Ignet

Gene Information

Gene symbol: PCSK9

Gene name: proprotein convertase subtilisin/kexin type 9

HGNC ID: 20001

Synonyms: NARC-1, FH3

Related Genes

#	Gene Symbol	Number of hits
1	ABCA1	1 hits
2	ABCG1	1 hits
3	ANGPTL3	1 hits
4	CETP	1 hits
5	CRTC1	1 hits
6	GALNT2	1 hits
7	GCKR	1 hits
8	HMGCR	1 hits
9	INS	1 hits
10	LDLR	1 hits
11	LIPC	1 hits
12	LIPG	1 hits
13	LPL	1 hits
14	MBTPS1	1 hits
15	MLXIPL	1 hits
16	MME	1 hits
17	NCAN	1 hits
18	RETN	1 hits
19	RPGR	1 hits
20	SCARB1	1 hits
21	STN	1 hits
22	VLDLR	1 hits

Related Sentences

#	PMID	Sentence
1	16215768	Two additional PC subtypes--called subtilisin kexin isozyme 1 (SKI-1) or site 1 protease (S1P) and neural apoptosis regulated convertase 1 (NARC-1), also known as PCSK9--that cleave at the carboxy terminus of nonbasic amino acids were discovered later.
2	17012247	Proteolysis occurring at basic residues is mediated by the basic amino acid-specific proprotein convertases, namely: PC1/3, PC2, furin, PACE4, PC4, PC5/6, and PC7.
3	17012247	In contrast, proteolysis at nonbasic residues is performed by the subtilisin/kexin-like isozyme-1 (SKI-1/S1P) and the newly identified neural apoptosis-regulated convertase-1 (PCSK9/NARC-1).
4	17578886	Hepatic LDL receptors (LDLRs), scavenger receptor class B type 1, and proprotein convertase subtilisin/kexin type 9 serine protease (PCSK9) transcripts were unchanged in old animals.
5	17578886	GH treatment induced LDLRs, PCSK9 transcripts, and BA synthesis.
6	17578886	Hepatic LDL receptors (LDLRs), scavenger receptor class B type 1, and proprotein convertase subtilisin/kexin type 9 serine protease (PCSK9) transcripts were unchanged in old animals.
7	17578886	GH treatment induced LDLRs, PCSK9 transcripts, and BA synthesis.
8	17804797	The self-inhibited structure of full-length PCSK9 at 1.9 A reveals structural homology with resistin within the C-terminal domain.
9	17804797	This structural relationship between the CRD of PCSK9 and the resistin family is not observed in primary sequence comparisons and strongly suggests a distant evolutionary link between the two molecules.
10	17804797	The self-inhibited structure of full-length PCSK9 at 1.9 A reveals structural homology with resistin within the C-terminal domain.
11	17804797	This structural relationship between the CRD of PCSK9 and the resistin family is not observed in primary sequence comparisons and strongly suggests a distant evolutionary link between the two molecules.
12	18054320	Diabetes alters LDL receptor and PCSK9 expression in rat liver.
13	18054320	Further investigation revealed that protein levels of PCSK9, which has been shown to enhance the degradation of the LDL receptor protein, were significantly decreased in the diabetic rats explaining the lack of reduction in LDL receptor protein levels.
14	18054320	Diabetes alters LDL receptor and PCSK9 expression in rat liver.
15	18054320	Further investigation revealed that protein levels of PCSK9, which has been shown to enhance the degradation of the LDL receptor protein, were significantly decreased in the diabetic rats explaining the lack of reduction in LDL receptor protein levels.
16	18193043	Overall, we identify strongly associated variants in eleven loci previously implicated in lipid metabolism (ABCA1, the APOA5-APOA4-APOC3-APOA1 and APOE-APOC clusters, APOB, CETP, GCKR, LDLR, LPL, LIPC, LIPG and PCSK9) and also in several newly identified loci (near MVK-MMAB and GALNT2, with variants primarily associated with high-density lipoprotein (HDL) cholesterol; near SORT1, with variants primarily associated with low-density lipoprotein (LDL) cholesterol; near TRIB1, MLXIPL and ANGPTL3, with variants primarily associated with triglycerides; and a locus encompassing several genes near NCAN, with variants strongly associated with both triglycerides and LDL cholesterol).
17	20130116	Our results show that diabetic animals exhibited a lower intestinal CHOL uptake, which was associated with a decrease in 1) the gene and protein expression of Niemann-Pick C1 like 1 that plays a pivotal role in CHOL incorporation in the enterocytes; and 2) mRNA of ATP-binding cassette transporters (ABC)A1 that mediates CHOL efflux from intestinal cells to apolipoprotein A-I and high-density lipoprotein.
18	20130116	On the other hand, in diabetic animals, a significant mRNA decrease was noticed in intestinal ABCG5 and ABCG8 responsible for the secretion of absorbed CHOL back into the lumen.
19	20130116	Furthermore, jejunal PCSK9 protein was diminished and low-density lipoprotein receptor was raised, along with a significant down-regulation in jejunal 3-hydroxy-3-methylglutaryl-coenzyme A reductase in P. obesus with T2D.
20	20130116	In the liver, there was 1) an augmentation in the protein mass of Niemann-Pick C1 like 1, SR-BI, and annexin 2; 2) an up-regulation of SR-BI mRNA; 3) a fall in ABCG8 protein content as well as in ABCG5 and ABCA1 mRNA; and 4) an augmentation in liver X receptors alpha and peroxisome proliferator-activated receptors beta/delta mRNA, together with a drop in sterol regulatory element binding protein-2 protein.
21	20649626	Fenofibrate concomitantly decreases serum proprotein convertase subtilisin/kexin type 9 and very-low-density lipoprotein particle concentrations in statin-treated type 2 diabetic patients.
22	21149300	A two-step binding model of PCSK9 interaction with the low density lipoprotein receptor.
23	21149300	Insofar as PCSK9 inhibition induces a decrease in plasma cholesterol levels, understanding the nature of the binding interaction between PCSK9 and the LDLR is of critical importance.
24	21149300	Using a direct binding interaction assay, we show that the PCSK9 CT domain bound to the LDLR in a calcium-dependent manner and that co-incubation with the prodomain and catalytic domain had no effect on this binding.
25	21149300	To further characterize this interaction, two LDLR fragments, the classical ligand-binding domain (LBD) and the EGF precursor homology domain, were expressed in stably transfected HEK 293 cells and isolated.
26	21149300	Thus, CT domain interaction with the LBD of the LDLR at endosomal pH constitutes a second step in the PCSK9-mediated LDLR binding that leads to receptor degradation.
27	21149300	A two-step binding model of PCSK9 interaction with the low density lipoprotein receptor.
28	21149300	Insofar as PCSK9 inhibition induces a decrease in plasma cholesterol levels, understanding the nature of the binding interaction between PCSK9 and the LDLR is of critical importance.
29	21149300	Using a direct binding interaction assay, we show that the PCSK9 CT domain bound to the LDLR in a calcium-dependent manner and that co-incubation with the prodomain and catalytic domain had no effect on this binding.
30	21149300	To further characterize this interaction, two LDLR fragments, the classical ligand-binding domain (LBD) and the EGF precursor homology domain, were expressed in stably transfected HEK 293 cells and isolated.
31	21149300	Thus, CT domain interaction with the LBD of the LDLR at endosomal pH constitutes a second step in the PCSK9-mediated LDLR binding that leads to receptor degradation.
32	21149300	A two-step binding model of PCSK9 interaction with the low density lipoprotein receptor.
33	21149300	Insofar as PCSK9 inhibition induces a decrease in plasma cholesterol levels, understanding the nature of the binding interaction between PCSK9 and the LDLR is of critical importance.
34	21149300	Using a direct binding interaction assay, we show that the PCSK9 CT domain bound to the LDLR in a calcium-dependent manner and that co-incubation with the prodomain and catalytic domain had no effect on this binding.
35	21149300	To further characterize this interaction, two LDLR fragments, the classical ligand-binding domain (LBD) and the EGF precursor homology domain, were expressed in stably transfected HEK 293 cells and isolated.
36	21149300	Thus, CT domain interaction with the LBD of the LDLR at endosomal pH constitutes a second step in the PCSK9-mediated LDLR binding that leads to receptor degradation.
37	21149300	A two-step binding model of PCSK9 interaction with the low density lipoprotein receptor.
38	21149300	Insofar as PCSK9 inhibition induces a decrease in plasma cholesterol levels, understanding the nature of the binding interaction between PCSK9 and the LDLR is of critical importance.
39	21149300	Using a direct binding interaction assay, we show that the PCSK9 CT domain bound to the LDLR in a calcium-dependent manner and that co-incubation with the prodomain and catalytic domain had no effect on this binding.
40	21149300	To further characterize this interaction, two LDLR fragments, the classical ligand-binding domain (LBD) and the EGF precursor homology domain, were expressed in stably transfected HEK 293 cells and isolated.
41	21149300	Thus, CT domain interaction with the LBD of the LDLR at endosomal pH constitutes a second step in the PCSK9-mediated LDLR binding that leads to receptor degradation.
42	21596380	Proprotein convertase subtilisin kexin type 9 (PCSK9) is a circulating protein that impairs LDL clearance by promoting the LDL receptor (LDLR) degradation.
43	22426206	Regulation of hepatic LDL receptors by mTORC1 and PCSK9 in mice.
44	22426206	Recent studies have also suggested that hepatic insulin signaling sustains LDLR levels.
45	22426206	We therefore sought to elucidate the mechanisms linking hepatic insulin signaling to regulation of LDLR levels.
46	22426206	In WT mice, insulin receptor knockdown by shRNA resulted in decreased hepatic mTORC1 signaling and LDLR protein levels.
47	22426206	It also led to increased expression of PCSK9, a known post-transcriptional regulator of LDLR expression.
48	22426206	Administration of the mTORC1 inhibitor rapamycin caused increased expression of PCSK9, decreased levels of hepatic LDLR protein, and increased levels of VLDL/LDL cholesterol in WT but not Pcsk9-/- mice.
49	22426206	Conversely, mice with increased hepatic mTORC1 activity exhibited decreased expression of PCSK9 and increased levels of hepatic LDLR protein levels.
50	22426206	Pcsk9 is regulated by the transcription factor HNF1α, and our further detailed analyses suggest that increased mTORC1 activity leads to activation of PKCδ, reduced activity of HNF4α and HNF1α, decreased PCSK9 expression, and ultimately increased hepatic LDLR protein levels, which result in decreased circulating LDL levels.
51	22426206	Regulation of hepatic LDL receptors by mTORC1 and PCSK9 in mice.
52	22426206	Recent studies have also suggested that hepatic insulin signaling sustains LDLR levels.
53	22426206	We therefore sought to elucidate the mechanisms linking hepatic insulin signaling to regulation of LDLR levels.
54	22426206	In WT mice, insulin receptor knockdown by shRNA resulted in decreased hepatic mTORC1 signaling and LDLR protein levels.
55	22426206	It also led to increased expression of PCSK9, a known post-transcriptional regulator of LDLR expression.
56	22426206	Administration of the mTORC1 inhibitor rapamycin caused increased expression of PCSK9, decreased levels of hepatic LDLR protein, and increased levels of VLDL/LDL cholesterol in WT but not Pcsk9-/- mice.
57	22426206	Conversely, mice with increased hepatic mTORC1 activity exhibited decreased expression of PCSK9 and increased levels of hepatic LDLR protein levels.
58	22426206	Pcsk9 is regulated by the transcription factor HNF1α, and our further detailed analyses suggest that increased mTORC1 activity leads to activation of PKCδ, reduced activity of HNF4α and HNF1α, decreased PCSK9 expression, and ultimately increased hepatic LDLR protein levels, which result in decreased circulating LDL levels.
59	22426206	Regulation of hepatic LDL receptors by mTORC1 and PCSK9 in mice.
60	22426206	Recent studies have also suggested that hepatic insulin signaling sustains LDLR levels.
61	22426206	We therefore sought to elucidate the mechanisms linking hepatic insulin signaling to regulation of LDLR levels.
62	22426206	In WT mice, insulin receptor knockdown by shRNA resulted in decreased hepatic mTORC1 signaling and LDLR protein levels.
63	22426206	It also led to increased expression of PCSK9, a known post-transcriptional regulator of LDLR expression.
64	22426206	Administration of the mTORC1 inhibitor rapamycin caused increased expression of PCSK9, decreased levels of hepatic LDLR protein, and increased levels of VLDL/LDL cholesterol in WT but not Pcsk9-/- mice.
65	22426206	Conversely, mice with increased hepatic mTORC1 activity exhibited decreased expression of PCSK9 and increased levels of hepatic LDLR protein levels.
66	22426206	Pcsk9 is regulated by the transcription factor HNF1α, and our further detailed analyses suggest that increased mTORC1 activity leads to activation of PKCδ, reduced activity of HNF4α and HNF1α, decreased PCSK9 expression, and ultimately increased hepatic LDLR protein levels, which result in decreased circulating LDL levels.
67	22426206	Regulation of hepatic LDL receptors by mTORC1 and PCSK9 in mice.
68	22426206	Recent studies have also suggested that hepatic insulin signaling sustains LDLR levels.
69	22426206	We therefore sought to elucidate the mechanisms linking hepatic insulin signaling to regulation of LDLR levels.
70	22426206	In WT mice, insulin receptor knockdown by shRNA resulted in decreased hepatic mTORC1 signaling and LDLR protein levels.
71	22426206	It also led to increased expression of PCSK9, a known post-transcriptional regulator of LDLR expression.
72	22426206	Administration of the mTORC1 inhibitor rapamycin caused increased expression of PCSK9, decreased levels of hepatic LDLR protein, and increased levels of VLDL/LDL cholesterol in WT but not Pcsk9-/- mice.
73	22426206	Conversely, mice with increased hepatic mTORC1 activity exhibited decreased expression of PCSK9 and increased levels of hepatic LDLR protein levels.
74	22426206	Pcsk9 is regulated by the transcription factor HNF1α, and our further detailed analyses suggest that increased mTORC1 activity leads to activation of PKCδ, reduced activity of HNF4α and HNF1α, decreased PCSK9 expression, and ultimately increased hepatic LDLR protein levels, which result in decreased circulating LDL levels.
75	22426206	Regulation of hepatic LDL receptors by mTORC1 and PCSK9 in mice.
76	22426206	Recent studies have also suggested that hepatic insulin signaling sustains LDLR levels.
77	22426206	We therefore sought to elucidate the mechanisms linking hepatic insulin signaling to regulation of LDLR levels.
78	22426206	In WT mice, insulin receptor knockdown by shRNA resulted in decreased hepatic mTORC1 signaling and LDLR protein levels.
79	22426206	It also led to increased expression of PCSK9, a known post-transcriptional regulator of LDLR expression.
80	22426206	Administration of the mTORC1 inhibitor rapamycin caused increased expression of PCSK9, decreased levels of hepatic LDLR protein, and increased levels of VLDL/LDL cholesterol in WT but not Pcsk9-/- mice.
81	22426206	Conversely, mice with increased hepatic mTORC1 activity exhibited decreased expression of PCSK9 and increased levels of hepatic LDLR protein levels.
82	22426206	Pcsk9 is regulated by the transcription factor HNF1α, and our further detailed analyses suggest that increased mTORC1 activity leads to activation of PKCδ, reduced activity of HNF4α and HNF1α, decreased PCSK9 expression, and ultimately increased hepatic LDLR protein levels, which result in decreased circulating LDL levels.
83	23221398	Cholesterol is taken up by the placenta as part of lipoproteins through the scavenger receptor class B type I receptor (SRBI), low-density lipoprotein receptor (LDLR), and very low density lipoprotein receptor (VLDLR), and its efflux is then mediated by ABCA1 and ABCG1.
84	23221398	PCSK9 is involved in the degradation of LDLR and VLDLR.
85	23221398	Messenger RNA and protein expression levels (LDLR, VLDLR, SRBI, ABCA1, ABCG1, proprotein convertase subtilisin/kexin type 9, liver x receptors, peroxisome proliferator-activated receptors) were assessed in human full-term placenta, respectively, by real-time RT-PCR and Western blots.
86	23221398	Cholesterol is taken up by the placenta as part of lipoproteins through the scavenger receptor class B type I receptor (SRBI), low-density lipoprotein receptor (LDLR), and very low density lipoprotein receptor (VLDLR), and its efflux is then mediated by ABCA1 and ABCG1.
87	23221398	PCSK9 is involved in the degradation of LDLR and VLDLR.
88	23221398	Messenger RNA and protein expression levels (LDLR, VLDLR, SRBI, ABCA1, ABCG1, proprotein convertase subtilisin/kexin type 9, liver x receptors, peroxisome proliferator-activated receptors) were assessed in human full-term placenta, respectively, by real-time RT-PCR and Western blots.
89	23579862	New trial data are also described for interventional cardiology (revascularization in multivessel disease, fractional flow reserve-guided intervention, radial access, bioabsorbable polymer stents, drug-eluting balloons, intraaortic balloon pump use, transcatheter aortic valve implantation), in heart failure (copeptin, angiotensin receptor neprilysin inhibition, aldosterone blockade in diastolic heart failure, biventricular pacing), atrial fibrillation (surgical ablation, antithrombotic strategy after stenting), implantable defibrillator use, and in prevention (renal denervation in hypertension, dalcetrapib, lomitapide, proprotein convertase subtilisin/kexin type 9 in dyslipidemia, insulin glargine/fish oils, and bariatric surgery in diabetes).
90	23714205	By downregulating LDLR, PCSK9 reduces hepatic clearance of LDL-cholesterol.