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Protein Page:
NPC1 (human)
p Phosphorylation
ac Acetylation
me Methylation
m1 Mono-methylation
m2 Di-methylation
m3 Tri-methylation
ub Ubiquitylation
sm Sumoylation
ne Neddylation
gl O-GlcNAc
ga O-GalNAc
pa Palmitoylation
ad Adenylation
sn S-Nitrosylation
ca Caspase cleavage
sc Succinylation

Overview
NPC1 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. Defects in NPC1 are the cause of Niemann-Pick disease type C1 (NPC1). 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. Belongs to the patched family. Note: This description may include information from UniProtKB.
Protein type: Membrane protein, integral; Membrane protein, multi-pass
Chromosomal Location of Human Ortholog: 18q11.2
Cellular Component: endoplasmic reticulum; extracellular region; Golgi apparatus; integral to membrane; integral to plasma membrane; late endosome membrane; lipid raft; lysosomal membrane; lysosome; membrane; nuclear envelope; perinuclear region of cytoplasm
Molecular Function: cholesterol binding; hedgehog receptor activity; protein binding; receptor activity; sterol transporter activity; transmembrane receptor activity; viral receptor activity
Biological Process: adult walking behavior; autophagy; bile acid metabolic process; cholesterol efflux; cholesterol homeostasis; cholesterol metabolic process; cholesterol transport; endocytosis; entry of virus into host cell; lipid raft organization and biogenesis; lysosomal transport; negative regulation of macroautophagy; protein amino acid glycosylation; response to cadmium ion; response to drug; signal transduction
Disease: Niemann-pick Disease, Type C1
Reference #:  O15118 (UniProtKB)
Gene Symbols: NPC1
Molecular weight: 142,167 Da
Basal Isoelectric point: 5.17  Predict pI for various phosphorylation states
Select Structure to View Below

NPC1

Protein Structure Not Found.
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Modification Sites and Domains Show Modification Legend
Click here to view phosphorylation modifications only

Modification Sites in Parent Protein, Orthologs, and Isoforms Show Modification Legend
 

Show Multiple Sequence Alignment


 LTP 

LTP: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.


 HTP 

HTP: The number of records in which this modification site was assigned using ONLY proteomic discovery-mode mass spectrometry.


       human

 
0 2 K84‑ub VRQLQTLkDNLQLPL
0 1 S95‑p QLPLQFLsRCPSCFY
0 1 Y297 VWCYRKRYFVSEyTP
0 1 Y302‑p KRYFVSEyTPIDSNI
0 1 S307 SEyTPIDSNIAFSVN
0 1 R341 CLRRLFTRWGSFCVR
0 1 S382‑p TNPVDLWsAPssQAR
0 1 S385‑p VDLWsAPssQARLEk
0 1 S386‑p DLWsAPssQARLEkE
0 1 K392‑ub ssQARLEkEyFDQHF
0 1 Y394‑p QARLEkEyFDQHFGP
0 2 K585‑ub QRAQAWEkEFINFVK
0 1 K822‑ub SCLFRFFkNSYsPLL
0 1 S826‑p RFFkNSYsPLLLKDW
0 2 K903‑ac GHDYTSSkGQNMVCG
0 6 K1180‑ub RAFTVSMkGSRVERA
0 1 T1270‑p TEERYKGtERERLLN
  mouse

 
K84 IQQLQTLKSNLQLPL
S95 QLPLQFLSRCPSCFY
Y297‑p VWCHRRRyFVSEYTP
Y302 RRyFVSEYTPIDsNI
S307‑p SEYTPIDsNIAFSVN
K341‑ac CLRRMFTkWGAFCVR
S382 TNPVELWSAPHSQAR
H385 VELWSAPHSQARLEK
S386 ELWSAPHSQARLEKE
K392 HSQARLEKEYFDKHF
Y394 QARLEKEYFDKHFGP
K585 QRAWAWEKEFISFVK
K822 SYLFRFFKNYFAPLL
A826 RFFKNYFAPLLLKDW
K903 GYNYSSRKGQNMVCG
K1179‑ub RAFTMSTkGSRVSRA
T1269 TYERYRGTERERLLN
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