MINT MINT, Dpt of Biology, University of Rome Tor Vergata MINT http://mint.bio.uniroma2.it/mint url>http://mint.bio.uniroma2.it/mint/ https://mint.bio.uniroma2.it MINT-[0-9]+ https://mint.bio.uniroma2.it/index.php/results-interactions/?id=${ac} The Molecular INTeraction database (MINT) is a relational database designed to store interactions between biological molecules. http://mint.bio.uniroma2.it Mechanistic implications for LDL receptor degradation from the PCSK9/LDLR structure at neutral pH. Mechanistic implications for LDL receptor degradation from the PCSK9/LDLR structure at neutral pH. EMBO Rep. (1469-221X) 2011 imex curation Lo Surdo P., Bottomley MJ., Calzetta A., Settembre EC., Cirillo A., Pandit S., Ni YG., Hubbard B., Sitlani A., Carfí A. Only protein-protein interactions in vitro In vitro x-ray diffraction x-ray crystallography X-ray X-ray x-ray diffraction predetermined predetermined participant predetermined Lo Surdo P., Bottomley MJ., Calzetta A., Settembre EC., Cirillo A., Pandit S., Ni YG., Hubbard B., Sitlani A., Carfí A. EMBO Rep. (1469-221X) 2011 Only protein-protein interactions imex curation Mechanistic implications for LDL receptor degradation from the PCSK9/LDLR structure at neutral pH. Mechanistic implications for LDL receptor degradation from the PCSK9/LDLR structure at neutral pH. EMBO Rep. (1469-221X) 2011 imex curation Lo Surdo P., Bottomley MJ., Calzetta A., Settembre EC., Cirillo A., Pandit S., Ni YG., Hubbard B., Sitlani A., Carfí A. Only protein-protein interactions in vitro In vitro spr surface plasmon resonance Optical biosensor BIAcore(r) BIAcore(r) Optical biosensor spr predetermined predetermined participant predetermined Lo Surdo P., Bottomley MJ., Calzetta A., Settembre EC., Cirillo A., Pandit S., Ni YG., Hubbard B., Sitlani A., Carfí A. EMBO Rep. (1469-221X) 2011 Only protein-protein interactions imex curation pcsk9_human Proprotein convertase subtilisin/kexin type 9 Subtilisin/kexin-like protease PC9 Neural apoptosis-regulated convertase 1 Proprotein convertase 9 PCSK9 NARC1 PSEC0052 protein protein human Homo sapiens Human MGTVSSRRSWWPLPLLLLLLLLLGPAGARAQEDEDGDYEELVLALRSEEDGLAEAPEHGTTATFHRCAKDPWRLPGTYVVVLKEETHLSQSERTARRLQAQAARRGYLTKILHVFHGLLPGFLVKMSGDLLELALKLPHVDYIEEDSSVFAQSIPWNLERITPPRYRADEYQPPDGGSLVEVYLLDTSIQSDHREIEGRVMVTDFENVPEEDGTRFHRQASKCDSHGTHLAGVVSGRDAGVAKGASMRSLRVLNCQGKGTVSGTLIGLEFIRKSQLVQPVGPLVVLLPLAGGYSRVLNAACQRLARAGVVLVTAAGNFRDDACLYSPASAPEVITVGATNAQDQPVTLGTLGTNFGRCVDLFAPGEDIIGASSDCSTCFVSQSGTSQAAAHVAGIAAMMLSAEPELTLAELRQRLIHFSAKDVINEAWFPEDQRVLTPNLVAALPPSTHGAGWQLFCRTVWSAHSGPTRMATAVARCAPDEELLSCSSFSRSGKRRGERMEAQGGKLVCRAHNAFGGEGVYAIARCCLLPQANCSVHTAPPAEASMGTRVHCHQQGHVLTGCSSHWEVEDLGTHKPPVLRPRGQPNQCVGHREASIHASCCHAPGLECKVKEHGIPAPQEQVTVACEEGWTLTGCSALPGTSHVLGAYAVDNTCVVRSRDVSTTGSTSEGAVTAVAICCRSRHLAQASQELQ mint homomint May be implicated in the differentiation of cortical neurons and may play a role in cholesterol homeostasis Defects in PCSK9 are the cause of familial hypercholesterolemia 3 (FH3) [MIM:603776]. FH3 inheritance is autosomal dominant 9BCB9418B90AEE23 ldlr_human Low-density lipoprotein receptor LDLR protein protein human Homo sapiens Human MGPWGWKLRWTVALLLAAAGTAVGDRCERNEFQCQDGKCISYKWVCDGSAECQDGSDESQETCLSVTCKSGDFSCGGRVNRCIPQFWRCDGQVDCDNGSDEQGCPPKTCSQDEFRCHDGKCISRQFVCDSDRDCLDGSDEASCPVLTCGPASFQCNSSTCIPQLWACDNDPDCEDGSDEWPQRCRGLYVFQGDSSPCSAFEFHCLSGECIHSSWRCDGGPDCKDKSDEENCAVATCRPDEFQCSDGNCIHGSRQCDREYDCKDMSDEVGCVNVTLCEGPNKFKCHSGECITLDKVCNMARDCRDWSDEPIKECGTNECLDNNGGCSHVCNDLKIGYECLCPDGFQLVAQRRCEDIDECQDPDTCSQLCVNLEGGYKCQCEEGFQLDPHTKACKAVGSIAYLFFTNRHEVRKMTLDRSEYTSLIPNLRNVVALDTEVASNRIYWSDLSQRMICSTQLDRAHGVSSYDTVISRDIQAPDGLAVDWIHSNIYWTDSVLGTVSVADTKGVKRKTLFRENGSKPRAIVVDPVHGFMYWTDWGTPAKIKKGGLNGVDIYSLVTENIQWPNGITLDLLSGRLYWVDSKLHSISSIDVNGGNRKTILEDEKRLAHPFSLAVFEDKVFWTDIINEAIFSANRLTGSDVNLLAENLLSPEDMVLFHNLTQPRGVNWCERTTLSNGGCQYLCLPAPQINPHSPKFTCACPDGMLLARDMRSCLTEAEAAVATQETSTVRLKVSSTAVRTQHTTTRPVPDTSRLPGATPGLTTVEIVTMSHQALGDVAGRGNEKKPSSVRALSIVLPIVLLVFLCLGVFLLWKNWRLKNINSINFDNPVYQKTTEDEVHICHNQDGYSYPSRQMVSLEDDVA DIP protein P01130 original sequence version: 115 DIP protein P01130 original sequence version: 122 DIP protein P01130 original sequence version: 140 DIP protein P01130 original sequence version: 173 A4C28E9B8BADAD5E ldlr-pcsk9 1 PCSK9 3 predetermined predetermined participant predetermined predetermined predetermined participant predetermined unspecified role unspecified role neutral component neutral component purified purified binding site binding region binding-associated region binding region certain certain sequence position certain certain certain sequence position certain PCSK9 3 predetermined predetermined participant predetermined predetermined predetermined participant predetermined unspecified role unspecified role neutral component neutral component purified purified binding site binding region binding-associated region binding region certain certain sequence position certain certain certain sequence position certain Low density lipoprotein receptor 4 predetermined predetermined participant predetermined predetermined predetermined participant predetermined unspecified role unspecified role neutral component neutral component purified purified binding site binding region binding-associated region binding region certain certain sequence position certain certain certain sequence position certain direct interaction direct interaction homomint mint Atomic coordinates have been deposited in the PDB with accession codes 3P5B (3.3Å resolution structure) and 3P5C (4.2Å resolution structure) st1 sf1 f2 f3 q59fq1-pcsk9 2 PCSK9 3 predetermined predetermined participant predetermined predetermined predetermined participant predetermined unspecified role unspecified role prey prey purified purified LDLR 4 predetermined predetermined participant predetermined predetermined predetermined participant predetermined unspecified role unspecified role bait bait purified purified binding site binding region binding-associated region binding region certain certain sequence position certain certain certain sequence position certain direct interaction direct interaction homomint mint sf3.1 t1 The interaction between PCSK9 and LDLR (wild type and mutants) was also assessed by SPR at acidic pH. In agreement with previous reports (Cunningham et al, 2007; Fisher et al, 2007; Piper et al, 2007), at low pH, the binding affinity was enhanced 50- to 100-fold (Kd¼8 nM for LDLR wild type; see Table 1). q59fq1-pcsk9-1 2 PCSK9 3 predetermined predetermined participant predetermined predetermined predetermined participant predetermined unspecified role unspecified role prey prey purified purified LDLR 4 predetermined predetermined participant predetermined predetermined predetermined participant predetermined unspecified role unspecified role bait bait purified purified undefined mutation mutation decreasing interaction mutation decreasing mutation decreasing interaction hotspot hotspot mutation decreasing mutation analysis mutation analysis certain certain sequence position certain certain certain sequence position certain Wed Jul 06 16:40:01 BST 2016 Sequence change details about this feature cannot be ascertained or do not fit with the current version of the referenced protein, so they have been deleted as a result of our quality control procedures. The original label was 'mutation decreasing' Leu659Ala binding site binding region binding-associated region binding region certain certain sequence position certain certain certain sequence position certain direct interaction direct interaction homomint mint sf3.2 t1 The interaction between PCSK9 and LDLR (wild type and mutants) was also assessed by SPR at acidic pH. In agreement with previous reports (Cunningham et al, 2007; Fisher et al, 2007; Piper et al, 2007), at low pH, the binding affinity was enhanced 50- to 100-fold (Kd¼8 nM for LDLR wild type; see Table 1). q59fq1-pcsk9-2 2 PCSK9 3 predetermined predetermined participant predetermined predetermined predetermined participant predetermined unspecified role unspecified role prey prey purified purified LDLR 4 predetermined predetermined participant predetermined predetermined predetermined participant predetermined unspecified role unspecified role bait bait purified purified binding site binding region binding-associated region binding region certain certain sequence position certain certain certain sequence position certain undefined mutation mutation decreasing interaction mutation decreasing mutation decreasing interaction hotspot hotspot mutation decreasing mutation analysis mutation analysis certain certain sequence position certain certain certain sequence position certain Wed Jul 06 16:40:31 BST 2016 Sequence change details about this feature cannot be ascertained or do not fit with the current version of the referenced protein, so they have been deleted as a result of our quality control procedures. The original label was 'mutation decreasing' Leu659Arg direct interaction direct interaction homomint mint sf3.3 t1 The interaction between PCSK9 and LDLR (wild type and mutants) was also assessed by SPR at acidic pH. In agreement with previous reports (Cunningham et al, 2007; Fisher et al, 2007; Piper et al, 2007), at low pH, the binding affinity was enhanced 50- to 100-fold (Kd¼8 nM for LDLR wild type; see Table 1). q59fq1-pcsk9-3 2 PCSK9 3 predetermined predetermined participant predetermined predetermined predetermined participant predetermined unspecified role unspecified role prey prey purified purified LDLR 4 predetermined predetermined participant predetermined predetermined predetermined participant predetermined unspecified role unspecified role bait bait purified purified binding site binding region binding-associated region binding region certain certain sequence position certain certain certain sequence position certain undefined mutation mutation decreasing interaction mutation decreasing mutation decreasing interaction hotspot hotspot mutation decreasing mutation analysis mutation analysis certain certain sequence position certain certain certain sequence position certain Wed Jul 06 16:40:57 BST 2016 Sequence change details about this feature cannot be ascertained or do not fit with the current version of the referenced protein, so they have been deleted as a result of our quality control procedures. The original label was 'mutation decreasing' Leu659Glu direct interaction direct interaction homomint mint sf3.4 t1 The interaction between PCSK9 and LDLR (wild type and mutants) was also assessed by SPR at acidic pH. In agreement with previous reports (Cunningham et al, 2007; Fisher et al, 2007; Piper et al, 2007), at low pH, the binding affinity was enhanced 50- to 100-fold (Kd¼8 nM for LDLR wild type; see Table 1). q59fq1-pcsk9-4 2 PCSK9 3 predetermined predetermined participant predetermined predetermined predetermined participant predetermined unspecified role unspecified role prey prey purified purified LDLR 4 predetermined predetermined participant predetermined predetermined predetermined participant predetermined unspecified role unspecified role bait bait purified purified binding site binding region binding-associated region binding region certain certain sequence position certain certain certain sequence position certain undefined mutation mutation decreasing interaction mutation decreasing mutation decreasing interaction hotspot hotspot mutation decreasing mutation analysis mutation analysis certain certain sequence position certain certain certain sequence position certain Wed Jul 06 16:42:40 BST 2016 Sequence change details about this feature cannot be ascertained or do not fit with the current version of the referenced protein, so they have been deleted as a result of our quality control procedures. The original label was 'mutation decreasing' His668Asn direct interaction direct interaction homomint mint sf3.5 t1 The interaction between PCSK9 and LDLR (wild type and mutants) was also assessed by SPR at acidic pH. In agreement with previous reports (Cunningham et al, 2007; Fisher et al, 2007; Piper et al, 2007), at low pH, the binding affinity was enhanced 50- to 100-fold (Kd¼8 nM for LDLR wild type; see Table 1). ldlr-pcsk9-1 2 PCSK9 3 predetermined predetermined participant predetermined predetermined predetermined participant predetermined unspecified role unspecified role prey prey purified purified L7-LDLR 4 predetermined predetermined participant predetermined predetermined predetermined participant predetermined unspecified role unspecified role bait bait purified purified binding site binding region binding-associated region binding region certain certain sequence position certain certain certain sequence position certain direct interaction direct interaction homomint mint sf3.6 t1 The interaction between PCSK9 and LDLR (wild type and mutants) was also assessed by SPR at acidic pH. In agreement with previous reports (Cunningham et al, 2007; Fisher et al, 2007; Piper et al, 2007), at low pH, the binding affinity was enhanced 50- to 100-fold (Kd¼8 nM for LDLR wild type; see Table 1). ldlr-pcsk9-2 2 PCSK9 3 predetermined predetermined participant predetermined predetermined predetermined participant predetermined unspecified role unspecified role prey prey purified purified L7-LDLR 4 predetermined predetermined participant predetermined predetermined predetermined participant predetermined unspecified role unspecified role bait bait purified purified undefined mutation mutation decreasing interaction mutation decreasing mutation decreasing interaction hotspot hotspot mutation decreasing mutation analysis mutation analysis certain certain sequence position certain certain certain sequence position certain Wed Jul 06 16:43:08 BST 2016 Sequence change details about this feature cannot be ascertained or do not fit with the current version of the referenced protein, so they have been deleted as a result of our quality control procedures. The original label was 'mutation decreasing' Ser409Pro binding site binding region binding-associated region binding region certain certain sequence position certain certain certain sequence position certain undefined mutation mutation decreasing interaction mutation decreasing mutation decreasing interaction hotspot hotspot mutation decreasing mutation analysis mutation analysis certain certain sequence position certain certain certain sequence position certain Wed Jul 06 16:43:07 BST 2016 Sequence change details about this feature cannot be ascertained or do not fit with the current version of the referenced protein, so they have been deleted as a result of our quality control procedures. The original label was 'mutation decreasing' Gly408Pro direct interaction direct interaction homomint mint sf3.7 t1 ldlr-pcsk9-3 2 PCSK9 3 predetermined predetermined participant predetermined predetermined predetermined participant predetermined unspecified role unspecified role prey prey purified purified binding site binding region binding-associated region binding region certain certain sequence position certain certain certain sequence position certain L7-LDLR 4 predetermined predetermined participant predetermined predetermined predetermined participant predetermined unspecified role unspecified role bait bait purified purified binding site binding region binding-associated region binding region certain certain sequence position certain certain certain sequence position certain direct interaction direct interaction homomint mint sf3.8 t1