Background: PCSK9 binds to the EGF-A domain of the LDLR and signals LDLR degradation. Reduced LDLR levels result in decreased LDL (low density lipid) metabolism leading to hypercholesterolemia. Additioanlly, PCSK9 may be implicated in the differentiation of cortical neurons and may also play a role in cholesterol homeostasis. Defects in PCSK9 gene are the cause of familial hypercholesterolemia 3 (FH3). The protein is thought to play a central role in cholesterol homeostais. For an antibody that targets the blocking epitope of the PCSK-LDLR interaction use X2404P.
Positive Control: Expressed in neuro-epithelioma, colon carcinoma, hepatic and pancreatic cell lines, and in Schwann cells.
Immunogen: Synthetic peptide (internal sequence) targeting a non-blocking epitope.
Purification Method: Ammonium Sulfate Precipitation
Concentration: See vial for concentration
Formulation: Provided as solution in phosphate buffered saline with 0.08% sodium azide
References: 1. Proc Natl Acad Sci U S A. 2003 Feb 4;100(3):928-33. Epub 2003 Jan 27. The secretory proprotein convertase neural apoptosis-regulated convertase 1 (NARC-1): liver regeneration and neuronal differentiation. Seidah NG, et al2. Nat Genet. 2003 Jun;34(2):154-6. Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Abifadel et al3. Hum Mutat. 2005 Nov;26(5):497. Novel mutations of the PCSK9 gene cause variable phenotype of autosomal dominant hypercholesterolemia. Allard D et al4. Am J Hum Genet. 2006 Mar;78(3):410-22. Epub 2006 Jan 20. A spectrum of PCSK9 alleles contributes to plasma levels of low-density lipoprotein cholesterol. Kotowski IK, et al5. Clin Genet. 2004 May;65(5):419-22. Mutations in the PCSK9 gene in Norwegian subjects with autosomal dominant hypercholesterolemia. Leren TP.6. PLoS One. 2007 Oct 31;2(10):e1098. Evidence for positive selection in the C-terminal domain of the cholesterol metabolism gene PCSK9 based on phylogenetic analysis in 14 primate species. Ding K, McDonough SJ, Kullo IJ.7. J Hum Genet. 2004;49(2):109-14. Epub 2004 Jan 15. Genetic variants in PCSK9 affect the cholesterol level in Japanese. Shioji K, et al8. Atherosclerosis. 2005 Oct;182(2):331-40. Genetic screening protocol for familial hypercholesterolemia which includes splicing defects gives an improved mutation detection rate. Graham CA et al9. Cell. 2006 Nov 3;127(3):635-48. Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Olsen J V et al10. J Am Coll Cardiol. 2005 May 17;45(10):1611-9. Epub 2005 Apr 21. A common PCSK9 haplotype, encompassing the E670G coding single nucleotide polymorphism, is a novel genetic marker for plasma low-density lipoprotein cholesterol levels and severity of coronary atherosclerosis. Chen SN et al
UniProt: Q8NBP7
Caution: This product is intended FOR RESEARCH USE ONLY, and FOR TESTS IN VITRO, not for use in diagnostic or therapeutic procedures involving humans or animals.