Proprotein convertase subtilisin/kexin type 9

Details

Name
Proprotein convertase subtilisin/kexin type 9
Synonyms
  • 3.4.21.-
  • NARC-1
  • NARC1
  • Neural apoptosis-regulated convertase 1
  • PC9
  • Proprotein convertase 9
  • Subtilisin/kexin-like protease PC9
Gene Name
PCSK9
Organism
Humans
Amino acid sequence
>lcl|BSEQ0037664|Proprotein convertase subtilisin/kexin type 9
MGTVSSRRSWWPLPLLLLLLLLLGPAGARAQEDEDGDYEELVLALRSEEDGLAEAPEHGT
TATFHRCAKDPWRLPGTYVVVLKEETHLSQSERTARRLQAQAARRGYLTKILHVFHGLLP
GFLVKMSGDLLELALKLPHVDYIEEDSSVFAQSIPWNLERITPPRYRADEYQPPDGGSLV
EVYLLDTSIQSDHREIEGRVMVTDFENVPEEDGTRFHRQASKCDSHGTHLAGVVSGRDAG
VAKGASMRSLRVLNCQGKGTVSGTLIGLEFIRKSQLVQPVGPLVVLLPLAGGYSRVLNAA
CQRLARAGVVLVTAAGNFRDDACLYSPASAPEVITVGATNAQDQPVTLGTLGTNFGRCVD
LFAPGEDIIGASSDCSTCFVSQSGTSQAAAHVAGIAAMMLSAEPELTLAELRQRLIHFSA
KDVINEAWFPEDQRVLTPNLVAALPPSTHGAGWQLFCRTVWSAHSGPTRMATAVARCAPD
EELLSCSSFSRSGKRRGERMEAQGGKLVCRAHNAFGGEGVYAIARCCLLPQANCSVHTAP
PAEASMGTRVHCHQQGHVLTGCSSHWEVEDLGTHKPPVLRPRGQPNQCVGHREASIHASC
CHAPGLECKVKEHGIPAPQEQVTVACEEGWTLTGCSALPGTSHVLGAYAVDNTCVVRSRD
VSTTGSTSEGAVTAVAICCRSRHLAQASQELQ
Number of residues
692
Molecular Weight
74285.545
Theoretical pI
Not Available
GO Classification
Functions
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
Processes
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 / proteolysis / regulation of neuron apoptotic process / regulation of receptor activity / triglyceride metabolic process
Components
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
General Function
Very-low-density lipoprotein particle receptor binding
Specific 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.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0018910|Proprotein convertase subtilisin/kexin type 9 (PCSK9)
ATGGGCACCGTCAGCTCCAGGCGGTCCTGGTGGCCGCTGCCACTGCTGCTGCTGCTGCTG
CTGCTCCTGGGTCCCGCGGGCGCCCGTGCGCAGGAGGACGAGGACGGCGACTACGAGGAG
CTGGTGCTAGCCTTGCGTTCCGAGGAGGACGGCCTGGCCGAAGCACCCGAGCACGGAACC
ACAGCCACCTTCCACCGCTGCGCCAAGGATCCGTGGAGGTTGCCTGGCACCTACGTGGTG
GTGCTGAAGGAGGAGACCCACCTCTCGCAGTCAGAGCGCACTGCCCGCCGCCTGCAGGCC
CAGGCTGCCCGCCGGGGATACCTCACCAAGATCCTGCATGTCTTCCATGGCCTTCTTCCT
GGCTTCCTGGTGAAGATGAGTGGCGACCTGCTGGAGCTGGCCTTGAAGTTGCCCCATGTC
GACTACATCGAGGAGGACTCCTCTGTCTTTGCCCAGAGCATCCCGTGGAACCTGGAGCGG
ATTACCCCTCCACGGTACCGGGCGGATGAATACCAGCCCCCCGACGGAGGCAGCCTGGTG
GAGGTGTATCTCCTAGACACCAGCATACAGAGTGACCACCGGGAAATCGAGGGCAGGGTC
ATGGTCACCGACTTCGAGAATGTGCCCGAGGAGGACGGGACCCGCTTCCACAGACAGGCC
AGCAAGTGTGACAGTCATGGCACCCACCTGGCAGGGGTGGTCAGCGGCCGGGATGCCGGC
GTGGCCAAGGGTGCCAGCATGCGCAGCCTGCGCGTGCTCAACTGCCAAGGGAAGGGCACG
GTTAGCGGCACCCTCATAGGCCTGGAGTTTATTCGGAAAAGCCAGCTGGTCCAGCCTGTG
GGGCCACTGGTGGTGCTGCTGCCCCTGGCGGGTGGGTACAGCCGCGTCCTCAACGCCGCC
TGCCAGCGCCTGGCGAGGGCTGGGGTCGTGCTGGTCACCGCTGCCGGCAACTTCCGGGAC
GATGCCTGCCTCTACTCCCCAGCCTCAGCTCCCGAGGTCATCACAGTTGGGGCCACCAAT
GCCCAAGACCAGCCGGTGACCCTGGGGACTTTGGGGACCAACTTTGGCCGCTGTGTGGAC
CTCTTTGCCCCAGGGGAGGACATCATTGGTGCCTCCAGCGACTGCAGCACCTGCTTTGTG
TCACAGAGTGGGACATCACAGGCTGCTGCCCACGTGGCTGGCATTGCAGCCATGATGCTG
TCTGCCGAGCCGGAGCTCACCCTGGCCGAGTTGAGGCAGAGACTGATCCACTTCTCTGCC
AAAGATGTCATCAATGAGGCCTGGTTCCCTGAGGACCAGCGGGTACTGACCCCCAACCTG
GTGGCCGCCCTGCCCCCCAGCACCCATGGGGCAGGTTGGCAGCTGTTTTGCAGGACTGTA
TGGTCAGCACACTCGGGGCCTACACGGATGGCCACAGCCGTCGCCCGCTGCGCCCCAGAT
GAGGAGCTGCTGAGCTGCTCCAGTTTCTCCAGGAGTGGGAAGCGGCGGGGCGAGCGCATG
GAGGCCCAAGGGGGCAAGCTGGTCTGCCGGGCCCACAACGCTTTTGGGGGTGAGGGTGTC
TACGCCATTGCCAGGTGCTGCCTGCTACCCCAGGCCAACTGCAGCGTCCACACAGCTCCA
CCAGCTGAGGCCAGCATGGGGACCCGTGTCCACTGCCACCAACAGGGCCACGTCCTCACA
GGCTGCAGCTCCCACTGGGAGGTGGAGGACCTTGGCACCCACAAGCCGCCTGTGCTGAGG
CCACGAGGTCAGCCCAACCAGTGCGTGGGCCACAGGGAGGCCAGCATCCACGCTTCCTGC
TGCCATGCCCCAGGTCTGGAATGCAAAGTCAAGGAGCATGGAATCCCGGCCCCTCAGGAG
CAGGTGACCGTGGCCTGCGAGGAGGGCTGGACCCTGACTGGCTGCAGTGCCCTCCCTGGG
ACCTCCCACGTCCTGGGGGCCTACGCCGTAGACAACACGTGTGTAGTCAGGAGCCGGGAC
GTCAGCACTACAGGCAGCACCAGCGAAGGGGCCGTGACAGCCGTTGCCATCTGCTGCCGG
AGCCGGCACCTGGCGCAGGCCTCCCAGGAGCTCCAGTGA
Chromosome Location
1
Locus
Not Available
External Identifiers
ResourceLink
UniProtKB IDQ8NBP7
UniProtKB Entry NamePCSK9_HUMAN
HGNC IDHGNC:20001
General References
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB09302AlirocumabapprovedyesinhibitorDetails
DB14901Inclisiranapproved, investigationalyesantisense oligonucleotideDetails
DB09303EvolocumabapprovedyesinhibitorDetails