Nicastrin

Nicastrin, also known as NCSTN, is a protein that in humans is encoded by the NCSTN gene.^[5][6][7]

NCSTN
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4UPC, 5A63, 4UIS, 5FN3, 5FN4, 5FN5, 5FN2, 2N7R, 2N7Q
Identifiers
Aliases	NCSTN, ATAG1874, nicastrin
External IDs	OMIM: 605254; MGI: 1891700; HomoloGene: 41029; GeneCards: NCSTN; OMA:NCSTN - orthologs
Gene location (Human) Chr. Chromosome 1 (human)[1] Band 1q23.2 Start 160,343,316 bp[1] End 160,358,952 bp[1]
Gene location (Mouse) Chr. Chromosome 1 (mouse)[2] Band 1 H3|1 79.54 cM Start 171,893,580 bp[2] End 171,910,362 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in stromal cell of endometrium monocyte body of pancreas granulocyte rectum islet of Langerhans olfactory bulb right lung minor salivary glands ventricular zone Top expressed in spermatocyte lip genital tubercle granulocyte tail of embryo right kidney ventricular zone epithelium of small intestine stroma of bone marrow superior frontal gyrus More reference expression data BioGPS More reference expression data
Gene ontology Molecular function peptidase activity protein binding endopeptidase activity Cellular component Golgi apparatus membrane focal adhesion melanosome plasma membrane integral component of plasma membrane lysosomal membrane endoplasmic reticulum extracellular exosome integral component of membrane azurophil granule membrane gamma-secretase complex cytoplasmic vesicle membrane cytoplasmic vesicle cytoplasm mitochondrion lysosome early endosome synaptic vesicle endosome membrane protein-containing complex sarcolemma synapse synaptic membrane integral component of presynaptic membrane Biological process Notch signaling pathway ephrin receptor signaling pathway myeloid cell homeostasis protein processing positive regulation of catalytic activity amyloid-beta metabolic process epithelial cell proliferation proteolysis T cell proliferation membrane protein ectodomain proteolysis membrane protein intracellular domain proteolysis positive regulation of apoptotic process Notch receptor processing amyloid precursor protein catabolic process amyloid-beta formation amyloid precursor protein metabolic process neutrophil degranulation cerebellum development Notch receptor processing, ligand-dependent dopamine receptor signaling pathway glutamate receptor signaling pathway learning or memory central nervous system myelination adult behavior amyloid precursor protein biosynthetic process positive regulation of amyloid precursor protein biosynthetic process neuron apoptotic process neuron death cellular response to calcium ion regulation of long-term synaptic potentiation short-term synaptic potentiation Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 23385 59287 Ensembl ENSG00000162736 ENSMUSG00000003458 UniProt Q92542 P57716 RefSeq (mRNA) NM_001290184 NM_001290186 NM_015331 NM_001349729 NM_021607 RefSeq (protein) NP_001277113 NP_001277115 NP_056146 NP_001336658 NP_067620 Location (UCSC) Chr 1: 160.34 – 160.36 Mb Chr 1: 171.89 – 171.91 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Function

Nicastrin (abbreviated NCT) is a protein that is part of the gamma secretase protein complex, which is one of the proteases involved in processing amyloid precursor protein (APP) to the short Alzheimer's disease-associated peptide amyloid beta. The other proteins in the complex are PSEN1 (presenilin-1), which is the catalytically active component of the complex, APH-1 (anterior pharynx-defective 1), and PEN-2 (presenilin enhancer 2).^[8] Nicastrin itself is not catalytically active, but instead promotes the maturation and proper trafficking of the other proteins in the complex, all of which undergo significant post-translational modification before becoming active in the cell.^[9] Nicastrin has also been identified as a regulator of neprilysin, an enzyme involved in the degradation of amyloid beta fragment.^[10]

History

The protein was named after the Italian country Nicastro, reflecting the fact that Alzheimer's disease was described in 1963 after studying descendants of an extended family originating in the country of Nicastro that had familial Alzheimer's disease (FAD).^[11]

Interactions

Nicastrin has been shown to interact with PSEN1^{[12][13][14][15][16]} and PSEN2.^[12][16]