Proprotein convertase subtilisin/kexin type 9

A proprotein convertase subtilisin/kexin type 9 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q8NBP7]

Synonyms

EC 3.4.21.-;
Neural apoptosis-regulated convertase 1;
NARC-1;
Proprotein convertase 9;
PC9;
Subtilisin/kexin-like protease PC9

Research

Bioassay Publications (2)

Timeframe	Studies on this Protein(%)	All Drugs %
pre-1990	0 (0.00)	18.7374
1990's	0 (0.00)	18.2507
2000's	0 (0.00)	29.6817
2010's	0 (0.00)	24.3611
2020's	2 (100.00)	2.80

Compounds (2)

Drugs with Inhibition Measurements

Drug	Taxonomy	Measurement	Average (mM)	Bioassay(s)	Publication(s)
s 1033	Homo sapiens (human)	IC50	9.8000	1	1
PF-06446846	Homo sapiens (human)	IC50	0.7500	1	1

Enables

This protein enables 11 target(s):

Target	Category	Definition
RNA binding	molecular function	Binding to an RNA molecule or a portion thereof. [GOC:jl, GOC:mah]
serine-type endopeptidase activity	molecular function	Catalysis of the hydrolysis of internal, alpha-peptide bonds in a polypeptide chain by a catalytic mechanism that involves a catalytic triad consisting of a serine nucleophile that is activated by a proton relay involving an acidic residue (e.g. aspartate or glutamate) and a basic residue (usually histidine). [GOC:mah, https://www.ebi.ac.uk/merops/about/glossary.shtml#CATTYPE]
protein binding	molecular function	Binding to a protein. [GOC:go_curators]
sodium channel inhibitor activity	molecular function	Binds to and stops, prevents, or reduces the activity of a sodium channel. [GOC:mah]
low-density lipoprotein particle binding	molecular function	Binding to a low-density lipoprotein particle, a lipoprotein particle that is rich in cholesterol esters and low in triglycerides, is typically composed of APOB100 and APOE, and has a density of 1.02-1.06 g/ml and a diameter of between 20-25 nm. [GOC:mah]
signaling receptor inhibitor activity	molecular function	Binds to and modulates the activity of a signaling receptor. [GOC:ceb]
apolipoprotein binding	molecular function	Binding to an apolipoprotein, the protein component of a lipoprotein complex. [GOC:BHF, GOC:rl]
very-low-density lipoprotein particle binding	molecular function	Binding to a very-low-density lipoprotein particle, a triglyceride-rich lipoprotein particle that is typically composed of APOB100, APOE and APOCs and has a density of about 1.006 g/ml and a diameter of between 20-80 nm. [GOC:BHF, GOC:mah]
apolipoprotein receptor binding	molecular function	Binding to an apolipoprotein receptor. [GOC:BHF, GOC:rl]
low-density lipoprotein particle receptor binding	molecular function	Binding to a low-density lipoprotein receptor. [GOC:ai]
very-low-density lipoprotein particle receptor binding	molecular function	Binding to a very-low-density lipoprotein receptor. [GOC:BHF, GOC:mah]

Located In

This protein is located in 16 target(s):

Target	Category	Definition
extracellular region	cellular component	The space external to the outermost structure of a cell. For cells without external protective or external encapsulating structures this refers to space outside of the plasma membrane. This term covers the host cell environment outside an intracellular parasite. [GOC:go_curators]
extracellular space	cellular component	That part of a multicellular organism outside the cells proper, usually taken to be outside the plasma membranes, and occupied by fluid. [ISBN:0198547684]
cytoplasm	cellular component	The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures. [ISBN:0198547684]
lysosome	cellular component	A small lytic vacuole that has cell cycle-independent morphology found in most animal cells and that contains a variety of hydrolases, most of which have their maximal activities in the pH range 5-6. The contained enzymes display latency if properly isolated. About 40 different lysosomal hydrolases are known and lysosomes have a great variety of morphologies and functions. [GOC:mah, ISBN:0198506732]
lysosomal membrane	cellular component	The lipid bilayer surrounding the lysosome and separating its contents from the cell cytoplasm. [GOC:ai]
early endosome	cellular component	A membrane-bounded organelle that receives incoming material from primary endocytic vesicles that have been generated by clathrin-dependent and clathrin-independent endocytosis; vesicles fuse with the early endosome to deliver cargo for sorting into recycling or degradation pathways. [GOC:mah, NIF_Subcellular:nlx_subcell_20090701, PMID:19696797]
late endosome	cellular component	A prelysosomal endocytic organelle differentiated from early endosomes by lower lumenal pH and different protein composition. Late endosomes are more spherical than early endosomes and are mostly juxtanuclear, being concentrated near the microtubule organizing center. [NIF_Subcellular:nlx_subcell_20090702, PMID:11964142, PMID:2557062]
endoplasmic reticulum	cellular component	The irregular network of unit membranes, visible only by electron microscopy, that occurs in the cytoplasm of many eukaryotic cells. The membranes form a complex meshwork of tubular channels, which are often expanded into slitlike cavities called cisternae. The ER takes two forms, rough (or granular), with ribosomes adhering to the outer surface, and smooth (with no ribosomes attached). [ISBN:0198506732]
endoplasmic reticulum lumen	cellular component	The volume enclosed by the membranes of the endoplasmic reticulum. [ISBN:0198547684]
Golgi apparatus	cellular component	A membrane-bound cytoplasmic organelle of the endomembrane system that further processes the core oligosaccharides (e.g. N-glycans) added to proteins in the endoplasmic reticulum and packages them into membrane-bound vesicles. The Golgi apparatus operates at the intersection of the secretory, lysosomal, and endocytic pathways. [ISBN:0198506732]
plasma membrane	cellular component	The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins. [ISBN:0716731363]
cell surface	cellular component	The external part of the cell wall and/or plasma membrane. [GOC:jl, GOC:mtg_sensu, GOC:sm]
COPII-coated ER to Golgi transport vesicle	cellular component	A vesicle with a coat formed of the COPII coat complex proteins. The COPII coat complex is formed by the Sec23p/Sec24p and the Sec13p/Sec31p heterodimers. COPII-associated vesicles transport proteins from the rough endoplasmic reticulum to the Golgi apparatus (anterograde transport). [PMID:11252894, PMID:17499046, PMID:22160157, PMID:8004676, Wikipedia:COPII]
extrinsic component of external side of plasma membrane	cellular component	The component of a plasma membrane consisting of gene products and protein complexes that are loosely bound to its external surface, but not integrated into the hydrophobic region. [GOC:dos, GOC:mah]
endolysosome membrane	cellular component	The lipid bilayer surrounding an endolysosome. An endolysosome is a transient hybrid organelle formed by fusion of a late endosome with a lysosome. [GOC:pde]
perinuclear region of cytoplasm	cellular component	Cytoplasm situated near, or occurring around, the nucleus. [GOC:jid]

Active In

This protein is active in 1 target(s):

Target	Category	Definition
extracellular space	cellular component	That part of a multicellular organism outside the cells proper, usually taken to be outside the plasma membranes, and occupied by fluid. [ISBN:0198547684]

Part Of

This protein is part of 2 target(s):

Target	Category	Definition
PCSK9-AnxA2 complex	cellular component	A protein complex consisting of the serine protease PCSK9 (proprotein convertase subtilisin/kexin-9) and annexin A2 (AnxA2). [GOC:BHF, GOC:nc, PMID:22848640]
PCSK9-LDLR complex	cellular component	A protein complex consisting of the serine protease PCSK9 (proprotein convertase subtilisin/kexin-9) and a low-density lipoprotein receptor (LDLR). Interaction typically occurs through the epidermal growth factor-like repeat A (EGF-A) domain of the LDLR, and complex formation promotes degradation of the LDLR through the endosome/lysosome pathway. [GOC:BHF, GOC:nc, PMID:18250299, PMID:24440079]

Involved In

This protein is involved in 27 target(s):

Target	Category	Definition
kidney development	biological process	The process whose specific outcome is the progression of the kidney over time, from its formation to the mature structure. The kidney is an organ that filters the blood and/or excretes the end products of body metabolism in the form of urine. [GOC:dph, GOC:mtg_kidney_jan10, ISBN:0124020607, ISBN:0721662544]
liver development	biological process	The process whose specific outcome is the progression of the liver over time, from its formation to the mature structure. The liver is an exocrine gland which secretes bile and functions in metabolism of protein and carbohydrate and fat, synthesizes substances involved in the clotting of the blood, synthesizes vitamin A, detoxifies poisonous substances, stores glycogen, and breaks down worn-out erythrocytes. [GOC:add, ISBN:068340007X]
negative regulation of receptor recycling	biological process	Any process that stops, prevents, or reduces the rate of receptor recycling. [GOC:add]
negative regulation of receptor internalization	biological process	Any process that stops, prevents, or reduces the frequency, rate or extent of receptor internalization. [GOC:hjd]
positive regulation of receptor internalization	biological process	Any process that activates or increases the frequency, rate or extent of receptor internalization. [GOC:hjd]
triglyceride metabolic process	biological process	The chemical reactions and pathways involving triglyceride, any triester of glycerol. The three fatty acid residues may all be the same or differ in any permutation. Triglycerides are important components of plant oils, animal fats and animal plasma lipoproteins. [ISBN:0198506732]
phospholipid metabolic process	biological process	The chemical reactions and pathways involving phospholipids, any lipid containing phosphoric acid as a mono- or diester. [ISBN:0198506732]
apoptotic process	biological process	A programmed cell death process which begins when a cell receives an internal (e.g. DNA damage) or external signal (e.g. an extracellular death ligand), and proceeds through a series of biochemical events (signaling pathway phase) which trigger an execution phase. The execution phase is the last step of an apoptotic process, and is typically characterized by rounding-up of the cell, retraction of pseudopodes, reduction of cellular volume (pyknosis), chromatin condensation, nuclear fragmentation (karyorrhexis), plasma membrane blebbing and fragmentation of the cell into apoptotic bodies. When the execution phase is completed, the cell has died. [GOC:cjm, GOC:dhl, GOC:ecd, GOC:go_curators, GOC:mtg_apoptosis, GOC:tb, ISBN:0198506732, PMID:18846107, PMID:21494263]
lysosomal transport	biological process	The directed movement of substances into, out of or within a lysosome. [GOC:ai]
cholesterol metabolic process	biological process	The chemical reactions and pathways involving cholesterol, cholest-5-en-3 beta-ol, the principal sterol of vertebrates and the precursor of many steroids, including bile acids and steroid hormones. It is a component of the plasma membrane lipid bilayer and of plasma lipoproteins and can be found in all animal tissues. [ISBN:0198506732]
cellular response to starvation	biological process	Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of deprivation of nourishment. [GOC:jl]
regulation of signaling receptor activity	biological process	Any process that modulates the frequency, rate or extent of a signaling receptor activity. Receptor activity is when a molecule combines with an extracellular or intracellular messenger to initiate a change in cell activity. [GOC:dph, GOC:tb]
negative regulation of low-density lipoprotein particle clearance	biological process	Any process that decreases the rate, frequency or extent of low-density lipoprotein particle clearance. Low-density lipoprotein particle clearance is the process in which a low-density lipoprotein particle is removed from the blood via receptor-mediated endocytosis and its constituent parts degraded. [GOC:BHF, GOC:dph, GOC:tb]
protein autoprocessing	biological process	Processing which a protein carries out itself. This involves actions such as the autolytic removal of residues to generate the mature form of the protein. [GOC:ai, PMID:9335337]
neurogenesis	biological process	Generation of cells within the nervous system. [GO_REF:0000021, GOC:cls, GOC:curators, GOC:dgh, GOC:dph, GOC:jid]
neuron differentiation	biological process	The process in which a relatively unspecialized cell acquires specialized features of a neuron. [GOC:mah]
low-density lipoprotein particle receptor catabolic process	biological process	The chemical reactions and pathways resulting in the breakdown of a low-density lipoprotein particle receptor molecule, a macromolecule that undergoes combination with a hormone, neurotransmitter, drug or intracellular messenger to initiate a change in cell function. [GOC:mah]
positive regulation of low-density lipoprotein particle receptor catabolic process	biological process	Any process that activates or increases the frequency, rate or extent of the chemical reactions and pathways resulting in the breakdown of low-density lipoprotein particle receptors. [GOC:mah]
cellular response to insulin stimulus	biological process	Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an insulin stimulus. Insulin is a polypeptide hormone produced by the islets of Langerhans of the pancreas in mammals, and by the homologous organs of other organisms. [GOC:mah, ISBN:0198506732]
lipoprotein metabolic process	biological process	The chemical reactions and pathways involving any conjugated, water-soluble protein in which the covalently attached nonprotein group consists of a lipid or lipids. [ISBN:0198506732]
cholesterol homeostasis	biological process	Any process involved in the maintenance of an internal steady state of cholesterol within an organism or cell. [GOC:go_curators]
regulation of neuron apoptotic process	biological process	Any process that modulates the occurrence or rate of cell death by apoptotic process in neurons. [GOC:go_curators, GOC:mtg_apoptosis]
positive regulation of neuron apoptotic process	biological process	Any process that activates or increases the frequency, rate or extent of cell death of neurons by apoptotic process. [GOC:go_curators, GOC:mtg_apoptosis]
negative regulation of low-density lipoprotein particle receptor binding	biological process	Any process that stops, prevents or reduces the frequency, rate or extent of low-density lipoprotein particle receptor binding. [GO_REF:0000059, GOC:BHF, GOC:nc, GOC:TermGenie, PMID:22848640]
negative regulation of low-density lipoprotein receptor activity	biological process	Any process that stops, prevents or reduces the frequency, rate or extent of low-density lipoprotein receptor activity. [GO_REF:0000059, GOC:BHF, GOC:nc, GOC:TermGenie, PMID:22848640]
negative regulation of receptor-mediated endocytosis involved in cholesterol transport	biological process	Any process that stops, prevents or reduces the frequency, rate or extent of receptor-mediated endocytosis involved in cholesterol transport. [GO_REF:0000058, GOC:BHF, GOC:nc, GOC:TermGenie, PMID:22848640]
negative regulation of sodium ion transmembrane transporter activity	biological process	Any process that stops, prevents or reduces the frequency, rate or extent of sodium ion transmembrane transporter activity. [GOC:obol]