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Human PCSK9 Protein 4469

$315.00$1,050.00

Summary

  • Expression: HEK293
  • Functional: Yes (ELISA)
  • Amino Acid Range: Gln31-Gln692
SKU: 4469parent Categories: , Tags: , , ,
Weight1 lbs
Dimensions9 × 5 × 2 in
accession

Q8NBP7

express system

HEK293

product tag

C-His

purity

> 95% as determined by Tris-Bis PAGE;> 95% as determined by HPLC

background

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is an enzyme encoded by the PCSK9 gene in humans on chromosome 1.The first two PCSK9 inhibitors, alirocumab and evolocumab, were approved as once every two week injections, by the U.S. Food and Drug Administration in 2015 for lowering LDL-particle concentrations when statins and other drugs were not sufficiently effective or poorly tolerated.

molecular weight

Due to autocatalytic cleavage, the protein release the pro-form (59 kDa) and mature form (14 kDa). Due to glycosylation, the protein migrates to 65-68 kDa (pro-form) and 15kDa (mature form) based on Tris-Bis PAGE result.

available size

100 µg, 500 µg

endotoxin

Less than 1EU per μg by the LAL method.

Human PCSK9 Protein 4469

protein
Size and concentration
100, 500µg and liquid
Form
Liquid
Storage Instructions
Valid for 12 months from date of receipt when stored at -80°C. Recommend to aliquot the protein into smaller quantities for optimal storage. Please minimize freeze-thaw cycles.
Storage buffer
Shipped with dry ice.
Purity
> 95% as determined by Tris-Bis PAGE
target relevance
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is an enzyme encoded by the PCSK9 gene in humans on chromosome 1.The first two PCSK9 inhibitors, alirocumab and evolocumab, were approved as once every two week injections, by the U.S. Food and Drug Administration in 2015 for lowering LDL-particle concentrations when statins and other drugs were not sufficiently effective or poorly tolerated.
Protein 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)
Gene names
PCSK9,PCSK9 NARC1 PSEC0052
Protein family
Peptidase S8 family
Mass
9606Da
Function
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. {ECO:0000269|PubMed:17461796, ECO:0000269|PubMed:18039658, ECO:0000269|PubMed:18197702, ECO:0000269|PubMed:18660751, ECO:0000269|PubMed:18799458, ECO:0000269|PubMed:22074827, ECO:0000269|PubMed:22493497, ECO:0000269|PubMed:22580899}.
Subellular location
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.
Tissues
TISSUE SPECIFICITY: Expressed in neuro-epithelioma, colon carcinoma, hepatic and pancreatic cell lines, and in Schwann cells.
Structure
SUBUNIT: Monomer. Can self-associate to form dimers and higher multimers which may have increased LDLR degrading activity. The precursor protein but not the mature protein may form multimers. Interacts with APOB, VLDLR, LRP8/APOER2 and BACE1. The full-length immature form (pro-PCSK9) interacts with SCNN1A, SCNN1B and SCNN1G. The pro-PCSK9 form (via C-terminal domain) interacts with LDLR. Interacts (via the C-terminal domain) with ANXA2 (via repeat Annexin 1); the interaction inhibits the degradation of LDLR (PubMed:18799458). {ECO:0000269|PubMed:17461796, ECO:0000269|PubMed:18039658, ECO:0000269|PubMed:18197702, ECO:0000269|PubMed:18660751, ECO:0000269|PubMed:18799458, ECO:0000269|PubMed:21149300, ECO:0000269|PubMed:22493497, ECO:0000269|PubMed:22580899, ECO:0000269|PubMed:24808179}.
Post-translational modification
PTM: Cleavage by furin and PCSK5 generates a truncated inactive protein that is unable to induce LDLR degradation. {ECO:0000269|PubMed:16912035}.; PTM: 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. {ECO:0000269|PubMed:14622975}.; PTM: Phosphorylation protects the propeptide against proteolysis. {ECO:0000269|PubMed:18498363}.
Domain
DOMAIN: Th
Target Relevance information above includes information from UniProt accession : Q8NBP7
The UniProt Consortium

Data

SPR with Human PCSK9 Protein
Human LDLR, His Tag immobilized on CM5 Chip can bind Human PCSK9, His Tag with an affinity constant of 0.35 nM as determined in SPR assay (Biacore T200).
ELISA with Human PCSK9 Protein
Immobilized Human PCSK9, His Tag at 2µg/ml (100µl/Well) on the plate. Dose response curve for Anti-PCSK9 antibody, hFc Tag with the EC50 of 0.16µg/ml determined by ELISA (QC Test).
HPLC of Human PCSK9 Protein
The purity of Human PCSK9 is greater than 95% as determined by SEC-HPLC.
SDS-PAGE gel of Human PCSK9 Protein
Human PCSK9 on Tris-Bis PAGE under reduced condition. The purity is greater than 95%.

Publications

Published literature highly relevant to the biological target of this product and referencing this antibody or clone are retrieved from PubMed database provided by The United States National Library of Medicine at the National Institutes of Health.




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