Tclin PCSK9 Proprotein convertase subtilisin/kexin type 9

Protein Summary

Description

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. 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. [provided by RefSeq, Feb 2014]

Uniprot Accession IDs

• Q8NBP7
• A8T640
• C0JYY9
• Q5PSM5
• Q5SZQ2

Gene Name

• PCSK9

Ensembl ID

• ENST00000302118
• ENSP00000303208
• ENSG00000169174

Symbol

• NARC1
• FH3
• PC9
• NARC1
• LDLCQ1
• NARC-1
• HCHOLA3

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
molecular function	0.98
biological process	0.97
ligand (protein) perturbation	0.83
disease	0.66
biological term	0.65

Protein Classes

PANTHER Classes

Protein / ... / Serine Protease / Proprotein Convertase Subtilisin/kexin Type 9

DTO Classes

Protein / Enzyme / Protease / Serine Protease / Proprotein Convertase Subtilisin/kexin Type 9

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 4743.62   (req: < 5)

Gene RIFs: 683   (req: <= 3)

Antibodies: 572   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 4743.62   (req: >= 5)

Gene RIFs: 683   (req: > 3)

Antibodies: 572   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 40

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 62

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drugs: 3