Human Gene NCSTN (uc001fvx.3) Description and Page Index
Description: Homo sapiens nicastrin (NCSTN), mRNA. RefSeq Summary (NM_015331): 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]. Transcript (Including UTRs) Position: hg19 chr1:160,313,063-160,328,742 Size: 15,680 Total Exon Count: 17 Strand: + Coding Region Position: hg19 chr1:160,313,187-160,328,061 Size: 14,875 Coding Exon Count: 17
ID:NICA_HUMAN DESCRIPTION: RecName: Full=Nicastrin; Flags: Precursor; FUNCTION: 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. SUBUNIT: 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). INTERACTION: P49755:TMED10; NbExp=5; IntAct=EBI-998440, EBI-998422; SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein (Potential). Melanosome. Note=Identified by mass spectrometry in melanosome fractions from stage I to stage IV. TISSUE SPECIFICITY: Widely expressed. INDUCTION: Constitutively expressed in neural cells. DISEASE: Defects in NCSTN are the cause of familial acne inversa type 1 (ACNINV1) [MIM:142690]. 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. SIMILARITY: Belongs to the nicastrin family.
Genetic Association Studies of Complex Diseases and Disorders
Alzheimer's Disease Helisalmi, S. et al. 2004, Possible association of nicastrin polymorphisms and Alzheimer disease in the Finnish population., Neurology. 2004 Jul;63(1):173-5.
A significant difference in one haplotype was observed in AD patients without the APOE epsilon4 allele.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q92542
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.