PSENEN

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. [provided by RefSeq]

Full Name

presenilin enhancer 2 homolog (C. elegans)

Function

Essential subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (amyloid-beta precursor protein) (PubMed:12522139, PubMed:12763021, PubMed:12740439, PubMed:12679784, PubMed:24941111, PubMed:30598546, PubMed:30630874).
The gamma-secretase complex plays a role in Notch and Wnt signaling cascades and regulation of downstream processes via its role in processing key regulatory proteins, and by regulating cytosolic CTNNB1 levels (Probable). PSENEN modulates both endoproteolysis of presenilin and gamma-secretase activity (PubMed:12522139, PubMed:12763021, PubMed:12740439, PubMed:12679784, PubMed:24941111).

Biological Process

Amyloid precursor protein catabolic processManual Assertion Based On ExperimentIDA:ComplexPortal
Amyloid precursor protein metabolic processManual Assertion Based On ExperimentIDA:UniProtKB
Amyloid-beta formationManual Assertion Based On ExperimentIMP:UniProtKB
Membrane protein ectodomain proteolysisManual Assertion Based On ExperimentIDA:HGNC-UCL
Membrane protein intracellular domain proteolysisManual Assertion Based On ExperimentIDA:ComplexPortal
Notch receptor processingManual Assertion Based On ExperimentIBA:GO_Central
Notch signaling pathwayIEA:UniProtKB-KW
Positive regulation of catalytic activityManual Assertion Based On ExperimentIDA:HGNC-UCL
Positive regulation of endopeptidase activityManual Assertion Based On ExperimentIMP:UniProtKB
Protein processingManual Assertion Based On ExperimentIDA:HGNC-UCL

Cellular Location

Endoplasmic reticulum membrane
Golgi apparatus, Golgi stack membrane
Cell membrane
Membrane
Predominantly located in the endoplasmic reticulum and in the cis-Golgi.

Involvement in disease

Acne inversa, familial, 2, with or without Dowling-Degos disease (ACNINV2):
An autosomal dominant form of acne inversa, a chronic relapsing inflammatory disease of the hair follicles characterized by recurrent draining sinuses, painful skin abscesses, and disfiguring scars. Manifestations typically appear after puberty. Some ACNINV2 patients also exhibit reticulate hyperpigmentation consistent with Dowling-Degos disease.

Topology

Cytoplasmic: 1-17
Helical: 18-36
Cytoplasmic: 37-57
Helical: 58-78
Lumenal: 79-101