Target General Infomation
Target ID
T86652
Former ID
TTDR01439
Target Name
mRNA of proprotein convertase subtilisin/kexin type 9
Gene Name
PCSK9
Synonyms
mRNA of NARC-1; mRNA of Neural apoptosis-regulated convertase 1; mRNA of PC9; mRNA of PCSK9; mRNA of Proprotein convertase 9; mRNA of Subtilisin/kexin-like protease PC9; PCSK9
Target Type
Clinical Trial
Disease Cardiovascular disorder [ICD10: I00-I99]
Coronary artery disease [ICD9: 410-414, 429.2; ICD10: I20-I25]
Hypercholesterolemia [ICD10: E78]
Metabolic disorders [ICD9: 270-279; ICD10: E70-E89]
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 inthe 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.
BioChemical Class
Peptidase
UniProt ID
EC Number
EC3.4.21.-
Sequence
MGTVSSRRSWWPLPLLLLLLLLLGPAGARAQEDEDGDYEELVLALRSEEDGLAEAPEHGT
TATFHRCAKDPWRLPGTYVVVLKEETHLSQSERTARRLQAQAARRGYLTKILHVFHGLLP
GFLVKMSGDLLELALKLPHVDYIEEDSSVFAQSIPWNLERITPPRYRADEYQPPDGGSLV
EVYLLDTSIQSDHREIEGRVMVTDFENVPEEDGTRFHRQASKCDSHGTHLAGVVSGRDAG
VAKGASMRSLRVLNCQGKGTVSGTLIGLEFIRKSQLVQPVGPLVVLLPLAGGYSRVLNAA
CQRLARAGVVLVTAAGNFRDDACLYSPASAPEVITVGATNAQDQPVTLGTLGTNFGRCVD
LFAPGEDIIGASSDCSTCFVSQSGTSQAAAHVAGIAAMMLSAEPELTLAELRQRLIHFSA
KDVINEAWFPEDQRVLTPNLVAALPPSTHGAGWQLFCRTVWSAHSGPTRMATAVARCAPD
EELLSCSSFSRSGKRRGERMEAQGGKLVCRAHNAFGGEGVYAIARCCLLPQANCSVHTAP
PAEASMGTRVHCHQQGHVLTGCSSHWEVEDLGTHKPPVLRPRGQPNQCVGHREASIHASC
CHAPGLECKVKEHGIPAPQEQVTVACEEGWTLTGCSALPGTSHVLGAYAVDNTCVVRSRD
VSTTGSTSEGAVTAVAICCRSRHLAQASQELQ
Drugs and Mode of Action
Drug(s) MPSK3169A Drug Info Phase 2 Cardiovascular disorder [523923]
MPSK3169A Drug Info Phase 1 Metabolic disorders [549836]
ALN-PCS Drug Info Preclinical Hypercholesterolemia [550232]
BMS-PCSK9 Drug Info Preclinical Coronary artery disease [551053]
Modulator MPSK3169A Drug Info [543615]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
WikiPathways PCSK9-mediated LDLR degradation
References
Ref 523923ClinicalTrials.gov (NCT01609140) A Phase II Study of the Safety and Efficacy of MPSK3169A in Patients With Coronary Heart Disease or High Risk of Coronary Heart Disease. U.S. National Institutes of Health.
Ref 549836GW24-e2907??ffects of RG7652, a fully human mAb against proprotein convertase subtilisin/kexin type 9, on LDL-c: a Phase I, randomised, double-blind, placebo-controlled, single- and multiple-dose study. Heart 2013;99:A153.
Ref 550232Clinical pipeline report, company report or official report of Alnylam Pharmaceuticals, Inc (2011).
Ref 551053Clinical pipeline report, company report or official report of ISIS Pharmaceuticals (2011).
Ref 543615(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2388).
Ref 550232Clinical pipeline report, company report or official report of Alnylam Pharmaceuticals, Inc (2011).
Ref 551053Clinical pipeline report, company report or official report of ISIS Pharmaceuticals (2011).

If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.