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FLASH GENE
Symbol NPC2 contributors: mct/npt/pgu - updated : 11-02-2015
HGNC name Niemann-Pick disease, type C2
HGNC id 14537
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
5 - 921 26 151 - 2008 18823126
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Endocrinepancreas   highly
 parathyroid   highly
 thyroid   highly
reproductiveepididymis    
Reproductivemale systemtestis  highly
Urinarykidney    
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES globular
STRUCTURE
motifs/domains
  • a signal peptide, a 19-amino acid signal that represents a major secretory component of the epididymal fluid
  • three potential glycosylation sites
  • three cysteine-disulfide bonds
  • conjugated GlycoP
    isoforms Precursor
    HOMOLOGY
    interspecies homolog to rattus Npc2 (80.95 pc)
    homolog to murine Npc2 (81.21 pc)
    Homologene
    FAMILY
  • NPC2 family
  • CATEGORY secretory , transport
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,endosome
    intracellular,cytoplasm,organelle,lysosome
    text
  • soluble
  • within late endosomes and lysosomes, NPC1 and NPC2 proteins are required for the subsequent delivery of cholesterol to other intracellular compartments
  • basic FUNCTION
  • potential contributor with NPC1 in transport of cholesterol out the lysosome
  • relevant to cholesterol transport and secretory protein from human epididymis
  • soluble lysosomal glycoprotein that binds cholesterol, an have specialized function in lysosomal sterol transport
  • intralysosomal protein that binds cholesterol
  • plays an important role in endo/lysosomal cholesterol trafficking by markedly accelerating the rates of cholesterol transport
  • might regulate sodium reabsorption in the terminal nephron by interacting with SCNN1A system
  • participates in SCNN1A ubiquitination by binding with the NEDD4L C2 domain
  • required for efficient membrane fission events from nascent hybrid organelles, which is thought to be required for the reformation of lysosomes and the release of lysosomal cargo-containing membrane vesicles
  • with NPC1 can function independently of one another in the egress of certain membrane-impermeable lysosomal cargo
  • role of endosomal membrane lipids and NPC2 in cholesterol transfer and membrane fusion
  • soluble NPC2 and membrane-bound NPC1 are cholesterol-binding lysosomal proteins required for export of lipoprotein-derived cholesterol from lysosomes
  • action for NPC1 and NPC2 in mediating cholesterol efflux
  • by negatively regulating ERK 1/2 MAPK phosphorylation may efficiently suppress development of maladaptive tissue remodeling and inflammation
  • positive regulator of biliary cholesterol secretion via stimulation of ABCG5/ABCG8-mediated cholesterol transport
  • function of NPC1, NPC2 within lysosomes are linked closely
  • thought to play an important role in extracting cholesterol from intralysosomal membranes that are rich in cholesterol and bis(monoacylglycerol) phosphate
  • importance of the interaction between NPC1 and NPC2 proteins to accomplish cholesterol delivery from lysosomes into the cytoplasm
  • NPC2 delivers cholesterol to the perimeter membrane of late endosomes, where it becomes available for transport to mitochondria without requiring NPC1
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS cellular trafficking transport
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • specific interaction with DHDDS
  • is an NUS1-interacting protein
  • interacting with NPC1 (after lysosomal hydrolysis of LDL-cholesteryl esters, cholesterol binds NPC2, which transfers it to NPC1(NTD), reversing its orientation and allowing insertion of its isooctyl side chain into the outer lysosomal membranes)
  • bind C2 domain of NEDD4L
  • NPC2 is a positive regulator of biliary cholesterol secretion via stimulation of ABCG5/G8-mediated cholesterol transport
  • NPC2 binding is necessary for NPC1 function
  • binds cholesterol in an opposite orientation via cholesterol isooctyl side chain
  • interaction of NPC1 and NPC2 proteins appears to be central to the process by which NPC1 facilitates cholesterol egress from endolysosomal compartments
  • NEGR1 interacts with NPC2 and increases its protein stability
  • cell & other
  • cholesterol binding
  • REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) NPC2
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS