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This gene encodes a member of the subtilisin-like proprotein convertase family, which includes proteases that process protein and peptide precursors trafficking through regulated or constitutive branches of the secretory pathway. The encoded protein undergoes an autocatalytic processing event with its prosegment in the ER and is constitutively secreted as an inactive protease into the extracellular matrix and trans-Golgi network. It is expressed in liver, intestine and kidney tissues and escorts specific receptors for lysosomal degradation. It plays a role in cholesterol and fatty acid metabolism. Mutations in this gene have been associated with autosomal dominant familial hypercholesterolemia. Alternative splicing results in multiple transcript variants.
Protein class

Disease related genes, Enzymes, FDA approved drug targets, Human disease related genes, Plasma proteins

Predicted location

Intracellular, Secreted (different isoforms)

Single cell type specificity

Cell type enhanced (Hepatocytes, Alveolar cells type 2, Alveolar cells type 1, Gastric mucus-secreting cells)

Immune cell specificity

Not detected in immune cells

Cell line specificity

Cell line enhanced (A-431, CACO-2, HaCaT, HeLa, RPTEC TERT1)


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. Interacts (via the C-terminal domain) with ANXA2 (via repeat Annexin 1); the interaction inhibits the degradation of LDLR (PubMed:18799458).

Molecular function

Hydrolase, Protease, Serine protease

More Types Infomation

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