UniProtKB - P61916 (NPC2_HUMAN)
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:17018531, PubMed:11125141, PubMed:18772377, PubMed:29580834, PubMed:15937921).
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 (PubMed:17018531, PubMed:18772377, PubMed:27238017).
May bind and mobilize cholesterol that is associated with membranes (PubMed:18823126).
NPC2 binds cholesterol with a 1:1 stoichiometry (PubMed:17018531).
Can bind a variety of sterols, including lathosterol, desmosterol and the plant sterols stigmasterol and beta-sitosterol (PubMed:17018531).
The secreted form of NCP2 regulates biliary cholesterol secretion via stimulation of ABCG5/ABCG8-mediated cholesterol transport (By similarity).
By similarity7 PublicationsCatalytic activityi
- This reaction proceeds in the forward1 Publication direction.
GO - Molecular functioni
- cholesterol binding Source: UniProtKB
- cholesterol transfer activity Source: BHF-UCL
- enzyme binding Source: UniProtKB
- sterol binding Source: GO_Central
GO - Biological processi
- cholesterol efflux Source: BHF-UCL
- cholesterol homeostasis Source: UniProtKB
- cholesterol metabolic process Source: UniProtKB-KW
- cholesterol transport Source: UniProtKB
- glycolipid transport Source: HGNC-UCL
- intracellular cholesterol transport Source: UniProtKB
- intracellular sterol transport Source: HGNC-UCL
- phospholipid transport Source: HGNC-UCL
- regulation of isoprenoid metabolic process Source: UniProtKB
- response to virus Source: UniProtKB
- sterol transport Source: GO_Central
Keywordsi
Biological process | Cholesterol metabolism, Lipid metabolism, Lipid transport, Steroid metabolism, Sterol metabolism, Transport |
Enzyme and pathway databases
PathwayCommonsi | P61916 |
Reactomei | R-HSA-6798695, Neutrophil degranulation R-HSA-8964038, LDL clearance |
SignaLinki | P61916 |
SIGNORi | P61916 |
Protein family/group databases
TCDBi | 2.A.6.6.1, the resistance-nodulation-cell division (rnd) superfamily |
Chemistry databases
SwissLipidsi | SLP:000000475 |
Names & Taxonomyi
Protein namesi | Recommended name: NPC intracellular cholesterol transporter 2ImportedAlternative name(s): Epididymal secretory protein E1 Human epididymis-specific protein 1 Short name: He12 Publications Niemann-Pick disease type C2 protein1 Publication |
Gene namesi | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:14537, NPC2 |
MIMi | 601015, gene |
neXtProti | NX_P61916 |
VEuPathDBi | HostDB:ENSG00000119655 |
Subcellular locationi
Lysosome
- Lysosome 1 Publication2 Publications
Endoplasmic reticulum
- Endoplasmic reticulum 1 Publication
Extracellular region or secreted
- Secreted 4 Publications
Note: Interaction with cell-surface M6PR mediates endocytosis and targeting to lysosomes.1 Publication
Endoplasmic reticulum
- endoplasmic reticulum Source: UniProtKB-SubCell
Extracellular region or secreted
- extracellular exosome Source: UniProtKB
- extracellular region Source: Reactome
- extracellular space Source: UniProtKB
Lysosome
- azurophil granule lumen Source: Reactome
- lysosomal lumen Source: Reactome
- lysosome Source: UniProtKB
Keywords - Cellular componenti
Endoplasmic reticulum, Lysosome, SecretedPathology & Biotechi
Involvement in diseasei
Niemann-Pick disease C2 (NPC2)7 Publications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_043303 | 30 | V → M in NPC2. 1 PublicationCorresponds to variant dbSNP:rs151220873EnsemblClinVar. | 1 | |
Natural variantiVAR_015848 | 39 | V → M in NPC2; results in the synthesis of functional recombinant proteins correctly targeted to lysosomes. 2 PublicationsCorresponds to variant dbSNP:rs80358261EnsemblClinVar. | 1 | |
Natural variantiVAR_043304 | 47 | C → F in NPC2; leads to the synthesis of misfolded recombinant proteins that colocalized with an endoplasmic reticulum marker; normally secreted but unable to correct cholesterol storage in NPC2-deficient cells. 2 PublicationsCorresponds to variant dbSNP:rs1555345993EnsemblClinVar. | 1 | |
Natural variantiVAR_015849 | 67 | S → P in NPC2; leads to the synthesis of misfolded recombinant proteins that colocalized with an endoplasmic reticulum marker; normally secreted but unable to correct cholesterol storage in NPC2-deficient cells. 2 PublicationsCorresponds to variant dbSNP:rs11694EnsemblClinVar. | 1 | |
Natural variantiVAR_043305 | 93 | C → F in NPC2; leads to the synthesis of misfolded recombinant proteins that colocalized with an endoplasmic reticulum marker; normally secreted but unable to correct cholesterol storage in NPC2-deficient cells. 2 PublicationsCorresponds to variant dbSNP:rs143960270Ensembl. | 1 | |
Natural variantiVAR_043306 | 99 | C → R in NPC2; leads to the synthesis of misfolded recombinant proteins that colocalized with an endoplasmic reticulum marker; normally secreted but unable to correct cholesterol storage in NPC2-deficient cells. 1 PublicationCorresponds to variant dbSNP:rs80358264EnsemblClinVar. | 1 | |
Natural variantiVAR_043307 | 120 | P → S in NPC2; unable to bind cholesterol. 2 PublicationsCorresponds to variant dbSNP:rs104894458EnsemblClinVar. | 1 |
Keywords - Diseasei
Disease variant, Niemann-Pick diseaseOrganism-specific databases
DisGeNETi | 10577 |
GeneReviewsi | NPC2 |
MalaCardsi | NPC2 |
MIMi | 607625, phenotype |
OpenTargetsi | ENSG00000119655 |
Orphaneti | 216986, Niemann-Pick disease type C, adult neurologic onset 216981, Niemann-Pick disease type C, juvenile neurologic onset 216978, Niemann-Pick disease type C, late infantile neurologic onset 216975, Niemann-Pick disease type C, severe early infantile neurologic onset 216972, Niemann-Pick disease type C, severe perinatal form |
PharmGKBi | PA31700 |
Miscellaneous databases
Pharosi | P61916, Tbio |
Genetic variation databases
BioMutai | NPC2 |
DMDMi | 48429027 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 19 | 2 PublicationsAdd BLAST | 19 | |
ChainiPRO_0000019854 | 20 – 151 | NPC intracellular cholesterol transporter 2Add BLAST | 132 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 27 ↔ 140 | Combined sources1 Publication | ||
Disulfide bondi | 42 ↔ 47 | Combined sources1 Publication | ||
Glycosylationi | 58 | N-linked (GlcNAc...) asparagineCombined sources2 Publications | 1 | |
Disulfide bondi | 93 ↔ 99 | Combined sources1 Publication | ||
Modified residuei | 116 | N6-acetyllysineBy similarity | 1 | |
Glycosylationi | 135 | N-linked (GlcNAc...) asparagineCombined sources3 Publications | 1 |
Keywords - PTMi
Acetylation, Disulfide bond, GlycoproteinProteomic databases
EPDi | P61916 |
jPOSTi | P61916 |
MassIVEi | P61916 |
MaxQBi | P61916 |
PaxDbi | P61916 |
PeptideAtlasi | P61916 |
PRIDEi | P61916 |
ProteomicsDBi | 4905 57337 [P61916-1] |
TopDownProteomicsi | P61916-2 [P61916-2] |
PTM databases
GlyConnecti | 1215, 2 N-Linked glycans (1 site) |
GlyGeni | P61916, 2 sites, 2 N-linked glycans (1 site) |
iPTMneti | P61916 |
MetOSitei | P61916 |
PhosphoSitePlusi | P61916 |
Expressioni
Tissue specificityi
Inductioni
Gene expression databases
Bgeei | ENSG00000119655, Expressed in corpus epididymis and 242 other tissues |
ExpressionAtlasi | P61916, baseline and differential |
Genevisiblei | P61916, HS |
Organism-specific databases
HPAi | ENSG00000119655, Tissue enriched (epididymis) |
Interactioni
Subunit structurei
Interacts with NPC1 (via the second lumenal domain) in a cholestrol-dependent manner (PubMed:18772377, PubMed:27238017, PubMed:27551080).
Interacts with NUS1/NgBR, the interaction stabilizes NCP2 and regulates cholesterol trafficking (PubMed:19723497).
Interacts with DHDDS (PubMed:15110773).
Interacts with NEDD4L (via C2 domain) (PubMed:19664597).
Interacts with NPC1L1 (PubMed:22095670).
7 PublicationsBinary interactionsi
GO - Molecular functioni
- enzyme binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 115828, 42 interactors |
IntActi | P61916, 19 interactors |
MINTi | P61916 |
STRINGi | 9606.ENSP00000451112 |
Miscellaneous databases
RNActi | P61916, protein |
Structurei
Secondary structure
3D structure databases
SMRi | P61916 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domaini
Sequence similaritiesi
Keywords - Domaini
SignalPhylogenomic databases
eggNOGi | KOG4063, Eukaryota |
GeneTreei | ENSGT00390000006223 |
InParanoidi | P61916 |
PhylomeDBi | P61916 |
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 |
s (2+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 7 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MRFLAATFLL LALSTAAQAE PVQFKDCGSV DGVIKEVNVS PCPTQPCQLS
60 70 80 90 100
KGQSYSVNVT FTSNIQSKSS KAVVHGILMG VPVPFPIPEP DGCKSGINCP
110 120 130 140 150
IQKDKTYSYL NKLPVKSEYP SIKLVVEWQL QDDKNQSLFC WEIPVQIVSH
L
Computationally mapped potential isoform sequencesi
There are 7 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketG3V3E8 | G3V3E8_HUMAN | Epididymal secretory protein E1 | NPC2 | 174 | Annotation score: | ||
G3V3D1 | G3V3D1_HUMAN | Epididymal secretory protein E1 | NPC2 | 221 | Annotation score: | ||
E7EMS2 | E7EMS2_HUMAN | Epididymal secretory protein E1 | NPC2 | 201 | Annotation score: | ||
G3V2V8 | G3V2V8_HUMAN | Epididymal secretory protein E1 | NPC2 | 122 | Annotation score: | ||
J3KMY5 | J3KMY5_HUMAN | Epididymal secretory protein E1 | NPC2 | 148 | Annotation score: | ||
H0YIZ1 | H0YIZ1_HUMAN | Epididymal secretory protein E1 | NPC2 | 173 | Annotation score: | ||
H0YJE2 | H0YJE2_HUMAN | NPC intracellular cholesterol trans... | NPC2 | 53 | Annotation score: |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_043303 | 30 | V → M in NPC2. 1 PublicationCorresponds to variant dbSNP:rs151220873EnsemblClinVar. | 1 | |
Natural variantiVAR_015848 | 39 | V → M in NPC2; results in the synthesis of functional recombinant proteins correctly targeted to lysosomes. 2 PublicationsCorresponds to variant dbSNP:rs80358261EnsemblClinVar. | 1 | |
Natural variantiVAR_043304 | 47 | C → F in NPC2; leads to the synthesis of misfolded recombinant proteins that colocalized with an endoplasmic reticulum marker; normally secreted but unable to correct cholesterol storage in NPC2-deficient cells. 2 PublicationsCorresponds to variant dbSNP:rs1555345993EnsemblClinVar. | 1 | |
Natural variantiVAR_015849 | 67 | S → P in NPC2; leads to the synthesis of misfolded recombinant proteins that colocalized with an endoplasmic reticulum marker; normally secreted but unable to correct cholesterol storage in NPC2-deficient cells. 2 PublicationsCorresponds to variant dbSNP:rs11694EnsemblClinVar. | 1 | |
Natural variantiVAR_011899 | 86 | P → L. Corresponds to variant dbSNP:rs4688Ensembl. | 1 | |
Natural variantiVAR_043305 | 93 | C → F in NPC2; leads to the synthesis of misfolded recombinant proteins that colocalized with an endoplasmic reticulum marker; normally secreted but unable to correct cholesterol storage in NPC2-deficient cells. 2 PublicationsCorresponds to variant dbSNP:rs143960270Ensembl. | 1 | |
Natural variantiVAR_043306 | 99 | C → R in NPC2; leads to the synthesis of misfolded recombinant proteins that colocalized with an endoplasmic reticulum marker; normally secreted but unable to correct cholesterol storage in NPC2-deficient cells. 1 PublicationCorresponds to variant dbSNP:rs80358264EnsemblClinVar. | 1 | |
Natural variantiVAR_043307 | 120 | P → S in NPC2; unable to bind cholesterol. 2 PublicationsCorresponds to variant dbSNP:rs104894458EnsemblClinVar. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_056459 | 122 – 147 | Missing in isoform 2. 1 PublicationAdd BLAST | 26 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | X67698 mRNA Translation: CAA47928.1 AK298975 mRNA Translation: BAG61069.1 AC005479 Genomic DNA No translation available. BC002532 mRNA Translation: AAH02532.1 |
CCDSi | CCDS32121.1 [P61916-1] |
PIRi | I38365 |
RefSeqi | NP_006423.1, NM_006432.3 [P61916-1] |
Genome annotation databases
Ensembli | ENST00000541064; ENSP00000442488; ENSG00000119655 [P61916-2] ENST00000555619; ENSP00000451112; ENSG00000119655 |
GeneIDi | 10577 |
KEGGi | hsa:10577 |
MANE-Selecti | ENST00000555619.6; ENSP00000451112.2; NM_006432.5; NP_006423.1 |
UCSCi | uc001xpy.4, human [P61916-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | X67698 mRNA Translation: CAA47928.1 AK298975 mRNA Translation: BAG61069.1 AC005479 Genomic DNA No translation available. BC002532 mRNA Translation: AAH02532.1 |
CCDSi | CCDS32121.1 [P61916-1] |
PIRi | I38365 |
RefSeqi | NP_006423.1, NM_006432.3 [P61916-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
5KWY | X-ray | 2.40 | C/D | 20-151 | [»] | |
6W5V | electron microscopy | 4.00 | D | 1-151 | [»] | |
SMRi | P61916 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 115828, 42 interactors |
IntActi | P61916, 19 interactors |
MINTi | P61916 |
STRINGi | 9606.ENSP00000451112 |
Chemistry databases
SwissLipidsi | SLP:000000475 |
Protein family/group databases
TCDBi | 2.A.6.6.1, the resistance-nodulation-cell division (rnd) superfamily |
PTM databases
GlyConnecti | 1215, 2 N-Linked glycans (1 site) |
GlyGeni | P61916, 2 sites, 2 N-linked glycans (1 site) |
iPTMneti | P61916 |
MetOSitei | P61916 |
PhosphoSitePlusi | P61916 |
Genetic variation databases
BioMutai | NPC2 |
DMDMi | 48429027 |
Proteomic databases
EPDi | P61916 |
jPOSTi | P61916 |
MassIVEi | P61916 |
MaxQBi | P61916 |
PaxDbi | P61916 |
PeptideAtlasi | P61916 |
PRIDEi | P61916 |
ProteomicsDBi | 4905 57337 [P61916-1] |
TopDownProteomicsi | P61916-2 [P61916-2] |
Protocols and materials databases
Antibodypediai | 88, 319 antibodies from 34 providers |
DNASUi | 10577 |
Genome annotation databases
Ensembli | ENST00000541064; ENSP00000442488; ENSG00000119655 [P61916-2] ENST00000555619; ENSP00000451112; ENSG00000119655 |
GeneIDi | 10577 |
KEGGi | hsa:10577 |
MANE-Selecti | ENST00000555619.6; ENSP00000451112.2; NM_006432.5; NP_006423.1 |
UCSCi | uc001xpy.4, human [P61916-1] |
Organism-specific databases
CTDi | 10577 |
DisGeNETi | 10577 |
GeneCardsi | NPC2 |
GeneReviewsi | NPC2 |
HGNCi | HGNC:14537, NPC2 |
HPAi | ENSG00000119655, Tissue enriched (epididymis) |
MalaCardsi | NPC2 |
MIMi | 601015, gene 607625, phenotype |
neXtProti | NX_P61916 |
OpenTargetsi | ENSG00000119655 |
Orphaneti | 216986, Niemann-Pick disease type C, adult neurologic onset 216981, Niemann-Pick disease type C, juvenile neurologic onset 216978, Niemann-Pick disease type C, late infantile neurologic onset 216975, Niemann-Pick disease type C, severe early infantile neurologic onset 216972, Niemann-Pick disease type C, severe perinatal form |
PharmGKBi | PA31700 |
VEuPathDBi | HostDB:ENSG00000119655 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG4063, Eukaryota |
GeneTreei | ENSGT00390000006223 |
InParanoidi | P61916 |
PhylomeDBi | P61916 |
TreeFami | TF317963 |
Enzyme and pathway databases
PathwayCommonsi | P61916 |
Reactomei | R-HSA-6798695, Neutrophil degranulation R-HSA-8964038, LDL clearance |
SignaLinki | P61916 |
SIGNORi | P61916 |
Miscellaneous databases
BioGRID-ORCSi | 10577, 18 hits in 1062 CRISPR screens |
ChiTaRSi | NPC2, human |
GenomeRNAii | 10577 |
Pharosi | P61916, Tbio |
PROi | PR:P61916 |
RNActi | P61916, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000119655, Expressed in corpus epididymis and 242 other tissues |
ExpressionAtlasi | P61916, baseline and differential |
Genevisiblei | P61916, HS |
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_HUMAN | |
Accessioni | P61916Primary (citable) accession number: P61916 Secondary accession number(s): B4DQV7, Q15668, Q29413 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | June 7, 2004 |
Last sequence update: | June 7, 2004 | |
Last modified: | February 23, 2022 | |
This is version 164 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Direct protein sequencing, Reference proteomeDocuments
- Human chromosome 14
Human chromosome 14: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families