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
-
amyloid
- ectodomain
- sheddase
- alpha-secretase
- endothelial
- metalloproteases
-
neuroprotective
- plaque
-
amyloidogenic
-
non-amyloidogenic
- tnf
-
sh-sy5y
- synaptic
-
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 (Engineering
Engineering on EC 3.4.24.81 - ADAM10 endopeptidase
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PROTEIN VARIANTS 
ORGANISM
UNIPROT
COMMENTARY 
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
N439
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mutation at the N-glycosylation site N439 increase ADAM10s susceptibility to proteolytical degradation
Q170H
R181G
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
Q170H
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Alzheimers disease-associated non-synonymous mutations, Q170H and R181G. These mutations are found in 11 of 16 affected individuals (average onset age 69.5 years) from seven late-onset Alzheimers disease families. Each mutation is also found in one unaffected subject implying incomplete penetrance. Functionally, both mutations significantly attenuate alpha-secretase activity of ADAM10 (more than 70% decrease), and elevate Abeta levels (1.53.5-fold) in cell-based studies
Q170H
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significant evidence for an association of Alzheimers disease with the metalloproteinase with respect to two mutations: Q170H and R181G
Q170H
the mutation in the pro-domain region of the ADAM10 gene reduce alpha-secretase activity of the enzyme
R181G
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Alzheimers disease-associated non-synonymous mutations, Q170H and R181G. These mutations are found in 11 of 16 affected individuals (average onset age 69.5 years) from seven late-onset Alzheimers disease families. Each mutation is also found in one unaffected subject implying incomplete penetrance. Functionally, both mutations significantly attenuate alpha-secretase activity of ADAM10 (more than 70% decrease), and elevate Abeta levels (1.5-3.5fold) in cell-based studies
R181G
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significant evidence for an association of Alzheimers disease with the metalloproteinase with respect to two mutations: Q170H and R181G
R181G
the mutation in the pro-domain region of the ADAM10 gene reduce alpha-secretase activity of the enzyme
additional information
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consensus sequence RKKR mutated for NAQA resulting in no expression of mature protein
additional information
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ADAM10 mutant lacking the prodomain is inactive, the prodomain is probably involved in the maturation of the enzyme
additional information
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to assess the influence of ADAM10 on the gene expression profile in the brain, a microarray analysis using RNA isolated from brains of five months old mice overexpressing either ADAM10, or a dominant-negative mutant of this enzyme. Overexpression of proteolytically active ADAM10 affects several physiological pathways, such as cell communication, nervous system development, neuron projection as well as synaptic transmission. Although ADAM10 is implicated in Notch and beta-catenin signaling, no significant changes in the respective target genes are observed in adult ADAM10 transgenic mice. RT-PCR confirms a downregulation of genes coding for the inflammation-associated proteins S100a8 and S100a9 induced by moderate ADAM10 overexpression. Overexpression of the dominant-negative form dnADAM10 leads to a significant increase in the expression of the fatty acid-binding protein Fabp7, which is found in higher amounts in brains of Down syndrome patients
additional information
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a GPI-anchored form of ADAM10 lacking the cytosolic, transmembrane and a-helical juxtamembrane regions of the wild-type protein is shed in a similar manner. Mutant fusion construct consists of the first 652 residues of wild-type ADAM10 fused, via a two residue linker, to the 24 residue GPI anchor signal sequence of human carboxypeptidase M
additional information
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increased ADAM10 expression is functionally associated with an increase in endothelial permeability. ADAM10 activity also contributes to the thrombin-induced decrease of endothelial cell-cell adhesion
additional information
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knockdown of ADAM10 in HUVECs as well as in T cells by small interfering RNA impairs T-cell transmigration
additional information
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RNA interference (RNAi)-induced knockdown of ADAM10 in human astroglioma cell line U373 has no influence on NRG-1 (neuregulin-1) shedding
additional information
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using siRNA to knockdown ADAM10 in highly invasive glioblastoma cell line U251 it is shown that CD44 shedding is compromised in a dose-dependent manner
additional information
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in ADAM10 deficient mouse embryonic cells the constitutive release of soluble epidermal growth factor and also beta-cellulin is strongly reduced when compared with wild type controls and can be reintroduced by adding of wild type ADAM10. Overexpression of ADAM10 causes an increase in beta-cellulin shedding, whereas the overexpression of catalytically inactive ADAM10 decreases the beta-cellulin shedding
additional information
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in vivo investigations of mice overexpressing either ADAM10 or dominant negative ADAM10 show unaltered cleavage of neuregulin-1 compared to wild-type animals. As a consequence, the myelin sheath thickness of peripheral nerves is unaffected in mice with altered ADAM10 activity
additional information
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inhibition of ADAM10 expression using short interfering RNA reduces N-cadherin cleavage and decreases glioblastoma cell migration
additional information
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mouse embryonic fibroblast cells deficient of ADAM10 are not able to produce cleaved RAGE (receptor for advanced glycation endproducts). Stable transfection of MEF deficient with a plasmid coding for mouse ADAM10 is able to rescue the phenotype
additional information
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the ADAM10 knockout mouse virtually represents a phenocopy of a presenilin 1/presenilin 2 double deficient mouse and thus features many traits attributable to defective Notch signalling
additional information
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the in vivo relevance of the processing of E-cadherin is supported by data from cell extracts from ADAM10 deficient mouse embryos at embryonic day 9.5, indicating that the generation is completely abolished in the knockout mice
