NPC1
entrez
4864
canonical
uniprot
O15118
canonical
ensembl
ENSG00000141458
resolver
ensp
ENSP00000269228
resolver
ensp
ENSP00000567585
resolver
ensp
ENSP00000780034
resolver
ensp
ENSP00000780035
resolver
genesymbol
NPC1
resolver
hgnc
HGNC:7897
resolver
uniprot
B4DET3
resolver
uniprot
Q9P130
resolver
uniprot_entry
NPC1_HUMAN
resolver
uniprot_sec
B4DET3
resolver
uniprot_sec
Q9P130
resolver
amino_acid_sequence
MTARGLALGLLLLLLCPAQVFSQSCVWYGECGIAYGDKRYNCEYSGPPKPLPKDGYDLVQELCPGFFFGNVSLCCDVRQLQTLKDNLQLPLQFLSRCPSCFYNLLNLFCELTCSPRQSQFLNVTATEDYVDPVTNQTKTNVKELQYYVGQSFANAMYNACRDVEAPSSNDKALGLLCGKDADACNATNWIEYMFNKDNGQAPFTITPVFSDFPVHGMEPMNNATKGCDESVDEVTAPCSCQDCSIVCGPKPQPPPPPAPWTILGLDAMYVIMWITYMAFLLVFFGAFFAVWCYRKRYFVSEYTPIDSNIAFSVNASDKGEASCCDPVSAAFEGCLRRLFTRWGSFCVRNPGCVIFFSLVFITACSSGLVFVRVTTNPVDLWSAPSSQARLEKEYFDQHFGPFFRTEQLIIRAPLTDKHIYQPYPSGADVPFGPPLDIQILHQVLDLQIAIENITASYDNETVTLQDICLAPLSPYNTNCTILSVLNYFQNSHSVLDHKKGDDFFVYADYHTHFLYCVRAPASLNDTSLLHDPCLGTFGGPVFPWLVLGGYDDQNYNNATALVITFPVNNYYNDTEKLQRAQAWEKEFINFVKNYKNPNLTISFTAERSIEDELNRESDSDVFTVVISYAIMFLYISLALGHMKSCRRLLVDSKVSLGIAGILIVLSSVACSLGVFSYIGLPLTLIVIEVIPFLVLAVGVDNIFILVQAYQRDERLQGETLDQQLGRVLGEVAPSMFLSSFSETVAFFLGALSVMPAVHTFSLFAGLAVFIDFLLQITCFVSLLGLDIKRQEKNRLDIFCCVRGAEDGTSVQASESCLFRFFKNSYSPLLLKDWMRPIVIAIFVGVLSFSIAVLNKVDIGLDQSLSMPDDSYMVDYFKSISQYLHAGPPVYFVLEEGHDYTSSKGQNMVCGGMGCNNDSLVQQIFNAAQLDNYTRIGFAPSSWIDDYFDWVKPQSSCCRVDNITDQFCNASVVDPACVRCRPLTPEGKQRPQGGDFMRFLPMFLSDNPNPKCGKGGHAAYSSAVNILLGHGTRVGATYFMTYHTVLQTSADFIDALKKARLIASNVTETMGINGSAYRVFPYSVFYVFYEQYLTIIDDTIFNLGVSLGAIFLVTMVLLGCELWSAVIMCATIAMVLVNMFGVMWLWGISLNAVSLVNLVMSCGISVEFCSHITRAFTVSMKGSRVERAEEALAHMGSSVFSGITLTKFGGIVVLAFAKSQIFQIFYFRMYLAMVLLGATHGLIFLPVLLSYIGPSVNKAKSCATEERYKGTERERLLNF
uniprot
proteins
disease_involvement
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. {ECO:0000269|PubMed:10480349, ECO:0000269|PubMed:10521290, ECO:0000269|PubMed:10521297, ECO:0000269|PubMed:11182931, ECO:0000269|PubMed:11333381, ECO:0000269|PubMed:11349231, ECO:0000269|PubMed:11479732, ECO:0000269|PubMed:11545687, ECO:0000269|PubMed:11754101, ECO:0000269|PubMed:12401890, ECO:0000269|PubMed:12408188, ECO:0000269|PubMed:12554680, ECO:0000269|PubMed:12955717, ECO:0000269|PubMed:15774455, ECO:0000269|PubMed:16098014, ECO:0000269|PubMed:16126423, ECO:0000269|PubMed:16802107, ECO:0000269|PubMed:27238017, ECO:0000269|PubMed:9211849, ECO:0000269|PubMed:9634529}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
function
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 (PubMed:10821832, PubMed:12554680, PubMed:18772377, PubMed:27238017, PubMed:9211849, PubMed:9927649). Unesterified cholesterol that has been released from LDLs in the lumen of the late endosomes/lysosomes is transferred by NPC2 to the cholesterol-binding pocket in the N-terminal domain of NPC1 (PubMed:18772377, PubMed:19563754, PubMed:27238017, PubMed:27378690, PubMed:28784760, PubMed:9211849, PubMed:9927649). Cholesterol binds to NPC1 with the hydroxyl group buried in the binding pocket (PubMed:19563754). Mediates cholesterol transfer from lysosomes to endoplasmic reticulum by tethering endosomal/lysosomal compartments and endoplasmic reticulum membrane contact sites where it interacts with sterol transport protein GRAMD1B (PubMed:31537798). 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 (Probable). Inhibits cholesterol-mediated mTORC1 activation throught its interaction with SLC38A9 (PubMed:28336668). {ECO:0000269|PubMed:10821832, ECO:0000269|PubMed:12554680, ECO:0000269|PubMed:18772377, ECO:0000269|PubMed:19563754, ECO:0000269|PubMed:27238017, ECO:0000269|PubMed:27378690, ECO:0000269|PubMed:28336668, ECO:0000269|PubMed:28784760, ECO:0000269|PubMed:31537798, ECO:0000269|PubMed:9211849, ECO:0000269|PubMed:9927649, ECO:0000305}.; FUNCTION: (Microbial infection) Acts as an endosomal entry receptor for ebolavirus. {ECO:0000269|PubMed:21866103, ECO:0000269|PubMed:25855742, ECO:0000269|PubMed:32855215}.
uniprot
proteins
mass_dalton
142167
uniprot
proteins
mutagenesis
MUTAGEN 25..257; /note="Missing: Decreases affinity for NPC2. Abolishes cholesterol transfer from NPC2 to NPC1."; /evidence="ECO:0000269|PubMed:27238017"; MUTAGEN 26..27; /note="VW->AA: Nearly abolishes 25-hydroxycholesterol binding. Reduces cholesterol binding."; /evidence="ECO:0000269|PubMed:19563754"; MUTAGEN 39..41; /note="RYN->AAA: Strongly reduces cholesterol and 25-hydroxycholesterol binding."; /evidence="ECO:0000269|PubMed:19563754"; MUTAGEN 41; /note="N->A: Nearly abolishes cholesterol and 25-hydroxycholesterol binding."; /evidence="ECO:0000269|PubMed:19563754"; MUTAGEN 63; /note="C->S: Loss of function."; /evidence="ECO:0000269|PubMed:9927649"; MUTAGEN 70; /note="N->Q: Reduces glycosylation; when associated with Q-122 and Q-185. No effect on cholesterol and 25-hydroxycholesterol binding."; /evidence="ECO:0000269|PubMed:19563754"; MUTAGEN 74..75; /note="CC->SS: Loss of function."; /evidence="ECO:0000269|PubMed:9927649"; MUTAGEN 82..83; /note="TL->AA: Strongly reduces cholesterol and 25-hydroxycholesterol binding."; /evidence="ECO:0000269|PubMed:19563754"; MUTAGEN 88; /note="Q->A: Decreased affinity for NPC2 and decreased cholesterol transfer from NPC2 to NPC1; when associated with A-92 and A-96."; /evidence="ECO:0000269|PubMed:27238017"; MUTAGEN 92; /note="Q->A: Decreased affinity for NPC2 and decreased cholesterol transfer from NPC2 to NPC1; when associated with A-88 and A-96."; /evidence="ECO:0000269|PubMed:27238017"; MUTAGEN 96; /note="R->A: Decreased affinity for NPC2 and decreased cholesterol transfer from NPC2 to NPC1; when associated with A-88 and A-92."; /evidence="ECO:0000269|PubMed:27238017"; MUTAGEN 97; /note="C->S: Loss of function."; /evidence="ECO:0000269|PubMed:9927649"; MUTAGEN 101..102; /note="FY->AA: Strongly reduces 25-hydroxycholesterol binding. No effect on cholesterol binding."; /evidence="ECO:0000269|PubMed:19563754"; MUTAGEN 106..108; /note="NLF->AAA: Nearly abolishes cholesterol and 25-hydroxycholesterol binding."; /evidence="ECO:0000269|PubMed:19563754"; MUTAGEN 110..112; /note="ELT->AAA: No effect on cholesterol and 25-hydroxycholesterol binding and transfer."; /evidence="ECO:0000269|PubMed:19563754"; MUTAGEN 122; /note="N->Q: Reduces glycosylation; when associated with Q-70 and Q-185. No effect on cholesterol and 25-hydroxycholesterol binding."; /evidence="ECO:0000269|PubMed:19563754"; MUTAGEN 144..145; /note="LQ->AA: Strongly reduces 25-hydroxycholesterol binding. No effect on cholesterol binding."; /evidence="ECO:0000269|PubMed:19563754"; MUTAGEN 146..147; /note="YY->AA: Strongly reduces 25-hydroxycholesterol binding. No effect on cholesterol binding."; /evidence="ECO:0000269|PubMed:19563754"; MUTAGEN 175..176; /note="LL->AA: No effect on cholesterol or 25-hydroxycholesterol binding. Decreases affinity for NPC2. Strongly reduces cholesterol transfer to liposomes in a NPC2-dependent manner."; /evidence="ECO:0000269|PubMed:19563754, ECO:0000269|PubMed:27238017"; MUTAGEN 180..182; /note="DAD->AAA: Strongly reduces cholesterol transfer to liposomes in a NPC2-dependent manner."; /evidence="ECO:0000269|PubMed:19563754"; MUTAGEN 185; /note="N->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."; /evidence="ECO:0000269|PubMed:19563754"; MUTAGEN 187..188; /note="TN->AA: Strongly reduces 25-hydroxycholesterol binding and cholesterol transfer to liposomes in a NPC2-dependent manner."; /evidence="ECO:0000269|PubMed:19563754"; MUTAGEN 191..192; /note="EY->AA: No effect on cholesterol or 25-hydroxycholesterol binding. Nearly abolishes cholesterol transfer to liposomes in a NPC2-dependent manner."; /evidence="ECO:0000269|PubMed:19563754"; MUTAGEN 195..196; /note="NK->AA: Strongly reduces 25-hydroxycholesterol binding. No effect on cholesterol binding."; /evidence="ECO:0000269|PubMed:19563754"; MUTAGEN 197..198; /note="DN->AA: Strongly reduces cholesterol and 25-hydroxycholesterol binding."; /evidence="ECO:0000269|PubMed:19563754"; MUTAGEN 199..200; /note="GQ->AA: Strongly reduces 25-hydroxycholesterol binding and cholesterol transfer to liposomes in a NPC2-dependent manner."; /evidence="ECO:0000269|PubMed:19563754"; MUTAGEN 202..203; /note="PF->AA: Abolishes cholesterol and 25-hydroxycholesterol binding. Abolishes cholesterol transfer from NPC2 to NPC1."; /evidence="ECO:0000269|PubMed:19563754, ECO:0000269|PubMed:27238017"; MUTAGEN 204..205; /note="TI->AA: Strongly reduces cholesterol and 25-hydroxycholesterol binding."; /evidence="ECO:0000269|PubMed:19563754"; MUTAGEN 230..234; /note="Missing: Decreased cholesterol transport."; /evidence="ECO:0000269|PubMed:28784760"; MUTAGEN 249..257; /note="Missing: Decreases affinity for NPC2. Abolishes cholesterol transfer from NPC2 to NPC1."; /evidence="ECO:0000269|PubMed:27238017"; MUTAGEN 423..424; /note="YP->GG: Strongly reduces interaction with ebolavirus glycoprotein."; /evidence="ECO:0000269|PubMed:26771495"; MUTAGEN 503; /note="F->A,G: Loss of interaction with ebolavirus glycoprotein."; /evidence="ECO:0000269|PubMed:26771495"; MUTAGEN 504; /note="F->A,G: Loss of interaction with ebolavirus glycoprotein."; /evidence="ECO:0000269|PubMed:26771495"; MUTAGEN 506; /note="Y->A: Loss of interaction with ebolavirus glycoprotein."; /evidence="ECO:0000269|PubMed:26771495"; MUTAGEN 660; /note="G->R: Loss of function."; /evidence="ECO:0000269|PubMed:19563754"; MUTAGEN 691; /note="P->S: Abolishes cholesterol transport. No effect on subcellular location."; /evidence="ECO:0000269|PubMed:28784760"; MUTAGEN 909..917; /note="CGGMGCNND->A: Abolishes cholesterol transport. No effect on subcellular location."; /evidence="ECO:0000269|PubMed:28784760"; MUTAGEN 1275..1278; /note="Missing: Loss of location in lysosomes."; /evidence="ECO:0000269|PubMed:9927649
uniprot
proteins
post_translational_modification
PTM: N-glycosylated. {ECO:0000269|PubMed:10821832, ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:19563754}.
uniprot
proteins
protein_family
Patched family
uniprot
proteins
pubmed
10425213
uniprot
proteins
pubmed
10480349
uniprot
proteins
pubmed
10521290
uniprot
proteins
pubmed
10521297
uniprot
proteins
pubmed
10821832
uniprot
proteins
pubmed
11182931
uniprot
proteins
pubmed
11333381
uniprot
proteins
pubmed
11349231
uniprot
proteins
pubmed
11479732
uniprot
proteins
pubmed
11545687
uniprot
proteins
pubmed
11754101
uniprot
proteins
pubmed
12401890
uniprot
proteins
pubmed
12408188
uniprot
proteins
pubmed
12554680
uniprot
proteins
pubmed
12955717
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15774455
uniprot
proteins
pubmed
16098014
uniprot
proteins
pubmed
16126423
uniprot
proteins
pubmed
16177791
uniprot
proteins
pubmed
16802107
uniprot
proteins
pubmed
17897319
uniprot
proteins
pubmed
18772377
uniprot
proteins
pubmed
18832164
uniprot
proteins
pubmed
19159218
uniprot
proteins
pubmed
19563754
uniprot
proteins
pubmed
19583955
uniprot
proteins
pubmed
20674853
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21412152
uniprot
proteins
pubmed
21866103
uniprot
proteins
pubmed
23453666
uniprot
proteins
pubmed
25855742
uniprot
proteins
pubmed
25944712
uniprot
proteins
pubmed
26771495
uniprot
proteins
pubmed
26846330
uniprot
proteins
pubmed
27238017
uniprot
proteins
pubmed
27378690
uniprot
proteins
pubmed
27551080
uniprot
proteins
pubmed
28336668
uniprot
proteins
pubmed
28784760
uniprot
proteins
pubmed
31537798
uniprot
proteins
pubmed
32855215
uniprot
proteins
pubmed
34799735
uniprot
proteins
pubmed
9211849
uniprot
proteins
pubmed
9634529
uniprot
proteins
pubmed
9927649
uniprot
proteins
sequence_length
1278
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Late endosome membrane {ECO:0000269|PubMed:12554680, ECO:0000269|PubMed:27378690, ECO:0000269|PubMed:31537798}; Multi-pass membrane protein {ECO:0000269|PubMed:10821832, ECO:0000269|PubMed:27238017, ECO:0000269|PubMed:28784760}. Lysosome membrane {ECO:0000269|PubMed:17897319, ECO:0000269|PubMed:27378690, ECO:0000269|PubMed:31537798, ECO:0000269|PubMed:9927649}; Multi-pass membrane protein {ECO:0000269|PubMed:10821832, ECO:0000269|PubMed:27238017, ECO:0000269|PubMed:28784760}.
uniprot
proteins
transmembrane_region
TRANSMEM 262..282; /note="Helical"; /evidence="ECO:0000269|PubMed:27238017"; TRANSMEM 351..371; /note="Helical"; /evidence="ECO:0000269|PubMed:27238017, ECO:0000269|PubMed:28784760"; TRANSMEM 621..641; /note="Helical"; /evidence="ECO:0000269|PubMed:27238017, ECO:0000269|PubMed:28784760"; TRANSMEM 654..675; /note="Helical"; /evidence="ECO:0000269|PubMed:28784760"; TRANSMEM 686..706; /note="Helical"; /evidence="ECO:0000269|PubMed:28784760"; TRANSMEM 731..751; /note="Helical"; /evidence="ECO:0000269|PubMed:28784760"; TRANSMEM 760..783; /note="Helical"; /evidence="ECO:0000269|PubMed:28784760"; TRANSMEM 833..853; /note="Helical"; /evidence="ECO:0000269|PubMed:28784760"; TRANSMEM 1098..1118; /note="Helical"; /evidence="ECO:0000269|PubMed:28784760"; TRANSMEM 1125..1145; /note="Helical"; /evidence="ECO:0000269|PubMed:28784760"; TRANSMEM 1151..1171; /note="Helical"; /evidence="ECO:0000269|PubMed:28784760"; TRANSMEM 1195..1215; /note="Helical"; /evidence="ECO:0000269|PubMed:28784760"; TRANSMEM 1224..1244; /note="Helical"; /evidence="ECO:0000269|PubMed:28784760
uniprot
proteins