UniProt UniProt http://www.uniprot.org High-affinity interactions and signal transduction between Aβ oligomers and TREM2. High-affinity interactions and signal transduction between Aβ oligomers and TREM2. EMBO molecular medicine 2018 imex curation Lessard CB., Malnik SL., Zhou Y., Ladd TB., Cruz PE., Ran Y., Mahan TE., Chakrabaty P., Holtzman DM., Ulrich JD., Colonna M., Golde TE. Neurodegeneration - Publications depicting interactions involved in neurodegenerative diseases. Alzheimers - Interactions investigated in the context of Alzheimers disease I'm not adding an expressed-in for fibruallar APP - I'm sure its human, less clear where it has been expressed. Also only using CPX for oligomeric APP, fibular is a higher level structure. APOE3 = UniProt canonical, APOE4 =canonical + 1 variant. Source of fibrullar APP has been inferred to be human APP as described in PMID:20368278. tgolde@ufl.edu 25-Jul-2019: Contacted by IntAct-Help. Only protein-protein interactions imex curation in vitro In vitro affinity techniques affinity technology affinity techniques western blot western blot Immuno blot Immuno blot Lessard CB., Malnik SL., Zhou Y., Ladd TB., Cruz PE., Ran Y., Mahan TE., Chakrabaty P., Holtzman DM., Ulrich JD., Colonna M., Golde TE. Neurodegeneration - Publications depicting interactions involved in neurodegenerative diseases. I'm not adding an expressed-in for fibruallar APP - I'm sure its human, less clear where it has been expressed. Also only using CPX for oligomeric APP, fibular is a higher level structure. APOE3 = UniProt canonical, APOE4 =canonical + 1 variant. Detergent extracted cell lysate incubated with APP peptide fibrils. Mixture then centrifuged to pulldown fibrils and bound proteins. Source of fibrullar APP has been inferred to be human APP as described in PMID:20368278. tgolde@ufl.edu Accepted 2019-JUN-26 AT 10:26 BST AT 10:26 BST by MGT EMBO molecular medicine 2018 Only protein-protein interactions imex curation imex curation I had added the APP twice and linked them, which is how I've dealt with fibrils elsewhere, but I then removed it, because in this case they haven't actually shown that the interaction is with fibrils. The gels show both high and low mw entities and I assume the lmw could well be monomers, so I decided it was probably more correct (or less incorrect) just to add them once with stoichiometry unknown. High-affinity interactions and signal transduction between Aβ oligomers and TREM2. High-affinity interactions and signal transduction between Aβ oligomers and TREM2. EMBO molecular medicine 2018 imex curation Lessard CB., Malnik SL., Zhou Y., Ladd TB., Cruz PE., Ran Y., Mahan TE., Chakrabaty P., Holtzman DM., Ulrich JD., Colonna M., Golde TE. Neurodegeneration - Publications depicting interactions involved in neurodegenerative diseases. Alzheimers - Interactions investigated in the context of Alzheimers disease I'm not adding an expressed-in for fibruallar APP - I'm sure its human, less clear where it has been expressed. Also only using CPX for oligomeric APP, fibular is a higher level structure. APOE3 = UniProt canonical, APOE4 =canonical + 1 variant. Source of fibrullar APP has been inferred to be human APP as described in PMID:20368278. tgolde@ufl.edu 25-Jul-2019: Contacted by IntAct-Help. Only protein-protein interactions imex curation human-293t Homo sapiens 293 cells transformed with SV40 large T antigen 293t 293 cells expressing SV40 large T antigen. The original designation of this cell line was 293tsA1609neo. It is not in Cabri,ATCC or HyperCLDB. anti tag coip anti tag coimmunoprecipitation anti tag coip western blot western blot Immuno blot Immuno blot Lessard CB., Malnik SL., Zhou Y., Ladd TB., Cruz PE., Ran Y., Mahan TE., Chakrabaty P., Holtzman DM., Ulrich JD., Colonna M., Golde TE. Neurodegeneration - Publications depicting interactions involved in neurodegenerative diseases. I'm not adding an expressed-in for fibruallar APP - I'm sure its human, less clear where it has been expressed. Also only using CPX for oligomeric APP, fibular is a higher level structure. APOE3 = UniProt canonical, APOE4 =canonical + 1 variant. Source of fibrullar APP has been inferred to be human APP as described in PMID:20368278. tgolde@ufl.edu Accepted 2019-JUN-26 AT 10:26 BST AT 10:26 BST by MGT EMBO molecular medicine 2018 Only protein-protein interactions imex curation imex curation I had added the APP twice and linked them, which is how I've dealt with fibrils elsewhere, but I then removed it, because in this case they haven't actually shown that the interaction is with fibrils. The gels show both high and low mw entities and I assume the lmw could well be monomers, so I decided it was probably more correct (or less incorrect) just to add them once with stoichiometry unknown. 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 High-affinity interactions and signal transduction between Aβ oligomers and TREM2. High-affinity interactions and signal transduction between Aβ oligomers and TREM2. EMBO molecular medicine 2018 imex curation Lessard CB., Malnik SL., Zhou Y., Ladd TB., Cruz PE., Ran Y., Mahan TE., Chakrabaty P., Holtzman DM., Ulrich JD., Colonna M., Golde TE. Neurodegeneration - Publications depicting interactions involved in neurodegenerative diseases. Alzheimers - Interactions investigated in the context of Alzheimers disease I'm not adding an expressed-in for fibruallar APP - I'm sure its human, less clear where it has been expressed. Also only using CPX for oligomeric APP, fibular is a higher level structure. APOE3 = UniProt canonical, APOE4 =canonical + 1 variant. Source of fibrullar APP has been inferred to be human APP as described in PMID:20368278. tgolde@ufl.edu 25-Jul-2019: 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 Lessard CB., Malnik SL., Zhou Y., Ladd TB., Cruz PE., Ran Y., Mahan TE., Chakrabaty P., Holtzman DM., Ulrich JD., Colonna M., Golde TE. Neurodegeneration - Publications depicting interactions involved in neurodegenerative diseases. I'm not adding an expressed-in for fibruallar APP - I'm sure its human, less clear where it has been expressed. Also only using CPX for oligomeric APP, fibular is a higher level structure. APOE3 = UniProt canonical, APOE4 =canonical + 1 variant. Source of fibrullar APP has been inferred to be human APP as described in PMID:20368278. tgolde@ufl.edu Accepted 2019-JUN-26 AT 10:26 BST AT 10:26 BST by MGT EMBO molecular medicine 2018 Only protein-protein interactions imex curation imex curation I had added the APP twice and linked them, which is how I've dealt with fibrils elsewhere, but I then removed it, because in this case they haven't actually shown that the interaction is with fibrils. The gels show both high and low mw entities and I assume the lmw could well be monomers, so I decided it was probably more correct (or less incorrect) just to add them once with stoichiometry unknown. High-affinity interactions and signal transduction between Aβ oligomers and TREM2. High-affinity interactions and signal transduction between Aβ oligomers and TREM2. EMBO molecular medicine 2018 imex curation Lessard CB., Malnik SL., Zhou Y., Ladd TB., Cruz PE., Ran Y., Mahan TE., Chakrabaty P., Holtzman DM., Ulrich JD., Colonna M., Golde TE. Neurodegeneration - Publications depicting interactions involved in neurodegenerative diseases. Alzheimers - Interactions investigated in the context of Alzheimers disease I'm not adding an expressed-in for fibruallar APP - I'm sure its human, less clear where it has been expressed. Also only using CPX for oligomeric APP, fibular is a higher level structure. APOE3 = UniProt canonical, APOE4 =canonical + 1 variant. Source of fibrullar APP has been inferred to be human APP as described in PMID:20368278. tgolde@ufl.edu 25-Jul-2019: 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 Lessard CB., Malnik SL., Zhou Y., Ladd TB., Cruz PE., Ran Y., Mahan TE., Chakrabaty P., Holtzman DM., Ulrich JD., Colonna M., Golde TE. Neurodegeneration - Publications depicting interactions involved in neurodegenerative diseases. I'm not adding an expressed-in for fibruallar APP - I'm sure its human, less clear where it has been expressed. Also only using CPX for oligomeric APP, fibular is a higher level structure. APOE3 = UniProt canonical, APOE4 =canonical + 1 variant. Source of fibrullar APP has been inferred to be human APP as described in PMID:20368278. tgolde@ufl.edu Accepted 2019-JUN-26 AT 10:26 BST AT 10:26 BST by MGT EMBO molecular medicine 2018 Only protein-protein interactions imex curation imex curation I had added the APP twice and linked them, which is how I've dealt with fibrils elsewhere, but I then removed it, because in this case they haven't actually shown that the interaction is with fibrils. The gels show both high and low mw entities and I assume the lmw could well be monomers, so I decided it was probably more correct (or less incorrect) just to add them once with stoichiometry unknown. trem1_mouse Triggering receptor expressed on myeloid cells 1 Trem1 protein protein mouse Mus musculus Mouse MRKAGLWGLLCVFFVSEVKAAIVLEEERYDLVEGQTLTVKCPFNIMKYANSQKAWQRLPDGKEPLTLVVTQRPFTRPSEVHMGKFTLKHDPSEAMLQVQMTDLQVTDSGLYRCVIYHPPNDPVVLFHPVRLVVTKGSSDVFTPVIIPITRLTERPILITTKYSPSDTTTTRSLPKPTAVVSSPGLGVTIINGTDADSVSTSSVTISVICGLLSKSLVFIILFIVTKRTFG 51A1B7FD095A1990 apoe_human Apolipoprotein E APOE protein protein human Homo sapiens Human MKVLWAALLVTFLAGCQAKVEQAVETEPEPELRQQTEWQSGQRWELALGRFWDYLRWVQTLSEQVQEELLSSQVTQELRALMDETMKELKAYKSELEEQLTPVAEETRARLSKELQAAQARLGADMEDVCGRLVQYRGEVQAMLGQSTEELRVRLASHLRKLRKRLLRDADDLQKRLAVYQAGAREGAERGLSAIRERLGPLVEQGRVRAATVGSLAGQPLQERAQAWGERLRARMEEMGSRTRDRLDEVKEQVAEVRAKLEEQAQQIRLQAEAFQARLKSWFEPLVEDMQRQWAGLVEKVQAAVGTSAAPVPSDNH DIP protein P02649 original sequence version: 197 DIP protein P02649 original sequence version: 146 91AFC04210A30689 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 trem1_human Triggering receptor expressed on myeloid cells 1 TREM1 Triggering receptor expressed on monocytes 1 protein protein human Homo sapiens Human MRKTRLWGLLWMLFVSELRAATKLTEEKYELKEGQTLDVKCDYTLEKFASSQKAWQIIRDGEMPKTLACTERPSKNSHPVQVGRIILEDYHDHGLLRVRMVNLQVEDSGLYQCVIYQPPKEPHMLFDRIRLVVTKGFSGTPGSNENSTQNVYKIPPTTTKALCPLYTSPRTVTQAPPKSTADVSTPDSEINLTNVTDIIRVPVFNIVILLAGGFLSKSLVFSVLFAVTLRSFVP AA114696E35D4D45 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 trem2_mouse Triggering receptor expressed on myeloid cells 2 Trem2 Trem2a Trem2b Trem2c Triggering receptor expressed on monocytes 2 protein protein mouse Mus musculus Mouse MGPLHQFLLLLITALSQALNTTVLQGMAGQSLRVSCTYDALKHWGRRKAWCRQLGEEGPCQRVVSTHGVWLLAFLKKRNGSTVIADDTLAGTVTITLKNLQAGDAGLYQCQSLRGREAEVLQKVLVEVLEDPLDDQDAGDLWVPEESSSFEGAQVEHSTSRNQETSFPPTSILLLLACVLLSKFLAASILWAVARGRQKPGTPVVRGLDCGQDAGHQLQILTGPGGT DIP protein Q99NH8 original sequence version: 82 trml1_mouse Trem-like transcript 1 protein Treml1 Tlt1 Triggering receptor expressed on myeloid cells-like protein 1 protein protein mouse Mus musculus Mouse MDCYLLLLLLLLGLAGQGSADSHPEVLQAPVGSSILVQCHYRLQDVRALKVWCQFLQEGCHPLVTSAVDRRAPGNGRIFLTDLGGGLLQVEMVTLQEEDTGEYGCVVEGAAGPQTLHRVSLLVLPPVPGPREGEEAEDEKETYRIGTGSLLEDPSLDPSASAGPHEFRRRENSIPLIWGAVLLLALVVVAVVIFAVMARKKGNRLVVCGPSQSTGVPGMDPPSAAHRSSDSGLPSDIPHVRLDSPPSFDSIYTGSSLDPPSSEPPAPPSQPPLPPKVLMSSKSVTYATVVFPGGDKGKIASCEPVQDPPNSQTPPSK mint 097E16B34D03E87B trml1_human Trem-like transcript 1 protein TREML1 TLT1 Triggering receptor expressed on myeloid cells-like protein 1 UNQ1825/PRO3438 protein protein human Homo sapiens Human MGLTLLLLLLLGLEGQGIVGSLPEVLQAPVGSSILVQCHYRLQDVKAQKVWCRFLPEGCQPLVSSAVDRRAPAGRRTFLTDLGGGLLQVEMVTLQEEDAGEYGCMVDGARGPQILHRVSLNILPPEEEEETHKIGSLAENAFSDPAGSANPLEPSQDEKSIPLIWGAVLLVGLLVAAVVLFAVMAKRKQGNRLGVCGRFLSSRVSGMNPSSVVHHVSDSGPAAELPLDVPHIRLDSPPSFDNTTYTSLPLDSPSGKPSLPAPSSLPPLPPKVLVCSKPVTYATVIFPGGNKGGGTSCGPAQNPPNNQTPSS trem2_human Triggering receptor expressed on myeloid cells 2 TREM2 Triggering receptor expressed on monocytes 2 protein protein human Homo sapiens Human MEPLRLLILLFVTELSGAHNTTVFQGVAGQSLQVSCPYDSMKHWGRRKAWCRQLGEKGPCQRVVSTHNLWLLSFLRRWNGSTAITDDTLGGTLTITLRNLQPHDAGLYQCQSLHGSEADTLRKVLVEVLADPLDHRDAGDLWFPGESESFEDAHVEHSISRSLLEGEIPFPPTSILLLLACIFLIKILAASALWAAAWHGQKPGTHPPSELDCGHDPGYQLQTLPGLRDT C894AA210F708AF7 app-trem2-1 1 14 unspecified role unspecified role prey prey conditioned medium conditioned medium region v5 tag v5 tag GKPIPNPLLGLDST epitope tag GKPIPNPLLGLDST epitope tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined ectodomain region sufficient to bind sufficient binding region sufficient to bind range range range range region fc-igg tag fc-igg tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined Q9NZC2:p.Arg47His mutation with no effect mutation with no effect mutation with no effect mutation not affecting interaction certain certain sequence position certain certain certain sequence position certain R H Tue Jun 30 16:10:12 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Arg47His' Q9NZC2:p.Arg62His mutation with no effect mutation with no effect mutation with no effect mutation not affecting interaction certain certain sequence position certain certain certain sequence position certain R H Tue Jun 30 18:54:12 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Arg62His' human-293 Homo sapiens transformed primary embryonal kidney cells Human 293 Transformed human primary embryonal kidney cells. The Cell type named 293 is synonymous with HEK-293. 10 unspecified role unspecified role bait bait synthetic construct synthetic construct physical association physical association Fig. 1A, 1D app-trem2-2 1 14 unspecified role unspecified role prey prey cell lysate cell lysate region flag tag flag tag FLAG-tagged FLAG DYKDDDDKV epitope tag DYKDDDDKV epitope tag FLAG FLAG-tagged undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined region ha tag ha tag YPYDVPDYA epitope tag YPYDVPDYA epitope tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined Q9NZC2:p.Arg47His mutation increasing strength mutation increasing interaction strength mutation increasing strength certain certain sequence position certain certain certain sequence position certain R H Tue Jun 30 16:34:16 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Arg47His' Q9NZC2:p.Arg62His mutation increasing strength mutation increasing interaction strength mutation increasing strength certain certain sequence position certain certain certain sequence position certain R H Tue Jun 30 16:38:02 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Arg62His' human-293 Homo sapiens transformed primary embryonal kidney cells Human 293 Transformed human primary embryonal kidney cells. The Cell type named 293 is synonymous with HEK-293. 10 unspecified role unspecified role bait bait synthetic construct synthetic construct physical association physical association Fig. 1B trem2-apoe-1 2 14 unspecified role unspecified role bait bait conditioned medium conditioned medium region v5 tag v5 tag GKPIPNPLLGLDST epitope tag GKPIPNPLLGLDST epitope tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined ectodomain region sufficient to bind sufficient binding region sufficient to bind range range range range region fc-igg tag fc-igg tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined Q9NZC2:p.Arg47His mutation with no effect mutation with no effect mutation with no effect mutation not affecting interaction certain certain sequence position certain certain certain sequence position certain R H Tue Jun 30 17:42:19 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Arg47His' Q9NZC2:p.Arg62His mutation with no effect mutation with no effect mutation with no effect mutation not affecting interaction certain certain sequence position certain certain certain sequence position certain R H Tue Jun 30 16:53:12 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Arg62His' 7 unspecified role unspecified role prey prey conditioned medium conditioned medium physical association physical association Fig. 1C, 1E app-treml1-1 1 13 unspecified role unspecified role prey prey conditioned medium conditioned medium region v5 tag v5 tag GKPIPNPLLGLDST epitope tag GKPIPNPLLGLDST epitope tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined ectodomain region sufficient to bind sufficient binding region sufficient to bind range range range range region fc-igg tag fc-igg tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined human-293 Homo sapiens transformed primary embryonal kidney cells Human 293 Transformed human primary embryonal kidney cells. The Cell type named 293 is synonymous with HEK-293. 10 unspecified role unspecified role bait bait synthetic construct synthetic construct physical association physical association Fig. 1D treml1-apoe-1 2 7 unspecified role unspecified role prey prey conditioned medium conditioned medium 9 unspecified role unspecified role bait bait conditioned medium conditioned medium region v5 tag v5 tag GKPIPNPLLGLDST epitope tag GKPIPNPLLGLDST epitope tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined ectodomain region sufficient to bind sufficient binding region sufficient to bind range range range range region fc-igg tag fc-igg tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined physical association physical association Fig. 1E trem2-apoe-2 4 14 unspecified role unspecified role bait bait purified purified ectodomain region sufficient to bind sufficient binding region sufficient to bind range range range range region fc-igg tag fc-igg tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined Q9NZC2:p.Arg47His mutation with no effect mutation with no effect mutation with no effect mutation not affecting interaction certain certain sequence position certain certain certain sequence position certain R H Tue Jun 30 19:05:33 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Arg47His' region v5 tag v5 tag GKPIPNPLLGLDST epitope tag GKPIPNPLLGLDST epitope tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined Q9NZC2:p.Arg62His mutation with no effect mutation with no effect mutation with no effect mutation not affecting interaction certain certain sequence position certain certain certain sequence position certain R H Tue Jun 30 19:41:05 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Arg62His' human-293t Homo sapiens 293 cells transformed with SV40 large T antigen 293t 293 cells expressing SV40 large T antigen. The original designation of this cell line was 293tsA1609neo. It is not in Cabri,ATCC or HyperCLDB. 7 unspecified role unspecified role prey prey region lipoconjugated residue lipoconjugated residue undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined direct interaction direct interaction Fig. 2C trem2-apoe-3 4 14 unspecified role unspecified role bait bait purified purified ectodomain region sufficient to bind sufficient binding region sufficient to bind range range range range Q9NZC2:p.Arg47His mutation increasing strength mutation increasing interaction strength mutation increasing strength certain certain sequence position certain certain certain sequence position certain R H Tue Jun 30 18:02:39 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Arg47His' region fc-igg tag fc-igg tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined region v5 tag v5 tag GKPIPNPLLGLDST epitope tag GKPIPNPLLGLDST epitope tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined Q9NZC2:p.Arg62His mutation increasing strength mutation increasing interaction strength mutation increasing strength certain certain sequence position certain certain certain sequence position certain R H Tue Jun 30 16:57:24 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Arg62His' human-293t Homo sapiens 293 cells transformed with SV40 large T antigen 293t 293 cells expressing SV40 large T antigen. The original designation of this cell line was 293tsA1609neo. It is not in Cabri,ATCC or HyperCLDB. 7 unspecified role unspecified role prey prey region lipoconjugated residue lipoconjugated residue undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined p.Cys130Arg variant variant certain certain sequence position certain certain certain sequence position certain C R direct interaction direct interaction Fig. 2C trem2-abeta_42_oligomer_human-1 4 71 unspecified role unspecified role prey prey chemical synthesis Chemical synthesis (Chemical synthesis) 14 unspecified role unspecified role bait bait purified purified ectodomain region sufficient to bind sufficient binding region sufficient to bind range range range range Q9NZC2:p.Arg47His mutation with no effect mutation with no effect mutation with no effect mutation not affecting interaction certain certain sequence position certain certain certain sequence position certain R H Tue Jun 30 17:38:58 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Arg47His' region fc-igg tag fc-igg tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined region v5 tag v5 tag GKPIPNPLLGLDST epitope tag GKPIPNPLLGLDST epitope tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined Q9NZC2:p.Arg62His mutation with no effect mutation with no effect mutation with no effect mutation not affecting interaction certain certain sequence position certain certain certain sequence position certain R H Tue Jun 30 15:36:03 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Arg62His' human-293t Homo sapiens 293 cells transformed with SV40 large T antigen 293t 293 cells expressing SV40 large T antigen. The original designation of this cell line was 293tsA1609neo. It is not in Cabri,ATCC or HyperCLDB. direct interaction direct interaction Fig. 2C, 2D trem2-app-1 4 10 unspecified role unspecified role prey prey chemical synthesis Chemical synthesis (Chemical synthesis) 14 unspecified role unspecified role bait bait purified purified ectodomain region sufficient to bind sufficient binding region sufficient to bind range range range range Q9NZC2:p.Arg47His mutation with no effect mutation with no effect mutation with no effect mutation not affecting interaction certain certain sequence position certain certain certain sequence position certain R H Tue Jun 30 16:48:25 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Arg47His' region fc-igg tag fc-igg tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined region v5 tag v5 tag GKPIPNPLLGLDST epitope tag GKPIPNPLLGLDST epitope tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined Q9NZC2:p.Arg62His mutation with no effect mutation with no effect mutation with no effect mutation not affecting interaction certain certain sequence position certain certain certain sequence position certain R H Tue Jun 30 17:45:33 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Arg62His' human-293t Homo sapiens 293 cells transformed with SV40 large T antigen 293t 293 cells expressing SV40 large T antigen. The original designation of this cell line was 293tsA1609neo. It is not in Cabri,ATCC or HyperCLDB. direct interaction direct interaction Fig. 2C trem2-app-2 4 8 unspecified role unspecified role prey prey chemical synthesis Chemical synthesis (Chemical synthesis) 14 unspecified role unspecified role bait bait purified purified ectodomain region sufficient to bind sufficient binding region sufficient to bind range range range range Q9NZC2:p.Arg47His mutation with no effect mutation with no effect mutation with no effect mutation not affecting interaction certain certain sequence position certain certain certain sequence position certain R H Tue Jun 30 16:24:00 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Arg47His' region fc-igg tag fc-igg tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined region v5 tag v5 tag GKPIPNPLLGLDST epitope tag GKPIPNPLLGLDST epitope tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined Q9NZC2:p.Arg62His mutation with no effect mutation with no effect mutation with no effect mutation not affecting interaction certain certain sequence position certain certain certain sequence position certain R H Tue Jun 30 19:51:23 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Arg62His' human-293t Homo sapiens 293 cells transformed with SV40 large T antigen 293t 293 cells expressing SV40 large T antigen. The original designation of this cell line was 293tsA1609neo. It is not in Cabri,ATCC or HyperCLDB. direct interaction direct interaction Fig. 2C trem1-abeta_42_oligomer_human-1 4 71 unspecified role unspecified role prey prey chemical synthesis Chemical synthesis (Chemical synthesis) 9 unspecified role unspecified role bait bait purified purified ectodomain region sufficient to bind sufficient binding region sufficient to bind range range range range region fc-igg tag fc-igg tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined region v5 tag v5 tag GKPIPNPLLGLDST epitope tag GKPIPNPLLGLDST epitope tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined human-293t Homo sapiens 293 cells transformed with SV40 large T antigen 293t 293 cells expressing SV40 large T antigen. The original designation of this cell line was 293tsA1609neo. It is not in Cabri,ATCC or HyperCLDB. direct interaction direct interaction Fig. 2D treml1-abeta_42_oligomer_human-1 4 71 unspecified role unspecified role prey prey chemical synthesis Chemical synthesis (Chemical synthesis) 13 unspecified role unspecified role bait bait purified purified ectodomain region sufficient to bind sufficient binding region sufficient to bind range range range range region fc-igg tag fc-igg tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined region v5 tag v5 tag GKPIPNPLLGLDST epitope tag GKPIPNPLLGLDST epitope tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined human-293t Homo sapiens 293 cells transformed with SV40 large T antigen 293t 293 cells expressing SV40 large T antigen. The original designation of this cell line was 293tsA1609neo. It is not in Cabri,ATCC or HyperCLDB. direct interaction direct interaction Fig. 2D trem1-abeta_42_oligomer_human-2 4 71 unspecified role unspecified role prey prey chemical synthesis Chemical synthesis (Chemical synthesis) 6 unspecified role unspecified role bait bait purified purified ectodomain region sufficient to bind sufficient binding region sufficient to bind range range range range region fc-igg tag fc-igg tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined region v5 tag v5 tag GKPIPNPLLGLDST epitope tag GKPIPNPLLGLDST epitope tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined human-293t Homo sapiens 293 cells transformed with SV40 large T antigen 293t 293 cells expressing SV40 large T antigen. The original designation of this cell line was 293tsA1609neo. It is not in Cabri,ATCC or HyperCLDB. direct interaction direct interaction Fig. 2D trem2-abeta_42_oligomer_human-2 4 71 unspecified role unspecified role prey prey chemical synthesis Chemical synthesis (Chemical synthesis) 11 unspecified role unspecified role bait bait purified purified ectodomain region sufficient to bind sufficient binding region sufficient to bind range range range range region fc-igg tag fc-igg tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined region v5 tag v5 tag GKPIPNPLLGLDST epitope tag GKPIPNPLLGLDST epitope tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined human-293t Homo sapiens 293 cells transformed with SV40 large T antigen 293t 293 cells expressing SV40 large T antigen. The original designation of this cell line was 293tsA1609neo. It is not in Cabri,ATCC or HyperCLDB. direct interaction direct interaction Fig. 2D treml1-abeta_42_oligomer_human-2 4 12 unspecified role unspecified role bait bait purified purified region fc-igg tag fc-igg tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined region v5 tag v5 tag GKPIPNPLLGLDST epitope tag GKPIPNPLLGLDST epitope tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined ectodomain region sufficient to bind sufficient binding region sufficient to bind range range range range human-293t Homo sapiens 293 cells transformed with SV40 large T antigen 293t 293 cells expressing SV40 large T antigen. The original designation of this cell line was 293tsA1609neo. It is not in Cabri,ATCC or HyperCLDB. 71 unspecified role unspecified role prey prey chemical synthesis Chemical synthesis (Chemical synthesis) direct interaction direct interaction Fig. 2D trem2-apoe-4 4 71 competitor competitor competitor prey prey chemical synthesis Chemical synthesis (Chemical synthesis) 14 unspecified role unspecified role bait bait purified purified ectodomain region sufficient to bind sufficient binding region sufficient to bind range range range range region fc-igg tag fc-igg tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined region v5 tag v5 tag GKPIPNPLLGLDST epitope tag GKPIPNPLLGLDST epitope tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined human-293t Homo sapiens 293 cells transformed with SV40 large T antigen 293t 293 cells expressing SV40 large T antigen. The original designation of this cell line was 293tsA1609neo. It is not in Cabri,ATCC or HyperCLDB. 7 unspecified role unspecified role prey prey region lipoconjugated residue lipoconjugated residue undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined physical association physical association Fig. 3 Binding of alpha-beta42 oligomers blocked APOE3 binding. In contrast, addition of alpha-beta42 oligomers to TREM2 previously bound to APOE3 did not block subsequent interaction with alpha-beta42 oligomers. trem2-abeta_42_oligomer_human-3 5 71 unspecified role unspecified role prey prey chemical synthesis Chemical synthesis (Chemical synthesis) 14 unspecified role unspecified role bait bait purified purified Q9NZC2:p.Arg47His mutation with no effect mutation with no effect mutation with no effect mutation not affecting interaction certain certain sequence position certain certain certain sequence position certain R H Tue Jun 30 20:00:26 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Arg47His' Q9NZC2:p.Arg62His mutation with no effect mutation with no effect mutation with no effect mutation not affecting interaction certain certain sequence position certain certain certain sequence position certain R H Tue Jun 30 19:03:06 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Arg62His' ectodomain region sufficient to bind sufficient binding region sufficient to bind range range range range region fc-igg tag fc-igg tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined region v5 tag v5 tag GKPIPNPLLGLDST epitope tag GKPIPNPLLGLDST epitope tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined human-293t Homo sapiens 293 cells transformed with SV40 large T antigen 293t 293 cells expressing SV40 large T antigen. The original designation of this cell line was 293tsA1609neo. It is not in Cabri,ATCC or HyperCLDB. direct interaction direct interaction Fig. 4B, EV3B trem2-app-3 5 10 unspecified role unspecified role prey prey chemical synthesis Chemical synthesis (Chemical synthesis) 11 unspecified role unspecified role bait bait purified purified ectodomain region sufficient to bind sufficient binding region sufficient to bind range range range range region fc-igg tag fc-igg tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined region v5 tag v5 tag GKPIPNPLLGLDST epitope tag GKPIPNPLLGLDST epitope tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined human-293t Homo sapiens 293 cells transformed with SV40 large T antigen 293t 293 cells expressing SV40 large T antigen. The original designation of this cell line was 293tsA1609neo. It is not in Cabri,ATCC or HyperCLDB. direct interaction direct interaction Fig. 4A treml1-app-1 5 71 unspecified role unspecified role prey prey chemical synthesis Chemical synthesis (Chemical synthesis) 13 unspecified role unspecified role bait bait purified purified region fc-igg tag fc-igg tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined region v5 tag v5 tag GKPIPNPLLGLDST epitope tag GKPIPNPLLGLDST epitope tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined ectodomain region sufficient to bind sufficient binding region sufficient to bind range range range range human-293t Homo sapiens 293 cells transformed with SV40 large T antigen 293t 293 cells expressing SV40 large T antigen. The original designation of this cell line was 293tsA1609neo. It is not in Cabri,ATCC or HyperCLDB. direct interaction direct interaction Fig. 4B app-trem2-3 1 11 unspecified role unspecified role prey prey conditioned medium conditioned medium region v5 tag v5 tag GKPIPNPLLGLDST epitope tag GKPIPNPLLGLDST epitope tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined ectodomain region sufficient to bind sufficient binding region sufficient to bind range range range range region fc-igg tag fc-igg tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined human-293 Homo sapiens transformed primary embryonal kidney cells Human 293 Transformed human primary embryonal kidney cells. The Cell type named 293 is synonymous with HEK-293. 10 unspecified role unspecified role bait bait synthetic construct synthetic construct physical association physical association Fig. 1A trem2-app-4 5 10 unspecified role unspecified role prey prey chemical synthesis Chemical synthesis (Chemical synthesis) 14 unspecified role unspecified role bait bait purified purified Q9NZC2:p.Arg62His mutation with no effect mutation with no effect mutation with no effect mutation not affecting interaction certain certain sequence position certain certain certain sequence position certain R H Tue Jun 30 19:05:40 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Arg62His' ectodomain region sufficient to bind sufficient binding region sufficient to bind range range range range region fc-igg tag fc-igg tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined region v5 tag v5 tag GKPIPNPLLGLDST epitope tag GKPIPNPLLGLDST epitope tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined Q9NZC2:p.Arg47His mutation with no effect mutation with no effect mutation with no effect mutation not affecting interaction certain certain sequence position certain certain certain sequence position certain R H Tue Jun 30 16:07:23 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Arg47His' human-293t Homo sapiens 293 cells transformed with SV40 large T antigen 293t 293 cells expressing SV40 large T antigen. The original designation of this cell line was 293tsA1609neo. It is not in Cabri,ATCC or HyperCLDB. direct interaction direct interaction Fig. 4A 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 10 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 10 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 167 169 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