Recombinant Human Npc1-Like Intracellular Cholesterol Transporter 1 (NPC1L1) Protein (His&HA)

Name: Recombinant Human Npc1-Like Intracellular Cholesterol Transporter 1 (NPC1L1) Protein (His&HA)
Brand: Beta LifeScience
SKU: BLC-00269P
Availability: InStock

Greater than 85% as determined by SDS-PAGE.

Collections: All products, High-quality recombinant proteins, Other recombinant proteins

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Product Overview

Description	Recombinant Human Npc1-Like Intracellular Cholesterol Transporter 1 (NPC1L1) Protein (His&HA) is produced by our E.coli expression system. This is a protein fragment.
Purity	Greater than 85% as determined by SDS-PAGE.
Uniprotkb	Q9UHC9
Target Symbol	NPC1L1
Species	Homo sapiens (Human)
Expression System	E.coli
Tag	N-6His&C-HA
Target Protein Sequence	EPYTTIHQPGYCAFYDECGKNPELSGSLMTLSNVSCLSNTPARKITGDHLILLQKICPRLYTGPNTQACCSAKQLVSLEASLSITKALLTRCPACSDNFVNLHCHNTCSPNQSLFINVTRVAQLGAGQLPAVVAYEAFYQHSFAEQSYDSCSRVRVPAAATLAVGTMCGVYGSALCNAQRWLNFQGDTGNGLAPLDITFHLLEPGQAVGSGIQPLNEGVARCNESQGDDVATCSCQDCAASCPAIARPQALDSTFYLGQMPGS
Expression Range	22-284aa
Protein Length	Partial
Mol. Weight	33.1 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	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.
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
Database References	HGNC: 7898 OMIM: 608010 KEGG: hsa:29881 STRING: 9606.ENSP00000289547 UniGene: PMID: 29601818 Lifelong, genetic inhibition of NPC1L1, mimicking treatment with ezetimibe, does not associate with risk of cancer. PMID: 29106532 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 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 Novel sequencing techniques are detecting rare variants with larger effect sizes (eg, NPC1L1) , which may further improve on Cardiovascular disease risk prediction. PMID: 27650930 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 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 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 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 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 Study suggests that the G allele of the NPC1L1 polymorphism g1679C>G may be a positive marker of gallstone formation risk. PMID: 26800364 To study whether human NPC1L1 gene is regulated transcriptionally by LRH-1, we have analyzed evolutionary conserved regions (ECRs) in HepG2 cells. PMID: 25739390 No significant association between investigated NPC1L1 variants and risk of coronary atherosclerosis could be observed. PMID: 26253792 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 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 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 Lipid-lowering response to ezetimibe is not impacted by the NPC1L1 polymorphisms studied in Chilean hypercholesterolemic subjects. PMID: 25589339 NPC1L1-mediated cholesterol absorption is a major determinant of blood levels of apolipoprotein B-containing atherogenic lipoproteins PMID: 25463095 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 NPC1L1 polymorphism is associated with sitosterolaemia. PMID: 25056759 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 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 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 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 NPC1L1-133A > G SNP influences the ApoA1 response to ezetimibe monotherapy PMID: 24974575 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 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 Glucose appears to directly modulate NPC1L1 expression via transcriptional mechanisms and the involvement of phosphatase-dependent pathways. PMID: 23139223 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 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 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 the mechanism of cholesterol sensing by NPC1L1 and proposes a mechanism for selective cholesterol absorption PMID: 21602275 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 The structure of NPC1L1(NTD) reveals a degree of flexibility surrounding the entrance to the sterol binding pocket. PMID: 21525977 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 dysfunction of the 19 variants on cholesterol absorption is due to the impairment of recycling, subcellular localization, glycosylation, or stability of NPC1L1 PMID: 21189420 inhibition of NPC1L1 by ezetimibe is effective in non-obese patients with nonalcoholic fatty liver disease PMID: 20222991 hepatic NPC1L1 in the liver from Chinese female gallstone patients may be mediated by SREBP2 PMID: 20144195 Polyunsaturated fatty acids down-regulate in vitro expression of the key intestinal cholesterol absorption protein NPC1L1 PMID: 19443194 The transport activity of NPC1L1 variants between cholesterol and alpha-tocopherol, were compared. PMID: 19823104 Single nucleotide polymorphism in NPC1L1 is associated with enhanced cholesterol absorption from the intestine. PMID: 20379057 regulation by SREBP2 and HNF1alpha on the NPC1L1 promoter activity PMID: 20460578 NPC1L1 gene is associated with plasma total and LDL-C levels and coronary heart disease risk. PMID: 19752398 NPC1L1 promoter variants might explain in part the hypercholesterolemic phenotype of some subjects with non-LDL receptor/apolipoprotein B autosomal dominant hypercholesterolemia PMID: 19747803 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 expression is enriched in the small intestine and is in the brush border membrane of enterocytes PMID: 14976318 NPC1L1 has a role in lipid transport and in diet-induced hypercholesterolemia PMID: 15671032 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 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 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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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.

Reminder: Before opening the tube cap, we recommend that you quickly centrifuge for 20-30 seconds in a small centrifuge, so that the protein attached to the tube cap or the tube wall can be aggregated at the bottom of the tube. Our quality control procedures ensure that each tube contains the correct amount of protein, and although sometimes you can't see the protein powder, the amount of protein in the tube is still very precise.

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