NPC1L1

The protein encoded by this gene is a multi-pass membrane protein. It contains a conserved N-terminal Niemann-Pick C1 (NPC1) domain and a putative sterol-sensing domain (SSD) which includes a YQRL motif functioning as a plasma membrane to trans-Golgi network transport signal in other proteins. This protein takes up free cholesterol into cells through vesicular endocytosis and plays a critical role in the absorption of intestinal cholesterol. It also has the ability to transport alpha-tocopherol (vitamin E). The drug ezetimibe targets this protein and inhibits the absorption of intestinal cholesterol and alpha-tocopherol. In addition, this protein may play a critical role in regulating lipid metabolism. Polymorphic variations in this gene are associated with plasma total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels and coronary heart disease (CHD) risk. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Full Name

NPC1 Like Intracellular Cholesterol Transporter 1

Function

Plays a major role in cholesterol homeostasis. Is critical for the uptake of cholesterol across the plasma membrane of the intestinal enterocyte. Is the direct molecular target of ezetimibe, a drug that inhibits cholesterol absorption. Lack of activity leads to multiple lipid transport defects. The protein may have a function in the transport of multiple lipids and their homeostasis, and may play a critical role in regulating lipid metabolism. Acts as a negative regulator of NPC2 and down-regulates its expression and secretion by inhibiting its maturation and accelerating its degradation.

Biological Process

Cellular response to sterol depletionManual Assertion Based On ExperimentIDA:UniProtKB
Cholesterol biosynthetic processManual Assertion Based On ExperimentIMP:HGNC-UCL
Cholesterol transportManual Assertion Based On ExperimentIMP:HGNC-UCL
Intestinal cholesterol absorptionManual Assertion Based On ExperimentIMP:HGNC-UCL
Lipoprotein metabolic processManual Assertion Based On ExperimentIMP:HGNC-UCL

Cellular Location

Apical cell membrane
Cell membrane
Cytoplasmic vesicle membrane
Subfractionation of brush border membranes from proximal enterocytes suggests considerable association with the apical membrane fraction. Exists as a predominantly cell surface membrane expressed protein (By similarity).
According to PubMed:15671032, localizes in a subcellular vesicular compartment rich in RAB5.

Topology

Extracellular: 22-284
Helical: 285-305
Cytoplasmic: 306-351
Helical: 352-372
Extracellular: 373-632
Helical: 633-653
Cytoplasmic: 654-666
Helical: 667-687
Extracellular: 688-696
Helical: 697-717
Cytoplasmic: 718-742
Helical: 743-763
Extracellular: 764-776
Helical: 777-797
Cytoplasmic: 798-846
Helical: 847-867
Extracellular: 868-1139
Helical: 1140-1160
Cytoplasmic: 1161-1168
Helical: 1169-1189
Extracellular: 1190-1191
Helical: 1192-1212
Cytoplasmic: 1213-1236
Helical: 1237-1257
Extracellular: 1258-1268
Helical: 1269-1289
Cytoplasmic: 1290-1359

PTM

Highly glycosylated.