Recombinant Human Npc Intracellular Cholesterol Transporter 1 (NPC1) Protein (His-Myc)

Name: Recombinant Human Npc Intracellular Cholesterol Transporter 1 (NPC1) Protein (His-Myc)
Brand: Beta LifeScience
SKU: BLC-07732P
Availability: InStock

Greater than 90% as determined by SDS-PAGE.

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Product Overview

Description	Recombinant Human Npc Intracellular Cholesterol Transporter 1 (NPC1) Protein (His-Myc) is produced by our Yeast expression system. This is a protein fragment.
Purity	Greater than 90% as determined by SDS-PAGE.
Uniprotkb	O15118
Target Symbol	NPC1
Synonyms	Niemann-Pick C1 protein
Species	Homo sapiens (Human)
Expression System	Yeast
Tag	C-6His-Myc
Target Protein Sequence	QSCVWYGECGIAYGDKRYNCEYSGPPKPLPKDGYDLVQELCPGFFFGNVSLCCDVRQLQTLKDNLQLPLQFLSRCPSCFYNLLNLFCELTCSPRQSQFLNVTATEDYVDPVTNQTKTNVKELQYYVGQSFANAMYNACRDVEAPSSNDKALGLLCGKDADACNATNWIEYMFNKDNGQAPFTITPVFSDFPVHGMEPMNNATKGCDESVDEVTAPCSCQDCSIVCGPKPQPPPPPAPWT
Expression Range	23-261aa
Protein Length	Partial
Mol. Weight	30.2 kDa
Research Area	Cardiovascular
Form	Liquid or Lyophilized powder
Buffer	Liquid form: default storage buffer is Tris/PBS-based buffer, 5%-50% glycerol. Lyophilized powder form: the buffer before lyophilization is Tris/PBS-based buffer, 6% Trehalose, pH 8.0.
Reconstitution	Briefly centrifuged the vial prior to opening to bring the contents to the bottom. Reconstitute protein in deionized sterile water to a concentration of 0.1-1.0 mg/mL. It is recommended to add 5-50% of glycerol (final concentration) and aliquot for long-term storage at -20°C/-80°C. The default final concentration of glycerol is 50%.
Storage	1. Store at -20°C/-80°C upon receipt, aliquoting is necessary for mutiple use. 2. Avoid repeated freeze-thaw cycles. 3. Store working aliquots at 4°C for up to one week. 4. In general, protein in liquid form is stable for up to 6 months at -20°C/-80°C. Protein in lyophilized powder form is stable for up to 12 months at -20°C/-80°C.
Notes	Repeated freezing and thawing is not recommended. Store working aliquots at 4°C for up to one week.

Target Details

Target Function	Intracellular cholesterol transporter which acts in concert with NPC2 and plays an important role in the egress of cholesterol from the endosomal/lysosomal compartment. 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. Cholesterol binds to NPC1 with the hydroxyl group buried in the binding pocket. Binds oxysterol with higher affinity than cholesterol. May play a role in vesicular trafficking in glia, a process that may be crucial for maintaining the structural and functional integrity of nerve terminals (Probable).; (Microbial infection) Acts as an endosomal entry receptor for ebolavirus.
Subcellular Location	Late endosome membrane; Multi-pass membrane protein. Lysosome membrane; Multi-pass membrane protein.
Protein Families	Patched family
Database References	HGNC: 7897 OMIM: 257220 KEGG: hsa:4864 STRING: 9606.ENSP00000269228 UniGene: Hs.464779
Associated Diseases	Niemann-Pick disease C1 (NPC1)

Gene Functions References

Results propose that, depending on the location of the cholesterol ligand, a dynamical interface between the NPC2 and NPC1 N-terminal domain (NTD) proteins exists. Structural features of a particular interface can lower the energy barrier and stabilize the passage of the cholesterol substrate from NPC2 to NPC1(NTD). PMID: 30181526
These data support the hypothesis that cholesterol is transported through interactions between two or more NPC1 molecules. PMID: 30047864
Mutation in the NPC1 gene is associated with Niemann-Pick type C. PMID: 28167839
pronounced alterations in several proteins linked to autophagy and lysosomal catabolism reflecting vesicular transport obstruction and defective lysosomal turnover resulting from NPC1 deficiency, were observed. PMID: 28134274
Niemann-Pick C1 (NPC1) protein structures suggest mapping of all of the disease-causing mutations for future molecular insights into the pathogenesis of Niemann-Pick type C disease (NPC) disease. PMID: 28784760
This study demonistrated that heterozygous mutations of NPC1 genes could contribute to dementia plus, at least in a subset of patients. PMID: 27792009
Docking of the NPC1-NPC2 complex onto the full-length NPC1 structure reveals a direct cholesterol transfer tunnel between NPC2 and N-terminal domain cholesterol binding pockets, supporting the "hydrophobic hand-off" cholesterol transfer model. PMID: 27551080
Taken together, these studies suggest that Ebola virus requires phosphatidylinositol (3,5) bisphosphate production in cells to promote efficient delivery to NPC1. PMID: 29031163
identification of NPC1 and/or NPC2 mutations combined with descriptions of clinical phenotype, will improve our knowledge of pathogenic mutations and our understanding of genotype-phenotype correlations. PMID: 27339554
Here we report a crystal structure of a large fragment of human NPC1 at 3.6 A resolution, which reveals internal twofold pseudosymmetry along TM 2-13 and two structurally homologous domains that protrude 60 A into the endosomal lumen, and we propose a model for NPC1 function in cholesterol sensing and transport. PMID: 27307437
Sequencing of genomic DNA from GM03123 Led to the identification of a mutation in NPC1 GENE, g.41940G>C (c.1947 + 5G>C; rs770321568) (Fig. 1A), with a minor allele frequency of 0.0000082 PMID: 28328115
this case provides support for the V950M variant being sufficient for adult-onset Niemann-Pick type C disease. PMID: 27900365
We identified major events in NPC1 evolution and revealed and compared orthologs and paralogs of the human NPC1 gene through phylogenetic and protein sequence analyses. We predicted whether an amino acid substitution affects protein function by reducing the organism's fitness. PMID: 26890452
The mutant NPC1 did not significantly reduce cholesterol accumulation, but approximately 85% of the mutants showed reduced cholesterol accumulation when treated with vorinostat or panobinostat. PMID: 28193631
knockdown of TMEM97 also increases levels of residual NPC1 in NPC1-mutant patient fibroblasts and reduces cholesterol storage in an NPC1-dependent manner. Our findings propose TMEM97 inhibition as a novel strategy to increase residual NPC1 levels in cells and a potential therapeutic target for Niemann-Pick type C disease (NP-C). PMID: 27378690
The splicing mutation IVS23 + 3insT was associated in homozygocity with a severe biochemical and clinical phenotype. A possible founder effect for this mutation was demonstrated in the Greek Island, as well as a different origin for each novel mutation PMID: 28472934
Rare loss-of-function NPC1 mutations were identified as being associated with human adiposity with a high penetrance in a Chinese population. PMID: 28130309
Furthermore saturation and intracellular distribution of alpha-Toc seem to be strongly dependent on the availability of this vitamin as well as on the presence of the lysosomal protein NPC1 PMID: 27095633
Two mutations were identified in the NPC1 gene, one of which was novel and its pathogenetic nature was unknown PMID: 26790753
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. PMID: 25764212
Fibroblasts from Niemann-Pick type C (NPC) disease patients with low levels of NPC1 protein have high amounts of procathepsin D but reduced quantities of the mature protein, thus showing a diminished cathepsin D activity. PMID: 26507101
Results identified six novel mutations (PKHD1: p.Thr777Met, p.Tyr2260Cys; ABCB11: p.Val1112Phe, c.611+1G > A, p.Gly628Trpfs*3 and NPC1: p.Glu391Lys) for the diagnostic of inherited infantile cholestatic disorders. PMID: 25771912
NPC1 mutations are substantially enriched in unexplained early onset ataxia, making it high risk group for Niemann-Pick disease type C. PMID: 26338816
these results clearly demonstrated that the over-expression of NPC1 with a defective function in an imatinib-resistant Ph+ acute lymphoblastic leukemia cell line PMID: 26818574
Structure of glycosylated NPC1 luminal domain C reveals insights into NPC2 and Ebola virus interactions PMID: 26846330
Study determined the crystal structure of the primed GP (GPcl) of Ebola virus bound to domain C of NPC1 (NPC1-C); NPC1-C utilizes two protruding loops to engage a hydrophobic cavity on head of GPcl. Upon enzymatic cleavage and NPC1-C binding, conformational change in the GPcl further affects the state of the internal fusion loop, triggering membrane fusion. PMID: 26771495
Here, using live cell imaging, the authors obtained evidence that in contrast to the new model, ebolavirus enters cells through endolysosomes that contain both NPC1 and TPC2. PMID: 26468524
These experiments support a model in which NPC1 protein functions to transfer cholesterol past a lysosomal glycocalyx. PMID: 26578804
An isobaric labeling-based quantitative analysis of proteome of NPC1(I1061T) primary fibroblasts when compared with wild-type cells identified 281 differentially expressed proteins based on stringent data analysis criteria, is reported. PMID: 25873482
NPC1 gene sequencing revealed that he was a compound heterozygote for the p.S954L and p.N1156S mutations. PMID: 25238906
results uncover Akt as a key regulator of NPC1 degradation and link NPC1 to cancer cell proliferation and migration. PMID: 26283546
heterozygous mutations in the NPC1/2 gene might be a risk factor for Alzheimer's disease PMID: 25220527
In a transgenic mouse model, human NPC1 disease was faithfully recapitulated in a NPC1 I1061T mutation knock-in model. PMID: 26019327
This study showed that Niemann-Pick C1 (NPC1), is required for Lloviu virus (LLOV) entry, suggesting that receptor binding would not impose a barrier to LLOV infection. PMID: 25310500
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. PMID: 25251378
A novel NPC1 mutation causing the Niemann-Pick type C disease and segregating to a Greek island has been identified. PMID: 23701245
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 PMID: 24915861
elevated mitochondrial cholesterol levels in NPC1-depleted cells and in NPC2-depleted cells expressing mutant NPC2 that allows endosomal cholesterol trafficking to mitochondria were associated with increased expression of antioxidant response factor Nrf2 PMID: 24790103
role of NPC1 in regulating intracellular cholesterol trafficking and atherosclerosis. PMID: 24296264
These findings show that the AD-like phenotype of NPC model cells can be partly reverted by promoting a non-amyloidogenic processing of APP through the upregulation of GGA1 supporting its preventive role against AD PMID: 24866237
The minor G allele frequency of the rs1788799 polymorphisms in NPC1 might be a protective factor while the rs3764650 polymorphisms of ABCA7 might not be related to sporadic Alzheimer's disease in the Han Chinese population. PMID: 24064683
the NPC1 promoter methylation is a probable mechanism that can result in reduced/impaired NPC1 expression/activity and may thus contribute to progression of cardiovascular diseases. PMID: 23567849
Case Report: loss of NPC1 function, with attendant changes in membrane cholesterol composition, does not significantly modify the insulin resistance phenotype, even in the context of severely impaired INSR function. PMID: 20521171
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 PMID: 24001314
there is an additional sterol-binding site on NPC1 PMID: 23521797
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. PMID: 23733943
lack of Npc1 protein can alter the expression profile of selected transcripts as well as proteins, and APP overexpression influences cerebral pathology by enhancing changes triggered by Npc1 deficiency in the bigenic line. PMID: 23382922
Neuron-only expression of NPC1 does not completely prevent neurodegeneration; the addition of astrocyte expression decreases the rate of decline. PMID: 22495346
this is the first report, showing a role of NPC1 in platelet function and formation but further studies are needed to define how cholesterol storage interferes with these processes PMID: 23010472
Characterization of novel chromosomal microdeletions at 18q11-q12 involving the NPC1 gene in two patients with Niemann-Pick type C disease. PMID: 23142039

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Proteins are sensitive to heat, and freeze-drying can preserve the activity of the majority of proteins. It improves protein stability, extends storage time, and reduces shipping costs. However, freeze-drying can also lead to the loss of the active portion of the protein and cause aggregation and denaturation issues. Nonetheless, these adverse effects can be minimized by incorporating protective agents such as stabilizers, additives, and excipients, and by carefully controlling various lyophilization conditions.

Commonly used protectant include saccharides, polyols, polymers, surfactants, some proteins and amino acids etc. We usually add 8% (mass ratio by volume) of trehalose and mannitol as lyoprotectant. Trehalose can significantly prevent the alter of the protein secondary structure, the extension and aggregation of proteins during freeze-drying process; mannitol is also a universal applied protectant and fillers, which can reduce the aggregation of certain proteins after lyophilization.

Our protein products do not contain carrier protein or other additives (such as bovine serum albumin (BSA), human serum albumin (HSA) and sucrose, etc., and when lyophilized with the solution with the lowest salt content, they often cannot form A white grid structure, but a small amount of protein is deposited in the tube during the freeze-drying process, forming a thin or invisible transparent protein layer.

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