Relation Results

Summary

Name gamma-secretase
Primary ID SIGNOR-C98
Links CPX-2176
Type complex
Formed by PSEN1, PSENEN, NCSTN, APH1A
Relations 16
Pathways Alzheimer, FAP: Notch, NOTCH Signaling, NOTCH Signaling and Myogenesis, Tnfa_Notch_crosstalk

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Type: Score: Layout: SPV 
0.5760.20.20.5960.5620.6690.9640.9570.6690.520.960.20.959gamma-secretaseNOTCH2IFITM3DSCAMAPPNOTCH3NOTCH1NCSTNPSEN1NOTCHNOTCH4PSENENDSCAML1APH1A

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Relations
Regulator
Mechanism
target
score ℹ
+ gamma-secretaseup-regulates activity img/direct-activation.png cleavage NOTCH2 0.576
Identifier Residue Sequence Organism Cell Line
SIGNOR-209723 Homo sapiens
pmid sentence
The membrane-bound Notch segment that results from this cleavage, known as Notch Intracellular Truncation domain (NEXT), is a -secretase substrate (Kopan and Ilagan, 2009). -Secretase performs the subsequent cleavage at S3 (De Strooper et al., 1999), releasing Notch intracellular domain (NICD) from the membrane and allowing for signal transduction through binding with the CBL-1, Su(H), Lag-1 (CSL; Schroeter et al., 1998; Struhl and Adachi, 1998) family of DNA binding proteins.
Publications: 1 Organism: Homo Sapiens
+ IFITM3up-regulates activity img/direct-activation.png binding gamma-secretase 0.2
Identifier Residue Sequence Organism Cell Line
SIGNOR-266303 Mus musculus
pmid sentence
IFITM3 directly binds to γ-secretase. IFITM3 KO reduced γ-secretase activity for both Aβ40 and Aβ42 cleavages as compared to the EV (empty vector guide RNA) cell line by 36% and 27%, respectively (Fig. 2d, bar 1 and 3).
Publications: 1 Organism: Mus Musculus
+ gamma-secretasedown-regulates quantity img/direct_inhibition.png cleavage DSCAM 0.2
Identifier Residue Sequence Organism Cell Line
SIGNOR-264271 Homo sapiens Neuron
pmid sentence
γ‐secretase‐mediated intra‐membrane cleavage of DSCAM receptors results in the release of the DSCAM ICD, which is likely proceeded by shedding of the DSCAM ectodomain. Interaction of IPO5 with the NLS of DSCAM then leads to importin‐mediated nuclear import of the DSCAM ICD. In the nucleus, the DSCAM ICD may regulate the transcription of genes involved in neuronal development and function, thereby regulating processes such as neurite outgrowth, branching, and repulsion, as well as synapse formation, axon guidance, and neuronal cell death and survival.
Publications: 1 Organism: Homo Sapiens
+ gamma-secretaseup-regulates activity img/direct-activation.png cleavage APP 0.596
Identifier Residue Sequence Organism Cell Line
SIGNOR-251576 Homo sapiens Alzheimer Disease Specific Cell Type
pmid sentence
The production and accumulation of the beta amyloid protein (Abeta) is a key event in the cascade of oxidative and inflammatory processes that characterizes Alzheimer's disease (AD). A multi-subunit enzyme complex, referred to as gamma (gamma) secretase, plays a pivotal role in the generation of Abeta from its parent molecule, the amyloid precursor protein (APP).
Publications: 1 Organism: Homo Sapiens
Pathways:Alzheimer
+ gamma-secretaseup-regulates activity img/direct-activation.png cleavage NOTCH3 0.562
Identifier Residue Sequence Organism Cell Line
SIGNOR-209726 Homo sapiens
pmid sentence
The membrane-bound Notch segment that results from this cleavage, known as Notch Intracellular Truncation domain (NEXT), is a -secretase substrate (Kopan and Ilagan, 2009). -Secretase performs the subsequent cleavage at S3 (De Strooper et al., 1999), releasing Notch intracellular domain (NICD) from the membrane and allowing for signal transduction through binding with the CBL-1, Su(H), Lag-1 (CSL; Schroeter et al., 1998; Struhl and Adachi, 1998) family of DNA binding proteins.
Publications: 1 Organism: Homo Sapiens
+ gamma-secretaseup-regulates activity img/direct-activation.png cleavage NOTCH1 0.669
Identifier Residue Sequence Organism Cell Line
SIGNOR-209717 Homo sapiens
pmid sentence
The membrane-bound Notch segment that results from this cleavage, known as Notch Intracellular Truncation domain (NEXT), is a γ-secretase substrate. γ-Secretase performs the subsequent cleavage at S3, releasing Notch intracellular domain (NICD) from the membrane and allowing for signal transduction through binding with the CBL-1, Su(H), Lag-1 family of DNA binding proteins.
Publications: 1 Organism: Homo Sapiens
Pathways:NOTCH Signaling, NOTCH Signaling and Myogenesis
+ NCSTNform complex img/form-complex.png binding gamma-secretase 0.964
Identifier Residue Sequence Organism Cell Line
SIGNOR-209711 Homo sapiens
pmid sentence
-Secretase is a four subunit, 19-pass transmembrane enzymeBiochemical studies indicated that -secretase activity is catalyzed by the presenilin (PS)-containing macromolecular complex (Li et al., 2000a). The search for other components of the complex revealed three additional proteins: nicastrin (Nct), anterior pharynx-defective-1 (Aph-1), and presenilin enhancer-2 (Pen-2)
Publications: 1 Organism: Homo Sapiens
Pathways:Alzheimer
+ PSEN1up-regulates img/direct-activation.png cleavage gamma-secretase 0.957
Identifier Residue Sequence Organism Cell Line
SIGNOR-217743 Homo sapiens
pmid sentence
Presenilin-1 (ps1), a polytopic membrane protein primarily localized to the endoplasmic reticulum, is required for efficient proteolysis of both notch and beta-amyloid precursor protein (app) within their trans- membrane domains.
Identifier Residue Sequence Organism Cell Line
SIGNOR-217746 Homo sapiens
pmid sentence
Presenilin-1 (ps1), a polytopic membrane protein primarily localized to the endoplasmic reticulum, is required for efficient proteolysis of both notch and beta-amyloid precursor protein (app) within their trans- membrane domains.
Publications: 2 Organism: Homo Sapiens
Pathways:Alzheimer
+ gamma-secretaseup-regulates activity img/direct-activation.png cleavage NOTCH 0.669
Identifier Residue Sequence Organism Cell Line
SIGNOR-254328 Homo sapiens
pmid sentence
The membrane-bound Notch segment that results from this cleavage, known as Notch Intracellular Truncation domain (NEXT), is a -secretase substrate (Kopan and Ilagan, 2009). -Secretase performs the subsequent cleavage at S3 (De Strooper et al., 1999), releasing Notch intracellular domain (NICD) from the membrane and allowing for signal transduction through binding with the CBL-1, Su(H), Lag-1 (CSL; Schroeter et al., 1998; Struhl and Adachi, 1998) family of DNA binding proteins.
Publications: 1 Organism: Homo Sapiens
+ gamma-secretaseup-regulates activity img/direct-activation.png cleavage NOTCH4 0.52
Identifier Residue Sequence Organism Cell Line
SIGNOR-209729 Homo sapiens
pmid sentence
The membrane-bound Notch segment that results from this cleavage, known as Notch Intracellular Truncation domain (NEXT), is a -secretase substrate (Kopan and Ilagan, 2009). -Secretase performs the subsequent cleavage at S3 (De Strooper et al., 1999), releasing Notch intracellular domain (NICD) from the membrane and allowing for signal transduction through binding with the CBL-1, Su(H), Lag-1 (CSL; Schroeter et al., 1998; Struhl and Adachi, 1998) family of DNA binding proteins.
Publications: 1 Organism: Homo Sapiens
+ PSENENform complex img/form-complex.png binding gamma-secretase 0.96
Identifier Residue Sequence Organism Cell Line
SIGNOR-209708 Homo sapiens
pmid sentence
-Secretase is a four subunit, 19-pass transmembrane enzymeBiochemical studies indicated that -secretase activity is catalyzed by the presenilin (PS)-containing macromolecular complex (Li et al., 2000a). The search for other components of the complex revealed three additional proteins: nicastrin (Nct), anterior pharynx-defective-1 (Aph-1), and presenilin enhancer-2 (Pen-2)
Publications: 1 Organism: Homo Sapiens
+ PSEN1form complex img/form-complex.png binding gamma-secretase 0.957
Identifier Residue Sequence Organism Cell Line
SIGNOR-209705 Homo sapiens
pmid sentence
-Secretase is a four subunit, 19-pass transmembrane enzymeBiochemical studies indicated that -secretase activity is catalyzed by the presenilin (PS)-containing macromolecular complex (Li et al., 2000a). The search for other components of the complex revealed three additional proteins: nicastrin (Nct), anterior pharynx-defective-1 (Aph-1), and presenilin enhancer-2 (Pen-2)
Publications: 1 Organism: Homo Sapiens
Pathways:Alzheimer
+ gamma-secretaseup-regulates img/direct-activation.png cleavage NOTCH 0.669
Identifier Residue Sequence Organism Cell Line
SIGNOR-255372
pmid sentence
Receptor–ligand engagement triggers a second NECD cleavage (S2 cleavage) by a metalloproteinase ADAM (known as Kuzbanian in Drosophila melanogaster), which in turn facilitates a further crucial signaling cleavage within the Notch transmembrane domain by a γ-secretase complex that contains Presenilin (S3 cleavage)
Publications: 1
+ gamma-secretasedown-regulates quantity img/direct_inhibition.png cleavage DSCAML1 0.2
Identifier Residue Sequence Organism Cell Line
SIGNOR-264272 Homo sapiens Neuron
pmid sentence
γ‐secretase‐mediated intra‐membrane cleavage of DSCAM receptors results in the release of the DSCAM ICD, which is likely proceeded by shedding of the DSCAM ectodomain. Interaction of IPO5 with the NLS of DSCAM then leads to importin‐mediated nuclear import of the DSCAM ICD. In the nucleus, the DSCAM ICD may regulate the transcription of genes involved in neuronal development and function, thereby regulating processes such as neurite outgrowth, branching, and repulsion, as well as synapse formation, axon guidance, and neuronal cell death and survival.
Publications: 1 Organism: Homo Sapiens
+ APH1Aform complex img/form-complex.png binding gamma-secretase 0.959
Identifier Residue Sequence Organism Cell Line
SIGNOR-209714 Homo sapiens
pmid sentence
-Secretase is a four subunit, 19-pass transmembrane enzymeBiochemical studies indicated that -secretase activity is catalyzed by the presenilin (PS)-containing macromolecular complex (Li et al., 2000a). The search for other components of the complex revealed three additional proteins: nicastrin (Nct), anterior pharynx-defective-1 (Aph-1), and presenilin enhancer-2 (Pen-2)
Publications: 1 Organism: Homo Sapiens
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