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  4. Recombinant Human Proprotein convertase subtilisin/kexin type 9 (PCSK9) (Active)

Recombinant Human Proprotein convertase subtilisin/kexin type 9 (PCSK9) (Active)

Unavailable
  • 货号：
    CSB-AP005741HU
  • 规格：
    ￥1170
  • 图片：
    • (Tris-Glycine gel) Discontinuous SDS-PAGE (reduced) with 5% enrichment gel and 15% separation gel.
  • 其他：

产品详情

  • 纯度：
    Greater than 95% as determined by SDS-PAGE.
  • 内毒素：
    Less than 1.0 EU/μg as determined by LAL method.
  • 生物活性：
    The ED50 as determined by its ability to bind Human LDLR in functional ELISA is less than 200 ug/ml
  • 基因名：
  • Uniprot No.：
  • 别名：
    Convertase subtilisin/kexin type 9 preproprotein; FH3; HCHOLA3; Hypercholesterolemia autosomal dominant 3; LDLCQ1; NARC 1; NARC-1; NARC1; Neural apoptosis regulated convertase 1; Neural apoptosis-regulated convertase 1; PC 9; PC9; PCSK 9; PCSK9; PCSK9_HUMAN; Proprotein convertase 9; Proprotein convertase PC9; Proprotein convertase subtilisin/kexin type 9; PSEC0052; Subtilisin/kexin like protease PC9; Subtilisin/kexin-like protease PC9
  • 种属：
    Homo sapiens (Human)
  • 蛋白长度：
    Full LengthFull Length of Mature Protein
  • 来源：
    Mammalian cell
  • 分子量：
    14 & 59 kDa
  • 表达区域：
    31-152aa & 153-692aa(V474I,G670E)
  • 氨基酸序列
    QEDEDGDYEELVLALRSEEDGLAEAPEHGTTATFHRCAKDPWRLPGTYVVVLKEETHLSQSERTARRLQAQAARRGYLTKILHVFHGLLPGFLVKMSGDLLELALKLPHVDYIEEDSSVFAQ?&?SIPWNLERITPPRYRADEYQPPDGGSLVEVYLLDTSIQSDHREIEGRVMVTDFENVPEEDGTRFHRQASKCDSHGTHLAGVVSGRDAGVAKGASMRSLRVLNCQGKGTVSGTLIGLEFIRKSQLVQPVGPLVVLLPLAGGYSRVLNAACQRLARAGVVLVTAAGNFRDDACLYSPASAPEVITVGATNAQDQPVTLGTLGTNFGRCVDLFAPGEDIIGASSDCSTCFVSQSGTSQAAAHVAGIAAMMLSAEPELTLAELRQRLIHFSAKDVINEAWFPEDQRVLTPNLVAALPPSTHGAGWQLFCRTVWSAHSGPTRMATAIARCAPDEELLSCSSFSRSGKRRGERMEAQGGKLVCRAHNAFGGEGVYAIARCCLLPQANCSVHTAPPAEASMGTRVHCHQQGHVLTGCSSHWEVEDLGTHKPPVLRPRGQPNQCVGHREASIHASCCHAPGLECKVKEHGIPAPQEQVTVACEEGWTLTGCSALPGTSHVLGAYAVDNTCVVRSRDVSTTGSTSEEAVTAVAICCRSRHLAQASQELQ
  • 蛋白标签：
    C-terminal Avi-tagged
  • 产品提供形式：
    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.
  • 缓冲液：
    0.2 μm Filtered 50 mM HEPES, 150 mM NaCl, 20% Glycerol, pH 7.4
  • 储存条件：
    Store at -20°C/-80°C upon receipt, aliquoting is necessary for mutiple use. Avoid repeated freeze-thaw cycles.
  • 保质期：
    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.
  • 货期：
    Basically, we can dispatch the products out in 1-3 working days after receiving your orders. Delivery time may differ from different purchasing way or location, please kindly consult your local distributors for specific delivery time.
    Note: All of our proteins are default shipped with normal blue ice packs, if you request to ship with dry ice, please communicate with us in advance and extra fees will be charged.
  • Datasheet & COA：
    Please contact us to get it.

产品评价

靶点详情

  • 功能：
    Crucial player in the regulation of plasma cholesterol homeostasis. Binds to low-density lipid receptor family members: low density lipoprotein receptor (LDLR), very low density lipoprotein receptor (VLDLR), apolipoprotein E receptor (LRP1/APOER) and apolipoprotein receptor 2 (LRP8/APOER2), and promotes their degradation in intracellular acidic compartments. Acts via a non-proteolytic mechanism to enhance the degradation of the hepatic LDLR through a clathrin LDLRAP1/ARH-mediated pathway. May prevent the recycling of LDLR from endosomes to the cell surface or direct it to lysosomes for degradation. Can induce ubiquitination of LDLR leading to its subsequent degradation. Inhibits intracellular degradation of APOB via the autophagosome/lysosome pathway in a LDLR-independent manner. Involved in the disposal of non-acetylated intermediates of BACE1 in the early secretory pathway. Inhibits epithelial Na(+) channel (ENaC)-mediated Na(+) absorption by reducing ENaC surface expression primarily by increasing its proteasomal degradation. Regulates neuronal apoptosis via modulation of LRP8/APOER2 levels and related anti-apoptotic signaling pathways.
  • 基因功能参考文献：
    1. The present study shows that serum PCSK9 levels, but not PCSK9 polymorphisms, are associated with coronary artery disease risk in Southern Chinese Han population, and that serum PCSK9 levels are positively associated with AIP PMID: 30205809
    2. In Japanese male subjects, the concentrations of serum PCSK9 and TBIL were correlated with periodontal parameters. PMID: 29516504
    3. C679X loss-of-function PCSK9 variant lowers fasting glucose levels. PMID: 30227170
    4. There was no protective or no deleterious effect of carrying PCSK9 LOF mutations on AD [Alzheimer disease]prevalence nor on age of onset, even when stratified by apolipoprotein E epsilon 4 genotype or by gender. Conclusion: Our data indicate that carrying PCSK9 LOF mutations has a neutral effect on neurocognitive health and the prevalence of AD [Alzheimer disease]. PMID: 29562810
    5. High serum PCSK9 levels predict acute coronary syndrome occurrence at 24-month follow-up after carotid endarterectomy in patients with severe carotid artery stenosis. PMID: 29754909
    6. Taken together, the present study provides evidence of a pro-inflammatory action of PCSK9 on macrophages, mainly dependent by the LDLR. PMID: 29396513
    7. HepG2 cell lines transfected with siRNA directed to PCSK9 were challenged with Hcy, homocysteine thiolactone (HTL), testosterone, 5alpha-dihydroxytestosterone (5alpha-DHT), or estradiol for 24h, leading to an overt expression of PCSK9 and down-regulated expression of LDLR. PMID: 29660344
    8. Plasma PCSK9 levels and lipoprotein distribution are preserved in hypolipoproteinemia carriers. PMID: 29852278
    9. Inverse correlation between PCSK9 and CD36 in hypertrophic adipocytes may be associated with AAA development. PMID: 30210081
    10. Plasma Lp(a) level was associated with PCSK9 in patients with heterozygous familial hypercholesterolemia PMID: 29129821
    11. s performed an analysis of public databases and literature for every variant published associated with FH, in the genes LDLR, APOB, and PCSK9. PMID: 29261184
    12. PCSK9 levels increase as glucose metabolism deteriorated. Serum PCSK9 levels positively correlated with 2-hPG (2-h postchallenge plasma glucose) in Chinese Han patients with glucose metabolic diseases. PMID: 29343301
    13. PCSK9i-treated patients had higher rates of cardiovascular comorbidities. PMID: 28849360
    14. PCSK9 overexpression in the aorta may promote acute aortic dissection. PMID: 29197601
    15. High PCSK9 expression is associated with metabolic syndrome. PMID: 28283395
    16. A positive association between plasma PCSK9 concentration and coronary artery calcification in untreated patients with angina-like chest pain was observed in our study, suggesting that further investigation may be needed in order to confirm our primary findings and explore the clinical implications PMID: 28166668
    17. In conclusion, PCSK9 inhibitors such as alirocumab may be an excellent lipid lowering agent in patients with statin intolerance and myotonic dystrophy. PMID: 29056268
    18. Obesity and type 2 diabetes were associated with significantly higher serum levels in young women, but not in young men PMID: 28093849
    19. Reduction of LDL-C With PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder (RUTHERFORD; phase 2) and RUTHERFORD-2 (phase 3). PMID: 29066265
    20. We present a case of homozygous familial defective apolipoprotein B-100 due to APOB R3500Q (rs5742904) treated with evolocumab ..Identification of a patient homozygous for familial defective apolipoprotein B-100(FDB) and successful treatment with PCSK9 inhibition PMID: 28988723
    21. A complex link between hepatitis C virus infection and PCSK9 has emerged, in which a bidirectional loop of interactions is conceivable. (Review) PMID: 28722331
    22. Genetically determined PCSK9 deficiency might be associated with ectopic fat accumulation. PMID: 28758421
    23. These results suggest that PCSK9 rs7552841 is associated with plasma lipids profiles only in female adolescents, but not in male students. This association can be modified and negated by posttraumatic stress disorder. PMID: 29081489
    24. PCSK9 carriers tended to be associated with an increased response to simvastatin therapy PMID: 28851085
    25. PCSK9 polymorphism may affect HIV pathogenesis, particularly in HIV/hepatitis C coinfected women. A likely mechanism for this effect is PCSK9-mediated regulation of cholesterol metabolism. PMID: 29120899
    26. There was no relationship between plasma PCSK9 levels and arterial stiffness. PMID: 28816230
    27. PCSK9 variants associated with lower LDL cholesterol were also associated with circulating higher fasting glucose concentration, body weight and an increased risk of type 2 diabetes. PMID: 27908689
    28. ABGL4, LRP8 and PCSK9 polymorphisms and gene interactions increase cardiometabolic risk. PMID: 27853278
    29. these results provide insights into a novel coordinated interplay among three important molecular players in lipid homeostasis - circulating miR-24, miR-223 and PCSK9 - whose regulation is affected by HCV infection and treatment-based viral cure. PMID: 28864162
    30. The present study aimed to explore the direct toxicity of proprotein convertase subtilisin/kexin type 9 (PCSK9) to atherosclerosis (AS) and its association with apoptotic endothelial cells. PMID: 28656218
    31. The minor allele frequency of the PCSK9 A443T, I474V, E670G, and C679X polymorphisms in healthy and malaria-infected Malian children was 0.12, 0.20, 0.26, and 0.02, respectively. 17.6% of subjects carried two of the four SNPs examined. Carriers of the minor allele of the E670G PCSK9 polymorphism might be more susceptible to severe malaria. PMID: 29447211
    32. Circulating PCSK9 concentration as a continuous variable was not significantly associated with the risk of cardiovascular events. More well-designed studies are needed to clarify the role of PCSK9 in cardiovascular risk. PMID: 28413188
    33. Data indicate that the elevation in plasma apoB-48 levels associated with FH is independent of PCSK9 levels. PMID: 28619117
    34. we discuss current experimental and clinical evidence of the role of PCSK9 and its inhibition on lipid metabolism and several pathologic conditions with a focus on clinical outcomes--{REVIEW} PMID: 27533061
    35. The E670G polymorphism of the PCSK9 gene is associated with the lipid levels and risk for coronary heart disease. PMID: 28981947
    36. Here, we assess the available evidence for the association of PCSK9 status with the incidence and control of diabetes mellitus in preclinical and clinical studies, and identify molecular mechanisms regulating PCSK9 expression in the diabetic state. [Review] PMID: 28111330
    37. These results demonstrated the molecular mechanisms of how HCV modulates PCSK9 promoter activity and advanced our understanding on the mutual interactions between HCV and PCSK9. PMID: 29397939
    38. These findings provide useful information for researchers interested in the fields of PCSK9 genetics and cardiovascular risk prediction not only for designing future studies, but also for clinical and public health applications PMID: 28606094
    39. Circulating PCSK9 is significantly related to arterial stiffness, independent of sex and menopausal status in women. PMID: 28468788
    40. Study demonstrated PCSK9 as a direct target of miR-224 and increased miR-224 or decreased PCSK9 could promote apoptosis and suppress proliferation, invasion of tumor cell line in pancreatic neuroendocrine neoplasms. PMID: 28036293
    41. There are no associations between PCSK9 levels and either glucose or lipid homeostasis parameters. Nevertheless, a statistically significant link was observed between PCSK9 and markers of insulin homeostasis, solely in CF patients who presented normal glucose tolerance. PMID: 28447578
    42. PCSK9 interacts with heparan sulfate proteoglycans.Heparan sulfate proteoglycans binding is required for PCSK9-induced LDLR degradation. PMID: 28894089
    43. The results of this study suggest that these biomarker PCSK9 can serve as a potential non-invasive early diagnosis platform reflecting PiB-PET imaging for Mild Cognitive Impairment and Alzheimer's Disease. PMID: 27392853
    44. PCSK9 is not altered specifically in PCOS. PMID: 29109005
    45. A high-throughput time-resolved fluorescence resonance energy transfer assay for autocleavage has been developed using a PCSK9 monoclonal antibody that is sensitive to the conformational changes that occur upon maturation of the proprotein. PMID: 27412534
    46. These studies provide a definitive characterization of the composition and activity of the truncated form of PCSK9 found in human serum PMID: 24776539
    47. PCSK9 loss-of-function variants were associated with a pooled odds ratio for coronary heart disease of 0.51 in blacks and 0.82 in whites. PMID: 28768753
    48. Mature PCSK9 associated with atheroma volume and impaired vessel remodeling in HeFH patients with coronary artery disease PMID: 28502498
    49. Despite having lower LDL-C, circulating PCSK9 levels were increased in patients coinfected with HIV and HCV in parallel with elevations in the inflammatory, proatherogenic cytokine interleukin-6. PMID: 27130349
    50. Circulating PCSK9 is associated with New-onset diabetes after transplantation (NODAT) in renal transplant recipients. The PCSK9 pathway may contribute to the pathogenesis of NODAT. PMID: 28461454

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  • 相关疾病：
    Hypercholesterolemia, autosomal dominant, 3 (HCHOLA3)
  • 亚细胞定位：
    Cytoplasm. Secreted. Endosome. Lysosome. Cell surface. Endoplasmic reticulum. Golgi apparatus. Note=Autocatalytic cleavage is required to transport it from the endoplasmic reticulum to the Golgi apparatus and for the secretion of the mature protein. Localizes to the endoplasmic reticulum in the absence of LDLR and colocalizes to the cell surface and to the endosomes/lysosomes in the presence of LDLR. The sorting to the cell surface and endosomes is required in order to fully promote LDLR degradation.
  • 蛋白家族：
    Peptidase S8 family
  • 组织特异性：
    Expressed in neuro-epithelioma, colon carcinoma, hepatic and pancreatic cell lines, and in Schwann cells.
  • 数据库链接：

    HGNC: 20001

    OMIM: 603776

    KEGG: hsa:255738

    STRING: 9606.ENSP00000303208

    UniGene: Hs.18844