======= PCSK9 =======
== Gene Information ==
* **Official Symbol**: PCSK9
* **Official Name**: proprotein convertase subtilisin/kexin type 9
* **Aliases and Previous Symbols**: N/A
* **Entrez ID**: [[https://www.ncbi.nlm.nih.gov/gene/?term=255738|255738]]
* **UniProt**: [[https://www.uniprot.org/uniprot/Q8NBP7|Q8NBP7]]
* **Interactions**: [[https://thebiogrid.org/search.php?search=PCSK9&organism=9606|BioGRID]]
* **PubMed articles**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20PCSK9|Open PubMed]]
* **OMIM**: [[https://omim.org/entry/607786|Open OMIM]]
== Function Summary ==
* **Entrez 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].
* **UniProt Summary**: 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. {ECO:0000269|PubMed:17461796, ECO:0000269|PubMed:18039658, ECO:0000269|PubMed:18197702, ECO:0000269|PubMed:18660751, ECO:0000269|PubMed:18799458, ECO:0000269|PubMed:22074827, ECO:0000269|PubMed:22493497, ECO:0000269|PubMed:22580899}.
|Inhibitor I9|
|Peptidase S8|
|negative regulation of intracellular lipid transport|
|negative regulation of receptor-mediated endocytosis involved in cholesterol transport|
|negative regulation of low-density lipoprotein particle receptor binding|
|negative regulation of intracellular cholesterol transport|
|negative regulation of intracellular sterol transport|
|positive regulation of low-density lipoprotein particle receptor catabolic process|
|receptor inhibitor activity|
|PCSK9-AnxA2 complex|
|PCSK9-LDLR complex|
|regulation of low-density lipoprotein particle receptor binding|
|apolipoprotein receptor binding|
|negative regulation of low-density lipoprotein receptor activity|
|very-low-density lipoprotein particle binding|
|regulation of receptor-mediated endocytosis involved in cholesterol transport|
|negative regulation of receptor recycling|
|very-low-density lipoprotein particle receptor binding|
|positive regulation of receptor catabolic process|
|negative regulation of low-density lipoprotein particle clearance|
|regulation of low-density lipoprotein particle receptor catabolic process|
|sodium channel inhibitor activity|
|negative regulation of lipoprotein particle clearance|
|extrinsic component of external side of plasma membrane|
|regulation of intracellular sterol transport|
|regulation of intracellular lipid transport|
|regulation of intracellular cholesterol transport|
|regulation of receptor catabolic process|
|low-density lipoprotein particle receptor catabolic process|
|low-density lipoprotein receptor particle metabolic process|
|regulation of low-density lipoprotein particle clearance|
|negative regulation of cholesterol transport|
|negative regulation of sterol transport|
|negative regulation of sodium ion transmembrane transporter activity|
|negative regulation of receptor binding|
|negative regulation of sodium ion transmembrane transport|
|endolysosome membrane|
|low-density lipoprotein particle binding|
|apolipoprotein binding|
|protein autoprocessing|
|negative regulation of sodium ion transport|
|regulation of lipoprotein particle clearance|
|low-density lipoprotein particle receptor binding|
|negative regulation of receptor-mediated endocytosis|
|low-density lipoprotein particle clearance|
|regulation of receptor binding|
|regulation of receptor recycling|
|positive regulation of receptor internalization|
|negative regulation of lipid transport|
|receptor catabolic process|
|plasma lipoprotein particle clearance|
|negative regulation of lipid localization|
|COPII-coated ER to Golgi transport vesicle|
|negative regulation of endocytosis|
|regulation of cholesterol transport|
|regulation of sterol transport|
|positive regulation of receptor-mediated endocytosis|
|regulation of sodium ion transmembrane transporter activity|
|regulation of receptor internalization|
|positive regulation of neuron apoptotic process|
|protein self-association|
|negative regulation of signaling receptor activity|
|rough endoplasmic reticulum|
|negative regulation of intracellular transport|
|regulation of sodium ion transmembrane transport|
|negative regulation of ion transmembrane transporter activity|
|regulation of plasma lipoprotein particle levels|
|triglyceride metabolic process|
|cholesterol homeostasis|
|negative regulation of transporter activity|
|sterol homeostasis|
|negative regulation of cation transmembrane transport|
|regulation of sodium ion transport|
|positive regulation of neuron death|
|negative regulation of ion transmembrane transport|
|acylglycerol metabolic process|
|positive regulation of endocytosis|
|neutral lipid metabolic process|
|regulation of receptor-mediated endocytosis|
|negative regulation of protein binding|
|receptor metabolic process|
|lysosomal transport|
|regulation of lipid transport|
|negative regulation of transmembrane transport|
|cholesterol metabolic process|
|lipoprotein metabolic process|
|liver development|
|late endosome|
|hepaticobiliary system development|
|secondary alcohol metabolic process|
|lipid homeostasis|
|sterol metabolic process|
|regulation of lipid localization|
|positive regulation of cellular protein catabolic process|
|vacuolar transport|
|negative regulation of ion transport|
|cellular response to starvation|
|protein processing|
|cellular response to insulin stimulus|
|serine-type endopeptidase activity|
|negative regulation of binding|
|regulation of signaling receptor activity|
|response to starvation|
|regulation of endocytosis|
|regulation of neuron apoptotic process|
|positive regulation of protein catabolic process|
|regulation of protein binding|
|protein maturation|
|response to insulin|
|cellular response to nutrient levels|
|regulation of cellular protein catabolic process|
|lysosome|
|early endosome|
|regulation of ion transmembrane transporter activity|
|steroid metabolic process|
|cellular response to extracellular stimulus|
|regulation of transmembrane transporter activity|
|cellular response to peptide hormone stimulus|
|kidney development|
|regulation of transporter activity|
|renal system development|
|lysosomal membrane|
|endoplasmic reticulum lumen|
|regulation of neuron death|
|alcohol metabolic process|
|urogenital system development|
|cellular response to peptide|
|regulation of cation transmembrane transport|
|cellular response to external stimulus|
|regulation of intracellular transport|
|post-translational protein modification|
|positive regulation of cellular catabolic process|
|phospholipid metabolic process|
|regulation of binding|
|glycerolipid metabolic process|
|regulation of protein catabolic process|
|regulation of metal ion transport|
|response to peptide hormone|
|gland development|
|positive regulation of catabolic process|
|organic hydroxy compound metabolic process|
|response to peptide|
|regulation of ion transmembrane transport|
|negative regulation of transport|
|response to nutrient levels|
|response to extracellular stimulus|
|regulation of vesicle-mediated transport|
|regulation of transmembrane transport|
|cellular response to organonitrogen compound|
|cellular response to hormone stimulus|
|cell surface|
|cellular protein catabolic process|
|positive regulation of apoptotic process|
|positive regulation of programmed cell death|
|cellular response to nitrogen compound|
|protein catabolic process|
|perinuclear region of cytoplasm|
|positive regulation of cell death|
|regulation of ion transport|
|negative regulation of cellular component organization|
|regulation of cellular catabolic process|
|organophosphate metabolic process|
|cellular macromolecule catabolic process|
|response to hormone|
|regulation of cellular localization|
|apoptotic process|
|cellular lipid metabolic process|
|Golgi apparatus|
|positive regulation of transport|
|regulation of catabolic process|
|response to organonitrogen compound|
|neuron differentiation|
|endoplasmic reticulum|
|macromolecule catabolic process|
|programmed cell death|
|cellular response to oxygen-containing compound|
|organonitrogen compound catabolic process|
|response to nitrogen compound|
|cell death|
|chemical homeostasis|
|negative regulation of molecular function|
|negative regulation of multicellular organismal process|
|positive regulation of cellular component organization|
|lipid metabolic process|
|cellular response to endogenous stimulus|
|proteolysis|
|negative regulation of signaling|
|RNA binding|
|response to endogenous stimulus|
|generation of neurons|
|regulation of apoptotic process|
|response to oxygen-containing compound|
|regulation of programmed cell death|
|extracellular space|
|positive regulation of cellular protein metabolic process|
|neurogenesis|
|homeostatic process|
|regulation of cell death|
|cellular response to stress|
|positive regulation of protein metabolic process|
|small molecule metabolic process|
|organic substance catabolic process|
|cellular catabolic process|
|regulation of transport|
|extracellular region|
|gene expression|
\\
=== CRISPR Data ===
^Screen^Score^
|[[:results:exp329|Hydroxyurea 100μM R07 exp329]]|-1.92|
|[[:results:exp129|Isonicotinamide 500μM R03 exp129]]|1.82|
No correlation found to any other genes in chemogenomics.
Global Fraction of Cell Lines Where Essential: 0/739
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|0/28|
|bone|0/26|
|breast|0/33|
|central nervous system|0/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/16|
|kidney|0/21|
|liver|0/20|
|lung|0/75|
|lymphocyte|0/16|
|ovary|0/26|
|pancreas|0/24|
|peripheral nervous system|0/16|
|plasma cell|0/15|
|prostate|0/1|
|skin|0/24|
|soft tissue|0/9|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/29|
|uterus|0/5|
== Essentiality in NALM6 ==
* **Essentiality Rank**: 8265
* **Expression level (log2 read counts)**: -2.14
{{:chemogenomics:nalm6 dist.png?nolink |}}