NCSTN

This gene encodes a type I transmembrane glycoprotein that is an integral component of the multimeric gamma-secretase complex. The encoded protein cleaves integral membrane proteins, including Notch receptors and beta-amyloid precursor protein, and may be a stabilizing cofactor required for gamma-secretase complex assembly. The cleavage of beta-amyloid precursor protein yields amyloid beta peptide, the main component of the neuritic plaque and the hallmark lesion in the brains of patients with Alzheimer's disease; however, the nature of the encoded protein's role in Alzheimer's disease is not known for certain. Mutations in this gene are associated with familial acne inversa. A pseudogene of this gene is present on chromosome 21. Alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Feb 2014]

Nicastrin

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:10993067, PubMed:12679784, PubMed:25043039, PubMed:26280335, 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.

Adult behavior Source: Ensembl
Amyloid-beta formation Source: ARUK-UCL
Amyloid precursor protein biosynthetic process Source: Ensembl
Amyloid precursor protein catabolic process Source: ARUK-UCL
Amyloid precursor protein metabolic process Source: UniProtKB
Cellular response to calcium ion Source: Ensembl
Central nervous system myelination Source: Ensembl
Cerebellum development Source: Ensembl
Dopamine receptor signaling pathway Source: Ensembl
Epithelial cell proliferation Source: Ensembl
Glutamate receptor signaling pathway Source: Ensembl
Learning or memory Source: Ensembl
Membrane protein ectodomain proteolysis Source: HGNC-UCL
Membrane protein intracellular domain proteolysis Source: ComplexPortal
Myeloid cell homeostasis Source: Ensembl
Neuron apoptotic process Source: Ensembl
Notch receptor processing Source: ARUK-UCL
Notch signaling pathway Source: UniProtKB-KW
Positive regulation of amyloid precursor protein biosynthetic process Source: Ensembl
Positive regulation of catalytic activity Source: HGNC-UCL
Positive regulation of endopeptidase activity Source: ARUK-UCL
Protein processing Source: HGNC-UCL
Proteolysis Source: UniProtKB
Regulation of long-term synaptic potentiation Source: Ensembl
Short-term synaptic potentiation Source: Ensembl
T cell proliferation Source: Ensembl

Other locations
Membrane
Cytoplasmic vesicle membrane
Melanosome
Note: Identified by mass spectrometry in melanosome fractions from stage I to stage IV.

Acne inversa, familial, 1 (ACNINV1):
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.

Extracellular: 34-669
Helical: 670-690
Cytoplasmic: 691-709

N-glycosylated.