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UniProtKB - O15118 (NPC1_HUMAN)

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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
Complete GO annotation...

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
  • low-density lipoprotein particle clearance Source: Reactome
  • 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...

Keywordsi

Molecular functionHost cell receptor for virus entry, Receptor
Biological processCholesterol metabolism, Host-virus interaction, Lipid metabolism, Steroid metabolism, Sterol metabolism

Enzyme and pathway databases

ReactomeiR-HSA-8964038. LDL clearance.

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 lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
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 dbSNP:rs747049347Ensembl.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 dbSNP:rs120074136Ensembl.1
Natural variantiVAR_043176137T → M in NPC1. 3 PublicationsCorresponds to variant dbSNP:rs372947142Ensembl.1
Natural variantiVAR_043178166P → S in NPC1. 2 PublicationsCorresponds to variant dbSNP:rs866966704Ensembl.1
Natural variantiVAR_008815177C → G in NPC1; late infantile form. 1 Publication1
Natural variantiVAR_015561177C → Y in NPC1. 3 PublicationsCorresponds to variant dbSNP:rs80358252Ensembl.1
Natural variantiVAR_043179222N → S in NPC1. 1 PublicationCorresponds to variant dbSNP:rs55680026Ensembl.1
Natural variantiVAR_043180231V → G in NPC1. 1 Publication1
Natural variantiVAR_008817237P → S in NPC1; late infantile form. 5 PublicationsCorresponds to variant dbSNP:rs80358251Ensembl.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 dbSNP:rs120074134Ensembl.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 dbSNP:rs139751448Ensembl.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 dbSNP:rs774333145Ensembl.1
Natural variantiVAR_043199451E → K in NPC1. 1 PublicationCorresponds to variant dbSNP:rs781065429Ensembl.1
Natural variantiVAR_008820473S → P in NPC1; late infantile form. 1 Publication1
Natural variantiVAR_043200474P → L in NPC1. 2 PublicationsCorresponds to variant dbSNP:rs372445155Ensembl.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 dbSNP:rs483352886Ensembl.1
Natural variantiVAR_043205518R → W in NPC1. 1 PublicationCorresponds to variant dbSNP:rs377515417Ensembl.1
Natural variantiVAR_043206521A → S in NPC1. 1 PublicationCorresponds to variant dbSNP:rs138184115Ensembl.1
Natural variantiVAR_043207537F → L in NPC1. 1 Publication1
Natural variantiVAR_043208543P → L in NPC1. 2 PublicationsCorresponds to variant dbSNP:rs369368181Ensembl.1
Natural variantiVAR_043209574T → K in NPC1. 1
Natural variantiVAR_043210576K → R in NPC1. 1 PublicationCorresponds to variant dbSNP:rs761660695Ensembl.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 dbSNP:rs745777805Ensembl.1
Natural variantiVAR_043214615R → L in NPC1. 1 PublicationCorresponds to variant dbSNP:rs773351341Ensembl.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 dbSNP:rs376213990Ensembl.1
Natural variantiVAR_043220666S → N in NPC1. 1 PublicationCorresponds to variant dbSNP:rs750480579Ensembl.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 dbSNP:rs370323921Ensembl.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 dbSNP:rs757475924Ensembl.1
Natural variantiVAR_043231742E → K in NPC1. 1 Publication1
Natural variantiVAR_043232745A → E in NPC1. 1 PublicationCorresponds to variant dbSNP:rs752386083Ensembl.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 dbSNP:rs80358253Ensembl.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 dbSNP:rs550562774Ensembl.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 dbSNP:rs372030650Ensembl.1
Natural variantiVAR_043246888P → S in NPC1. 1 Publication1
Natural variantiVAR_008826889V → M in NPC1; adult form. 1 PublicationCorresponds to variant dbSNP:rs120074130Ensembl.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 dbSNP:rs768999208Ensembl.1
Natural variantiVAR_043250917D → Y in NPC1. 1 Publication1
Natural variantiVAR_043251926A → T in NPC1. 1 PublicationCorresponds to variant dbSNP:rs564631426Ensembl.1
Natural variantiVAR_043252927A → V in NPC1. 1 PublicationCorresponds to variant dbSNP:rs753768576Ensembl.1
Natural variantiVAR_008827928Q → P in NPC1. Corresponds to variant dbSNP:rs28940897Ensembl.1
Natural variantiVAR_043253929L → P in NPC1. 1 Publication1
Natural variantiVAR_008828934R → Q in NPC1. 3 PublicationsCorresponds to variant dbSNP:rs786204714Ensembl.1
Natural variantiVAR_008829940S → L in NPC1. 3 PublicationsCorresponds to variant dbSNP:rs143124972Ensembl.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 dbSNP:rs748837410Ensembl.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 dbSNP:rs120074135Ensembl.1
Natural variantiVAR_008831954S → L in NPC1. 3 PublicationsCorresponds to variant dbSNP:rs543206298Ensembl.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 dbSNP:rs120074132Ensembl.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 dbSNP:rs34084984Ensembl.1
Natural variantiVAR_043264968N → S in NPC1. 2 PublicationsCorresponds to variant dbSNP:rs773767253Ensembl.1
Natural variantiVAR_043266976C → R in NPC1. 1 Publication1
Natural variantiVAR_015565978R → C in NPC1. 2 PublicationsCorresponds to variant dbSNP:rs28942108Ensembl.1
Natural variantiVAR_043267986G → S in NPC1. 1 Publication1
Natural variantiVAR_043268992G → A in NPC1. 1 PublicationCorresponds to variant dbSNP:rs757534240Ensembl.1
Natural variantiVAR_015566992G → R in NPC1. 2 PublicationsCorresponds to variant dbSNP:rs80358254Ensembl.1
Natural variantiVAR_008833992G → W in NPC1; found in the Nova Scotian clinical variant. 5 PublicationsCorresponds to variant dbSNP:rs80358254Ensembl.1
Natural variantiVAR_043269996M → R in NPC1. 1 Publication1
Natural variantiVAR_0432701004S → L in NPC1. 1 PublicationCorresponds to variant dbSNP:rs150334966Ensembl.1
Natural variantiVAR_0088341007P → A in NPC1. 7 PublicationsCorresponds to variant dbSNP:rs80358257Ensembl.1
Natural variantiVAR_0432711012G → D in NPC1. 1 Publication1
Natural variantiVAR_0432721015G → V in NPC1. 1 PublicationCorresponds to variant dbSNP:rs761773567Ensembl.1
Natural variantiVAR_0432731016H → R in NPC1. 1 PublicationCorresponds to variant dbSNP:rs140211089Ensembl.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 dbSNP:rs28942107Ensembl.1
Natural variantiVAR_0432761036T → K in NPC1. 1 Publication1
Natural variantiVAR_0088351036T → M in NPC1. 1 PublicationCorresponds to variant dbSNP:rs28942104Ensembl.1
Natural variantiVAR_0432781054A → T in NPC1. 1 PublicationCorresponds to variant dbSNP:rs80358258Ensembl.1
Natural variantiVAR_0432791059R → Q in NPC1. 1 PublicationCorresponds to variant dbSNP:rs771000314Ensembl.1
Natural variantiVAR_0088361061I → T in NPC1; late infantile form. 10 PublicationsCorresponds to variant dbSNP:rs80358259Ensembl.1
Natural variantiVAR_0432801062A → V in NPC1. 1 Publication1
Natural variantiVAR_0432811066T → N in NPC1. 1 PublicationCorresponds to variant dbSNP:rs772622214Ensembl.1
Natural variantiVAR_0432821087F → L in NPC1. 1 PublicationCorresponds to variant dbSNP:rs746715353Ensembl.1
Natural variantiVAR_0088371088Y → C in NPC1; juvenile form. 1 PublicationCorresponds to variant dbSNP:rs28942106Ensembl.1
Natural variantiVAR_0432831089E → K in NPC1. 1 PublicationCorresponds to variant dbSNP:rs374526072Ensembl.1
Natural variantiVAR_0432841094I → T in NPC1. 1 Publication1
Natural variantiVAR_0432851097D → N in NPC1. 1 PublicationCorresponds to variant dbSNP:rs758829443Ensembl.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 dbSNP:rs778878523Ensembl.1
Natural variantiVAR_0432891150N → K in NPC1. 1 Publication1
Natural variantiVAR_0432901156N → I in NPC1. 1 PublicationCorresponds to variant dbSNP:rs28942105Ensembl.1
Natural variantiVAR_0088381156N → S in NPC1. 4 PublicationsCorresponds to variant dbSNP:rs28942105Ensembl.1
Natural variantiVAR_0432911165V → M in NPC1. 1 PublicationCorresponds to variant dbSNP:rs748862167Ensembl.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 dbSNP:rs780175800Ensembl.1
Natural variantiVAR_0088401186R → H in NPC1. 3 PublicationsCorresponds to variant dbSNP:rs200444084Ensembl.1
Natural variantiVAR_0432941189E → G in NPC1. 1 PublicationCorresponds to variant dbSNP:rs369098773Ensembl.1
Natural variantiVAR_0432951205T → K in NPC1. 1 PublicationCorresponds to variant dbSNP:rs758902805Ensembl.1
Natural variantiVAR_0432961205T → R in NPC1. 1 Publication1
Natural variantiVAR_0432971212V → L in NPC1. 1 PublicationCorresponds to variant dbSNP:rs753419933Ensembl.1
Natural variantiVAR_0088411213L → F in NPC1; juvenile form. 1 PublicationCorresponds to variant dbSNP:rs120074131Ensembl.1
Natural variantiVAR_0088421213L → V in NPC1. 1 PublicationCorresponds to variant dbSNP:rs766178353Ensembl.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 dbSNP:rs761653115Ensembl.1
Natural variantiVAR_0433011240G → R in NPC1. 1 PublicationCorresponds to variant dbSNP:rs745892286Ensembl.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...) asparagine1 Publication1
Disulfide bondi75 ↔ 1131 Publication
Disulfide bondi97 ↔ 2381 Publication
Disulfide bondi100 ↔ 1601 Publication
Glycosylationi122N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi135N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi158N-linked (GlcNAc...) asparagine; atypical1 Publication1
Disulfide bondi177 ↔ 1841 Publication
Glycosylationi185N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi222N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi227 ↔ 2431 Publication
Disulfide bondi240 ↔ 2471 Publication
Glycosylationi452N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi459N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi478N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi524N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi961N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi968N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi1064N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi1072N-linked (GlcNAc...) asparagineSequence 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

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi110925. 13 interactors.
DIPiDIP-53217N.
IntActiO15118. 8 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
Turni132 – 134Combined sources3
Beta strandi137 – 148Combined sources12
Helixi150 – 160Combined sources11
Beta strandi168 – 171Combined sources4
Helixi173 – 176Combined sources4
Beta strandi177 – 179Combined sources3
Turni181 – 183Combined sources3
Helixi186 – 193Combined sources8
Helixi196 – 198Combined sources3
Beta strandi199 – 209Combined sources11
Helixi240 – 242Combined sources3
Helixi244 – 246Combined sources3
Helixi350 – 365Combined sources16
Beta strandi367 – 371Combined sources5
Helixi380 – 382Combined sources3
Helixi385 – 398Combined sources14
Turni399 – 402Combined sources4
Beta strandi403 – 411Combined sources9
Beta strandi418 – 420Combined sources3
Beta strandi423 – 425Combined sources3
Beta strandi429 – 431Combined sources3
Helixi433 – 435Combined sources3
Helixi437 – 451Combined sources15
Beta strandi454 – 457Combined sources4
Beta strandi460 – 463Combined sources4
Helixi464 – 467Combined sources4
Turni471 – 475Combined sources5
Helixi484 – 488Combined sources5
Helixi492 – 495Combined sources4
Beta strandi505 – 507Combined sources3
Helixi509 – 516Combined sources8
Turni526 – 530Combined sources5
Beta strandi536 – 538Combined sources3
Helixi543 – 546Combined sources4
Beta strandi547 – 549Combined sources3
Helixi555 – 557Combined sources3
Beta strandi559 – 568Combined sources10
Helixi574 – 592Combined sources19
Beta strandi600 – 603Combined sources4
Helixi608 – 611Combined sources4
Helixi621 – 638Combined sources18
Helixi660 – 671Combined sources12
Beta strandi672 – 674Combined sources3
Helixi677 – 679Combined sources3
Beta strandi680 – 682Combined sources3
Helixi685 – 687Combined sources3
Helixi690 – 707Combined sources18
Turni728 – 730Combined sources3
Helixi731 – 746Combined sources16
Helixi755 – 775Combined sources21
Turni776 – 778Combined sources3
Helixi779 – 789Combined sources11
Helixi834 – 851Combined sources18
Helixi866 – 874Combined sources9
Helixi906 – 911Combined sources6
Helixi912 – 915Combined sources4
Beta strandi916 – 918Combined sources3
Helixi928 – 932Combined sources5
Helixi940 – 943Combined sources4
Turni954 – 957Combined sources4
Beta strandi959 – 961Combined sources3
Helixi1038 – 1051Combined sources14
Turni1052 – 1054Combined sources3
Helixi1084 – 1088Combined sources5
Helixi1094 – 1115Combined sources22
Helixi1125 – 1137Combined sources13
Turni1138 – 1140Combined sources3
Helixi1147 – 1152Combined sources6
Helixi1155 – 1157Combined sources3
Helixi1158 – 1170Combined sources13
Turni1186 – 1190Combined sources5
Helixi1191 – 1200Combined sources10
Beta strandi1203 – 1205Combined sources3
Turni1217 – 1220Combined sources4
Helixi1222 – 1235Combined sources14
Helixi1238 – 1242Combined sources5
Turni1243 – 1245Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3GKHX-ray1.81A23-252[»]
3GKIX-ray1.80A23-252[»]
3GKJX-ray1.60A23-252[»]
3JD8electron microscopy4.43A1-1267[»]
5F18X-ray2.00A374-620[»]
5F1BX-ray2.30C374-620[»]
5HNSX-ray2.45A/B387-618[»]
5I31X-ray3.35A341-1246[»]
5JNXelectron microscopy6.56A1-1278[»]
5KWYX-ray2.40A/B374-620[»]
ProteinModelPortaliO15118.
SMRiO15118.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO15118.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini620 – 785SSDPROSITE-ProRule annotationAdd BLAST166

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni175 – 205Important for cholesterol binding and cholesterol transfer from NPC1 to liposomesAdd BLAST31

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi1275 – 1278Di-leucine motif4

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi249 – 259Poly-ProAdd BLAST11

Domaini

A cysteine-rich N-terminal domain and a C-terminal domain containing a di-leucine motif necessary for lysosomal targeting are critical for mobilization of cholesterol from lysosomes.

Sequence similaritiesi

Belongs to the patched family.Curated

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1933. Eukaryota.
ENOG410XR54. LUCA.
GeneTreeiENSGT00800000124043.
HOGENOMiHOG000036674.
HOVERGENiHBG003913.
InParanoidiO15118.
KOiK12385.
OMAiMYNACRD.
OrthoDBiEOG091G00JD.
PhylomeDBiO15118.
TreeFamiTF300416.

Family and domain databases

InterProiView protein in InterPro
IPR004765. NP_C_type.
IPR032190. NPC1_N.
IPR003392. Ptc/Disp.
IPR000731. SSD.
PANTHERiPTHR10796:SF176. PTHR10796:SF176. 1 hit.
PfamiView protein in Pfam
PF16414. NPC1_N. 1 hit.
PF02460. Patched. 1 hit.
PF12349. Sterol-sensing. 1 hit.
TIGRFAMsiTIGR00917. 2A060601. 1 hit.
PROSITEiView protein in PROSITE
PS50156. SSD. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O15118-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MTARGLALGL LLLLLCPAQV FSQSCVWYGE CGIAYGDKRY NCEYSGPPKP 
        60         70         80         90        100
LPKDGYDLVQ ELCPGFFFGN VSLCCDVRQL QTLKDNLQLP LQFLSRCPSC 
       110        120        130        140        150
FYNLLNLFCE LTCSPRQSQF LNVTATEDYV DPVTNQTKTN VKELQYYVGQ 
       160        170        180        190        200
SFANAMYNAC RDVEAPSSND KALGLLCGKD ADACNATNWI EYMFNKDNGQ 
       210        220        230        240        250
APFTITPVFS DFPVHGMEPM NNATKGCDES VDEVTAPCSC QDCSIVCGPK 
       260        270        280        290        300
PQPPPPPAPW TILGLDAMYV IMWITYMAFL LVFFGAFFAV WCYRKRYFVS 
       310        320        330        340        350
EYTPIDSNIA FSVNASDKGE ASCCDPVSAA FEGCLRRLFT RWGSFCVRNP 
       360        370        380        390        400
GCVIFFSLVF ITACSSGLVF VRVTTNPVDL WSAPSSQARL EKEYFDQHFG 
       410        420        430        440        450
PFFRTEQLII RAPLTDKHIY QPYPSGADVP FGPPLDIQIL HQVLDLQIAI 
       460        470        480        490        500
ENITASYDNE TVTLQDICLA PLSPYNTNCT ILSVLNYFQN SHSVLDHKKG 
       510        520        530        540        550
DDFFVYADYH THFLYCVRAP ASLNDTSLLH DPCLGTFGGP VFPWLVLGGY 
       560        570        580        590        600
DDQNYNNATA LVITFPVNNY YNDTEKLQRA QAWEKEFINF VKNYKNPNLT 
       610        620        630        640        650
ISFTAERSIE DELNRESDSD VFTVVISYAI MFLYISLALG HMKSCRRLLV 
       660        670        680        690        700
DSKVSLGIAG ILIVLSSVAC SLGVFSYIGL PLTLIVIEVI PFLVLAVGVD 
       710        720        730        740        750
NIFILVQAYQ RDERLQGETL DQQLGRVLGE VAPSMFLSSF SETVAFFLGA 
       760        770        780        790        800
LSVMPAVHTF SLFAGLAVFI DFLLQITCFV SLLGLDIKRQ EKNRLDIFCC 
       810        820        830        840        850
VRGAEDGTSV QASESCLFRF FKNSYSPLLL KDWMRPIVIA IFVGVLSFSI 
       860        870        880        890        900
AVLNKVDIGL DQSLSMPDDS YMVDYFKSIS QYLHAGPPVY FVLEEGHDYT 
       910        920        930        940        950
SSKGQNMVCG GMGCNNDSLV QQIFNAAQLD NYTRIGFAPS SWIDDYFDWV 
       960        970        980        990       1000
KPQSSCCRVD NITDQFCNAS VVDPACVRCR PLTPEGKQRP QGGDFMRFLP 
      1010       1020       1030       1040       1050
MFLSDNPNPK CGKGGHAAYS SAVNILLGHG TRVGATYFMT YHTVLQTSAD 
      1060       1070       1080       1090       1100
FIDALKKARL IASNVTETMG INGSAYRVFP YSVFYVFYEQ YLTIIDDTIF 
      1110       1120       1130       1140       1150
NLGVSLGAIF LVTMVLLGCE LWSAVIMCAT IAMVLVNMFG VMWLWGISLN 
      1160       1170       1180       1190       1200
AVSLVNLVMS CGISVEFCSH ITRAFTVSMK GSRVERAEEA LAHMGSSVFS 
      1210       1220       1230       1240       1250
GITLTKFGGI VVLAFAKSQI FQIFYFRMYL AMVLLGATHG LIFLPVLLSY 
      1260       1270 
IGPSVNKAKS CATEERYKGT ERERLLNF
Length:1,278
Mass (Da):142,167
Last modified:May 10, 2005 - v2
Checksum:iDA1523E09822E5C7
GO
Isoform 2 (identifier: O15118-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-267: Missing.
     318-318: K → KGTAWLLTSTFPSSPVLP
     519-586: Missing.

Note: No experimental confirmation available.
Show »
Length:960
Mass (Da):107,025
Checksum:i2018AA28A418DC22
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04317263C → R in NPC1. 1 PublicationCorresponds to variant dbSNP:rs747049347Ensembl.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 dbSNP:rs120074136Ensembl.1
Natural variantiVAR_043176137T → M in NPC1. 3 PublicationsCorresponds to variant dbSNP:rs372947142Ensembl.1
Natural variantiVAR_043177151S → G1 PublicationCorresponds to variant dbSNP:rs17855819Ensembl.1
Natural variantiVAR_043178166P → S in NPC1. 2 PublicationsCorresponds to variant dbSNP:rs866966704Ensembl.1
Natural variantiVAR_008815177C → G in NPC1; late infantile form. 1 Publication1
Natural variantiVAR_015561177C → Y in NPC1. 3 PublicationsCorresponds to variant dbSNP:rs80358252Ensembl.1
Natural variantiVAR_008816215H → R Common polymorphism in Japanese. 7 PublicationsCorresponds to variant dbSNP:rs1805081Ensembl.1
Natural variantiVAR_043179222N → S in NPC1. 1 PublicationCorresponds to variant dbSNP:rs55680026Ensembl.1
Natural variantiVAR_043180231V → G in NPC1. 1 Publication1
Natural variantiVAR_008817237P → S in NPC1; late infantile form. 5 PublicationsCorresponds to variant dbSNP:rs80358251Ensembl.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_008818333G → D. 1
Natural variantiVAR_043187372R → W in NPC1. 1 Publication1
Natural variantiVAR_015562378V → A in NPC1. 1 PublicationCorresponds to variant dbSNP:rs120074134Ensembl.1
Natural variantiVAR_043188380L → F in NPC1. 1 Publication1
Natural variantiVAR_043189381W → C1 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 dbSNP:rs139751448Ensembl.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 dbSNP:rs774333145Ensembl.1
Natural variantiVAR_043198434P → S1 PublicationCorresponds to variant dbSNP:rs61731962Ensembl.1
Natural variantiVAR_043199451E → K in NPC1. 1 PublicationCorresponds to variant dbSNP:rs781065429Ensembl.1
Natural variantiVAR_008819472L → P. 1
Natural variantiVAR_008820473S → P in NPC1; late infantile form. 1 Publication1
Natural variantiVAR_043200474P → L in NPC1. 2 PublicationsCorresponds to variant dbSNP:rs372445155Ensembl.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_043203511T → M1 PublicationCorresponds to variant dbSNP:rs13381670Ensembl.1
Natural variantiVAR_043204512H → R in NPC1. 1 Publication1
Natural variantiVAR_008822518R → Q in NPC1; late infantile form; Common in Japanese. 2 PublicationsCorresponds to variant dbSNP:rs483352886Ensembl.1
Natural variantiVAR_043205518R → W in NPC1. 1 PublicationCorresponds to variant dbSNP:rs377515417Ensembl.1
Natural variantiVAR_043206521A → S in NPC1. 1 PublicationCorresponds to variant dbSNP:rs138184115Ensembl.1
Natural variantiVAR_043207537F → L in NPC1. 1 Publication1
Natural variantiVAR_043208543P → L in NPC1. 2 PublicationsCorresponds to variant dbSNP:rs369368181Ensembl.1
Natural variantiVAR_043209574T → K in NPC1. 1
Natural variantiVAR_043210576K → R in NPC1. 1 PublicationCorresponds to variant dbSNP:rs761660695Ensembl.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 dbSNP:rs745777805Ensembl.1
Natural variantiVAR_043214615R → L in NPC1. 1 PublicationCorresponds to variant dbSNP:rs773351341Ensembl.1
Natural variantiVAR_043215631M → R in NPC1. 2 Publications1
Natural variantiVAR_043216640G → R in NPC1. 1 Publication1
Natural variantiVAR_008823642M → I8 PublicationsCorresponds to variant dbSNP:rs1788799Ensembl.1
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 dbSNP:rs376213990Ensembl.1
Natural variantiVAR_043220666S → N in NPC1. 1 PublicationCorresponds to variant dbSNP:rs750480579Ensembl.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 dbSNP:rs370323921Ensembl.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 dbSNP:rs757475924Ensembl.1
Natural variantiVAR_043231742E → K in NPC1. 1 Publication1
Natural variantiVAR_043232745A → E in NPC1. 1 PublicationCorresponds to variant dbSNP:rs752386083Ensembl.1
Natural variantiVAR_043233754M → K in NPC1. 1 Publication1
Natural variantiVAR_008824757V → A. 1
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 dbSNP:rs80358253Ensembl.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 dbSNP:rs550562774Ensembl.1
Natural variantiVAR_043240849S → I in NPC1. 1 Publication1
Natural variantiVAR_008825858I → V Common polymorphism in Japanese. 6 PublicationsCorresponds to variant dbSNP:rs1805082Ensembl.1
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_043244873V → A1 Publication1
Natural variantiVAR_043245874D → V in NPC1. 3 PublicationsCorresponds to variant dbSNP:rs372030650Ensembl.1
Natural variantiVAR_043246888P → S in NPC1. 1 Publication1
Natural variantiVAR_008826889V → M in NPC1; adult form. 1 PublicationCorresponds to variant dbSNP:rs120074130Ensembl.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 dbSNP:rs768999208Ensembl.1
Natural variantiVAR_043250917D → Y in NPC1. 1 Publication1
Natural variantiVAR_043251926A → T in NPC1. 1 PublicationCorresponds to variant dbSNP:rs564631426Ensembl.1
Natural variantiVAR_043252927A → V in NPC1. 1 PublicationCorresponds to variant dbSNP:rs753768576Ensembl.1
Natural variantiVAR_008827928Q → P in NPC1. Corresponds to variant dbSNP:rs28940897Ensembl.1
Natural variantiVAR_043253929L → P in NPC1. 1 Publication1
Natural variantiVAR_008828934R → Q in NPC1. 3 PublicationsCorresponds to variant dbSNP:rs786204714Ensembl.1
Natural variantiVAR_008829940S → L in NPC1. 3 PublicationsCorresponds to variant dbSNP:rs143124972Ensembl.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 dbSNP:rs748837410Ensembl.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 dbSNP:rs120074135Ensembl.1
Natural variantiVAR_008831954S → L in NPC1. 3 PublicationsCorresponds to variant dbSNP:rs543206298Ensembl.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 dbSNP:rs120074132Ensembl.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 dbSNP:rs34084984Ensembl.1
Natural variantiVAR_043264968N → S in NPC1. 2 PublicationsCorresponds to variant dbSNP:rs773767253Ensembl.1
Natural variantiVAR_043265971V → G1 Publication1
Natural variantiVAR_043266976C → R in NPC1. 1 Publication1
Natural variantiVAR_015565978R → C in NPC1. 2 PublicationsCorresponds to variant dbSNP:rs28942108Ensembl.1
Natural variantiVAR_043267986G → S in NPC1. 1 Publication1
Natural variantiVAR_043268992G → A in NPC1. 1 PublicationCorresponds to variant dbSNP:rs757534240Ensembl.1
Natural variantiVAR_015566992G → R in NPC1. 2 PublicationsCorresponds to variant dbSNP:rs80358254Ensembl.1
Natural variantiVAR_008833992G → W in NPC1; found in the Nova Scotian clinical variant. 5 PublicationsCorresponds to variant dbSNP:rs80358254Ensembl.1
Natural variantiVAR_043269996M → R in NPC1. 1 Publication1
Natural variantiVAR_0432701004S → L in NPC1. 1 PublicationCorresponds to variant dbSNP:rs150334966Ensembl.1
Natural variantiVAR_0088341007P → A in NPC1. 7 PublicationsCorresponds to variant dbSNP:rs80358257Ensembl.1
Natural variantiVAR_0432711012G → D in NPC1. 1 Publication1
Natural variantiVAR_0432721015G → V in NPC1. 1 PublicationCorresponds to variant dbSNP:rs761773567Ensembl.1
Natural variantiVAR_0432731016H → R in NPC1. 1 PublicationCorresponds to variant dbSNP:rs140211089Ensembl.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 dbSNP:rs28942107Ensembl.1
Natural variantiVAR_0432761036T → K in NPC1. 1 Publication1
Natural variantiVAR_0088351036T → M in NPC1. 1 PublicationCorresponds to variant dbSNP:rs28942104Ensembl.1
Natural variantiVAR_0432771049A → V1 Publication1
Natural variantiVAR_0432781054A → T in NPC1. 1 PublicationCorresponds to variant dbSNP:rs80358258Ensembl.1
Natural variantiVAR_0432791059R → Q in NPC1. 1 PublicationCorresponds to variant dbSNP:rs771000314Ensembl.1
Natural variantiVAR_0088361061I → T in NPC1; late infantile form. 10 PublicationsCorresponds to variant dbSNP:rs80358259Ensembl.1
Natural variantiVAR_0432801062A → V in NPC1. 1 Publication1
Natural variantiVAR_0432811066T → N in NPC1. 1 PublicationCorresponds to variant dbSNP:rs772622214Ensembl.1
Natural variantiVAR_0432821087F → L in NPC1. 1 PublicationCorresponds to variant dbSNP:rs746715353Ensembl.1
Natural variantiVAR_0088371088Y → C in NPC1; juvenile form. 1 PublicationCorresponds to variant dbSNP:rs28942106Ensembl.1
Natural variantiVAR_0432831089E → K in NPC1. 1 PublicationCorresponds to variant dbSNP:rs374526072Ensembl.1
Natural variantiVAR_0432841094I → T in NPC1. 1 Publication1
Natural variantiVAR_0432851097D → N in NPC1. 1 PublicationCorresponds to variant dbSNP:rs758829443Ensembl.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 dbSNP:rs778878523Ensembl.1
Natural variantiVAR_0432891150N → K in NPC1. 1 Publication1
Natural variantiVAR_0432901156N → I in NPC1. 1 PublicationCorresponds to variant dbSNP:rs28942105Ensembl.1
Natural variantiVAR_0088381156N → S in NPC1. 4 PublicationsCorresponds to variant dbSNP:rs28942105Ensembl.1
Natural variantiVAR_0432911165V → M in NPC1. 1 PublicationCorresponds to variant dbSNP:rs748862167Ensembl.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 dbSNP:rs780175800Ensembl.1
Natural variantiVAR_0088401186R → H in NPC1. 3 PublicationsCorresponds to variant dbSNP:rs200444084Ensembl.1
Natural variantiVAR_0432941189E → G in NPC1. 1 PublicationCorresponds to variant dbSNP:rs369098773Ensembl.1
Natural variantiVAR_0432951205T → K in NPC1. 1 PublicationCorresponds to variant dbSNP:rs758902805Ensembl.1
Natural variantiVAR_0432961205T → R in NPC1. 1 Publication1
Natural variantiVAR_0432971212V → L in NPC1. 1 PublicationCorresponds to variant dbSNP:rs753419933Ensembl.1
Natural variantiVAR_0088411213L → F in NPC1; juvenile form. 1 PublicationCorresponds to variant dbSNP:rs120074131Ensembl.1
Natural variantiVAR_0088421213L → V in NPC1. 1 PublicationCorresponds to variant dbSNP:rs766178353Ensembl.1
Natural variantiVAR_0432981216A → V in NPC1. 1 Publication1
Natural variantiVAR_0088431220I → T. 1
Natural variantiVAR_0432991224F → L in NPC1. 1 Publication1
Natural variantiVAR_0433001236G → E in NPC1. 1 PublicationCorresponds to variant dbSNP:rs761653115Ensembl.1
Natural variantiVAR_0433011240G → R in NPC1. 1 PublicationCorresponds to variant dbSNP:rs745892286Ensembl.1
Natural variantiVAR_0433021249S → G in NPC1. 1 Publication1
Natural variantiVAR_0088441266R → Q Common polymorphism in Japanese. 4 PublicationsCorresponds to variant dbSNP:rs1805084Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0564311 – 267Missing in isoform 2. 1 PublicationAdd BLAST267
Alternative sequenceiVSP_056432318K → KGTAWLLTSTFPSSPVLP in isoform 2. 1 Publication1
Alternative sequenceiVSP_056433519 – 586Missing in isoform 2. 1 PublicationAdd BLAST68

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF002020 mRNA. Translation: AAB63982.1.
AF157379
, AF157365, AF157366, AF157367, AF157368, AF157369, AF157370, AF157371, AF157372, AF157373, AF157374, AF157375, AF157376, AF157377, AF157378 Genomic DNA. Translation: AAD48006.1.
AF338230 Genomic DNA. Translation: AAK25791.1.
AH009108 Genomic DNA. Translation: AAF28875.1.
AK293779 mRNA. Translation: BAG57194.1.
AC010853 Genomic DNA. No translation available.
AC026634 Genomic DNA. No translation available.
BC063302 mRNA. Translation: AAH63302.1.
CCDSiCCDS11878.1. [O15118-1]
RefSeqiNP_000262.2. NM_000271.4. [O15118-1]
UniGeneiHs.464779.
Hs.715623.

Genome annotation databases

EnsembliENST00000269228; ENSP00000269228; ENSG00000141458. [O15118-1]
GeneIDi4864.
KEGGihsa:4864.
UCSCiuc002kum.5. human. [O15118-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.

Entry informationi

Entry nameiNPC1_HUMAN
AccessioniPrimary (citable) accession number: O15118
Secondary accession number(s): B4DET3, Q9P130
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: May 10, 2005
Last modified: July 5, 2017
This is version 171 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 18
    Human chromosome 18: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families