Product Details

Purity

Greater than 95% as determined by SDS-PAGE.

Endotoxin

Less than 1.0 EU/ug as determined by LAL method.

Activity

①Measured by its binding ability in a functional ELISA. Immobilized Anti-PCSK9 recombinant antibody (CSB-RA017647MA2HU) at 2 μg/mL can bind Human PCSK9 protein. The EC50 is 7.450-8.692 ng/mL.
②Measured by its binding ability in a functional ELISA. Immobilized Human PCSK9 at 1 μg/mL on streptavidin coated plates can bind Anti-PCSK9 recombinant antibody (CSB-RA017647MA2HU) . The EC50 is 0.3792-1.157 ng/mL.

Target Names

PCSK9

Uniprot No.

Q8NBP7

Alternative Names

Proprotein convertase subtilisin/kexin type 9; EC:3.4.21.-; Neural apoptosis-regulated convertase 1 (NARC-1); Proprotein convertase 9 (PC9); Subtilisin/kexin-like protease PC9; PCSK9; NARC1; PSEC0052

Species

Homo sapiens (Human)

Source

Mammalian cell

Expression Region

31-692aa(D374Y)

Target Protein Sequence

QEDEDGDYEELVLALRSEEDGLAEAPEHGTTATFHRCAKDPWRLPGTYVVVLKEETHLSQSERTARRLQAQAARRGYLTKILHVFHGLLPGFLVKMSGDLLELALKLPHVDYIEEDSSVFAQSIPWNLERITPPRYRADEYQPPDGGSLVEVYLLDTSIQSDHREIEGRVMVTDFENVPEEDGTRFHRQASKCDSHGTHLAGVVSGRDAGVAKGASMRSLRVLNCQGKGTVSGTLIGLEFIRKSQLVQPVGPLVVLLPLAGGYSRVLNAACQRLARAGVVLVTAAGNFRDDACLYSPASAPEVITVGATNAQDQPVTLGTLGTNFGRCVDLFAPGEDIIGASSYCSTCFVSQSGTSQAAAHVAGIAAMMLSAEPELTLAELRQRLIHFSAKDVINEAWFPEDQRVLTPNLVAALPPSTHGAGWQLFCRTVWSAHSGPTRMATAVARCAPDEELLSCSSFSRSGKRRGERMEAQGGKLVCRAHNAFGGEGVYAIARCCLLPQANCSVHTAPPAEASMGTRVHCHQQGHVLTGCSSHWEVEDLGTHKPPVLRPRGQPNQCVGHREASIHASCCHAPGLECKVKEHGIPAPQEQVTVACEEGWTLTGCSALPGTSHVLGAYAVDNTCVVRSRDVSTTGSTSEGAVTAVAICCRSRHLAQASQELQ

Mol. Weight

76.0 kDa

Protein Length

Full Length

Tag Info

C-terminal 10xHis-Avi-tagged

Form

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

Lyophilized from a 0.2 μm filtered PBS, 6% Trehalose, pH 7.4

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°C/-80°C. Our default final concentration of glycerol is 50%. Customers could use it as reference.

Troubleshooting and FAQs

Protein 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.

Description

PCSK9 regulates cholesterol homeostasis by promoting degradation of the LDL receptor, and the D374Y gain-of-function mutation intensifies this interaction, making it a critical tool for studying hypercholesterolemia mechanisms and therapeutic intervention strategies. This full-length variant (aa 31–692) demonstrates robust binding activity in functional ELISA, achieving an EC50 of 7.450–8.692 ng/mL when captured by immobilized anti-PCSK9 antibody and an EC50 of 0.3792–1.157 ng/mL in the reverse orientation with immobilized biotinylated protein binding soluble antibody, providing quantitative benchmarks for inhibitor screening and IC50 determination in drug candidate evaluation. The C-terminal His-Avi tag enables oriented immobilization via streptavidin without interfering with the catalytic domain, supporting kinetic parameter analysis and substrate specificity profiling where precise orientation is essential. Purity exceeding 95% by SDS-PAGE and endotoxin below 1.0 EU/μg satisfy the quality thresholds commonly required for enzymatic activity assays and structural studies including crystallography.

Target Background

Function

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.

Gene References into Functions

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
In Japanese male subjects, the concentrations of serum PCSK9 and TBIL were correlated with periodontal parameters. PMID: 29516504
C679X loss-of-function PCSK9 variant lowers fasting glucose levels. PMID: 30227170
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
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
Taken together, the present study provides evidence of a pro-inflammatory action of PCSK9 on macrophages, mainly dependent by the LDLR. PMID: 29396513
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
Plasma PCSK9 levels and lipoprotein distribution are preserved in hypolipoproteinemia carriers. PMID: 29852278
Inverse correlation between PCSK9 and CD36 in hypertrophic adipocytes may be associated with AAA development. PMID: 30210081
Plasma Lp(a) level was associated with PCSK9 in patients with heterozygous familial hypercholesterolemia PMID: 29129821
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
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
PCSK9i-treated patients had higher rates of cardiovascular comorbidities. PMID: 28849360
PCSK9 overexpression in the aorta may promote acute aortic dissection. PMID: 29197601
High PCSK9 expression is associated with metabolic syndrome. PMID: 28283395
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
In conclusion, PCSK9 inhibitors such as alirocumab may be an excellent lipid lowering agent in patients with statin intolerance and myotonic dystrophy. PMID: 29056268
Obesity and type 2 diabetes were associated with significantly higher serum levels in young women, but not in young men PMID: 28093849
Reduction of LDL-C With PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder (RUTHERFORD; phase 2) and RUTHERFORD-2 (phase 3). PMID: 29066265
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
A complex link between hepatitis C virus infection and PCSK9 has emerged, in which a bidirectional loop of interactions is conceivable. (Review) PMID: 28722331
Genetically determined PCSK9 deficiency might be associated with ectopic fat accumulation. PMID: 28758421
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
PCSK9 carriers tended to be associated with an increased response to simvastatin therapy PMID: 28851085
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
There was no relationship between plasma PCSK9 levels and arterial stiffness. PMID: 28816230
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
ABGL4, LRP8 and PCSK9 polymorphisms and gene interactions increase cardiometabolic risk. PMID: 27853278
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
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
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
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
Data indicate that the elevation in plasma apoB-48 levels associated with FH is independent of PCSK9 levels. PMID: 28619117
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
The E670G polymorphism of the PCSK9 gene is associated with the lipid levels and risk for coronary heart disease. PMID: 28981947
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
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
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
Circulating PCSK9 is significantly related to arterial stiffness, independent of sex and menopausal status in women. PMID: 28468788
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
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
PCSK9 interacts with heparan sulfate proteoglycans.Heparan sulfate proteoglycans binding is required for PCSK9-induced LDLR degradation. PMID: 28894089
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
PCSK9 is not altered specifically in PCOS. PMID: 29109005
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
These studies provide a definitive characterization of the composition and activity of the truncated form of PCSK9 found in human serum PMID: 24776539
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
Mature PCSK9 associated with atheroma volume and impaired vessel remodeling in HeFH patients with coronary artery disease PMID: 28502498
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
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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Involvement in disease

Hypercholesterolemia, autosomal dominant, 3 (HCHOLA3)

Subcellular Location

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.

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

Code	CSB-MP017647HU(M)-B
Abbreviation	Recombinant Human PCSK9 protein (D374Y), Biotinylated (Active)
MSDS	MSDS Datasheet
Size	$182
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Image	(Tris-Glycine gel) Discontinuous SDS-PAGE (reduced) with 5% enrichment gel and 15% separation gel. Activity Measured by its binding ability in a functional ELISA. Immobilized Anti-PCSK9 recombinant antibody (CSB-RA017647MA2HU) at 2 μg/ml can bind Human PCSK9 protein. The EC₅₀ is 7.450-8.692 ng/mL. Biological Activity Assay Activity Measured by its binding ability in a functional ELISA. Immobilized Human PCSK9 at 1 μg/ml on streptavidin coated plates can bind Anti-PCSK9 recombinant antibody (CSB-RA017647MA2HU) . The EC₅₀ is 0.3792-1.157 ng/mL. Biological Activity Assay The purity of PCSK9 was greater than 95% as determined by SEC-HPLC
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Recombinant Human Proprotein convertase subtilisin/kexin type 9 (PCSK9) (D374Y), Biotinylated (Active)

Product Details

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