Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Basket 0
(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

O15118

- NPC1_HUMAN

UniProt

O15118 - NPC1_HUMAN

Protein

Niemann-Pick C1 protein

Gene

NPC1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
    • BLAST
    • Align
    • Format
    • Add to basket
    • History
      Entry version 141 (01 Oct 2014)
      Sequence version 2 (10 May 2005)
      Previous versions | rss
    • Help video
    • Feedback
    • Comment

    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 – 411Cholesterol1 Publication
    Binding sitei79 – 791Cholesterol1 Publication
    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

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

    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 Source: UniProtKB
    11. membrane raft Source: Ensembl
    12. nuclear envelope Source: UniProtKB
    13. perinuclear region of cytoplasm Source: UniProtKB

    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.19 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    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. 3 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.
    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. 7 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.
    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.
    Mutagenesisi110 – 1123ELT → AAA: No effect on cholesterol and 25-hydroxycholesterol binding and transfer.
    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.
    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 – 2222Sequence AnalysisAdd
    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...)1 Publication
    Disulfide bondi75 ↔ 1131 Publication
    Disulfide bondi97 ↔ 2381 Publication
    Disulfide bondi100 ↔ 1601 Publication
    Glycosylationi122 – 1221N-linked (GlcNAc...)1 Publication
    Glycosylationi135 – 1351N-linked (GlcNAc...)2 Publications
    Glycosylationi158 – 1581N-linked (GlcNAc...); atypical2 Publications
    Disulfide bondi177 ↔ 1841 Publication
    Glycosylationi185 – 1851N-linked (GlcNAc...)1 Publication
    Glycosylationi222 – 2221N-linked (GlcNAc...)2 Publications
    Disulfide bondi227 ↔ 2431 Publication
    Disulfide bondi240 ↔ 2471 Publication
    Glycosylationi452 – 4521N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi459 – 4591N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi478 – 4781N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi524 – 5241N-linked (GlcNAc...)2 Publications
    Glycosylationi961 – 9611N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi968 – 9681N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi1064 – 10641N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi1072 – 10721N-linked (GlcNAc...)Sequence Analysis

    Post-translational modificationi

    Glycosylated.3 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.By similarity

    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.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiO15118.

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini23 – 269247LumenalSequence AnalysisAdd
    BLAST
    Topological domaini291 – 35060CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini372 – 620249LumenalSequence AnalysisAdd
    BLAST
    Topological domaini642 – 65413CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini676 – 6772LumenalSequence Analysis
    Topological domaini699 – 73436CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini756 – 7594LumenalSequence Analysis
    Topological domaini781 – 83252CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini854 – 1098245LumenalSequence AnalysisAdd
    BLAST
    Topological domaini1120 – 11245CytoplasmicSequence Analysis
    Topological domaini1146 – 11461LumenalSequence Analysis
    Topological domaini1168 – 119528CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini1217 – 122711LumenalSequence AnalysisAdd
    BLAST
    Topological domaini1249 – 127830CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei270 – 29021HelicalSequence AnalysisAdd
    BLAST
    Transmembranei351 – 37121HelicalSequence AnalysisAdd
    BLAST
    Transmembranei621 – 64121HelicalSequence AnalysisAdd
    BLAST
    Transmembranei655 – 67521HelicalSequence AnalysisAdd
    BLAST
    Transmembranei678 – 69821HelicalSequence AnalysisAdd
    BLAST
    Transmembranei735 – 75521HelicalSequence AnalysisAdd
    BLAST
    Transmembranei760 – 78021HelicalSequence AnalysisAdd
    BLAST
    Transmembranei833 – 85321HelicalSequence AnalysisAdd
    BLAST
    Transmembranei1099 – 111921HelicalSequence AnalysisAdd
    BLAST
    Transmembranei1125 – 114521HelicalSequence AnalysisAdd
    BLAST
    Transmembranei1147 – 116721HelicalSequence AnalysisAdd
    BLAST
    Transmembranei1196 – 121621HelicalSequence AnalysisAdd
    BLAST
    Transmembranei1228 – 124821HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini620 – 785166SSDPROSITE-ProRule annotationAdd
    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.Curated
    Contains 1 SSD (sterol-sensing) domain.PROSITE-ProRule annotation

    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]

    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. Align

    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

    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
    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)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