Selected-GenAtlas references	SOURCE	GeneCards	NCBI Gene	Swiss-Prot	Orphanet	Ensembl
	HGNC	UniGene	Nucleotide	OMIM		UCSC

Home Page

FLASH GENE

Symbol

NPC2

contributors: mct/npt/pgu - updated : 11-02-2015

HGNC name	Niemann-Pick disease, type C2
HGNC id	14537

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

EXPRESSION

Type	ubiquitous

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Endocrine pancreas       highly   parathyroid       highly   thyroid       highly reproductive epididymis         Reproductive male system testis     highly Urinary kidney

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