UniProt UniProt http://www.uniprot.org TLR5 decoy receptor as a novel anti-amyloid therapeutic for Alzheimer's disease. TLR5 decoy receptor as a novel anti-amyloid therapeutic for Alzheimer's disease. The Journal of experimental medicine 2018 imex curation Chakrabarty P., Li A., Ladd TB., Strickland MR., Koller EJ., Burgess JD., Funk CC., Cruz PE., Allen M., Yaroshenko M., Wang X., Younkin C., Reddy J., Lohrer B., Mehrke L., Moore BD., Liu X., Ceballos-Diaz C., Rosario AM., Medway C., Janus C., Li HD., Dickson DW., Giasson BI., Price ND., Younkin SG., Ertekin-Taner N., Golde TE. Alzheimers - Interactions investigated in the context of Alzheimers disease pchakrabarty@ufl.edu, tgolde@ufl.edu 04-05-20: Contacted by IntAct-Help. Only protein-protein interactions imex curation in vitro In vitro bio-layer interferometry bio-layer interferometry bli bli predetermined predetermined participant predetermined Chakrabarty P., Li A., Ladd TB., Strickland MR., Koller EJ., Burgess JD., Funk CC., Cruz PE., Allen M., Yaroshenko M., Wang X., Younkin C., Reddy J., Lohrer B., Mehrke L., Moore BD., Liu X., Ceballos-Diaz C., Rosario AM., Medway C., Janus C., Li HD., Dickson DW., Giasson BI., Price ND., Younkin SG., Ertekin-Taner N., Golde TE. Alzheimers - Interactions investigated in the context of Alzheimers disease Supp fig 5 uses an anti-V5 tag but I can't find any mention of V5 added to the construct so I've just added the Fig. Legend to the appropriate entry pchakrabarty@ufl.edu, tgolde@ufl.edu Accepted 2019-NOV-29 AT 10:36 GMT AT 10:36 GMT by MGT The Journal of experimental medicine 2018 Only protein-protein interactions imex curation imex curation Mock publication and experiment for abstract interactions that are not interaction evidences. Mock publication and experiment for abstract interactions that are not interaction evidences. unspecified method TLR5 decoy receptor as a novel anti-amyloid therapeutic for Alzheimer's disease. TLR5 decoy receptor as a novel anti-amyloid therapeutic for Alzheimer's disease. The Journal of experimental medicine 2018 imex curation Chakrabarty P., Li A., Ladd TB., Strickland MR., Koller EJ., Burgess JD., Funk CC., Cruz PE., Allen M., Yaroshenko M., Wang X., Younkin C., Reddy J., Lohrer B., Mehrke L., Moore BD., Liu X., Ceballos-Diaz C., Rosario AM., Medway C., Janus C., Li HD., Dickson DW., Giasson BI., Price ND., Younkin SG., Ertekin-Taner N., Golde TE. Alzheimers - Interactions investigated in the context of Alzheimers disease pchakrabarty@ufl.edu, tgolde@ufl.edu 04-05-20: Contacted by IntAct-Help. Only protein-protein interactions imex curation mouse-brain Mus musculus brain brain Brain [cerebrum] anti bait coip anti bait coimmunoprecipitation anti bait coip western blot western blot Immuno blot Immuno blot Chakrabarty P., Li A., Ladd TB., Strickland MR., Koller EJ., Burgess JD., Funk CC., Cruz PE., Allen M., Yaroshenko M., Wang X., Younkin C., Reddy J., Lohrer B., Mehrke L., Moore BD., Liu X., Ceballos-Diaz C., Rosario AM., Medway C., Janus C., Li HD., Dickson DW., Giasson BI., Price ND., Younkin SG., Ertekin-Taner N., Golde TE. Alzheimers - Interactions investigated in the context of Alzheimers disease pchakrabarty@ufl.edu, tgolde@ufl.edu Accepted 2019-NOV-29 AT 10:36 GMT AT 10:36 GMT by MGT The Journal of experimental medicine 2018 Only protein-protein interactions imex curation imex curation TLR5 decoy receptor as a novel anti-amyloid therapeutic for Alzheimer's disease. TLR5 decoy receptor as a novel anti-amyloid therapeutic for Alzheimer's disease. The Journal of experimental medicine 2018 imex curation Chakrabarty P., Li A., Ladd TB., Strickland MR., Koller EJ., Burgess JD., Funk CC., Cruz PE., Allen M., Yaroshenko M., Wang X., Younkin C., Reddy J., Lohrer B., Mehrke L., Moore BD., Liu X., Ceballos-Diaz C., Rosario AM., Medway C., Janus C., Li HD., Dickson DW., Giasson BI., Price ND., Younkin SG., Ertekin-Taner N., Golde TE. Alzheimers - Interactions investigated in the context of Alzheimers disease pchakrabarty@ufl.edu, tgolde@ufl.edu 04-05-20: Contacted by IntAct-Help. Only protein-protein interactions imex curation in vitro In vitro elisa enzyme linked immunosorbent assay ELISA ELISA elisa antibody detection identification by antibody antibody detection Chakrabarty P., Li A., Ladd TB., Strickland MR., Koller EJ., Burgess JD., Funk CC., Cruz PE., Allen M., Yaroshenko M., Wang X., Younkin C., Reddy J., Lohrer B., Mehrke L., Moore BD., Liu X., Ceballos-Diaz C., Rosario AM., Medway C., Janus C., Li HD., Dickson DW., Giasson BI., Price ND., Younkin SG., Ertekin-Taner N., Golde TE. Alzheimers - Interactions investigated in the context of Alzheimers disease Supp fig 5 uses an anti-V5 tag but I can't find any mention of V5 added to the construct so I've just added the Fig. Legend to the appropriate entry pchakrabarty@ufl.edu, tgolde@ufl.edu Accepted 2019-NOV-29 AT 10:36 GMT AT 10:36 GMT by MGT The Journal of experimental medicine 2018 Only protein-protein interactions imex curation imex curation TLR5 decoy receptor as a novel anti-amyloid therapeutic for Alzheimer's disease. TLR5 decoy receptor as a novel anti-amyloid therapeutic for Alzheimer's disease. The Journal of experimental medicine 2018 imex curation Chakrabarty P., Li A., Ladd TB., Strickland MR., Koller EJ., Burgess JD., Funk CC., Cruz PE., Allen M., Yaroshenko M., Wang X., Younkin C., Reddy J., Lohrer B., Mehrke L., Moore BD., Liu X., Ceballos-Diaz C., Rosario AM., Medway C., Janus C., Li HD., Dickson DW., Giasson BI., Price ND., Younkin SG., Ertekin-Taner N., Golde TE. Alzheimers - Interactions investigated in the context of Alzheimers disease pchakrabarty@ufl.edu, tgolde@ufl.edu 04-05-20: Contacted by IntAct-Help. Only protein-protein interactions imex curation in vitro In vitro atomic force microsc atomic force microscopy AFM AFM atomic force microsc predetermined predetermined participant predetermined Chakrabarty P., Li A., Ladd TB., Strickland MR., Koller EJ., Burgess JD., Funk CC., Cruz PE., Allen M., Yaroshenko M., Wang X., Younkin C., Reddy J., Lohrer B., Mehrke L., Moore BD., Liu X., Ceballos-Diaz C., Rosario AM., Medway C., Janus C., Li HD., Dickson DW., Giasson BI., Price ND., Younkin SG., Ertekin-Taner N., Golde TE. Alzheimers - Interactions investigated in the context of Alzheimers disease Supp fig 5 uses an anti-V5 tag but I can't find any mention of V5 added to the construct so I've just added the Fig. Legend to the appropriate entry pchakrabarty@ufl.edu, tgolde@ufl.edu Accepted 2019-NOV-29 AT 10:36 GMT AT 10:36 GMT by MGT The Journal of experimental medicine 2018 Only protein-protein interactions imex curation imex curation p05067-pro_0000000093 Amyloid-beta protein 40 APP A4 AD1 ABPP Alzheimer disease amyloid protein Cerebral vascular amyloid peptide PreA4 Protease nexin-II APPI Amyloid precursor protein Amyloid-beta A4 protein Alzheimer disease amyloid A4 protein homolog Amyloid-beta (A4) precursor protein protein protein human Homo sapiens Human DAEFRHDSGYEVHHQKLVFFAEDVGSNKGAIIGLMVGGVV 672 711 D563D7858C3768F1 p05067-pro_0000000092 Amyloid-beta protein 42 Alzheimer disease amyloid protein Cerebral vascular amyloid peptide APP A4 AD1 ABPP PreA4 Protease nexin-II APPI Amyloid precursor protein Amyloid-beta A4 protein Alzheimer disease amyloid A4 protein homolog Amyloid-beta (A4) precursor protein protein protein human Homo sapiens Human DAEFRHDSGYEVHHQKLVFFAEDVGSNKGAIIGLMVGGVVIA 672 713 3AC85563D7858C37 a4_human Amyloid-beta precursor protein APP A4 AD1 Alzheimer disease amyloid protein ABPP PreA4 Cerebral vascular amyloid peptide Protease nexin-II APPI Amyloid precursor protein Amyloid-beta A4 protein Alzheimer disease amyloid A4 protein homolog Amyloid-beta (A4) precursor protein protein protein human Homo sapiens Human MLPGLALLLLAAWTARALEVPTDGNAGLLAEPQIAMFCGRLNMHMNVQNGKWDSDPSGTKTCIDTKEGILQYCQEVYPELQITNVVEANQPVTIQNWCKRGRKQCKTHPHFVIPYRCLVGEFVSDALLVPDKCKFLHQERMDVCETHLHWHTVAKETCSEKSTNLHDYGMLLPCGIDKFRGVEFVCCPLAEESDNVDSADAEEDDSDVWWGGADTDYADGSEDKVVEVAEEEEVAEVEEEEADDDEDDEDGDEVEEEAEEPYEEATERTTSIATTTTTTTESVEEVVREVCSEQAETGPCRAMISRWYFDVTEGKCAPFFYGGCGGNRNNFDTEEYCMAVCGSAMSQSLLKTTQEPLARDPVKLPTTAASTPDAVDKYLETPGDENEHAHFQKAKERLEAKHRERMSQVMREWEEAERQAKNLPKADKKAVIQHFQEKVESLEQEAANERQQLVETHMARVEAMLNDRRRLALENYITALQAVPPRPRHVFNMLKKYVRAEQKDRQHTLKHFEHVRMVDPKKAAQIRSQVMTHLRVIYERMNQSLSLLYNVPAVAEEIQDEVDELLQKEQNYSDDVLANMISEPRISYGNDALMPSLTETKTTVELLPVNGEFSLDDLQPWHSFGADSVPANTENEVEPVDARPAADRGLTTRPGSGLTNIKTEEISEVKMDAEFRHDSGYEVHHQKLVFFAEDVGSNKGAIIGLMVGGVVIATVIVITLVMLKKKQYTSIHHGVVEVDAAVTPEERHLSKMQQNGYENPTYKFFEQMQN DIP protein P05067 original sequence version: 160 DIP protein P05067 original sequence version: 207 DIP protein P05067 original sequence version: 185 DIP protein P05067 original sequence version: 188 A12EE761403740F5 tlr5_human Toll-like receptor 5 TLR5 TIL3 Toll/interleukin-1 receptor-like protein 3 protein protein human Homo sapiens Human MGDHLDLLLGVVLMAGPVFGIPSCSFDGRIAFYRFCNLTQVPQVLNTTERLLLSFNYIRTVTASSFPFLEQLQLLELGSQYTPLTIDKEAFRNLPNLRILDLGSSKIYFLHPDAFQGLFHLFELRLYFCGLSDAVLKDGYFRNLKALTRLDLSKNQIRSLYLHPSFGKLNSLKSIDFSSNQIFLVCEHELEPLQGKTLSFFSLAANSLYSRVSVDWGKCMNPFRNMVLEILDVSGNGWTVDITGNFSNAISKSQAFSLILAHHIMGAGFGFHNIKDPDQNTFAGLARSSVRHLDLSHGFVFSLNSRVFETLKDLKVLNLAYNKINKIADEAFYGLDNLQVLNLSYNLLGELYSSNFYGLPKVAYIDLQKNHIAIIQDQTFKFLEKLQTLDLRDNALTTIHFIPSIPDIFLSGNKLVTLPKINLTANLIHLSENRLENLDILYFLLRVPHLQILILNQNRFSSCSGDQTPSENPSLEQLFLGENMLQLAWETELCWDVFEGLSHLQVLYLNHNYLNSLPPGVFSHLTALRGLSLNSNRLTVLSHNDLPANLEILDISRNQLLAPNPDVFVSLSVLDITHNKFICECELSTFINWLNHTNVTIAGPPADIYCVYPDSFSGVSLFSLSTEGCDEEEVLKSLKFSLFIVCTVTLTLFLMTILTVTKFRGFCFICYKTAQRLVFKDHPQGTEPDMYKYDAYLCFSSKDFTWVQNALLKHLDTQYSDQNRFNLCFEERDFVPGENRIANIQDAIWNSRKIVCLVSRHFLRDGWCLEAFSYAQGRCLSDLNSALIMVVVGSLSQYQLMKHQSIRGFVQKQQYLRWPEDFQDVGWFLHKLSQQILKKEKEKKKDNNIPLQTVATIS 9EE0AB6EEFEA9051 app-tlr5-1 3 8 unspecified role unspecified role bait bait physiological level physiological level endogenous level endogenous endogenous endogenous level 9 unspecified role unspecified role prey prey physiological level physiological level endogenous level endogenous endogenous endogenous level c-terminal fc-igg tag fc-igg tag c-term range C-terminal range c-term range c-term range C-terminal range c-term range region v5 tag v5 tag GKPIPNPLLGLDST epitope tag GKPIPNPLLGLDST epitope tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined physical association physical association Fig. 2N Using the anti–Aβ1-16 antibody Ab5, sTR5Fc could be immunoprecipitated from the Tris-buffered saline brain extracts of sTLR5Fc-expressing APP mice, suggesting that sTLR5Fc forms a complex with Aβ in vivo (Fig. 2 N). app-tlr5-2 4 7 unspecified role unspecified role bait bait purified purified chemical synthesis Chemical synthesis (Chemical synthesis) 9 unspecified role unspecified role prey prey purified purified c-terminal fc-igg tag fc-igg tag c-term range C-terminal range c-term range c-term range C-terminal range c-term range region v5 tag v5 tag GKPIPNPLLGLDST epitope tag GKPIPNPLLGLDST epitope tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined crigr-cho chinese hamster ovary cell line cho chinese hamster ovary cell line Also called LR73 cells. direct interaction direct interaction Fig.4I, Supp Fig 5I app-tlr5-3 4 22 unspecified role unspecified role bait bait purified purified chemical synthesis Chemical synthesis (Chemical synthesis) 9 unspecified role unspecified role prey prey purified purified c-terminal fc-igg tag fc-igg tag c-term range C-terminal range c-term range c-term range C-terminal range c-term range region v5 tag v5 tag GKPIPNPLLGLDST epitope tag GKPIPNPLLGLDST epitope tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined crigr-cho chinese hamster ovary cell line cho chinese hamster ovary cell line Also called LR73 cells. direct interaction direct interaction Fig.4I app-tlr5-4 4 7 unspecified role unspecified role bait bait chemical synthesis Chemical synthesis (Chemical synthesis) 7 unspecified role unspecified role bait bait chemical synthesis Chemical synthesis (Chemical synthesis) 9 unspecified role unspecified role prey prey purified purified c-terminal fc-igg tag fc-igg tag c-term range C-terminal range c-term range c-term range C-terminal range c-term range region v5 tag v5 tag GKPIPNPLLGLDST epitope tag GKPIPNPLLGLDST epitope tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined crigr-cho chinese hamster ovary cell line cho chinese hamster ovary cell line Also called LR73 cells. direct interaction direct interaction Fig.4I, Supp. Fig. 5H I've used this throughout to represent fibular, rather than oligomeric, peptide. app-tlr5-5 4 6 unspecified role unspecified role bait bait chemical synthesis Chemical synthesis (Chemical synthesis) 6 unspecified role unspecified role bait bait chemical synthesis Chemical synthesis (Chemical synthesis) 9 unspecified role unspecified role prey prey purified purified c-terminal fc-igg tag fc-igg tag c-term range C-terminal range c-term range c-term range C-terminal range c-term range region v5 tag v5 tag GKPIPNPLLGLDST epitope tag GKPIPNPLLGLDST epitope tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined crigr-cho chinese hamster ovary cell line cho chinese hamster ovary cell line Also called LR73 cells. direct interaction direct interaction Fig.4I I've used this throughout to represent fibular, rather than oligomeric, peptide. app-tlr5-6 4 6 unspecified role unspecified role bait bait purified purified chemical synthesis Chemical synthesis (Chemical synthesis) 9 unspecified role unspecified role prey prey purified purified c-terminal fc-igg tag fc-igg tag c-term range C-terminal range c-term range c-term range C-terminal range c-term range region v5 tag v5 tag GKPIPNPLLGLDST epitope tag GKPIPNPLLGLDST epitope tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined crigr-cho chinese hamster ovary cell line cho chinese hamster ovary cell line Also called LR73 cells. direct interaction direct interaction Fig.4I tlr5-app-1 1 7 unspecified role unspecified role prey prey purified purified region sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain region required to bind necessary binding region required to bind certain certain sequence position certain certain certain sequence position certain chemical synthesis Chemical synthesis (Chemical synthesis) 9 unspecified role unspecified role bait bait purified purified c-terminal fc-igg tag fc-igg tag c-term range C-terminal range c-term range c-term range C-terminal range c-term range region v5 tag v5 tag GKPIPNPLLGLDST epitope tag GKPIPNPLLGLDST epitope tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined crigr-cho chinese hamster ovary cell line cho chinese hamster ovary cell line Also called LR73 cells. direct interaction direct interaction Fig.4J, 4L, Supp. Fig. 5J tlr5-abeta_42_oligomer_human-1 1 22 unspecified role unspecified role prey prey purified purified chemical synthesis Chemical synthesis (Chemical synthesis) 9 unspecified role unspecified role bait bait purified purified c-terminal fc-igg tag fc-igg tag c-term range C-terminal range c-term range c-term range C-terminal range c-term range region v5 tag v5 tag GKPIPNPLLGLDST epitope tag GKPIPNPLLGLDST epitope tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined crigr-cho chinese hamster ovary cell line cho chinese hamster ovary cell line Also called LR73 cells. direct interaction direct interaction Fig.4K, 4L tlr5-app-2 1 6 unspecified role unspecified role prey prey purified purified C-terminal region required to bind necessary binding region required to bind certain certain sequence position certain certain certain sequence position certain chemical synthesis Chemical synthesis (Chemical synthesis) 9 unspecified role unspecified role bait bait purified purified c-terminal fc-igg tag fc-igg tag c-term range C-terminal range c-term range c-term range C-terminal range c-term range region v5 tag v5 tag GKPIPNPLLGLDST epitope tag GKPIPNPLLGLDST epitope tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined crigr-cho chinese hamster ovary cell line cho chinese hamster ovary cell line Also called LR73 cells. direct interaction direct interaction Fig.4I app-123 5 7 unspecified role unspecified role neutral component neutral component chemical synthesis Chemical synthesis (Chemical synthesis) 7 unspecified role unspecified role neutral component neutral component chemical synthesis Chemical synthesis (Chemical synthesis) direct interaction direct interaction Supp. Fig. 5C abeta-42-oligomer_human pre-fibrillar amyloid-beta oligomer prefibrillar amyloid-beta oligomer Type 2 amyloid-beta oligomer fibrillar amyloid-beta oligomer Annular protofibril complex Amyloid-beta fibrils beta-amyloid protein 42 heterooligomer beta-amyloid protein 42 complex beta-amyloid-42 complex beta amyloid protein 42 complex amyloid-beta-42 complex amyloid beta protein 42 complex amyloid-beta protein 42 heterooligomer amyloid-beta-42 heterooligomer amyloid beta protein 42 heterooligomer beta-amyloid-42 heterooligomer beta amyloid protein 42 heterooligomer Abeta protein 42 complex Amyloid-beta protein 42 oligomeric complex APP oligomer Type 1 amyloid-beta oligomer ADDL complex 7 unspecified role unspecified role protein 42 binding region binding region binding-associated region binding region certain certain sequence position certain certain certain sequence position certain 7 unspecified role unspecified role protein 42 binding region binding region binding-associated region binding region certain certain sequence position certain certain certain sequence position certain 65 67 direct interaction direct interaction human Homo sapiens Human stable complex stable complex biological system reconstruction evidence based on paralogy evidence used in manual assertion biological system reconstruction evidence based on paralogy evidence used in manual assertion Protein complex involved in modulation of signaling and synaptic function in the brain, predominantly in the cerebral cortex and hippocampus. This oligomer of protein 42 only has positive neurogenetic effects by activating synaptic protein kinases. May have a role in depressing synaptic activity thus preventing excitotoxicity. Influences synaptic plasticity through various receptors, including NMDAR, mGluR and alpha7 nicotinic acetylcholine receptors (CPX-236). Mediates dendritic spine loss leading to decreased synapse density, inhibition of long-term potentiation (LTP), enhancement of long-term depression (LTD), excessive calcium influx, mitochondrial impairment, endoplasmic reticulum stress and activation of apoptotic processes. May bind plasma membrane lipids affecting their stability and leading to cytotoxicity. May affect metal ion homeostasis by chelating synaptic copper, zinc or iron ions. Mostly found in the extracellular space with a small proportion occurring as membrane-bound species. Dimers (CPX-1062) and oligomers of soluble amyloid-beta peptides are the main pathogenic species linked to Alzheimer's disease. Cellular prion protein (PrPC/PRNP, P04156) binds amyloid-beta oligomers mediating their synaptic dysfunction. Insoluble fibrils and plaques form during the latter stages of the disease. Chaperones, such as alphaB-crystallins or clusterin (P10909), bind to misfolded oligomeric species and form long-lived complexes, thereby preventing both their further growth into fibrils and their dissociation into synaptotoxic dimers. Amyloid-beta peptide may act as transcription factor for its own precursor protein APP and its cleavage enzyme BACE1 (P56817) initiating a positive feedback mechanism that ultimately leads to amyloidogenesis and Alzheimer's disease. Heterooligomer Alzheimers disease [EFO:0000249]: a progressive, neurodegenerative disease characterized by loss of function and death of nerve cells in several areas of the brain leading to loss of cognitive function such as memory and language, starting in late middle age or in old age. Marked histologically by the degeneration of brain neurons especially in the cerebral cortex and by the presence of neurofibrillary tangles and plaques containing beta-amyloid. Many forms of amyloid-beta oligomers exist in a dynamic equilibrium: from low-n amyloid-beta oligomer complexes such as dimers and trimers to high-n amyloid-beta oligomer complexes, such as pre-fibrilar and fibrilar oligomers to inactive fibrils. Pre-fibrilar oligomers form random coils and beta-turns and fibrils and oligomeric fibrils form anti-parallel beta-sheets. The oligomers are inherently thermodynamically more stable than the dimers. Barbara Kramarz, ARUK-UCL Accepted 2017-MAY-25 by ORCHARD