Information on EC 3.4.24.81 - ADAM10 endopeptidase

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The expected taxonomic range for this enzyme is: Coelomata

EC NUMBER
COMMENTARY hide
3.4.24.81
-
RECOMMENDED NAME
GeneOntology No.
ADAM10 endopeptidase
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REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
endopeptidase of broad specificity
show the reaction diagram
-
-
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of peptide bond
-
-
-
-
additional information
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ADAM10 mediates the epidermal growth factor-induced CD44 cleavage by the small monomeric GTPase Rac1
CAS REGISTRY NUMBER
COMMENTARY hide
193099-09-1
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
green monkey cell line
-
-
Manually annotated by BRENDA team
Drosophila melanogaster Oregon R
strain Oregon R
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-
Manually annotated by BRENDA team
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UniProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
metabolism
-
ADAM10 as a major alpha-secretase in the ectodomain shedding of nectin-1
physiological function
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
2,4-dinitrophenyl-EVHHQKLVFFAE + H2O
?
show the reaction diagram
-
-
-
-
?
2,4-dinitrophenyl-HGDQMAQKSQST + H2O
?
show the reaction diagram
-
-
-
-
?
2,4-dinitrophenyl-LPQLENVKGTED + H2O
?
show the reaction diagram
-
-
-
-
?
2,4-dinitrophenyl-RAEQQRLKSQDL + H2O
?
show the reaction diagram
-
-
-
-
?
2,4-dinitrophenyl-SPLAQAVRSSSR + H2O
?
show the reaction diagram
-
-
-
-
?
Abz-Leu-Ala-Gln-Ala-Val-Arg-Ser-Ser-Ser-Arg-Dap(dnp)-NH2 + H2O
?
show the reaction diagram
amyloid precursor protein + H2O
?
show the reaction diagram
amyloid precursor-like protein 2 + H2O
soluble amyloid precursor-like protein 2 ectodomain + C-terminal fragments
show the reaction diagram
-
ADAM10 cleaves after Arg670
-
-
?
annexin A1 + H2O
?
show the reaction diagram
-
ADAM10 cleaves within the N-terminal domain after Phe7, cleavage occurs on the outer cell surface during secondary but not primary necrosis
-
-
?
beta-amyloid precursor protein
sAPP-alpha fragment + C-terminal fragment
show the reaction diagram
beta-amyloid precursor protein + H2O
?
show the reaction diagram
-
-
-
-
?
beta-amyloid precursor protein + H2O
sAPP-alpha fragment + C-terminal fragment
show the reaction diagram
beta-amyloid precursor protein + H2O
sAPP-alpha fragment of beta-amyloid precursor protein + C-terminal fragment of beta-amyloid precursor protein
show the reaction diagram
betacellulin + H2O
?
show the reaction diagram
-
-
-
-
?
biotin-SPLAQAVRSSSRTPS-NH2 + H2O
?
show the reaction diagram
-
-
-
-
?
Bri2 protein + H2O
?
show the reaction diagram
-
-
the ADAM10 cleavage liberates the BRICHOS domain of Bri2
-
?
C4.4A + H2O
?
show the reaction diagram
-
the proteomic identification of a novel substrate for ADAM10 and ADAM17 is presented by using SILAC (Stable Isotope Labeling by Amino acids in Cell culture), a proteomic technique based on the differential metabolic labeling of cells in different conditions. This is applied to MCF7 cells derived from an invasive mammary tumor, and the same cells expressing shRNAs that knock down ADAM10 or -17. C4.4A is a member of the Ly-6 family originally identified in a screening designed to select membrane proteins differentially expressed on metastatic pancreatic adenocarcinoma cells
-
-
?
CD23 + H2O
?
show the reaction diagram
CD46 + H2O
sCD46-ectodomain + ?
show the reaction diagram
-
-
-
-
?
CD84 + H2O
?
show the reaction diagram
cell adhesion molecule CADM1 + H2O
?
show the reaction diagram
type I transmembrane glycoprotein, endopeptidase ADAM10 mediates endogenous CADM1 shedding. The membrane-bound fragment generated by shedding is further cleaved by gammaetase and generates CADM1-intracellular domain
-
-
?
cell surface VEGF receptor Flt + H2O
?
show the reaction diagram
-
-
release of an N-terminal extracellular fragment which can antagonize the effects of vascular endothelial growth factor, substrate can be cleaved to release an N-terminal extracellular fragment. Overexpression of ADAM10 and ADAM17, EC 3.4.24.86, increase cleavage while knockdown of ADAM10 and ADAM17 reduce N-terminal cleavage
-
?
cellular prion protein
N1 fragment + C-terminal fragment
show the reaction diagram
collagen XVII/BP180 + H2O
?
show the reaction diagram
-
ADAM9 and ADAM10 are the most prominent collagen XVII sheddases in primary keratinocytes
-
-
?
CXCL16 + H2O
?
show the reaction diagram
-
-
-
-
?
dabcyl-LAQA(homoPhe)RSC(fluorescein)-NH2 + H2O
?
show the reaction diagram
discoidin domain receptor 1 + H2O
?
show the reaction diagram
-
-
-
-
?
E-cadherin + H2O
?
show the reaction diagram
-
-
-
-
?
ephrin-A2 + H2O
?
show the reaction diagram
-
-
-
-
?
ephrin-A5 + H2O
?
show the reaction diagram
-
-
-
-
?
epidermal growth factor + H2O
?
show the reaction diagram
-
-
-
-
?
epithelial cadherin + H2O
38-kDa C-terminal fragment + ?
show the reaction diagram
epithelial growth factor receptor
?
show the reaction diagram
-
activation of the receptor leads to cleavage of transmembrane heparin-binding site by ADAM10 in response to infection by Staphylococcus aureus
-
-
?
extracellular domain of Klotho + H2O
130000 Da Klotho fragment + 68000 Da Klotho fragment
show the reaction diagram
-
-
-
-
?
Fas ligand + H2O
soluble Fas ligand ectodomain + ?
show the reaction diagram
-
transmembrane protein
-
-
?
FcalphaR + H2O
?
show the reaction diagram
gamma-protocadherin C3 + H2O
25-kDa C-terminal fragment of gamma-protocadherin C3 + ?
show the reaction diagram
-
-
-
-
?
Glu(EDANS)-Pro-Leu-Ala-Gln-Ala-Val-Arg-Ser-Ser(glycosyl)-Ser-Lys(DABCYL) + H2O
Glu(EDANS)-Pro-Leu-Ala-Gln-Ala + Val-Arg-Ser-Ser(glycosyl)-Ser-Lys(DABCYL)
show the reaction diagram
-
-
-
-
?
Glu(EDANS)-Pro-Leu-Ala-Gln-Ala-Val-Arg-Ser-Ser-Ser-Lys(DABCYL) + H2O
Glu(EDANS)-Pro-Leu-Ala-Gln-Ala + Val-Arg-Ser-Ser-Ser-Lys(DABCYL)
show the reaction diagram
-
-
-
-
?
interleukin-6 receptor + H2O
?
show the reaction diagram
-
apoptosis-induced shedding of interleukin-6 receptor is mediated by ADAM10
-
-
?
interleukin-6 receptor subunit alpha + H2O
?
show the reaction diagram
-
-
cleavage occurs between residues LPVQ357-DSSV. Substrate shows N-linked glycosylation 7 residues apart from scissile bond
-
?
L-selectin + H2O
?
show the reaction diagram
L1 adhesion molecule
L1-200 fragment + L1-32 fragment + ?
show the reaction diagram
-
ADAM10 cleaves L1
-
?
L1 cell adhesion molecule + H2O
?
show the reaction diagram
-
-
-
-
?
L1 cell-adhesion molecule + H2O
?
show the reaction diagram
L1-CAM extracellular domain + H2O
?
show the reaction diagram
-
-
-
-
?
meprin A + H2O
?
show the reaction diagram
-
-
during ischemia-reperfusion-induced acute kidney injury, meprin A is shed from proximal tubule membranes. ADAM10 inhibition is sufficient to block shedding, small interfering RNA to ADAM10 inhibits shedding
-
?
meprin beta + H2O
?
show the reaction diagram
-
-
during ischemia-reperfusion-induced acute kidney injury, meprin beta is shed from proximal tubule membranes. ADAM10 inhibition is sufficient to block shedding, small interfering RNA to ADAM10 inhibits shedding
-
?
N-cadherin + H2O
?
show the reaction diagram
nectin 1 + H2O
?
show the reaction diagram
-
ADAM10 is the major secretase responsible for nectin-1 ectodomain cleavage in neurons and the brain
-
-
?
neuronal cadherin + H2O
?
show the reaction diagram
-
-
-
-
?
neuronal cadherin + H2O
neuronal cadherin C-terminal fragment + ?
show the reaction diagram
-
-
-
-
?
Notch1 + H2O
?
show the reaction diagram
probetacellulin + H2O
?
show the reaction diagram
-
-
cleavage occurs between residues CVVA31-DGNS. Substrate shows N-linked glycosylation 3 residues apart from scissile bond
-
?
proheparin-binding EGF-like growth factor + H2O
?
show the reaction diagram
-
-
cleavage occurs between residues RKVR62-DLQE. Substrate shows O-linked glycosylation 13 residues apart from scissile bond
-
?
protocadherin + H2O
?
show the reaction diagram
-
ADAM10 cleaves the extracellular domain of protocadherin
-
-
?
protransforming growth factor alpha + H2O
?
show the reaction diagram
-
-
cleavage occurs between residues AAA39-VVSH. Substrate shows N-linked glycosylation 14 residues apart from scissile bond
-
?
RAGE + H2O
?
show the reaction diagram
receptor protein tyrosine phosphatase K + H2O
?
show the reaction diagram
-
-
-
-
?
syndecan-1 + H2O
?
show the reaction diagram
-
both ADAM10 and ADAM17 contribute to SDC1 shedding
-
-
?
thyrotropin receptor + H2O
?
show the reaction diagram
-
-
-
?
TNF-alpha + H2O
?
show the reaction diagram
-
-
-
-
?
transforming growth factor alpha + H2O
?
show the reaction diagram
tumor necrosis factor alpha + H2O
?
show the reaction diagram
VE-cadherin + H2O
?
show the reaction diagram
-
VE-cadherin is specifically cleaved by the disintegrin and metalloprotease ADAM10 in its ectodomain, releasing a soluble fragment and generating a carboxyl-terminal membrane-bound stub, which is a substrate for a subsequent gamma-secretase cleavage
-
-
?
betacellulin precursor + H2O
additional information
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NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
amyloid precursor protein + H2O
?
show the reaction diagram
annexin A1 + H2O
?
show the reaction diagram
-
ADAM10 cleaves within the N-terminal domain after Phe7, cleavage occurs on the outer cell surface during secondary but not primary necrosis
-
-
?
beta-amyloid precursor protein
sAPP-alpha fragment + C-terminal fragment
show the reaction diagram
beta-amyloid precursor protein + H2O
?
show the reaction diagram
-
-
-
-
?
beta-amyloid precursor protein + H2O
sAPP-alpha fragment of beta-amyloid precursor protein + C-terminal fragment of beta-amyloid precursor protein
show the reaction diagram
-
-
-
-
?
CD23 + H2O
?
show the reaction diagram
-
-
-
-
?
cellular prion protein
N1 fragment + C-terminal fragment
show the reaction diagram
collagen XVII/BP180 + H2O
?
show the reaction diagram
-
ADAM9 and ADAM10 are the most prominent collagen XVII sheddases in primary keratinocytes
-
-
?
E-cadherin + H2O
?
show the reaction diagram
-
-
-
-
?
epithelial growth factor receptor
?
show the reaction diagram
-
activation of the receptor leads to cleavage of transmembrane heparin-binding site by ADAM10 in response to infection by Staphylococcus aureus
-
-
?
FcalphaR + H2O
?
show the reaction diagram
-
FcaR (CD89) is the Fc receptor for immunoglobulin A. ADAM10 and ADAM17 are involved in the shedding of FcalphaR
-
-
?
L-selectin + H2O
?
show the reaction diagram
-
ADAMs 10 and 17 represent differentially regulated components of a general shedding machinery for membrane proteins such as transforming growth factor alpha, L-selectin, and tumor necrosis factor alpha
-
-
?
L1 adhesion molecule
L1-200 fragment + L1-32 fragment + ?
show the reaction diagram
-
ADAM10 cleaves L1
-
?
L1 cell-adhesion molecule + H2O
?
show the reaction diagram
-
the ectodomain of L1 cell-adhesion molecule is cleaved at the plasma membrane by ADAM10. Regulated proteolytic processing by ADAM10 and PS/gamma-secretase is essential for the nuclear signalling of L1 in human carcinoma cell lines
-
-
?
Notch1 + H2O
?
show the reaction diagram
transforming growth factor alpha + H2O
?
show the reaction diagram
-
ADAMs 10 and 17 represent differentially regulated components of a general shedding machinery for membrane proteins such as transforming growth factor alpha, L-selectin, and tumor necrosis factor alpha
-
-
?
tumor necrosis factor alpha + H2O
?
show the reaction diagram
-
ADAMs 10 and 17 represent differentially regulated components of a general shedding machinery for membrane proteins such as transforming growth factor alpha, L-selectin, and tumor necrosis factor alpha
-
-
?
additional information
?
-
-
TIMP1 and TIMP-3 (tissue inhibitors of metalloproteinase) interact and inhibit ADAM10
-
-
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Ca2+
-
ADAM10-mediated proteolysis of VE-cadherin is induced by Ca2+ influx
Zn2+
-
dependent on
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
((2R,3S)-3-(formyl-hydroxyamino)-2-(3-phenyl-1-propyl)butanoic acid)[(1S)-2,2-dimethyl-1-methylcarbamoyl-1-propyl]amide
-
compound GI254023X, IC50: 5.3
(2S)-N4-hydroxy-N1-[(1S)-1-(1H-indol-3-ylmethyl)-2-(methylamino)-2-oxoethyl]-2-isobutylsuccinamide
1,10-phenanthroline
-
inhibits shedding of Eph-A5
ADAM10 prodomain Pro-A10 WT 23-213 (C-terminal His tag)
-
48 nM, specific inhibitor
-
ADAM10 prodomain Pro-A10 WT 23-213 (N-terminal His tag)
-
75 nM, specific inhibitor
-
ADAM10 prodomain ProA10 C173S 23-213 (C-terminal His tag)
-
36 nM, specific inhibitor
-
ADAM8 prodomain Pro-A8
-
25% inhibition at 0.003 mM
-
AEBSF
-
0.1 mM
atorvastatin
-
80mg/day
BB3103
decanoyl-RVKR-chloromethylketone
-
0.03 mM of this proprotein convertase inhibitor decreases the formation of the ADAM10 mature form
EDTA
-
10 mM
EGTA
-
10 mM
G1254023X
-
specific inhibitor
GI254023
-
0.005 mM
GI254023X
GM6001
GW 280264X
-
ADAM10/17 inhibitor
GW280264
-
0.005 mM
GW280264X
GW280623X
-
inhibits RAGE (receptor for advanced glycation endproducts) cleavage
GW4023
-
-
-
o-phenanthroline
pepstatin A
-
0.001 mM
rottlerin
-
protein kinase Cdelta inhibitor causes a dramatic decrease in the activation of pro-BTC shedding by calcium ionophore A23187
TACE prodomain Pro-A17
-
11% inhibition at 0.0035 mM
-
TAPI-1
TAPI-2
TIMP-1
TIMP-2
-
modest inhibitory activity toward CD23 shedding
-
TIMP-3
tissue inhibitor of metalloproteases 1
-
500 nM TIMP-1
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tissue inhibitor of metalloproteases 3
-
500 nM TIMP-3
-
Tissue inhibitor of metalloproteinase-1
-
-
-
TNFalpha protease inhibitor
-
0.05 mM
-
Wortmannin
-
-
additional information
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(4-aminophenyl)mercuric acetate
-
-
5alpha-dihydrotestosterone
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10 nM, in the presence of 10 or 50 ng/ml insulin-like growth factor, 1.8fold upregulation of the 100-kDa proform and 3 to 4 fold stimulation of the active 60-kDa form
A23187
-
calcium ionophore
alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid hydrate
-
-
donepezil
-
because donepezil-treated cells show an increase in the metabolic active form of ADAM 10, this suggests that donepezil may cause a direct increase in the level of ADAM 10 in cellular membranes
Epidermal growth factor
-
50 ng/ml, 2fold stimulation of 100-kDa proform and 3fold stimulation of 60-kDa form
Insulin
-
0.001 mM, stimulates the cleavage of the extracellular domain of Klotho
-
insulin-like growth factor I
-
10 ng/ml or 50 ng/ml, in the presence of 10 nM 5alpha-dihydrotestosterone, 1.8fold upregulation of the 100-kDa proform and 3 to 4fold stimulation of the active 60-kDa form
-
interleukin-1alpha
-
2 ng/ml stimulates ADAM-10 level 2.1 fold after 16h treatment
-
ionomycin
phorbol 12-myristate 13-acetate
-
-
phorbol myristate acetate
-
100 nM, induces the expression of the highly processed form of ADAM10
phorbol-12 myristate 13-acetate
S100A7
-
expression of exogenous S100A7, a biomarker protein for alzheimer’s disease known to be involved in immune responses, in primary cortico-hippocampal neuron cultures derived from Tg2576 transgenic mice embryos inhibits the generation of beta-amyloid (Abeta)1-42 and Abeta1-40 peptides, coincidental with a selective promotion of non-amyloidogenic alpha-secretase activity via promotion of ADAM10. A selective expression of human S100A7, in the brain of transgenic mice results in significant promotion of alpha-secretase activity
-
staurosporine
tetraspanin
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several anti-tetraspanin mAbs (CD9, CD81, CD82) increase epidermal growth factor and/or TNF-alpha secretion through a mechanism dependent on ADAM10. The effect of anti-tetraspanin mAb on TNF-alpha release is rapid, not relayed by intercellular signaling, and depends on an intact MEK/Erk1/2 pathway. It is also associated with a concentration of ADAM10 in tetraspanin-containing patches. A large fraction of ADAM10 associates with several tetraspanins
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thyrotropin
increases dose dependently thyrotropin receptor ectodomain cleavage
-
additional information
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0085
Glu(EDANS)-Pro-Leu-Ala-Gln-Ala-Val-Arg-Ser-Ser(glycosyl)-Ser-Lys(DABCYL)
-
pH 7.5, 22°C
-
0.012
Glu(EDANS)-Pro-Leu-Ala-Gln-Ala-Val-Arg-Ser-Ser-Ser-Lys(DABCYL)
-
pH 7.5, 22°C
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.06
Glu(EDANS)-Pro-Leu-Ala-Gln-Ala-Val-Arg-Ser-Ser(glycosyl)-Ser-Lys(DABCYL)
Homo sapiens
-
pH 7.5, 22°C
-
0.28
Glu(EDANS)-Pro-Leu-Ala-Gln-Ala-Val-Arg-Ser-Ser-Ser-Lys(DABCYL)
Homo sapiens
-
pH 7.5, 22°C
-
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
8
Glu(EDANS)-Pro-Leu-Ala-Gln-Ala-Val-Arg-Ser-Ser(glycosyl)-Ser-Lys(DABCYL)
Homo sapiens
-
pH 7.5, 22°C
206921
25
Glu(EDANS)-Pro-Leu-Ala-Gln-Ala-Val-Arg-Ser-Ser-Ser-Lys(DABCYL)
Homo sapiens
-
pH 7.5, 22°C
206922
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.4
-
assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
A-172 cell line has potent alpha-secretase activity, higher than HEK-293 cell line
Manually annotated by BRENDA team
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strain U373 MG
Manually annotated by BRENDA team
-
N-Cadherin cleavage occurs at a higher level in glioblastoma cells than in non-neoplastic astrocytes
Manually annotated by BRENDA team
-
expression of ADAM 10, 12 and 17 is analyzed by immunohistochemistry in skin tissues obtained from 25 patients with different types of basal cell carcinomas. Immunoreactivity of ADAM 10, 12 and 17 is increased at the peripheral tumor margin compared with central areas of basal cell carcinomas tumor cell nests. Immunoreactivity of ADAM 10 and 12 is increased in the deep margin of invading tumor cell nests in mixed basal cell carcinomas
Manually annotated by BRENDA team
-
there is expression of the enzyme
Manually annotated by BRENDA team
-
the expression is increased 2-fold in Alzheimer disease
Manually annotated by BRENDA team
-
COS7 cell line transfected with ADAM10 produces transactivation of epidermal growth factor receptor
Manually annotated by BRENDA team
-
ADAM10 specifically localizes in the CD31+ endothelial cells in normal human cardiac tissues and in cultured primary arterial endothelial cells
Manually annotated by BRENDA team
-
HM3 cell line
Manually annotated by BRENDA team
both ADAM10 and ADAM17, EC 3.4.24.86, are present during all stages of spermatogenesis
Manually annotated by BRENDA team
-
confirmation of ADAM10-TSPAN12 association
Manually annotated by BRENDA team
-
both ADAM10 and ADAM17 contribute to SDC1 shedding and IL-8 production by HVECs in response to staphylococcal superantigen toxic shock syndrome toxin TSST-1
Manually annotated by BRENDA team
-
intestinal stem cell
Manually annotated by BRENDA team
-
there is expression of the enzyme
Manually annotated by BRENDA team
-
there is expression of the enzyme
Manually annotated by BRENDA team
-
confirmation of ADAM10-TSPAN12 association
Manually annotated by BRENDA team
-
human mesenchymal stem cells interfere with cell–cell adhesion and enhance migration of breast cancer cells by activating ADAM10
Manually annotated by BRENDA team
-
strain SH-SY5Y
Manually annotated by BRENDA team
-
TSM1 cell line
Manually annotated by BRENDA team
-
acinar cell during embryogenesis, endocrinic cell and exocrinic cell in adult
Manually annotated by BRENDA team
-
ADAM10 is necessary for epidermal growth factor receptor transactivation
Manually annotated by BRENDA team
-
cell line LNCaP, localized to the secretory cells of prostate glands, with additional basal cell expression in benign glands
Manually annotated by BRENDA team
-
human salivary gland cells are used
Manually annotated by BRENDA team
both ADAM10 and ADAM17, EC 3.4.24.86, are present during all stages of spermatogenesis
Manually annotated by BRENDA team
-
there is expression of the enzyme
Manually annotated by BRENDA team
-
stomach epithelial cell
Manually annotated by BRENDA team
both ADAM10 and ADAM17, EC 3.4.24.86, 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
Manually annotated by BRENDA team
-
there is expression of the enzyme
Manually annotated by BRENDA team
additional information
-
endothelial cells of venules and arterioles do not express ADAM10
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
in untreated cells
Manually annotated by BRENDA team
-
identification of an endoplasmic reticulum retention motif within the ADAM10 intracellular C-terminal tail. Sequential deletion/mutagenesis analyses shows that an arginine-rich (723RRR) sequence is responsible for the retention of ADAM10 in the endoplasmic reticulum and its inefficient surface trafficking. Mutating the second arginine to alanine is sufficient to allow endoplasmic reticulum exit and surface expression in both heterologous cells and hippocampal neurons
Manually annotated by BRENDA team
-
most of the activity of the enzyme
Manually annotated by BRENDA team
-
in untreated cells
Manually annotated by BRENDA team
-
predominant localization of the protein at the perinuclear region and at the cell surface where it appears as punctuated dots evenly distributed at the plasma membrane
-
Manually annotated by BRENDA team
-
exosomal
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
UNIPROT
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
45000
-
highly processed mature form, SDS-PAGE
62000 - 64000
-
active form, amino-terminal sequencing
70000
-
SDS-PAGE, mature form wild-type
98000
-
SDS-PAGE, immature form wild-type
100000
-
SDS-PAGE, proform of ADAM-10
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
glycoprotein
proteolytic modification
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
hanging-drop vapour diffusion
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
Ni2+-NTA column chromatography and Superdex-75 gel filtration
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SDS-PAGE
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
a C-terminal HA-tagged fusion protein is transfected in human ovarian cancer SKOV3 cells and human embryonic kidney HEK293 cells
ADAM10 is expressed as a wild-type protein and as a FLAG-tagged ADAM10 fusion protein in which the tag is inserted immediately C-terminal to the proprotein convertase recognition sequence RKKR. Expression is carried out by stable transfection of a human neuroblastoma SH-SY5Y cell line. Internally tagged ADAM10 fusion protein is easily detected in Western blot analysis. Catalytic activity of wild-type and internally tagged protein is indistinguishable
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expressed in Escherichia coli
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expressed in Escherichia coli BL21(DE3)Star cells
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expressed in HEK-293 cells
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expressed in human embryonic kidney HEK293 cell line
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expressed in HUVEC and COS-7 cells
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expressed in Ls174T human colon cancer cells
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expressed in MEF cells and 293-T cells
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expressed in U-251 cells
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expression in CHO cells
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generation of ADAM10—chimeras of the extracellular domain of the human interleukin-2 receptor with the intracellular C-terminal domain of mouse ADAM10. Transfection into COS7 cells
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produced in insect cells by baculoviral expression as truncated constructs consisting of the signal sequence, pro- and catalytic domains fused to a C-terminal His6 (hexahistidine) tag (residues 1–460 of mouse ADAM10).
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
ADAM10 levels are significantly enhanced on germinal center B cells
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ADAM10 mRNA is lowered in moderate to severe Alzheimer’s disease
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amount and activity of ADAM10 is increased by application of low doses of statins
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retinoids induce gene expression of ADAM10. The vitamin A analog acitretin stimulates ADAM10 promoter activity with an EC50 of 0.0015 mM
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
S269A
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mutant is detected at lower molecular masses than the wild-type form, which indicates that the N-glycosylation site is occupied
S441A
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mutant is detected at lower molecular masses than the wild-type form, which indicates that the N-glycosylation site is occupied, mutant shows increased ADAM10 susceptibility to proteolysis
T280A
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mutant is detected at lower molecular masses than the wild-type form, which indicates that the N-glycosylation site is occupied, T280A is found to accumulate in the endoplasmic reticulum as the non-processed precursor of the enzyme. Mutant exhibits only residual levels of metalloprotease activity
T553A
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mutant is detected at lower molecular masses than the wild-type form, which indicates that the N-glycosylation site is occupied
DELTA672
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a truncated soluble construct of ADAM10 lacking the transmembrane and cytosolic domains (truncation after Glu680), although correctly post-translationally processed and catalytically active with respect to a synthetic peptide substrate, is incapable of shedding cell-associated amyloid precursor protein (APP)
E384A
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the point mutation which compromises the zinc-binding consensus motif, leads to a substantial decrease in amyloid precursor protein-alpha secretion
E385A
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inactive
N439
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mutation at the N-glycosylation site N439 increase ADAM10s susceptibility to proteolytical degradation
S441A
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the mutant displays higher susceptibility to proteolysis
C173S
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mutation does not impair the inhibitory potency of the ADAM10 prodomain against ADAM10
E384A
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the point mutation which compromises the zinc-binding consensus motif, leads to a substantial decrease in amyloid precursor protein-alpha secretion
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
molecular biology