Niemann Pick C2

Domain

Binds cholesterol in a hydrophobic pocket; there are no hydrogen bonds between the sterol and the protein.

Function

Intracellular cholesterol transporter which acts in concert with NPC1 and plays an important role in the egress of cholesterol from the lysosomal compartment (PubMed:17018531, PubMed:11125141, PubMed:18772377, PubMed:29580834, PubMed:15937921). Unesterified cholesterol that has been released from LDLs in the lumen of the late endosomes/lysosomes is transferred by NPC2 to the cholesterol-binding pocket in the N-terminal domain of NPC1 (PubMed:17018531, PubMed:18772377, PubMed:27238017). May bind and mobilize cholesterol that is associated with membranes (PubMed:18823126). NPC2 binds cholesterol with a 1:1 stoichiometry (PubMed:17018531). Can bind a variety of sterols, including lathosterol, desmosterol and the plant sterols stigmasterol and beta-sitosterol (PubMed:17018531). The secreted form of NCP2 regulates biliary cholesterol secretion via stimulation of ABCG5/ABCG8-mediated cholesterol transport (By similarity).

Involvement in disease

Niemann-Pick disease C2

NPC2

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.

None

The disease is caused by variants affecting the gene represented in this entry.

Sequence similarities

Belongs to the NPC2 family.

Tissue specificity

Detected in gallbladder bile (PubMed:21315718). Detected in fibroblasts, kidney, liver, spleen, small intestine, placenta and testis (at protein level) (PubMed:11125141). Epididymis.

Cellular localization

• Secreted
• Endoplasmic reticulum
• Lysosome
• Interaction with cell-surface M6PR mediates endocytosis and targeting to lysosomes.

Alternative names

• NPC intracellular cholesterol transporter 2
• Epididymal secretory protein E1
• Human epididymis-specific protein 1
• Niemann-Pick disease type C2 protein
• He1
• HE1
• NPC2

Database links

• entrezGene:10577
• omim:601015
• swissprot:P61916

Target type

Proteins

Molecular weight

16570Da