InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: NPC2

Summary

InnateDB Protein

IDBP-601869.3

Last Modified

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

Gene Symbol

NPC2

Protein Name

Niemann-Pick disease, type C2

Synonyms

EDDM1; HE1;

Species

Homo sapiens

Ensembl Protein

ENSP00000451112

InnateDB Gene

IDBG-12155 (NPC2)

Protein Structure

UniProt Annotation

Function

Intracellular cholesterol transporter which acts in concert with NPC1 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. The secreted form of NCP2 regulates biliary cholesterol secretion via stimulation of ABCG5/ABCG8-mediated cholesterol transport. {ECO:0000269PubMed:17018531, ECO:0000269PubMed:18772377, ECO:0000269PubMed:18823126}.

Subcellular Localization

Secreted {ECO:0000269PubMed:19723497}. Endoplasmic reticulum {ECO:0000269PubMed:19723497}. Lysosome {ECO:0000269PubMed:19723497}.

Disease Associations

Niemann-Pick disease C2 (NPC2) [MIM:607625]: 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 C2 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. {ECO:0000269PubMed:11125141, ECO:0000269PubMed:11567215, ECO:0000269PubMed:12447927, ECO:0000269PubMed:12955717, ECO:0000269PubMed:15937921, ECO:0000269PubMed:16126423}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Epididymis. {ECO:0000269PubMed:19664597}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 14 experimentally validated interaction(s) in this database.

Experimentally validated
Total	14 [view]
Protein-Protein	14 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Gene Ontology

Molecular Function

Accession	GO Term
GO:0005515	protein binding
GO:0015485	cholesterol binding
GO:0019899	enzyme binding

Biological Process

GO:0008203	cholesterol metabolic process
GO:0009615	response to virus
GO:0015914	phospholipid transport
GO:0019747	regulation of isoprenoid metabolic process
GO:0030301	cholesterol transport
GO:0032366	intracellular sterol transport
GO:0032367	intracellular cholesterol transport
GO:0033344	cholesterol efflux
GO:0042632	cholesterol homeostasis
GO:0046836	glycolipid transport