UNIPROT #

Q8NBP7

PROTEIN NAME

PCSK9

SYNONYMS

Convertase subtilisin/kexin type 9 preproprotein antibody; FH3 antibody; HCHOLA3 antibody; Hypercholesterolemia autosomal dominant 3 antibody; LDLCQ1 antibody; NARC 1 antibody; NARC-1 antibody; NARC1 antibody; Neural apoptosis regulated convertase 1 antibody; Neural apoptosis-regulated convertase 1 antibody; PC 9 antibody; PC9 antibody; PCSK 9 antibody; PCSK9 antibody; PCSK9_HUMAN antibody; Proprotein convertase 9 antibody; Proprotein convertase PC9 antibody; Proprotein convertase subtilisin/kexin type 9 antibody; PSEC0052 antibody; Subtilisin/kexin like protease PC9 antibody; Subtilisin/kexin-like protease PC9 antibody

SEQUENCE SIMILARITIES

Belongs to the peptidase S8 family.

TISSUE SPECIFICITY

Expressed in neuro-epithelioma, colon carcinoma, hepatic and pancreatic cell lines, and in Schwann cells.

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.

SUBCELLULAR LOCATION

Secreted.

FUNCTION

Proprotein convertase subtilisin/kexin type 9 (PCSK9), also known as NARC-1, is a 692 amino acid protein that belongs to the peptidase S8 family and contains one peptidase S8 domain. Important in the regulation of plasma cholesterol homeostasis, PCSK9 binds to low-density lipid receptor family members LDLR, very low-density lipid receptor (VLDLR) and apolipoprotein receptor 2 (ApoER2) and promotes their degradation in intracellular acidic compartments. PCSK9 also plays a role in neuronal differentiation and apoptosis. PCSK9 is expressed in Shwann cells, neuro-epithelioma, colon carcinoma, and hepatic and pancreatic cell lines. PCSK9 levels in the brain are highest in the cerebellum during perinatal development, with ischemia causing increased levels in the adult brain. Defects in the gene encoding this protein causes the autosomal dominant disorder familial hypercholesterolemia 3 (HCHOLA3).