Npc1
entrez
18145
canonical
uniprot
O35604
canonical
ensembl
ENSMUSG00000024413
resolver
ensp
ENSMUSP00000025279
resolver
ensp
ENSMUSP00000175461
resolver
enst
ENSMUST00000025279
resolver
genesymbol
Npc1
resolver
uniprot
G3X8W9
resolver
uniprot
O35605
resolver
uniprot
Q7TMD4
resolver
uniprot_entry
NPC1_MOUSE
resolver
uniprot_entry
Q7TMD4_MOUSE
resolver
uniprot_sec
G3X8W9
resolver
uniprot_sec
O35605
resolver
amino_acid_sequence
MGAHHPALGLLLLLLCPAQVFSQSCVWYGECGIATGDKRYNCKYSGPPKPLPKDGYDLVQELCPGLFFDNVSLCCDIQQLQTLKSNLQLPLQFLSRCPSCFYNLMTLFCELTCSPHQSQFLNVTATEDYFDPKTQENKTNVKELEYFVGQSFANAMYNACRDVEAPSSNEKALGLLCGRDARACNATNWIEYMFNKDNGQAPFTIIPVFSDLSILGMEPMRNATKGCNESVDEVTGPCSCQDCSIVCGPKPQPPPPPMPWRIWGLDAMYVIMWVTYVAFLFVFFGALLAVWCHRRRYFVSEYTPIDSNIAFSVNSSDKGEASCCDPLGAAFDDCLRRMFTKWGAFCVRNPTCIIFFSLAFITVCSSGLVFVQVTTNPVELWSAPHSQARLEKEYFDKHFGPFFRTEQLIIQAPNTSVHIYEPYPAGADVPFGPPLNKEILHQVLDLQIAIESITASYNNETVTLQDICVAPLSPYNKNCTIMSVLNYFQNSHAVLDSQVGDDFYIYADYHTHFLYCVRAPASLNDTSLLHGPCLGTFGGPVFPWLVLGGYDDQNYNNATALVITFPVNNYYNDTERLQRAWAWEKEFISFVKNYKNPNLTISFTAERSIEDELNRESNSDVFTVIISYVVMFLYISLALGHIQSCSRLLVDSKISLGIAGILIVLSSVACSLGIFSYMGMPLTLIVIEVIPFLVLAVGVDNIFILVQTYQRDERLQEETLDQQLGRILGEVAPTMFLSSFSETSAFFFGALSSMPAVHTFSLFAGMAVLIDFLLQITCFVSLLGLDIKRQEKNHLDILCCVRGADDGQGSHASESYLFRFFKNYFAPLLLKDWLRPIVVAVFVGVLSFSVAVVNKVDIGLDQSLSMPNDSYVIDYFKSLAQYLHSGPPVYFVLEEGYNYSSRKGQNMVCGGMGCDNDSLVQQIFNAAELDTYTRVGFAPSSWIDDYFDWVSPQSSCCRLYNVTHQFCNASVMDPTCVRCRPLTPEGKQRPQGKEFMKFLPMFLSDNPNPKCGKGGHAAYGSAVNIVGDDTYIGATYFMTYHTILKTSADYTDAMKKARLIASNITETMRSKGSDYRVFPYSVFYVFYEQYLTIIDDTIFNLSVSLGSIFLVTLVVLGCELWSAVIMCITIAMILVNMFGVMWLWGISLNAVSLVNLVMSCGISVEFCSHITRAFTMSTKGSRVSRAEEALAHMGSSVFSGITLTKFGGIVVLAFAKSQIFEIFYFRMYLAMVLLGATHGLIFLPVLLSYIGPSVNKAKRHTTYERYRGTERERLLNF
uniprot
proteins
disease_involvement
DISEASE: Note=Defects in Npc1 cause a lysosomal storage disorder characterized by accumulation of cholesterol in lysosomes and impaired cholesterol homeostasis. Causes age-dependent loss of Purkinje cells, loss of body weight and leads then to ataxia and premature death at a median age of 72 days. {ECO:0000269|PubMed:22048958, ECO:0000269|PubMed:9211850}.
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:21896731, PubMed:22048958, PubMed:27551080). 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. Cholesterol binds to NPC1 with the hydroxyl group buried in the binding pocket (By similarity). 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 (By similarity). 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 (By similarity). {ECO:0000250|UniProtKB:O15118, ECO:0000269|PubMed:21896731, ECO:0000269|PubMed:22048958, ECO:0000269|PubMed:27551080, ECO:0000305}.
uniprot
proteins
mass_dalton
142885
uniprot
proteins
mutagenesis
MUTAGEN 202..203; /note="PF->AA: Loss of function giving rise to cholesterol accumulation in kidney, liver, lung and spleen. No effect on lysosomal location. Mice display age-dependent weight loss, neurodegeneration with loss of Purkinje cells, ataxia and premature death at a median age of 84 days."; /evidence="ECO:0000269|PubMed:21896731"; MUTAGEN 378; /note="V->A: No effect on affinity for NPC2."; /evidence="ECO:0000269|PubMed:22065762"; MUTAGEN 404; /note="R->Q: Decreased affinity for NPC2."; /evidence="ECO:0000269|PubMed:22065762"; MUTAGEN 421; /note="E->A: Strongly decreased affinity for NPC2; when associated with 503-A-A-504."; /evidence="ECO:0000269|PubMed:27551080"; MUTAGEN 502..504; /note="DFY->AAA: Strongly decreased affinity for NPC2."; /evidence="ECO:0000269|PubMed:27551080"; MUTAGEN 503..504; /note="FY->AA: Decreased affinity for NPC2. Loss of function in cholesterol transport. No effect on subcellular location. Strongly decreased affinity for NPC2; when associated with A-421."; /evidence="ECO:0000269|PubMed:27551080"; MUTAGEN 518; /note="R->Q: Strongly decreased affinity for NPC2. No effect on lysosomal location."; /evidence="ECO:0000269|PubMed:22065762"; MUTAGEN 1005; /note="D->G: In Npc1-nmf164; strongly decreased protein levels. Causes abnormal lipid storage in the spleen and liver, loss of cerebellar Purkinje cells and age-dependent ataxia."; /evidence="ECO:0000269|PubMed:22048958
uniprot
proteins
post_translational_modification
PTM: N-glycosylated. {ECO:0000269|PubMed:21896731, ECO:0000269|PubMed:22065762}.
uniprot
proteins
protein_family
Patched family
uniprot
proteins
pubmed
16340014
uniprot
proteins
pubmed
19468303
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
21412152
uniprot
proteins
pubmed
21896731
uniprot
proteins
pubmed
22048958
uniprot
proteins
pubmed
22065762
uniprot
proteins
pubmed
27551080
uniprot
proteins
pubmed
9211850
uniprot
proteins
sequence_length
1277
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Late endosome membrane {ECO:0000250|UniProtKB:O15118}; Multi-pass membrane protein {ECO:0000250|UniProtKB:O15118}. Lysosome membrane {ECO:0000269|PubMed:21896731, ECO:0000269|PubMed:22065762, ECO:0000269|PubMed:27551080}; Multi-pass membrane protein {ECO:0000250|UniProtKB:O15118}.
uniprot
proteins
transmembrane_region
TRANSMEM 270..290; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 351..371; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 622..642; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 654..674; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 684..704; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 731..751; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 760..780; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 833..853; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 1098..1118; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 1124..1144; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 1146..1166; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 1195..1215; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 1227..1247; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins