Recombinant Human Proprotein Convertase 9/PCSK9 Protein, CF

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 to 30), a pro peptide (residue 31 to 152), and a mature chain (residues 153 to 692) that contains a serine protease domain (residues 161 to 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.