Property Summary

NCBI Gene PubMed Count 66
PubMed Score 163.41
PubTator Score 163.99

Knowledge Summary

Patent

No data available

Expression

  Differential Expression (15)

Disease log2 FC p
glioblastoma 2.800 2.7e-05
posterior fossa group A ependymoma 1.300 8.3e-07
astrocytoma 1.800 2.4e-02
atypical teratoid / rhabdoid tumor 1.300 2.4e-04
medulloblastoma, large-cell -1.100 3.2e-05
Duchenne muscular dystrophy 1.263 1.0e-09
intraductal papillary-mucinous carcinoma... -1.100 8.5e-04
intraductal papillary-mucinous neoplasm ... -1.100 5.2e-03
lung cancer -3.100 6.6e-07
pediatric high grade glioma 1.400 1.6e-03
pilocytic astrocytoma 1.500 8.6e-07
subependymal giant cell astrocytoma 2.513 1.0e-02
lung carcinoma -2.200 6.1e-34
ovarian cancer 2.300 7.8e-05
Down syndrome 1.100 1.3e-03

 IMPC Phenotype (1)

Protein-protein Interaction (5)

Gene RIF (49)

PMID Text
26846330 Structure of glycosylated NPC1 luminal domain C reveals insights into NPC2 and Ebola virus interactions
26296895 hypothesize that, in part, NPC2 rapidly traffics cholesterol between closely appositioned membranes within the multilamellar interior of late endosomal/lysosomal proteins, ultimately effecting cholesterol egress from this compartment
25764212 Our data suggest an incidence rate for NPC1 and NPC2 of 1/92,104 and 1/2,858,998, respectively. Evaluation of common NPC1 variants, however, suggests that there may be a late-onset NPC1 phenotype with a markedly higher incidence.
25754535 NPC2 may play an important role in negatively regulate cell proliferation.
25251378 Data suggest that in order for the ligand cholesterol to slide from one binding pocket to the other (from NPC2 to NPC1), cholesterol undergoes conformational change/isomerization to accommodate the bent transfer pathway between the 2 binding pockets.
25220527 heterozygous mutations in the NPC1/2 gene might be a risk factor for Alzheimer's disease
24915861 twelve individuals were subsequently confirmed to be NP-C by DNA analysis of NPC1 and NPC2 genes, with the early infantile form, the late infantile form, the juvenile form, and the adult form
24709320 Suggest role for mouse epididymal NPC2 in regulating male fertility.
24501203 these results suggest that the vitamin A-mediated antimicrobial mechanism against M. tuberculosis requires NPC2-dependent expression and function, indicating a key role for cellular cholesterol regulation in the innate immune response.
24438076 Recombinant NPC2 protein increases triglyceride levels in body fat.
24001314 an atomistic model is proposed of the transfer of cholesterol from NPC2 to NPC1(NTD) through the formation of an intermediate NPC1(NTD)-NPC2 complex
23814065 NPC2-deficiency leads to a dramatic up-regulation of the arachidonic acid (AA) metabolic pathway in human fibroblasts.
23791309 The p.Pro120Ser causing mutation in NPC2 observed in the Iranian patients was earlier observed in the only other NPC2 patient reported from the Middle East.
23733943 Treatment of NPC1-null or NPC2-deficient cells with cyclodextrin was effective in reducing cholesterol storage as well as the endocytic accumulation of sialoglycoproteins, demonstrating a direct link between cholesterol storage and abnormal recycling.
22962690 The NPC2 delivers cholesterol to the perimeter membrane of late endosomes, where it becomes available for transport to mitochondria without requiring NPC1.
22273177 Loss of Niemann Pick type C proteins 1 and 2 greatly enhances HIV infectivity and is associated with accumulation of HIV Gag and cholesterol in late endosomes/lysosomes.
22273177 NPC2-deficient cells exhibit Gag accumulation in late endosomal/lysosomal (LE/L) compartments of these cells as well as decreased NPC1 expression after HIV infection
22183894 This is the first report demonstrating that GNMT plays an important role in regulating cholesterol homeostasis via interaction with NPC2
22179027 overexpression of ABCA1 alone is able to correct the mobilization of cholesterol from late endosomes/lysosomes and the formation of HDL particles in NPC1- but not NPC2-deficient human fibroblasts
21740003 mechanism of sterol transport by cyclodextrins using in vitro model systems and fluorescence spectroscopy and NPC2-deficient fibroblasts
21253586 NPC2 protein of certain cells forms papillae coupled with apoptosis that creates open space
21084287 a novel mechanism where NPC2 by negatively regulating ERK 1/2 MAPK phosphorylation may efficiently suppress development of maladaptive tissue remodeling and inflammation.
20674861 NPC2 protein interacts N-ternimal domain of NPC1 protein, thereby opening an entry pore on NPC1 protein and allowing cholesterol to transfer without passing through the water phase.
20650896 NPC2 as a novel intracrine/autocrine factor that controls adipocyte differentiation and function
20628086 Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
20007703 The results suggest that NPC1 and NPC2 can function independently of one another in the egress of certain membrane-impermeable lysosomal cargo.
19913121 Observational study of gene-disease association. (HuGE Navigator)
19746448 physiological and coordinate downregulation of the NPC1 and NPC2 genes/proteins promotes the sequestration of LDL-derived cholesterol within endocytic compartments and serves a role in maintaining intracellular cholesterol homeostasis
19723497 Niemann-Pick type C2 protein levels are increased in the presence of Nogo-B receptor, and Nogo-B receptor enhances Niemann-Pick type C2 protein protein stability.
19664597 NPC2 binds C2 domain of human Nedd4L.
19252935 Results characterize mutations in the NPC1 and 2 genes in 34 unrelated patients including 32 patients with mutations in NPC1 gene and two patients in NPC2 gene, with 33 distinct genotypes encountered.
19252935 Observational study of gene-disease association. (HuGE Navigator)
18823126 NPC2 plays an important role in endo/lysosomal cholesterol trafficking by markedly accelerating the rates of cholesterol transport. Rates of sterol transfer from and between membranes were increased by as much as 2 orders of magnitude by NPC2.
18636124 Observational study of gene-disease association. (HuGE Navigator)
17895371 role of the AP-3 pathway in targeting of NP-C proteins; study found although mouse NPC1 & hNPC2 co-localize with AP-3 to a similar extent in fibroblasts, hNPC2 preferentially co-localizes with AP-1; targeting of both NPC1 & NPC2 is dependent on AP-3
17470133 p.P120S mutation, the first naturally occurring missense mutation located in the cholesterol-binding Evolutionarily Constrained Regions D domain, results in reduced amounts of a protein capable to reach the lysosome, but unable to bind cholesterol.
17387528 Observational study of gene-disease association. (HuGE Navigator)
17018531 NPC2 has a direct and specialized function in lysosomal sterol transport
16772431 Compared with normal men, seminal plasma of vasectomized men is characterized by a major decrease in immunodetectable HE1/NPC2 and surgical vasectomy reversal will normalize seminal plasma HE1/NPC2 amount to similar level of that of normal mem.
16606609 NPC2 protein has a role in the egress of LDL derived cholesterol out of the endosomal/lysosomal compartment
16374838 NPC2 is secreted from the liver into bile and plasma, where it may have a functional role in cholesterol transport in normal and disease conditions.
15937921 Functional characterization of the mutant proteins showed an excellent genotype-phenotype correlation in the three cases for whom a clinical history was available
14662784 The HE1 transcript was affected by the obstruction of the epididymis with little or no mRNA detectable along the epididymis.
12719428 NPC1 and NPC2 have a role in the regulation of sterol homeostasis through generation of LDL cholesterol-derived oxysterols
12591949 NPC2 protein has binding sites with a role in efficient secretion
12447927 Adult-onset NPC2 with lysosomal storage virtually restricted to neurons represents a novel phenotypic and genotypic variant with diffuse cognitive impairment and focal frontal involvement described for the first time.
12398991 NPC2, NPC1 and MLN64 may act in an ordered sequence to sense cholesterol, effect sterol movement, and consequently, influence the process of vesicular trafficking.
12125814 Review of NPC1 and HE1/NPC2 roles regulating cholesterol transport through endosomal/lysosomal system and in Niemann-Pick type C disease
11567215 mutational analysis and genotype/phenotype correlation in NPC2 group

AA Sequence

MRFLAATFLLLALSTAAQAEPVQFKDCGSVDGVIKEVNVSPCPTQPCQLSKGQSYSVNVTFTSNIQSKSS      1 - 70
KAVVHGILMGVPVPFPIPEPDGCKSGINCPIQKDKTYSYLNKLPVKSEYPSIKLVVEWQLQDDKNQSLFC     71 - 140
WEIPVQIVSHL                                                               141 - 151
//

Text Mined References (76)

PMID Year Title
26846330 2016 Structure of glycosylated NPC1 luminal domain C reveals insights into NPC2 and Ebola virus interactions.
26296895 2015 Multiple Surface Regions on the Niemann-Pick C2 Protein Facilitate Intracellular Cholesterol Transport.
25944712 2015 N-terminome analysis of the human mitochondrial proteome.
25764212 2016 High incidence of unrecognized visceral/neurological late-onset Niemann-Pick disease, type C1, predicted by analysis of massively parallel sequencing data sets.
25754535 2015 Niemann-Pick type C2 protein regulates liver cancer progression via modulating ERK1/2 pathway: Clinicopathological correlations and therapeutical implications.
25251378 2014 Niemann-Pick type C disease: a QM/MM study of conformational changes in cholesterol in the NPC1(NTD) and NPC2 binding pockets.
25220527 2014 Mutations in Niemann Pick type C gene are risk factor for Alzheimer's disease.
24915861 2014 Diagnosis of Niemann-Pick disease type C with 7-ketocholesterol screening followed by NPC1/NPC2 gene mutation confirmation in Chinese patients.
24709320 2014 Spermatozoa from mice deficient in Niemann-Pick disease type C2 (NPC2) protein have defective cholesterol content and reduced in vitro fertilising ability.
24501203 2014 All-trans retinoic acid-triggered antimicrobial activity against Mycobacterium tuberculosis is dependent on NPC2.
24438076 2014 Niemann-Pick disease type C2 protein induces triglyceride accumulation in silkworm and mammalian cell lines.
24275569 2014 An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.
24001314 2013 Computational studies of the cholesterol transport between NPC2 and the N-terminal domain of NPC1 (NPC1(NTD)).
23814065 2013 Niemann-pick type C2 deficiency in human fibroblasts confers robust and selective activation of prostaglandin E2 biosynthesis.
23791309 Identification of mutation in NPC2 by exome sequencing results in diagnosis of Niemann-Pick disease type C.
23733943 2013 Abnormal accumulation and recycling of glycoproteins visualized in Niemann-Pick type C cells using the chemical reporter strategy.
23533145 2013 In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine.
23376485 2013 Proteomic analysis of podocyte exosome-enriched fraction from normal human urine.
22962690 2012 Niemann-Pick Type C2 protein contributes to the transport of endosomal cholesterol to mitochondria without interacting with NPC1.
22273177 2012 Loss of Niemann Pick type C proteins 1 and 2 greatly enhances HIV infectivity and is associated with accumulation of HIV Gag and cholesterol in late endosomes/lysosomes.
22183894 2012 Glycine N-methyltransferase deficiency affects Niemann-Pick type C2 protein stability and regulates hepatic cholesterol homeostasis.
22179027 2012 ABCA1-dependent mobilization of lysosomal cholesterol requires functional Niemann-Pick C2 but not Niemann-Pick C1 protein.
22095670 2012 Novel function of Niemann-Pick C1-like 1 as a negative regulator of Niemann-Pick C2 protein.
21811417 2011 Adaptations to endosymbiosis in a cnidarian-dinoflagellate association: differential gene expression and specific gene duplications.
21740003 2011 Sterol transfer between cyclodextrin and membranes: similar but not identical mechanism to NPC2-mediated cholesterol transfer.
21412152 2011 Function of the Niemann-Pick type C proteins and their bypass by cyclodextrin.
21269460 2011 Initial characterization of the human central proteome.
21253586 2011 A novel role for Niemann-Pick disease type 2C protein in papillae formation.
21084287 2011 Somatic cell plasticity and Niemann-Pick type C2 protein: fibroblast activation.
20674861 2010 Identification of surface residues on Niemann-Pick C2 essential for hydrophobic handoff of cholesterol to NPC1 in lysosomes.
20674853 2010 Transfer of cholesterol by the NPC team.
20650896 2010 Somatic cell plasticity and Niemann-pick type C2 protein: adipocyte differentiation and function.
20628086 2010 Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
20007703 2010 Niemann-Pick C1 functions independently of Niemann-Pick C2 in the initial stage of retrograde transport of membrane-impermeable lysosomal cargo.
19913121 2009 Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.
19746448 2009 Physiological and coordinate downregulation of the NPC1 and NPC2 genes are associated with the sequestration of LDL-derived cholesterol within endocytic compartments.
19723497 2009 Nogo-B receptor stabilizes Niemann-Pick type C2 protein and regulates intracellular cholesterol trafficking.
19664597 2009 Identification of NPC2 protein as interaction molecule with C2 domain of human Nedd4L.
19252935 2009 Molecular analysis of NPC1 and NPC2 gene in 34 Niemann-Pick C Italian patients: identification and structural modeling of novel mutations.
19232397 2009 Niemann-Pick C2 (NPC2) and intracellular cholesterol trafficking.
19159218 2009 Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry.
18832164 2008 NPC1/NPC2 function as a tag team duo to mobilize cholesterol.
18823126 2008 Regulation of sterol transport between membranes and NPC2.
18772377 2008 NPC2 facilitates bidirectional transfer of cholesterol between NPC1 and lipid bilayers, a step in cholesterol egress from lysosomes.
18636124 2008 Polymorphisms in the estrogen receptor 1 and vitamin C and matrix metalloproteinase gene families are associated with susceptibility to lymphoma.
18029348 2008 Toward a confocal subcellular atlas of the human proteome.
17895371 2007 The subcellular localization of the Niemann-Pick Type C proteins depends on the adaptor complex AP-3.
17470133 2007 Niemann-Pick C disease: functional characterization of three NPC2 mutations and clinical and molecular update on patients with NPC2.
17387528 2007 Association study of cholesterol-related genes in Alzheimer's disease.
17018531 2006 NPC2, the protein deficient in Niemann-Pick C2 disease, consists of multiple glycoforms that bind a variety of sterols.
16772431 2006 HE1/NPC2 status in human reproductive tract and ejaculated spermatozoa: consequence of vasectomy.
16606609 2006 Mechanism of cholesterol transfer from the Niemann-Pick type C2 protein to model membranes supports a role in lysosomal cholesterol transport.
16548883 2006 Transcriptomic and proteomic analyses of rhabdomyosarcoma cells reveal differential cellular gene expression in response to enterovirus 71 infection.
16374838 2006 NPC2 is expressed in human and murine liver and secreted into bile: potential implications for body cholesterol homeostasis.
16141411 2005 Liver X receptor activation controls intracellular cholesterol trafficking and esterification in human macrophages.
16126423 Niemann-Pick C disease: use of denaturing high performance liquid chromatography for the detection of NPC1 and NPC2 genetic variations and impact on management of patients and families.
15937921 2005 Niemann-Pick type C disease: subcellular location and functional characterization of NPC2 proteins with naturally occurring missense mutations.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15110773 2004 In vivo interaction between the human dehydrodolichyl diphosphate synthase and the Niemann-Pick C2 protein revealed by a yeast two-hybrid system.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
14662784 Vasectomy influences expression of HE1 but not HE2 and HE5 genes in human epididymis.
12955717 2003 Identification of 58 novel mutations in Niemann-Pick disease type C: correlation with biochemical phenotype and importance of PTC1-like domains in NPC1.
12719428 2003 NPC1 and NPC2 regulate cellular cholesterol homeostasis through generation of low density lipoprotein cholesterol-derived oxysterols.
12591949 2003 The integrity of a cholesterol-binding pocket in Niemann-Pick C2 protein is necessary to control lysosome cholesterol levels.
12508121 2003 The DNA sequence and analysis of human chromosome 14.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12447927 2002 Frontal lobe atrophy due to a mutation in the cholesterol binding protein HE1/NPC2.
12398991 2002 Sterols and intracellular vesicular trafficking: lessons from the study of NPC1.
12125814 2002 The Niemann-Pick C proteins and trafficking of cholesterol through the late endosomal/lysosomal system.
11567215 2001 Niemann-Pick disease type C: spectrum of HE1 mutations and genotype/phenotype correlations in the NPC2 group.
11125141 2000 Identification of HE1 as the second gene of Niemann-Pick C disease.
10479477 1999 Niemann-Pick C1 is a late endosome-resident protein that transiently associates with lysosomes and the trans-Golgi network.
8924505 1996 Molecular cloning and characterization of HE1, a major secretory protein of the human epididymis.
8418812 1993 Region-specific variation of gene expression in the human epididymis as revealed by in situ hybridization with tissue-specific cDNAs.
8125298 1994 Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides.
1693137 1990 Cloning and analysis of mRNAs expressed specifically in the human epididymis.