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APH-1 stabilizes the presenilin holoprotein in the complex, whereas PEN-2 is required for endoproteolytic processing of presenilin and conferring gamma-secretase activity to the complex.
presenilin, nicastrin (show NCSTN Proteins), APH-1, and PEN-2, are present and enriched on phagosome membranes from both murine macrophages and Drosophila S2 phagocytes
All gamma-secretase subunits: PS1/PS2, APH-1, PEN-2, and NCT colocalize and interact with each other in Arabidopsis thaliana protoplasts. [AtPEN-2]
zinc, copper inhibited Abeta (show APP Proteins) production by directly targeting the subunits presenilin and nicastrin (show NCSTN Proteins) in the gamma-secretase complex
PSENEN may play a crucial role in the progression of atopic dermatitis by participating in the Notch (show NOTCH1 Proteins) signaling pathway.
Remarkably, PEN-2 was identified besides nicastrin (show NCSTN Proteins) as additional substrate-binding subunit.
TRPC6 (show TRPC6 Proteins) specifically interacts with APP (show APP Proteins) leading to inhibition of its cleavage by gamma-secretase and reduction in Abeta (show APP Proteins) production.
secondary mutations in presenilin 1 (show PSEN1 Proteins) alone activated the gamma-secretase activity.
Data indicate that familial Alzheimer's disease (FAD (show BRCA2 Proteins)) and control brain samples had similar overall gamma-secretase activity levels, and therefore, loss of overall (endopeptidase) gamma-secretase function cannot be an essential part of the pathogenic mechanism.
We for the first time identify PEN-2 as the causative gene of familial comedones.
The first hydrophobic domain of Pen-2 forms a structure similar to a reentrant loop while the second hydrophobic domain spans the lipid bilayer.
shedding of BCMA (show TNFRSF17 Proteins) by gamma-secretase controls plasma cells in the bone marrow and yields a potential biomarker for B-cell involvement in human autoimmune diseases
Tumor necrosis factor-alpha (show TNF Proteins) and interleukin-10 (show IL10 Proteins) levels were elevated in acne inversa patients with nicastrin (show NCSTN Proteins) or presenilin enhancer mutation.
the G206D mutation reduced presenilin-1 (show PSEN1 Proteins)-presenilin enhancer 2 interaction, but did not abolish gamma-secretase formation and presenilin-1 (show PSEN1 Proteins) endoproteolysis
Data show that the expression level of presenilin enhancer-2 (Pen-2) is relatively high in central nervous system at the early stages of postnatal development, but declines, gradually in adult mice.
rather than solely being a catalyst for gamma-secretase endoproteolysis, Pen-2 may also stabilize the complex prior to PS1 (show PSEN1 Proteins) endoproteolysis, allowing time for full assembly and proper trafficking.
Pen-2, as well as nicastrin and Aph-1alpha, is dispensable for presenilin endoproteolysis
Nct (show NCSTN Proteins) has a critical role in the stability and proper intracellular trafficking of other components of the PS1 (show PSEN1 Proteins)/ gamma-secretase complex but not in maintaining the association of PEN-2, APH-1, and full-length PS1 (show PSEN1 Proteins)
The PSENEN gene is down-regulated in bovine intramuscular fibroblast cells during differentiation into adipocytes.
Presenilins, which are components of the gamma-secretase protein complex, are required for intramembranous processing of some type I transmembrane proteins, such as the Notch proteins and the beta-amyloid precursor protein. Signaling by Notch receptors mediates a wide range of developmental cell fates. Processing of the beta-amyloid precursor protein generates neurotoxic amyloid beta peptides, the major component of senile plaques associated with Alzheimer's disease. This gene encodes a protein that is required for Notch pathway signaling, and for the activity and accumulation of gamma-secretase.
, presenilin enhancer 2
, gamma-secretase subunit PEN-2
, hematopoietic stem/progenitor cells protein MDS033
, presenilin enhancer protein 2
, LRRGT00140 mRNA
, liver regeneration-related protein LRRGT00140