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AB223014

Recombinant human PCSK9 (mutated D374Y) protein (Active)

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Recombinant human PCSK9 (mutated D374Y) protein (Active) is a Human Full Length protein, in the 31 to 692 aa range, expressed in HEK 293 cells, with >92%, < 1 EU/µg endotoxin level, suitable for FuncS, ELISA, SDS-PAGE.

View Alternative Names

NARC1, PSEC0052, PCSK9, Proprotein convertase subtilisin/kexin type 9, Neural apoptosis-regulated convertase 1, Proprotein convertase 9, Subtilisin/kexin-like protease PC9, NARC-1, PC9

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Functional Studies - Recombinant human PCSK9 (mutated D374Y) protein (Active) (AB223014)
  • FuncS

Unknown

Functional Studies - Recombinant human PCSK9 (mutated D374Y) protein (Active) (AB223014)

FACS analysis shows that ab223014 inhibits LDL uptake in HepG2 cells. The EC50 for this effect is 0.0689-0.3049 μg/mL.

Functional Studies - Recombinant human PCSK9 (mutated D374Y) protein (Active) (AB223014)
  • FuncS

Supplier Data

Functional Studies - Recombinant human PCSK9 (mutated D374Y) protein (Active) (AB223014)

Loaded Recombinant human LDL Receptor protein (Active) (ab220570) on Protein A Biosensor, can bind Recombinant human PCSK9 protein (ab223014) with an affinity constant of 0.329 nM as determined in BLI assay.

Functional Studies - Recombinant human PCSK9 (mutated D374Y) protein (Active) (AB223014)
  • FuncS

Unknown

Functional Studies - Recombinant human PCSK9 (mutated D374Y) protein (Active) (AB223014)

FACS analysis shows that the effect of ab223014 inhibiting LDL uptake in HepG2 cells was neutralized by anti-human PCSK9 antibody. The concentration of PCSK9 used is 5 μg/ml. The EC50 for anti-human PCSK9 antibody is 6.816-12.67 μg/mL.

ELISA - Recombinant human PCSK9 (mutated D374Y) protein (Active) (AB223014)
  • ELISA

Supplier Data

ELISA - Recombinant human PCSK9 (mutated D374Y) protein (Active) (AB223014)

Immobilized Human LDL R, His Tag at 10 μg/mL (100 μL/well) can bind Recombinant human PCSK9 protein (ab223014) with a linear range of 0.004-0.063 μg/mL.

SDS-PAGE - Recombinant human PCSK9 (mutated D374Y) protein (Active) (AB223014)
  • SDS-PAGE

Unknown

SDS-PAGE - Recombinant human PCSK9 (mutated D374Y) protein (Active) (AB223014)

Human PCSK9 (D374Y), His Tag on SDS-PAGE under reducing (R) condition. The gel was stained overnight with Coomassie Blue. The protein migrates as 17 kDa and 66 kDa due to glycosylation and proteolytic digestion.

Key facts

Purity

>92% SDS-PAGE

Endotoxin level

< 1 EU/µg

Expression system

HEK 293 cells

Tags

His tag C-Terminus

Applications

FuncS, SDS-PAGE, ELISA

applications

Biologically active

Yes

Biological activity

Measured by its binding ability in a functional ELISA. Immobilized Human LDL R, His Tag at 10 μg/mL (100 μL/well) can bind Recombinant human PCSK9 protein (ab223014) with a linear range of 0.004-0.063 μg/mL.

Measured by its binding ability in a BLI assay. Loaded Recombinant human LDL Receptor protein (Active) (ab220570) on Protein A Biosensor, can bind Recombinant human PCSK9 protein (ab223014) with an affinity constant of 0.329 nM.

Accession

Q8NBP7

Animal free

No

Carrier free

No

Species

Human

Reconstitution

Reconstitute at 200 µg/mL in water

Storage buffer

pH: 7.4 Constituents: PBS, 5% Trehalose

storage-buffer

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Reactivity data

{ "title": "Reactivity Data", "filters": { "stats": ["", "Reactivity", "Dilution Info", "Notes"] }, "values": { "FuncS": { "reactivity":"TESTED_AND_REACTS", "dilution-info":"", "notes":"<p></p>" }, "ELISA": { "reactivity":"TESTED_AND_REACTS", "dilution-info":"", "notes":"<p></p>" }, "SDS-PAGE": { "reactivity":"TESTED_AND_REACTS", "dilution-info":"", "notes":"<p>ab223014 carries a polyhistidine tag at the C-terminus. This protein undergoes autocatalytic cleavage to release the pro-peptide and mature chain. The pro-peptide and mature chain are associated through non‑covalent interactions and with a calculated MW of 13.8 kDa and 58.2 kDa respectively. The protein migrates as 17 kDa and 66 kDa under reducing condition (SDS-PAGE) due to glycosylation. The D374Y mutation results in higher affinity of PCSK9 for LDLR.</p>" } } }
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Sequence info

[{"sequence":"QEDEDGDYEELVLALRSEEDGLAEAPEHGTTATFHRCAKDPWRLPGTYVVVLKEETHLSQSERTARRLQAQAARRGYLTKILHVFHGLLPGFLVKMSGDLLELALKLPHVDYIEEDSSVFAQSIPWNLERITPPRYRADEYQPPDGGSLVEVYLLDTSIQSDHREIEGRVMVTDFENVPEEDGTRFHRQASKCDSHGTHLAGVVSGRDAGVAKGASMRSLRVLNCQGKGTVSGTLIGLEFIRKSQLVQPVGPLVVLLPLAGGYSRVLNAACQRLARAGVVLVTAAGNFRDDACLYSPASAPEVITVGATNAQDQPVTLGTLGTNFGRCVDLFAPGEDIIGASSYCSTCFVSQSGTSQAAAHVAGIAAMMLSAEPELTLAELRQRLIHFSAKDVINEAWFPEDQRVLTPNLVAALPPSTHGAGWQLFCRTVWSAHSGPTRMATAVARCAPDEELLSCSSFSRSGKRRGERMEAQGGKLVCRAHNAFGGEGVYAIARCCLLPQANCSVHTAPPAEASMGTRVHCHQQGHVLTGCSSHWEVEDLGTHKPPVLRPRGQPNQCVGHREASIHASCCHAPGLECKVKEHGIPAPQEQVTVACEEGWTLTGCSALPGTSHVLGAYAVDNTCVVRSRDVSTTGSTSEGAVTAVAICCRSRHLAQASQELQ","proteinLength":"Full Length","predictedMolecularWeight":"72 kDa","actualMolecularWeight":null,"aminoAcidEnd":692,"aminoAcidStart":31,"nature":"Recombinant","expressionSystem":"HEK 293 cells","accessionNumber":"Q8NBP7","tags":[{"tag":"His","terminus":"C-Terminus"}]}]
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Properties and storage information

Shipped at conditions
Blue Ice
Appropriate short-term storage conditions
-20°C
Appropriate long-term storage conditions
-20°C
Storage information
Avoid freeze / thaw cycle
True
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Supplementary information

This supplementary information is collated from multiple sources and compiled automatically.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a protein responsible for the regulation of cholesterol levels by binding to low-density lipoprotein receptors (LDLR) on hepatocytes. This interaction marks the LDLRs for degradation reducing the liver's ability to clear LDL cholesterol from the blood. PCSK9 has a molecular weight of approximately 74 kDa. The protein is mainly expressed in the liver but is also found in the intestine and kidneys. PCSK9 is referred to as NARC-1 standing for neural apoptosis-regulated convertase 1 highlighting its role in the liver's cholesterol management system.
Biological function summary

PCSK9 influences cholesterol homeostasis by its important role in degrading LDL receptors. It functions independently rather than as part of larger protein complexes. PCSK9 gains particular interest in therapeutic contexts where its inhibition can lead to increased LDLR levels and enhanced clearance of LDL cholesterol. Biotinylated PCSK9 and mouse PCSK9 variants provide significant tools for experimental study. Kits such as the PCSK9 ELISA kit enable detailed measurement of PCSK9 levels in blood samples providing insights into cholesterol metabolism dynamics.

Pathways

PCSK9 operates within the lipid metabolism pathway and the cholesterol biosynthesis pathway. The protein's activity affects the fate of LDL cholesterol within these pathways. It interacts with proteins such as apolipoprotein B (ApoB) which plays a central role in the structural component of LDL particles. The modulation of these pathways by PCSK9 highlights the significance of its function in maintaining cardiovascular health and managing cholesterol levels.

PCSK9 is closely linked to hypercholesterolemia and coronary artery disease. Mutations in PCSK9 can lead to autosomal dominant hypercholesterolemia due to its effect on LDL receptor degradation. Other proteins such as ApoB and LDLR are involved in these conditions tightly interacting with PCSK9's regulatory function. A better understanding of PCSK9's role offers potential therapeutic targets for cardiovascular disease interventions especially through the development of PCSK9 antibodies and PCSK9 assays that adjust cholesterol levels.
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Specifications

Form

Lyophilized

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General info

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 (PubMed : 18039658). 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 (PubMed : 17461796, PubMed : 18197702, PubMed : 18799458, PubMed : 22074827). 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 (PubMed : 18660751). 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.

Sequence similarities

Belongs to the peptidase S8 family.

Post-translational modifications

Cleavage by furin and PCSK5 generates a truncated inactive protein that is unable to induce LDLR degradation.. Undergoes autocatalytic cleavage in the endoplasmic reticulum to release the propeptide from the N-terminus and the cleavage of the propeptide is strictly required for its maturation and activation. The cleaved propeptide however remains associated with the catalytic domain through non-covalent interactions, preventing potential substrates from accessing its active site. As a result, it is secreted from cells as a propeptide-containing, enzymatically inactive protein.. Phosphorylation protects the propeptide against proteolysis.

Subcellular localisation

Endosome

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Product protocols

For this product, it's our understanding that no specific protocols are required. You can visit:
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Target data

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 (PubMed : 18039658). 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 (PubMed : 17461796, PubMed : 18197702, PubMed : 18799458, PubMed : 22074827). 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 (PubMed : 18660751). 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.
See full target information PCSK9 mutated D374Y
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