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  2. Nodes
  3. complex(FPLX:"Gamma_secretase")

complex(FPLX:"Gamma_secretase")

Appears in Networks 5

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

Clearance of Amyloid Beta and Tau in Alzheimer’s Disease:from Mechanisms to Therapy v1.0.1

In-Edges 2

complex(a(HBP:HBP00024), complex(FPLX:"Gamma_secretase"), p(HGNC:GSAP)) hasComponent complex(FPLX:"Gamma_secretase") View Subject | View Object

Appears in Networks:

complex(complex(FPLX:"Gamma_secretase"), p(HGNC:APP)) hasComponent complex(FPLX:"Gamma_secretase") View Subject | View Object

Appears in Networks:

Out-Edges 27

complex(FPLX:"Gamma_secretase") hasComponent p(HGNC:PSENEN) View Subject | View Object

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complex(FPLX:"Gamma_secretase") hasComponent p(HGNC:PSEN1) View Subject | View Object

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complex(FPLX:"Gamma_secretase") hasComponent p(HGNC:PSEN2) View Subject | View Object

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complex(FPLX:"Gamma_secretase") hasComponent p(HGNC:NCSTN) View Subject | View Object

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complex(FPLX:"Gamma_secretase") hasComponent p(HGNC:APH1A) View Subject | View Object

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complex(FPLX:"Gamma_secretase") hasComponent p(HGNC:APH1B) View Subject | View Object

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complex(FPLX:"Gamma_secretase") increases a(MESH:"Amyloid beta-Peptides") View Subject | View Object

γ-Secretase cleaves at multiple sites within the transmembrane domain of APP, generating Aβ peptides ranging in length from 38 to 43 residues (4). PubMed:18650430

Appears in Networks:
Annotations
Confidence
Medium

complex(FPLX:"Gamma_secretase") increases a(HBP:HBP00071) View Subject | View Object

As mentioned above, γ-secretase processing of APP also releases AICD (Fig. 1). PubMed:18650430

Appears in Networks:
Annotations
Confidence
High

complex(FPLX:"Gamma_secretase") increases rxn(reactants(p(HGNC:APP)), products(a(CHEBI:"amyloid-beta"))) View Subject | View Object

Abeta is generated from b-amyloid precursor protein (APP) through sequential cleavages first by beta-secretase and then by gamma-secretase complex PubMed:21214928

Appears in Networks:
Annotations
Confidence
Medium

complex(FPLX:"Gamma_secretase") increases rxn(reactants(a(HBP:HBP00024)), products(a(CHEBI:"amyloid-beta"), a(HBP:HBP00072))) View Subject | View Object

APP alphaCTF and betaCTF are further cleaved by gamma-secretase to generate p83 and Abeta, respectively PubMed:21214928

Appears in Networks:
Annotations
MeSH
Endosomes
Confidence
Medium
MeSH
Neurons

complex(FPLX:"Gamma_secretase") increases p(HBP:HBP00024, frag("?")) View Subject | View Object

In addition to cleaving APP CTFs, gamma-secretase cleaves a series of functionally important transmembrane proteins, including Notch [120], cadherin [114], tyrosinase [121], ErbB4 [79], CD44 [70], etc.) (see review [122]) PubMed:21214928

Appears in Networks:
Annotations
MeSH
Endosomes
Confidence
Medium
MeSH
Neurons

complex(FPLX:"Gamma_secretase") increases p(HGNC:NOTCH1, frag("?")) View Subject | View Object

In addition to cleaving APP CTFs, gamma-secretase cleaves a series of functionally important transmembrane proteins, including Notch [120], cadherin [114], tyrosinase [121], ErbB4 [79], CD44 [70], etc.) (see review [122]) PubMed:21214928

Appears in Networks:
Annotations
MeSH
Endosomes
Confidence
Medium
MeSH
Neurons

complex(FPLX:"Gamma_secretase") increases p(FPLX:Cadherin, frag("?")) View Subject | View Object

In addition to cleaving APP CTFs, gamma-secretase cleaves a series of functionally important transmembrane proteins, including Notch [120], cadherin [114], tyrosinase [121], ErbB4 [79], CD44 [70], etc.) (see review [122]) PubMed:21214928

Appears in Networks:
Annotations
MeSH
Endosomes
Confidence
Medium
MeSH
Neurons

complex(FPLX:"Gamma_secretase") increases p(HGNC:TYR, frag("?")) View Subject | View Object

In addition to cleaving APP CTFs, gamma-secretase cleaves a series of functionally important transmembrane proteins, including Notch [120], cadherin [114], tyrosinase [121], ErbB4 [79], CD44 [70], etc.) (see review [122]) PubMed:21214928

Appears in Networks:
Annotations
MeSH
Endosomes
Confidence
Medium
MeSH
Neurons

complex(FPLX:"Gamma_secretase") increases p(HGNC:ERBB4, frag("?")) View Subject | View Object

In addition to cleaving APP CTFs, gamma-secretase cleaves a series of functionally important transmembrane proteins, including Notch [120], cadherin [114], tyrosinase [121], ErbB4 [79], CD44 [70], etc.) (see review [122]) PubMed:21214928

Appears in Networks:
Annotations
MeSH
Endosomes
Confidence
Medium
MeSH
Neurons

complex(FPLX:"Gamma_secretase") increases p(HGNC:CD44, frag("?")) View Subject | View Object

In addition to cleaving APP CTFs, gamma-secretase cleaves a series of functionally important transmembrane proteins, including Notch [120], cadherin [114], tyrosinase [121], ErbB4 [79], CD44 [70], etc.) (see review [122]) PubMed:21214928

Appears in Networks:
Annotations
MeSH
Endosomes
Confidence
Medium
MeSH
Neurons

complex(FPLX:"Gamma_secretase") increases rxn(reactants(p(HGNC:APP)), products(a(CHEBI:"amyloid-beta"))) View Subject | View Object

The processing of APP to generate Abeta is executed by beta- and gamma-secretase and is highly regulated PubMed:22122372

Appears in Networks:
Annotations
Confidence
Medium

complex(FPLX:"Gamma_secretase") increases rxn(reactants(a(HBP:HBP00072)), products(a(HBP:HBP00071), a(HBP:HBP00080))) View Subject | View Object

APP C83 is further cleaved by gamma-secretase to release a P3 peptide and the AICD, both of which are degraded rapidly PubMed:22122372

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Neurons

complex(FPLX:"Gamma_secretase") increases rxn(reactants(a(HBP:HBP00081)), products(a(HBP:HBP00071), a(MESH:"Amyloid beta-Peptides"))) View Subject | View Object

gamma-Secretase further cleaves C99 to release AICD and the amyloidogenic Abeta peptide which aggregates and fibrillates to form amyloid plaques in the brain PubMed:22122372

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Neurons

complex(FPLX:"Gamma_secretase") increases p(HGNC:APP, frag("1_38")) View Subject | View Object

gamma-Secretase cleaves APP at multiple sites and in sequential steps to generate Abeta peptides of different lengths (Fig. 1). The majority of Abeta peptides produced are 40 amino acids long, however, peptides ranging from 38 to 43 amino acids are found in vivo PubMed:22122372

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Neurons

complex(FPLX:"Gamma_secretase") increases p(HGNC:APP, frag("1_43")) View Subject | View Object

gamma-Secretase cleaves APP at multiple sites and in sequential steps to generate Abeta peptides of different lengths (Fig. 1). The majority of Abeta peptides produced are 40 amino acids long, however, peptides ranging from 38 to 43 amino acids are found in vivo PubMed:22122372

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Neurons

complex(FPLX:"Gamma_secretase") increases p(HGNC:APP, frag("672_711")) View Subject | View Object

gamma-Secretase cleaves APP at multiple sites and in sequential steps to generate Abeta peptides of different lengths (Fig. 1). The majority of Abeta peptides produced are 40 amino acids long, however, peptides ranging from 38 to 43 amino acids are found in vivo PubMed:22122372

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Neurons

complex(FPLX:"Gamma_secretase") increases a(HBP:HBP00071) View Subject | View Object

Accordingly, various AICDs (C50, C53, C57 and C59) can be generated during these multi-site cleavages executed by gamma-secretase. However, all of the endogenous AICD forms are rarely detected, probably because of their very rapid degradation (Lu et al. 2000; Passer et al. 2000; Sastre et al. 2001; Yu et al. 2001; Sato et al. 2003) PubMed:22122372

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Neurons

complex(FPLX:"Gamma_secretase") increases deg(a(HBP:C99)) 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:

complex(FPLX:"Gamma_secretase") increases a(CHEBI:"amyloid-beta") 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:

complex(FPLX:"Gamma_secretase") increases a(HBP:AICD) 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:

complex(FPLX:"Gamma_secretase") increases a(CHEBI:"amyloid-beta") View Subject | View Object

Under normal conditions, Aβ production in brain parenchyma results from hydrolyzing amyloid precursor proteins via beta-secreted enzymes and gamma-secreted enzymes, and the most common subtypes of Aβ in human body are Aβ1–40 and Aβ1–42 PubMed:29626319

Appears in Networks:

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BEL Commons is developed and maintained in an academic capacity by Charles Tapley Hoyt and Daniel Domingo-Fernández at the Fraunhofer SCAI Department of Bioinformatics with support from the IMI project, AETIONOMY. It is built on top of PyBEL, an open source project. Please feel free to contact us here to give us feedback or report any issues. Also, see our Publishing Notes and Data Protection information.

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.