LDLR and PCSK9

Number of citations: 0 (PubMedID 17435765)
Data Source: HPRD (in vitro)

		LDLR	PCSK9
Name		low density lipoprotein receptor	proprotein convertase subtilisin/kexin type 9
Structure
GO Annotations	Cellular Component	Lysosome Endosome Early Endosome Late Endosome Golgi Apparatus Plasma Membrane Clathrin-coated Pit External Side Of Plasma Membrane Cell Surface Endosome Membrane Membrane Basolateral Plasma Membrane Clathrin-coated Endocytic Vesicle Membrane Low-density Lipoprotein Particle Endolysosome Membrane Somatodendritic Compartment Receptor Complex Apical Part Of Cell Sorting Endosome PCSK9-LDLR Complex	Extracellular Region Extracellular Space Cytoplasm Lysosome Lysosomal Membrane Endosome Early Endosome Late Endosome Endoplasmic Reticulum Endoplasmic Reticulum Lumen Golgi Apparatus Plasma Membrane Cell Surface COPII-coated ER To Golgi Transport Vesicle Extrinsic Component Of External Side Of Plasma Membrane Endolysosome Membrane Perinuclear Region Of Cytoplasm PCSK9-LDLR Complex PCSK9-AnxA2 Complex
	Molecular Function	Amyloid-beta Binding Virus Receptor Activity Protease Binding Low-density Lipoprotein Particle Receptor Activity Calcium Ion Binding Protein Binding Low-density Lipoprotein Particle Binding Very-low-density Lipoprotein Particle Receptor Activity Clathrin Heavy Chain Binding Identical Protein Binding Molecular Adaptor Activity Lipoprotein Particle Binding	RNA Binding Serine-type Endopeptidase Activity Protein Binding Peptidase Activity Serine-type Peptidase Activity Hydrolase Activity Sodium Channel Inhibitor Activity Low-density Lipoprotein Particle Binding Signaling Receptor Inhibitor Activity Apolipoprotein Binding Very-low-density Lipoprotein Particle Binding Apolipoprotein Receptor Binding Low-density Lipoprotein Particle Receptor Binding Very-low-density Lipoprotein Particle Receptor Binding
	Biological Process	Retinoid Metabolic Process Negative Regulation Of Receptor Recycling Lipid Metabolic Process Lipid Transport Endocytosis Receptor-mediated Endocytosis Phagocytosis Long-term Memory Steroid Metabolic Process Cholesterol Metabolic Process Negative Regulation Of Macromolecule Metabolic Process Positive Regulation Of Gene Expression Negative Regulation Of Gene Expression Positive Regulation Of Triglyceride Biosynthetic Process Regulation Of Phosphatidylcholine Catabolic Process Negative Regulation Of Low-density Lipoprotein Particle Clearance Phospholipid Transport Intestinal Cholesterol Absorption Cholesterol Transport Plasma Lipoprotein Particle Clearance Low-density Lipoprotein Particle Clearance High-density Lipoprotein Particle Clearance Lipoprotein Metabolic Process Lipoprotein Catabolic Process Cholesterol Homeostasis Symbiont Entry Into Host Cell Artery Morphogenesis Positive Regulation Of Inflammatory Response Negative Regulation Of Multicellular Organismal Process Regulation Of Protein Metabolic Process Negative Regulation Of Protein Metabolic Process Establishment Of Localization In Cell Artery Development Response To Caloric Restriction Negative Regulation Of Astrocyte Activation Cholesterol Import Cellular Response To Fatty Acid Cellular Response To Low-density Lipoprotein Particle Stimulus Receptor-mediated Endocytosis Involved In Cholesterol Transport Regulation Of Cholesterol Metabolic Process Amyloid-beta Clearance Amyloid-beta Clearance By Cellular Catabolic Process Negative Regulation Of Microglial Cell Activation Positive Regulation Of Lysosomal Protein Catabolic Process Negative Regulation Of Amyloid Fibril Formation	Kidney Development Liver Development Negative Regulation Of Receptor Recycling Negative Regulation Of Receptor Internalization Positive Regulation Of Receptor Internalization Proteolysis Lipid Metabolic Process Triglyceride Metabolic Process Phospholipid Metabolic Process Apoptotic Process Lysosomal Transport Steroid Metabolic Process Cholesterol Metabolic Process Cellular Response To Starvation Negative Regulation Of Low-density Lipoprotein Particle Clearance Protein Processing Protein Autoprocessing Neurogenesis Neuron Differentiation Low-density Lipoprotein Receptor Particle Metabolic Process Low-density Lipoprotein Particle Receptor Catabolic Process Regulation Of Low-density Lipoprotein Particle Receptor Catabolic Process Positive Regulation Of Low-density Lipoprotein Particle Receptor Catabolic Process Cellular Response To Insulin Stimulus Lipoprotein Metabolic Process Cholesterol Homeostasis Regulation Of Neuron Apoptotic Process Positive Regulation Of Neuron Apoptotic Process Negative Regulation Of Sodium Ion Import Across Plasma Membrane Negative Regulation Of Receptor-mediated Endocytosis Involved In Cholesterol Transport
Pathways		Cargo recognition for clathrin-mediated endocytosis Clathrin-mediated endocytosis Chylomicron clearance Chylomicron clearance LDL clearance Retinoid metabolism and transport	Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) VLDLR internalisation and degradation Post-translational protein phosphorylation LDL clearance
Drugs		Porfimer sodium	Alirocumab Evolocumab Inclisiran
Diseases		Hypercholesterolemia, autosomal dominant; Hyperlipoproteinemia, type IIa	Hypercholesterolemia, autosomal dominant; Hyperlipoproteinemia, type IIa
GWAS		Abdominal aortic aneurysm ( 27899403 24046328 ) Aging traits (healthspan, parental lifespan or longevity) (multivariate analysis) ( 32678081 ) Apolipoprotein B levels ( 32203549 ) C-reactive protein levels or LDL-cholesterol levels (pleiotropy) ( 27286809 ) Cardiovascular disease risk factors ( 21943158 ) Carotid intima media thickness ( 21909108 ) Carotid plaque ( 30510157 ) Cholesterol ( 31902109 ) Cholesterol, total ( 20686565 24097068 26582766 19060911 25961943 ) Coronary artery disease ( 32469254 26343387 24262325 33020668 29212778 ) Coronary artery disease (myocardial infarction, percutaneous transluminal coronary angioplasty, coronary artery bypass grafting, angina or chromic ischemic heart disease) ( 28714975 ) Coronary artery disease or ischemic stroke ( 24262325 ) Coronary artery disease or large artery stroke ( 24262325 ) Coronary heart disease ( 21378990 ) Cortisol levels (saliva) ( 28843169 ) Disorders of lipid metabolism ( 30166351 ) HDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df) ( 30698716 ) LDL cholesterol ( 26582766 30275531 18193044 24097068 23726366 25961943 21347282 20864672 20686565 19060906 18193043 19060910 19060911 ) LDL cholesterol levels ( 32203549 26690388 30698716 28334899 ) LDL cholesterol levels in current drinkers ( 30698716 ) LDL cholesterol levels in HIV infection ( 33109212 ) LDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df) ( 30698716 ) LDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df) ( 30698716 ) LDL cholesterol levels x long total sleep time interaction (2df test) ( 31719535 ) LDL cholesterol levels x short total sleep time interaction (2df test) ( 31719535 ) Lipid metabolism phenotypes ( 19936222 22286219 ) Lipoprotein (a) levels ( 33730874 ) Lipoprotein phospholipase A2 activity in cardiovascular disease ( 28753643 ) Lipoprotein-associated phospholipase A2 activity and mass ( 22003152 ) Low density lipoprotein cholesterol levels ( 30911093 33339817 31217584 29403010 ) Medication use (agents acting on the renin-angiotensin system) ( 31015401 ) Medication use (antithrombotic agents) ( 31015401 ) Medication use (HMG CoA reductase inhibitors) ( 31015401 ) Medication use (salicylic acid and derivatives) ( 31015401 ) Metabolite levels ( 21909109 22916037 23823483 ) Myocardial infarction ( 33532862 26343387 ) Myocardial infarction (early onset) ( 19198609 ) Parental lifespan ( 30642433 ) Parental longevity (combined parental attained age, Martingale residuals) ( 29227965 ) Peripheral artery disease ( 31285632 ) Serum metabolite levels ( 31636271 ) Serum metabolite levels (CMS) ( 31636271 ) Total cholesterol levels ( 28334899 31217584 30911093 33339817 29403010 )	Abdominal aortic aneurysm ( 32981348 ) Apolipoprotein A1 levels ( 32203549 ) Apolipoprotein B levels ( 32203549 ) Blood protein levels ( 30072576 ) Carotid intima media thickness x smoking interaction ( 32117412 ) Cholesterol, total ( 25961943 20686565 28270201 26582766 24097068 ) Coronary artery disease ( 33020668 26343387 32469254 29212778 ) Coronary artery disease (myocardial infarction, percutaneous transluminal coronary angioplasty, coronary artery bypass grafting, angina or chromic ischemic heart disease) ( 28714975 ) Coronary heart disease ( 21378990 ) LDL cholesterol ( 24507774 26582766 30275531 26160806 25961943 24097068 23726366 20864672 20686565 18193043 19060906 18193044 ) LDL cholesterol levels ( 31087446 30698716 28334899 26690388 32203549 ) LDL cholesterol levels in current drinkers ( 30698716 ) LDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df) ( 30698716 ) LDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df) ( 30698716 ) LDL cholesterol levels x long total sleep time interaction (2df test) ( 31719535 ) LDL cholesterol levels x short total sleep time interaction (2df test) ( 31719535 ) Lipid metabolism phenotypes ( 22286219 ) Lipoprotein (a) levels ( 33730874 ) Low density lipoprotein cholesterol levels ( 30718733 33339817 32154731 ) Medication use (HMG CoA reductase inhibitors) ( 31015401 ) Metabolite levels ( 22916037 23823483 ) Mitochondrial DNA copy number ( 30704525 ) Myocardial infarction ( 33532862 26343387 ) Myocardial infarction (early onset) ( 19198609 ) Plasma proprotein convertase subtilisin/kexin type 9 levels in stable coronary artery disease ( 29748315 ) Response to statins (LDL cholesterol change) ( 22331829 ) Serum metabolite levels ( 31636271 ) Serum metabolite levels (CMS) ( 31636271 ) Total cholesterol levels ( 29403010 28334899 26690388 30275531 33339817 31087446 30718733 )
Interacting Genes		18 interacting genes: AP1M2 APOB APOE CD36 CREBBP DAB1 DAB2 HSPA5 LDLRAP1 LRPAP1 MAP4 MTIF3 MYLIP PCSK9 PF4 SNX17 TLE5 WEE2-AS1	3 interacting genes: BACE1 BIRC2 LDLR
Entrez ID		3949	255738
HPRD ID		06091	07080
Ensembl ID		ENSG00000130164	ENSG00000169174
Uniprot IDs		H0YMQ3 P01130	A0A669KBG0 A0AAQ5BGX4 Q8NBP7
PDB IDs		1AJJ 1D2J 1F5Y 1F8Z 1HJ7 1HZ8 1I0U 1IJQ 1LDL 1LDR 1N7D 1XFE 2FCW 2KRI 2LGP 2M7P 2MG9 2W2M 2W2N 2W2O 2W2P 2W2Q 3BPS 3GCW 3GCX 3M0C 3P5B 3P5C 3SO6 4NE9 5OY9 5OYL 9BD8 9BDE 9BDT 9COO	2P4E 2PMW 2QTW 2W2M 2W2N 2W2O 2W2P 2W2Q 2XTJ 3BPS 3GCW 3GCX 3H42 3M0C 3P5B 3P5C 3SQO 4K8R 4NE9 4NMX 4OV6 5OCA 5VL7 5VLA 5VLH 5VLK 5VLL 5VLP 6E4Y 6E4Z 6MV5 6OLZ 6OM0 6OM7 6U26 6U2F 6U2N 6U2P 6U36 6U38 6U3I 6U3X 7ANQ
GO Terms Enriched among Interactors		Low-density Lipoprotein Particle Receptor Binding Very-low-density Lipoprotein Particle Receptor Binding Plasma Lipoprotein Particle Clearance Regulation Of Endocytosis Regulation Of Low-density Lipoprotein Particle Receptor Catabolic Process Sterol Homeostasis Cholesterol Homeostasis Cholesterol Metabolic Process Sterol Metabolic Process Negative Regulation Of Cellular Component Organization Low-density Lipoprotein Particle Clearance Positive Regulation Of Endocytosis Cholesterol Transport Lipid Homeostasis Negative Regulation Of Lipoprotein Particle Clearance Receptor-mediated Endocytosis Regulation Of Vesicle-mediated Transport Clathrin Adaptor Activity Negative Regulation Of Cell Projection Organization Regulation Of Low-density Lipoprotein Particle Clearance Chylomicron Remnant Cerebellum Structural Organization Positive Regulation Of Macrophage Derived Foam Cell Differentiation Sterol Transport Amyloid-beta Binding Positive Regulation Of Low-density Lipoprotein Particle Receptor Catabolic Process Steroid Metabolic Process Regulation Of Steroid Metabolic Process Lipoprotein Metabolic Process Regulation Of Macrophage Derived Foam Cell Differentiation Regulation Of Cellular Component Organization Negative Regulation Of Neuron Projection Development Regulation Of Receptor-mediated Endocytosis Cellular Response To Lipoprotein Particle Stimulus Alcohol Metabolic Process Receptor Ligand Activity Intermediate-density Lipoprotein Particle Positive Regulation Of Steroid Metabolic Process Regulation Of Lipid Transport Intracellular Membrane-bounded Organelle Lipoprotein Biosynthetic Process Early Endosome Regulation Of Cholesterol Metabolic Process Heparin Binding Cellular Response To Amyloid-beta Organic Hydroxy Compound Transport Positive Regulation Of Cholesterol Storage Positive Regulation Of Receptor-mediated Endocytosis Lipoprotein Particle Binding Positive Regulation Of Amyloid-beta Clearance	Amyloid-beta Metabolic Process Negative Regulation Of Ripoptosome Assembly Involved In Necroptotic Process FBXO Family Protein Binding Amyloid-beta Binding Receptor-mediated Endocytosis Involved In Cholesterol Transport Late Endosome PCSK9-LDLR Complex Golgi-associated Vesicle Lumen Beta-aspartyl-peptidase Activity Positive Regulation Of Protein K48-linked Ubiquitination Negative Regulation Of Astrocyte Activation Regulation Of Phosphatidylcholine Catabolic Process Regulation Of Protein K48-linked Ubiquitination Positive Regulation Of Protein K63-linked Ubiquitination XY Body Response To Bleomycin Positive Regulation Of Protein Monoubiquitination CD40 Receptor Complex Regulation Of Protein K63-linked Ubiquitination Regulation Of Protein Monoubiquitination Regulation Of Nucleotide-binding Domain, Leucine Rich Repeat Containing Receptor Signaling Pathway Regulation Of Inflammatory Response Necroptotic Process Negative Regulation Of Amyloid Fibril Formation Intestinal Cholesterol Absorption Regulation Of Astrocyte Activation Early Endosome Negative Regulation Of Astrocyte Differentiation Positive Regulation Of Lysosomal Protein Catabolic Process Regulation Of Phosphatidylcholine Metabolic Process Positive Regulation Of Triglyceride Biosynthetic Process Regulation Of Lysosomal Protein Catabolic Process Very-low-density Lipoprotein Particle Receptor Activity Negative Regulation Of Receptor Recycling Cholesterol Import Clathrin Heavy Chain Binding Lipoprotein Particle Binding Negative Regulation Of Low-density Lipoprotein Particle Clearance Low-density Lipoprotein Particle Regulation Of Phospholipid Catabolic Process Low-density Lipoprotein Particle Receptor Activity Positive Regulation Of Protein Catabolic Process In The Vacuole Intestinal Lipid Absorption Lipoprotein Catabolic Process Negative Regulation Of Microglial Cell Activation Sorting Endosome Endosome Membrane Low-density Lipoprotein Particle Clearance Negative Regulation Of Neuroinflammatory Response Golgi Apparatus