Details of the Target

General Information of Target

Target ID LDTP09062
Target Name Proprotein convertase subtilisin/kexin type 9 (PCSK9)
Gene Name PCSK9
Gene ID 255738
Synonyms
NARC1; 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
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MGTVSSRRSWWPLPLLLLLLLLLGPAGARAQEDEDGDYEELVLALRSEEDGLAEAPEHGT
TATFHRCAKDPWRLPGTYVVVLKEETHLSQSERTARRLQAQAARRGYLTKILHVFHGLLP
GFLVKMSGDLLELALKLPHVDYIEEDSSVFAQSIPWNLERITPPRYRADEYQPPDGGSLV
EVYLLDTSIQSDHREIEGRVMVTDFENVPEEDGTRFHRQASKCDSHGTHLAGVVSGRDAG
VAKGASMRSLRVLNCQGKGTVSGTLIGLEFIRKSQLVQPVGPLVVLLPLAGGYSRVLNAA
CQRLARAGVVLVTAAGNFRDDACLYSPASAPEVITVGATNAQDQPVTLGTLGTNFGRCVD
LFAPGEDIIGASSDCSTCFVSQSGTSQAAAHVAGIAAMMLSAEPELTLAELRQRLIHFSA
KDVINEAWFPEDQRVLTPNLVAALPPSTHGAGWQLFCRTVWSAHSGPTRMATAVARCAPD
EELLSCSSFSRSGKRRGERMEAQGGKLVCRAHNAFGGEGVYAIARCCLLPQANCSVHTAP
PAEASMGTRVHCHQQGHVLTGCSSHWEVEDLGTHKPPVLRPRGQPNQCVGHREASIHASC
CHAPGLECKVKEHGIPAPQEQVTVACEEGWTLTGCSALPGTSHVLGAYAVDNTCVVRSRD
VSTTGSTSEGAVTAVAICCRSRHLAQASQELQ
Target Type
Successful
Target Bioclass
Enzyme
Family
Peptidase S8 family
Subcellular location
Cytoplasm
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.
TTD ID
T62206
Uniprot ID
Q8NBP7
DrugMap ID
TTBRG7E
Ensemble ID
ENST00000302118.5
HGNC ID
HGNC:20001
ChEMBL ID
CHEMBL2929

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
IGROV1 SNV: p.G337E .
KMS27 SNV: p.V261F .
NCIH2286 SNV: p.A100S .
SW756 SNV: p.S329Ter .

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 4 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
DBIA
 Probe Info  		C588(1.45)  LDD0531  [1]
TFBX
 Probe Info  		N.A.  LDD0027  [2]
IPM
 Probe Info  		C255(0.00); C223(0.00); C301(0.00)  LDD0147  [2]
Methacrolein
 Probe Info  		C301(0.00); C601(0.00)  LDD0218  [3]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0214  AC1 HCT 116 C588(1.45)  LDD0531  [1]
 LDCM0279  AC2 HCT 116 C588(1.37)  LDD0596  [1]
 LDCM0290  AC3 HCT 116 C588(1.25)  LDD0607  [1]
 LDCM0296  AC35 HCT 116 C588(1.20)  LDD0613  [1]
 LDCM0297  AC36 HCT 116 C588(1.33)  LDD0614  [1]
 LDCM0298  AC37 HCT 116 C588(0.85)  LDD0615  [1]
 LDCM0299  AC38 HCT 116 C588(1.28)  LDD0616  [1]
 LDCM0300  AC39 HCT 116 C588(1.06)  LDD0617  [1]
 LDCM0301  AC4 HCT 116 C588(1.19)  LDD0618  [1]
 LDCM0302  AC40 HCT 116 C588(1.53)  LDD0619  [1]
 LDCM0303  AC41 HCT 116 C588(1.48)  LDD0620  [1]
 LDCM0304  AC42 HCT 116 C588(1.25)  LDD0621  [1]
 LDCM0305  AC43 HCT 116 C588(1.01)  LDD0622  [1]
 LDCM0306  AC44 HCT 116 C588(1.09)  LDD0623  [1]
 LDCM0307  AC45 HCT 116 C588(1.22)  LDD0624  [1]
 LDCM0308  AC46 HCT 116 C588(0.91)  LDD0625  [1]
 LDCM0309  AC47 HCT 116 C588(0.95)  LDD0626  [1]
 LDCM0310  AC48 HCT 116 C588(1.04)  LDD0627  [1]
 LDCM0311  AC49 HCT 116 C588(1.14)  LDD0628  [1]
 LDCM0312  AC5 HCT 116 C588(1.27)  LDD0629  [1]
 LDCM0313  AC50 HCT 116 C588(1.20)  LDD0630  [1]
 LDCM0314  AC51 HCT 116 C588(0.95)  LDD0631  [1]
 LDCM0315  AC52 HCT 116 C588(0.94)  LDD0632  [1]
 LDCM0316  AC53 HCT 116 C588(0.98)  LDD0633  [1]
 LDCM0317  AC54 HCT 116 C588(1.05)  LDD0634  [1]
 LDCM0318  AC55 HCT 116 C588(1.21)  LDD0635  [1]
 LDCM0319  AC56 HCT 116 C588(1.14)  LDD0636  [1]
 LDCM0320  AC57 HCT 116 C588(1.22)  LDD0637  [1]
 LDCM0321  AC58 HCT 116 C588(1.09)  LDD0638  [1]
 LDCM0322  AC59 HCT 116 C588(1.18)  LDD0639  [1]
 LDCM0324  AC60 HCT 116 C588(1.18)  LDD0641  [1]
 LDCM0325  AC61 HCT 116 C588(1.17)  LDD0642  [1]
 LDCM0326  AC62 HCT 116 C588(1.16)  LDD0643  [1]
 LDCM0327  AC63 HCT 116 C588(1.02)  LDD0644  [1]
 LDCM0328  AC64 HCT 116 C588(1.11)  LDD0645  [1]
 LDCM0329  AC65 HCT 116 C588(0.66)  LDD0646  [1]
 LDCM0330  AC66 HCT 116 C588(0.70)  LDD0647  [1]
 LDCM0331  AC67 HCT 116 C588(0.71)  LDD0648  [1]
 LDCM0369  CL100 HCT 116 C588(1.26)  LDD0686  [1]
 LDCM0387  CL117 HCT 116 C588(1.25)  LDD0704  [1]
 LDCM0388  CL118 HCT 116 C588(0.98)  LDD0705  [1]
 LDCM0389  CL119 HCT 116 C588(0.94)  LDD0706  [1]
 LDCM0391  CL120 HCT 116 C588(1.04)  LDD0708  [1]
 LDCM0392  CL121 HCT 116 C588(1.26)  LDD0709  [1]
 LDCM0393  CL122 HCT 116 C588(0.88)  LDD0710  [1]
 LDCM0394  CL123 HCT 116 C588(0.77)  LDD0711  [1]
 LDCM0395  CL124 HCT 116 C588(0.98)  LDD0712  [1]
 LDCM0396  CL125 HCT 116 C588(0.86)  LDD0713  [1]
 LDCM0397  CL126 HCT 116 C588(0.69)  LDD0714  [1]
 LDCM0398  CL127 HCT 116 C588(0.71)  LDD0715  [1]
 LDCM0399  CL128 HCT 116 C588(1.26)  LDD0716  [1]
 LDCM0486  CL91 HCT 116 C588(1.11)  LDD0803  [1]
 LDCM0487  CL92 HCT 116 C588(0.71)  LDD0804  [1]
 LDCM0488  CL93 HCT 116 C588(0.86)  LDD0805  [1]
 LDCM0489  CL94 HCT 116 C588(0.78)  LDD0806  [1]
 LDCM0490  CL95 HCT 116 C588(0.81)  LDD0807  [1]
 LDCM0491  CL96 HCT 116 C588(0.79)  LDD0808  [1]
 LDCM0492  CL97 HCT 116 C588(0.86)  LDD0809  [1]
 LDCM0493  CL98 HCT 116 C588(0.91)  LDD0810  [1]
 LDCM0494  CL99 HCT 116 C588(1.21)  LDD0811  [1]
 LDCM0022  KB02 A2780 C588(1.65); C301(1.91)  LDD2254  [4]
 LDCM0023  KB03 A2780 C588(1.71); C301(1.75)  LDD2671  [4]
 LDCM0024  KB05 UACC257 C588(2.60)  LDD3325  [4]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Enzyme
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
72 kDa type IV collagenase (MMP2) Peptidase M10A family P08253
Transporter and channel
Click To Hide/Show 2 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Annexin A2 (ANXA2) Annexin family P07355
Low-density lipoprotein receptor (LDLR) LDLR family P01130

The Drug(s) Related To This Target

Approved
Click To Hide/Show 4 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Regn-727 Antibody D00GNI
Alirocumab BiotechDrug DB09302
Evolocumab . DB09303
Inclisiran . DB14901
Phase 3
Click To Hide/Show 3 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Bococizumab Antibody D03DJT
Pf-04950615 Antibody D03FBV
Amg 145 . D0OW2S
Phase 2
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Ly3015014 Antibody D07SKJ
Phase 1
Click To Hide/Show 2 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Pcsk9 Adnectin . D05EBY
Spc5001 . D0U3GA
Investigative
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
1d05 Antibody D0R0RW

References

1 Reimagining high-throughput profiling of reactive cysteines for cell-based screening of large electrophile libraries. Nat Biotechnol. 2021 May;39(5):630-641. doi: 10.1038/s41587-020-00778-3. Epub 2021 Jan 4.
2 Chemoproteomic Profiling by Cysteine Fluoroalkylation Reveals Myrocin G as an Inhibitor of the Nonhomologous End Joining DNA Repair Pathway. J Am Chem Soc. 2021 Dec 8;143(48):20332-20342. doi: 10.1021/jacs.1c09724. Epub 2021 Nov 24.
Mass spectrometry data entry: PXD029255
3 ACR-Based Probe for the Quantitative Profiling of Histidine Reactivity in the Human Proteome. J Am Chem Soc. 2023 Mar 8;145(9):5252-5260. doi: 10.1021/jacs.2c12653. Epub 2023 Feb 27.
4 DrugMap: A quantitative pan-cancer analysis of cysteine ligandability. Cell. 2024 May 9;187(10):2536-2556.e30. doi: 10.1016/j.cell.2024.03.027. Epub 2024 Apr 22.
Mass spectrometry data entry: PXD047840