Recombinant Human NPC1-like intracellular cholesterol transporter 1 (NPC1L1), partial

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Code CSB-EP890689HUl1
Size $388
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  • (Tris-Glycine gel) Discontinuous SDS-PAGE (reduced) with 5% enrichment gel and 15% separation gel.
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Product Details

Purity
Greater than 85% as determined by SDS-PAGE.
Target Names
NPC1L1
Uniprot No.
Research Area
Cardiovascular
Species
Homo sapiens (Human)
Source
E.coli
Expression Region
22-284aa
Target Protein Sequence
EPYTTIHQPGYCAFYDECGKNPELSGSLMTLSNVSCLSNTPARKITGDHLILLQKICPRLYTGPNTQACCSAKQLVSLEASLSITKALLTRCPACSDNFVNLHCHNTCSPNQSLFINVTRVAQLGAGQLPAVVAYEAFYQHSFAEQSYDSCSRVRVPAAATLAVGTMCGVYGSALCNAQRWLNFQGDTGNGLAPLDITFHLLEPGQAVGSGIQPLNEGVARCNESQGDDVATCSCQDCAASCPAIARPQALDSTFYLGQMPGS
Note: The complete sequence including tag sequence, target protein sequence and linker sequence could be provided upon request.
Mol. Weight
33.1 kDa
Protein Length
Partial
Tag Info
N-terminal 6xHis-tagged and C-terminal HA-tagged
Form
Liquid or Lyophilized powder
Note: We will preferentially ship the format that we have in stock, however, if you have any special requirement for the format, please remark your requirement when placing the order, we will prepare according to your demand.
Buffer
If the delivery form is liquid, the default storage buffer is Tris/PBS-based buffer, 5%-50% glycerol. If the delivery form is lyophilized powder, the buffer before lyophilization is Tris/PBS-based buffer, 6% Trehalose, pH 8.0.
Reconstitution
We recommend that this vial be briefly centrifuged prior to opening to bring the contents to the bottom. Please reconstitute protein in deionized sterile water to a concentration of 0.1-1.0 mg/mL.We recommend to add 5-50% of glycerol (final concentration) and aliquot for long-term storage at -20℃/-80℃. Our default final concentration of glycerol is 50%. Customers could use it as reference.
Troubleshooting and FAQs
Storage Condition
Store at -20°C/-80°C upon receipt, aliquoting is necessary for mutiple use. Avoid repeated freeze-thaw cycles.
Shelf Life
The shelf life is related to many factors, storage state, buffer ingredients, storage temperature and the stability of the protein itself.
Generally, the shelf life of liquid form is 6 months at -20°C/-80°C. The shelf life of lyophilized form is 12 months at -20°C/-80°C.
Lead Time
3-7 business days
Notes
Repeated freezing and thawing is not recommended. Store working aliquots at 4°C for up to one week.
Datasheet & COA
Please contact us to get it.

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Target Background

Function
Plays a major role in cholesterol homeostasis. Is critical for the uptake of cholesterol across the plasma membrane of the intestinal enterocyte. Is the direct molecular target of ezetimibe, a drug that inhibits cholesterol absorption. Lack of activity leads to multiple lipid transport defects. The protein may have a function in the transport of multiple lipids and their homeostasis, and may play a critical role in regulating lipid metabolism. Acts as a negative regulator of NPC2 and down-regulates its expression and secretion by inhibiting its maturation and accelerating its degradation.
Gene References into Functions
  1. The results obtained from liver-specific NPC1L1 transgenic mouse (L1-Tg) crossed with LDLR-/- mouse indicated no feedback mechanism to inhibit NPC1L1 function in liver and hepatic expression of NPC1L1 correlated with VLDL secretion in hypercholesterolemia state. PMID: 29601818
  2. Lifelong, genetic inhibition of NPC1L1, mimicking treatment with ezetimibe, does not associate with risk of cancer. PMID: 29106532
  3. Due to their high affinity for the N-terminal domain of NPC1L1, black and cowpea bean peptides produced in the digestive track have the potential to disrupt interactions between NPC1L1 and membrane proteins that lead to cholesterol absorption PMID: 28259659
  4. These experiments demonstrate that cholesterol uptake by NPC1L1 does not require endocytosis; moreover, ezetimibe interferes with NPC1L1's cholesterol adsorption activity without blocking NPC1L1 internalization in RH7777 cells. PMID: 27075173
  5. Novel sequencing techniques are detecting rare variants with larger effect sizes (eg, NPC1L1) , which may further improve on Cardiovascular disease risk prediction. PMID: 27650930
  6. The results demonstrate that NPC1L1 recognizes alpha-tocopherol via its N-terminal domain and mediates alpha-tocopherol uptake through the same mechanism as cholesterol absorption. PMID: 28315682
  7. Simultaneously, these data indicate that R174H, V177I and V1284L NPC1L1 variations in high or low LDL-C individuals may not directly influence cholesterol absorption by NPC1L1. PMID: 27697530
  8. The results of this study identified the association between genetic susceptibility of the NPC1L1 gene and HCV infection, as well as biochemical characteristics of HCV-infected persons in Yunnan, China. PMID: 27769799
  9. exposure to LDL-C-lowering genetic variants in or near NPC1L1 and other genes was associated with a higher risk of type 2 diabetes. These data provide insights into potential adverse effects of LDL-C-lowering therapy. PMID: 27701660
  10. Detailed analysis of the role of NPC1L1 mutations in an exceptional responder to ezetimibe. The results point to a complex set of events in which the combined mutations were shown to affect cholesterol uptake in the presence of ezetimibe. Proteomic analysis suggests that the exceptional response may also lie in the nature of interactions with cytosolic proteins. PMID: 26761771
  11. Study suggests that the G allele of the NPC1L1 polymorphism g1679C>G may be a positive marker of gallstone formation risk. PMID: 26800364
  12. To study whether human NPC1L1 gene is regulated transcriptionally by LRH-1, we have analyzed evolutionary conserved regions (ECRs) in HepG2 cells. PMID: 25739390
  13. No significant association between investigated NPC1L1 variants and risk of coronary atherosclerosis could be observed. PMID: 26253792
  14. Results show that genetic variation in NPC1L1 is associated with a reduction in risk of IVD, with a corresponding reduction in LDL cholesterol, but with a concomitant increased risk of gallstone disease PMID: 25841872
  15. The frequencies of NPC1L1 polymorphisms in Chinese Hans are comparable to Japanese population but totally different from Caucasians, African-Americans and Hispanic individuals PMID: 26492642
  16. demonstrate that Niemann-Pick C1-like 1 (NPC1L1) protein, a cholesterol transporter, plays a central role in intestinal VK uptake and modulates the anticoagulant effect of warfarin. In PMID: 25696002
  17. Lipid-lowering response to ezetimibe is not impacted by the NPC1L1 polymorphisms studied in Chilean hypercholesterolemic subjects. PMID: 25589339
  18. NPC1L1-mediated cholesterol absorption is a major determinant of blood levels of apolipoprotein B-containing atherogenic lipoproteins PMID: 25463095
  19. The effect of lower LDL-C on the risk of coronary heart disease mediated by polymorphisms in NPC1L1, HMGCR, or both is approximately the same per unit lower LDL-C and log-linearly proportional to the absolute exposure to lower LDL-C. PMID: 25770315
  20. NPC1L1 polymorphism is associated with sitosterolaemia. PMID: 25056759
  21. Our study is the first report concerning the genotype and allele frequencies of the gene coding for NPC1L1 in Japanese patients with dyslipidemia. PMID: 24861377
  22. DNA methylation in the promoter region of the NPC1L1 gene appears to be a major mechanism underlying differential expression of NPC1L1 along the length of the gastrointestinal tract. PMID: 24904062
  23. Naturally occurring mutations that disrupt NPC1L1 function were found to be associated with reduced plasma LDL cholesterol levels and a reduced risk of coronary heart disease. PMID: 25390462
  24. Endoplasmic reticulum-associated degradation of Niemann-Pick C1: evidence for the role of heat shock proteins and identification of lysine residues that accept ubiquitin. PMID: 24891511
  25. NPC1L1-133A > G SNP influences the ApoA1 response to ezetimibe monotherapy PMID: 24974575
  26. Herein, authors identify the host cell hepatitis C virus entry factor NPC1L1 as also being required for hepatitis C virus cell-to-cell spread. PMID: 24554660
  27. in patients with hyperlipidemias, G allele of NPC1L1 and APO E4 could account for some of the inter-individual variability in cholesterol absorption PMID: 23415434
  28. Glucose appears to directly modulate NPC1L1 expression via transcriptional mechanisms and the involvement of phosphatase-dependent pathways. PMID: 23139223
  29. The present study suggests that the rs2072183 SNP in NPC1L1 gene and its association with serum lipid profiles are different between the Mulao and Han populations. PMID: 22646906
  30. Lutein absorption is, at least in part, mediated by influx transporters NPC1L1 and SR-B1 rather than mediated by efflux transporters such as ABC (ATP-binding cassette) transporters PMID: 22579005
  31. NPC1L1 down-regulates the expression and secretion of NPC2 by inhibiting its maturation and accelerating its degradation. Hepatic NPC1L1 may control cholesterol homeostasis via the down-regulation of NPC2. PMID: 22095670
  32. the mechanism of cholesterol sensing by NPC1L1 and proposes a mechanism for selective cholesterol absorption PMID: 21602275
  33. These findings demonstrated a direct role of hepatic NPC1L1 in regulating biliary cholesterol excretion and hepatic/blood cholesterol levels, and unequivocally established hepatic NPC1L1 as a target of ezetimibe. PMID: 21683156
  34. The structure of NPC1L1(NTD) reveals a degree of flexibility surrounding the entrance to the sterol binding pocket. PMID: 21525977
  35. PPARalpha positively regulates human NPC1L1 transcription via direct binding to a PPRE. Additionally, PGC1alpha stimulates the SREBP2/HNF4alpha- and PPARalpha/RXRalpha- mediated transactivation of human NPC1L1 PMID: 20953676
  36. dysfunction of the 19 variants on cholesterol absorption is due to the impairment of recycling, subcellular localization, glycosylation, or stability of NPC1L1 PMID: 21189420
  37. inhibition of NPC1L1 by ezetimibe is effective in non-obese patients with nonalcoholic fatty liver disease PMID: 20222991
  38. hepatic NPC1L1 in the liver from Chinese female gallstone patients may be mediated by SREBP2 PMID: 20144195
  39. Polyunsaturated fatty acids down-regulate in vitro expression of the key intestinal cholesterol absorption protein NPC1L1 PMID: 19443194
  40. The transport activity of NPC1L1 variants between cholesterol and alpha-tocopherol, were compared. PMID: 19823104
  41. Single nucleotide polymorphism in NPC1L1 is associated with enhanced cholesterol absorption from the intestine. PMID: 20379057
  42. regulation by SREBP2 and HNF1alpha on the NPC1L1 promoter activity PMID: 20460578
  43. NPC1L1 gene is associated with plasma total and LDL-C levels and coronary heart disease risk. PMID: 19752398
  44. NPC1L1 promoter variants might explain in part the hypercholesterolemic phenotype of some subjects with non-LDL receptor/apolipoprotein B autosomal dominant hypercholesterolemia PMID: 19747803
  45. The -762C allele of NPC1L1 had a higher promoter activity and was associated with a higher serum total cholesterol and LDL-cholesterol level. PMID: 19265861
  46. expression is enriched in the small intestine and is in the brush border membrane of enterocytes PMID: 14976318
  47. NPC1L1 has a role in lipid transport and in diet-induced hypercholesterolemia PMID: 15671032
  48. DNA sequence variants in NPC1L1 are associated with an improvement in response to ezetimibe, a cholesterol absorption inhibitor demonstrated to reduce LDL-cholesterol. PMID: 16297596
  49. nonsynonymous variant technique to demonstrate that genetic variation in NPC1L1 contributes to variability in cholesterol absorption and plasma levels of low-density lipoproteins PMID: 16449388
  50. Intestinal gene expression is altred in type 2 diabetees. Diabetic patients have more NPC1L1 mRNA than the control subjects. PMID: 16518588

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Subcellular Location
Apical cell membrane; Multi-pass membrane protein. Cell membrane; Multi-pass membrane protein. Cytoplasmic vesicle membrane; Multi-pass membrane protein.
Protein Families
Patched family
Tissue Specificity
Widely expressed. Expressed in liver. Also expressed in small intestine, pancreas, kidney, lung, pancreas, spleen, heart, gall bladder, brain, testis, stomach and muscle.
Database Links

HGNC: 7898

OMIM: 608010

KEGG: hsa:29881

STRING: 9606.ENSP00000289547

UniGene: Hs.567486

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