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Protein

Niemann-Pick C1 protein

Gene

NPC1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.2 Publications
(Microbial infection) Acts as an endosomal entry receptor for ebolavirus.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei41Cholesterol1 Publication1
Binding sitei79Cholesterol1 Publication1
Sitei108Important for cholesterol binding1

GO - Molecular functioni

  • cholesterol binding Source: UniProtKB
  • receptor activity Source: ProtInc
  • sterol transporter activity Source: ProtInc
  • transmembrane signaling receptor activity Source: ProtInc
  • virus receptor activity Source: UniProtKB-KW

GO - Biological processi

  • adult walking behavior Source: Ensembl
  • autophagy Source: MGI
  • bile acid metabolic process Source: UniProtKB
  • cellular response to low-density lipoprotein particle stimulus Source: Ensembl
  • cellular response to steroid hormone stimulus Source: Ensembl
  • cholesterol efflux Source: BHF-UCL
  • cholesterol homeostasis Source: UniProtKB
  • cholesterol metabolic process Source: UniProtKB-KW
  • cholesterol transport Source: UniProtKB
  • endocytosis Source: Ensembl
  • establishment of protein localization to membrane Source: UniProtKB
  • lysosomal transport Source: UniProtKB
  • membrane raft organization Source: UniProtKB
  • negative regulation of cell death Source: Ensembl
  • negative regulation of macroautophagy Source: Ensembl
  • positive regulation of cholesterol homeostasis Source: CACAO
  • protein glycosylation Source: UniProtKB
  • response to cadmium ion Source: Ensembl
  • response to drug Source: Ensembl
  • viral entry into host cell Source: CACAO
Complete GO annotation...

Keywords - Molecular functioni

Host cell receptor for virus entry, Receptor

Keywords - Biological processi

Cholesterol metabolism, Host-virus interaction, Lipid metabolism, Steroid metabolism, Sterol metabolism

Enzyme and pathway databases

BioCyciZFISH:ENSG00000141458-MONOMER.

Protein family/group databases

TCDBi2.A.6.6.1. the resistance-nodulation-cell division (rnd) superfamily.

Chemistry databases

SwissLipidsiSLP:000000478.

Names & Taxonomyi

Protein namesi
Recommended name:
Niemann-Pick C1 protein
Gene namesi
Name:NPC1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 18

Organism-specific databases

HGNCiHGNC:7897. NPC1.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini23 – 269LumenalSequence analysisAdd BLAST247
Transmembranei270 – 290HelicalSequence analysisAdd BLAST21
Topological domaini291 – 350CytoplasmicSequence analysisAdd BLAST60
Transmembranei351 – 371HelicalSequence analysisAdd BLAST21
Topological domaini372 – 620LumenalSequence analysisAdd BLAST249
Transmembranei621 – 641HelicalSequence analysisAdd BLAST21
Topological domaini642 – 654CytoplasmicSequence analysisAdd BLAST13
Transmembranei655 – 675HelicalSequence analysisAdd BLAST21
Topological domaini676 – 677LumenalSequence analysis2
Transmembranei678 – 698HelicalSequence analysisAdd BLAST21
Topological domaini699 – 734CytoplasmicSequence analysisAdd BLAST36
Transmembranei735 – 755HelicalSequence analysisAdd BLAST21
Topological domaini756 – 759LumenalSequence analysis4
Transmembranei760 – 780HelicalSequence analysisAdd BLAST21
Topological domaini781 – 832CytoplasmicSequence analysisAdd BLAST52
Transmembranei833 – 853HelicalSequence analysisAdd BLAST21
Topological domaini854 – 1098LumenalSequence analysisAdd BLAST245
Transmembranei1099 – 1119HelicalSequence analysisAdd BLAST21
Topological domaini1120 – 1124CytoplasmicSequence analysis5
Transmembranei1125 – 1145HelicalSequence analysisAdd BLAST21
Topological domaini1146LumenalSequence analysis1
Transmembranei1147 – 1167HelicalSequence analysisAdd BLAST21
Topological domaini1168 – 1195CytoplasmicSequence analysisAdd BLAST28
Transmembranei1196 – 1216HelicalSequence analysisAdd BLAST21
Topological domaini1217 – 1227LumenalSequence analysisAdd BLAST11
Transmembranei1228 – 1248HelicalSequence analysisAdd BLAST21
Topological domaini1249 – 1278CytoplasmicSequence analysisAdd BLAST30

GO - Cellular componenti

  • endoplasmic reticulum Source: UniProtKB
  • extracellular exosome Source: UniProtKB
  • extracellular region Source: UniProtKB
  • Golgi apparatus Source: Ensembl
  • integral component of membrane Source: ProtInc
  • integral component of plasma membrane Source: UniProtKB
  • late endosome membrane Source: UniProtKB-SubCell
  • lysosomal membrane Source: UniProtKB
  • lysosome Source: UniProtKB
  • membrane Source: UniProtKB
  • membrane raft Source: Ensembl
  • nuclear envelope Source: UniProtKB
  • perinuclear region of cytoplasm Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Endosome, Lysosome, Membrane

Pathology & Biotechi

Involvement in diseasei

Niemann-Pick disease C1 (NPC1)19 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:257220
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04317263C → R in NPC1. 1 PublicationCorresponds to variant rs747049347dbSNPEnsembl.1
Natural variantiVAR_04317374C → Y in NPC1. 1 Publication1
Natural variantiVAR_04317492Q → R in NPC1. 2 Publications1
Natural variantiVAR_043175113C → R in NPC1; partially mislocalized from late endocytic organelles diffusely to the cell periphery; localizes to the endoplasmic reticulum Rab7-negative endosomes and the cell surface; does not clears the lysosomal cholesterol accumulation in NPC1-deficient cells. 1 PublicationCorresponds to variant rs120074136dbSNPEnsembl.1
Natural variantiVAR_043176137T → M in NPC1. 3 PublicationsCorresponds to variant rs372947142dbSNPEnsembl.1
Natural variantiVAR_043178166P → S in NPC1. 2 Publications1
Natural variantiVAR_008815177C → G in NPC1; late infantile form. 1 Publication1
Natural variantiVAR_015561177C → Y in NPC1. 3 PublicationsCorresponds to variant rs80358252dbSNPEnsembl.1
Natural variantiVAR_043179222N → S in NPC1. 1 PublicationCorresponds to variant rs55680026dbSNPEnsembl.1
Natural variantiVAR_043180231V → G in NPC1. 1 Publication1
Natural variantiVAR_008817237P → S in NPC1; late infantile form. 5 PublicationsCorresponds to variant rs80358251dbSNPEnsembl.1
Natural variantiVAR_043181242D → H in NPC1. 1 Publication1
Natural variantiVAR_043182242D → N in NPC1. 1 Publication1
Natural variantiVAR_043183247C → Y in NPC1. 1 Publication1
Natural variantiVAR_043184248G → V in NPC1. 1 Publication1
Natural variantiVAR_043185272M → R in NPC1. 1 Publication1
Natural variantiVAR_043186273W → S Colocalizes with the wild-type protein with Rab7-positive late endosomes; clears the lysosomal cholesterol accumulation in NPC1-deficient cells. 1 Publication1
Natural variantiVAR_043187372R → W in NPC1. 1 Publication1
Natural variantiVAR_015562378V → A in NPC1. 1 PublicationCorresponds to variant rs120074134dbSNPEnsembl.1
Natural variantiVAR_043188380L → F in NPC1. 1 Publication1
Natural variantiVAR_043190388A → P in NPC1. 1 Publication1
Natural variantiVAR_043191389R → C in NPC1. 1 Publication1
Natural variantiVAR_043192401P → T in NPC1. 1 Publication1
Natural variantiVAR_043193404R → P in NPC1. 1 Publication1
Natural variantiVAR_043194404R → Q in NPC1. 3 PublicationsCorresponds to variant rs139751448dbSNPEnsembl.1
Natural variantiVAR_043195404R → W in NPC1. 1 Publication1
Natural variantiVAR_043196433P → L in NPC1. 1 Publication1
Natural variantiVAR_043197434P → L in NPC1. 1 PublicationCorresponds to variant rs774333145dbSNPEnsembl.1
Natural variantiVAR_043199451E → K in NPC1. 1 PublicationCorresponds to variant rs781065429dbSNPEnsembl.1
Natural variantiVAR_008820473S → P in NPC1; late infantile form. 1 Publication1
Natural variantiVAR_043200474P → L in NPC1. 2 PublicationsCorresponds to variant rs372445155dbSNPEnsembl.1
Natural variantiVAR_043201479C → Y in NPC1. 1 Publication1
Natural variantiVAR_043202509Y → S in NPC1. 1 Publication1
Natural variantiVAR_008821510H → P in NPC1; late infantile form. 1 Publication1
Natural variantiVAR_043204512H → R in NPC1. 1 Publication1
Natural variantiVAR_008822518R → Q in NPC1; late infantile form; Common in Japanese. 2 PublicationsCorresponds to variant rs483352886dbSNPEnsembl.1
Natural variantiVAR_043205518R → W in NPC1. 1 PublicationCorresponds to variant rs377515417dbSNPEnsembl.1
Natural variantiVAR_043206521A → S in NPC1. 1 PublicationCorresponds to variant rs138184115dbSNPEnsembl.1
Natural variantiVAR_043207537F → L in NPC1. 1 Publication1
Natural variantiVAR_043208543P → L in NPC1. 2 PublicationsCorresponds to variant rs369368181dbSNPEnsembl.1
Natural variantiVAR_043209574T → K in NPC1. 1
Natural variantiVAR_043210576K → R in NPC1. 1 PublicationCorresponds to variant rs761660695dbSNPEnsembl.1
Natural variantiVAR_043211605A → V in NPC1. 1 Publication1
Natural variantiVAR_043212612E → D in NPC1. 1 Publication1
Natural variantiVAR_043213615R → C in NPC1. 1 PublicationCorresponds to variant rs745777805dbSNPEnsembl.1
Natural variantiVAR_043214615R → L in NPC1. 1 PublicationCorresponds to variant rs773351341dbSNPEnsembl.1
Natural variantiVAR_043215631M → R in NPC1. 2 Publications1
Natural variantiVAR_043216640G → R in NPC1. 1 Publication1
Natural variantiVAR_043217652S → W in NPC1. 1 Publication1
Natural variantiVAR_043218660G → S in NPC1. 1 Publication1
Natural variantiVAR_043219664V → M in NPC1. 2 PublicationsCorresponds to variant rs376213990dbSNPEnsembl.1
Natural variantiVAR_043220666S → N in NPC1. 1 PublicationCorresponds to variant rs750480579dbSNPEnsembl.1
Natural variantiVAR_043221670C → W in NPC1. 1 Publication1
Natural variantiVAR_043222673G → V in NPC1. 1 Publication1
Natural variantiVAR_043223684L → F in NPC1. 1 Publication1
Natural variantiVAR_043224691P → L in NPC1. 1 Publication1
Natural variantiVAR_043225695L → V in NPC1. 1 PublicationCorresponds to variant rs370323921dbSNPEnsembl.1
Natural variantiVAR_043226700D → N in NPC1. 1 Publication1
Natural variantiVAR_043227703F → S in NPC1. 1 Publication1
Natural variantiVAR_043228724L → P in NPC1. 1 Publication1
Natural variantiVAR_043229727V → F in NPC1. 1 Publication1
Natural variantiVAR_043230734S → I in NPC1. 1 PublicationCorresponds to variant rs757475924dbSNPEnsembl.1
Natural variantiVAR_043231742E → K in NPC1. 1 Publication1
Natural variantiVAR_043232745A → E in NPC1. 1 PublicationCorresponds to variant rs752386083dbSNPEnsembl.1
Natural variantiVAR_043233754M → K in NPC1. 1 Publication1
Natural variantiVAR_043234763F → L in NPC1. 1 Publication1
Natural variantiVAR_043235767A → V in NPC1. 1 Publication1
Natural variantiVAR_043236775Q → P in NPC1. 2 PublicationsCorresponds to variant rs80358253dbSNPEnsembl.1
Natural variantiVAR_043237789R → C in NPC1. 1 Publication1
Natural variantiVAR_043238789R → G in NPC1. 1 Publication1
Natural variantiVAR_043239825Y → C in NPC1. 4 PublicationsCorresponds to variant rs550562774dbSNPEnsembl.1
Natural variantiVAR_043240849S → I in NPC1. 1 Publication1
Natural variantiVAR_043241862Q → L in NPC1. 1 Publication1
Natural variantiVAR_043242865S → L in NPC1. 2 Publications1
Natural variantiVAR_043243871Y → C in NPC1. 1 Publication1
Natural variantiVAR_043245874D → V in NPC1. 3 PublicationsCorresponds to variant rs372030650dbSNPEnsembl.1
Natural variantiVAR_043246888P → S in NPC1. 1 Publication1
Natural variantiVAR_008826889V → M in NPC1; adult form. 1 PublicationCorresponds to variant rs120074130dbSNPEnsembl.1
Natural variantiVAR_043247890Y → C in NPC1. 1 Publication1
Natural variantiVAR_043248899Y → D in NPC1. 1 Publication1
Natural variantiVAR_043249910G → S in NPC1. 1 PublicationCorresponds to variant rs768999208dbSNPEnsembl.1
Natural variantiVAR_043250917D → Y in NPC1. 1 Publication1
Natural variantiVAR_043251926A → T in NPC1. 1 PublicationCorresponds to variant rs564631426dbSNPEnsembl.1
Natural variantiVAR_043252927A → V in NPC1. 1 PublicationCorresponds to variant rs753768576dbSNPEnsembl.1
Natural variantiVAR_008827928Q → P in NPC1. Corresponds to variant rs28940897dbSNPEnsembl.1
Natural variantiVAR_043253929L → P in NPC1. 1 Publication1
Natural variantiVAR_008828934R → Q in NPC1. 3 PublicationsCorresponds to variant rs786204714dbSNPEnsembl.1
Natural variantiVAR_008829940S → L in NPC1. 3 PublicationsCorresponds to variant rs143124972dbSNPEnsembl.1
Natural variantiVAR_043254942W → C in NPC1. 2 Publications1
Natural variantiVAR_043255943I → M in NPC1. 1 Publication1
Natural variantiVAR_043256944D → N in NPC1. 3 PublicationsCorresponds to variant rs748837410dbSNPEnsembl.1
Natural variantiVAR_043257945D → N in NPC1. 1 Publication1
Natural variantiVAR_043258948D → H in NPC1. 1 Publication1
Natural variantiVAR_008830948D → N in NPC1. 3 Publications1
Natural variantiVAR_043259948D → Y in NPC1. 1 Publication1
Natural variantiVAR_015563950V → M in NPC1; adult form. 2 PublicationsCorresponds to variant rs120074135dbSNPEnsembl.1
Natural variantiVAR_008831954S → L in NPC1. 3 PublicationsCorresponds to variant rs543206298dbSNPEnsembl.1
Natural variantiVAR_008832956C → Y in NPC1; late infantile form. 1 Publication1
Natural variantiVAR_043260958R → L in NPC1. 1 Publication1
Natural variantiVAR_015564958R → Q in NPC1. 1 PublicationCorresponds to variant rs120074132dbSNPEnsembl.1
Natural variantiVAR_043261959V → E in NPC1. 1 Publication1
Natural variantiVAR_043262961 – 966NITDQF → S in NPC1. 1 Publication6
Natural variantiVAR_043263961N → S in NPC1. 1 PublicationCorresponds to variant rs34084984dbSNPEnsembl.1
Natural variantiVAR_043264968N → S in NPC1. 2 PublicationsCorresponds to variant rs773767253dbSNPEnsembl.1
Natural variantiVAR_043266976C → R in NPC1. 1 Publication1
Natural variantiVAR_015565978R → C in NPC1. 2 PublicationsCorresponds to variant rs28942108dbSNPEnsembl.1
Natural variantiVAR_043267986G → S in NPC1. 1 Publication1
Natural variantiVAR_043268992G → A in NPC1. 1 PublicationCorresponds to variant rs757534240dbSNPEnsembl.1
Natural variantiVAR_015566992G → R in NPC1. 2 PublicationsCorresponds to variant rs80358254dbSNPEnsembl.1
Natural variantiVAR_008833992G → W in NPC1; found in the Nova Scotian clinical variant. 5 PublicationsCorresponds to variant rs80358254dbSNPEnsembl.1
Natural variantiVAR_043269996M → R in NPC1. 1 Publication1
Natural variantiVAR_0432701004S → L in NPC1. 1 PublicationCorresponds to variant rs150334966dbSNPEnsembl.1
Natural variantiVAR_0088341007P → A in NPC1. 7 PublicationsCorresponds to variant rs80358257dbSNPEnsembl.1
Natural variantiVAR_0432711012G → D in NPC1. 1 Publication1
Natural variantiVAR_0432721015G → V in NPC1. 1 PublicationCorresponds to variant rs761773567dbSNPEnsembl.1
Natural variantiVAR_0432731016H → R in NPC1. 1 PublicationCorresponds to variant rs140211089dbSNPEnsembl.1
Natural variantiVAR_0432741023V → G in NPC1. 1 Publication1
Natural variantiVAR_0432751034G → R in NPC1. 1 Publication1
Natural variantiVAR_0155671035A → V in NPC1. 2 PublicationsCorresponds to variant rs28942107dbSNPEnsembl.1
Natural variantiVAR_0432761036T → K in NPC1. 1 Publication1
Natural variantiVAR_0088351036T → M in NPC1. 1 PublicationCorresponds to variant rs28942104dbSNPEnsembl.1
Natural variantiVAR_0432781054A → T in NPC1. 1 PublicationCorresponds to variant rs80358258dbSNPEnsembl.1
Natural variantiVAR_0432791059R → Q in NPC1. 1 PublicationCorresponds to variant rs771000314dbSNPEnsembl.1
Natural variantiVAR_0088361061I → T in NPC1; late infantile form. 10 PublicationsCorresponds to variant rs80358259dbSNPEnsembl.1
Natural variantiVAR_0432801062A → V in NPC1. 1 Publication1
Natural variantiVAR_0432811066T → N in NPC1. 1 PublicationCorresponds to variant rs772622214dbSNPEnsembl.1
Natural variantiVAR_0432821087F → L in NPC1. 1 PublicationCorresponds to variant rs746715353dbSNPEnsembl.1
Natural variantiVAR_0088371088Y → C in NPC1; juvenile form. 1 PublicationCorresponds to variant rs28942106dbSNPEnsembl.1
Natural variantiVAR_0432831089E → K in NPC1. 1 PublicationCorresponds to variant rs374526072dbSNPEnsembl.1
Natural variantiVAR_0432841094I → T in NPC1. 1 Publication1
Natural variantiVAR_0432851097D → N in NPC1. 1 PublicationCorresponds to variant rs758829443dbSNPEnsembl.1
Natural variantiVAR_0432861137N → I in NPC1. 1 Publication1
Natural variantiVAR_0432871140G → V in NPC1. 1 Publication1
Natural variantiVAR_0432881142M → T in NPC1. 2 PublicationsCorresponds to variant rs778878523dbSNPEnsembl.1
Natural variantiVAR_0432891150N → K in NPC1. 1 Publication1
Natural variantiVAR_0432901156N → I in NPC1. 1 PublicationCorresponds to variant rs28942105dbSNPEnsembl.1
Natural variantiVAR_0088381156N → S in NPC1. 4 PublicationsCorresponds to variant rs28942105dbSNPEnsembl.1
Natural variantiVAR_0432911165V → M in NPC1. 1 PublicationCorresponds to variant rs748862167dbSNPEnsembl.1
Natural variantiVAR_0088391167F → L in NPC1. 1
Natural variantiVAR_0432921168C → Y in NPC1. 1 Publication1
Natural variantiVAR_0432931174A → V in NPC1. 1 PublicationCorresponds to variant rs780175800dbSNPEnsembl.1
Natural variantiVAR_0088401186R → H in NPC1. 3 PublicationsCorresponds to variant rs200444084dbSNPEnsembl.1
Natural variantiVAR_0432941189E → G in NPC1. 1 PublicationCorresponds to variant rs369098773dbSNPEnsembl.1
Natural variantiVAR_0432951205T → K in NPC1. 1 PublicationCorresponds to variant rs758902805dbSNPEnsembl.1
Natural variantiVAR_0432961205T → R in NPC1. 1 Publication1
Natural variantiVAR_0432971212V → L in NPC1. 1 PublicationCorresponds to variant rs753419933dbSNPEnsembl.1
Natural variantiVAR_0088411213L → F in NPC1; juvenile form. 1 PublicationCorresponds to variant rs120074131dbSNPEnsembl.1
Natural variantiVAR_0088421213L → V in NPC1. 1 PublicationCorresponds to variant rs766178353dbSNPEnsembl.1
Natural variantiVAR_0432981216A → V in NPC1. 1 Publication1
Natural variantiVAR_0432991224F → L in NPC1. 1 Publication1
Natural variantiVAR_0433001236G → E in NPC1. 1 PublicationCorresponds to variant rs761653115dbSNPEnsembl.1
Natural variantiVAR_0433011240G → R in NPC1. 1 PublicationCorresponds to variant rs745892286dbSNPEnsembl.1
Natural variantiVAR_0433021249S → G in NPC1. 1 Publication1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi26 – 27VW → AA: Nearly abolishes 25-hydroxycholesterol binding. Reduces cholesterol binding. 1 Publication2
Mutagenesisi39 – 41RYN → AAA: Strongly reduces cholesterol and 25-hydroxycholesterol binding. 1 Publication3
Mutagenesisi41N → A: Nearly abolishes cholesterol and 25-hydroxycholesterol binding. 1 Publication1
Mutagenesisi63C → S: Loss of function. 1 Publication1
Mutagenesisi70N → Q: Reduces glycosylation; when associated with Q-122 and Q-185. No effect on cholesterol and 25-hydroxycholesterol binding. 1 Publication1
Mutagenesisi82 – 83TL → AA: Strongly reduces cholesterol and 25-hydroxycholesterol binding. 1 Publication2
Mutagenesisi97C → S: Loss of function. 1 Publication1
Mutagenesisi101 – 102FY → AA: Strongly reduces 25-hydroxycholesterol binding. No effect on cholesterol binding. 1 Publication2
Mutagenesisi106 – 108NLF → AAA: Nearly abolishes cholesterol and 25-hydroxycholesterol binding. 1 Publication3
Mutagenesisi110 – 112ELT → AAA: No effect on cholesterol and 25-hydroxycholesterol binding and transfer. 1 Publication3
Mutagenesisi122N → Q: Reduces glycosylation; when associated with Q-70 and Q-185. No effect on cholesterol and 25-hydroxycholesterol binding. 1 Publication1
Mutagenesisi144 – 145LQ → AA: Strongly reduces 25-hydroxycholesterol binding. No effect on cholesterol binding. 1 Publication2
Mutagenesisi146 – 147YY → AA: Strongly reduces 25-hydroxycholesterol binding. No effect on cholesterol binding. 1 Publication2
Mutagenesisi175 – 176LL → AA: No effect on cholesterol or 25-hydroxycholesterol binding. Strongly reduces cholesterol transfer to liposomes in a NPC2-dependent manner. 1 Publication2
Mutagenesisi180 – 182DAD → AAA: Strongly reduces cholesterol transfer to liposomes in a NPC2-dependent manner. 1 Publication3
Mutagenesisi185N → Q: Reduces glycosylation; when associated with Q-70 and Q-122. No effect on cholesterol and 25-hydroxycholesterol binding. Strongly reduces cholesterol transfer to liposomes in a NPC2-dependent manner. 1 Publication1
Mutagenesisi187 – 188TN → AA: Strongly reduces 25-hydroxycholesterol binding and cholesterol transfer to liposomes in a NPC2-dependent manner. 1 Publication2
Mutagenesisi191 – 192EY → AA: No effect on cholesterol or 25-hydroxycholesterol binding. Nearly abolishes cholesterol transfer to liposomes in a NPC2-dependent manner. 1 Publication2
Mutagenesisi195 – 196NK → AA: Strongly reduces 25-hydroxycholesterol binding. No effect on cholesterol binding. 1 Publication2
Mutagenesisi197 – 198DN → AA: Strongly reduces cholesterol and 25-hydroxycholesterol binding. 1 Publication2
Mutagenesisi199 – 200GQ → AA: Strongly reduces 25-hydroxycholesterol binding and cholesterol transfer to liposomes in a NPC2-dependent manner. 1 Publication2
Mutagenesisi202 – 203PF → AA: Abolishes cholesterol and 25-hydroxycholesterol binding. 1 Publication2
Mutagenesisi204 – 205TI → AA: Strongly reduces cholesterol and 25-hydroxycholesterol binding. 1 Publication2
Mutagenesisi660G → R: Loss of function. 1 Publication1

Keywords - Diseasei

Disease mutation, Niemann-Pick disease

Organism-specific databases

DisGeNETi4864.
MalaCardsiNPC1.
MIMi257220. phenotype.
OpenTargetsiENSG00000141458.
Orphaneti216986. Niemann-Pick disease type C, adult neurologic onset.
216981. Niemann-Pick disease type C, juvenile neurologic onset.
216978. Niemann-Pick disease type C, late infantile neurologic onset.
216975. Niemann-Pick disease type C, severe early infantile neurologic onset.
216972. Niemann-Pick disease type C, severe perinatal form.
PharmGKBiPA31698.

Chemistry databases

ChEMBLiCHEMBL1293277.

Polymorphism and mutation databases

BioMutaiNPC1.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 22Sequence analysisAdd BLAST22
ChainiPRO_000002326123 – 1278Niemann-Pick C1 proteinAdd BLAST1256

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi25 ↔ 741 Publication
Disulfide bondi31 ↔ 421 Publication
Disulfide bondi63 ↔ 1091 Publication
Glycosylationi70N-linked (GlcNAc...)1 Publication1
Disulfide bondi75 ↔ 1131 Publication
Disulfide bondi97 ↔ 2381 Publication
Disulfide bondi100 ↔ 1601 Publication
Glycosylationi122N-linked (GlcNAc...)1 Publication1
Glycosylationi135N-linked (GlcNAc...)1 Publication1
Glycosylationi158N-linked (GlcNAc...); atypical1 Publication1
Disulfide bondi177 ↔ 1841 Publication
Glycosylationi185N-linked (GlcNAc...)1 Publication1
Glycosylationi222N-linked (GlcNAc...)1 Publication1
Disulfide bondi227 ↔ 2431 Publication
Disulfide bondi240 ↔ 2471 Publication
Glycosylationi452N-linked (GlcNAc...)Sequence analysis1
Glycosylationi459N-linked (GlcNAc...)Sequence analysis1
Glycosylationi478N-linked (GlcNAc...)Sequence analysis1
Glycosylationi524N-linked (GlcNAc...)1 Publication1
Glycosylationi961N-linked (GlcNAc...)Sequence analysis1
Glycosylationi968N-linked (GlcNAc...)Sequence analysis1
Glycosylationi1064N-linked (GlcNAc...)Sequence analysis1
Glycosylationi1072N-linked (GlcNAc...)Sequence analysis1

Post-translational modificationi

Glycosylated.3 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

EPDiO15118.
MaxQBiO15118.
PaxDbiO15118.
PeptideAtlasiO15118.
PRIDEiO15118.

PTM databases

iPTMnetiO15118.
PhosphoSitePlusiO15118.
SwissPalmiO15118.

Expressioni

Gene expression databases

BgeeiENSG00000141458.
CleanExiHS_NPC1.
ExpressionAtlasiO15118. baseline and differential.
GenevisibleiO15118. HS.

Organism-specific databases

HPAiCAB070132.
HPA026618.

Interactioni

Subunit structurei

Interacts with TMEM97. Interacts (via the second lumenal domain) with NPC2 in a cholestrol-dependent manner (By similarity). Interacts with TIM1 (PubMed:25855742).By similarity1 Publication
(Microbial infection) Interacts with ebolavirus glycoprotein.1 Publication

Protein-protein interaction databases

BioGridi110925. 13 interactors.
DIPiDIP-53217N.
IntActiO15118. 4 interactors.
STRINGi9606.ENSP00000269228.

Chemistry databases

BindingDBiO15118.

Structurei

Secondary structure

11278
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi26 – 35Combined sources10
Beta strandi38 – 43Combined sources6
Helixi53 – 55Combined sources3
Helixi56 – 62Combined sources7
Helixi64 – 66Combined sources3
Beta strandi72 – 74Combined sources3
Helixi77 – 85Combined sources9
Helixi88 – 94Combined sources7
Helixi98 – 113Combined sources16
Helixi117 – 120Combined sources4
Beta strandi121 – 130Combined sources10
Turni