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. 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. 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. 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.
|Gene References into Functions
- up-regulation of intestinal gene expression of LDL-R and PCSK9 following voluntary wheel running PMID: 29938676
- This is the first report about the expression of PCSK9 in adult terminal differentiated ventricular cardiomyocytes PMID: 28913715
- PCSK9 is regulated in vascular smooth muscle cells by TLR-4 - SAPK/JNK signaling, a pathway important in inflammation and metabolism. PMID: 28232185
- Hnf1alpha gene expression is upregulated in the liver of rats with experimentally induced chronic renal failure, showing an association between circulating PCSK9 and TAGs PMID: 26978583
- PCSK9 could serve as a novel molecular biomarker for the non-invasive prenatal screening of neural tube defects. PMID: 26691006
- coordinated up-regulation of Pcsk9 and Srebf-2 genes expression suggests that SREBF-2 may play a key role in regulation of Pcsk9 gene expression, circulating PCSK9 level, and hypercholesterolemia in experimental CRF PMID: 26481479
- LDLR deficiency, hypercholesterolemia and elevated plasma LDL in NS are associated with upregulation of PCSK9 and IDOL. PMID: 24166456
- Gene expression of hepatic LDL-R, Lrp1, Pcsk9, SREBP-2 and HMGCoA-r were reduced (p<0.05) in ovariectomy compared to Sham rats. PMID: 24619822
- data provided the first line of the evidence that BBR, similar to the Sim, could increase the expression of PCSK9 levels in HFD rats through SREBP-2 activation PMID: 24755036
- Elevated serum PCSK9 concentration by ezetimibe, Xuezhikang and pitavastatin alone or in combination was found prior to the alterations of lipid profile in rats. PMID: 24533584
- Phaleria macrocarpa fruit aqueous extract reduced body weight/improved blood lipid profile of hypercholesterolemic rats. The improvement is likely to be regulated by LDL receptor and PCSK9. PMID: 21763412
- Our functional characterization of Narc 1 reinforces the inference drawn that this enzyme is most closely related to representatives of the proteinase K family, but it is also sufficiently different to warrant its classification in a separate sub-family. PMID: 14622975
- Human, mouse, and rat PCSK9 promoters contain 2 typical conserved motifs for cholesterol regulation: a sterol regulatory element (SRE) and an Sp1 site. PMID: 15178557
- Proprotein convertase subtilisin/kexin type 9 (PCSK9) is processed in the Endoplasmic Reticulum, and the mature convertase is secreted in the plasma. PMID: 16462892
- mechanism by which NARC 1 overexpression induces cell death in cerebellar granule neurons remains unclear; correlation seen between Narc 1 active site serine in transiently expressed protein and induction of BAF-sensitive component of cell death phenotype PMID: 17051583
- explaining the lack of reduction in LDL receptor protein levels. These observations indicate that the rate of LDL receptor cycling (function) in diabetic rats is decreased resulting in higher serum LDL levels. PMID: 18054320
- The hormonal and dietary regulation of hepatic LDLRs also involves posttranscriptional regulation by PCSK9. PMID: 19008317
- NARC-1 is a proteinase K-like subtilase with a role in the differentiation of cortical neurons. PMID: 12552133
||Cytoplasm. Secreted. Endosome. Lysosome. Cell surface. Endoplasmic reticulum. Golgi apparatus.
||Peptidase S8 family
||Highly expressed in 12-day embryo. In the adult, strongly expressed in liver, small intestine, jejunum, and to a lesser extent in kidney, lung, spleen and thymus. Expression in the liver is up-regulated following partial hepatectomy.