Target Information
Target General Infomation | |||||
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Target ID |
T86652
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Former ID |
TTDR01439
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Target Name |
mRNA of proprotein convertase subtilisin/kexin type 9
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Gene Name |
PCSK9
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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
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Target Type |
Clinical Trial
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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.
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BioChemical Class |
Peptidase
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UniProt ID | |||||
EC Number |
EC3.4.21.-
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Sequence |
MGTVSSRRSWWPLPLLLLLLLLLGPAGARAQEDEDGDYEELVLALRSEEDGLAEAPEHGT
TATFHRCAKDPWRLPGTYVVVLKEETHLSQSERTARRLQAQAARRGYLTKILHVFHGLLP GFLVKMSGDLLELALKLPHVDYIEEDSSVFAQSIPWNLERITPPRYRADEYQPPDGGSLV EVYLLDTSIQSDHREIEGRVMVTDFENVPEEDGTRFHRQASKCDSHGTHLAGVVSGRDAG VAKGASMRSLRVLNCQGKGTVSGTLIGLEFIRKSQLVQPVGPLVVLLPLAGGYSRVLNAA CQRLARAGVVLVTAAGNFRDDACLYSPASAPEVITVGATNAQDQPVTLGTLGTNFGRCVD LFAPGEDIIGASSDCSTCFVSQSGTSQAAAHVAGIAAMMLSAEPELTLAELRQRLIHFSA KDVINEAWFPEDQRVLTPNLVAALPPSTHGAGWQLFCRTVWSAHSGPTRMATAVARCAPD EELLSCSSFSRSGKRRGERMEAQGGKLVCRAHNAFGGEGVYAIARCCLLPQANCSVHTAP PAEASMGTRVHCHQQGHVLTGCSSHWEVEDLGTHKPPVLRPRGQPNQCVGHREASIHASC CHAPGLECKVKEHGIPAPQEQVTVACEEGWTLTGCSALPGTSHVLGAYAVDNTCVVRSRD VSTTGSTSEGAVTAVAICCRSRHLAQASQELQ |
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Drugs and Mode of Action | |||||
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM) | |||||
TEP | EXP Info | ||||
Pathways | |||||
WikiPathways | PCSK9-mediated LDLR degradation | ||||
References | |||||
Ref 523923 | ClinicalTrials.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 549836 | GW24-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 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). |
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