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

GO curators for mouse genes have assigned the following annotations to the gene product of Npc1. (This text reflects annotations as of Wednesday, January 23, 2013.)

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Summary from NCBI RefSeq

[Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a large protein that resides in the limiting membrane of endosomes and lysosomes and mediates intracellular cholesterol trafficking via binding of cholesterol to its N-terminal domain. It is predicted to have a cytoplasmic C-terminus, 13 transmembrane domains, and 3 large loops in the lumen of the endosome - the last loop being at the N-terminus. This protein transports low-density lipoproteins to late endosomal/lysosomal compartments where they are hydrolized and released as free cholesterol. Defects in this gene cause Niemann-Pick type C disease, a rare autosomal recessive neurodegenerative disorder characterized by over accumulation of cholesterol and glycosphingolipids in late endosomal/lysosomal compartments.[provided by RefSeq, Aug 2009]

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

• Researchers have inferred from direct assay, that the gene product of Npc1
  • participates in the following biological processes:
    • cellular response to low-density lipoprotein particle stimulus ^[2]
    • cellular response to steroid hormone stimulus ^[2]
    • protein glycosylation ^[1]
    • response to drug ^[2]
  • is located in the following cellular components:
    • endosome ^{[2, 4]}
    • extracellular region ^[1]
    • Golgi apparatus ^[2]
    • lysosome ^{[1, 2]}
    • membrane ^[2]
    • membrane raft ^[2]
    • nuclear envelope ^[3]
    • plasma membrane ^[2]
    • vesicle ^[2]
• The gene product of Npc1 has been shown to bind to the gene products of Vps4b. ^{[1, 4]}
• Researchers have inferred, based on phenotypic analysis of mouse mutants, that the gene product of Npc1
  • participates in the following biological processes:
    • cholesterol efflux ^[8]
    • endocytosis ^[7]
    • negative regulation of macroautophagy ^[5]
• Researchers have inferred, based on genetic interactions, that the gene product of Npc1
  • participates in the following biological processes:
    • adult walking behavior based on interactions with Mapt ^[6]
    • negative regulation of macroautophagy based on interactions with Becn1 ^[5]

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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 Npc1:
  • participates in the following biological processes:
    • autophagy
    • cholesterol efflux
    • cholesterol homeostasis
    • cholesterol transport
    • protein glycosylation
    • response to cadmium ion
  • performs the following molecular functions:
    • cholesterol binding
  • is located in the following cellular components:
    • endoplasmic reticulum
    • integral to plasma membrane
    • nuclear envelope
    • perinuclear region of cytoplasm

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Summary text based on GO annotations supported by structural data

• Npc1 encodes a protein or proteins that contain the following InterPro domains: Niemann-Pick C type protein, Patched, Sterol-sensing domain, indicating that the gene product:
  • performs the following molecular functions:
    • hedgehog receptor activity
  • is located in the following cellular components:
    • integral to membrane

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Summary text for additional MGI annotations

• Automated translation to GO terms of SwissProt keywords that describe Npc1 indicates that it:
  • participates in the following biological processes:
    • cholesterol metabolic process
    • lipid metabolic process
    • steroid metabolic process
  • is located in the following cellular components:
    • integral to membrane

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References

1. Deffieu MS et al. (2011) Niemann-Pick type C 1 function requires lumenal domain residues that mediate cholesterol-dependent NPC2 binding. Proc Natl Acad Sci U S A, 108:18932-6. (PubMed:22065762)
2. Garver WS et al. (2000) Localization of the murine Niemann-Pick C1 protein to two distinct intracellular compartments. J Lipid Res, 41:673-87. (PubMed:10787428)
3. Kim CE et al. (2010) A molecular mechanism underlying the neural-specific defect in torsinA mutant mice. Proc Natl Acad Sci U S A, 107:9861-6. (PubMed:20457914)
4. Ohsaki Y et al. (2006) Cholesterol depletion facilitates ubiquitylation of NPC1 and its association with SKD1/Vps4. J Cell Sci, 119:2643-53. (PubMed:16757520)
5. Pacheco CD et al. (2007) Autophagy in Niemann-Pick C disease is dependent upon Beclin-1 and responsive to lipid trafficking defects. Hum Mol Genet, 16:1495-503. (PubMed:17468177)
6. Pacheco CD et al. (2009) Tau deletion exacerbates the phenotype of Niemann-Pick type C mice and implicates autophagy in pathogenesis. Hum Mol Genet, 18:956-65. (PubMed:19074461)
7. te Vruchte D et al. (2004) Accumulation of glycosphingolipids in Niemann-Pick C disease disrupts endosomal transport. J Biol Chem, 279:26167-75. (PubMed:15078881)
8. Wang MD et al. (2007) Different cellular traffic of LDL-cholesterol and acetylated LDL-cholesterol leads to distinct reverse cholesterol transport pathways. J Lipid Res, 48:633-45. (PubMed:17148552)

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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

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