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NPC2 binds CHOL
Stable Identifier
R-HSA-8876472
Type
Reaction [binding]
Species
Homo sapiens
Compartment
lysosomal lumen
ReviewStatus
5/5
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Transport of small molecules (Homo sapiens)
Plasma lipoprotein assembly, remodeling, and clearance (Homo sapiens)
Plasma lipoprotein clearance (Homo sapiens)
LDL clearance (Homo sapiens)
NPC2 binds CHOL (Homo sapiens)
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The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout
In macrophages, the hydrolysis of cholesteryl esters (CHESTs) is the rate-limiting step in the removal of free cholesterol (CHOL) from these cells. CHOL is transported via transport vesicles and can be used for cellular functions or removed from the cell by ABCA1 to create new HDL particles. Accumulation of CHESTs in macrophage foam cells is key to atherosclerotic plaque formation (Dubland & Francis 2015). Exit from lysosomes of CHOL derived from the hydrolysis of CHESTs in low-density lipoproteins (LDLs) requires the concerted effort of two proteins, membrane-bound Niemann-Pick C1 (NPC1) and soluble NPC2. In the first step, NPC2 binds unesterified CHOL that has been released from LDLs in the lumen of lysosomes (Liou et al. 2006).
Literature References
PubMed ID
Title
Journal
Year
25699256
Lysosomal acid lipase: at the crossroads of normal and atherogenic cholesterol metabolism
Francis, GA
,
Dubland, JA
Front Cell Dev Biol
2015
17018531
NPC2, the protein deficient in Niemann-Pick C2 disease, consists of multiple glycoforms that bind a variety of sterols
Dixit, SS
,
Stock, AM
,
Liou, HL
,
Tint, GS
,
Lobel, P
,
Xu, S
J. Biol. Chem.
2006
Participants
Input
CHOL [lysosomal lumen]
NPC2 [lysosomal lumen]
(Homo sapiens)
Output
NPC2:CHOL [lysosomal lumen]
(Homo sapiens)
Participates
as an event of
LDL clearance (Homo sapiens)
Orthologous Events
NPC2 binds CHOL (Bos taurus)
NPC2 binds CHOL (Caenorhabditis elegans)
NPC2 binds CHOL (Canis familiaris)
NPC2 binds CHOL (Danio rerio)
NPC2 binds CHOL (Dictyostelium discoideum)
NPC2 binds CHOL (Drosophila melanogaster)
NPC2 binds CHOL (Gallus gallus)
NPC2 binds CHOL (Mus musculus)
NPC2 binds CHOL (Rattus norvegicus)
NPC2 binds CHOL (Saccharomyces cerevisiae)
NPC2 binds CHOL (Schizosaccharomyces pombe)
NPC2 binds CHOL (Sus scrofa)
NPC2 binds CHOL (Xenopus tropicalis)
Authored
Jassal, B (2016-06-15)
Reviewed
D'Eustachio, P (2016-10-19)
Created
Jassal, B (2016-06-15)
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