Search
Niemann-Pick C1 protein (NPC1)
Function:
- role in the intracellular trafficking of cholesterol
- may play a role in vesicular trafficking in glia, a process that may be crucial for maintaining the structural & functional integrity of nerve terminals
Structure:
- glycosylated
- cysteine-rich N-terminal domain & a C-terminal domain containing di-leucine motif necessary for lysosomal targeting are critical for mobilization of cholesterol from lysosomes
- belongs to the patched family
- contains 1 SSD (sterol-sensing) domain
- has homology to resistance-nodulation-division (RND) family of prokaryotic permeases
- also has similarity to patched family of proteins
Compartment:
- late endosome membrane; multi-pass membrane protein
- lysosome membrane; multi-pass membrane protein
Pathology:
- mutations associated with Niemann-Pick disease type 2
a) Niemann-Pick disease type C1
b) Niemann-Pick disease type D
Laboratory:
- NPC1 gene mutation
General
glycoprotein
transmembrane 11 protein
Properties
SIZE: entity length = 1278 aa
MW = 142 kD
COMPARTMENT: lysosome
MOTIF: signal sequence {1-22}
N-glycosylation site {N70}
N-glycosylation site {N122}
N-glycosylation site {N135}
N-glycosylation site {N185}
N-glycosylation site {N222}
proline-rich region
SITE: 249-259
MOTIF: proline residue (SEVERAL)
transmembrane domain {270-290}
transmembrane domain {351-371}
N-glycosylation site {N452}
N-glycosylation site {N459}
N-glycosylation site {N478}
N-glycosylation site {N524}
sterol-sensing domain {620-785}
MOTIF: binding site
FOR-BINDING-OF: sterol
transmembrane domain {622-642}
transmembrane domain {655-675}
transmembrane domain {678-698}
transmembrane domain {760-780}
transmembrane domain {833-853}
N-glycosylation site {N916}
N-glycosylation site {N1064}
transmembrane domain {1099-1119}
transmembrane domain {1125-1145}
transmembrane domain {1196-1216}
transmembrane domain {1228-1248}
Di-leucine {1275-1278}
Database Correlations
OMIM correlations
MORBIDMAP 607623
UniProt O15118
Pfam PF02460
Entrez Gene 4864
Kegg hsa:4864
References
- UniProt :accession O15118
- Niemann-Pick type C disease gene variation database
http://npc.fzk.de
- GeneReviews
http://www.ncbi.nlm.nih.gov/sites/genetests/lab/gene/NPC1
- Davies JP et al
Transmembrane molecular pump activity of Niemann-Pick C1
protein.
Science 290:2295-8, 2000
PMID: 11125140