UniProt UniProt http://www.uniprot.org Characterization of the Alzheimer's disease-associated CLAC protein and identification of an amyloid beta-peptide-binding site. Characterization of the Alzheimer's disease-associated CLAC protein and identification of an amyloid beta-peptide-binding site. The Journal of biological chemistry 2005 imex curation Söderberg L., Kakuyama H., Möller A., Ito A., Winblad B., Tjernberg LO., Näslund J. Not added 8E as its a chimeric molecule. inda.soderberg@ neurotec.ki.se 09-May-2019: Contacted by IntAct-Help. Only protein-protein interactions imex curation in vitro In vitro affinity chrom affinity chromatography technology Affinity purification Affinity purification affinity chrom anti tag western anti tag western blot anti tag western Söderberg L., Kakuyama H., Möller A., Ito A., Winblad B., Tjernberg LO., Näslund J. Not added 8E as its a chimeric molecule. inda.soderberg@ neurotec.ki.se Accepted 2019-APR-29 AT 13:18 BST AT 13:18 BST by MGT The Journal of biological chemistry 2005 Only protein-protein interactions imex curation imex curation 8F added to EBI-20993967 Characterization of the Alzheimer's disease-associated CLAC protein and identification of an amyloid beta-peptide-binding site. Characterization of the Alzheimer's disease-associated CLAC protein and identification of an amyloid beta-peptide-binding site. The Journal of biological chemistry 2005 imex curation Söderberg L., Kakuyama H., Möller A., Ito A., Winblad B., Tjernberg LO., Näslund J. Not added 8E as its a chimeric molecule. inda.soderberg@ neurotec.ki.se 09-May-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 Söderberg L., Kakuyama H., Möller A., Ito A., Winblad B., Tjernberg LO., Näslund J. Not added 8E as its a chimeric molecule. inda.soderberg@ neurotec.ki.se Accepted 2019-APR-29 AT 13:18 BST AT 13:18 BST by MGT The Journal of biological chemistry 2005 Only protein-protein interactions imex curation imex curation 8F added to EBI-20993967 Characterization of the Alzheimer's disease-associated CLAC protein and identification of an amyloid beta-peptide-binding site. Characterization of the Alzheimer's disease-associated CLAC protein and identification of an amyloid beta-peptide-binding site. The Journal of biological chemistry 2005 imex curation Söderberg L., Kakuyama H., Möller A., Ito A., Winblad B., Tjernberg LO., Näslund J. Not added 8E as its a chimeric molecule. inda.soderberg@ neurotec.ki.se 09-May-2019: Contacted by IntAct-Help. Only protein-protein interactions imex curation in vitro In vitro comigration in gel comigration in gel electrophoresis comigration in gel anti tag western anti tag western blot anti tag western Söderberg L., Kakuyama H., Möller A., Ito A., Winblad B., Tjernberg LO., Näslund J. Not added 8E as its a chimeric molecule. inda.soderberg@ neurotec.ki.se Accepted 2019-APR-29 AT 13:18 BST AT 13:18 BST by MGT The Journal of biological chemistry 2005 Only protein-protein interactions imex curation imex curation 8F added to EBI-20993967 Characterization of the Alzheimer's disease-associated CLAC protein and identification of an amyloid beta-peptide-binding site. Characterization of the Alzheimer's disease-associated CLAC protein and identification of an amyloid beta-peptide-binding site. The Journal of biological chemistry 2005 imex curation Söderberg L., Kakuyama H., Möller A., Ito A., Winblad B., Tjernberg LO., Näslund J. Not added 8E as its a chimeric molecule. inda.soderberg@ neurotec.ki.se 09-May-2019: Contacted by IntAct-Help. Only protein-protein interactions imex curation in vitro In vitro filter binding filter binding Filter overlay assay Filter overlay assay autoradiography autoradiography Söderberg L., Kakuyama H., Möller A., Ito A., Winblad B., Tjernberg LO., Näslund J. Not added 8E as its a chimeric molecule. inda.soderberg@ neurotec.ki.se Accepted 2019-APR-29 AT 13:18 BST AT 13:18 BST by MGT The Journal of biological chemistry 2005 Only protein-protein interactions imex curation imex curation 8F added to EBI-20993967 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 Characterization of the Alzheimer's disease-associated CLAC protein and identification of an amyloid beta-peptide-binding site. Characterization of the Alzheimer's disease-associated CLAC protein and identification of an amyloid beta-peptide-binding site. The Journal of biological chemistry 2005 imex curation Söderberg L., Kakuyama H., Möller A., Ito A., Winblad B., Tjernberg LO., Näslund J. Not added 8E as its a chimeric molecule. inda.soderberg@ neurotec.ki.se 09-May-2019: Contacted by IntAct-Help. Only protein-protein interactions imex curation in vitro In vitro cd circular dichroism CD CD cd predetermined predetermined participant predetermined Söderberg L., Kakuyama H., Möller A., Ito A., Winblad B., Tjernberg LO., Näslund J. Not added 8E as its a chimeric molecule. inda.soderberg@ neurotec.ki.se Accepted 2019-APR-29 AT 13:18 BST AT 13:18 BST by MGT The Journal of biological chemistry 2005 Only protein-protein interactions imex curation imex curation 8F added to EBI-20993967 Characterization of the Alzheimer's disease-associated CLAC protein and identification of an amyloid beta-peptide-binding site. Characterization of the Alzheimer's disease-associated CLAC protein and identification of an amyloid beta-peptide-binding site. The Journal of biological chemistry 2005 imex curation Söderberg L., Kakuyama H., Möller A., Ito A., Winblad B., Tjernberg LO., Näslund J. Not added 8E as its a chimeric molecule. inda.soderberg@ neurotec.ki.se 09-May-2019: Contacted by IntAct-Help. Only protein-protein interactions imex curation in vitro In vitro enzymatic footprint enzymatic footprinting enzymatic footprint edman degradation edman degradation Söderberg L., Kakuyama H., Möller A., Ito A., Winblad B., Tjernberg LO., Näslund J. Not added 8E as its a chimeric molecule. inda.soderberg@ neurotec.ki.se Accepted 2019-APR-29 AT 13:18 BST AT 13:18 BST by MGT The Journal of biological chemistry 2005 Only protein-protein interactions imex curation imex curation 8F added to EBI-20993967 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 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 q9bxs0-3 Collagen alpha-1(XXV) chain COL25A1 Alzheimer disease amyloid-associated protein CLAC-P protein protein human Homo sapiens Human MLLKKHAGKGGGREPRSEDPTPAEQHCARTMPPCAVLAALLSVVAVVSCLYLGVKTNDLQARIAALESAKGAPSIHLLPDTLDHLKTMVQEKVERLLAQKSYEHMAKIRIAREAPSECNCPAGPPGKRGKRGRRGESGPPGPPGPKGDKGEQGDQGPRMVFPKINHGFLSADQQLIKRRLIKGDQGQAGPPGPPGPPGPRGPPGDTGKDGPRGMPGVPGEPGKPGEQGLMGPLGPPGQKGSIGAPGIPGMNGQKGEPGLPGAVGQNGIPGPKGEPGEQGEKGDAGENGPKGDTGEKGDPGSSAAGIKGEPGESGRPGQKGEPGFIGPQGEPGLPGLPGTKGERGEAGPPGRGERGEPGAPGPKGKQGESGTRGPKGSKGDRGEKGDSGAQGPRGPPGQKGDQGATEIIDYNGNLHEALQRITTLTVTGPPGPPGPQGLQGPKGEQGSPGIPGMDGEQGLKGSKGDMGDPGMTGEKGGIGLPGLPGANGMKGEKGDSGMPGPQGPSIIGPPGPPGPHGPPGPMGPHGLPGPKGTDGPMGPHGPAGPKGERGEKGAMGEPGPRGPYGLPLGPDGLPMPGCWQK D4F26C1293B70F3B heparin Heparin small molecule small molecule chemical synthesis Chemical synthesis (Chemical synthesis) syua_human Alpha-synuclein Non-A beta component of AD amyloid Non-A4 component of amyloid precursor SNCA NACP PARK1 protein protein human Homo sapiens Human MDVFMKGLSKAKEGVVAAAEKTKQGVAEAAGKTKEGVLYVGSKTKEGVVHGVATVAEKTKEQVTNVGGAVVTGVTAVAQKTVEGAGSIAAATGFVKKDQLGKNEEGAPQEGILEDMPVDPDNEAYEMPSEEGYQDYEPEA DIP protein P37840 original sequence version: 124 DIP protein P37840 original sequence version: 175 DIP protein P37840 original sequence version: 178 6BB2F12128931663 col25a1-heparin-1 1 10 unspecified role unspecified role prey prey over-expressed over expressed level over-expressed c-terminal myc tag myc tag EUKLISEED epitope tag EUKLISEED epitope tag c-term range C-terminal range c-term range c-term range C-terminal range c-term range c-terminal his tag his tag Hexa-His-tag 6-His-tag Histidine-tag Hexa-His-tag Histidine-tag 6-His-tag c-term range C-terminal range c-term range c-term range C-terminal range c-term range 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. 11 unspecified role unspecified role bait bait purified purified physical association physical association Fig 3A heparin-col25a1-1 2 20 unspecified role unspecified role prey prey over-expressed over expressed level over-expressed c-terminal myc tag myc tag EUKLISEED epitope tag EUKLISEED epitope tag c-term range C-terminal range c-term range c-term range C-terminal range c-term range c-terminal his tag his tag Hexa-His-tag 6-His-tag Histidine-tag Hexa-His-tag Histidine-tag 6-His-tag c-term range C-terminal range c-term range c-term range C-terminal range c-term range 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. 11 unspecified role unspecified role bait bait purified purified direct interaction direct interaction Fig 3B col25a1-col25a1-1 7 10 unspecified role unspecified role neutral component neutral component over-expressed over expressed level over-expressed c-terminal myc tag myc tag EUKLISEED epitope tag EUKLISEED epitope tag c-term range C-terminal range c-term range c-term range C-terminal range c-term range c-terminal his tag his tag Hexa-His-tag 6-His-tag Histidine-tag Hexa-His-tag Histidine-tag 6-His-tag c-term range C-terminal range c-term range c-term range C-terminal range c-term range region sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain greater-than greater-than 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 neutral component neutral component purified purified c-terminal his tag his tag Hexa-His-tag 6-His-tag Histidine-tag Hexa-His-tag Histidine-tag 6-His-tag c-term range C-terminal range c-term range c-term range C-terminal range c-term range c-terminal myc tag myc tag EUKLISEED epitope tag EUKLISEED epitope tag c-term range C-terminal range c-term range c-term range C-terminal range c-term range region sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain greater-than greater-than direct interaction direct interaction Fig 4B col25a1-1 3 10 unspecified role unspecified role neutral component neutral component purified purified c-terminal myc tag myc tag EUKLISEED epitope tag EUKLISEED epitope tag c-term range C-terminal range c-term range c-term range C-terminal range c-term range c-terminal his tag his tag Hexa-His-tag 6-His-tag Histidine-tag Hexa-His-tag Histidine-tag 6-His-tag c-term range C-terminal range c-term range c-term range C-terminal range c-term range 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. direct interaction direct interaction Fig 5A col25a1-2 3 10 unspecified role unspecified role neutral component neutral component purified purified c-terminal myc tag myc tag EUKLISEED epitope tag EUKLISEED epitope tag c-term range C-terminal range c-term range c-term range C-terminal range c-term range c-terminal his tag his tag Hexa-His-tag 6-His-tag Histidine-tag Hexa-His-tag Histidine-tag 6-His-tag c-term range C-terminal range c-term range c-term range C-terminal range c-term range 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. direct interaction direct interaction Fig 5A col25a1-3 6 10 unspecified role unspecified role neutral component neutral component purified purified c-terminal myc tag myc tag EUKLISEED epitope tag EUKLISEED epitope tag c-term range C-terminal range c-term range c-term range C-terminal range c-term range c-terminal his tag his tag Hexa-His-tag 6-His-tag Histidine-tag Hexa-His-tag Histidine-tag 6-His-tag c-term range C-terminal range c-term range c-term range C-terminal range c-term range region sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain certain certain sequence position certain certain certain sequence position certain 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. direct interaction direct interaction Fig 5B, 8D abeta_42_oligomer_human-collagen_xxv_3_human-1 2 20 unspecified role unspecified role prey prey over-expressed over expressed level over-expressed c-terminal myc tag myc tag EUKLISEED epitope tag EUKLISEED epitope tag c-term range C-terminal range c-term range c-term range C-terminal range c-term range c-terminal his tag his tag Hexa-His-tag 6-His-tag Histidine-tag Hexa-His-tag Histidine-tag 6-His-tag c-term range C-terminal range c-term range c-term range C-terminal range c-term range 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. 51 unspecified role unspecified role bait bait purified purified chemical synthesis Chemical synthesis (Chemical synthesis) direct interaction direct interaction Fig 6C abeta_40_oligomer_human-collagen_xxv_3_human-1 2 20 unspecified role unspecified role prey prey over-expressed over expressed level over-expressed c-terminal myc tag myc tag EUKLISEED epitope tag EUKLISEED epitope tag c-term range C-terminal range c-term range c-term range C-terminal range c-term range c-terminal his tag his tag Hexa-His-tag 6-His-tag Histidine-tag Hexa-His-tag Histidine-tag 6-His-tag c-term range C-terminal range c-term range c-term range C-terminal range c-term range col25a1 binding region required to bind necessary binding region required to bind certain certain sequence position certain certain certain sequence position certain region sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain certain certain sequence position certain certain certain sequence position certain p.Lys127_Arg134del 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 KRGKRGRR . 59 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. 61 unspecified role unspecified role bait bait purified purified chemical synthesis Chemical synthesis (Chemical synthesis) direct interaction direct interaction Fig 6A, 6B, 6C, 8A, 8F Collagen type XXV trimer, variant 3 binding to the Amyloid-beta protein 40 oligomeric complex was inversely related to NaCl concentration snca-collagen_xxv_3_human-1 2 20 unspecified role unspecified role prey prey over-expressed over expressed level over-expressed c-terminal myc tag myc tag EUKLISEED epitope tag EUKLISEED epitope tag c-term range C-terminal range c-term range c-term range C-terminal range c-term range c-terminal his tag his tag Hexa-His-tag 6-His-tag Histidine-tag Hexa-His-tag Histidine-tag 6-His-tag c-term range C-terminal range c-term range c-term range C-terminal range c-term range 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. 12 unspecified role unspecified role bait bait purified purified region sufficient to bind sufficient binding region sufficient to bind range range range range chemical synthesis Chemical synthesis (Chemical synthesis) direct interaction direct interaction Fig6C abeta_40_oligomer_human-collagen_xxv_3_human-2 4 10 unspecified role unspecified role prey prey over-expressed over expressed level over-expressed region sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain chemical synthesis Chemical synthesis (Chemical synthesis) 61 unspecified role unspecified role bait bait purified purified region 125i radiolabel 125i radiolabel I125 125I 125I I125 undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined chemical synthesis Chemical synthesis (Chemical synthesis) physical association physical association Fig 7 abeta_40_oligomer_human-col25a1-2 2 10 predetermined predetermined participant predetermined antibody detection identification by antibody antibody detection competitor competitor competitor prey prey region sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain chemical synthesis Chemical synthesis (Chemical synthesis) 20 unspecified role unspecified role prey prey over-expressed over expressed level over-expressed c-terminal myc tag myc tag EUKLISEED epitope tag EUKLISEED epitope tag c-term range C-terminal range c-term range c-term range C-terminal range c-term range c-terminal his tag his tag Hexa-His-tag 6-His-tag Histidine-tag Hexa-His-tag Histidine-tag 6-His-tag c-term range C-terminal range c-term range c-term range C-terminal range c-term range 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. 61 unspecified role unspecified role bait bait purified purified chemical synthesis Chemical synthesis (Chemical synthesis) direct interaction direct interaction Fig 8C Collagen type XXV trimer, variant 3 binding to the Amyloid-beta protein 40 oligomeric complex was inversely related to NaCl concentration collagen-xxv-3_human Type XXV collagen Collagen type XXV trimer, variant 3 Type XXV collagen COL25A1 trimer 10 unspecified role unspecified role direct interaction direct interaction human Homo sapiens Human stable complex stable complex biological system reconstruction evidence based on inference from background scientific knowledge used in manual assertion biological system reconstruction evidence based on inference from background scientific knowledge used in manual assertion Type II orientated transmembrane collagen. Inhibits fibrillization of beta amyloid peptide during the elongation phase. Has also been shown to assemble amyloid fibrils into protease-resistant aggregates. Binds heparin. Homotrimer Triple-helices consisting of about 1000 amino acids per chain forming a coiled coil structure. Each polypeptide forms a left-handed helix in which every third residue, glycine, comes into the centre of the superhelix. Sylvie Ricard-Blum, MatrixDB Accepted 2016-MAR-31 by ORCHARD abeta-40-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 40 homooligomer beta-amyloid protein 40 complex beta-amyloid-40 complex beta amyloid protein 40 complex amyloid-beta-40 complex amyloid beta protein 40 complex amyloid-beta protein 40 homooligomer amyloid-beta-40 homooligomer amyloid beta protein 40 homooligomer beta-amyloid-40 heterooligomer beta amyloid protein 40 homooligomer Abeta protein 40 complex Amyloid-beta protein 40 oligomeric complex APP oligomer Type 1 amyloid-beta oligomer ADDL complex 9 unspecified role unspecified role protein 40 binding region binding region binding-associated region binding region certain certain sequence position certain certain certain sequence position certain 9 unspecified role unspecified role protein 40 binding region binding region binding-associated region binding region certain certain sequence position certain certain certain sequence position certain 83 81 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. 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-1069) 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. Homooligomer 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-JUL-25 by ORCHARD 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 8 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 8 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 85 87 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