Npc2 NPC intracellular cholesterol transporter 2 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Npc2provided by MGI
Official Full Name: NPC intracellular cholesterol transporter 2provided by MGI
Primary source: MGI:MGI:1915213
See related: Ensembl:ENSMUSG00000021242 AllianceGenome:MGI:1915213
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: HE1; 2700012J19Rik
Summary: Enables cholesterol binding activity. Involved in cholesterol efflux and intracellular cholesterol transport. Located in lysosome. Is expressed in nervous system; respiratory system; and stomach. Used to study Niemann-Pick disease. Human ortholog(s) of this gene implicated in Niemann-Pick disease and Niemann-Pick disease type C2. Orthologous to human NPC2 (NPC intracellular cholesterol transporter 2). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Broad expression in genital fat pad adult (RPKM 400.1), lung adult (RPKM 212.6) and 17 other tissues See more
Orthologs: human all
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Genomic context

Location:: 12 D1; 12 39.37 cM

Exon count:: 4

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	12	NC_000078.7 (84801333..84819886, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	12	NC_000078.6 (84754559..84773112, complement)

Chromosome 12 - NC_000078.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Ezh2 is essential for the generation of functional yolk sac derived erythro-myeloid progenitors.
Title: Ezh2 is essential for the generation of functional yolk sac derived erythro-myeloid progenitors.
these data demonstrate the benefit of a one-time intracisternal administration of AAVrh.10-mNpc2-HA as a life-long treatment for Niemann-Pick type C2 disease
Title: Attenuation of the Niemann-Pick type C2 disease phenotype by intracisternal administration of an AAVrh.10 vector expressing Npc2.
accumulation of free cholesterol in late endosomes/lysosomes of Arf6 knockout mouse embryonic fibroblasts results from mistrafficking of Niemann-Pick type C protein
Title: Arf6 controls retromer traffic and intracellular cholesterol distribution via a phosphoinositide-based mechanism.
GARP complex contributes to intracellular cholesterol transport by targeting NPC2 to lysosomes in a CI-MPR-dependent manner.
Title: The GARP Complex Is Involved in Intracellular Cholesterol Transport via Targeting NPC2 to Lysosomes.
AAV9-mediated NPC1 delivery significantly promoted Purkinje cell survival, restored locomotor activity and coordination, and increased the lifespan of NPC1(-/-) mice. Our work suggests that AAV-based gene therapy is a promising means to treat NPC disease.
Title: AAV9-NPC1 significantly ameliorates Purkinje cell death and behavioral abnormalities in mouse NPC disease.
These findings show that NPC2 secreted by premalignant lung tumours suppresses immature macrophage-lineage cell recruitment to the microenvironment in a paracrine manner.
Title: The cholesterol-binding protein NPC2 restrains recruitment of stromal macrophage-lineage cells to early-stage lung tumours.
Using the inhibitors of cathepsin enzymatic activity, it was found that cathepsins B and L regulate TNF-alpha production, the expression and secretion of NPC2 protein, and the mRNA levels of the genes involved in cholesterol trafficking in macrophages.
Title: Involvement of cathepsins B and L in inflammation and cholesterol trafficking protein NPC2 secretion in macrophages.
Npc1 and npc2 deficiencies result in pulmonary abnormalities observed in human Niemann-Pick type C disease.
Title: Pulmonary abnormalities in animal models due to Niemann-Pick type C1 (NPC1) or C2 (NPC2) disease.
This is the first report demonstrating that GNMT plays an important role in regulating cholesterol homeostasis via interaction with NPC2
Title: Glycine N-methyltransferase deficiency affects Niemann-Pick type C2 protein stability and regulates hepatic cholesterol homeostasis.
NPC1 and NPC2 proteins participate in endosomal/lysosomal processing of both sphingolipids and cholesterol
Title: Endosomal/lysosomal processing of gangliosides affects neuronal cholesterol sequestration in Niemann-Pick disease type C.

Submit: New GeneRIF Correction See all GeneRIFs (26)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Gene trapped (1) 1 citation
Targeted (4) 1 citation
Endonuclease-mediated (2)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D12Mit238 (e-PCR), detects polymorphism
- UniSTS:126794

RH126518 (e-PCR)
- UniSTS:208842

AU045843 (e-PCR)
- UniSTS:160233

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables cholesterol binding	IBA Inferred from Biological aspect of Ancestor more info
enables cholesterol binding	IMP Inferred from Mutant Phenotype more info	PubMed
enables cholesterol binding	ISO Inferred from Sequence Orthology more info
enables cholesterol binding	ISS Inferred from Sequence or Structural Similarity more info	PubMed
enables cholesterol transfer activity	ISO Inferred from Sequence Orthology more info
enables enzyme binding	ISO Inferred from Sequence Orthology more info
enables sterol binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in cholesterol efflux	IBA Inferred from Biological aspect of Ancestor more info
involved_in cholesterol efflux	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cholesterol efflux	ISO Inferred from Sequence Orthology more info
involved_in cholesterol homeostasis	ISO Inferred from Sequence Orthology more info
involved_in cholesterol homeostasis	ISS Inferred from Sequence or Structural Similarity more info	PubMed
acts_upstream_of_or_within cholesterol metabolic process	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within cholesterol storage	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cholesterol transport	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cholesterol transport	ISO Inferred from Sequence Orthology more info
involved_in cholesterol transport	ISS Inferred from Sequence or Structural Similarity more info	PubMed
acts_upstream_of_or_within gene expression	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in intracellular cholesterol transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in intracellular cholesterol transport	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within intracellular cholesterol transport	ISO Inferred from Sequence Orthology more info
involved_in intracellular sterol transport	ISO Inferred from Sequence Orthology more info
involved_in intracellular sterol transport	ISS Inferred from Sequence or Structural Similarity more info	PubMed
acts_upstream_of_or_within lipid metabolic process	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within lipid transport	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within steroid metabolic process	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within sterol metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within sterol transport	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in endoplasmic reticulum	IEA Inferred from Electronic Annotation more info
located_in extracellular region	IEA Inferred from Electronic Annotation more info
located_in extracellular space	HDA more info	PubMed
located_in extracellular space	ISO Inferred from Sequence Orthology more info
is_active_in lysosome	IDA Inferred from Direct Assay more info	PubMed
located_in lysosome	IDA Inferred from Direct Assay more info	PubMed
is_active_in lysosome	ISO Inferred from Sequence Orthology more info
located_in lysosome	ISS Inferred from Sequence or Structural Similarity more info	PubMed

General protein information

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Preferred Names: NPC intracellular cholesterol transporter 2

Names: Niemann-Pick type C2; epididymal secretory protein E1; mE1; niemann Pick type C2 protein homolog

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_023409.4 → NP_075898.1 NPC intracellular cholesterol transporter 2 precursor

See identical proteins and their annotated locations for NP_075898.1

Status: VALIDATED

Source sequence(s)

AC122310, AI391386, AK158624, BE952809

Consensus CDS

CCDS26050.1

UniProtKB/Swiss-Prot

Q3UB23, Q9Z0J0

UniProtKB/TrEMBL

Q3TXQ4, Q3U3C2

Related

ENSMUSP00000021668.9, ENSMUST00000021668.10

Conserved Domains (1) summary

cd00916
Location:24 → 145

Npc2_like; Niemann-Pick type C2 (Npc2) is a lysosomal protein in which a mutation in the gene causes a rare form of Niemann-Pick type C disease, an autosomal recessive lipid storage disorder characterized by accumulation of low-density lipoprotein-derived ...