Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

NPC intracellular cholesterol transporter 2

Gene

NPC2

Organism
Bos taurus (Bovine)
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

GO - Biological processi

Keywordsi

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

Enzyme and pathway databases

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

Chemistry databases

SwissLipidsiSLP:000000474

Names & Taxonomyi

Protein namesi
Recommended name:
NPC intracellular cholesterol transporter 2By similarity
Alternative name(s):
EPV20
Epididymal secretory protein E1
Niemann Pick type C2 protein homolog
Gene namesi
Name:NPC2By similarity
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Chromosome 10

Organism-specific databases

VGNCiVGNC:32196 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 – 19Add BLAST19
ChainiPRO_000001985220 – 149NPC intracellular cholesterol transporter 2Add BLAST130

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi27 ↔ 1401 Publication
Disulfide bondi42 ↔ 471 Publication
Glycosylationi58N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi93 ↔ 991 Publication
Modified residuei116N6-acetyllysineBy similarity1

Keywords - PTMi

Acetylation, Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP79345
PeptideAtlasiP79345
PRIDEiP79345

Expressioni

Tissue specificityi

Expressed in kidney, spleen, liver and mammary gland, but not in testis.

Gene expression databases

BgeeiENSBTAG00000021955

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 similarity1 Publication

GO - Molecular functioni

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000029271

Structurei

Secondary structure

1149
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi25 – 27Combined sources3
Beta strandi31 – 41Combined sources11
Beta strandi43 – 50Combined sources8
Beta strandi54 – 65Combined sources12
Beta strandi71 – 78Combined sources8
Beta strandi81 – 84Combined sources4
Helixi92 – 94Combined sources3
Beta strandi99 – 101Combined sources3
Beta strandi106 – 114Combined sources9
Beta strandi121 – 131Combined sources11
Beta strandi137 – 148Combined sources12

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1NEPX-ray1.70A20-149[»]
2HKAX-ray1.81A/B/C20-149[»]
ProteinModelPortaliP79345
SMRiP79345
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP79345

Family & Domainsi

Sequence similaritiesi

Belongs to the NPC2 family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG4063 Eukaryota
ENOG4111Q8S LUCA
GeneTreeiENSGT00390000006223
HOGENOMiHOG000007181
HOVERGENiHBG018181
InParanoidiP79345
KOiK13443
OMAiCKSGISC
OrthoDBiEOG091G0W4T
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.

P79345-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MRFLTVAFLF LALSASALAE PVKFKDCGSW VGVIKEVNVS PCPTQPCKLH
60 70 80 90 100
RGQSYSVNVT FTSNTQSQSS KAVVHGIVMG IPVPFPIPES DGCKSGIRCP
110 120 130 140
IEKDKTYNYV NKLPVKNEYP SIKVVVEWEL TDDKNQRFFC WQIPIEVEA
Length:149
Mass (Da):16,640
Last modified:May 1, 1997 - v1
Checksum:i91156DC7E805B655
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X85799 mRNA Translation: CAA59794.1
BT021533 mRNA Translation: AAX46380.1
BC102504 mRNA Translation: AAI02505.1
RefSeqiNP_776343.1, NM_173918.2
UniGeneiBt.23268

Genome annotation databases

EnsembliENSBTAT00000029271; ENSBTAP00000029271; ENSBTAG00000021955
GeneIDi280815
KEGGibta:280815

Similar proteinsi

Entry informationi

Entry nameiNPC2_BOVIN
AccessioniPrimary (citable) accession number: P79345
Secondary accession number(s): Q3T091, Q58DR4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: May 1, 1997
Last modified: March 28, 2018
This is version 125 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

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome