InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: NPC1

Summary

InnateDB Protein

IDBP-1602.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

NPC1

Protein Name

Niemann-Pick disease, type C1

Synonyms

NPC;

Species

Homo sapiens

Ensembl Protein

ENSP00000269228

InnateDB Gene

IDBG-1600 (NPC1)

Protein Structure

UniProt Annotation

Function

Intracellular cholesterol transporter which acts in concert with NPC2 and plays an important role in the egress of cholesterol from the endosomal/lysosomal compartment. Both NPC1 and NPC2 function as the cellular 'tag team duo' (TTD) to catalyze the mobilization of cholesterol within the multivesicular environment of the late endosome (LE) to effect egress through the limiting bilayer of the LE. NPC2 binds unesterified cholesterol that has been released from LDLs in the lumen of the late endosomes/lysosomes and transfers it to the cholesterol-binding pocket of the N-terminal domain of NPC1. Cholesterol binds to NPC1 with the hydroxyl group buried in the binding pocket and is exported from the limiting membrane of late endosomes/ lysosomes to the ER and plasma membrane by an unknown mechanism. Binds oxysterol with higher affinity than cholesterol. May play a role in vesicular trafficking in glia, a process that may be crucial for maintaining the structural and functional integrity of nerve terminals. {ECO:0000269PubMed:18772377, ECO:0000269PubMed:19563754}.

Subcellular Localization

Late endosome membrane {ECO:0000269PubMed:17897319}; Multi-pass membrane protein {ECO:0000269PubMed:17897319}. Lysosome membrane {ECO:0000269PubMed:17897319}; Multi-pass membrane protein {ECO:0000269PubMed:17897319}.

Disease Associations

Niemann-Pick disease C1 (NPC1) [MIM:257220]: A lysosomal storage disorder that affects the viscera and the central nervous system. It is due to defective intracellular processing and transport of low-density lipoprotein derived cholesterol. It causes accumulation of cholesterol in lysosomes, with delayed induction of cholesterol homeostatic reactions. Niemann-Pick disease type C1 has a highly variable clinical phenotype. Clinical features include variable hepatosplenomegaly and severe progressive neurological dysfunction such as ataxia, dystonia and dementia. The age of onset can vary from infancy to late adulthood. An allelic variant of Niemann-Pick disease type C1 is found in people with Nova Scotia ancestry. Patients with the Nova Scotian clinical variant are less severely affected. {ECO:0000269PubMed:10480349, ECO:0000269PubMed:10521290, ECO:0000269PubMed:10521297, ECO:0000269PubMed:11182931, ECO:0000269PubMed:11333381, ECO:0000269PubMed:11349231, ECO:0000269PubMed:11479732, ECO:0000269PubMed:11545687, ECO:0000269PubMed:11754101, ECO:0000269PubMed:12401890, ECO:0000269PubMed:12408188, ECO:0000269PubMed:12554680, ECO:0000269PubMed:12955717, ECO:0000269PubMed:15774455, ECO:0000269PubMed:16098014, ECO:0000269PubMed:16126423, ECO:0000269PubMed:16802107, ECO:0000269PubMed:9211849, ECO:0000269PubMed:9634529}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 17 experimentally validated interaction(s) in this database.

Experimentally validated
Total	17 [view]
Protein-Protein	16 [view]
Protein-DNA	1 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004872	receptor activity
GO:0004888	transmembrane signaling receptor activity
GO:0005515	protein binding
GO:0008158	hedgehog receptor activity
GO:0015248	sterol transporter activity
GO:0015485	cholesterol binding

Biological Process

GO:0006486	protein glycosylation
GO:0006897	endocytosis
GO:0006914	autophagy
GO:0007041	lysosomal transport
GO:0007165	signal transduction
GO:0007628	adult walking behavior
GO:0008203	cholesterol metabolic process
GO:0008206	bile acid metabolic process
GO:0016242	negative regulation of macroautophagy
GO:0030301	cholesterol transport
GO:0031579	membrane raft organization
GO:0033344	cholesterol efflux
GO:0042493	response to drug
GO:0042632	cholesterol homeostasis
GO:0046686	response to cadmium ion
GO:0060548	negative regulation of cell death
GO:0071383	cellular response to steroid hormone stimulus
GO:0071404	cellular response to low-density lipoprotein particle stimulus
GO:0090150	establishment of protein localization to membrane

Cellular Component

GO:0005576	extracellular region
GO:0005635	nuclear envelope
GO:0005764	lysosome
GO:0005765	lysosomal membrane
GO:0005768	endosome
GO:0005783	endoplasmic reticulum
GO:0005794	Golgi apparatus
GO:0005886	plasma membrane
GO:0005887	integral component of plasma membrane
GO:0016020	membrane
GO:0016021	integral component of membrane
GO:0031902	late endosome membrane
GO:0031982	vesicle
GO:0045121	membrane raft
GO:0048471	perinuclear region of cytoplasm
GO:0070062	extracellular vesicular exosome