(Rhesus Macaque) Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Macaca Mulatta Recombinant Protein

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

By similarity.

Cofactor: Calcium

By similarity.

Enzyme regulation: Its proteolytic activity is autoinhibited by the non-covalent binding of the propeptide to the catalytic domain. Inhibited by EGTA

By similarity.

Subunit structure: 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

By similarity.

Subcellular location: Cytoplasm

By similarity. Secreted

By similarity. Endosome

By similarity. Lysosome

By similarity. Cell surface

By similarity. Endoplasmic reticulum

By similarity. Golgi apparatus

By similarity. 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 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.

Domain: The C-terminal domain (CRD) is essential for the LDLR-binding and degrading activities

By similarity.The catalytic domain is responsible for mediating its self-association

By similarity.

Post-translational modification: Cleavage by furin and PCSK5 generates a truncated inactive protein that is unable to induce LDLR degradation

By similarity.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

By similarity.

Sequence similarities: Belongs to the peptidase S8 family.Contains 1 peptidase S8 domain.