PSEN2

Alzheimer's disease (AD) patients with an inherited form of the disease carry mutations in the presenilin proteins (PSEN1 or PSEN2) or the amyloid precursor protein (APP). These disease-linked mutations result in increased production of the longer form of amyloid-beta (main component of amyloid deposits found in AD brains). Presenilins are postulated to regulate APP processing through their effects on gamma-secretase, an enzyme that cleaves APP.

Presenilin 2

Probable catalytic 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). Requires the other members of the gamma-secretase complex to have a protease activity. May play a role in intracellular signaling and gene expression or in linking chromatin to the nuclear membrane. May function in the cytoplasmic partitioning of proteins. The holoprotein functions as a calcium-leak channel that allows the passive movement of calcium from endoplasmic reticulum to cytosol and is involved in calcium homeostasis (PubMed:16959576).
Is a regulator of mitochondrion-endoplasmic reticulum membrane tethering and modulates calcium ions shuttling between ER and mitochondria (PubMed:21285369).

Amyloid precursor protein catabolic processManual Assertion Based On ExperimentIDA:ARUK-UCL
Amyloid-beta formationManual Assertion Based On ExperimentIDA:ARUK-UCL
Amyloid-beta metabolic processManual Assertion Based On ExperimentIBA:GO_Central
Calcium ion transportManual Assertion Based On ExperimentIBA:GO_Central
Intracellular signal transductionIEA:InterPro
Membrane protein ectodomain proteolysisManual Assertion Based On ExperimentIDA:HGNC-UCL
Mitochondrion-endoplasmic reticulum membrane tetheringManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of apoptotic processManual Assertion Based On ExperimentIBA:GO_Central
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
Protein processingManual Assertion Based On ExperimentIDA:HGNC-UCL
Regulation of calcium import into the mitochondrionManual Assertion Based On ExperimentIMP:UniProtKB
Response to hypoxiaIEA:Ensembl

Endoplasmic reticulum membrane
Golgi apparatus membrane

Alzheimer disease 4 (AD4):
A familial early-onset form of Alzheimer disease. Alzheimer disease is a neurodegenerative disorder characterized by progressive dementia, loss of cognitive abilities, and deposition of fibrillar amyloid proteins as intraneuronal neurofibrillary tangles, extracellular amyloid plaques and vascular amyloid deposits. The major constituents of these plaques are neurotoxic amyloid-beta protein 40 and amyloid-beta protein 42, that are produced by the proteolysis of the transmembrane APP protein. The cytotoxic C-terminal fragments (CTFs) and the caspase-cleaved products, such as C31, are also implicated in neuronal death.
Cardiomyopathy, dilated 1V (CMD1V):
A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.

Cytoplasmic: 1-87
Helical: 88-108
Lumenal: 109-138
Helical: 139-159
Cytoplasmic: 160-166
Helical: 167-187
Lumenal: 188-200
Helical: 201-221
Cytoplasmic: 222-223
Helical: 224-244
Lumenal: 245-249
Helical: 250-270
Cytoplasmic: 271-361
Helical: 362-382
Lumenal: 383-388
Helical: 389-409
Cytoplasmic: 410-413
Helical: 414-434
Lumenal: 435-448

Heterogeneous proteolytic processing generates N-terminal and C-terminal fragments.
Phosphorylated on serine residues.