Pcsk9
GeneName
PCSK9
Summary
PCSK9, also known as PC9, PCSK-9, or PC-9, is a 74kDa serine protease that plays a critical role in cholesterol metabolism and homeostasis. It is predominantly expressed in the liver and is secreted into the bloodstream, where it binds to low-density lipoprotein receptors (LDLR) on the surface of cells. This binding leads to the degradation of LDLR, thereby reducing the clearance of LDL particles from the bloodstream. PCSK9 is involved in several biological processes, including lipoprotein metabolism, cellular responses to insulin and starvation, and the regulation of apoptotic processes. It is localised to various cellular compartments, including the endoplasmic reticulum, Golgi apparatus, endosomes, and lysosomes, and is also found at the cell surface and in the extracellular space.
Importance
PCSK9 is relevant to: - Cardiovascular disease, as it is a target for cholesterol-lowering therapies, particularly PCSK9 inhibitors, which enhance LDLR availability and lower LDL cholesterol levels. - Metabolic disorders, given its role in cholesterol homeostasis and response to insulin. - Neurodegenerative diseases, due to its involvement in neurogenesis and neuron differentiation processes. - Kidney development and function, as it is implicated in various developmental processes and metabolic pathways.
Top Products
For researchers investigating PCSK9, we highly recommend the top-selling recombinant antibody, Anti-PCSK9 antibody [EPR7627(2)] (ab181142). This antibody has been validated for use in Western blotting (WB) and immunoprecipitation (IP), making it a versatile tool for your experiments. With 26 citations, it demonstrates a solid reputation within the research community, reflecting its reliability and effectiveness in detecting PCSK9. This recombinant antibody offers the added benefit of batch-to-batch consistency, ensuring that you can trust your results across different experiments. The Human PCSK9 ELISA Kit, Fluorescent (ab229406) is an excellent option for researchers looking to measure PCSK9 levels in their samples.
Abcam Product Citation Summary
The data indicates that PCSK9 is being studied in the context of intestinal cholesterol biosynthesis, specifically using human Caco-2 cells. This suggests a focus on the role of PCSK9 in cholesterol metabolism and its potential implications for gastrointestinal health.
Abcam Product Citation Table
Developmental stage
In the embryo, expressed in the liver at 9 dpc, in the skin and transiently in the telencephalon at 12 dpc, and in the kidney, small intestine and cerebellum at 15 dpc.
Domain
The C-terminal domain (CRD) is essential for the LDLR-binding and degrading activities.
The catalytic domain is responsible for mediating its self-association.
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.
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 (By similarity).
Phosphorylation protects the propeptide against proteolysis.
Sequence Similarities
Belongs to the peptidase S8 family.
Tissue Specificity
Hepatocytes, kidney mesenchymal cells, intestinal ileum, colon epithelia and embryonic brain telencephalon neurons.
Cellular localization
- Cytoplasm
- Secreted
- Endosome
- Lysosome
- Cell surface
- Endoplasmic reticulum
- Golgi apparatus
- 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 co-localizes 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 (By similarity).
Alternative names
Narc1, Pcsk9, Proprotein convertase subtilisin/kexin type 9, Neural apoptosis-regulated convertase 1, Proprotein convertase 9, Subtilisin/kexin-like protease PC9, NARC-1, PC9