo sapiens, Mus musculus, Rattus norvegicus, Rattus norvegicus Lewis
Katakowski, M.; Chen, J.; Zhang, Z.G.; Santra, M.; Wang, Y.; Chopp, M.
Stroke-induced subventricular zone proliferation is promoted by tumor necrosis factor-alpha-converting enzyme protease activity
J. Cereb. Blood Flow Metab.
27
669-678
2006
Rattus norvegicus
Lomniczi, A.; Cornea, A.; Costa, M.E.; Ojeda, S.R.
Hypothalamic tumor necrosis factor-alpha converting enzyme mediates excitatory amino acid-dependent neuron-to-glia signaling in the neuroendocrine brain
J. Neurosci.
26
51-62
2006
Rattus norvegicus
Kurz, M.; Pischel, H.; Hartung, H.; Kieseier, B.C.
Tumor necrosis factor-alpha-converting enzyme is expressed in the inflamed peripheral nervous system
J. Peripher. Nerv. Syst.
10
311-318
2005
Homo sapiens, Rattus norvegicus
Wang, X.; Feuerstein, G.Z.; Xu, L.; Wang, H.; Schumacher, W.A.; Ogletree, M.L.; Taub, R.; Duan, J.J.; Decicco, C.P.; Liu, R.
Inhibition of tumor necrosis factor-alpha-converting enzyme by a selective antagonist protects brain from focal ischemic injury in rats
Mol. Pharmacol.
65
890-896
2004
Rattus norvegicus
Charbonneau, M.; Harper, K.; Grondin, F.; Pelmus, M.; McDonald, P.P.; Dubois, C.M.
Hypoxia-inducible factor mediates hypoxic and tumor necrosis factor alpha-induced increases in tumor necrosis factor-alpha converting enzyme/ADAM17 expression by synovial cells
J. Biol. Chem.
282
33714-33724
2007
Rattus norvegicus
Canault, M.; Tellier, E.; Bonardo, B.; Mas, E.; Aumailley, M.; Juhan-Vague, I.; Nalbone, G.; Peiretti, F.
FHL2 interacts with both ADAM-17 and the cytoskeleton and regulates ADAM-17 localization and activity
J. Cell. Physiol.
208
363-372
2006
Rattus norvegicus
Deng, X.; Lu, J.; Lehman-McKeeman, L.D.; Malle, E.; Crandall, D.L.; Ganey, P.E.; Roth, R.A.
p38 mitogen-activated protein kinase-dependent tumor necrosis factor-alpha-converting enzyme is important for liver injury in hepatotoxic interaction between lipopolysaccharide and ranitidine
J. Pharmacol. Exp. Ther.
326
144-152
2008
Rattus norvegicus
Bigdeli, M.R.; Khoshbaten, A.
In vivo preconditioning with normobaric hyperoxia induces ischemic tolerance partly by triggering tumor necrosis factor-alpha converting enzyme/tumor necrosis factor-alpha/nuclear factor-kappaB
Neuroscience
153
671-678
2008
Rattus norvegicus
Lin, X.M.; Liu, Y.B.; Zhou, F.; Wu, Y.L.; Chen, L.; Fang, H.Q.
Expression of tumor necrosis factor-alpha converting enzyme in liver regeneration after partial hepatectomy
World J. Gastroenterol.
14
1353-1357
2008
Rattus norvegicus
Xu, J.; Liu, X.; Chen, J.; Zacharek, A.; Cui, X.; Savant-Bhonsale, S.; Chopp, M.; Liu, Z.
Cell-cell interaction promotes rat marrow stromal cell differentiation into endothelial cell via activation of TACE/TNF-alpha signaling
Cell Transplant.
19
43-53
2010
Homo sapiens, Rattus norvegicus
Dusso, A.; Arcidiacono, M.V.; Yang, J.; Tokumoto, M.
Vitamin D inhibition of TACE and prevention of renal osteodystrophy and cardiovascular mortality
J. Steroid Biochem. Mol. Biol.
121
193-198
2010
Rattus norvegicus
EXTERNAL LINKS (specific for EC-Number 3.4.24.86)
Transporter Classification Database (TCDB): 8.A.77.1.2
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