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O15118 (NPC1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 136. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Niemann-Pick C1 protein
Gene names
Name:NPC1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1278 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.8 Ref.15

Subunit structure

Interacts with TMEM97. Interacts (via the second lumenal domain) with NPC2 in a cholestrol-dependent manner By similarity. Ref.9

Subcellular location

Late endosome membrane; Multi-pass membrane protein. Lysosome membrane; Multi-pass membrane protein Ref.7.

Domain

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.

Post-translational modification

Glycosylated. Ref.6 Ref.15

Involvement in disease

Niemann-Pick disease C1 (NPC1) [MIM:257220]: 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 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1 Ref.3 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21 Ref.22 Ref.23 Ref.24 Ref.25 Ref.26 Ref.27 Ref.28 Ref.29 Ref.30 Ref.31 Ref.32

Sequence similarities

Belongs to the patched family.

Contains 1 SSD (sterol-sensing) domain.

Ontologies

Keywords
   Biological processCholesterol metabolism
Lipid metabolism
Steroid metabolism
Sterol metabolism
   Cellular componentEndosome
Lysosome
Membrane
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
Niemann-Pick disease
   DomainSignal
Transmembrane
Transmembrane helix
   PTMDisulfide bond
Glycoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processadult walking behavior

Inferred from electronic annotation. Source: Ensembl

autophagy

Inferred from genetic interaction PubMed 19074461. Source: MGI

bile acid metabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

cellular response to low-density lipoprotein particle stimulus

Inferred from electronic annotation. Source: Ensembl

cellular response to steroid hormone stimulus

Inferred from electronic annotation. Source: Ensembl

cholesterol efflux

Inferred from direct assay PubMed 16141411. Source: BHF-UCL

cholesterol homeostasis

Inferred from direct assay PubMed 12719428. Source: UniProtKB

cholesterol metabolic process

Inferred from electronic annotation. Source: UniProtKB-KW

cholesterol transport

Inferred from direct assay Ref.8. Source: UniProtKB

endocytosis

Inferred from electronic annotation. Source: Ensembl

lysosomal transport

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of cell death

Inferred from electronic annotation. Source: Ensembl

negative regulation of macroautophagy

Inferred from electronic annotation. Source: Ensembl

protein glycosylation

Inferred from direct assay Ref.6. Source: UniProtKB

response to cadmium ion

Inferred from electronic annotation. Source: Ensembl

response to drug

Inferred from electronic annotation. Source: Ensembl

signal transduction

Traceable author statement Ref.17. Source: GOC

   Cellular_componentGolgi apparatus

Inferred from electronic annotation. Source: Ensembl

endoplasmic reticulum

Inferred from direct assay Ref.27. Source: UniProtKB

extracellular region

Inferred from sequence or structural similarity. Source: UniProtKB

extracellular vesicular exosome

Inferred from direct assay PubMed 19056867. Source: UniProt

integral component of membrane

Traceable author statement Ref.17. Source: ProtInc

integral component of plasma membrane

Inferred from direct assay Ref.6. Source: UniProtKB

late endosome membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

lysosomal membrane

Inferred from direct assay Ref.7. Source: UniProtKB

lysosome

Inferred from sequence or structural similarity. Source: UniProtKB

membrane raft

Inferred from electronic annotation. Source: Ensembl

nuclear envelope

Inferred from direct assay Ref.27. Source: UniProtKB

perinuclear region of cytoplasm

Inferred from direct assay Ref.27. Source: UniProtKB

   Molecular_functioncholesterol binding

Inferred from direct assay Ref.8. Source: UniProtKB

hedgehog receptor activity

Inferred from electronic annotation. Source: InterPro

receptor activity

Traceable author statement Ref.1. Source: ProtInc

sterol transporter activity

Traceable author statement Ref.5. Source: ProtInc

transmembrane signaling receptor activity

Traceable author statement Ref.17. Source: ProtInc

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2222 Potential
Chain23 – 12781256Niemann-Pick C1 protein
PRO_0000023261

Regions

Topological domain23 – 269247Lumenal Potential
Transmembrane270 – 29021Helical; Potential
Topological domain291 – 35060Cytoplasmic Potential
Transmembrane351 – 37121Helical; Potential
Topological domain372 – 620249Lumenal Potential
Transmembrane621 – 64121Helical; Potential
Topological domain642 – 65413Cytoplasmic Potential
Transmembrane655 – 67521Helical; Potential
Topological domain676 – 6772Lumenal Potential
Transmembrane678 – 69821Helical; Potential
Topological domain699 – 73436Cytoplasmic Potential
Transmembrane735 – 75521Helical; Potential
Topological domain756 – 7594Lumenal Potential
Transmembrane760 – 78021Helical; Potential
Topological domain781 – 83252Cytoplasmic Potential
Transmembrane833 – 85321Helical; Potential
Topological domain854 – 1098245Lumenal Potential
Transmembrane1099 – 111921Helical; Potential
Topological domain1120 – 11245Cytoplasmic Potential
Transmembrane1125 – 114521Helical; Potential
Topological domain11461Lumenal Potential
Transmembrane1147 – 116721Helical; Potential
Topological domain1168 – 119528Cytoplasmic Potential
Transmembrane1196 – 121621Helical; Potential
Topological domain1217 – 122711Lumenal Potential
Transmembrane1228 – 124821Helical; Potential
Topological domain1249 – 127830Cytoplasmic Potential
Domain620 – 785166SSD
Region175 – 20531Important for cholesterol binding and cholesterol transfer from NPC1 to liposomes
Motif1275 – 12784Di-leucine motif
Compositional bias249 – 25911Poly-Pro

Sites

Binding site411Cholesterol
Binding site791Cholesterol
Site1081Important for cholesterol binding

Amino acid modifications

Glycosylation701N-linked (GlcNAc...) Probable
Glycosylation1221N-linked (GlcNAc...) Probable
Glycosylation1351N-linked (GlcNAc...) Ref.10
Glycosylation1581N-linked (GlcNAc...); atypical Ref.15
Glycosylation1851N-linked (GlcNAc...) Probable
Glycosylation2221N-linked (GlcNAc...) Ref.15
Glycosylation4521N-linked (GlcNAc...) Potential
Glycosylation4591N-linked (GlcNAc...) Potential
Glycosylation4781N-linked (GlcNAc...) Potential
Glycosylation5241N-linked (GlcNAc...) Ref.10
Glycosylation9611N-linked (GlcNAc...) Potential
Glycosylation9681N-linked (GlcNAc...) Potential
Glycosylation10641N-linked (GlcNAc...) Potential
Glycosylation10721N-linked (GlcNAc...) Potential
Disulfide bond25 ↔ 74 Ref.15
Disulfide bond31 ↔ 42 Ref.15
Disulfide bond63 ↔ 109 Ref.15
Disulfide bond75 ↔ 113 Ref.15
Disulfide bond97 ↔ 238 Ref.15
Disulfide bond100 ↔ 160 Ref.15
Disulfide bond177 ↔ 184 Ref.15
Disulfide bond227 ↔ 243 Ref.15
Disulfide bond240 ↔ 247 Ref.15

Natural variations

Natural variant631C → R in NPC1. Ref.23
VAR_043172
Natural variant741C → Y in NPC1. Ref.28
VAR_043173
Natural variant921Q → R in NPC1. Ref.21 Ref.24
VAR_043174
Natural variant1131C → 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. Ref.27
VAR_043175
Natural variant1371T → M in NPC1. Ref.21 Ref.29 Ref.33
VAR_043176
Natural variant1511S → G. Ref.4
Corresponds to variant rs17855819 [ dbSNP | Ensembl ].
VAR_043177
Natural variant1661P → S in NPC1. Ref.28 Ref.31
VAR_043178
Natural variant1771C → G in NPC1; late infantile form. Ref.20
VAR_008815
Natural variant1771C → Y in NPC1. Ref.24 Ref.29 Ref.31
VAR_015561
Natural variant2151H → R Common polymorphism in Japanese. Ref.3 Ref.19 Ref.24 Ref.26 Ref.28 Ref.29 Ref.30
Corresponds to variant rs1805081 [ dbSNP | Ensembl ].
VAR_008816
Natural variant2221N → S in NPC1. Ref.28
Corresponds to variant rs55680026 [ dbSNP | Ensembl ].
VAR_043179
Natural variant2311V → G in NPC1. Ref.25
VAR_043180
Natural variant2371P → S in NPC1; late infantile form. Ref.20 Ref.21 Ref.22 Ref.25 Ref.28
Corresponds to variant rs80358251 [ dbSNP | Ensembl ].
VAR_008817
Natural variant2421D → H in NPC1. Ref.22
VAR_043181
Natural variant2421D → N in NPC1. Ref.21
VAR_043182
Natural variant2471C → Y in NPC1. Ref.28
VAR_043183
Natural variant2481G → V in NPC1. Ref.21
VAR_043184
Natural variant2721M → R in NPC1. Ref.22
VAR_043185
Natural variant2731W → S Colocalizes with the wild-type protein with Rab7-positive late endosomes; clears the lysosomal cholesterol accumulation in NPC1-deficient cells. Ref.27
VAR_043186
Natural variant3331G → D.
VAR_008818
Natural variant3721R → W in NPC1. Ref.29
VAR_043187
Natural variant3781V → A in NPC1. Ref.22
VAR_015562
Natural variant3801L → F in NPC1. Ref.28
VAR_043188
Natural variant3811W → C. Ref.25
VAR_043189
Natural variant3881A → P in NPC1. Ref.28
VAR_043190
Natural variant3891R → C in NPC1. Ref.28
VAR_043191
Natural variant4011P → T in NPC1. Ref.21
VAR_043192
Natural variant4041R → P in NPC1. Ref.31
VAR_043193
Natural variant4041R → Q in NPC1. Ref.21 Ref.22 Ref.23
VAR_043194
Natural variant4041R → W in NPC1. Ref.28
VAR_043195
Natural variant4331P → L in NPC1. Ref.28
VAR_043196
Natural variant4341P → L in NPC1. Ref.29
VAR_043197
Natural variant4341P → S. Ref.28
Corresponds to variant rs61731962 [ dbSNP | Ensembl ].
VAR_043198
Natural variant4511E → K in NPC1. Ref.26
VAR_043199
Natural variant4721L → P.
VAR_008819
Natural variant4731S → P in NPC1; late infantile form. Ref.20
VAR_008820
Natural variant4741P → L in NPC1. Ref.26 Ref.29
VAR_043200
Natural variant4791C → Y in NPC1. Ref.29
VAR_043201
Natural variant5091Y → S in NPC1. Ref.28
VAR_043202
Natural variant5101H → P in NPC1; late infantile form. Ref.20
VAR_008821
Natural variant5111T → M. Ref.31
Corresponds to variant rs13381670 [ dbSNP | Ensembl ].
VAR_043203
Natural variant5121H → R in NPC1. Ref.3
VAR_043204
Natural variant5181R → Q in NPC1; late infantile form; Common in Japanese. Ref.20 Ref.22
VAR_008822
Natural variant5181R → W in NPC1. Ref.24
VAR_043205
Natural variant5211A → S in NPC1. Ref.28
VAR_043206
Natural variant5371F → L in NPC1. Ref.31
VAR_043207
Natural variant5431P → L in NPC1. Ref.28 Ref.31
VAR_043208
Natural variant5741T → K in NPC1.
VAR_043209
Natural variant5761K → R in NPC1. Ref.29
VAR_043210
Natural variant6051A → V in NPC1. Ref.22
VAR_043211
Natural variant6121E → D in NPC1. Ref.21
VAR_043212
Natural variant6151R → C in NPC1. Ref.28
VAR_043213
Natural variant6151R → L in NPC1. Ref.31
VAR_043214
Natural variant6311M → R in NPC1. Ref.22 Ref.31
VAR_043215
Natural variant6401G → R in NPC1. Ref.28
VAR_043216
Natural variant6421M → I. Ref.1 Ref.3 Ref.4 Ref.24 Ref.25 Ref.26 Ref.29 Ref.30
Corresponds to variant rs1788799 [ dbSNP | Ensembl ].
VAR_008823
Natural variant6521S → W in NPC1. Ref.21
VAR_043217
Natural variant6601G → S in NPC1. Ref.28
VAR_043218
Natural variant6641V → M in NPC1. Ref.28 Ref.29
VAR_043219
Natural variant6661S → N in NPC1. Ref.32
VAR_043220
Natural variant6701C → W in NPC1. Ref.3
VAR_043221
Natural variant6731G → V in NPC1. Ref.28
VAR_043222
Natural variant6841L → F in NPC1. Ref.28
VAR_043223
Natural variant6911P → L in NPC1. Ref.28
VAR_043224
Natural variant6951L → V in NPC1. Ref.28
VAR_043225
Natural variant7001D → N in NPC1. Ref.28
VAR_043226
Natural variant7031F → S in NPC1. Ref.20
VAR_043227
Natural variant7241L → P in NPC1. Ref.22
VAR_043228
Natural variant7271V → F in NPC1. Ref.29
VAR_043229
Natural variant7341S → I in NPC1. Ref.28
VAR_043230
Natural variant7421E → K in NPC1. Ref.28
VAR_043231
Natural variant7451A → E in NPC1. Ref.28
VAR_043232
Natural variant7541M → K in NPC1. Ref.29
VAR_043233
Natural variant7571V → A.
VAR_008824
Natural variant7631F → L in NPC1. Ref.31
VAR_043234
Natural variant7671A → V in NPC1. Ref.28
VAR_043235
Natural variant7751Q → P in NPC1. Ref.22 Ref.29
VAR_043236
Natural variant7891R → C in NPC1. Ref.21
VAR_043237
Natural variant7891R → G in NPC1. Ref.28
VAR_043238
Natural variant8251Y → C in NPC1. Ref.3 Ref.21 Ref.22 Ref.31
VAR_043239
Natural variant8491S → I in NPC1. Ref.3
VAR_043240
Natural variant8581I → V Common polymorphism in Japanese. Ref.3 Ref.19 Ref.24 Ref.26 Ref.29 Ref.30
Corresponds to variant rs1805082 [ dbSNP | Ensembl ].
VAR_008825
Natural variant8621Q → L in NPC1. Ref.31
VAR_043241
Natural variant8651S → L in NPC1. Ref.29 Ref.31
VAR_043242
Natural variant8711Y → C in NPC1. Ref.31
VAR_043243
Natural variant8731V → A. Ref.20
VAR_043244
Natural variant8741D → V in NPC1. Ref.3 Ref.21 Ref.22 Ref.25
VAR_043245
Natural variant8881P → S in NPC1. Ref.21
VAR_043246
Natural variant8891V → M in NPC1; adult form. Ref.20
VAR_008826
Natural variant8901Y → C in NPC1. Ref.26
VAR_043247
Natural variant8991Y → D in NPC1. Ref.26
VAR_043248
Natural variant9101G → S in NPC1. Ref.26
VAR_043249
Natural variant9171D → Y in NPC1. Ref.31
VAR_043250
Natural variant9261A → T in NPC1. Ref.29
VAR_043251
Natural variant9271A → V in NPC1. Ref.23
VAR_043252
Natural variant9281Q → P in NPC1.
Corresponds to variant rs28940897 [ dbSNP | Ensembl ].
VAR_008827
Natural variant9291L → P in NPC1. Ref.21
VAR_043253
Natural variant9341R → Q in NPC1. Ref.17 Ref.22 Ref.31
VAR_008828
Natural variant9401S → L in NPC1. Ref.17 Ref.21 Ref.31
VAR_008829
Natural variant9421W → C in NPC1. Ref.24 Ref.29
VAR_043254
Natural variant9431I → M in NPC1. Ref.22
VAR_043255
Natural variant9441D → N in NPC1. Ref.21 Ref.22 Ref.29
VAR_043256
Natural variant9451D → N in NPC1. Ref.28
VAR_043257
Natural variant9481D → H in NPC1. Ref.29
VAR_043258
Natural variant9481D → N in NPC1. Ref.17 Ref.21 Ref.25
VAR_008830
Natural variant9481D → Y in NPC1. Ref.3
VAR_043259
Natural variant9501V → M in NPC1; adult form. Ref.22 Ref.31
VAR_015563
Natural variant9541S → L in NPC1. Ref.3 Ref.17 Ref.20
VAR_008831
Natural variant9561C → Y in NPC1; late infantile form. Ref.20
VAR_008832
Natural variant9581R → L in NPC1. Ref.3
VAR_043260
Natural variant9581R → Q in NPC1. Ref.21
VAR_015564
Natural variant9591V → E in NPC1. Ref.29
VAR_043261
Natural variant961 – 9666NITDQF → S in NPC1. Ref.32
VAR_043262
Natural variant9611N → S in NPC1. Ref.32
Corresponds to variant rs34084984 [ dbSNP | Ensembl ].
VAR_043263
Natural variant9681N → S in NPC1. Ref.30 Ref.31
VAR_043264
Natural variant9711V → G. Ref.3
VAR_043265
Natural variant9761C → R in NPC1. Ref.21
VAR_043266
Natural variant9781R → C in NPC1. Ref.21 Ref.24
Corresponds to variant rs28942108 [ dbSNP | Ensembl ].
VAR_015565
Natural variant9861G → S in NPC1. Ref.22
VAR_043267
Natural variant9921G → A in NPC1. Ref.31
VAR_043268
Natural variant9921G → R in NPC1. Ref.22 Ref.31
VAR_015566
Natural variant9921G → W in NPC1; found in the Nova Scotian clinical variant. Ref.16 Ref.17 Ref.23 Ref.26 Ref.31
VAR_008833
Natural variant9961M → R in NPC1. Ref.20
VAR_043269
Natural variant10041S → L in NPC1. Ref.21
VAR_043270
Natural variant10071P → A in NPC1. Ref.3 Ref.17 Ref.21 Ref.22 Ref.24 Ref.26 Ref.29 Ref.31
VAR_008834
Natural variant10121G → D in NPC1. Ref.23
VAR_043271
Natural variant10151G → V in NPC1. Ref.30
VAR_043272
Natural variant10161H → R in NPC1. Ref.28
VAR_043273
Natural variant10231V → G in NPC1. Ref.21
VAR_043274
Natural variant10341G → R in NPC1. Ref.30
VAR_043275
Natural variant10351A → V in NPC1. Ref.24 Ref.29
Corresponds to variant rs28942107 [ dbSNP | Ensembl ].
VAR_015567
Natural variant10361T → K in NPC1. Ref.29
VAR_043276
Natural variant10361T → M in NPC1. Ref.31
Corresponds to variant rs28942104 [ dbSNP | Ensembl ].
VAR_008835
Natural variant10491A → V. Ref.3
VAR_043277
Natural variant10541A → T in NPC1. Ref.22
VAR_043278
Natural variant10591R → Q in NPC1. Ref.28
VAR_043279
Natural variant10611I → T in NPC1; late infantile form. Ref.3 Ref.17 Ref.18 Ref.20 Ref.21 Ref.22 Ref.24 Ref.26 Ref.29 Ref.31
VAR_008836
Natural variant10621A → V in NPC1. Ref.31
VAR_043280
Natural variant10661T → N in NPC1. Ref.29
VAR_043281
Natural variant10871F → L in NPC1. Ref.28
VAR_043282
Natural variant10881Y → C in NPC1; juvenile form. Ref.20
Corresponds to variant rs28942106 [ dbSNP | Ensembl ].
VAR_008837
Natural variant10891E → K in NPC1. Ref.21
VAR_043283
Natural variant10941I → T in NPC1. Ref.25
VAR_043284
Natural variant10971D → N in NPC1. Ref.31
VAR_043285
Natural variant11371N → I in NPC1. Ref.28
VAR_043286
Natural variant11401G → V in NPC1. Ref.28
VAR_043287
Natural variant11421M → T in NPC1. Ref.21 Ref.22
VAR_043288
Natural variant11501N → K in NPC1. Ref.21
VAR_043289
Natural variant11561N → I in NPC1. Ref.29
Corresponds to variant rs28942105 [ dbSNP | Ensembl ].
VAR_043290
Natural variant11561N → S in NPC1. Ref.21 Ref.23 Ref.26 Ref.29
Corresponds to variant rs28942105 [ dbSNP | Ensembl ].
VAR_008838
Natural variant11651V → M in NPC1. Ref.21
VAR_043291
Natural variant11671F → L in NPC1.
VAR_008839
Natural variant11681C → Y in NPC1. Ref.22
VAR_043292
Natural variant11741A → V in NPC1. Ref.31
VAR_043293
Natural variant11861R → H in NPC1. Ref.21 Ref.22 Ref.31
Corresponds to variant rs200444084 [ dbSNP | Ensembl ].
VAR_008840
Natural variant11891E → G in NPC1. Ref.21
VAR_043294
Natural variant12051T → K in NPC1. Ref.28
VAR_043295
Natural variant12051T → R in NPC1. Ref.20
VAR_043296
Natural variant12121V → L in NPC1. Ref.30
VAR_043297
Natural variant12131L → F in NPC1; juvenile form. Ref.20
VAR_008841
Natural variant12131L → V in NPC1. Ref.17
VAR_008842
Natural variant12161A → V in NPC1. Ref.31
VAR_043298
Natural variant12201I → T.
VAR_008843
Natural variant12241F → L in NPC1. Ref.29
VAR_043299
Natural variant12361G → E in NPC1. Ref.20
VAR_043300
Natural variant12401G → R in NPC1. Ref.31
VAR_043301
Natural variant12491S → G in NPC1. Ref.28
VAR_043302
Natural variant12661R → Q Common polymorphism in Japanese. Ref.19 Ref.28 Ref.29 Ref.30
Corresponds to variant rs1805084 [ dbSNP | Ensembl ].
VAR_008844

Experimental info

Mutagenesis26 – 272VW → AA: Nearly abolishes 25-hydroxycholesterol binding. Reduces cholesterol binding.
Mutagenesis39 – 413RYN → AAA: Strongly reduces cholesterol and 25-hydroxycholesterol binding. Ref.15
Mutagenesis411N → A: Nearly abolishes cholesterol and 25-hydroxycholesterol binding. Ref.15
Mutagenesis631C → S: Loss of function. Ref.5
Mutagenesis701N → Q: Reduces glycosylation; when associated with Q-122 and Q-185. No effect on cholesterol and 25-hydroxycholesterol binding. Ref.15
Mutagenesis82 – 832TL → AA: Strongly reduces cholesterol and 25-hydroxycholesterol binding.
Mutagenesis971C → S: Loss of function. Ref.5
Mutagenesis101 – 1022FY → AA: Strongly reduces 25-hydroxycholesterol binding. No effect on cholesterol binding.
Mutagenesis106 – 1083NLF → AAA: Nearly abolishes cholesterol and 25-hydroxycholesterol binding. Ref.15
Mutagenesis110 – 1123ELT → AAA: No effect on cholesterol and 25-hydroxycholesterol binding and transfer. Ref.15
Mutagenesis1221N → Q: Reduces glycosylation; when associated with Q-70 and Q-185. No effect on cholesterol and 25-hydroxycholesterol binding. Ref.15
Mutagenesis144 – 1452LQ → AA: Strongly reduces 25-hydroxycholesterol binding. No effect on cholesterol binding.
Mutagenesis146 – 1472YY → AA: Strongly reduces 25-hydroxycholesterol binding. No effect on cholesterol binding.
Mutagenesis175 – 1762LL → AA: No effect on cholesterol or 25-hydroxycholesterol binding. Strongly reduces cholesterol transfer to liposomes in a NPC2-dependent manner.
Mutagenesis180 – 1823DAD → AAA: Strongly reduces cholesterol transfer to liposomes in a NPC2-dependent manner. Ref.15
Mutagenesis1851N → 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. Ref.15
Mutagenesis187 – 1882TN → AA: Strongly reduces 25-hydroxycholesterol binding and cholesterol transfer to liposomes in a NPC2-dependent manner.
Mutagenesis191 – 1922EY → AA: No effect on cholesterol or 25-hydroxycholesterol binding. Nearly abolishes cholesterol transfer to liposomes in a NPC2-dependent manner.
Mutagenesis195 – 1962NK → AA: Strongly reduces 25-hydroxycholesterol binding. No effect on cholesterol binding.
Mutagenesis197 – 1982DN → AA: Strongly reduces cholesterol and 25-hydroxycholesterol binding.
Mutagenesis199 – 2002GQ → AA: Strongly reduces 25-hydroxycholesterol binding and cholesterol transfer to liposomes in a NPC2-dependent manner.
Mutagenesis202 – 2032PF → AA: Abolishes cholesterol and 25-hydroxycholesterol binding.
Mutagenesis204 – 2052TI → AA: Strongly reduces cholesterol and 25-hydroxycholesterol binding.
Mutagenesis6601G → R: Loss of function. Ref.15

Secondary structure

........................................... 1278
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
O15118 [UniParc].

Last modified May 10, 2005. Version 2.
Checksum: DA1523E09822E5C7

FASTA1,278142,167
        10         20         30         40         50         60 
MTARGLALGL LLLLLCPAQV FSQSCVWYGE CGIAYGDKRY NCEYSGPPKP LPKDGYDLVQ 

        70         80         90        100        110        120 
ELCPGFFFGN VSLCCDVRQL QTLKDNLQLP LQFLSRCPSC FYNLLNLFCE LTCSPRQSQF 

       130        140        150        160        170        180 
LNVTATEDYV DPVTNQTKTN VKELQYYVGQ SFANAMYNAC RDVEAPSSND KALGLLCGKD 

       190        200        210        220        230        240 
ADACNATNWI EYMFNKDNGQ APFTITPVFS DFPVHGMEPM NNATKGCDES VDEVTAPCSC 

       250        260        270        280        290        300 
QDCSIVCGPK PQPPPPPAPW TILGLDAMYV IMWITYMAFL LVFFGAFFAV WCYRKRYFVS 

       310        320        330        340        350        360 
EYTPIDSNIA FSVNASDKGE ASCCDPVSAA FEGCLRRLFT RWGSFCVRNP GCVIFFSLVF 

       370        380        390        400        410        420 
ITACSSGLVF VRVTTNPVDL WSAPSSQARL EKEYFDQHFG PFFRTEQLII RAPLTDKHIY 

       430        440        450        460        470        480 
QPYPSGADVP FGPPLDIQIL HQVLDLQIAI ENITASYDNE TVTLQDICLA PLSPYNTNCT 

       490        500        510        520        530        540 
ILSVLNYFQN SHSVLDHKKG DDFFVYADYH THFLYCVRAP ASLNDTSLLH DPCLGTFGGP 

       550        560        570        580        590        600 
VFPWLVLGGY DDQNYNNATA LVITFPVNNY YNDTEKLQRA QAWEKEFINF VKNYKNPNLT 

       610        620        630        640        650        660 
ISFTAERSIE DELNRESDSD VFTVVISYAI MFLYISLALG HMKSCRRLLV DSKVSLGIAG 

       670        680        690        700        710        720 
ILIVLSSVAC SLGVFSYIGL PLTLIVIEVI PFLVLAVGVD NIFILVQAYQ RDERLQGETL 

       730        740        750        760        770        780 
DQQLGRVLGE VAPSMFLSSF SETVAFFLGA LSVMPAVHTF SLFAGLAVFI DFLLQITCFV 

       790        800        810        820        830        840 
SLLGLDIKRQ EKNRLDIFCC VRGAEDGTSV QASESCLFRF FKNSYSPLLL KDWMRPIVIA 

       850        860        870        880        890        900 
IFVGVLSFSI AVLNKVDIGL DQSLSMPDDS YMVDYFKSIS QYLHAGPPVY FVLEEGHDYT 

       910        920        930        940        950        960 
SSKGQNMVCG GMGCNNDSLV QQIFNAAQLD NYTRIGFAPS SWIDDYFDWV KPQSSCCRVD 

       970        980        990       1000       1010       1020 
NITDQFCNAS VVDPACVRCR PLTPEGKQRP QGGDFMRFLP MFLSDNPNPK CGKGGHAAYS 

      1030       1040       1050       1060       1070       1080 
SAVNILLGHG TRVGATYFMT YHTVLQTSAD FIDALKKARL IASNVTETMG INGSAYRVFP 

      1090       1100       1110       1120       1130       1140 
YSVFYVFYEQ YLTIIDDTIF NLGVSLGAIF LVTMVLLGCE LWSAVIMCAT IAMVLVNMFG 

      1150       1160       1170       1180       1190       1200 
VMWLWGISLN AVSLVNLVMS CGISVEFCSH ITRAFTVSMK GSRVERAEEA LAHMGSSVFS 

      1210       1220       1230       1240       1250       1260 
GITLTKFGGI VVLAFAKSQI FQIFYFRMYL AMVLLGATHG LIFLPVLLSY IGPSVNKAKS 

      1270 
CATEERYKGT ERERLLNF 

« Hide

References

« Hide 'large scale' references
[1]"Niemann-Pick C1 disease gene: homology to mediators of cholesterol homeostasis."
Carstea E.D., Morris J.A., Coleman K.G., Loftus S.K., Zhang D., Cummings C., Gu J., Rosenfeld M.A., Pavan W.J., Krizman D.B., Nagle J., Polymeropoulos M.H., Sturley S.L., Ioannou Y.A., Higgins M.E., Comly M., Cooney A., Brown A. expand/collapse author list , Kaneski C.R., Blanchette-Mackie E.J., Dwyer N.K., Neufeld E.B., Chang T.-Y., Liscum L., Strauss J.F. III, Ohno K., Zeigler M., Carmi R., Sokol J., Markie D., O'Neill R.R., van Diggelen O.P., Elleder M., Patterson M.C., Brady R.O., Vanier M.T., Pentchev P.G., Tagle D.A.
Science 277:228-231(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ILE-642, VARIANTS NPC1.
[2]"The genomic organization and polymorphism analysis of the human Niemann-Pick C1 gene."
Morris J.A., Zhang D., Coleman K.G., Nagle J., Pentchev P.G., Carstea E.D.
Biochem. Biophys. Res. Commun. 261:493-498(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS.
[3]"NPC1: complete genomic sequence, mutation analysis, and characterization of haplotypes."
Bauer P., Knoblich R., Bauer C., Finckh U., Hufen A., Kropp J., Braun S., Kustermann-Kuhn B., Schmidt D., Harzer K., Rolfs A.
Hum. Mutat. 19:30-38(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS NPC1 ARG-512; TRP-670; CYS-825; ILE-849; VAL-874; TYR-948; LEU-954; LEU-958; ALA-1007 AND THR-1061, VARIANTS ARG-215; ILE-642; VAL-858; GLY-971 AND VAL-1049.
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS GLY-151 AND ILE-642.
Tissue: Placenta.
[5]"Niemann-Pick C1 protein: obligatory roles for N-terminal domains and lysosomal targeting in cholesterol mobilization."
Watari H., Blanchette-Mackie E.J., Dwyer N.K., Glick J.M., Patel S., Neufeld E.B., Brady R.O., Pentchev P.G., Strauss J.F. III
Proc. Natl. Acad. Sci. U.S.A. 96:805-810(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION, MUTAGENESIS OF CYS-63 AND CYS-97.
[6]"Topological analysis of Niemann-Pick C1 protein reveals that the membrane orientation of the putative sterol-sensing domain is identical to those of 3-hydroxy-3-methylglutaryl-CoA reductase and sterol regulatory element binding protein cleavage-activating protein."
Davies J.P., Ioannou Y.A.
J. Biol. Chem. 275:24367-24374(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: TOPOLOGY, GLYCOSYLATION.
[7]"Integral and associated lysosomal membrane proteins."
Schroeder B., Wrocklage C., Pan C., Jaeger R., Koesters B., Schaefer H., Elsaesser H.-P., Mann M., Hasilik A.
Traffic 8:1676-1686(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
Tissue: Placenta.
[8]"NPC2 facilitates bidirectional transfer of cholesterol between NPC1 and lipid bilayers, a step in cholesterol egress from lysosomes."
Infante R.E., Wang M.L., Radhakrishnan A., Kwon H.J., Brown M.S., Goldstein J.L.
Proc. Natl. Acad. Sci. U.S.A. 105:15287-15292(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[9]"Identification of cholesterol-regulating genes by targeted RNAi screening."
Bartz F., Kern L., Erz D., Zhu M., Gilbert D., Meinhof T., Wirkner U., Erfle H., Muckenthaler M., Pepperkok R., Runz H.
Cell Metab. 10:63-75(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TMEM97.
[10]"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry."
Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.
J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-135 AND ASN-524.
Tissue: Liver.
[11]"NPC1/NPC2 function as a tag team duo to mobilize cholesterol."
Subramanian K., Balch W.E.
Proc. Natl. Acad. Sci. U.S.A. 105:15223-15224(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION.
[12]"Transfer of cholesterol by the NPC team."
Vance J.E.
Cell Metab. 12:105-106(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION.
[13]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[14]"Function of the Niemann-Pick type C proteins and their bypass by cyclodextrin."
Vance J.E., Peake K.B.
Curr. Opin. Lipidol. 22:204-209(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION.
[15]"Structure of N-terminal domain of NPC1 reveals distinct subdomains for binding and transfer of cholesterol."
Kwon H.J., Abi-Mosleh L., Wang M.L., Deisenhofer J., Goldstein J.L., Brown M.S., Infante R.E.
Cell 137:1213-1224(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) OF 23-252 OF MUTANT GLN-70; GLN-122 AND GLN-185 IN COMPLEX WITH CHOLESTEROL, FUNCTION, DISULFIDE BONDS, GLYCOSYLATION AT ASN-158 AND ASN-222, MUTAGENESIS OF 26-VAL-TRP-27; 39-ARG--ASN-41; ASN-41; ASN-70; 82-THR-LEU-83; 101-PHE-TYR-102; 106-ASN--PHE-108; 110-GLU--THR-112; ASN-122; 144-LEU-GLN-145; 146-TYR-TYR-147; 175-LEU-LEU-176; 180-ASP--ASP-182; ASN-185; 187-TYR-ASN-188; 191-GLU-TYR-192; 195-ASN-LYS-196; 197-ASP-ASN-198; 199-GLY-GLN-200; 202-PRO-PHE-203; 204-THR-ILE-205 AND GLY-660.
[16]"The Nova Scotia (type D) form of Niemann-Pick disease is caused by a G3097-->T transversion in NPC1."
Greer W.L., Riddell D.C., Gillan T.L., Girouard G.S., Sparrow S.M., Byers D.M., Dobson M.J., Neumann P.E.
Am. J. Hum. Genet. 63:52-54(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT NPC1 TRP-992.
[17]"Mutations in NPC1 highlight a conserved NPC1-specific cysteine-rich domain."
Greer W.L., Dobson M.J., Girouard G.S., Byers D.M., Riddell D.C., Neumann P.E.
Am. J. Hum. Genet. 65:1252-1260(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NPC1 GLN-934; LEU-940; ASN-948; LEU-954; TRP-992; ALA-1007; THR-1061 AND VAL-1213.
[18]"Niemann-Pick C1 disease: the I1061T substitution is a frequent mutant allele in patients of Western European descent and correlates with a classic juvenile phenotype."
Millat G., Marcais C., Rafi M.A., Yamamoto T., Morris J.A., Pentchev P.G., Ohno K., Wenger D.A., Vanier M.T.
Am. J. Hum. Genet. 65:1321-1329(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT NPC1 THR-1061.
[19]"NPC1 gene mutations in Japanese patients with Niemann-Pick disease type C."
Yamamoto T., Nanba E., Ninomiya H., Higaki K., Taniguchi M., Zhang H., Akaboshi S., Watanabe Y., Takeshima T., Inui K., Okada S., Tanaka A., Sakuragawa N., Millat G., Vanier M.T., Morris J.A., Pentchev P.G., Ohno K.
Hum. Genet. 105:10-16(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NPC1, VARIANTS ARG-215; VAL-858 AND GLN-1266.
[20]"Genotype-phenotype relationship of Niemann-Pick disease type C: a possible correlation between clinical onset and levels of NPC1 protein in isolated skin fibroblasts."
Yamamoto T., Ninomiya H., Matsumoto M., Ohta Y., Nanba E., Tsutsumi Y., Yamakawa K., Millat G., Vanier M.T., Pentchev P.G., Ohno K.
J. Med. Genet. 37:707-712(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NPC1 GLY-177; SER-237; PRO-473; PRO-510; GLN-518; SER-703; MET-889; LEU-954; TYR-956; ARG-996; THR-1061; CYS-1088; ARG-1205; PHE-1213 AND GLU-1236, VARIANT ALA-873.
[21]"Niemann-Pick C variant detection by altered sphingolipid trafficking and correlation with mutations within a specific domain of NPC1."
Sun X., Marks D.L., Park W.D., Wheatley C.L., Puri V., O'Brien J.F., Kraft D.L., Lundquist P.A., Patterson M.C., Pagano R.E., Snow K.
Am. J. Hum. Genet. 68:1361-1372(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NPC1 ARG-92; MET-137; SER-237; ASN-242; VAL-248; THR-401; GLN-404; ASP-612; TRP-652; CYS-789; CYS-825; VAL-874; SER-888; PRO-929; LEU-940; ASN-944; ASN-948; GLN-958; ARG-976; CYS-978; LEU-1004; ALA-1007; GLY-1023; THR-1061; LYS-1089; THR-1142; LYS-1150; SER-1156; MET-1165; HIS-1186 AND GLY-1189.
[22]"Niemann-Pick C1 disease: correlations between NPC1 mutations, levels of NPC1 protein, and phenotypes emphasize the functional significance of the putative sterol-sensing domain and of the cysteine-rich luminal loop."
Millat G., Marcais C., Tomasetto C., Chikh K., Fensom A.H., Harzer K., Wenger D.A., Ohno K., Vanier M.T.
Am. J. Hum. Genet. 68:1373-1385(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NPC1 SER-237; HIS-242; ARG-272; ALA-378; GLN-404; GLN-518; VAL-605; ARG-631; PRO-724; PRO-775; CYS-825; VAL-874; GLN-934; MET-943; ASN-944; MET-950; SER-986; ARG-992; ALA-1007; THR-1054; THR-1061; THR-1142; TYR-1168 AND HIS-1186.
[23]"Clinical-biochemical correlation in molecularly characterized patients with Niemann-Pick type C."
Meiner V., Shpitzen S., Mandel H., Klar A., Ben-Neriah Z., Zlotogora J., Sagi M., Lossos A., Bargal R., Sury V., Carmi R., Leitersdorf E., Zeigler M.
Genet. Med. 3:343-348(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NPC1 ARG-63; GLN-404; VAL-927; TRP-992; ASP-1012 AND SER-1156.
[24]"Niemann-Pick type C disease: NPC1 mutations associated with severe and mild cellular cholesterol trafficking alterations."
Ribeiro I., Marcao A., Amaral O., Sa Miranda M.C., Vanier M.T., Millat G.
Hum. Genet. 109:24-32(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NPC1 ARG-92; TYR-177; TRP-518; CYS-942; CYS-978; ALA-1007 VAL-1035 AND THR-1061, VARIANTS ARG-215; ILE-642 AND VAL-858.
[25]"Identification of novel mutations in the NPC1 gene in German patients with Niemann-Pick C disease."
Kaminski W.E., Kluenemann H.H., Ibach B., Aslanidis C., Klein H.E., Schmitz G.
J. Inherit. Metab. Dis. 25:385-389(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NPC1 GLY-231; SER-237; VAL-874 ASN-948 AND THR-1094, VARIANTS CYS-381 AND ILE-642.
[26]"Niemann-Pick type C disease: mutations of NPC1 gene and evidence of abnormal expression of some mutant alleles in fibroblasts."
Tarugi P., Ballarini G., Bembi B., Battisti C., Palmeri S., Panzani F., Di Leo E., Martini C., Federico A., Calandra S.
J. Lipid Res. 43:1908-1919(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NPC1 LYS-451; LEU-474; CYS-890; ASP-899; SER-910; TRP-992; ALA-1007; THR-1061 AND SER-1156, VARIANTS ARG-215; ILE-642 AND VAL-858.
[27]"Defective endocytic trafficking of NPC1 and NPC2 underlying infantile Niemann-Pick type C disease."
Blom T.S., Linder M.D., Snow K., Pihko H., Hess M.W., Jokitalo E., Veckman V., Syvaenen A.-C., Ikonen E.
Hum. Mol. Genet. 12:257-272(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT NPC1 ARG-113, VARIANT SER-273, CHARACTERIZATION OF VARIANT NPC1 ARG-113, CHARACTERIZATION OF VARIANT SER-273.
[28]"Identification of 58 novel mutations in Niemann-Pick disease type C: correlation with biochemical phenotype and importance of PTC1-like domains in NPC1."
Park W.D., O'Brien J.F., Lundquist P.A., Kraft D.L., Vockley C.W., Karnes P.S., Patterson M.C., Snow K.
Hum. Mutat. 22:313-325(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NPC1 TYR-74; SER-166; SER-222; TYR-247; PHE-380; PRO-388; CYS-389; TRP-404; LEU-433; SER-509; SER-521; LEU-543; CYS-615; ARG-640; SER-660; MET-664; VAL-673; PHE-684; LEU-691; VAL-695; ASN-700; ILE-734; LYS-742; GLU-745; VAL-767; GLY-789; ASN-945; ARG-1016; GLN-1059; LEU-1087; ILE-1137; VAL-1140; LYS-1205 AND GLY-1249, VARIANTS ARG-215; SER-237; SER-434 AND GLN-1266.
[29]"Identification of 25 new mutations in 40 unrelated Spanish Niemann-Pick type C patients: genotype-phenotype correlations."
Fernandez-Valero E.M., Ballart A., Iturriaga C., Lluch M., Macias J., Vanier M.T., Pineda M., Coll M.J.
Clin. Genet. 68:245-254(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NPC1 MET-137; TYR-177; TRP-372; LEU-434; LEU-474; TYR-479; ARG-576; MET-664; PHE-727; LYS-754; PRO-775; LEU-865; THR-926; CYS-942; ASN-944; HIS-948; GLU-959; 961-ASN--PHE-966 DELINS SER; ALA-1007; VAL-1035; LYS-1036; THR-1061; ASN-1066; ILE-1156; SER-1156 AND LEU-1224, VARIANTS ARG-215; ILE-642; VAL-858 AND GLN-1266.
[30]"Six novel NPC1 mutations in Chinese patients with Niemann-Pick disease type C."
Yang C.-C., Su Y.-N., Chiou P.-C., Fietz M.J., Yu C.-L., Hwu W.-L., Lee M.-J.
J. Neurol. Neurosurg. Psych. 76:592-595(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NPC1 SER-968; VAL-1015; ARG-1034 AND LEU-1212, VARIANTS ARG-215; ILE-642; VAL-858 AND GLN-1266.
[31]"Niemann-Pick C disease: use of denaturing high performance liquid chromatography for the detection of NPC1 and NPC2 genetic variations and impact on management of patients and families."
Millat G., Baielo N., Molinero S., Rodriguez C., Chikh K., Vanier M.T.
Mol. Genet. Metab. 86:220-232(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NPC1 SER-166; TYR-177; PRO-404; LEU-537; LEU-543; LEU-615; ARG-631; LEU-763; CYS-825; LEU-862; LEU-865; CYS-871; TYR-917; GLN-934; LEU-940; MET-950; SER-968; ALA-992; ARG-992; TRP-992; ALA-1007; MET-1036; THR-1061; VAL-1062; ASN-1097; VAL-1174; HIS-1186; VAL-1216 AND ARG-1240, VARIANT MET-511.
[32]"Subclinical course of adult visceral Niemann-Pick type C1 disease. A rare or underdiagnosed disorder?"
Dvorakova L., Sikora J., Hrebicek M., Hulkova H., Bouckova M., Stolnaja L., Elleder M.
J. Inherit. Metab. Dis. 29:591-591(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NPC1 ASN-666 AND SER-961.
[33]"Whole-exome sequencing identifies mutated c12orf57 in recessive corpus callosum hypoplasia."
Akizu N., Shembesh N.M., Ben-Omran T., Bastaki L., Al-Tawari A., Zaki M.S., Koul R., Spencer E., Rosti R.O., Scott E., Nickerson E., Gabriel S., da Gente G., Li J., Deardorff M.A., Conlin L.K., Horton M.A., Zackai E.H., Sherr E.H., Gleeson J.G.
Am. J. Hum. Genet. 92:392-400(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT NCP1 MET-137.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF002020 mRNA. Translation: AAB63982.1.
AF157379 expand/collapse EMBL AC list , 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.
BC063302 mRNA. Translation: AAH63302.1.
RefSeqNP_000262.2. NM_000271.4.
UniGeneHs.464779.
Hs.715623.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3GKHX-ray1.81A23-252[»]
3GKIX-ray1.80A23-252[»]
3GKJX-ray1.60A23-252[»]
ProteinModelPortalO15118.
SMRO15118. Positions 23-247.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110925. 9 interactions.
IntActO15118. 4 interactions.
STRING9606.ENSP00000269228.

Chemistry

ChEMBLCHEMBL1293277.

Protein family/group databases

TCDB2.A.6.6.1. the resistance-nodulation-cell division (rnd) superfamily.

PTM databases

PhosphoSiteO15118.

Proteomic databases

PaxDbO15118.
PeptideAtlasO15118.
PRIDEO15118.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000269228; ENSP00000269228; ENSG00000141458.
GeneID4864.
KEGGhsa:4864.
UCSCuc002kum.4. human.

Organism-specific databases

CTD4864.
GeneCardsGC18M021111.
H-InvDBHIX0039703.
HGNCHGNC:7897. NPC1.
HPAHPA026618.
MIM257220. phenotype.
607623. gene.
neXtProtNX_O15118.
Orphanet216986. 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.
PharmGKBPA31698.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG149152.
HOVERGENHBG003913.
InParanoidO15118.
KOK12385.
OMAYEYTPFL.
OrthoDBEOG7QRQT0.
PhylomeDBO15118.
TreeFamTF300416.

Gene expression databases

ArrayExpressO15118.
BgeeO15118.
CleanExHS_NPC1.
GenevestigatorO15118.

Family and domain databases

InterProIPR004765. NP_C_type.
IPR003392. Patched.
IPR000731. SSD.
[Graphical view]
PfamPF02460. Patched. 1 hit.
[Graphical view]
TIGRFAMsTIGR00917. 2A060601. 1 hit.
PROSITEPS50156. SSD. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceO15118.
GeneWikiNPC1.
GenomeRNAi4864.
NextBio18738.
PROO15118.
SOURCESearch...

Entry information

Entry nameNPC1_HUMAN
AccessionPrimary (citable) accession number: O15118
Secondary accession number(s): Q9P130
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: May 10, 2005
Last modified: April 16, 2014
This is version 136 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 18

Human chromosome 18: entries, gene names and cross-references to MIM