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Validated All-in-One™ qPCR Primer for PCSK9(NM_174936.3) Search again
Product ID:
HQP097702
(click here to view gene annotation page)
Powered by BiozSpecies:
Human
Symbol:
Alias:
FH3, FHCL3, HCHOLA3, LDLCQ1, NARC-1, NARC1, PC9
Gene Description:
proprotein convertase subtilisin/kexin type 9
Target Gene Accession:
NM_174936.3(click here to view gene page)
Estimated Delivery:
Approximately 1-3 weeks, but may vary. Please email sales@genecopoeia.com or call 301-762-0888 to confirm ETA.
Important Note:
By default, qPCR primer pairs are designed to measure the expression level of the splice variant (accession number) you selected for this gene WITHOUT consideration of other possible variants of this gene. If this gene has multiple variants, and you would like to measure the expression levels of one particular variant, multiple variants, or all variants, please contact us for a custom service project at inquiry@genecopoeia.com.
Validated result:
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| A | B |
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Each All-in-One™ qPCR Primer is experimentally validated to yield a single dissociation curve peak and to generate a single amplification of the correct size for the targeted gene. A cDNA Pool, containing reverse transcript products of 8 different human tissue total RNA(Liver, Testis,Muscle,Thyroid,Brain,Spleen,Stomach,Small Intestine)),was used as the qPCR validation template. qPCR was performed using 0.2 µM primer with 2XAll-in-One™ qPCR Mix (Catalog#: QP001,QP002,QP004,QP005). Reactions were incubated for 10min. at 95°C, followed by 40 cycles of 95°C for 10 sec.; 60°C, 20 sec. and 72°C, 15sec. using Bio-Rad iQ5™ Instrument. At the end of the last cycle, temperature was increased from 72 to 95°C to produce a melting curve. Panel A: Validated Result for Amplification Curve; Panel B: Validated Result for Melting Curve. |
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Summary
This gene encodes a proprotein convertase belonging to the proteinase K subfamily of the secretory subtilase family. The encoded protein is synthesized as a soluble zymogen that undergoes autocatalytic intramolecular processing in the endoplasmic reticulum. The protein may function as a proprotein convertase.
Gene References into function
- two mutations in the gene PCSK9 (encoding proprotein convertase subtilisin/kexin type 9) that cause autosomal dominant hypercholesterolemia
- A mutation in PCSK9 causing autosomal-dominant hypercholesterolemia in a Utah pedigree. Mutation screening of genes in the region of interest identified a single nucleotide variant (G-->T).
- mutations in the PCSK9 gene cause autosomal dominant hypercholesterolemia.
- The effect of the S127R mutation of PCSK9 on plasma cholesterol homeostasis is mainly related to an overproduction of apolipoprotein B100.
- PCSK9 regulation is typical of that of cholesterogenic genes, suggesting a role in cholesterol homeostasis. Human, mouse, and rat PCSK9 promoters contain 2 typical conserved motifs for cholesterol regulation: a sterol regulatory element & an Sp1 site.
- NARC-1 has a role in regulating both the level of LDLR and that of circulating apoB-containing lipoproteins in an LDLR-dependent and -independent fashion
- PCSK9 has a role in LDL clearance but not in apoB-containing lipoprotein production
- The cause of unusually severe dominant hypercholesterolemia is due to the effect of mutant PCKS9 on apolipoprotein B secretion.
- Rare missense mutations of PCSK9 may worsen the clinical phenotype of familial hypercholesterolemia patients carrying LDLR mutations.
- Mutations in the PCSK9 gene are associated with variable phenotype of autosomal dominant hypercholesterolemia.
- British PCSK9 patients with the D374Y mutation have an unpredictably severe clinical phenotype
- Genetic polymorphisms are not associated with Alzheimer disease and cholesterol in Japanese patients.
- PCSK9 proximal promoter contains a functional sterol regulatory element binding transcription factor (SREBP-1c) located from 335 bp to 355 bp upstream of the ATG.
- A spectrum of sequence variations of PCSK9 ranging in frequency (from 0.2% to 34%) and magnitude of effect (from a 3% increase to a 49% decrease) contribute to interindividual differences in LDL-C levels.
- nonsense mutations in PCSK9 were associated with a reduction in mean LDL cholesterol and a reduction in the risk of coronary heart disease
- PCSK9 (or a factor acted upon by PCSK9) is secreted from transfected cells and degrades low-density lipoprotein receptors both in transfected and untransfected cells.
- A c.43_44insCTG variation in PCSK9 plays a role in lowering cholesterol in the general population.
- In a European population the E670G SNP in the PCSK9 gene is associated with increased LDL in men but not in women
- PCSK9 plays a major role in determining plasma levels of LDL-C.
- PCSK9 levels are finely regulated by the basic amino acid convertases furin and PC5/6A
- the PCSK9 C679X variant has a marked cholesterol-lowering effect.
- secreted PCSK9 associates with the LDL receptors and reduces hepatic LDL receptors protein levels
- Mutations and variations occur in hypercholesterolemia--a regulator of cholesterol metabolism.
- In a Japanese population, four missense mutations and one nonsense mutation inPCSK9 were identified only in individuals with low LDL-C; six missense mutations were identified only in individuals with high LDL-Cholesterol .
- PCSK9-mediated degradation of the LDLR appears to take place intracellularly and occurs even when endocytosis through clathrin-coated pits is blocked by hypertonic medium.
- REVIEW OF ROLE OF PCSK9 AND PROPROTEIN CONVERTASES IN LIPID METABOLISM, DYSLIPIDEMIAS, AND CARDIOVASCULAR DISORDERS.
- PCSK9 is definitely a major actor in cholesterol homeostasis--review
- PCSK9 binds the extracellular domain of LDL receptor; the D374Y gain-of-function mutant, associated with hypercholesterolemia and early-onset cardiovascular disease, binds the receptor 25 times more tightly than wild-type PCSK9
- secreted PCSK9 retains biological activity, is able to bind directly to the LDLR extracellular domain, and undergoes LDLR-ARH-mediated endocytosis, leading to accelerated intracellular degradation of the LDLR.
- proprotein convertase subtilisin/kexin type 9 binding to epidermal growth factor-like repeat A of low density lipoprotein receptor decreases receptor recycling and increases degradation
- The sorting of PCSK9 to the cell surface and endosomes is required for PCSK9 to fully promote LDLR degradation.
- PCSK9 promotes the degradation of the LDL receptor in hepatocytes apparently both intracellularly and by being a secreted protein that can bind the LDL receptor and be internalized [review]
- Crystal structure is reported; its LDLR-lowering mechanism remains uncertain. The C-terminal domain has a novel protein fold and may mediate protein-protein interactions.
- PCSK9 functions as a chaperone to prevent LDLR recycling and/or to target LDLRs for lysosomal degradation
- study analyzed association of 1 missense (R46L) & 2 nonsense (Y142X & C679X) PCSK9 mutations with serum LDL cholesterol in African-Americans & whites; results show these variants are associated with lower LDL cholesterol levels starting in childhood
- These results suggest a gender difference in PCSK9 regulation and function with PCSK9 correlated to total cholesterol and high density lipoprotein cholesterol in men but not women.
- The circulating concentrations of human PCSK9 are directly correlated with LDL and total cholesterol concentrations.
- PCSK9 mediated inhibition of the LDL receptor does not require PCSK9 autocatalytic cleavage or secretion, suggesting that PCSK9 may also function intracellularly.
- The self-inhibited structure of full-length PCSK9 at 1.9A reveals structural homology with resistin within the C-terminal domain.
- PCSK9 gene is a risk factor of large-vessel atherosclerosis stroke
- among primates, differential selective pressure has shaped evolutionary patterns in the functional domains of PCSK9, an important regulator of cholesterol homeostasis
- The association of PCSK9 variation with incidence of cancer was studied prospectively study. The frequency of the PCSK9 variants studied was 2.4% in blacks and 3.2% in whites. Neither was associated with increased cancer.
- REVIEW: overview of mutations reported for the LDLR gene, the APOB gene, the PCSK9 gene, resulting in ADH.
- after stimulation, the protease activity of PC5A is enhanced, as evidenced by the cleavage of the PC5A substrates Lefty, ADAMTS-4, endothelial lipase, and PCSK9.
- the activity of PCSK9 and its binding affinity on VLDLR and ApoER2 does not depend on the presence of LDLR.
- a novel human PCSK9 splicing variant had an in-frame deletion of the eighth exon of 58 amino acids and was expressed in multiple tissues, including liver, small intestine, prostate, uterus, brain, and adipose tissue
- PCSK9 also associated with LDL and HDL but not with VLDL. We conclude that self-association is an intrinsic property of PCSK9, correlated to its LDLR-degrading activity and affected by plasma lipoproteins
- fibrates simultaneously decreased PCSK9 expression while increasing PC5/6A and furin expression, indicating a broad action of PPARalpha activation in proprotein convertase-mediated lipid homeostasis.
- structure of PCSK9 in complex with the LDLR EGF-A domain defines potential therapeutic target sites for blocking agents that could interfere with this interaction in vivo, thereby increasing LDLR function and reducing plasma LDL-C levels
- This study has provided novel information about the structural requirements for the normal function of PCSK9. However, more studies are needed to determine the mechanisms by which gain-of-function mutations in PCSK9 cause hypercholesterolemia.
- PCSK9 expression has been shown to be regulated by sterol regulatory element binding proteins (SREBPs) and statins similar to other genes involved in cholesterol homeostasis[review]
- evolutionary dynamics may underlie the 'gain-of-function' mutations in PCSK9 that are associated with higher LDL cholesterol levels
- PCSK9 46L variant is associated with a significant reduction of LDL cholesterol.
- results suggest a model in which mutations at Ser127 and Asp374 residues modulate PCSK9's ability to regulate LDLR function through distinct mechanisms
- Secreted PCSK9 can potentially impact extrahepatic tissue cholesterol homeostasis by regulating extrahepatic tissue LDLR levels.
- PCSK9 is phosphorylated by a Golgi casein kinase-like kinase ex vivo and circulates as a phosphoprotein in humans
- PCSK9 missense variant is associated with a reduced risk of early-onset myocardial infarction.
- A new mutation that could cause autosomal dominant hypercholesterolemia by increasing the transcription of PCSK9.
- Report genome-wide expression analysis of cells expressing gain of function mutant D374Y-PCSK9.
- Site-directed mutagenesis experiments for 13 residues on a large conserved protrusion on the surface of the PCSK9 catalytic domain was performed.
- Ethnic differences in the frequency of the cardioprotective C679X PCSK9 mutation in a West African population are reported.
- Data show that the serine protease PCSK9 (proprotein convertase subtilisin kexin type 9) contributes to the disposal of non-acetylated BACE1.
- These data demonstrate that while PCSK9 binds several receptors via its EGF-A binding domain, additional contacts with other receptor domains are also involved.
- SNPs in PCSK9 were found as part of a chromosome 1p32 deletion, causing multiple abnormalities and low cholesterol levels.
- PCSK9 variants might contribute to FCHL phenotype and are to be taken into consideration in the study of this complex and multigenic disease with other genes implicated in dyslipidaemia
- Domains in both the LDLR and PCSK9 that are not required for binding (or internalization) are essential for PCSK9-mediated degradation of the LDLR.
- identification of the minimal inhibitory sequence of AnxA2 should pave the way toward the development of PCSK9 inhibitory lead molecules for the treatment of hypercholesterolemia
- Tyr-306 confers increased affinity for PCSK9