| http://purl.uniprot.org/citations/21602275 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/21602275 | http://www.w3.org/2000/01/rdf-schema#comment | "Niemann-Pick C1-like 1 (NPC1L1) is a multitransmembrane protein playing a crucial role in dietary and biliary cholesterol absorption. Cholesterol promotes the formation and endocytosis of NPC1L1-flotillin-cholesterol membrane microdomains, which is an early step in cholesterol uptake. How cholesterol is sensed in this step is unknown. Here, we find that the N-terminal domain (NTD) of NPC1L1 binds cholesterol. Mutation of residue Leu-216 in NPC1L1-NTD eliminates cholesterol binding, decreases the formation of NPC1L1-flotillin-cholesterol membrane microdomains, and prevents NPC1L1-mediated cholesterol uptake in culture cells and mice livers. NPC1L1-NTD specifically binds cholesterol but not plant sterols, which may account for the selective cholesterol absorption in intestine. Furthermore, 25- or 27-hydroxycholesterol competes with cholesterol to bind NPC1L1-NTD and inhibits the cholesterol induced endocytosis of NPC1L1. Together, these results demonstrate that plasma membrane-localized NPC1L1 binds exogenous cholesterol via its NTD, and facilitates the formation of NPC1L1-flotillin-cholesterol membrane microdomains that are then internalized into cells through the clathrin-AP2 pathway. Our study uncovers the mechanism of cholesterol sensing by NPC1L1 and proposes a mechanism for selective cholesterol absorption."xsd:string |
| http://purl.uniprot.org/citations/21602275 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m111.244475"xsd:string |
| http://purl.uniprot.org/citations/21602275 | http://purl.uniprot.org/core/author | "Qi W."xsd:string |
| http://purl.uniprot.org/citations/21602275 | http://purl.uniprot.org/core/author | "Zhang L."xsd:string |
| http://purl.uniprot.org/citations/21602275 | http://purl.uniprot.org/core/author | "Yang M."xsd:string |
| http://purl.uniprot.org/citations/21602275 | http://purl.uniprot.org/core/author | "Zhang J.H."xsd:string |
| http://purl.uniprot.org/citations/21602275 | http://purl.uniprot.org/core/author | "Ge L."xsd:string |
| http://purl.uniprot.org/citations/21602275 | http://purl.uniprot.org/core/author | "Li B.L."xsd:string |
| http://purl.uniprot.org/citations/21602275 | http://purl.uniprot.org/core/author | "Miao H.H."xsd:string |
| http://purl.uniprot.org/citations/21602275 | http://purl.uniprot.org/core/author | "Song B.L."xsd:string |
| http://purl.uniprot.org/citations/21602275 | http://purl.uniprot.org/core/date | "2011"xsd:gYear |
| http://purl.uniprot.org/citations/21602275 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/21602275 | http://purl.uniprot.org/core/pages | "25088-25097"xsd:string |
| http://purl.uniprot.org/citations/21602275 | http://purl.uniprot.org/core/title | "The N-terminal domain of NPC1L1 protein binds cholesterol and plays essential roles in cholesterol uptake."xsd:string |
| http://purl.uniprot.org/citations/21602275 | http://purl.uniprot.org/core/volume | "286"xsd:string |
| http://purl.uniprot.org/citations/21602275 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/21602275 |
| http://purl.uniprot.org/citations/21602275 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/21602275 |
| http://purl.uniprot.org/uniprot/Q9UHC9#attribution-7FA2DC5DB22B16EBEA1E1B65DF88F255 | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/21602275 |
| http://purl.uniprot.org/uniprot/#_A0A0C4DGG6-mappedCitation-21602275 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21602275 |
| http://purl.uniprot.org/uniprot/#_A0A0C4DFX6-mappedCitation-21602275 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21602275 |
| http://purl.uniprot.org/uniprot/#_A3KMG9-mappedCitation-21602275 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21602275 |
| http://purl.uniprot.org/uniprot/#_A2RRR0-mappedCitation-21602275 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21602275 |
| http://purl.uniprot.org/uniprot/#_Q6T3U4-mappedCitation-21602275 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21602275 |
| http://purl.uniprot.org/uniprot/#_Q9UHC9-mappedCitation-21602275 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21602275 |