research use only

PEN2 Antibody [E13J21]

Cat.No.: F4810

    Application: Reactivity:
    • F4810-wb
      Lane 1: 293T, Lane 2: Neuro-2a, Lane 3: Daudi

    Usage Information

    Dilution
    1:1000 - 1:10000
    1:100 - 1:250
    1:100
    Application
    WB, IHC, FCM
    Reactivity
    Mouse, Human
    Source
    Rabbit Monoclonal Antibody
    Storage Buffer
    PBS, pH 7.2+50% Glycerol+0.05% BSA+0.01% NaN3
    Storage (from the date of receipt)
    -20°C (avoid freeze-thaw cycles), 2 years
    Predicted MW Observed MW
    12 kDa 12 kDa
    *Why do the predicted and actual molecular weights differ?
    The following reasons may explain differences between the predicted and actual protein molecular weight.
    Positive Control Human skeletal muscle tissue; Fetal lung tissue; Human placenta; HEK-293 cells; Neuro-2a cells; Daudi cells
    Negative Control

    Datasheet & SDS

    Biological Description

    Specificity
    PEN2 Antibody [E13J21] detects endogenous levels of total PEN2 protein.
    Clone
    E13J21
    Synonym(s)
    PEN2; MDS033; PSENEN; Gamma-secretase subunit PEN-2; Presenilin enhancer protein 2
    Background
    PEN2 (Presenilin Enhancer 2), an integral membrane glycoprotein essential for γ-secretase complex assembly, features two transmembrane domains with N- and C-termini oriented toward the ER lumen/extracellular space, a conserved D-Y-L-S-F motif in its short C-terminal tail critical for complex stabilization, and key residues like I43 in the cytosolic loop plus charged D90/F94 that fine-tune presenilin endoproteolysis. As the final obligatory subunit binding to the presenilin (PS1/PS2)-nicastrin-APH1 tripartite intermediate, PEN2 triggers PS autoproteolysis at the TMD7-8 junction by stabilizing the catalytic Asp257/Asp385 residues in a horseshoe-shaped water-filled cavity, enabling intramembrane proteolysis of >100 type I transmembrane substrates including amyloid precursor protein (APP) to release Aβ40/42 peptides and Notch receptor to generate NICD transcription factor. This sequential ε→ζ→γ cleavages within the TMD proceed via substrate docking at nicastrin’s large ectodomain followed by lateral cleft entry to the central PS active site, where PEN2 rigidly positions the PS transmembrane bundle to enhance catalytic efficiency and trafficking from ER to plasma membrane/endosomes, critically regulating neuronal differentiation (Notch), synaptic plasticity (APP/Cadherins), and ER homeostasis while contributing to Alzheimer's disease through Aβ plaque formation and cancer via dysregulated Notch/EGFR signaling.
    References
    • https://pubmed.ncbi.nlm.nih.gov/24941111/
    • https://pubmed.ncbi.nlm.nih.gov/22315713/

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