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Information on EC 3.4.24.86 - ADAM 17 endopeptidase and Organism(s) Mus musculus and UniProt Accession Q9Z0F8
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3.4.24.86 ADAM 17 endopeptidaseSpecify your search results
Word Map
- 3.4.24.86
- adam10
- ectodomains
- sheddase
- metalloproteinases
- endothelial
-
phorbol
- sirna
-
amyloid
- egf
- alzheimer
- notch
- angiotensin
-
membrane-anchored
- arthritis
- amphiregulin
- ace2
- hb-egf
- hydroxamate
- timp-3
-
heparin-binding
- l-selectin
-
trans-signaling
-
angiotensin-converting
- covid-19
- alpha-secretase
- mmp-2
- sars-cov-2
-
egf-like
-
juxtamembrane
- medicine
- prodomains
- furin
-
secretase
- tgf-alpha
-
membrane-proximal
- tmprss2
-
sil-6r
-
non-amyloidogenic
- cxcl16
- rhomboid
- epiregulin
- gamma-secretase
- neuregulins
- molecular biology
- adamalysins
-
metzincins
-
membrane-tethered
- fractalkine
- betacellulin
- marimastat
- analysis
-
egfr-dependent
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
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
-
-
ADAM17 proteinase
-
-
-
-
metalloprotease TACE
-
-
-
-
metalloproteinase ADAM17
-
-
-
-
pro tumor necrosis factor cleavage enzyme
-
-
-
-
pro-tumor necrosis factor-alpha-processing enzyme
-
-
-
-
proteinase, pro-tumor necrosis factor (9CI)
-
-
-
-
TACE
TACE proteinase
-
-
-
-
TNF-alpha convertase
-
-
-
-
TNF-alpha converting enzyme
TNF-alpha processing protease
-
-
-
-
tumor necrosis factor alpha convertase
-
-
-
-
tumor necrosis factor alpha-converting enzyme
-
-
-
-
tumor necrosis factor-alpha converting enzyme
TACE
-
-
-
-
TNF-alpha converting enzyme
-
-
-
-
tumor necrosis factor-alpha converting enzyme
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
151769-16-3
-
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
interleukin (IL)-1R-II + H2O
?
exclusively the extracellular domains of ADAM17 are needed for interaction with substrate, whereas the transmembrane- and cytoplasmic-region are dispensable for this process. In the extracellular part solely the membrane-proximal domain of ADAM17 is mandatory for recognition
-
-
?
interleukin (IL)-6R + H2O
?
exclusively the extracellular domains of ADAM17 are needed for interaction with substrate, whereas the transmembrane- and cytoplasmic-region are dispensable for this process. In the extracellular part solely the membrane-proximal domain of ADAM17 is mandatory for recognition
-
-
?
proTGF-alpha + H2O
soluble TGF-alpha
the membrane-proximal domain in the extracellular part of ADAM17 is mandatory for recognition of the type-I transmembrane proteins, but not for the interaction with the type-II transmembrane molecule TNF-alpha
-
-
?
erbB4/HER4 + H2O
?
-
epidermal growth factor, essential function in heart and neural development, TACE is essential for regulated shedding of the HER4 JM-a receptor
-
-
?
growth hormone binding protein + H2O
?
-
shedding, TACE is critical for PMA-induced GH receptor proteolysis and GHBP generation
-
-
?
lipoprotein-related protein I + H2O
?
-
lipoprotein-related protein I shedding is significantly decreased in embryonic fibroblast cells lacking ADAM10 and/or ADAM17
-
-
?
proTNF-alpha + H2O
soluble TNF-alpha
-
-
638979, 638980, 638981, 638983, 638984, 638987, 638988, 638991, 638992, 638994, 638995, 639000, 639001, 639002, 639003, 639004, 639006, 639010, 639011, 639012, 639013, 679671, 681016
-
-
?
RA175/SynCAM1 + H2O
?
-
neuronal RA175/SynCAM1 isoforms, members of the immunoglobulin family 4, are processed by TACE
-
-
?
transforming growth factor alpha + H2O
?
-
-
638979, 638980, 638981, 638983, 638984, 638987, 638988, 638991, 638992, 638994, 638995, 639000, 639001, 639002, 639003, 639004, 639006, 639010, 639011, 639012, 639013
-
-
?
angiotensin-converting enzyme-2 + H2O
?
-
ADAM-17 is responsible for the ACE2 shedding
-
-
?
glycoprotein Ibalpha + H2O
?
-
ADAM17 is the key enzyme mediating shedding of glycoprotein Ibalpha
-
-
?
intercellular adhesion molecule-1 + H2O
?
-
ADAM-17 mediates shedding of intercellular adhesion molecule-1. The shedding of intercellular adhesion molecule-1 reduces the adhesive capacity of the cells. the cleavage site in the intercellular adhesion molecule-1 is not sequence-specific, but appears to be nonselective
-
-
?
L-selectin + H2O
?
-
during early events of death receptor-mediated neutrophil apoptosis, L-selectin downregulation occurs primarily by ADAM17-mediated shedding. During later stages of induced leukocyte apoptosis, soluble L-selectin production occurs independent of ADAM17
-
-
?
L-selectin + H2O
?
-
TACE is involved in cantharidin-induced shedding of L-selectin. Cantharidin induces sustained surface expression and cytoplasmic tail phosphorylation of TACE via p38 MAPK, while L-selectin is involved in promoting protein kinase C-dependent shedding
-
-
?
L-selectin + H2O
?
-
ADAM17 is the main sheddase of the adhesion protein L-selectin
-
-
?
p75 neurotrophin receptor + H2O
?
-
critical role of TACE in ectodomain shedding of the p75 neurotrophin receptor
-
-
?
additional information
?
-
-
angiotensin converting enzyme is not cleaved by TACE
-
-
?
additional information
?
-
-
in mice, the interleukin-6 receptor is not a target of ADAM17
-
-
?
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
angiotensin-converting enzyme-2 + H2O
?
-
ADAM-17 is responsible for the ACE2 shedding
-
-
?
glycoprotein Ibalpha + H2O
?
-
ADAM17 is the key enzyme mediating shedding of glycoprotein Ibalpha
-
-
?
intercellular adhesion molecule-1 + H2O
?
-
ADAM-17 mediates shedding of intercellular adhesion molecule-1. The shedding of intercellular adhesion molecule-1 reduces the adhesive capacity of the cells. the cleavage site in the intercellular adhesion molecule-1 is not sequence-specific, but appears to be nonselective
-
-
?
p75 neurotrophin receptor + H2O
?
-
critical role of TACE in ectodomain shedding of the p75 neurotrophin receptor
-
-
?
RA175/SynCAM1 + H2O
?
-
neuronal RA175/SynCAM1 isoforms, members of the immunoglobulin family 4, are processed by TACE
-
-
?
L-selectin + H2O
?
-
ADAM17 is the main sheddase of the adhesion protein L-selectin
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Zn2+
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(2R)-5-nitroguanyl-2-([(2R,3S)-2-(cyclohexylmethyl)-3-cyclopropyl-3-[formyl(hydroxy)amino]propanoyl]-amino)-N-(1,3-thiazol-2-yl)pentanamide
-
-
(2R,3S)-N-[(1S)-4-(2-pyridylsulfonyl)guanyl-1-[(1,3-thiazol-2-ylamino)-carbonyl]butyl]-3-[formyl(hydroxy)amino]-2-isobutylhexanamide
-
-
(2R,3S)-N-[(1S)-4-(2-pyridylsulfonyl)guanyl-1-[(1,3-thiazol-2-ylamino)-carbonyl]butyl]-3-[formyl(hydroxy)amino]-2-[(4-methylcyclohexyl)-methyl]hexanamide
-
-
(2R,3S)-N-[(1S)-4-(2-pyridylsulfonyl)guanyl-1-[(1,3-thiazol-2-ylamino)-carbonyl]butyl]-3-[formyl(hydroxy)amino]-2-[(5-methyl-2-thienyl)methyl]hexanamide
-
-
(2R,3S)-N-[(1S)-4-(2-pyridylsulfonyl)guanyl-1-[(1,3-thiazol-2-ylamino)-carbonyl]butyl]-3-[formyl(hydroxy)amino]-4-methyl-2-[(4-methylcyclohexyl)methyl]pentanamide
-
-
(2R,3S)-N-[(1S)-4-methanesulfonylguanyl-1-[(1,3-thiazol-2-ylamino)carbonyl]butyl]-3-[formyl(hydroxy)amino]-2-isobutyl-4-methylpentanamide
-
-
(2R,3S)-N-[(1S)-4-methanesulfonylguanyl-1-[(1,3-thiazol-2-ylamino)carbonyl]butyl]-3-[formyl(hydroxy)amino]-2-isobutylhexanamide
-
-
(2R,3S)-N-[(1S)-4-methanesulfonylguanyl-1-[(1,3-thiazol-2-ylamino)carbonyl]butyl]-3-[formyl(hydroxy)amino]-4-methyl-2-[(4-methylcyclohexyl)methyl]pentanamide
-
-
(2R,3S)-N-[(1S)-4-methanesulfonylguanyl-2-methyl-1-[(1,3-thiazol-2-ylamino)carbonyl]butyl]-3-[formyl-(hydroxy)amino]-2-isobutyl-4-methylpentanamide
-
-
(2R,3S)-N-[(1S)-4-methanesulfonylguanyl-2-methyl-1-[(1,3-thiazol-2-ylamino)carbonyl]butyl]-3-[formyl-(hydroxy)amino]-2-isobutylhexanamide
-
-
(2R,3S)-N-[(1S)-4-methanesulfonylguanyl-2-methyl-1-[(1,3-thiazol-2-ylamino)carbonyl]butyl]-6,6,6-trifluoro-3-[formyl(hydroxy)amino]-2-isobutylhexanamide
-
-
(2R,3S)-N-[(1S)-4-nitroguanyl-1-[(1,3-thiazol-2-ylamino)carbonyl]butyl]-2-(cyclohexylmethyl)-3-[formyl(hydroxy)amino]hexanamide
-
-
(2R,3S)-N-[(1S)-4-nitroguanyl-1-[(1,3-thiazol-2-ylamino)carbonyl]butyl]-2-(cyclohexylmethyl)-6,6,6-trifluoro-3-[formyl(hydroxy)amino]hexanamide
-
-
(2R,3S)-N-[(1S)-4-nitroguanyl-1-[(1,3-thiazol-2-ylamino)carbonyl]butyl]-2-[(1S)-1-[formyl(hydroxy)amino]-2-phenylethyl]-4-methylpentanamide
-
-
(2R,3S)-N-[(1S)-4-nitroguanyl-1-[(1,3-thiazol-2-ylamino)carbonyl]butyl]-3-[formyl(hydroxy)amino]-2-[5-methyl-2-thienylmethyl]hexanamide
-
-
(2R,3S)-N-[(1S)-4-nitroguanyl-1-[(1,3-thiazol-2-ylamino)carbonyl]butyl]-3-[formyl(hydroxy)amino]-4-methyl-2-[(4-methylcyclohexyl)methyl]hexanamide
-
-
(2R,3S)-N-[(1S)-4-nitroguanyl-1-[(1,3-thiazol-2-ylamino)carbonyl]butyl]-3-[formyl(hydroxy)amino]-4-methyl-2-[(4-methylcyclohexyl)methyl]pentanamide
-
-
(2R,3S)-N-[(1S,2R)-4-nitroguanyl-2-methyl-1-[(1,3-thiazol-2-ylamino)carbonyl]butyl]-3-[formyl(hydroxy)amino]-2-isobutylhexanamide
-
-
(2R,3S)-N-{(1R)-4-nitroguanyl-1-[(1,3-thiazol-2-ylamino)carbonyl]butyl}-3-[formyl(hydroxy)amino]-2-isobutylhexanamide
-
-
(2S)-2-amino-5-({(E)-amino[(methylsulfonyl)imino]-methyl}amino)-N-(1,3-thiazol-2-yl)pentanamide hydrochloride
-
-
(2S)-2-[(tert-butoxycarbonyl)amino]-5-({(Z)-(methyl-sulfanyl)[(methylsulfonyl)imino]methyl}amino)pentanoic acid
-
-
(2S,3R)-2-[(tert-butoxycarbonyl)amino]-5-{[imino(2-oxido-2-oxohydrazino)methyl]amino}-3-methylpentanoic acid (3R) Nalpha-boc-Ngamma-nitro-3-methyl L-arginine
-
-
(2S,3R)-2-{[(benzyloxy)carbonyl]amino}-3-methyl-5-({(Z)-(methylsulfanyl)[(methylsulfonyl)imino]methyl}-amino)pentanoic acid
-
-
(2S,3R)-5-methanesulfonylguanyl-2-[((2R)-2-[(1S)-1-[formyl(hydroxy)amino]ethyl]-4-methylpentanoyl)amino]-3-methyl-N-(1,3-thiazol-2-yl)pentanamide
-
-
(2S,3R)-5-nitroguanyl-2-[((2R)-2-[(1S)-1-[formyl(hydroxy)amino]ethyl]-4-methylpentanoyl)amino]-3-methyl-N-(1,3-thiazol-2-yl)pentanamide
-
-
4-[[4-(2-butynyloxy)phenyl]sulfonyl]-N-hydroxy-2,2-dimethyl-(3S)-thiomorpholinecarboxamide
-
IC50: 0.05 mM
benzyl (1S,2R)-4-({(E)-amino[(methylsulfonyl)imino]-methyl}amino)-2-methyl-1-[(1,3-thiazol-2-ylamino)carbonyl]butylcarbamate
-
-
N(R)-[2-(hydroxyaminocarbonyl)methyl]-4-methylpentanoyl-L-alanine amide
-
IC50: about 0.7 mM
TAPI-1
-
TAPI-1 blocks the processing of RA175/SynCAM1, a member of the immunoglobulin family 4. Furthermore, TAPI-1 increases the number of synaptophysin and RA175/SynCAM1 colocalization on the dendrites of neurons
tert-butyl (1S,2R)-4-{[imino(2-oxido-2-oxohydrazino)-methyl]amino}-2-methyl-1-[1,3-thiazol-2-ylaminocarbonyl]butylcarbamate
-
-
tert-butyl (2S,3R)-2-{[(benzyloxy)carbonyl]amino}-5-amino-3-methylpentanoate
-
-
tert-butyl (2S,3R)-2-{[(benzyloxy)carbonyl]amino}-5-azido-3-methylpentanoate
-
-
tert-butyl (2S,3R)-2-{[(benzyloxy)carbonyl]amino}-5-hydroxy-3-methylpentanoate
-
-
tert-butyl(1S)-4-({(Z)-(methylsulfanyl)[(methylsulfonyl)-imino]methyl}amino)-1-[(1,3-thiazol-2-ylamino)carbonyl]butylcarbamate
-
-
TIMP-3
-
presence of TIMP-3 inhibits shedding of lipoprotein-related protein I
-
[((3R,4S)-4-{[(benzyloxy)carbonyl]}-4-carboxy-3-methylbutyl)amino](imino)methanaminium nitrate (3R) 3-methyl L-arginine nitric acid salt
-
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
angiotensin II
treatment with angiotensin II results in angiotensin II type 1 receptor AT1R-mediated increase in myocardial TACE expression and activity, and membrane translocation of TACE
glutamate
-
the shedding activity of the enzyme is increased during glutamate stimulation
p38 mitogen-activated protein kinase
-
increased and sustained cell surface levels of TACE, and phosphorylation of its cytoplasmic tail, a hallmark of TACE activation, occur in lymphocytes and monocytes following p38 MAPK activation
-
additional information
actin cytoskeletal disruption causes endogenous activation of TACE and accumulation at the plasma membrane
-
additional information
TACE activation by stimulating epithelial growth factor receptor occurs via p38/ERK
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.05
4-[[4-(2-butynyloxy)phenyl]sulfonyl]-N-hydroxy-2,2-dimethyl-(3S)-thiomorpholinecarboxamide
Mus musculus
-
IC50: 0.05 mM
0.7
N(R)-[2-(hydroxyaminocarbonyl)methyl]-4-methylpentanoyl-L-alanine amide
Mus musculus
-
IC50: about 0.7 mM
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
actin cytoskeletal disruption causes endogenous activation of TACE and accumulation at the plasma membrane
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
malfunction
metabolism
-
the elevated activity of ADAM17 contributes to the glutamate-induced angiotensin-converting enzyme type 2 down-regulation
physiological function
physiological function
cardiomyocyte-specific deletion of TACE prevents shedding of ACE2. p47phoxKO mice are resistant to angiotensin II-induced TACE phosphorylation and activation with preservation of myocardial ACE2 which dampens angiotensin II-induced cardiac dysfunction and hypertrophy
physiological function
in ADAM17 hypomorphic mice, in which ADAM17 expression is reduced by 90-95% compared with wild-type littermates, ADAM17 deficiency results in spleen and lymph node enlargement, as well as increased levels of Ag-specific class-switched Ig production following immunization with OVA together with anti-CD40 mAbs and polyinosinic-polycytidylic acid. The costimulatory ligand ICOS (ICOSL) is selectively downregulated on the surface of B cells in an ADAM17-specific manner
physiological function
inhibition of ADAM17-mediated processing of TNF-alpha by CD8+ T cells significantly attenuates the diffuse alveolar damage that occurs after T-cell transfer, resulting in enhanced survival. TNF-alpha processing is required for lung epithelial cell expression of CXCL2 and the subsequent inflammatory infiltration. CXCL2 expression is important in acute lung injury
malfunction
-
ADAM17-deficient mice are not viable. Mice with dramatically reduced ADAM17 levels show substantially increased susceptibility to inflammation in dextran sulfate sodium colitis and develop eye, heart, and skin defects
malfunction
-
ADAM17-deficient mice have defects in the mammary epithelium, vascular system, lung, eye, hair, heart and skin and as a result die between embryonic day 17.5 and the first few days after birth
malfunction
-
inhibition of ADAM17 protects from lipopolysaccharide-induced sepsis
malfunction
-
enzyme inhibition prevents progression of aneurysmal growth. Enzyme deficiency in smooth muscle and endothelial cells is sufficient to suppress thoracic aortic aneurysm dilation markedly. Enzyme deficiency in smooth muscle cells prevented the contractile-to-synthetic phenotypic switching in these cells after TAA induction, preventing perivascular fibrosis, inflammation, and adverse aortic remodeling. Loss of enzyme in endothelial cells protects the integrity of the intimal barrier by preserving the adherens junction (vascular endothelial-cadherin) and tight junctions (junctional adhesion molecule-A and claudin)
physiological function
-
during early events of death receptor-mediated neutrophil apoptosis, L-selectin downregulation occurs primarily by ADAM17-mediated shedding. ADAM17 activity occurs during programmed cell death. The cleavage of particular ADAM17 substrates may be an additional component of the anti-inflammatory program initiated by apoptotic neutrophils. During later stages of induced leukocyte apoptosis, soluble L-selectin production occurs independent of ADAM17, as well as membrane events, such as blebbing and microparticle production
physiological function
-
in 1C11-derived neuronal cells, antibody-mediated prion protein ligation triggers TNF-alpha release, through recruitement of the metalloproteinase TNF-alpha converting enzyme TACE. TNF-alpha shed in response to prion protein acts as a second message signal, eliciting serotonin or norepinephrine degradation in 1C115-HT or 1C11NE cells, respectively
physiological function
-
vitamin B12 cellular deficiency produces a slower proliferation and a speedier differentiation of neuroblastoma cells through interacting signaling pathways that are related with increased expression of phophatase 2A, pro-nerve growth factor and TACE
physiological function
-
ADAM17 has pro-inflammatory activity, protects from osteoporosis and is necessary for the growth of lung cancer cells
physiological function
-
ADAM17 is needed for vital regenerative activities during the immune response. ADAM17 is not crucial for developmental Notch or Notch ligand function in vivo
physiological function
-
ADAM17 plays an in vivo role in controlling inflammation and tissue regeneration. ADAM17 modulates inflammation by activation of TNFR- and IL-6R-mediated signal transduction. ADAM17 activity regulates both homeostatic and activation-induced changes in cell surface L-selectin density and, thus, might direct the migration patterns of activated lymphocytes and neutrophils in vivo. Apoptosis leads to activation of ADAM17. During ADAM17 maturation, the prodomain is removed by furin cleavage. ADAM17 protects hepatocytes from apoptosis
physiological function
-
ADAM17is the main sheddase of interleukin-6 receptor to induce interleukin-6 trans-signaling
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_MOUSE
827
1
93056
Swiss-Prot
Secretory Pathway (Reliability: 3)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
100000
-
100 kDa reduced form represents mature TACE lacking the prodomain, immunoprecipitation
120000
-
full length form of TACE migrates as a 120 kDa protein under reducing conditions, immunoprecipitation
80000
-
migrates as a 80 kDa protein under non-reducing conditions, immunoprecipitation
85000
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
T735A
-
the mutant has a basal TGF-alpha shedding activity lower than that of wild type cells and shedding is not induced by p38 MAPK
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
reconstitution of TNF shedding in TACE-deficient cells by TACE cDNA transfection
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
treatment with angiotensin II results in angiotensin II type 1 receptor AT1R-mediated increase myocardial TACE expression and activity
ADAM17 is expressed in most tissues and is up-regulated during inflammation and cancer
-
in proliferating cells which are stably transfected to impose the anchorage of a chimeric B12-binding protein, transcobalamin-oleosin TO, to the intracellular membrane, a 2-fold increase of p75NTR-regulated intramembraneous proteolysis is observed that is associated with an increased expression of enzymes Adam-10 and Adam-17
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
analysis
development of a fluorescence resonance energy transfer-based biosensor that quantitatively reports the kinetics of TACE activity in live cells
medicine
inhibition of ADAM17-mediated processing of TNF-alpha by CD8+ T cells significantly attenuates the diffuse alveolar damage that occurs after T-cell transfer, resulting in enhanced survival. TNF-alpha processing is required for lung epithelial cell expression of CXCL2 and the subsequent inflammatory infiltration. CXCL2 expression is important in acute lung injury
medicine
molecular biology
-
TACE/ADAM17-like proteases might play a role in synaptic formation to generate specific neuronal connections by processing the excess amount of RA175/SynCAM1, a member of the immunoglobulin family 4, located in the non-synaptic region
medicine
-
treatment of mice in a lipopolysaccharide-induced endotoxemia model group with recombinant TACE prodomain protein prior to the injection of lipopolysaccharide. The recombinant prodomain protein decreases the release of the secreted TNF-alpha, which mediates the accumulation of TNF-alpha on the surface of macrophage cells. The recombinant protein can decrease the inflammatory response in internal organs of endotoxaemia mice
medicine
-
ADAM17 is a potential drug target in tumor necrosis factor and/or epidermal growth factor receptordependent pathologies in inflammation and cancer
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Buxbaum, J.D.; Liu, K.N.; Luo, Y.; Slack, J.L.; Stocking, K.L.; Peschon, J.J.; Johnson, R.S.; Castner, B.J.; Cerretti, D.P.; Black, R.A.
Evidence that tumor necrosis factor alpha converting enzyme is involved in regulated alpha-secretase cleavage of the Alzheimer amyloid protein precursor
J. Biol. Chem.
273
27765-27767
1998
Homo sapiens, Mus musculus
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
Cerretti, D.P.
Characterization of the tumor necrosis factor alpha-converting enzyme, TACE/ADAM17
Biochem. Soc. Trans.
27
219-223
1999
Homo sapiens, Mus musculus
Mizui, Y.; Yamazaki, K.; Sagane, K.; Tanaka, I.
cDNA cloning of mouse tumor necrosis factor-.alpha. converting enzyme (TACE) and partial analysis of its promoter
Gene
233
67-74
1999
Mus musculus
Moss, M.; Becherer, J.D.; Milla, M.; Pahel, G.; Lambert, M.; Andrews, R.; Frye, S.; Haffner, C.; Cowan, D.; Maloney, P.; Dixon, E.P.; Jansen, M.; Vitek, M.P.; Mitchell, J.; Leesnitzer, T.; Warner, J.; Conway, J.; Bickett, D.M.; Bird, M.; Priest, R.; Reinhard, J.; Lin, P.
TNF.alpha. converting enzyme
Metalloproteinases as targets for anti-inflammatory drugs, (Bottomley, K. M. K; Bradshaw, D. ; Nixon, J. S. eds. )
187-203
1999
Homo sapiens, Mus musculus, Mus musculus C3H/HEN
-
Becherer, J.D.; Lambert, M.H.; Andrews, R.C.
The tumor necrosis factor-alpha converting enzyme
Handbook of Experimental Pharmacology, (von der Helm, K. ; Korant, B. C. ; Cheronis, J. C. eds. )
140
235-258
2000
Homo sapiens, Mus musculus, Sus scrofa
-
Brou, C.; Logeat, F.; Gupta, N.; Bessia, C.; LeBail, O.; Doedens, J.R.; Cumano, A.; Roux, P.; Black, R.A.; Israel, A.
A novel proteolytic cleavage involved in notch signaling: the role of the disintegrin-metalloprotease TACE
Mol. Cell
5
207-216
2000
Homo sapiens, Mus musculus
Reddy, P.; Slack, J.L.; Davis, R.; Cerretti, D.P.; Kozlosky, C.J.; Blanton, R.A.; Shows, D.; Peschon, J.J.; Black, R.A.
Functional analysis of the domain structure of tumor necrosis factor-alpha converting enzyme
J. Biol. Chem.
275
14608-14614
2000
Homo sapiens, Homo sapiens (P78536), Mus musculus, Mus musculus EC-4
Rio, C.; Buxbaum, J.D.; Peschon, J.J.; Corfas, G.
Tumor necrosis factor-alpha-converting enzyme is required for cleavage of erbB4/HER4
J. Biol. Chem.
275
10379-10387
2000
Mus musculus
Schloendorff, J.; Becherer, J.D.; Blobel, C.P.
Intracellular maturation and localization of the tumor necrosis factor alpha convertase (TACE)
Biochem. J.
347
131-138
2000
Chlorocebus aethiops, Homo sapiens, Mus musculus
-
Zhang, Y.; Jiang, J.; Black, R.A.; Baumann, G.; Frank, S.J.
Tumor necrosis factor-alpha converting enzyme (TACE) is a growth hormone binding protein (GHBP) sheddase: the metalloprotease TACE/ADAM-17 is critical for (PMA-induced) GH receptor proteolysis and GHBP generation
Endocrinology
141
4342-4348
2000
Oryctolagus cuniculus, Homo sapiens, Mus musculus
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
Rovida, E.; Paccagnini, A.; Del Rosso, M.; Peschon, J.; Sbarba, P.D.
TNF-alpha-converting enzyme cleaves the macrophage colony-stimulating factor receptor in macrophages undergoing activation
J. Immunol.
166
1583-1589
2001
Homo sapiens, Mus musculus
Skovronsky, D.M.; Fath, S.; Lee, V.M.Y.; Milla, M.E.
Neuronal localization of the TNFalpha converting enzyme (TACE) in brain tissue and its correlation to amyloid plaques
J. Neurobiol.
49
40-46
2001
Homo sapiens, Mus musculus
Tsou, C.L.; Haskell, C.A.; Charo, I.F.
Tumor necrosis factor-alpha-converting enzyme mediates the inducible cleavage of fractalkine
J. Biol. Chem.
276
44622-44626
2001
Homo sapiens, Mus musculus
Vincent, B.; Paitel, E.; Saftig, P.; Frobert, Y.; Hartmann, D.; De Strooper, B.; Grassi, J.; Lopez-Perez, E.; Checler, F.
The disintegrins ADAM10 and TACE contribute to the constitutive and phorbol ester-regulated normal cleavage of the cellular prion protein
J. Biol. Chem.
276
37743-37746
2001
Homo sapiens, Mus musculus
Black, R.A.
Tumor necrosis factor-alpha converting enzyme
Int. J. Biochem. Cell Biol.
34
1-5
2002
Homo sapiens, Mus musculus
Mohan, M.J.; Seaton, T.; Mitchell, J.; Howe, A.; Blackburn, K.; Burkhart, W.; Moyer, M.; Patel, I.; Waitt, G.M.; Becherer, J.D.; Moss, M.L.; Milla, M.E.
The tumor necrosis factor-alpha converting enzyme (TACE): A unique metalloproteinase with highly defined substrate selectivity
Biochemistry
41
9462-9469
2002
Homo sapiens, Mus musculus
Parkin, E.T.; Trew, A.; Christie, G.; Faller, A.; Mayer, R.; Turner, A.J.; Hooper, N.M.
Structure-activity relationship of hydroxamate-based inhibitors on the secretases that cleave the amyloid precursor protein, angiotensin converting enzyme, CD23, and pro-tumor necrosis factor-alpha
Biochemistry
41
4972-4981
2002
Chlorocebus aethiops, Homo sapiens, Mus musculus
Sunnarborg, S.W.; Hinkle, C.L.; Stevenson, M.; Russell, W.E.; Raska, C.S.; Peschon, J.J.; Castner, B.J.; Gerhart, M.J.; Paxton, R.J.; Black, R.A.; Lee, D.C.
Tumor necrosis factor-alpha converting enzyme (TACE) regulates epidermal growth factor receptor ligand availability
J. Biol. Chem.
277
12838-12845
2002
Homo sapiens, Mus musculus
Xu, H.; Uysal, K.T.; Becherer, J.D.; Arner, P.; Hotamisligil, G.S.
Altered tumor necrosis factor-alpha (TNF-alpha) processing in adipocytes and increased expression of transmembrane TNF-alpha in obesity
Diabetes
51
1876-1883
2002
Homo sapiens, Mus musculus
Canault, M.; Peiretti, F.; Kopp, F.; Bonardo, B.; Bonzi, M.; Coudeyre, J.; Alessi, M.; Juhan-Vague, I.; Nalbone, G.
The TNF alpha converting enzyme (TACE/ADAM17) is expressed in the atherosclerotic lesions of apolipoprotein E-deficient mice: Possible contribution to elevated plasma levels of soluble TNF alpha receptors
Atherosclerosis
187
82-91
2006
Homo sapiens, Mus musculus
Bergmeier, W.; Piffath, C.L.; Cheng, G.; Dole, V.S.; Zhang, Y.; von Andrian, U.H.; Wagner, D.D.
Tumor necrosis factor-alpha-converting enzyme (ADAM17) mediates GPIba shedding from platelets in vitro and in vivo
Circ. Res.
95
677-683
2004
Homo sapiens, Mus musculus
Weskamp, G.; Schloendorff, J.; Lum, L.; Becherer, J.D.; Kim, T.; Saftig, P.; Hartmann, D.; Murphy, G.; Blobel, C.P.
Evidence for a critical role of the tumor necrosis factor a convertase (TACE) in ectodomain shedding of the p75 neurotrophin receptor (p75NTR)
J. Biol. Chem.
279
4241-4249
2004
Cricetulus griseus, Mus musculus
Lambert, D.W.; Yarski, M.; Warner, F.J.; Thornhill, P.; Parkin, E.T.; Smith, A.I.; Hooper, N.M.; Turner, A.J.
Tumor necrosis factor-alpha convertase (ADAM17) mediates regulated ectodomain shedding of the severe-acute respiratory syndrome-coronavirus (SARS-CoV) receptor, angiotensin-converting enzyme-2 (ACE2)
J. Biol. Chem.
280
30113-30119
2005
Mus musculus
Tsakadze, N.L.; Sithu, S.D.; Sen, U.; English, W.R.; Murphy, G.; DSouza, S.E.
Tumor necrosis factor-alpha-converting enzyme (TACE/ADAM-17) mediates the ectodomain cleavage of intercellular adhesion molecule-1 (ICAM-1)
J. Biol. Chem.
281
3157-3164
2006
Mus musculus
Sahin, U.; Weskamp, G.; Kelly, K.; Zhou, H.; Higashiyama, S.; Peschon, J.; Hartmann, D.; Saftig, P.; Blobel, C.P.
Distinct roles for ADAM10 and ADAM17 in ectodomain shedding of six EGFR ligands
J. Cell Biol.
164
769-779
2004
Mus musculus
Souza, D.G.; Ferreira, F.L.; Fagundes, C.T.; Amaral, F.A.; Vieira, A.T.; Lisboa, R.A.; Andrade, M.V.; Trifilieff, A.; Teixeira, M.M.
Effects of PKF242-484 and PKF241-466, novel dual inhibitors of TNF-alpha converting enzyme and matrix metalloproteinases, in a model of intestinal reperfusion injury in mice
Eur. J. Pharmacol.
571
72-80
2007
Mus musculus
Zhan, M.; Jin, B.; Chen, S.; Reecy, J.M.; Li, Y.
TACE release of TNF-alpha mediates mechanotransduction-induced activation of p38 MAPK and myogenesis
J. Cell Sci.
120
692-701
2007
Mus musculus
Tanabe, Y.; Kasahara, T.; Momoi, T.; Fujita, E.
Neuronal RA175/SynCAM1 isoforms are processed by tumor necrosis factor-alpha-converting enzyme (TACE)/ADAM17-like proteases
Neurosci. Lett.
444
16-21
2008
Mus musculus
Bozkulak, E.C.; Weinmaster, G.
Selective use of ADAM10 and ADAM17 in activation of Notch1 signaling
Mol. Cell. Biol.
29
5679-5695
2009
Mus musculus
Killock, D.J.; Ivetic, A.
The cytoplasmic domains of TNFalpha-converting enzyme (TACE/ADAM17) and L-selectin are regulated differently by p38 MAPK and PKC to promote ectodomain shedding
Biochem. J.
428
293-304
2010
Mus musculus
Li, X.; Yan, Y.; Huang, W.; Yang, Y.
The study of the inhibition of the recombinant TACE prodomain to endotoxemia in mice
Int. J. Mol. Sci.
10
5442-5454
2009
Mus musculus
Wang, Y.; Zhang, A.C.; Ni, Z.; Herrera, A.; Walcheck, B.
ADAM17 activity and other mechanisms of soluble L-selectin production during death receptor-induced leukocyte apoptosis
J. Immunol.
184
4447-4454
2010
Homo sapiens, Mus musculus
Pradines, E.; Loubet, D.; Mouillet-Richard, S.; Manivet, P.; Launay, J.M.; Kellermann, O.; Schneider, B.
Cellular prion protein coupling to TACE-dependent TNF-alpha shedding controls neurotransmitter catabolism in neuronal cells
J. Neurochem.
110
912-923
2009
Mus musculus
Liu, Q.; Zhang, J.; Tran, H.; Verbeek, M.; Reiss, K.; Estus, S.; Bu, G.
LRP1 shedding in human brain: Roles of ADAM10 and ADAM17
Mol. Neurodegener.
4
17
2009
Mus musculus
Battaglia-Hsu, S.F.; Akchiche, N.; Noel, N.; Alberto, J.M.; Jeannesson, E.; Orozco-Barrios, C.E.; Martinez-Fong, D.; Daval, J.L.; Gueant, J.L.
Vitamin B12 deficiency reduces proliferation and promotes differentiation of neuroblastoma cells and up-regulates PP2A, proNGF, and TACE
Proc. Natl. Acad. Sci. USA
106
21930-21935
2009
Mus musculus
Chalaris, A.; Rose-John, S.
Proteases. ADAM 17: Molecular switch between inflammation and regeneration
BIOspektrum
17
506-509
2011
Mus musculus
-
Garbers, C.; Jaenner, N.; Chalaris, A.; Moss, M.L.; Floss, D.M.; Meyer, D.; Koch-Nolte, F.; Rose-John, S.; Scheller, J.
Species specificity of ADAM10 and ADAM17 proteins in interleukin-6 (IL-6) trans-signaling and novel role of ADAM10 in inducible IL-6 receptor shedding
J. Biol. Chem.
286
14804-14811
2011
Mus musculus
Chalaris, A.; Adam, N.; Sina, C.; Rosenstiel, P.; Lehmann-Koch, J.; Schirmacher, P.; Hartmann, D.; Cichy, J.; Gavrilova, O.; Schreiber, S.; Jostock, T.; Matthews, V.; Haesler, R.; Becker, C.; Neurath, M.; Reiss, K.; Saftig, P.; Scheller, J.; Rose-John, S.
Critical role of the disintegrin metalloprotease ADAM17 for intestinal inflammation and regeneration in mice
J. Exp. Med.
207
1617-1624
2010
Mus musculus
Scheller, J.; Chalaris, A.; Garbers, C.; Rose-John, S.
ADAM17: A molecular switch to control inflammation and tissue regeneration
Trends Immunol.
32
380-387
2011
Mus musculus
Lorenzen, I.; Lokau, J.; Dsterhft, S.; Trad, A.; Garbers, C.; Scheller, J.; Rose-John, S.; Grtzinger, J.
The membrane-proximal domain of A disintegrin and metalloprotease 17 (ADAM17) is responsible for recognition of the interleukin-6 receptor and interleukin-1 receptor II
FEBS Lett.
586
1093-1100
2012
Mus musculus (Q9Z0F8)
Marczynska, J.; Ozga, A.; Wlodarczyk, A.; Majchrzak-Gorecka, M.; Kulig, P.; Banas, M.; Michalczyk-Wetula, D.; Majewski, P.; Hutloff, A.; Schwarz, J.; Chalaris, A.; Scheller, J.; Rose-John, S.; Cichy, J.
The role of metalloproteinase ADAM17 in regulating ICOS ligand-mediated humoral immune responses
J. Immunol.
193
2753-2763
2014
Mus musculus (Q9Z0F8)
Patel, V.B.; Clarke, N.; Wang, Z.; Fan, D.; Parajuli, N.; Basu, R.; Putko, B.; Kassiri, Z.; Turner, A.J.; Oudit, G.Y.
Angiotensin II induced proteolytic cleavage of myocardial ACE2 is mediated by TACE/ADAM-17: a positive feedback mechanism in the RAS
J. Mol. Cell. Cardiol.
66
167-176
2014
Homo sapiens (P78536), Mus musculus (Q9Z0F8)
DeBerge, M.; Ely, K.; Cheng, G.; Enelow, R.
ADAM17-mediated processing of TNF-alpha expressed by antiviral effector CD8+ T cells is required for severe T-cell-mediated lung injury
PLoS ONE
8
e79340
2013
Mus musculus (Q9Z0F8)
Chapnick, D.; Bunker, E.; Liu, X.
A biosensor for the activity of the "sheddase" TACE (ADAM17) reveals novel and cell type-specific mechanisms of TACE activation
Sci. Signal.
8
365
2015
Mus musculus (Q9Z0F8)
Xu, J.; Sriramula, S.; Lazartigues, E.
Excessive glutamate stimulation impairs ACE2 activity through ADAM17-mediated shedding in cultured cortical neurons
Cell. Mol. Neurobiol.
38
1235-1243
2018
Mus musculus
Shen, M.; Hu, M.; Fedak, P.; Oudit, G.; Kassiri, Z.
Cell-specific functions of ADAM17 regulate the progression of thoracic aortic aneurysm
Circ. Res.
123
372-388
2018
Mus musculus, Homo sapiens (P78536), Homo sapiens
Yoneyama, T.; Gorry, M.; Miller, M.; Gaither-Davis, A.; Lin, Y.; Moss, M.; Griffith, L.; Lauffenburger, D.; Stabile, L.; Herman, J.; Vujanovic, N.
Modification of proteolytic activity matrix analysis (PrAMA) to measure ADAM10 and ADAM17 sheddase activities in cell and tissue lysates
J. Cancer
8
3916-3932
2017
Mus musculus, Homo sapiens (P78536)
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