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Protein Page:
NPC1 (human)
p Phosphorylation
ac Acetylation
me Methylation
m1 Mono-methylation
m2 Di-methylation
m3 Tri-methylation
ub Ubiquitination
sm Sumoylation
ne Neddylation
gl O-GlcNAc
ga O-GalNAc
pa Palmitoylation
ad Adenylylation
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
Cellular Component: Golgi apparatus; membrane; late endosome membrane; perinuclear region of cytoplasm; endoplasmic reticulum; lysosomal membrane; lysosome; integral to plasma membrane; extracellular region; integral to membrane; nuclear envelope; lipid raft
Molecular Function: protein binding; transmembrane receptor activity; sterol transporter activity; hedgehog receptor activity; cholesterol binding; receptor activity
Biological Process: response to drug; cholesterol metabolic process; lysosomal transport; cholesterol transport; bile acid metabolic process; protein amino acid glycosylation; endocytosis; cholesterol efflux; signal transduction; adult walking behavior; negative regulation of macroautophagy; cholesterol homeostasis; response to cadmium ion; autophagy; lipid raft organization and biogenesis
Reference #:  O15118 (UniProtKB)
Alt. Names/Synonyms: FLJ98532; Niemann-Pick C1 protein; Niemann-Pick disease, type C1; NPC; NPC1
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


 SS 

SS: 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.


 MS 

MS: 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 Y302-p KRYFVSEyTPIDSNI
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 2 K585-ub QRAQAWEkEFINFVK
0 1 K822-ub SCLFRFFkNSYSPLL
0 2 K903-ac GHDYTSSkGQNMVCG
0 5 K1180-ub RAFTVSMkGSRVERA
0 1 T1270-p TEERYKGtERERLLN
  mouse

 
K84 IQQLQTLKSNLQLPL
S95 QLPLQFLSRCPSCFY
Y302 RRYFVSEYTPIDSNI
K341-ac CLRRMFTkWGAFCVR
S382 TNPVELWSAPHSQAR
H385 VELWSAPHSQARLEK
S386 ELWSAPHSQARLEKE
K392 HSQARLEKEYFDKHF
K585 QRAWAWEKEFISFVK
K822 SYLFRFFKNYFAPLL
K903 GYNYSSRKGQNMVCG
K1179-ub RAFTMSTkGSRVSRA
T1269 TYERYRGTERERLLN
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