Proprotein Convertase Subtilisin/Kexin Type 9 Human HEK293

Cat. No.	Size	Price
RD172473100	0.1 mg

Technical Data

Type

Recombinant protein

Description

Total 672 AA. MW: 72.4 kDa (calculated). UniProtKB acc. No. Q8NBP7 (Gln31–Gln692). C-terminal His-tag (10 extra AA). Protein identity confirmed by LC-MS/MS.

Amino Acid Sequence

QEDEDGDYEELVLALRSEEDGLAEAPEHGTTATFHRCAKDPWRLPGTYVVVLKEETHLSQSERTARRLQA QAARRGYLTKILHVFHGLLPGFLVKMSGDLLELALKLPHVDYIEEDSSVFAQSIPWNLERITPPRYRADE YQPPDGGSLVEVYLLDTSIQSDHREIEGRVMVTDFENVPEEDGTRFHRQASKCDSHGTHLAGVVSGRDAG VAKGASMRSLRVLNCQGKGTVSGTLIGLEFIRKSQLVQPVGPLVVLLPLAGGYSRVLNAACQRLARAGVV LVTAAGNFRDDACLYSPASAPEVITVGATNAQDQPVTLGTLGTNFGRCVDLFAPGEDIIGASSDCSTCFV SQSGTSQAAAHVAGIAAMMLSAEPELTLAELRQRLIHFSAKDVINEAWFPEDQRVLTPNLVAALPPSTHG AGWQLFCRTVWSAHSGPTRMATAVARCAPDEELLSCSSFSRSGKRRGERMEAQGGKLVCRAHNAFGGEGV YAIARCCLLPQANCSVHTAPPAEASMGTRVHCHQQGHVLTGCSSHWEVEDLGTHKPPVLRPRGQPNQCVG HREASIHASCCHAPGLECKVKEHGIPAPQEQVTVACEEGWTLTGCSALPGTSHVLGAYAVDNTCVVRSRD VSTTGSTSEGAVTAVAICCRSRHLAQASQELQHHHHHHHHHH

Source

HEK293

Purity

Purity as determined by densitometric image analysis: > 95%

SDS-PAGE Gel

12 % SDS-PAGE separation of Human PCSK9 (HEK):
1. M.W. marker – 14, 21, 31, 45, 66, 97 kDa
2. Reduced and boiled sample, 2.5 μg/lane
3. Non-reduced and non-boiled sample, 2.5 μg/lane

Endotoxin

< 0.1 EU/μg

Formulation

0.25–0.70 mg/mL solution in phosphate buffered saline pH 7.4, 20 % (w/v) glycerol, filtered (0.4 μm), frozen.

Reconstitution

Defrost at ambient temperature.Filter sterilize your culture media/working solutions containing this non-sterile product before using in cell culture.

Applications

Western blotting, ELISA, Cell culture and/or animal studies

Shipping

On ice. Upon receipt, store the product at the temperature recommended below.

Storage/Expiration

Store the lyophilized protein at -80 °C. Lyophilized protein remains stable until the expiry date when stored at -80 °C. Aliquot reconstituted protein to avoid repeated freezing/thawing cycles and store at -80 °C for long term storage. Reconstituted protein can be stored at 4 °C for three days.

Quality Control Test

BCA to determine quantity of the protein.

SDS PAGE to determine purity of the protein.

LAL to determine quantity of endotoxin.

Note

This product is intended for research use only.

Summary

Research topic

Atherosclerosis, Cardiovascular disease, Diabetology - Other Relevant Products, Energy metabolism and body weight regulation, Lipoprotein metabolism

Summary

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease that plays an important role in the regulation of serum low-density lipoprotein (LDL) cholesterol by downregulation of LDL receptor, and as such is considered a novel target in cholesterol lowering therapy. LDL cholesterol (LDL-C) binds to LDL receptors (LDLRs) on the surface of hepatic cell where the complex is internalized and transported to the endosome. LDL-C dissociates from the receptor and is catabolized whereas the LDLR is recycled to the cell surface for continued clearance of serum cholesterol. PCSK9 affects the receptor recycling pathway by binding to the LDLR and causing degradation of the receptor within the endosome/lysosome compartment. Degradation of the LDLR results in decreased clearance of serum cholesterol, and as a result a higher risk of hypercholesterolemia. Human genetic studies have shown that “gain-of-function” (GOF) mutations in the PCSK9 gene can lead to a form of familial hypercholesterolemia with a higher risk of cardiovascular disease. In contrast, humans with “loss-of-function” (LOF) mutations in the PCSK9 gene have lower serum cholesterol levels and a lower incidence of cardiovascular disease. Thus PCSK9 had a key impact not only on circulating LDL-C level but also on cardiovascular risk and atherosclerotic process.

Summary References (16)

References to PCSK9

Seidah NG, Benjannet S, Wickham L, Marcinkiewicz J, Jasmin SB, Stifani S, Basak A, Prat A, Chretien M: The secretory proprotein convertase neural apoptosis-regulated convertase 1 (NARC-1): liver regeneration and neuronal differentiation. Proc Natl Acad Sci U S A. 2003;100(3):928-33
Seidah NG, Prat A: The proprotein convertases are potential targets in the treatment of dyslipidemia. J Mol Med (Berl). 2007;85(7):685-96.
Seidah NG, Prat A: The biology and therapeutic targeting of the proprotein convertases. Nat Rev Drug Discov 2012;11(5):367-83
Seidah NG, Awan Z, Chrétien M, Mbikay M: PCSK9: a key modulator of cardiovascular health. Circ Res. 2014;114(6):1022-36
Colbert A, Umble-Romero A, Prokop S, Xu R, Gibbs J, Pederson S: Characterization of a quantitative method to measure free proprotein convertase subtilisin/kexin type 9 in human serum. MAb 2014;6(4):1103-13
Konrad RJ, Troutt JS, Cao G: Effects of currently prescribed LDL-C-lowering drugs on PCSK9 and implications for the next generation of LDL-C-lowering agents. Lipids Health Dis 2011;10:38
Chan JC, Piper DE, Cao Q, Liu D, King C, Wang W, Tang J, Liu Q, Higbee J, Xia Z, Di Y, Shetterly S, Arimura Z, Salomonis H, Romanow WG, Thibault ST, Zhang R, Cao P, Yang XP, Yu T, Lu M, Retter MW, Kwon G, Henne K, Pan O, Tsai MM, Fuchslocher B, Yang E, Zhou L, Lee KJ, Daris M, Sheng J, Wang Y, Shen WD, Yeh WC, Emery M, Walker NP, Shan B, Schwarz M, Jackson SM: A proprotein convertase subtilisin/kexin type 9 neutralizing antibody reduces serum cholesterol in mice and nonhuman primates. Proc Natl Acad Sci 2009;106(24):9820-5
Horton JD, Cohen JC, Hobbs HH: PCSK9: a convertase that coordinates LDL catabolism. J Lipid Res 2009;50 Suppl:S172-7
Welder G, Zineh I, Pacanowski MA, Troutt JS, Cao G, Konrad RJ: High-dose atorvastatin causes a rapid sustained increase in human serum PCSK9 and disrupts its correlation with LDL cholesterol. J Lipid Res. 2010;51(9):2714-21
Alborn WE, Cao G, Careskey HE, Qian YW, Subramaniam DR, Davies J, Conner EM, Konrad RJ: Serum proprotein convertase subtilisin kexin type 9 is correlated directly with serum LDL cholesterol. Clin Chem. 2007;53(10):1814-9
Careskey HE, Davis RA, Alborn WE, Troutt JS, Cao G, Konrad RJ: Atorvastatin increases human serum levels of proprotein convertase subtilisin/kexin type 9. J Lipid Res 2008 Feb;49(2):394-8
Guo YL, Zhang W, Li JJ: PCSK9 and lipid lowering drugs. Clin Chim Acta. 2014;437:66-71
Raal F, Panz V, Immelman A, Pilcher G: Elevated PCSK9 levels in untreated patients with heterozygous or homozygous familial hypercholesterolemia and the response to high-dose statin therapy. J Am Heart Assoc 2013;2(2)
Almontashiri NA, Vilmundarson RO, Ghasemzadeh N, Dandona S, Roberts R, Quyyumi AA, Chen HH, Stewart AF: Plasma PCSK9 levels are elevated with acute myocardial infarction in two independent retrospective angiographic studies. PLoS One 2014;9(9)
Leander K, Mälarstig A, Van't Hooft FM, Hyde C, Hellénius ML, Troutt JS, Konrad RJ, Öhrvik J, Hamsten A, de Faire 2: Circulating Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Predicts Future Risk of Cardiovascular Events Independently of Established Risk Factors. Circulation 2016;133(13):1230-9
Chao TH, Chen IC, Li YH, Lee PT, Tseng SY: Plasma Levels of Proprotein Convertase Subtilisin/Kexin Type 9 Are Elevated in Patients With Peripheral Artery Disease and Associated With Metabolic Disorders and Dysfunction in Circulating Progenitor Cells. J Am Heart Assoc. 2016;5(5)

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