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PSEN2 phospho S330

Domain

The PAL motif is required for normal active site conformation.

Function

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).

Involvement in disease

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.

None

The disease is caused by variants affecting the gene represented in this entry.

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.

None

The disease is caused by variants affecting the gene represented in this entry.

Post-translational modifications

Heterogeneous proteolytic processing generates N-terminal and C-terminal fragments.

Phosphorylated on serine residues.

Sequence similarities

Belongs to the peptidase A22A family.

Tissue specificity

Isoform 1 is seen in the placenta, skeletal muscle and heart while isoform 2 is seen in the heart, brain, placenta, liver, skeletal muscle and kidney.

Cellular localization

  • Endoplasmic reticulum membrane
  • Multi-pass membrane protein
  • Golgi apparatus membrane
  • Multi-pass membrane protein

Alternative names

AD4, PS2, PSNL2, STM2, PSEN2, Presenilin-2, PS-2, AD3LP, AD5, E5-1, STM-2

Target type

Proteins

Primary research area

Neuroscience

Molecular weight

50140Da

We found 2 products in 1 category

Primary Antibodies

Application

Reactive species