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p(HGNC:ADAM10)

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Entity

Name
ADAM10
Namespace
hgnc
Namespace Version
20180828
Namespace URL
https://raw.githubusercontent.com/pharmacome/terminology/1b20f0637c395f8aa89c2e2e342d7b704062c242/external/hgnc-symbols.belns

Appears in Networks 4

Amyloid Precursor Protein Trafficking, Processing, and Function v1.0.0

Amyloid Precursor Protein Trafficking, Processing, and Function by Thinakaran, et al., 2008

APP processing in Alzheimer's disease v1.0.1

APP processing in Alzheimer's disease

Proteolytic processing of Alzeimer's beta-amyloid precursor protein v1.0.1

M1 muscarinic acetylcholine receptor in Alzheimer’s disease v1.0.0

This file encodes the article M1 muscarinic acetylcholine receptor in Alzheimer’s disease by Jiang et al, 2014

In-Edges 4

path(MESH:"Alzheimer Disease") negativeCorrelation p(HGNC:ADAM10) View Subject | View Object

A dramatically reduced ADAM10 protein level in the platelets of sporadic AD patients was also found to correlate with the significantly decreased sAPPalpha levels found in their platlets and cerebrospinal fluid [55] and the reduced alpha-secretase activity in the temporal cortex homogenates of AD patients [56] PubMed:21214928

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Blood Platelets

path(MESH:"Alzheimer Disease") negativeCorrelation act(p(HGNC:ADAM10)) View Subject | View Object

A dramatically reduced ADAM10 protein level in the platelets of sporadic AD patients was also found to correlate with the significantly decreased sAPPalpha levels found in their platlets and cerebrospinal fluid [55] and the reduced alpha-secretase activity in the temporal cortex homogenates of AD patients [56] PubMed:21214928

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Temporal Lobe

bp(GO:"ERK1 and ERK2 cascade") regulates act(p(HGNC:ADAM10)) View Subject | View Object

Some studies suggest that M1 mAChR stimulation also leads to activation of ERK1/2, which can modulate alpha-secretase activity and APP processing[67, 73], PubMed:24590577

Appears in Networks:

act(p(FPLX:PKC)) increases act(p(HGNC:ADAM10)) View Subject | View Object

Interestingly, stimulation of M1 mAChR by agonists has been found to enhance sAPPalpha generation and reduce Abeta production[61-70]. Protein kinase C (PKC) is well-known to be activated upon stimulation of M1 mAChR. PKC may promote the activity of alpha-secretase[71] and the traffi cking of APP from the Golgi/ trans-Golgi network to the cell surface PubMed:24590577

Appears in Networks:

Out-Edges 18

act(p(HGNC:ADAM10), ma(pep)) increases rxn(reactants(p(HGNC:APP)), products(p(HGNC:APP, frag("17_*")), p(HGNC:APP, frag("1_16")))) View Subject | View Object

Several zinc metallo proteinases such asTACE/ADAM17, ADAM9, ADAM10 and MDC-9 and the aspartyl protease BACE2 can cleave APP at the α-secretase site, located within the Aβ domain between Lys 16 and Leu 17 , essentially precluding the generation of intact Aβ(1). PubMed:18650430

Appears in Networks:
Annotations
Confidence
High

p(HGNC:ADAM10) increases p(HBP:HBP00067) View Subject | View Object

Alternatively, APP can be cleaved by alpha-secretase within the Abeta domain to release soluble APPa and preclude Abeta generation PubMed:21214928

Appears in Networks:
Annotations
Confidence
Medium

p(HGNC:ADAM10) decreases a(CHEBI:"amyloid-beta") View Subject | View Object

Alternatively, APP can be cleaved by alpha-secretase within the Abeta domain to release soluble APPa and preclude Abeta generation PubMed:21214928

Appears in Networks:
Annotations
Confidence
Medium

p(HGNC:ADAM10) decreases a(CHEBI:"amyloid-beta") View Subject | View Object

Cleavage of APP by alpha-secretase precludes Abeta generation as the cleavage site is within the Abeta domain (at the Lys16- Leu17 bond), and releases a large soluble ectodomain of APP called sAPPalpha PubMed:21214928

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Neurons

p(HGNC:ADAM10) increases rxn(reactants(p(HGNC:APP)), products(a(HBP:HBP00067))) View Subject | View Object

From the TGN, APP can be transported in TGN-derived secretory vesicles to the cell surface where it is either cleaved by alpha-secretase to produce a soluble molecule, sAPPalpha [37], or re-internalized via an endosomal/ lysosomal degradation pathway [38,39] PubMed:21214928

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons

p(HGNC:ADAM10) increases rxn(reactants(p(HGNC:APP)), products(a(HBP:HBP00067))) View Subject | View Object

Cleavage of APP by alpha-secretase precludes Abeta generation as the cleavage site is within the Abeta domain (at the Lys16- Leu17 bond), and releases a large soluble ectodomain of APP called sAPPalpha PubMed:21214928

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Neurons

p(HGNC:ADAM10) increases rxn(reactants(p(HGNC:APP)), products(p(HGNC:APP, frag("17_*")), p(HGNC:APP, frag("1_16")))) View Subject | View Object

Cleavage of APP by alpha-secretase precludes Abeta generation as the cleavage site is within the Abeta domain (at the Lys16- Leu17 bond), and releases a large soluble ectodomain of APP called sAPPalpha PubMed:21214928

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Neurons

p(HGNC:ADAM10) negativeCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

A dramatically reduced ADAM10 protein level in the platelets of sporadic AD patients was also found to correlate with the significantly decreased sAPPalpha levels found in their platlets and cerebrospinal fluid [55] and the reduced alpha-secretase activity in the temporal cortex homogenates of AD patients [56] PubMed:21214928

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Blood Platelets

act(p(HGNC:ADAM10)) negativeCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

A dramatically reduced ADAM10 protein level in the platelets of sporadic AD patients was also found to correlate with the significantly decreased sAPPalpha levels found in their platlets and cerebrospinal fluid [55] and the reduced alpha-secretase activity in the temporal cortex homogenates of AD patients [56] PubMed:21214928

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Temporal Lobe

p(HGNC:ADAM10) increases rxn(reactants(p(HGNC:APP)), products(a(HBP:HBP00067))) View Subject | View Object

APP can also be cleaved by alpha-secretase to form a soluble or secreted APP ectodomain (sAPP-alpha) that has been shown to be mostly neuro-protective PubMed:22122372

Appears in Networks:
Annotations
Confidence
High

p(HGNC:ADAM10) increases rxn(reactants(p(HGNC:APP)), products(a(HBP:HBP00067))) View Subject | View Object

As APP was found to be constitutively cleaved at the alpha-site to yield sAPP-alpha (Esch et al. 1990), three members of the a disintegrin and metalloproteinase (ADAMs), ADAM-10,ADAM-17 and ADAM-9 have been proposed as the alpha-secretase (Buxbaum et al. 1998; Koike et al. 1999;Lammich et al. 1999) PubMed:22122372

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons

p(HGNC:ADAM10) increases sec(p(HGNC:APP)) View Subject | View Object

APP can also be cleaved by alpha-secretase to form a soluble or secreted APP ectodomain (sAPP-alpha) that has been shown to be mostly neuro-protective PubMed:22122372

Appears in Networks:
Annotations
Confidence
High

p(HGNC:ADAM10) increases rxn(reactants(p(HGNC:APP)), products(a(HBP:HBP00067), a(HBP:HBP00072))) View Subject | View Object

alpha-cleavage, which cuts APP at the 17th amino acid inside the Abeta peptide sequence (Fig. 1), releases a large secreted extracellular domain (sAPP-alpha) and a membrane-associated C-terminal fragment consisting of 83 amino acids (C83) PubMed:22122372

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons

p(HGNC:ADAM10) increases a(HBP:HBP00067) View Subject | View Object

Moderate neuronal over-expression of human ADAM10 increases sAPP-alpha production while reducing Abeta generation/ plaque formation in mice carrying the human APP V717I mutation, while expression of a catalytically-inactive form of the ADAM10 mutation increases the size and number of amyloid plaques in mouse brains (Postina et al. 2004) PubMed:22122372

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons

p(HGNC:ADAM10) decreases a(CHEBI:"amyloid-beta") View Subject | View Object

Moderate neuronal over-expression of human ADAM10 increases sAPP-alpha production while reducing Abeta generation/ plaque formation in mice carrying the human APP V717I mutation, while expression of a catalytically-inactive form of the ADAM10 mutation increases the size and number of amyloid plaques in mouse brains (Postina et al. 2004) PubMed:22122372

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons

p(HGNC:ADAM10) decreases path(MESH:"Plaque, Amyloid") View Subject | View Object

Moderate neuronal over-expression of human ADAM10 increases sAPP-alpha production while reducing Abeta generation/ plaque formation in mice carrying the human APP V717I mutation, while expression of a catalytically-inactive form of the ADAM10 mutation increases the size and number of amyloid plaques in mouse brains (Postina et al. 2004) PubMed:22122372

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons

p(HGNC:ADAM10) increases deg(p(HGNC:APP)) View Subject | View Object

Abeta, an important player in AD, is derived from beta-amyloid precursor protein (APP) through sequential cleavages by beta- and gamma-secretases: APP is cleaved by beta-secretase (BACE1) to generate the large secreted derivative sAPPbeta and the membrane-bound APP C-terminal fragment-beta; the latter can be further cleaved by gamma-secretase to generate Abeta and APP intracellular domain. Alternatively, APP can be cleaved by alpha-secretase within the Abeta domain, which precludes Abeta production and instead generates secreted sAPPalpha that has been shown to be neuroprotective PubMed:24590577

Appears in Networks:

p(HGNC:ADAM10) increases a(HBP:"sAPP-alpha") View Subject | View Object

Abeta, an important player in AD, is derived from beta-amyloid precursor protein (APP) through sequential cleavages by beta- and gamma-secretases: APP is cleaved by beta-secretase (BACE1) to generate the large secreted derivative sAPPbeta and the membrane-bound APP C-terminal fragment-beta; the latter can be further cleaved by gamma-secretase to generate Abeta and APP intracellular domain. Alternatively, APP can be cleaved by alpha-secretase within the Abeta domain, which precludes Abeta production and instead generates secreted sAPPalpha that has been shown to be neuroprotective PubMed:24590577

Appears in Networks:

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If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.