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

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Code CSB-AP005741HU
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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 95% as determined by SDS-PAGE.
Endotoxin Less than 1.0 EU/μg as determined by LAL method.
Activity The ED50 as determined by its ability to bind Human LDLR in functional ELISA is less than 200 ug/ml
Target Names PCSK9
Uniprot No. Q8NBP7
Research Area Cardiovascular
Alternative Names 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
Species Homo sapiens (Human)
Source Mammalian cell
Expression Region 31-152aa & 153-692aa(V474I,G670E)
Complete Sequence QEDEDGDYEELVLALRSEEDGLAEAPEHGTTATFHRCAKDPWRLPGTYVVVLKEETHLSQSERTARRLQAQAARRGYLTKILHVFHGLLPGFLVKMSGDLLELALKLPHVDYIEEDSSVFAQ & SIPWNLERITPPRYRADEYQPPDGGSLVEVYLLDTSIQSDHREIEGRVMVTDFENVPEEDGTRFHRQASKCDSHGTHLAGVVSGRDAGVAKGASMRSLRVLNCQGKGTVSGTLIGLEFIRKSQLVQPVGPLVVLLPLAGGYSRVLNAACQRLARAGVVLVTAAGNFRDDACLYSPASAPEVITVGATNAQDQPVTLGTLGTNFGRCVDLFAPGEDIIGASSDCSTCFVSQSGTSQAAAHVAGIAAMMLSAEPELTLAELRQRLIHFSAKDVINEAWFPEDQRVLTPNLVAALPPSTHGAGWQLFCRTVWSAHSGPTRMATAIARCAPDEELLSCSSFSRSGKRRGERMEAQGGKLVCRAHNAFGGEGVYAIARCCLLPQANCSVHTAPPAEASMGTRVHCHQQGHVLTGCSSHWEVEDLGTHKPPVLRPRGQPNQCVGHREASIHASCCHAPGLECKVKEHGIPAPQEQVTVACEEGWTLTGCSALPGTSHVLGAYAVDNTCVVRSRDVSTTGSTSEEAVTAVAICCRSRHLAQASQELQ
Mol. Weight 14 & 59 kDa
Protein Length Full Length of Mature Protein
Tag Info C-terminal Avi-tagged
Form Liquid
Buffer 0.2 μm filtered 50 mM HEPES, 150 mM NaCl, 20% Glycerol, pH 7.4
Troubleshooting
and FAQs
Protein FAQs
Storage Condition Store at -20°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 Basically, we can dispatch the products out in 5-10 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.
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.

Target Data

Function Crucial player in the regulation of plasma cholesterol homeostasis. Binds to low-density lipid receptor family members
Gene References into Functions
  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. Authors 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
  51. PCSK9 inhibits hepatitis C virus replication through interacting with NS5A. PMID: 29235977
  52. PCSK9 levels were significantly higher in patients with peripheral artery disease (PAD), especially those with advanced PAD. PMID: 27207972
  53. In statin treated asymptomatic familial hypercholesterolemia patients, elevated PCSK9 and Lp(a) levels are independently associated with the presence and severity of coronary artery calcification, a good predictor of coronary artery disease PMID: 27594539
  54. PCSK9 has a role in cardiovascular health; PCSK9 levels are modestly but significantly associated with increased risk of total CV events [review and meta-analysis] PMID: 27501130
  55. LY3015014 is a humanized immunoglobulin G4 (IgG4) monoclonal antibody that binds to the catalytic domain of PCSK9. PMID: 27822850
  56. Increased PCSK9 levels are associated with higher platelet reactivity and predictive of ischemic events in acute coronary syndrome. PMID: 27810295
  57. Identify LDLR, APOB and PCSK9 novel mutations causing familial hypercholesterolemia in the central south region of China. PMID: 28235710
  58. Both circulating PCSK9 and SORT1 levels are elevated in coronary artery disease patients. PMID: 27846466
  59. Rare variants of APOB or PCSK9 were identified in nine of the 22 study patients with extremely low LDL-C levels PMID: 29036232
  60. PCSK9 plays a direct role on Abca1-mediated cholesterol efflux through a downregulation of Abca1 gene and Abca1 protein expression. This extrahepatic effect may influence relevant steps in the pathogenesis of atherosclerosis, such as foam cell formation. PMID: 27940374
  61. kidney function per se does not impact significantly PCSK9 metabolism PMID: 28391915
  62. Sirolimus therapy in heart transplant patients is associated with elevation in PCSK9 levels which is not associated with sirolimus-induced hypercholesterolemia. PMID: 28028691
  63. results demonstrate that Fc-modified anti-PCKS9 antibodies may enable less frequent or lower dosing of antibodies by improved recycling into the blood PMID: 28817679
  64. PCSK9 inhibits lipoprotein(a) clearance through the LDLR. PMID: 28750079
  65. PCSK9 variants reduced fasting LDL-C as well as fasting triglycerides. PMID: 28673045
  66. Proprotein convertase subtilisin/kexin 9 V4I variant with LDLR mutations modifies the phenotype of familial hypercholesterolemia PMID: 27206942
  67. PCSK9 associated with Familial Hypercholesterolemia and Polygenic Hypercholesterolemia in patients with Acute Coronary Syndrome , age /=160 mg/dl. PMID: 28958330
  68. Results clearly that PCSK9 serum concentrations were associated to liver function and mortality, pointed to the disturbance of steroid regulation in patients with end-stage liver disease and an association of such disturbance with mortality. Further studies are required to acquire a more detailed understanding of the role of PCSK9 in liver-related mortality. PMID: 28727814
  69. Use Crispr-Cas system to introduce nonsense variants into PCSK9 to lower blood cholesterol levels. PMID: 28751571
  70. PCSK9 decreased in youth participating in an intensive dietary intervention. Change in HOMA-IR was associated with change in PCSK9, independent of weight loss, suggesting an important relationship with insulin sensitivity. PMID: 28228332
  71. these studies support that reductions in Lp(a) with PCSK9 inhibition are partly due to increased LDLR-mediated uptake. In most situations, Lp(a) appears to compete poorly with LDL for LDLR binding and internalization, but when LDLR expression is increased with evolocumab, particularly in the setting of low circulating LDL, Lp(a) is reduced. PMID: 27102113
  72. Plasma levels of proprotein convertase subtilisin/kexin type 9 (PCSK9), apolipoprotein C-III (apoC3) and small dense low density lipoprotein cholesterol (sdLDL-C) showed significant interactions with current dyslipidemias, and were predictive in the screening. PMID: 27713142
  73. Some loss of function variants in PCSK9 are associated with enhanced LDL cholesterol lowering response to statin therapy. PMID: 26902539
  74. These observations suggest positive feedback interplay between SMC-derived PCSK9 and mtDNA damage in the proinflammatory milieu involving mtROS. This interaction results in cellular injury, characterized by apoptosis-a hallmark of atherosclerosis. PMID: 27197615
  75. PCSK9 level is not associated with systolic or diastolic blood pressure in hypertensives or normotensives, but it positively correlates with carotid intima-media thickness in hypertensives in univariate but not multivariate analyses, and further researches are needed. PMID: 27075829
  76. results reveal that the tanshinone IIA modulates LDLR level and activity via down-regulation of PCSK9 expression in hepatic cells PMID: 27617748
  77. This article reviews the functions and regulatory mechanisms of PCSK9. The effects of PCSK9 on the LDL receptor, the relationship of this convertase with IDOL, and treatments currently available against hypercholesterolemia are also discussed. [review] PMID: 28587771
  78. LC n-3 PUFA intake is associated with a lower risk of nonfatal MI in C-allele carriers of PCSK9 rs11206510 (n = 799) but not in non-C-allele carriers (n = 3188). PMID: 28330911
  79. the zymogen form of PCSK9 adopts a structure that is distinct from the processed form and is unable to bind a mimetic peptide based on the EGF-A domain of the LDLr. PMID: 27534510
  80. CRP increased PCSK9 expression by activating p38MAPK-HNF1alpha pathway, with a certain downstream impairment in LDL metabolism in HepG2 cells. PMID: 27633999
  81. PCSK9 C-terminal domain (CTD) was found to be essential to induce LDLR degradation both upon its overexpression in cells or via the extracellular pathway. PMID: 27280970
  82. Results show that circulating PCSK9 concentration increases with the severity of hepatic fat accumulation in patients at risk of nonalcoholic fatty liver disease. PMID: 27222915
  83. PCSK9 inhibition with alirocumab on top of statin treatment has the potential to lower LDL cholesterol in some autosomal recessive hypercholesterolemia patients. PMID: 27079874
  84. CRISPR-Cas9 therapy targeting the human PCSK9 gene in chimeric liver-humanized mice bearing human hepatocytes. PMID: 26941020
  85. PCSK9 regulates monocyte CCR2 expression and chemotaxis. PMID: 28232185
  86. PCSK9 is down-regulated in patients with rheumatoid arthritis. PMID: 27606890
  87. Carriers of the PCSK9 R46L genetic variant have lower very low-density lipoprotein and low-density lipoprotein particle concentrations, lower lipoprotein(a) levels, and lower secretory phospholipase A2 and lipoprotein-associated phospholipase A2 activity, reducing cardiovascular risk. PMID: 27856457
  88. PCSK9 R46L carriers have lower levels of lipoprotein(a) and LDL cholesterol and is associated with reduced risk of aortic valve stenosis and myocardial infarction. PMID: 27218270
  89. Low LDL cholesterol levels due to PCSK9 and HMGCR variants had no causal effect on high risk of Alzheimer's disease, vascular dementia, any dementia, or Parkinson's disease; however, low LDL cholesterol levels may have a causal effect in reducing the risk of Alzheimer's disease. PMID: 28438747
  90. conditions that cause ER stress regardless of their ability to dysregulate ER Ca(2+) inhibit PCSK9 secretion, thereby reducing PCSK9-mediated LDLR degradation and promoting LDLR-dependent hepatic cholesterol uptake. PMID: 27909053
  91. Even though LDLR-R410S and LDLR-WT were similar in levels of cell surface and total receptor and bound equally well to LDL or extracellular PCSK9, the LDLR-R410S was resistant to exogenous PCSK9-mediated degradation in endosomes/lysosomes and showed reduced LDL internalization and degradation relative to LDLR-WT. PMID: 27998977
  92. Lipid therapy today and tomorrow: anti-PCSK9 PMID: 27241696
  93. First human antibodies were recently approved as the first immunotherapeutic agents for the treatment of severe hypercholesterolemia and in patients with statin intolerance. An additional PCSK9 antibody is presently being studied in phase III clinical trials.[review] PMID: 27215417
  94. Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to low-density lipoprotein (LDL) receptors leading to their degradation in the liver. Inhibition of PCSK9 leads to an increase in LDL receptors and as a result to a reduction of LDL cholesterol in blood. [review] PMID: 27215418
  95. Furthermore, the effect of reduction of LDL-C by proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition and by the cholesteryl ester transfer protein (CETP) inhibitor anacetrapib on cardiovascular events is currently being investigated in large clinical outcome study programs. [review] PMID: 27215419
  96. Further information on long-term efficacy, tolerability and cost-effectiveness of PCSK9 inhibition and possibilities of implementation in the healthcare system are awaited from ongoing clinical outcome trials, such as FOURIER, ODYSSEY OUTCOMES, SPIRE 1 and 2 involving more than 70,000 high-risk patients. [review] PMID: 27193908
  97. The 2 or 4week subcutaneous therapy with the recently approved antibodies alirocumab and evolocumab for inhibition of proprotein convertase subtilisin-kexin type 9 (PCSK9) reduces low-density lipoprotein cholesterol (LDL-C) in addition to statins and ezetimibe by 50-60 %. [review] PMID: 27207595
  98. study provides the first evidence that GPC3 can modulate the PCSK9 extracellular activity as a competitive binding partner to the LDLR in HepG2 cells. PMID: 27758865
  99. Proprotein convertase subtilisin kexin 9 (PCSK9) inhibitors reduce the production of LDL particles and this further reduces cholesterol delivery to the liver. PMID: 28424373
  100. PCSK9 level is differentially regulated by gender during aging. PMID: 27241838

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Involvement in disease Hypercholesterolemia, autosomal dominant, 3 (HCHOLA3)
Subcellular Location Cytoplasm, Secreted, Endosome, Lysosome, Cell surface, Endoplasmic reticulum, Golgi apparatus
Protein Families Peptidase S8 family
Tissue Specificity Expressed in neuro-epithelioma, colon carcinoma, hepatic and pancreatic cell lines, and in Schwann cells.
Database Links

HGNC: 20001

OMIM: 603776

KEGG: hsa:255738

STRING: 9606.ENSP00000303208

UniGene: Hs.18844

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