|Detection of Human Proprotein Convertase 9/PCSK9 by Western Blot. Western blot shows lysates of HeLa human cervical epithelial carcinoma cell line and Jurkat human acute T cell leukemia cell line. PVDF membrane was probed with 1 µg/mL of Sheep Anti-Human Proprotein Convertase 9/PCSK9 Antigen Affinity-purified Polyclonal Antibody (Catalog # AF3888) followed by HRP-conjugated Anti-Goat IgG Secondary Antibody (Catalog # HAF019). A specific band was detected for Pre-Proprotein Convertase 9/PCSK9 at approximately 80 kDa and mature Proprotein Convertase 9/PCSK9 60 kDa (as indicated). This experiment was conducted under reducing conditions and using Immunoblot Buffer Group 1.|
The human PCSK9 gene encodes Proprotein Convertase 9 (PC9), which is also known as Neural Apoptosis Regulated Convertase 1 (NARC1) (1). The deduced amino acid sequence of human PCSK9 consists of a signal peptide (residues 1-30), a pro peptide (residue 31-152), and a mature chain (residues 153-692) that contains a serine protease domain (residues 161-431) found in members of the furin/PC family. PCSK9 protease activity may be limited, since it has only been demonstrated through its own autocatalytic processing (2). After the autocleavage in the ER, the pro domain and mature chain exit the cell together through non-covalent interactions (3). PCSK9 is a key regulator of LDL-cholesterol levels (LDL-C) through binding of the LDL receptor, resulting in the reduction of receptor recycling to the cell surface and the acceleration of receptor degradation in lysosomes (3). Both gain of function (GOF) and loss-of-function (LOF) mutations have been found in the PCSK9 gene (3). GOF mutations are linked to familial autosomal dominant hypercholesterolemia, a disease characterized by elevated plasma levels of LDL-C. In comparison, LOF mutations lead to low levels of LDL-C and protection against coronary heart disease.
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