Go Annotations as Summary Text (Tabular View) (GO Graph)

GO curators for mouse genes have assigned the following annotations to the gene product of Ncstn. (This text reflects annotations as of Tuesday, May 21, 2013.)

---

Summary from NCBI RefSeq

[Summary is not available for the mouse gene. This summary is for the human ortholog.] 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. Alternatively spliced transcript variants have been described, but their full-length nature has not been determined. [provided by RefSeq, Jul 2008]

---

Summary text based on GO annotations supported by experimental evidence in mouse

• Researchers have inferred from direct assay, that the gene product of Ncstn
  • is located in the following cellular components:
    • endoplasmic reticulum ^[1]
    • Golgi apparatus ^[1]
    • membrane ^{[3, 5, 7]}
    • plasma membrane ^[1]
• The gene product of Ncstn has been shown to bind to the gene products of Aph1a, Herpud1, Psen1, Psen2, Vcp. ^{[2, 6]}
• Researchers have inferred, based on phenotypic analysis of mouse mutants, that the gene product of Ncstn
  • participates in the following biological processes:
    • beta-amyloid metabolic process ^[4]
    • epithelial cell proliferation ^[4]
    • myeloid cell homeostasis ^[4]
    • T cell proliferation ^[4]
  • performs the following molecular functions:
    • endopeptidase activity ^[4]
• Researchers have inferred, based on genetic interactions, that the gene product of Ncstn
  • participates in the following biological processes:
    • epithelial cell proliferation based on interactions with Psen1 ^[4]

---

Summary text based on GO annotations supported by experimental evidence in other organisms

• From comparative sequence analysis (see table for details), MGI curators have determined that the gene product of Ncstn:
  • participates in the following biological processes:
    • membrane protein ectodomain proteolysis
    • positive regulation of catalytic activity
    • protein processing
  • performs the following molecular functions:
    • peptidase activity
  • is located in the following cellular components:
    • endoplasmic reticulum
    • Golgi apparatus
    • integral to plasma membrane
    • lysosomal membrane

---

Summary text based on GO annotations supported by structural data

• Ncstn encodes a protein or proteins that contain the following InterPro domains: Nicastrin, indicating that the gene product:
  • is located in the following cellular components:
    • integral to membrane

---

Summary text for additional MGI annotations

• Automated translation to GO terms of SwissProt keywords that describe Ncstn indicates that it:
  • participates in the following biological processes:
    • Notch signaling pathway
  • is located in the following cellular components:
    • integral to membrane

---

References

1. Chen F et al. (2003) Presenilin 1 and presenilin 2 have differential effects on the stability and maturation of nicastrin in Mammalian brain. J Biol Chem, 278:19974-9. (PubMed:12646573)
2. Hebert SS et al. (2004) Coordinated and widespread expression of gamma-secretase in vivo: evidence for size and molecular heterogeneity. Neurobiol Dis, 17:260-72. (PubMed:15474363)
3. Leem JY et al. (2002) Presenilin 1 is required for maturation and cell surface accumulation of nicastrin. J Biol Chem, 277:19236-40. (PubMed:11943765)
4. Li T et al. (2007) Moderate reduction of gamma-secretase attenuates amyloid burden and limits mechanism-based liabilities. J Neurosci, 27:10849-59. (PubMed:17913918)
5. Ma G et al. (2005) APH-1a is the principal mammalian APH-1 isoform present in gamma-secretase complexes during embryonic development. J Neurosci, 25:192-8. (PubMed:15634781)
6. Marutani T et al. (2011) ER-stress-inducible Herp, facilitates the degradation of immature nicastrin. Biochim Biophys Acta, 1810:790-8. (PubMed:21600962)
7. Vetrivel KS et al. (2005) Spatial segregation of gamma-secretase and substrates in distinct membrane domains. J Biol Chem, 280:25892-900. (PubMed:15886206)

---

---

Gene Ontology Evidence Code Abbreviations:

EXP Inferred from experiment

IC Inferred by curator

IDA Inferred from direct assay

IEA Inferred from electronic annotation

IGI Inferred from genetic interaction

IMP Inferred from mutant phenotype

IPI Inferred from physical interaction

ISS Inferred from sequence or structural similarity

ISO Inferred from sequence orthology

ISA Inferred from sequence alignment

ISM Inferred from sequence model

NAS Non-traceable author statement

ND No biological data available

RCA Reviewed computational analysis

TAS Traceable author statement

---