Details of the BTS
General Information of Binding Target of SBP (BTS) (ID: ST00307) | ||||||
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BTS Name |
Proprotein convertase subtilisin/kexin type 9
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Synonyms |
EC 3.4.21.-; Neural apoptosis-regulated convertase 1; NARC-1; Proprotein convertase 9; PC9; Subtilisin/kexin-like protease PC9
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BTS Type |
Protein
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Family |
Peptidase S8 family
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Gene Name |
PCSK9
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Organism |
Homo sapiens (Human)
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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.
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UniProt ID | ||||||
UniProt Entry | ||||||
PFam | ||||||
Gene ID | ||||||
Sequence |
MGTVSSRRSWWPLPLLLLLLLLLGPAGARAQEDEDGDYEELVLALRSEEDGLAEAPEHGT
TATFHRCAKDPWRLPGTYVVVLKEETHLSQSERTARRLQAQAARRGYLTKILHVFHGLLP GFLVKMSGDLLELALKLPHVDYIEEDSSVFAQSIPWNLERITPPRYRADEYQPPDGGSLV EVYLLDTSIQSDHREIEGRVMVTDFENVPEEDGTRFHRQASKCDSHGTHLAGVVSGRDAG VAKGASMRSLRVLNCQGKGTVSGTLIGLEFIRKSQLVQPVGPLVVLLPLAGGYSRVLNAA CQRLARAGVVLVTAAGNFRDDACLYSPASAPEVITVGATNAQDQPVTLGTLGTNFGRCVD LFAPGEDIIGASSDCSTCFVSQSGTSQAAAHVAGIAAMMLSAEPELTLAELRQRLIHFSA KDVINEAWFPEDQRVLTPNLVAALPPSTHGAGWQLFCRTVWSAHSGPTRMATAVARCAPD EELLSCSSFSRSGKRRGERMEAQGGKLVCRAHNAFGGEGVYAIARCCLLPQANCSVHTAP PAEASMGTRVHCHQQGHVLTGCSSHWEVEDLGTHKPPVLRPRGQPNQCVGHREASIHASC CHAPGLECKVKEHGIPAPQEQVTVACEEGWTLTGCSALPGTSHVLGAYAVDNTCVVRSRD VSTTGSTSEGAVTAVAICCRSRHLAQASQELQ |
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Sequence Length |
692
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Synthetic Binding Protein (SBP) Targeting This BTS |
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SBP Name | Highest Status | Mechanism | Affinity | Application | Details | Ref |
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Macrocyclic peptide anti-PCSK9 MK-0616 | Phase III | Inhibitor | Ki: 0.005 nM | Tools for reducing plasma low-density lipoprotein cholesterol | [1] | |
Monobody BMS-962476 | Phase I | Inhibitor | Kd: 0.85 nM | Hypercholesterolaemia [ICD-11: 5C80.0] | [2], [3] | |
scFv anti-hPCSK9 h5E12-L230G | Research | Inhibitor | Kd: 1.72 nM | Human immunodeficiency virus type 1 [ICD-11: XN9LD] | [4] | |
References |
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