Gene/Proteome Database (LMPD)

LMPD ID
LMP000261
Gene ID
4864
Species
Homo sapiens (Human)
Gene Name
Niemann-Pick disease, type C1
Gene Symbol
NPC1
Synonyms
NPC
Alternate Names
Niemann-Pick C1 protein
Chromosome
18
Map Location
18q11.2
Summary
This gene encodes a large protein that resides in the limiting membrane of endosomes and lysosomes and mediates intracellular cholesterol trafficking via binding of cholesterol to its N-terminal domain. It is predicted to have a cytoplasmic C-terminus, 13 transmembrane domains, and 3 large loops in the lumen of the endosome - the last loop being at the N-terminus. This protein transports low-density lipoproteins to late endosomal/lysosomal compartments where they are hydrolized and released as free cholesterol. Defects in this gene cause Niemann-Pick type C disease, a rare autosomal recessive neurodegenerative disorder characterized by over accumulation of cholesterol and glycosphingolipids in late endosomal/lysosomal compartments.[provided by RefSeq, Aug 2009]
Orthologs
View orthologs and multiple alignments for NPC1

Proteins

Niemann-Pick C1 protein precursor
Refseq ID NP_000262
Protein GI 255652944
UniProt ID O15118
mRNA ID NM_000271
Length 1278
RefSeq Status REVIEWED
MTARGLALGLLLLLLCPAQVFSQSCVWYGECGIAYGDKRYNCEYSGPPKPLPKDGYDLVQELCPGFFFGNVSLCCDVRQLQTLKDNLQLPLQFLSRCPSCFYNLLNLFCELTCSPRQSQFLNVTATEDYVDPVTNQTKTNVKELQYYVGQSFANAMYNACRDVEAPSSNDKALGLLCGKDADACNATNWIEYMFNKDNGQAPFTITPVFSDFPVHGMEPMNNATKGCDESVDEVTAPCSCQDCSIVCGPKPQPPPPPAPWTILGLDAMYVIMWITYMAFLLVFFGAFFAVWCYRKRYFVSEYTPIDSNIAFSVNASDKGEASCCDPVSAAFEGCLRRLFTRWGSFCVRNPGCVIFFSLVFITACSSGLVFVRVTTNPVDLWSAPSSQARLEKEYFDQHFGPFFRTEQLIIRAPLTDKHIYQPYPSGADVPFGPPLDIQILHQVLDLQIAIENITASYDNETVTLQDICLAPLSPYNTNCTILSVLNYFQNSHSVLDHKKGDDFFVYADYHTHFLYCVRAPASLNDTSLLHDPCLGTFGGPVFPWLVLGGYDDQNYNNATALVITFPVNNYYNDTEKLQRAQAWEKEFINFVKNYKNPNLTISFTAERSIEDELNRESDSDVFTVVISYAIMFLYISLALGHMKSCRRLLVDSKVSLGIAGILIVLSSVACSLGVFSYIGLPLTLIVIEVIPFLVLAVGVDNIFILVQAYQRDERLQGETLDQQLGRVLGEVAPSMFLSSFSETVAFFLGALSVMPAVHTFSLFAGLAVFIDFLLQITCFVSLLGLDIKRQEKNRLDIFCCVRGAEDGTSVQASESCLFRFFKNSYSPLLLKDWMRPIVIAIFVGVLSFSIAVLNKVDIGLDQSLSMPDDSYMVDYFKSISQYLHAGPPVYFVLEEGHDYTSSKGQNMVCGGMGCNNDSLVQQIFNAAQLDNYTRIGFAPSSWIDDYFDWVKPQSSCCRVDNITDQFCNASVVDPACVRCRPLTPEGKQRPQGGDFMRFLPMFLSDNPNPKCGKGGHAAYSSAVNILLGHGTRVGATYFMTYHTVLQTSADFIDALKKARLIASNVTETMGINGSAYRVFPYSVFYVFYEQYLTIIDDTIFNLGVSLGAIFLVTMVLLGCELWSAVIMCATIAMVLVNMFGVMWLWGISLNAVSLVNLVMSCGISVEFCSHITRAFTVSMKGSRVERAEEALAHMGSSVFSGITLTKFGGIVVLAFAKSQIFQIFYFRMYLAMVLLGATHGLIFLPVLLSYIGPSVNKAKSCATEERYKGTERERLLNF
sig_peptide: 1..22 inference: COORDINATES: ab initio prediction:SignalP:4.0 calculated_mol_wt: 2301 peptide sequence: MTARGLALGLLLLLLCPAQVFS

Gene Information

Entrez Gene ID
4864
Gene Name
Niemann-Pick disease, type C1
Gene Symbol
NPC1
Species
Homo sapiens

Gene Ontology (GO Annotations)

GO ID Source Type Description
GO:0005794 IEA:Ensembl C Golgi apparatus
GO:0005783 IDA:UniProtKB C endoplasmic reticulum
GO:0005768 IEA:UniProtKB-KW C endosome
GO:0005576 ISS:UniProtKB C extracellular region
GO:0070062 IDA:UniProt C extracellular vesicular exosome
GO:0016021 TAS:ProtInc C integral component of membrane
GO:0005887 IDA:UniProtKB C integral component of plasma membrane
GO:0005765 IDA:UniProtKB C lysosomal membrane
GO:0005764 ISS:UniProtKB C lysosome
GO:0016020 IDA:UniProtKB C membrane
GO:0045121 IEA:Ensembl C membrane raft
GO:0005635 IDA:UniProtKB C nuclear envelope
GO:0048471 IDA:UniProtKB C perinuclear region of cytoplasm
GO:0015485 IDA:UniProtKB F cholesterol binding
GO:0008158 IEA:InterPro F hedgehog receptor activity
GO:0004872 TAS:ProtInc F receptor activity
GO:0015248 TAS:ProtInc F sterol transporter activity
GO:0004888 TAS:ProtInc F transmembrane signaling receptor activity
GO:0007628 IEA:Ensembl P adult walking behavior
GO:0006914 IGI:MGI P autophagy
GO:0008206 ISS:UniProtKB P bile acid metabolic process
GO:0071404 IEA:Ensembl P cellular response to low-density lipoprotein particle stimulus
GO:0071383 IEA:Ensembl P cellular response to steroid hormone stimulus
GO:0033344 IDA:BHF-UCL P cholesterol efflux
GO:0042632 IDA:UniProtKB P cholesterol homeostasis
GO:0008203 IEA:UniProtKB-KW P cholesterol metabolic process
GO:0030301 IDA:UniProtKB P cholesterol transport
GO:0006897 IEA:Ensembl P endocytosis
GO:0090150 IDA:UniProt P establishment of protein localization to membrane
GO:0007041 ISS:UniProtKB P lysosomal transport
GO:0031579 IMP:UniProt P membrane raft organization
GO:0060548 IEA:Ensembl P negative regulation of cell death
GO:0016242 IEA:Ensembl P negative regulation of macroautophagy
GO:0006486 IDA:UniProtKB P protein glycosylation
GO:0046686 IEA:Ensembl P response to cadmium ion
GO:0042493 IEA:Ensembl P response to drug
GO:0007165 TAS:GOC P signal transduction

KEGG Pathway Links

KEGG Pathway ID Description
hsa04142 Lysosome
ko04142 Lysosome

Domain Information

InterPro Annotations

Accession Description
IPR004765 Niemann-Pick C type protein
IPR003392 Patched
IPR000731 Sterol-sensing domain

UniProt Annotations

Entry Information

Gene Name
Niemann-Pick disease, type C1
Protein Entry
NPC1_HUMAN
UniProt ID
O15118
Species
Human

Comments

Comment Type Description
Alternative Products Event=Alternative splicing; Named isoforms=2; Name=1; IsoId=O15118-1; Sequence=Displayed; Name=2; IsoId=O15118-2; Sequence=VSP_056431, VSP_056432, VSP_056433; Note=No experimental confirmation available.;
Disease Niemann-Pick disease C1 (NPC1) [MIM
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.
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. {ECO
Ptm Glycosylated. {ECO
Similarity Belongs to the patched family.
Similarity Contains 1 SSD (sterol-sensing) domain.
Subcellular Location Late endosome membrane ; Multi-pass membrane protein . Lysosome membrane ; Multi-pass membrane protein .
Subunit Interacts with TMEM97. Interacts (via the second lumenal domain) with NPC2 in a cholestrol-dependent manner (By similarity).
Web Resource Name=Niemann-Pick type C disease gene variation database; URL="http://npc.fzk.de";

Identical and Related Proteins

Unique RefSeq proteins for LMP000261 (as displayed in Record Overview)

Protein GI Database Accession Length Protein Name
255652944 RefSeq NP_000262 1278 Niemann-Pick C1 protein precursor

Identical Sequences to LMP000261 proteins

Reference Database Accession Length Protein Name
GI:255652944 SwissProt O15118.2 1278 RecName: Full=Niemann-Pick C1 protein; Flags: Precursor [Homo sapiens]

Related Sequences to LMP000261 proteins

Reference Database Accession Length Protein Name
GI:255652944 GenBank AAN25753.1 1278 Sequence 2 from patent US 6426198
GI:255652944 GenBank ABH83290.1 1278 Sequence 2 from patent US 7045675
GI:255652944 GenBank ADA20576.1 1278 Sequence 2400 from patent US 7608413
GI:255652944 GenBank ADA20577.1 1278 Sequence 2401 from patent US 7608413
GI:255652944 GenBank ADA53431.1 1278 Sequence 1261 from patent US 7625699
GI:255652944 GenBank ADS46354.1 1278 Sequence 96 from patent US 7799530