PCSK9
Summary: 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].
| Name | OMIM ID | Ensembl ID | HGNC ID | PHARMGKB ID | Map Location |
|---|---|---|---|---|---|
| proprotein convertase subtilisin/kexin type 9 | MIM:607786 | Ensembl:ENSG00000169174 | HGNC:HGNC:20001 | PA38617 | 1p32.3 |
GO terms in PCSK9
| Term Type | Evidence Type | GO Term ID | GO Des. |
|---|---|---|---|
| MF | HDA | GO:0003723 | RNA binding |
| MF | IDA | GO:0004252 | serine-type endopeptidase activity |
| MF | IPI | GO:0005515 | protein binding |
| MF | IDA | GO:0019871 | sodium channel inhibitor activity |
| MF | ISS | GO:0030169 | low-density lipoprotein particle binding |
| MF | IDA | GO:0030547 | receptor inhibitor activity |
| MF | ISS | GO:0034185 | apolipoprotein binding |
| MF | ISS | GO:0034189 | very-low-density lipoprotein particle binding |
| MF | IDA | GO:0034190 | apolipoprotein receptor binding |
| MF | IDA | GO:0043621 | protein self-association |
| MF | IDA | GO:0050750 | low-density lipoprotein particle receptor binding |
| MF | IPI | GO:0050750 | low-density lipoprotein particle receptor binding |
| MF | IDA | GO:0070326 | very-low-density lipoprotein particle receptor binding |
| BP | ISS | GO:0001822 | kidney development |
| BP | ISS | GO:0001889 | liver development |
| BP | IDA | GO:0001920 | negative regulation of receptor recycling |
| BP | IDA | GO:0002092 | positive regulation of receptor internalization |
| BP | IEA | GO:0006641 | triglyceride metabolic process |
| BP | IEA | GO:0006644 | phospholipid metabolic process |
| BP | IEA | GO:0006915 | apoptotic process |
| BP | IDA | GO:0007041 | lysosomal transport |
| BP | IEA | GO:0008203 | cholesterol metabolic process |
| BP | ISS | GO:0009267 | cellular response to starvation |
| BP | IDA | GO:0010469 | regulation of signaling receptor activity |
| BP | IDA | GO:0010989 | negative regulation of low-density lipoprotein particle clearance |
| BP | IDA | GO:0016540 | protein autoprocessing |
| BP | ISS | GO:0022008 | neurogenesis |
| BP | ISS | GO:0030182 | neuron differentiation |
| BP | IDA | GO:0032802 | low-density lipoprotein particle receptor catabolic process |
| BP | TAS | GO:0032802 | low-density lipoprotein particle receptor catabolic process |
| BP | IDA | GO:0032805 | positive regulation of low-density lipoprotein particle receptor catabolic process |
| BP | ISS | GO:0032869 | cellular response to insulin stimulus |
| BP | TAS | GO:0034383 | low-density lipoprotein particle clearance |
| BP | IEA | GO:0042157 | lipoprotein metabolic process |
| BP | IMP | GO:0042632 | cholesterol homeostasis |
| BP | ISS | GO:0043523 | regulation of neuron apoptotic process |
| BP | IMP | GO:0043525 | positive regulation of neuron apoptotic process |
| BP | TAS | GO:0043687 | post-translational protein modification |
| BP | TAS | GO:0044267 | cellular protein metabolic process |
| BP | IDA | GO:1905596 | negative regulation of low-density lipoprotein particle receptor binding |
| BP | IDA | GO:1905598 | negative regulation of low-density lipoprotein receptor activity |
| BP | IDA | GO:1905601 | negative regulation of receptor-mediated endocytosis involved in cholesterol transport |
| BP | IEA | GO:2000272 | negative regulation of signaling receptor activity |
| BP | IDA | GO:2000650 | negative regulation of sodium ion transmembrane transporter activity |
| CC | TAS | GO:0005576 | extracellular region |
| CC | IDA | GO:0005615 | extracellular space |
| CC | IDA | GO:0005737 | cytoplasm |
| CC | IDA | GO:0005764 | lysosome |
| CC | TAS | GO:0005765 | lysosomal membrane |
| CC | IDA | GO:0005769 | early endosome |
| CC | IDA | GO:0005770 | late endosome |
| CC | IDA | GO:0005783 | endoplasmic reticulum |
| CC | TAS | GO:0005788 | endoplasmic reticulum lumen |
| CC | IEA | GO:0005791 | rough endoplasmic reticulum |
| CC | IDA | GO:0005794 | Golgi apparatus |
| CC | IDA | GO:0005886 | plasma membrane |
| CC | IDA | GO:0009986 | cell surface |
| CC | IEA | GO:0030134 | COPII-coated ER to Golgi transport vesicle |
| CC | IC | GO:0031232 | extrinsic component of external side of plasma membrane |
| CC | TAS | GO:0036020 | endolysosome membrane |
| CC | IDA | GO:0048471 | perinuclear region of cytoplasm |
| CC | IDA | GO:1990666 | PCSK9-LDLR complex |
| CC | IDA | GO:1990667 | PCSK9-AnxA2 complex |
Gene expression in normal tissue: PCSK9
Gene-model tissue-cancer distribution: Bubble Plot
Gene-drug pathway distribution
Pathways in PCSK9
| Database | Pathway ID | Pathway Des. |
|---|---|---|
| wikipathways | WP2846 | Proprotein convertase subtilisin-kexin type 9 (PCSK9) mediated LDL receptor degradation |
| wikipathways | WP3408 | Evolocumab Mechanism |
| kegg | hsa04979 | Cholesterol metabolism - Homo sapiens (human) |
| reactome | R-HSA-174824 | Plasma lipoprotein assembly, remodeling, and clearance |
| reactome | R-HSA-381426 | Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) |
| reactome | R-HSA-382551 | Transport of small molecules |
| reactome | R-HSA-392499 | Metabolism of proteins |
| reactome | R-HSA-597592 | Post-translational protein modification |
| reactome | R-HSA-8866427 | VLDLR internalisation and degradation |
| reactome | R-HSA-8957275 | Post-translational protein phosphorylation |
| reactome | R-HSA-8964038 | LDL clearance |
| reactome | R-HSA-8964043 | Plasma lipoprotein clearance |
Gene in drug-gene network: Network Plot
Gene-drug targets distribution
Gene Structure: PDB
Models in PCSK9
CLASSFICATION
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