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O15118

- NPC1_HUMAN

UniProt

O15118 - NPC1_HUMAN

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Protein

Niemann-Pick C1 protein

Gene
NPC1
Organism
Homo sapiens (Human)
Status
Reviewed - 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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei41 – 411Cholesterol
Binding sitei79 – 791Cholesterol
Sitei108 – 1081Important for cholesterol binding

GO - Molecular functioni

  1. cholesterol binding Source: UniProtKB
  2. hedgehog receptor activity Source: InterPro
  3. protein binding Source: UniProtKB
  4. receptor activity Source: ProtInc
  5. sterol transporter activity Source: ProtInc
  6. transmembrane signaling receptor activity Source: ProtInc

GO - Biological processi

  1. adult walking behavior Source: Ensembl
  2. autophagy Source: MGI
  3. bile acid metabolic process Source: UniProtKB
  4. cellular response to low-density lipoprotein particle stimulus Source: Ensembl
  5. cellular response to steroid hormone stimulus Source: Ensembl
  6. cholesterol efflux Source: BHF-UCL
  7. cholesterol homeostasis Source: UniProtKB
  8. cholesterol metabolic process Source: UniProtKB-KW
  9. cholesterol transport Source: UniProtKB
  10. endocytosis Source: Ensembl
  11. establishment of protein localization to membrane Source: UniProt
  12. lysosomal transport Source: UniProtKB
  13. membrane raft organization Source: UniProt
  14. negative regulation of cell death Source: Ensembl
  15. negative regulation of macroautophagy Source: Ensembl
  16. protein glycosylation Source: UniProtKB
  17. response to cadmium ion Source: Ensembl
  18. response to drug Source: Ensembl
  19. signal transduction Source: GOC
Complete GO annotation...

Keywords - Biological processi

Cholesterol metabolism, Lipid metabolism, Steroid metabolism, Sterol metabolism

Protein family/group databases

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

Names & Taxonomyi

Protein namesi
Recommended name:
Niemann-Pick C1 protein
Gene namesi
Name:NPC1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 18

Organism-specific databases

HGNCiHGNC:7897. NPC1.

Subcellular locationi

Late endosome membrane; Multi-pass membrane protein. Lysosome membrane; Multi-pass membrane protein 1 Publication

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini23 – 269247Lumenal Reviewed predictionAdd
BLAST
Transmembranei270 – 29021Helical; Reviewed predictionAdd
BLAST
Topological domaini291 – 35060Cytoplasmic Reviewed predictionAdd
BLAST
Transmembranei351 – 37121Helical; Reviewed predictionAdd
BLAST
Topological domaini372 – 620249Lumenal Reviewed predictionAdd
BLAST
Transmembranei621 – 64121Helical; Reviewed predictionAdd
BLAST
Topological domaini642 – 65413Cytoplasmic Reviewed predictionAdd
BLAST
Transmembranei655 – 67521Helical; Reviewed predictionAdd
BLAST
Topological domaini676 – 6772Lumenal Reviewed prediction
Transmembranei678 – 69821Helical; Reviewed predictionAdd
BLAST
Topological domaini699 – 73436Cytoplasmic Reviewed predictionAdd
BLAST
Transmembranei735 – 75521Helical; Reviewed predictionAdd
BLAST
Topological domaini756 – 7594Lumenal Reviewed prediction
Transmembranei760 – 78021Helical; Reviewed predictionAdd
BLAST
Topological domaini781 – 83252Cytoplasmic Reviewed predictionAdd
BLAST
Transmembranei833 – 85321Helical; Reviewed predictionAdd
BLAST
Topological domaini854 – 1098245Lumenal Reviewed predictionAdd
BLAST
Transmembranei1099 – 111921Helical; Reviewed predictionAdd
BLAST
Topological domaini1120 – 11245Cytoplasmic Reviewed prediction
Transmembranei1125 – 114521Helical; Reviewed predictionAdd
BLAST
Topological domaini1146 – 11461Lumenal Reviewed prediction
Transmembranei1147 – 116721Helical; Reviewed predictionAdd
BLAST
Topological domaini1168 – 119528Cytoplasmic Reviewed predictionAdd
BLAST
Transmembranei1196 – 121621Helical; Reviewed predictionAdd
BLAST
Topological domaini1217 – 122711Lumenal Reviewed predictionAdd
BLAST
Transmembranei1228 – 124821Helical; Reviewed predictionAdd
BLAST
Topological domaini1249 – 127830Cytoplasmic Reviewed predictionAdd
BLAST

GO - Cellular componenti

  1. endoplasmic reticulum Source: UniProtKB
  2. extracellular region Source: UniProtKB
  3. extracellular vesicular exosome Source: UniProt
  4. Golgi apparatus Source: Ensembl
  5. integral component of membrane Source: ProtInc
  6. integral component of plasma membrane Source: UniProtKB
  7. late endosome membrane Source: UniProtKB-SubCell
  8. lysosomal membrane Source: UniProtKB
  9. lysosome Source: UniProtKB
  10. membrane raft Source: Ensembl
  11. nuclear envelope Source: UniProtKB
  12. 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) [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.19 Publications
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti63 – 631C → R in NPC1. 1 Publication
VAR_043172
Natural varianti74 – 741C → Y in NPC1. 1 Publication
VAR_043173
Natural varianti92 – 921Q → R in NPC1. 2 Publications
VAR_043174
Natural varianti113 – 1131C → 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 Publication
VAR_043175
Natural varianti137 – 1371T → M in NPC1. 3 Publications
VAR_043176
Natural varianti166 – 1661P → S in NPC1. 2 Publications
VAR_043178
Natural varianti177 – 1771C → G in NPC1; late infantile form. 1 Publication
VAR_008815
Natural varianti177 – 1771C → Y in NPC1. 3 Publications
VAR_015561
Natural varianti222 – 2221N → S in NPC1. 1 Publication
Corresponds to variant rs55680026 [ dbSNP | Ensembl ].
VAR_043179
Natural varianti231 – 2311V → G in NPC1. 1 Publication
VAR_043180
Natural varianti237 – 2371P → S in NPC1; late infantile form. 5 Publications
Corresponds to variant rs80358251 [ dbSNP | Ensembl ].
VAR_008817
Natural varianti242 – 2421D → H in NPC1. 1 Publication
VAR_043181
Natural varianti242 – 2421D → N in NPC1. 1 Publication
VAR_043182
Natural varianti247 – 2471C → Y in NPC1. 1 Publication
VAR_043183
Natural varianti248 – 2481G → V in NPC1. 1 Publication
VAR_043184
Natural varianti272 – 2721M → R in NPC1. 1 Publication
VAR_043185
Natural varianti273 – 2731W → S Colocalizes with the wild-type protein with Rab7-positive late endosomes; clears the lysosomal cholesterol accumulation in NPC1-deficient cells. 1 Publication
VAR_043186
Natural varianti372 – 3721R → W in NPC1. 1 Publication
VAR_043187
Natural varianti378 – 3781V → A in NPC1. 1 Publication
VAR_015562
Natural varianti380 – 3801L → F in NPC1. 1 Publication
VAR_043188
Natural varianti388 – 3881A → P in NPC1. 1 Publication
VAR_043190
Natural varianti389 – 3891R → C in NPC1. 1 Publication
VAR_043191
Natural varianti401 – 4011P → T in NPC1. 1 Publication
VAR_043192
Natural varianti404 – 4041R → P in NPC1. 1 Publication
VAR_043193
Natural varianti404 – 4041R → Q in NPC1. 3 Publications
VAR_043194
Natural varianti404 – 4041R → W in NPC1. 1 Publication
VAR_043195
Natural varianti433 – 4331P → L in NPC1. 1 Publication
VAR_043196
Natural varianti434 – 4341P → L in NPC1. 1 Publication
VAR_043197
Natural varianti451 – 4511E → K in NPC1. 1 Publication
VAR_043199
Natural varianti473 – 4731S → P in NPC1; late infantile form. 1 Publication
VAR_008820
Natural varianti474 – 4741P → L in NPC1. 2 Publications
VAR_043200
Natural varianti479 – 4791C → Y in NPC1. 1 Publication
VAR_043201
Natural varianti509 – 5091Y → S in NPC1. 1 Publication
VAR_043202
Natural varianti510 – 5101H → P in NPC1; late infantile form. 1 Publication
VAR_008821
Natural varianti512 – 5121H → R in NPC1. 1 Publication
VAR_043204
Natural varianti518 – 5181R → Q in NPC1; late infantile form; Common in Japanese. 2 Publications
VAR_008822
Natural varianti518 – 5181R → W in NPC1. 1 Publication
VAR_043205
Natural varianti521 – 5211A → S in NPC1. 1 Publication
VAR_043206
Natural varianti537 – 5371F → L in NPC1. 1 Publication
VAR_043207
Natural varianti543 – 5431P → L in NPC1. 2 Publications
VAR_043208
Natural varianti574 – 5741T → K in NPC1.
VAR_043209
Natural varianti576 – 5761K → R in NPC1. 1 Publication
VAR_043210
Natural varianti605 – 6051A → V in NPC1. 1 Publication
VAR_043211
Natural varianti612 – 6121E → D in NPC1. 1 Publication
VAR_043212
Natural varianti615 – 6151R → C in NPC1. 1 Publication
VAR_043213
Natural varianti615 – 6151R → L in NPC1. 1 Publication
VAR_043214
Natural varianti631 – 6311M → R in NPC1. 2 Publications
VAR_043215
Natural varianti640 – 6401G → R in NPC1. 1 Publication
VAR_043216
Natural varianti652 – 6521S → W in NPC1. 1 Publication
VAR_043217
Natural varianti660 – 6601G → S in NPC1. 1 Publication
VAR_043218
Natural varianti664 – 6641V → M in NPC1. 2 Publications
VAR_043219
Natural varianti666 – 6661S → N in NPC1. 1 Publication
VAR_043220
Natural varianti670 – 6701C → W in NPC1. 1 Publication
VAR_043221
Natural varianti673 – 6731G → V in NPC1. 1 Publication
VAR_043222
Natural varianti684 – 6841L → F in NPC1. 1 Publication
VAR_043223
Natural varianti691 – 6911P → L in NPC1. 1 Publication
VAR_043224
Natural varianti695 – 6951L → V in NPC1. 1 Publication
VAR_043225
Natural varianti700 – 7001D → N in NPC1. 1 Publication
VAR_043226
Natural varianti703 – 7031F → S in NPC1. 1 Publication
VAR_043227
Natural varianti724 – 7241L → P in NPC1. 1 Publication
VAR_043228
Natural varianti727 – 7271V → F in NPC1. 1 Publication
VAR_043229
Natural varianti734 – 7341S → I in NPC1. 1 Publication
VAR_043230
Natural varianti742 – 7421E → K in NPC1. 1 Publication
VAR_043231
Natural varianti745 – 7451A → E in NPC1. 1 Publication
VAR_043232
Natural varianti754 – 7541M → K in NPC1. 1 Publication
VAR_043233
Natural varianti763 – 7631F → L in NPC1. 1 Publication
VAR_043234
Natural varianti767 – 7671A → V in NPC1. 1 Publication
VAR_043235
Natural varianti775 – 7751Q → P in NPC1. 2 Publications
VAR_043236
Natural varianti789 – 7891R → C in NPC1. 1 Publication
VAR_043237
Natural varianti789 – 7891R → G in NPC1. 1 Publication
VAR_043238
Natural varianti825 – 8251Y → C in NPC1. 4 Publications
VAR_043239
Natural varianti849 – 8491S → I in NPC1. 1 Publication
VAR_043240
Natural varianti862 – 8621Q → L in NPC1. 1 Publication
VAR_043241
Natural varianti865 – 8651S → L in NPC1. 2 Publications
VAR_043242
Natural varianti871 – 8711Y → C in NPC1. 1 Publication
VAR_043243
Natural varianti874 – 8741D → V in NPC1. 4 Publications
VAR_043245
Natural varianti888 – 8881P → S in NPC1. 1 Publication
VAR_043246
Natural varianti889 – 8891V → M in NPC1; adult form. 1 Publication
VAR_008826
Natural varianti890 – 8901Y → C in NPC1. 1 Publication
VAR_043247
Natural varianti899 – 8991Y → D in NPC1. 1 Publication
VAR_043248
Natural varianti910 – 9101G → S in NPC1. 1 Publication
VAR_043249
Natural varianti917 – 9171D → Y in NPC1. 1 Publication
VAR_043250
Natural varianti926 – 9261A → T in NPC1. 1 Publication
VAR_043251
Natural varianti927 – 9271A → V in NPC1. 1 Publication
VAR_043252
Natural varianti928 – 9281Q → P in NPC1.
Corresponds to variant rs28940897 [ dbSNP | Ensembl ].
VAR_008827
Natural varianti929 – 9291L → P in NPC1. 1 Publication
VAR_043253
Natural varianti934 – 9341R → Q in NPC1. 3 Publications
VAR_008828
Natural varianti940 – 9401S → L in NPC1. 3 Publications
VAR_008829
Natural varianti942 – 9421W → C in NPC1. 2 Publications
VAR_043254
Natural varianti943 – 9431I → M in NPC1. 1 Publication
VAR_043255
Natural varianti944 – 9441D → N in NPC1. 3 Publications
VAR_043256
Natural varianti945 – 9451D → N in NPC1. 1 Publication
VAR_043257
Natural varianti948 – 9481D → H in NPC1. 1 Publication
VAR_043258
Natural varianti948 – 9481D → N in NPC1. 3 Publications
VAR_008830
Natural varianti948 – 9481D → Y in NPC1. 1 Publication
VAR_043259
Natural varianti950 – 9501V → M in NPC1; adult form. 2 Publications
VAR_015563
Natural varianti954 – 9541S → L in NPC1. 3 Publications
VAR_008831
Natural varianti956 – 9561C → Y in NPC1; late infantile form. 1 Publication
VAR_008832
Natural varianti958 – 9581R → L in NPC1. 1 Publication
VAR_043260
Natural varianti958 – 9581R → Q in NPC1. 1 Publication
VAR_015564
Natural varianti959 – 9591V → E in NPC1. 1 Publication
VAR_043261
Natural varianti961 – 9666NITDQF → S in NPC1. 1 Publication
VAR_043262
Natural varianti961 – 9611N → S in NPC1. 1 Publication
Corresponds to variant rs34084984 [ dbSNP | Ensembl ].
VAR_043263
Natural varianti968 – 9681N → S in NPC1. 2 Publications
VAR_043264
Natural varianti976 – 9761C → R in NPC1. 1 Publication
VAR_043266
Natural varianti978 – 9781R → C in NPC1. 2 Publications
Corresponds to variant rs28942108 [ dbSNP | Ensembl ].
VAR_015565
Natural varianti986 – 9861G → S in NPC1. 1 Publication
VAR_043267
Natural varianti992 – 9921G → A in NPC1. 1 Publication
VAR_043268
Natural varianti992 – 9921G → R in NPC1. 2 Publications
VAR_015566
Natural varianti992 – 9921G → W in NPC1; found in the Nova Scotian clinical variant. 5 Publications
VAR_008833
Natural varianti996 – 9961M → R in NPC1. 1 Publication
VAR_043269
Natural varianti1004 – 10041S → L in NPC1. 1 Publication
VAR_043270
Natural varianti1007 – 10071P → A in NPC1. 8 Publications
VAR_008834
Natural varianti1012 – 10121G → D in NPC1. 1 Publication
VAR_043271
Natural varianti1015 – 10151G → V in NPC1. 1 Publication
VAR_043272
Natural varianti1016 – 10161H → R in NPC1. 1 Publication
VAR_043273
Natural varianti1023 – 10231V → G in NPC1. 1 Publication
VAR_043274
Natural varianti1034 – 10341G → R in NPC1. 1 Publication
VAR_043275
Natural varianti1035 – 10351A → V in NPC1. 2 Publications
Corresponds to variant rs28942107 [ dbSNP | Ensembl ].
VAR_015567
Natural varianti1036 – 10361T → K in NPC1. 1 Publication
VAR_043276
Natural varianti1036 – 10361T → M in NPC1. 1 Publication
Corresponds to variant rs28942104 [ dbSNP | Ensembl ].
VAR_008835
Natural varianti1054 – 10541A → T in NPC1. 1 Publication
VAR_043278
Natural varianti1059 – 10591R → Q in NPC1. 1 Publication
VAR_043279
Natural varianti1061 – 10611I → T in NPC1; late infantile form. 10 Publications
VAR_008836
Natural varianti1062 – 10621A → V in NPC1. 1 Publication
VAR_043280
Natural varianti1066 – 10661T → N in NPC1. 1 Publication
VAR_043281
Natural varianti1087 – 10871F → L in NPC1. 1 Publication
VAR_043282
Natural varianti1088 – 10881Y → C in NPC1; juvenile form. 1 Publication
Corresponds to variant rs28942106 [ dbSNP | Ensembl ].
VAR_008837
Natural varianti1089 – 10891E → K in NPC1. 1 Publication
VAR_043283
Natural varianti1094 – 10941I → T in NPC1. 1 Publication
VAR_043284
Natural varianti1097 – 10971D → N in NPC1. 1 Publication
VAR_043285
Natural varianti1137 – 11371N → I in NPC1. 1 Publication
VAR_043286
Natural varianti1140 – 11401G → V in NPC1. 1 Publication
VAR_043287
Natural varianti1142 – 11421M → T in NPC1. 2 Publications
VAR_043288
Natural varianti1150 – 11501N → K in NPC1. 1 Publication
VAR_043289
Natural varianti1156 – 11561N → I in NPC1. 1 Publication
Corresponds to variant rs28942105 [ dbSNP | Ensembl ].
VAR_043290
Natural varianti1156 – 11561N → S in NPC1. 4 Publications
Corresponds to variant rs28942105 [ dbSNP | Ensembl ].
VAR_008838
Natural varianti1165 – 11651V → M in NPC1. 1 Publication
VAR_043291
Natural varianti1167 – 11671F → L in NPC1.
VAR_008839
Natural varianti1168 – 11681C → Y in NPC1. 1 Publication
VAR_043292
Natural varianti1174 – 11741A → V in NPC1. 1 Publication
VAR_043293
Natural varianti1186 – 11861R → H in NPC1. 3 Publications
Corresponds to variant rs200444084 [ dbSNP | Ensembl ].
VAR_008840
Natural varianti1189 – 11891E → G in NPC1. 1 Publication
VAR_043294
Natural varianti1205 – 12051T → K in NPC1. 1 Publication
VAR_043295
Natural varianti1205 – 12051T → R in NPC1. 1 Publication
VAR_043296
Natural varianti1212 – 12121V → L in NPC1. 1 Publication
VAR_043297
Natural varianti1213 – 12131L → F in NPC1; juvenile form. 1 Publication
VAR_008841
Natural varianti1213 – 12131L → V in NPC1. 1 Publication
VAR_008842
Natural varianti1216 – 12161A → V in NPC1. 1 Publication
VAR_043298
Natural varianti1224 – 12241F → L in NPC1. 1 Publication
VAR_043299
Natural varianti1236 – 12361G → E in NPC1. 1 Publication
VAR_043300
Natural varianti1240 – 12401G → R in NPC1. 1 Publication
VAR_043301
Natural varianti1249 – 12491S → G in NPC1. 1 Publication
VAR_043302

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi26 – 272VW → AA: Nearly abolishes 25-hydroxycholesterol binding. Reduces cholesterol binding.
Mutagenesisi39 – 413RYN → AAA: Strongly reduces cholesterol and 25-hydroxycholesterol binding. 1 Publication
Mutagenesisi41 – 411N → A: Nearly abolishes cholesterol and 25-hydroxycholesterol binding. 1 Publication
Mutagenesisi63 – 631C → S: Loss of function. 1 Publication
Mutagenesisi70 – 701N → Q: Reduces glycosylation; when associated with Q-122 and Q-185. No effect on cholesterol and 25-hydroxycholesterol binding. 1 Publication
Mutagenesisi82 – 832TL → AA: Strongly reduces cholesterol and 25-hydroxycholesterol binding.
Mutagenesisi97 – 971C → S: Loss of function. 1 Publication
Mutagenesisi101 – 1022FY → AA: Strongly reduces 25-hydroxycholesterol binding. No effect on cholesterol binding.
Mutagenesisi106 – 1083NLF → AAA: Nearly abolishes cholesterol and 25-hydroxycholesterol binding. 1 Publication
Mutagenesisi110 – 1123ELT → AAA: No effect on cholesterol and 25-hydroxycholesterol binding and transfer. 1 Publication
Mutagenesisi122 – 1221N → Q: Reduces glycosylation; when associated with Q-70 and Q-185. No effect on cholesterol and 25-hydroxycholesterol binding. 1 Publication
Mutagenesisi144 – 1452LQ → AA: Strongly reduces 25-hydroxycholesterol binding. No effect on cholesterol binding.
Mutagenesisi146 – 1472YY → AA: Strongly reduces 25-hydroxycholesterol binding. No effect on cholesterol binding.
Mutagenesisi175 – 1762LL → AA: No effect on cholesterol or 25-hydroxycholesterol binding. Strongly reduces cholesterol transfer to liposomes in a NPC2-dependent manner.
Mutagenesisi180 – 1823DAD → AAA: Strongly reduces cholesterol transfer to liposomes in a NPC2-dependent manner. 1 Publication
Mutagenesisi185 – 1851N → 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 Publication
Mutagenesisi187 – 1882TN → AA: Strongly reduces 25-hydroxycholesterol binding and cholesterol transfer to liposomes in a NPC2-dependent manner.
Mutagenesisi191 – 1922EY → AA: No effect on cholesterol or 25-hydroxycholesterol binding. Nearly abolishes cholesterol transfer to liposomes in a NPC2-dependent manner.
Mutagenesisi195 – 1962NK → AA: Strongly reduces 25-hydroxycholesterol binding. No effect on cholesterol binding.
Mutagenesisi197 – 1982DN → AA: Strongly reduces cholesterol and 25-hydroxycholesterol binding.
Mutagenesisi199 – 2002GQ → AA: Strongly reduces 25-hydroxycholesterol binding and cholesterol transfer to liposomes in a NPC2-dependent manner.
Mutagenesisi202 – 2032PF → AA: Abolishes cholesterol and 25-hydroxycholesterol binding.
Mutagenesisi204 – 2052TI → AA: Strongly reduces cholesterol and 25-hydroxycholesterol binding.
Mutagenesisi660 – 6601G → R: Loss of function. 1 Publication

Keywords - Diseasei

Disease mutation, Niemann-Pick disease

Organism-specific databases

MIMi257220. phenotype.
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.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2222 Reviewed predictionAdd
BLAST
Chaini23 – 12781256Niemann-Pick C1 proteinPRO_0000023261Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi25 ↔ 741 Publication
Disulfide bondi31 ↔ 421 Publication
Disulfide bondi63 ↔ 1091 Publication
Glycosylationi70 – 701N-linked (GlcNAc...) Inferred
Disulfide bondi75 ↔ 1131 Publication
Disulfide bondi97 ↔ 2381 Publication
Disulfide bondi100 ↔ 1601 Publication
Glycosylationi122 – 1221N-linked (GlcNAc...) Inferred
Glycosylationi135 – 1351N-linked (GlcNAc...)1 Publication
Glycosylationi158 – 1581N-linked (GlcNAc...); atypical1 Publication
Disulfide bondi177 ↔ 1841 Publication
Glycosylationi185 – 1851N-linked (GlcNAc...) Inferred
Glycosylationi222 – 2221N-linked (GlcNAc...)1 Publication
Disulfide bondi227 ↔ 2431 Publication
Disulfide bondi240 ↔ 2471 Publication
Glycosylationi452 – 4521N-linked (GlcNAc...) Reviewed prediction
Glycosylationi459 – 4591N-linked (GlcNAc...) Reviewed prediction
Glycosylationi478 – 4781N-linked (GlcNAc...) Reviewed prediction
Glycosylationi524 – 5241N-linked (GlcNAc...)1 Publication
Glycosylationi961 – 9611N-linked (GlcNAc...) Reviewed prediction
Glycosylationi968 – 9681N-linked (GlcNAc...) Reviewed prediction
Glycosylationi1064 – 10641N-linked (GlcNAc...) Reviewed prediction
Glycosylationi1072 – 10721N-linked (GlcNAc...) Reviewed prediction

Post-translational modificationi

Glycosylated.2 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiO15118.
PaxDbiO15118.
PeptideAtlasiO15118.
PRIDEiO15118.

PTM databases

PhosphoSiteiO15118.

Expressioni

Gene expression databases

ArrayExpressiO15118.
BgeeiO15118.
CleanExiHS_NPC1.
GenevestigatoriO15118.

Organism-specific databases

HPAiHPA026618.

Interactioni

Subunit structurei

Interacts with TMEM97. Interacts (via the second lumenal domain) with NPC2 in a cholestrol-dependent manner By similarity.1 Publication

Protein-protein interaction databases

BioGridi110925. 10 interactions.
IntActiO15118. 4 interactions.
STRINGi9606.ENSP00000269228.

Structurei

Secondary structure

1
1278
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi26 – 3510
Beta strandi38 – 436
Helixi53 – 553
Helixi56 – 627
Helixi64 – 663
Beta strandi72 – 743
Helixi77 – 859
Helixi88 – 947
Helixi98 – 11316
Helixi117 – 1204
Beta strandi121 – 13010
Turni132 – 1343
Beta strandi137 – 14812
Helixi150 – 16011
Beta strandi168 – 1714
Helixi173 – 1764
Beta strandi177 – 1793
Turni181 – 1833
Helixi186 – 1938
Helixi196 – 1983
Beta strandi199 – 20911
Helixi240 – 2423
Helixi244 – 2463

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3GKHX-ray1.81A23-252[»]
3GKIX-ray1.80A23-252[»]
3GKJX-ray1.60A23-252[»]
ProteinModelPortaliO15118.
SMRiO15118. Positions 23-247.

Miscellaneous databases

EvolutionaryTraceiO15118.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini620 – 785166SSDAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni175 – 20531Important for cholesterol binding and cholesterol transfer from NPC1 to liposomesAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi1275 – 12784Di-leucine motif

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi249 – 25911Poly-ProAdd
BLAST

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.

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG149152.
HOVERGENiHBG003913.
InParanoidiO15118.
KOiK12385.
OMAiDNITETM.
OrthoDBiEOG7QRQT0.
PhylomeDBiO15118.
TreeFamiTF300416.

Family and domain databases

InterProiIPR004765. NP_C_type.
IPR003392. Patched.
IPR000731. SSD.
[Graphical view]
PfamiPF02460. Patched. 1 hit.
[Graphical view]
TIGRFAMsiTIGR00917. 2A060601. 1 hit.
PROSITEiPS50156. SSD. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

O15118-1 [UniParc]FASTAAdd to Basket

« Hide

MTARGLALGL LLLLLCPAQV FSQSCVWYGE CGIAYGDKRY NCEYSGPPKP     50
LPKDGYDLVQ ELCPGFFFGN VSLCCDVRQL QTLKDNLQLP LQFLSRCPSC 100
FYNLLNLFCE LTCSPRQSQF LNVTATEDYV DPVTNQTKTN VKELQYYVGQ 150
SFANAMYNAC RDVEAPSSND KALGLLCGKD ADACNATNWI EYMFNKDNGQ 200
APFTITPVFS DFPVHGMEPM NNATKGCDES VDEVTAPCSC QDCSIVCGPK 250
PQPPPPPAPW TILGLDAMYV IMWITYMAFL LVFFGAFFAV WCYRKRYFVS 300
EYTPIDSNIA FSVNASDKGE ASCCDPVSAA FEGCLRRLFT RWGSFCVRNP 350
GCVIFFSLVF ITACSSGLVF VRVTTNPVDL WSAPSSQARL EKEYFDQHFG 400
PFFRTEQLII RAPLTDKHIY QPYPSGADVP FGPPLDIQIL HQVLDLQIAI 450
ENITASYDNE TVTLQDICLA PLSPYNTNCT ILSVLNYFQN SHSVLDHKKG 500
DDFFVYADYH THFLYCVRAP ASLNDTSLLH DPCLGTFGGP VFPWLVLGGY 550
DDQNYNNATA LVITFPVNNY YNDTEKLQRA QAWEKEFINF VKNYKNPNLT 600
ISFTAERSIE DELNRESDSD VFTVVISYAI MFLYISLALG HMKSCRRLLV 650
DSKVSLGIAG ILIVLSSVAC SLGVFSYIGL PLTLIVIEVI PFLVLAVGVD 700
NIFILVQAYQ RDERLQGETL DQQLGRVLGE VAPSMFLSSF SETVAFFLGA 750
LSVMPAVHTF SLFAGLAVFI DFLLQITCFV SLLGLDIKRQ EKNRLDIFCC 800
VRGAEDGTSV QASESCLFRF FKNSYSPLLL KDWMRPIVIA IFVGVLSFSI 850
AVLNKVDIGL DQSLSMPDDS YMVDYFKSIS QYLHAGPPVY FVLEEGHDYT 900
SSKGQNMVCG GMGCNNDSLV QQIFNAAQLD NYTRIGFAPS SWIDDYFDWV 950
KPQSSCCRVD NITDQFCNAS VVDPACVRCR PLTPEGKQRP QGGDFMRFLP 1000
MFLSDNPNPK CGKGGHAAYS SAVNILLGHG TRVGATYFMT YHTVLQTSAD 1050
FIDALKKARL IASNVTETMG INGSAYRVFP YSVFYVFYEQ YLTIIDDTIF 1100
NLGVSLGAIF LVTMVLLGCE LWSAVIMCAT IAMVLVNMFG VMWLWGISLN 1150
AVSLVNLVMS CGISVEFCSH ITRAFTVSMK GSRVERAEEA LAHMGSSVFS 1200
GITLTKFGGI VVLAFAKSQI FQIFYFRMYL AMVLLGATHG LIFLPVLLSY 1250
IGPSVNKAKS CATEERYKGT ERERLLNF 1278
Length:1,278
Mass (Da):142,167
Last modified:May 10, 2005 - v2
Checksum:iDA1523E09822E5C7
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti63 – 631C → R in NPC1. 1 Publication
VAR_043172
Natural varianti74 – 741C → Y in NPC1. 1 Publication
VAR_043173
Natural varianti92 – 921Q → R in NPC1. 2 Publications
VAR_043174
Natural varianti113 – 1131C → 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 Publication
VAR_043175
Natural varianti137 – 1371T → M in NPC1. 3 Publications
VAR_043176
Natural varianti151 – 1511S → G.1 Publication
Corresponds to variant rs17855819 [ dbSNP | Ensembl ].
VAR_043177
Natural varianti166 – 1661P → S in NPC1. 2 Publications
VAR_043178
Natural varianti177 – 1771C → G in NPC1; late infantile form. 1 Publication
VAR_008815
Natural varianti177 – 1771C → Y in NPC1. 3 Publications
VAR_015561
Natural varianti215 – 2151H → R Common polymorphism in Japanese. 7 Publications
Corresponds to variant rs1805081 [ dbSNP | Ensembl ].
VAR_008816
Natural varianti222 – 2221N → S in NPC1. 1 Publication
Corresponds to variant rs55680026 [ dbSNP | Ensembl ].
VAR_043179
Natural varianti231 – 2311V → G in NPC1. 1 Publication
VAR_043180
Natural varianti237 – 2371P → S in NPC1; late infantile form. 5 Publications
Corresponds to variant rs80358251 [ dbSNP | Ensembl ].
VAR_008817
Natural varianti242 – 2421D → H in NPC1. 1 Publication
VAR_043181
Natural varianti242 – 2421D → N in NPC1. 1 Publication
VAR_043182
Natural varianti247 – 2471C → Y in NPC1. 1 Publication
VAR_043183
Natural varianti248 – 2481G → V in NPC1. 1 Publication
VAR_043184
Natural varianti272 – 2721M → R in NPC1. 1 Publication
VAR_043185
Natural varianti273 – 2731W → S Colocalizes with the wild-type protein with Rab7-positive late endosomes; clears the lysosomal cholesterol accumulation in NPC1-deficient cells. 1 Publication
VAR_043186
Natural varianti333 – 3331G → D.
VAR_008818
Natural varianti372 – 3721R → W in NPC1. 1 Publication
VAR_043187
Natural varianti378 – 3781V → A in NPC1. 1 Publication