| Description | This recombinant anti-PCSK9 antibody (clone 3D2) recognizes human proprotein convertase subtilisin/kexin type 9. The PCSK9/LDLR pathway of 3D2-treated HepG2 cells was inhibited in vitro. 3D2 is an potential PCSK9 inhibitor and 3D2 inhibits PCSK9 function in vitro and in vivo. |
| Clonality | Monoclonal |
| Host Species | Human |
| Target Species | Human |
| Affinity | KD = 0.196±0.156 nM |
| 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: 18799458, PubMed: 17461796, PubMed: 18197702, 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. |
| Isotype | Human IgG |
| Expression Species | HEK293F or CHO cell line |
| Conjugation | Unconjugated |
| Purity | >95% |
| Endotoxin | <1 EU/mg |
| Form | Liquid |
| Purification | Protein A purified |
| Sterility | 0.2 μM filtered |
| Formulation | PBS, pH 7.4 |
| Preservation | No preservatives |
| Stabilizer | No stabilizers |
| Storage | Store at 4°C within a week. For longer storage, aliquot and store at -20°C. |
| Application | ELISA; WB; Inhib |
| Application Notes | The binding of 3D2 to PCSK9 protein was detected by indirect ELISA. The levels of LDLR protein of 3D2- and/or mevinolin-treated HepG2 cells were assessed by Western Blotting (3D2 concentration: 5 µg/mL, 10 µg/mL). 3D2 inhibited the PCSK9/LDLR pathway of Hep-G2 cells and resulted in a 3-fold increase in hepatic LDLR levels. |
| ELISA | Enzyme-Linked Immunosorbent Assay Protocol |
| WB | Western Blot Protocol |
| FC | Flow Cytometry Protocol |
| Post Translational Modification | 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. |
