Drug Miner Browse

Names & Taxonomy

Uniprot ID:: Q8NBP7
Entry Name:: PCSK9_HUMAN
Status:: reviewed
Protein Names:: Proprotein convertase subtilisin/kexin type 9 (EC 3.4.21.-) (Neural apoptosis-regulated convertase 1) (NARC-1) (Proprotein convertase 9) (PC9) (Subtilisin/kexin-like protease PC9)
Gene Names:: PCSK9 NARC1 PSEC0052
Gene Names Orf:: PSEC0052
Gene Names Primary:: PCSK9
Organism:: Homo sapiens (Human)

Structure

Length:: 692
Sequence:: MGTVSSRRSWWPLPLLLLLLLLLGPAGARAQEDEDGDYEELVLALRSEEDGLAEAPEHGTTATFHRCAKDPWRLPGTYVVVLKEETHLSQSERTARRLQAQAARRGYLTKILHVFHGLLPGFLVKMSGDLLELALKLPHVDYIEEDSSVFAQSIPWNLERITPPRYRADEYQPPDGGSLVEVYLLDTSIQSDHREIEGRVMVTDFENVPEEDGTRFHRQASKCDSHGTHLAGVVSGRDAGVAKGASMRSLRVLNCQGKGTVSGTLIGLEFIRKSQLVQPVGPLVVLLPLAGGYSRVLNAACQRLARAGVVLVTAAGNFRDDACLYSPASAPEVITVGATNAQDQPVTLGTLGTNFGRCVDLFAPGEDIIGASSDCSTCFVSQSGTSQAAAHVAGIAAMMLSAEPELTLAELRQRLIHFSAKDVINEAWFPEDQRVLTPNLVAALPPSTHGAGWQLFCRTVWSAHSGPTRMATAVARCAPDEELLSCSSFSRSGKRRGERMEAQGGKLVCRAHNAFGGEGVYAIARCCLLPQANCSVHTAPPAEASMGTRVHCHQQGHVLTGCSSHWEVEDLGTHKPPVLRPRGQPNQCVGHREASIHASCCHAPGLECKVKEHGIPAPQEQVTVACEEGWTLTGCSALPGTSHVLGAYAVDNTCVVRSRDVSTTGSTSEGAVTAVAICCRSRHLAQASQELQ
Proteomes:: UP000005640

Subcellular location

Subcellular Location:: Cytoplasm. Secreted. Endosome. Lysosome. Cell surface. Endoplasmic reticulum. Golgi apparatus. Note=Autocatalytic cleavage is required to transport it from the endoplasmic reticulum to the Golgi apparatus and for the secretion of the mature protein. Localizes to the endoplasmic reticulum in the absence of LDLR and colocalizes to the cell surface and to the endosomes/lysosomes in the presence of LDLR. The sorting to the cell surface and endosomes is required in order to fully promote LDLR degradation.

Function

Function:: Crucial player in the regulation of plasma cholesterol homeostasis. Binds to low-density lipid receptor family members: low density lipoprotein receptor (LDLR), very low density lipoprotein receptor (VLDLR), apolipoprotein E receptor (LRP1/APOER) and apolipoprotein receptor 2 (LRP8/APOER2), and promotes their degradation in intracellular acidic compartments (PubMed:18039658). Acts via a non-proteolytic mechanism to enhance the degradation of the hepatic LDLR through a clathrin LDLRAP1/ARH-mediated pathway. May prevent the recycling of LDLR from endosomes to the cell surface or direct it to lysosomes for degradation. Can induce ubiquitination of LDLR leading to its subsequent degradation (PubMed:18799458, PubMed:17461796, PubMed:18197702, PubMed:22074827). Inhibits intracellular degradation of APOB via the autophagosome/lysosome pathway in a LDLR-independent manner. Involved in the disposal of non-acetylated intermediates of BACE1 in the early secretory pathway (PubMed:18660751). Inhibits epithelial Na(+) channel (ENaC)-mediated Na(+) absorption by reducing ENaC surface expression primarily by increasing its proteasomal degradation. Regulates neuronal apoptosis via modulation of LRP8/APOER2 levels and related anti-apoptotic signaling pathways.
Cofactor:: COFACTOR: Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
Enzyme Regulation:: ENZYME REGULATION: Its proteolytic activity is autoinhibited by the non-covalent binding of the propeptide to the catalytic domain. Inhibited by EGTA.
Active Site:: ACT_SITE 186 186 Charge relay system.
Cross Reference Drug Bank:: DB09302 DB09303
Gene Ontology Go:: cell surface
cytoplasm
early endosome
endoplasmic reticulum
ER to Golgi transport vesicle
extracellular space
extrinsic component of external side of plasma membrane
Golgi apparatus
late endosome
lysosome
PCSK9-AnxA2 complex
PCSK9-LDLR complex
perinuclear region of cytoplasm
plasma membrane
rough endoplasmic reticulum
apolipoprotein binding
apolipoprotein receptor binding
low-density lipoprotein particle binding
low-density lipoprotein particle receptor binding
poly(A) RNA binding
protein self-association
receptor inhibitor activity
serine-type endopeptidase activity
sodium channel inhibitor activity
very-low-density lipoprotein particle binding
very-low-density lipoprotein particle receptor binding
apoptotic process
cellular response to insulin stimulus
cellular response to starvation
cholesterol homeostasis
cholesterol metabolic process
kidney development
lipoprotein metabolic process
liver development
low-density lipoprotein particle receptor catabolic process
lysosomal transport
negative regulation of low-density lipoprotein particle clearance
negative regulation of receptor activity
negative regulation of receptor recycling
negative regulation of sodium ion transmembrane transporter activity
neurogenesis
neuron differentiation
phospholipid metabolic process
positive regulation of low-density lipoprotein particle receptor catabolic process
positive regulation of neuron apoptotic process
positive regulation of receptor internalization
protein autoprocessing
regulation of neuron apoptotic process
regulation of receptor activity
triglyceride metabolic process
Gene Ontology Biological Process:: apoptotic process
cellular response to insulin stimulus
cellular response to starvation
cholesterol homeostasis
cholesterol metabolic process
kidney development
lipoprotein metabolic process
liver development
low-density lipoprotein particle receptor catabolic process
lysosomal transport
negative regulation of low-density lipoprotein particle clearance
negative regulation of receptor activity
negative regulation of receptor recycling
negative regulation of sodium ion transmembrane transporter activity
neurogenesis
neuron differentiation
phospholipid metabolic process
positive regulation of low-density lipoprotein particle receptor catabolic process
positive regulation of neuron apoptotic process
positive regulation of receptor internalization
protein autoprocessing
regulation of neuron apoptotic process
regulation of receptor activity
triglyceride metabolic process
Gene Ontology Molecular Function:: apolipoprotein binding
apolipoprotein receptor binding
low-density lipoprotein particle binding
low-density lipoprotein particle receptor binding
poly(A) RNA binding
protein self-association
receptor inhibitor activity
serine-type endopeptidase activity
sodium channel inhibitor activity
very-low-density lipoprotein particle binding
very-low-density lipoprotein particle receptor binding
Gene Ontology Cellular Component:: cell surface
cytoplasm
early endosome
endoplasmic reticulum
ER to Golgi transport vesicle
extracellular space
extrinsic component of external side of plasma membrane
Golgi apparatus
late endosome
lysosome
PCSK9-AnxA2 complex
PCSK9-LDLR complex
perinuclear region of cytoplasm
plasma membrane
rough endoplasmic reticulum
Keywords:: 3D-structure
Alternative splicing
Apoptosis
Autocatalytic cleavage
Calcium
Cholesterol metabolism
Complete proteome
Cytoplasm
Direct protein sequencing
Disease mutation
Disulfide bond
Endoplasmic reticulum
Endosome
Glycoprotein
Golgi apparatus
Hydrolase
Lipid metabolism
Lysosome
Phosphoprotein
Polymorphism
Protease
Reference proteome
Secreted
Serine protease
Signal
Steroid metabolism
Sterol metabolism
Sulfation
Zymogen
Interacts With:: P07355; P01130; P08253

Names & Taxonomy

Structure

Subcellular location

Function

Publication