UniProtKB - P79345 (NPC2_BOVIN)
NPC intracellular cholesterol transporter 2
NPC2
Functioni
Intracellular cholesterol transporter which acts in concert with NPC1 and plays an important role in the egress of cholesterol from the lysosomal compartment (PubMed:29580834, PubMed:17552909).
Unesterified cholesterol that has been released from LDLs in the lumen of the late endosomes/lysosomes is transferred by NPC2 to the cholesterol-binding pocket in the N-terminal domain of NPC1 (By similarity).
May bind and mobilize cholesterol that is associated with membranes (PubMed:18823126).
NPC2 binds cholesterol with a 1:1 stoichiometry (PubMed:17573352).
Can bind a variety of sterols, including lathosterol, desmosterol and the plant sterols stigmasterol and beta-sitosterol (By similarity).
The secreted form of NCP2 regulates biliary cholesterol secretion via stimulation of ABCG5/ABCG8-mediated cholesterol transport (By similarity).
By similarity4 PublicationsCatalytic activityi
GO - Molecular functioni
- cholesterol binding Source: UniProtKB
- cholesterol transfer activity Source: Ensembl
- enzyme binding Source: Ensembl
- sterol binding Source: GO_Central
GO - Biological processi
- cholesterol efflux Source: UniProtKB
- cholesterol homeostasis Source: Ensembl
- cholesterol metabolic process Source: UniProtKB-KW
- cholesterol transport Source: UniProtKB
- intracellular cholesterol transport Source: UniProtKB
- response to virus Source: Ensembl
- sterol transport Source: GO_Central
Keywordsi
Biological process | Cholesterol metabolism, Lipid metabolism, Lipid transport, Steroid metabolism, Sterol metabolism, Transport |
Enzyme and pathway databases
Reactomei | R-BTA-6798695, Neutrophil degranulation R-BTA-8964038, LDL clearance |
Chemistry databases
SwissLipidsi | SLP:000000474 |
Names & Taxonomyi
Protein namesi | Recommended name: NPC intracellular cholesterol transporter 2By similarityAlternative name(s): EPV201 Publication Epididymal secretory protein E1 Niemann Pick type C2 protein homolog |
Gene namesi | Name:NPC2By similarity |
Organismi | Bos taurus (Bovine) |
Taxonomic identifieri | 9913 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Artiodactyla › Ruminantia › Pecora › Bovidae › Bovinae › Bos |
Proteomesi |
|
Organism-specific databases
VEuPathDBi | HostDB:ENSBTAG00000021955 |
VGNCi | VGNC:32196, NPC2 |
Subcellular locationi
Lysosome
- Lysosome By similarity
Endoplasmic reticulum
- Endoplasmic reticulum By similarity
Extracellular region or secreted
- Secreted By similarity
Note: Interaction with cell-surface M6PR mediates endocytosis and targeting to lysosomes.By similarity
Endoplasmic reticulum
- endoplasmic reticulum Source: UniProtKB-SubCell
Extracellular region or secreted
- extracellular space Source: Ensembl
Lysosome
- lysosome Source: UniProtKB-SubCell
Keywords - Cellular componenti
Endoplasmic reticulum, Lysosome, SecretedPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 19 | Add BLAST | 19 | |
ChainiPRO_0000019852 | 20 – 149 | NPC intracellular cholesterol transporter 2Add BLAST | 130 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 27 ↔ 140 | Combined sources3 Publications | ||
Disulfide bondi | 42 ↔ 47 | Combined sources3 Publications | ||
Glycosylationi | 58 | N-linked (GlcNAc...) asparagineCombined sources2 Publications | 1 | |
Disulfide bondi | 93 ↔ 99 | Combined sources3 Publications | ||
Modified residuei | 116 | N6-acetyllysineBy similarity | 1 |
Keywords - PTMi
Acetylation, Disulfide bond, GlycoproteinProteomic databases
PaxDbi | P79345 |
PeptideAtlasi | P79345 |
PRIDEi | P79345 |
PTM databases
iPTMneti | P79345 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSBTAG00000021955, Expressed in caput epididymis and 97 other tissues |
Interactioni
Subunit structurei
Interacts with NPC1 (via the second lumenal domain) in a cholestrol-dependent manner (PubMed:22065762, PubMed:27551080).
Interacts with NUS1/NgBR, the interaction stabilizes NCP2 and regulates cholesterol trafficking.
Interacts with DHDDS.
Interacts with NEDD4L (via C2 domain).
Interacts with NPC1L1 (By similarity).
By similarity2 PublicationsGO - Molecular functioni
- enzyme binding Source: Ensembl
Protein-protein interaction databases
STRINGi | 9913.ENSBTAP00000029271 |
Structurei
Secondary structure
3D structure databases
SMRi | P79345 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P79345 |
Family & Domainsi
Domaini
Sequence similaritiesi
Keywords - Domaini
SignalPhylogenomic databases
eggNOGi | KOG4063, Eukaryota |
GeneTreei | ENSGT00390000006223 |
HOGENOMi | CLU_109192_1_0_1 |
InParanoidi | P79345 |
OMAi | NLFCWEI |
OrthoDBi | 1612792at2759 |
TreeFami | TF317963 |
Family and domain databases
CDDi | cd00916, Npc2_like, 1 hit |
InterProi | View protein in InterPro IPR014756, Ig_E-set IPR003172, ML_dom IPR033916, ML_Npc2-like IPR039670, NPC2-like |
PANTHERi | PTHR11306, PTHR11306, 1 hit |
Pfami | View protein in Pfam PF02221, E1_DerP2_DerF2, 1 hit |
SMARTi | View protein in SMART SM00737, ML, 1 hit |
SUPFAMi | SSF81296, SSF81296, 1 hit |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
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
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 |
RefSeqi | NP_776343.1, NM_173918.2 |
Genome annotation databases
Ensembli | ENSBTAT00000029271; ENSBTAP00000029271; ENSBTAG00000021955 |
GeneIDi | 280815 |
KEGGi | bta:280815 |
Similar proteinsi
Cross-referencesi
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 |
RefSeqi | NP_776343.1, NM_173918.2 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1NEP | X-ray | 1.70 | A | 20-149 | [»] | |
2HKA | X-ray | 1.81 | A/B/C | 20-149 | [»] | |
SMRi | P79345 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
STRINGi | 9913.ENSBTAP00000029271 |
Chemistry databases
SwissLipidsi | SLP:000000474 |
PTM databases
iPTMneti | P79345 |
Proteomic databases
PaxDbi | P79345 |
PeptideAtlasi | P79345 |
PRIDEi | P79345 |
Genome annotation databases
Ensembli | ENSBTAT00000029271; ENSBTAP00000029271; ENSBTAG00000021955 |
GeneIDi | 280815 |
KEGGi | bta:280815 |
Organism-specific databases
CTDi | 10577 |
VEuPathDBi | HostDB:ENSBTAG00000021955 |
VGNCi | VGNC:32196, NPC2 |
Phylogenomic databases
eggNOGi | KOG4063, Eukaryota |
GeneTreei | ENSGT00390000006223 |
HOGENOMi | CLU_109192_1_0_1 |
InParanoidi | P79345 |
OMAi | NLFCWEI |
OrthoDBi | 1612792at2759 |
TreeFami | TF317963 |
Enzyme and pathway databases
Reactomei | R-BTA-6798695, Neutrophil degranulation R-BTA-8964038, LDL clearance |
Miscellaneous databases
EvolutionaryTracei | P79345 |
Gene expression databases
Bgeei | ENSBTAG00000021955, Expressed in caput epididymis and 97 other tissues |
Family and domain databases
CDDi | cd00916, Npc2_like, 1 hit |
InterProi | View protein in InterPro IPR014756, Ig_E-set IPR003172, ML_dom IPR033916, ML_Npc2-like IPR039670, NPC2-like |
PANTHERi | PTHR11306, PTHR11306, 1 hit |
Pfami | View protein in Pfam PF02221, E1_DerP2_DerF2, 1 hit |
SMARTi | View protein in SMART SM00737, ML, 1 hit |
SUPFAMi | SSF81296, SSF81296, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | NPC2_BOVIN | |
Accessioni | P79345Primary (citable) accession number: P79345 Secondary accession number(s): Q3T091, Q58DR4 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 15, 1998 |
Last sequence update: | May 1, 1997 | |
Last modified: | September 29, 2021 | |
This is version 142 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structure, Direct protein sequencing, Reference proteomeDocuments
- PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families