Pcsk9
entrez
100102
canonical
uniprot
Q80W65
canonical
ensembl
ENSMUSG00000044254
resolver
ensp
ENSMUSP00000055757
resolver
enst
ENSMUST00000049507
resolver
genesymbol
Pcsk9
resolver
genesymbol_syn
Narc1
resolver
uniprot
B1AZI4
resolver
uniprot
Q3UEH7
resolver
uniprot
Q8BXW9
resolver
uniprot
Q8CFT6
resolver
uniprot_entry
PCSK9_MOUSE
resolver
uniprot_sec
B1AZI4
resolver
uniprot_sec
Q3UEH7
resolver
uniprot_sec
Q8BXW9
resolver
uniprot_sec
Q8CFT6
resolver
activity_regulation
ACTIVITY REGULATION: Its proteolytic activity is autoinhibited by the non-covalent binding of the propeptide to the catalytic domain. Inhibited by EGTA.
uniprot
proteins
amino_acid_sequence
MGTHCSAWLRWPLLPLLPPLLLLLLLLCPTGAGAQDEDGDYEELMLALPSQEDGLADEAAHVATATFRRCSKEAWRLPGTYIVVLMEETQRLQIEQTAHRLQTRAARRGYVIKVLHIFYDLFPGFLVKMSSDLLGLALKLPHVEYIEEDSFVFAQSIPWNLERIIPAWHQTEEDRSPDGSSQVEVYLLDTSIQGAHREIEGRVTITDFNSVPEEDGTRFHRQASKCDSHGTHLAGVVSGRDAGVAKGTSLHSLRVLNCQGKGTVSGTLIGLEFIRKSQLIQPSGPLVVLLPLAGGYSRILNAACRHLARTGVVLVAAAGNFRDDACLYSPASAPEVITVGATNAQDQPVTLGTLGTNFGRCVDLFAPGKDIIGASSDCSTCFMSQSGTSQAAAHVAGIVARMLSREPTLTLAELRQRLIHFSTKDVINMAWFPEDQQVLTPNLVATLPPSTHETGGQLLCRTVWSAHSGPTRTATATARCAPEEELLSCSSFSRSGRRRGDWIEAIGGQQVCKALNAFGGEGVYAVARCCLVPRANCSIHNTPAARAGLETHVHCHQKDHVLTGCSFHWEVEDLSVRRQPALRSRRQPGQCVGHQAASVYASCCHAPGLECKIKEHGISGPSEQVTVACEAGWTLTGCNVLPGASLTLGAYSVDNLCVARVHDTARADRTSGEATVAAAICCRSRPSAKASWVQ
uniprot
proteins
ec_number
3.4.21.-
uniprot
proteins
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. 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. 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. 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. {ECO:0000269|PubMed:22481440, ECO:0000269|PubMed:22580899}.
uniprot
proteins
mass_dalton
74823
uniprot
proteins
post_translational_modification
PTM: Cleavage by furin and PCSK5 generates a truncated inactive protein that is unable to induce LDLR degradation. {ECO:0000250}.; PTM: Undergoes autocatalytic cleavage in the endoplasmic reticulum to release the propeptide from the N-terminus and the cleavage of the propeptide is strictly required for its maturation and activation. The cleaved propeptide however remains associated with the catalytic domain through non-covalent interactions, preventing potential substrates from accessing its active site. As a result, it is secreted from cells as a propeptide-containing, enzymatically inactive protein (By similarity). {ECO:0000250}.; PTM: Phosphorylation protects the propeptide against proteolysis. {ECO:0000250}.
uniprot
proteins
protein_family
Peptidase S8 family
uniprot
proteins
pubmed
12552133
uniprot
proteins
pubmed
12897189
uniprot
proteins
pubmed
14622975
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
18498363
uniprot
proteins
pubmed
19468303
uniprot
proteins
pubmed
22481440
uniprot
proteins
pubmed
22580899
uniprot
proteins
sequence_length
694
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Secreted. Endosome {ECO:0000250}. Lysosome {ECO:0000250}. Cell surface {ECO:0000250}. Endoplasmic reticulum {ECO:0000250}. Golgi apparatus {ECO:0000250}. 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 co-localizes 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 (By similarity). {ECO:0000250}.
uniprot
proteins