3.4.24.81: ADAM10 endopeptidase
This is an abbreviated version!
For detailed information about ADAM10 endopeptidase, go to the full flat file.
Word Map on EC 3.4.24.81
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3.4.24.81
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alzheimer
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adam17
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amyloid
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ectodomain
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sheddase
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alpha-secretase
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endothelial
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metalloproteases
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neuroprotective
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plaque
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amyloidogenic
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non-amyloidogenic
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tnf
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sh-sy5y
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synaptic
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secretase
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membrane-anchored
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tetraspanins
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gamma-secretase
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n-cadherin
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presenilins
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notch1
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intramembrane
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abeta
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cxcl16
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prpc
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prion
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amyloid-beta
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prodomains
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psen1
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beta-secretase
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sappalpha
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hb-egf
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beta-site
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trans-signaling
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amphiregulin
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fractalkine
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meprin
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disintegrin-like
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adam17-mediated
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app-cleaving
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betacellulin
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nicastrin
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timp-3
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molecular biology
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anti-amyloidogenic
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medicine
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srage
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notch-dependent
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ad-like
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juxtamembrane
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bace-1
- 3.4.24.81
- alzheimer
- adam17
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amyloid
- ectodomain
- sheddase
- alpha-secretase
- endothelial
- metalloproteases
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neuroprotective
- plaque
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amyloidogenic
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non-amyloidogenic
- tnf
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sh-sy5y
- synaptic
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secretase
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membrane-anchored
- tetraspanins
- gamma-secretase
- n-cadherin
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presenilins
- notch1
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intramembrane
- abeta
- cxcl16
- prpc
- prion
- amyloid-beta
- prodomains
- psen1
- beta-secretase
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sappalpha
- hb-egf
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beta-site
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trans-signaling
- amphiregulin
- fractalkine
- meprin
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disintegrin-like
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adam17-mediated
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app-cleaving
- betacellulin
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nicastrin
- timp-3
- molecular biology
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anti-amyloidogenic
- medicine
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srage
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notch-dependent
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ad-like
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juxtamembrane
- bace-1
Reaction
endopeptidase of broad specificity =
Synonyms
a disintegrin and metalloprotease 10, a disintegrin and metalloproteinase 10, a disintegrin and metalloproteinase-10, a-disintegrin-and-metalloprotease 10, AD10, ADAM 10, ADAM-10, ADAM10, CD156c, CD23 metalloprotease, HsT18717, kuz, kuzbanian, Kuzbanian protein, MADM, mammalian disintegrin-metalloprotease, metalloproteinase 10, metalloproteinase ADAM10, metalloproteinase Kuzbanian, metalloproteinase MADM, metalloproteinase-disintegrin, myelin-associated disintegrin metalloproteinase, notch proteinase, transmembrane metzinkin-protease of the a disintegrin and metalloproteinase family-10
ECTree
3.4.24.81 ADAM10 endopeptidaseAdvanced search results
results (
results (Substrates Products
Substrates Products on EC 3.4.24.81 - ADAM10 endopeptidase
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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
amyloid precursor-like protein 2 + H2O
soluble amyloid precursor-like protein 2 ectodomain + amyloid precursor-like protein 2 C-terminal fragments
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ADAM10 cleaves after Arg670
-
-
?
beta-amyloid precursor protein + H2O
sAPP-alpha fragment of beta-amyloid precursor protein + C-terminal fragment of beta-amyloid precursor protein
Bri2 protein + H2O
?
-
-
the ADAM10 cleavage liberates the BRICHOS domain of Bri2
-
?
cell adhesion molecule CADM1 + H2O
?
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
?
-
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
-
?
collagen XVII/BP180 + H2O
?
-
ADAM9 and ADAM10 are the most prominent collagen XVII sheddases in primary keratinocytes
-
-
?
E(Edans)-PLAQAVRSSS[O-(beta-D-Glc-(1->3)-alpha-D-GlcNAc]-K(Dabcyl) + H2O
E(Edans)-PLAQA + VRSSS[O-(beta-D-Glc-(1->3)-alpha-D-GlcNAc]-K(Dabcyl)
-
-
-
ir
epithelial growth factor receptor
?
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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
-
-
-
-
?
Fas ligand + H2O
soluble Fas ligand ectodomain + ?
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transmembrane protein
-
-
?
gamma-protocadherin C3 + H2O
25-kDa C-terminal fragment of gamma-protocadherin C3 + ?
-
-
-
-
?
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)
-
-
-
?
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)
-
-
-
?
interleukin-6 receptor + H2O
?
-
apoptosis-induced shedding of interleukin-6 receptor is mediated by ADAM10
-
-
?
interleukin-6 receptor + H2O
sIL-6R fragment + C-terminal fragment
-
-
-
?
interleukin-6 receptor subunit alpha + H2O
?
-
cleavage occurs between residues LPVQ357-DSSV. Substrate shows N-linked glycosylation 7 residues apart from scissile bond
-
?
L1 adhesion molecule
L1-200 fragment + L1-32 fragment + ?
-
ADAM10 cleaves L1
-
?
meprin A + H2O
?
-
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
?
-
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
-
?
nectin 1 + H2O
?
-
ADAM10 is the major secretase responsible for nectin-1 ectodomain cleavage in neurons and the brain
-
-
?
Notch S2 + H2O
Notch extracellular truncation fragment + ?
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the enzyme is responsible for proteolytic cleavage at the S2 cleavage site within the extracellular juxtamembrane region of the Notch C-terminal fragment, which leads to the removal of the Notch ectodomain and the generation of a membrane-anchored Notch C-terminal fragment, termed Notch extracellular truncation
-
-
?
probetacellulin + H2O
?
-
cleavage occurs between residues CVVA31-DGNS. Substrate shows N-linked glycosylation 3 residues apart from scissile bond
-
?
proheparin-binding EGF-like growth factor + H2O
?
-
cleavage occurs between residues RKVR62-DLQE. Substrate shows O-linked glycosylation 13 residues apart from scissile bond
-
?
protocadherin + H2O
?
-
ADAM10 cleaves the extracellular domain of protocadherin
-
-
?
protransforming growth factor alpha + H2O
?
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cleavage occurs between residues AAA39-VVSH. Substrate shows N-linked glycosylation 14 residues apart from scissile bond
-
?
syndecan-1 + H2O
?
both ADAM10 and ADAM17 contribute to SDC1 shedding
-
-
?
VE-cadherin + H2O
?
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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
-
-
?
amyloid precursor protein + H2O
?
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cleaves amyloid precursor protein in its transmembrane region alpha-secretase activity
-
-
?
amyloid precursor protein + H2O
?
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tetraspanin12 associates with mature ADAM10, promotes ADAM10 maturation, and enhances ADAM10 dependent cleavage of amyloid precursor protein
-
-
?
amyloid precursor protein + H2O
?
-
ADAM10 plays a central role in the developing brain by controlling mainly Notch-dependent pathways but likely also by reducing surface shedding of other neuronal membrane proteins including amyloid precursor protein
-
-
?
amyloid precursor protein + H2O
?
-
cleaves amyloid precursor protein in its transmembrane region alpha-secretase activity
-
-
?
annexin A1 + H2O
?
-
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
-
-
-
-
?
beta-amyloid precursor protein
sAPP-alpha fragment + C-terminal fragment
-
-
-
?
beta-amyloid precursor protein
sAPP-alpha fragment + C-terminal fragment
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A172 cell line has alpha-secretase activity
-
?
beta-amyloid precursor protein
sAPP-alpha fragment + C-terminal fragment
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LoVo cell line overexpressing ADAM10 secreted a 185% of sAPP-alpha over control values
-
?
beta-amyloid precursor protein
sAPP-alpha fragment + C-terminal fragment
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platelet and cerebrospinal fluid have lower levels of alpha-APP in Alzheimer patients
-
-
?
beta-amyloid precursor protein + H2O
sAPP-alpha fragment + C-terminal fragment
-
-
-
-
?
beta-amyloid precursor protein + H2O
sAPP-alpha fragment + C-terminal fragment
-
-
-
?
beta-amyloid precursor protein + H2O
sAPP-alpha fragment + C-terminal fragment
cleavage at Lys683-Leu684
-
-
?
beta-amyloid precursor protein + H2O
sAPP-alpha fragment + C-terminal fragment
-
-
-
-
?
beta-amyloid precursor protein + H2O
sAPP-alpha fragment + C-terminal fragment
-
-
-
?
beta-amyloid precursor protein + H2O
sAPP-alpha fragment of beta-amyloid precursor protein + C-terminal fragment of beta-amyloid precursor protein
-
-
-
-
?
beta-amyloid precursor protein + H2O
sAPP-alpha fragment of beta-amyloid precursor protein + C-terminal fragment of beta-amyloid precursor protein
-
-
-
-
?
C4.4A + H2O
?
-
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
-
-
?
CD84 + H2O
?
signaling lymphocyte activation molecule (SLAM) family receptor CD84
CD84 is cleaved from the surface of human platelets. ADAM10 is the principal sheddase responsible for CD84 cleavage
-
?
CD84 + H2O
?
signaling lymphocyte activation molecule (SLAM) family receptor CD84
CD84 is cleaved from the surface of murine platelets. ADAM10 is the principal sheddase responsible for CD84 cleavage
-
?
cellular prion protein
N1 fragment + C-terminal fragment
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constitutive protein cleavage
-
?
cellular prion protein
N1 fragment + C-terminal fragment
-
constitutive protein cleavage
-
?
cellular prion protein
N1 fragment + C-terminal fragment
-
knock out line has 51% of reduction in N1 formation
-
?
E-cadherin + H2O
?
efficient cleavage of the ADAM10 substrate epithelial cadherin (E-cadherin) requires supra-cytotoxic concentrations of alpha-toxin
-
-
?
FcalphaR + H2O
?
-
FcaR (CD89) is the Fc receptor for immunoglobulin A. ADAM10 and ADAM17 are involved in the shedding of FcalphaR
-
-
?
L-selectin + H2O
?
-
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 cell-adhesion molecule + H2O
?
-
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
-
-
?
N-cadherin + H2O
?
-
treatment with the PKC activator phorbol 12-myristate 13-acetate (PMA) increases N-cadherin cleavage. And treatment of the cells with PKC-alpha inhibitor Gö6976 [12-(2-cyanoethyl)-6,7,12,13-tetrahydro-13-methyl-5-oxo-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole] or PKC-alpha short hairpin RNA significantly reduces N-cadherin cleavage
-
-
?
N-cadherin + H2O
?
-
ADAM10/SAP97 interaction is required for ADAM10-mediated cleavage of synaptic N-cadherin
-
-
?
Notch1 + H2O
?
-
ADAM10 is required for site 2 cleavage of the single-pass transmembrane receptor Notch1
-
-
?
Notch1 + H2O
?
-
ADAM10 plays a central role in the developing brain by controlling mainly Notch-dependent pathways but likely also by reducing surface shedding of other neuronal membrane proteins including amyloid precursor protein
-
-
?
Notch1 + H2O
?
-
although Notch1 is a substrate for both ADAM10 and ADAM17, the particular ADAM required for receptor activation is context dependent. Specifically, ADAM10 is absolutely required for Notch1 signaling induced by ligands. Noth proteases participated in signaling intrinsic to Notch1 mutations associated with leukemia
-
-
?
RAGE + H2O
?
-
a soluble form of the receptor for advanced glycation endproducts (RAGE) is produced by proteolytic cleavage of the membrane-bound form by ADAM10
-
-
?
RAGE + H2O
?
-
a soluble form of the receptor for advanced glycation endproducts (RAGE) is produced by proteolytic cleavage of the membrane-bound form by ADAM10
-
-
?
transforming growth factor alpha + H2O
?
-
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
?
-
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
-
-
?
betacellulin precursor + H2O
additional information
-
-
-
one major (26-28 kDa) soluble form + two minor (20 and 15 kDa) soluble forms + cellular remnant lacking the ectodomain (12 kDa)
-
?
additional information
?
-
-
TIMP1 and TIMP-3 (tissue inhibitors of metalloproteinase) interact and inhibit ADAM10
-
-
?
additional information
?
-
-
ADAM10 cleaves ephrin from its membrane tether on the opposite cell (through its so-called sheddase activity), thereby separating the cell-cell connection and allowing the signalling complex to internalise. Ephrin-A5 shedding by ADAM10 is controlled by steric hindrance exerted by the membrane-proximal EphA3 kinase domain, which prevents the functional interaction with ADAM10 that is needed for efficient substrate (ephrin) cleavage to occur
-
-
?
additional information
?
-
-
peptide libraries are used to define the cleavage site selectivity of TACE (EC 3.4.24.86) and ADAM10. The two proteases have distinct primary sequence requirements at multiple positions surrounding the cleavage site in their substrates, which allows to generate peptide substrates that are highly specific for each of these proteases. The major difference between the two protease specificities maps to the P1' position (immediately downstream of the cleavage site) of the substrate. At this position, TACE is selective for smaller aliphatic residues, whereas ADAM10 can accommodate aromatic amino acids. Using mutagenesis three residues in the S1' pockets of these enzymes are identified that dramatically influence specificity for both peptide and protein substrates
-
-
?
additional information
?
-
the enzyme can cut normal prion proteins from the surface of neurons
-
-
?
neuronal cadherin + H2O
additional information
-
-
-
40 kDa C-terminal fragment + N-terminal 95 kDa fragment
-
?
