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Protein

NPC intracellular cholesterol transporter 2

Gene

Npc2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Intracellular cholesterol transporter which acts in concert with NPC1 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. The secreted form of NCP2 regulates biliary cholesterol secretion via stimulation of ABCG5/ABCG8-mediated cholesterol transport.1 Publication

GO - Molecular functioni

  • cholesterol binding Source: UniProtKB
  • cholesterol transporter activity Source: MGI
  • enzyme binding Source: MGI

GO - Biological processi

  • cholesterol efflux Source: UniProtKB
  • cholesterol homeostasis Source: HGNC
  • cholesterol metabolic process Source: UniProtKB-KW
  • cholesterol transport Source: UniProtKB
  • intracellular cholesterol transport Source: HGNC
  • intracellular sterol transport Source: HGNC
  • response to virus Source: Ensembl

Keywordsi

Biological processCholesterol metabolism, Lipid metabolism, Steroid metabolism, Sterol metabolism

Enzyme and pathway databases

ReactomeiR-MMU-6798695 Neutrophil degranulation
R-MMU-8964038 LDL clearance

Chemistry databases

SwissLipidsiSLP:000000473

Names & Taxonomyi

Protein namesi
Recommended name:
NPC intracellular cholesterol transporter 2Imported
Alternative name(s):
Epididymal secretory protein E1
Short name:
mE1
Niemann Pick type C2 protein homolog
Gene namesi
Name:Npc2Imported
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 12

Organism-specific databases

MGIiMGI:1915213 Npc2

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Endoplasmic reticulum, Lysosome, Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 19Sequence analysisAdd BLAST19
ChainiPRO_000001985620 – 149NPC intracellular cholesterol transporter 2Add BLAST130

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi27 ↔ 140By similarity
Disulfide bondi42 ↔ 47By similarity
Glycosylationi58N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi69N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi93 ↔ 99By similarity
Modified residuei116N6-acetyllysineCombined sources1

Post-translational modificationi

N-glycosylated.

Keywords - PTMi

Acetylation, Disulfide bond, Glycoprotein

Proteomic databases

EPDiQ9Z0J0
MaxQBiQ9Z0J0
PaxDbiQ9Z0J0
PeptideAtlasiQ9Z0J0
PRIDEiQ9Z0J0

PTM databases

iPTMnetiQ9Z0J0
PhosphoSitePlusiQ9Z0J0
SwissPalmiQ9Z0J0

Expressioni

Tissue specificityi

Highly expressed in epididymis.

Gene expression databases

BgeeiENSMUSG00000021242
CleanExiMM_NPC2
GenevisibleiQ9Z0J0 MM

Interactioni

Subunit structurei

Interacts with NUS1/NgBR, the interaction stabilizes NCP2 and regulates cholesterol trafficking. Interacts with DHDDS (By similarity). Interacts with NEDD4L (via C2 domain) (By similarity). Interacts with NPC1L1 (By similarity). Interacts with NPC1 (via the second lumenal domain) in a cholestrol-dependent manner (By similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases

IntActiQ9Z0J0, 1 interactor
MINTiQ9Z0J0
STRINGi10090.ENSMUSP00000021668

Structurei

3D structure databases

ProteinModelPortaliQ9Z0J0
SMRiQ9Z0J0
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the NPC2 family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG4063 Eukaryota
ENOG4111Q8S LUCA
GeneTreeiENSGT00390000006223
HOGENOMiHOG000007181
HOVERGENiHBG018181
InParanoidiQ9Z0J0
KOiK13443
OMAiCKSGISC
OrthoDBiEOG091G0W4T
PhylomeDBiQ9Z0J0
TreeFamiTF317963

Family and domain databases

CDDicd00916 Npc2_like, 1 hit
InterProiView protein in InterPro
IPR014756 Ig_E-set
IPR003172 ML_dom
IPR033916 ML_Npc2-like
PfamiView protein in Pfam
PF02221 E1_DerP2_DerF2, 1 hit
SMARTiView protein in SMART
SM00737 ML, 1 hit
SUPFAMiSSF81296 SSF81296, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q9Z0J0-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MRFLAATILL LALVAASQAE PLHFKDCGSK VGVIKEVNVS PCPTDPCQLH
60 70 80 90 100
KGQSYSVNIT FTSGTQSQNS TALVHGILEG IRVPFPIPEP DGCKSGINCP
110 120 130 140
IQKDKVYSYL NKLPVKNEYP SIKLVVEWKL EDDKKNNLFC WEIPVQITS
Length:149
Mass (Da):16,442
Last modified:May 1, 1999 - v1
Checksum:i6BDE56CF69791805
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB021289 mRNA Translation: BAA35183.1
AK008603 mRNA Translation: BAB25771.1
AK009127 mRNA Translation: BAB26090.1
AK151067 mRNA Translation: BAE30083.1
AK151133 mRNA Translation: BAE30141.1
AK153020 mRNA Translation: BAE31654.1
AK153203 mRNA Translation: BAE31803.1
AK158624 mRNA Translation: BAE34585.1
AK165263 mRNA Translation: BAE38111.1
AK167869 mRNA Translation: BAE39885.1
AK170327 mRNA Translation: BAE41721.1
BC003471 mRNA Translation: AAH03471.1
BC007190 mRNA Translation: AAH07190.1
CCDSiCCDS26050.1
RefSeqiNP_075898.1, NM_023409.4
UniGeneiMm.282556

Genome annotation databases

EnsembliENSMUST00000021668; ENSMUSP00000021668; ENSMUSG00000021242
GeneIDi67963
KEGGimmu:67963
UCSCiuc007oft.1 mouse

Similar proteinsi

Entry informationi

Entry nameiNPC2_MOUSE
AccessioniPrimary (citable) accession number: Q9Z0J0
Secondary accession number(s): Q3UB23
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 20, 2001
Last sequence update: May 1, 1999
Last modified: May 23, 2018
This is version 136 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
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Main funding by: National Institutes of Health