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 (beta- amyloid precursor protein). It probably represents a stabilizing cofactor required for the assembly of the gamma-secretase complex. Component of the gamma-secretase complex, a complex composed of a presenilin homodimer (PSEN1 or PSEN2), nicastrin (NCSTN), APH1 (APH1A or APH1B) and PEN2. Such minimal complex is sufficient for secretase activity, although other components may exist. Binds to proteolytic processed C-terminal fragments C83 and C99 of the amyloid precursor protein (APP). Constitutively expressed in neural cells. Widely expressed. Belongs to the nicastrin family. 2 isoforms of the human protein are produced by alternative splicing. Note: This description may include information from UniProtKB.
Protein type: Membrane protein, integral
Cellular Component: Golgi apparatus; integral to plasma membrane; lysosomal membrane; endoplasmic reticulum; integral to membrane; melanosome; plasma membrane
Molecular Function: protein binding; endopeptidase activity
Biological Process: positive regulation of catalytic activity; Notch signaling pathway; extracellular matrix organization and biogenesis; membrane protein intracellular domain proteolysis; nerve growth factor receptor signaling pathway; positive regulation of apoptosis; membrane protein ectodomain proteolysis; myeloid cell homeostasis; Notch receptor processing; proteolysis; T cell proliferation; extracellular matrix disassembly; epithelial cell proliferation; amyloid precursor protein catabolic process; beta-amyloid metabolic process; protein processing
SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.