General Information of the Protein
Protein ID
PT03976
Protein Name
Proprotein convertase subtilisin/kexin type 9
Secondarily
Protein Name
Neural apoptosis-regulated convertase 1
Proprotein convertase 9
Subtilisin/kexin-like protease PC9
Gene Name
PCSK9
Secondarily
Gene Name
NARC1
PSEC0052
Sequence
MGTVSSRRSWWPLPLLLLLLLLLGPAGARAQEDEDGDYEELVLALRSEEDGLAEAPEHGTTATFHRCAKDPWRLPGTYVVVLKEETHLSQSERTARRLQAQAARRGYLTKILHVFHGLLPGFLVKMSGDLLELALKLPHVDYIEEDSSVFAQSIPWNLERITPPRYRADEYQPPDGGSLVEVYLLDTSIQSDHREIEGRVMVTDFENVPEEDGTRFHRQASKCDSHGTHLAGVVSGRDAGVAKGASMRSLRVLNCQGKGTVSGTLIGLEFIRKSQLVQPVGPLVVLLPLAGGYSRVLNAACQRLARAGVVLVTAAGNFRDDACLYSPASAPEVITVGATNAQDQPVTLGTLGTNFGRCVDLFAPGEDIIGASSDCSTCFVSQSGTSQAAAHVAGIAAMMLSAEPELTLAELRQRLIHFSAKDVINEAWFPEDQRVLTPNLVAALPPSTHGAGWQLFCRTVWSAHSGPTRMATAVARCAPDEELLSCSSFSRSGKRRGERMEAQGGKLVCRAHNAFGGEGVYAIARCCLLPQANCSVHTAPPAEASMGTRVHCHQQGHVLTGCSSHWEVEDLGTHKPPVLRPRGQPNQCVGHREASIHASCCHAPGLECKVKEHGIPAPQEQVTVACEEGWTLTGCSALPGTSHVLGAYAVDNTCVVRSRDVSTTGSTSEGAVTAVAICCRSRHLAQASQELQ
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Organism
Homo sapiens, Human
Protein Classification
Enzyme
>
Protease
>
Serine protease
>
Serine protease SB clan
>
Serine protease S8A subfamily
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.
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Uniprot ID
Primary ID:
Q8NBP7

Secondarily ID:
A8T640
C0JYY9
Q5PSM5
Q5SZQ2
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HGNC ID
HGNC:20001
Subcellular Location
Cytoplasm
Secreted
Endosome
Lysosome
Cell surface
Endoplasmic reticulum
Golgi apparatus
Map of Molecular Bioactivity Related to the Protein
Map of Molecular Bioactivity Related to the Protein

Protein
Cell Line
Compound

Bioactivity Value:

<= 0.1 μM
> 0.1 μM and <= 10 μM
> 10 μM
Imprecise Activity
Table of Molecular Bioactivities Related to the Protein
Cell Line ID: CL000063 , Hep-G2
Compound ID Compound Name Compound Formula
CP0564815
(7-fluoro-1H-indol-3-yl)-(6-fluoro-1-methylbenzimidazol-2-yl)methanone
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C17H11F2N3O
 1
1
EC50 = 0.15 nM
   TI
   LI
   LO
   TS
CP0537865
(1-butyl-7-fluoroindol-3-yl)-(6-fluoro-1-methylbenzimidazol-2-yl)methanone
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C21H19F2N3O
 1
1
EC50 = 0.28 nM
   TI
   LI
   LO
   TS
CP0533902
(6-fluoro-1-methylbenzimidazol-2-yl)-[7-fluoro-1-(2-morpholin-4-ylethylsulfonyl)indol-3-yl]methanone
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C23H22F2N4O4S
 1
1
EC50 = 0.69 nM
   TI
   LI
   LO
   TS
CP0564816
(6-fluoro-1-methylbenzimidazol-2-yl)-(7-fluoro-1-methylindol-3-yl)methanone
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C18H13F2N3O
 1
1
EC50 = 1.21 nM
   TI
   LI
   LO
   TS
CP0533901
(6-fluoro-1H-benzimidazol-2-yl)-(7-fluoro-1H-indol-3-yl)methanone
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C16H9F2N3O
 1
1
EC50 = 2.46 nM
   TI
   LI
   LO
   TS
CP0537862
(6-fluoro-1-methylbenzimidazol-2-yl)-[7-fluoro-1-(2-morpholin-4-ylethyl)indol-3-yl]methanone
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C23H22F2N4O2
 1
1
EC50 = 11 nM
   TI
   LI
   LO
   TS
CP0537864
(6-fluoro-1-methylbenzimidazol-2-yl)-[7-fluoro-1-(3-morpholin-4-ylpropyl)indol-3-yl]methanone
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C24H24F2N4O2
 1
1
EC50 = 39.9 nM
   TI
   LI
   LO
   TS
CP0418645
(6-fluoro-1-methylbenzimidazol-2-yl)-[7-fluoro-1-(4-morpholin-4-ylbutyl)indol-3-yl]methanone
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C25H26F2N4O2
 1
1
EC50 = 88 nM
   TI
   LI
   LO
   TS
CP0578910
(6-fluoro-1-methylbenzimidazol-2-yl)-[7-fluoro-1-(2-piperazin-1-ylethylsulfonyl)indol-3-yl]methanone
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C23H23F2N5O3S
 1
1
EC50 = 161 nM
   TI
   LI
   LO
   TS
CP0573065
6-fluoro-2-[(7-fluoro-1H-indol-3-yl)methyl]-1H-benzimidazole
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C16H11F2N3
 1
1
EC50 = 348 nM
   TI
   LI
   LO
   TS
CP0564814
5-fluoro-2-[(7-fluoro-1H-indol-3-yl)methyl]-1H-indole
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C17H12F2N2
 1
1
IC50 = 201.7 nM
   TI
   LI
   LO
   TS
CP0564609
2-[(7-chloro-1H-indol-3-yl)methyl]-5-fluoro-1H-indole
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C17H12ClFN2
 1
1
IC50 = 250 nM
   TI
   LI
   LO
   TS
CP0530277
7-fluoro-3-(1H-indol-2-ylmethyl)-1H-indole
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C17H13FN2
 1
1
IC50 = 300 nM
   TI
   LI
   LO
   TS
CP0568541
3-(1H-indol-2-ylmethyl)-7-methyl-1H-indole
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C18H16N2
 1
1
IC50 = 900 nM
   TI
   LI
   LO
   TS
CP0558259
2-[(1-methylindol-3-yl)methyl]-1-(4-methylphenyl)sulfonyl-3-propan-2-ylindole
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C28H28N2O2S
 1
1
IC50 = 1100 nM
   TI
   LI
   LO
   TS
CP0482658
3-(1H-indol-2-ylmethyl)-6-methyl-1H-indole
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C18H16N2
 1
1
IC50 = 1400 nM
   TI
   LI
   LO
   TS
CP0568542
3-methyl-2-[(1-methylindol-3-yl)methyl]-1-(4-methylphenyl)sulfonylindole
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C26H24N2O2S
 1
1
IC50 = 1500 nM
   TI
   LI
   LO
   TS
CP0424357
2-[(1-methylindol-3-yl)methyl]-1-(4-methylphenyl)sulfonyl-3-phenylindole
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C31H26N2O2S
 1
1
IC50 = 2300 nM
   TI
   LI
   LO
   TS
CP0532926
2-[(7-chloro-1H-indol-3-yl)methyl]-3-methyl-1-(4-methylphenyl)sulfonylindole
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C25H21ClN2O2S
 1
1
IC50 = 2300 nM
   TI
   LI
   LO
   TS
CP0532925
7-chloro-3-(1H-indol-2-ylmethyl)-1H-indole
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C17H13ClN2
 1
1
IC50 = 2800 nM
   TI
   LI
   LO
   TS
CP0559368
3-(1H-indol-2-ylmethyl)-5-methyl-1H-indole
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C18H16N2
 1
1
IC50 = 5600 nM
   TI
   LI
   LO
   TS
CP0515418
5-chloro-3-(1H-indol-2-ylmethyl)-1H-indole
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C17H13ClN2
 1
1
IC50 = 10000 nM
   TI
   LI
   LO
   TS
Biochemical Assays
Compound ID Compound Name Compound Formula
CP0565336
1-methyl-2-[1-methyl-5-[1-methyl-5-(1-methylpyrrol-2-yl)pyrrol-2-yl]pyrrol-2-yl]-5-phenylpyrrole
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C26H26N4
 1
1 IC50 = 11200 nM
CP0954660
(4S)-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-acetamido-3-hydroxy-butanoyl]amino]-3-methyl-butanoyl]amino]-3-phenyl-propanoyl]amino]-3-hydroxy-butanoyl]amino]-3-hydroxy-propanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-hydroxy-5-oxo-pentanoyl]amino]-5-[[(1S)-2-[[(1S)-1-[[(1S)-1-[[(1S)-2-[[(1S)-1-carbamoyl-2-methyl-propyl]amino]-1-(1H-indol-3-ylmethyl)-2-oxo-ethyl]carbamoyl]-3-hydroxy-3-oxo-propyl]carbamoyl]-3-methyl-butyl]amino]-1-[(4-hydroxyphenyl)methyl]-2-oxo-ethyl]amino]-5-oxo-pentanoic acid
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C83H110N16O24
 1
1 Kd = 9700 nM
Clinical Information about the Protein
Target 1 ( Proprotein convertase subtilisin/kexin type 9 (PCSK9) )
Target Type Successful Target
Target 2 ( PCSK9 messenger RNA (PCSK9 mRNA) )
Target Type Successful Target