UniProt UniProt http://www.uniprot.org Humanin Specifically Interacts with Amyloid-β Oligomers and Counteracts Their in vivo Toxicity. Humanin Specifically Interacts with Amyloid-β Oligomers and Counteracts Their in vivo Toxicity. Journal of Alzheimer's disease : JAD 2016 imex curation Romeo M., Stravalaci M., Beeg M., Rossi A., Fiordaliso F., Corbelli A., Salmona M., Gobbi M., Cagnotto A., Diomede L. Alzheimers - Interactions investigated in the context of Alzheimers disease C.elegans data not added as all whole cell lysate - no purification luisa.diomede@marionegri.it 09-May-2019: 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 Romeo M., Stravalaci M., Beeg M., Rossi A., Fiordaliso F., Corbelli A., Salmona M., Gobbi M., Cagnotto A., Diomede L. Alzheimers - Interactions investigated in the context of Alzheimers disease C.elegans data not added as all whole cell lysate - no purification Aggregation measured by levels of thioflavin T (ThT), a small molecule that gives strong fluorescence upon binding to amyloids. luisa.diomede@marionegri.it Accepted 2019-APR-04 AT 13:28 BST AT 13:28 BST by LIVIAP Journal of Alzheimer's disease : JAD 2016 Only protein-protein interactions imex curation imex curation Again. N/A for chemical synthesis; Exp detail problem as before - with EM data, I tend to assume that if the expert reviewers accept it, its OK for us to. The crystals do look different with the humanin present.; I can't add an exp - prepaswe don't have one for chemical synthese. Purified doesn't work unless we change the definition but I've always regarded ending up with a pure product part of 'chemical synthesis' anyway. 3E, F are the oligomer not monomer so have added an interaction. IC50s switched round.; Interaction deleted, then realised I didn't have the Ab-AB, which was probably what I was intending to add. Humanin Specifically Interacts with Amyloid-β Oligomers and Counteracts Their in vivo Toxicity. Humanin Specifically Interacts with Amyloid-β Oligomers and Counteracts Their in vivo Toxicity. Journal of Alzheimer's disease : JAD 2016 imex curation Romeo M., Stravalaci M., Beeg M., Rossi A., Fiordaliso F., Corbelli A., Salmona M., Gobbi M., Cagnotto A., Diomede L. Alzheimers - Interactions investigated in the context of Alzheimers disease C.elegans data not added as all whole cell lysate - no purification luisa.diomede@marionegri.it 09-May-2019: Contacted by IntAct-Help. Only protein-protein interactions imex curation in vitro In vitro spr surface plasmon resonance Optical biosensor BIAcore(r) BIAcore(r) Optical biosensor spr antibody detection identification by antibody antibody detection Romeo M., Stravalaci M., Beeg M., Rossi A., Fiordaliso F., Corbelli A., Salmona M., Gobbi M., Cagnotto A., Diomede L. Alzheimers - Interactions investigated in the context of Alzheimers disease C.elegans data not added as all whole cell lysate - no purification luisa.diomede@marionegri.it Accepted 2019-APR-04 AT 13:28 BST AT 13:28 BST by LIVIAP Journal of Alzheimer's disease : JAD 2016 Only protein-protein interactions imex curation imex curation Again. N/A for chemical synthesis; Exp detail problem as before - with EM data, I tend to assume that if the expert reviewers accept it, its OK for us to. The crystals do look different with the humanin present.; I can't add an exp - prepaswe don't have one for chemical synthese. Purified doesn't work unless we change the definition but I've always regarded ending up with a pure product part of 'chemical synthesis' anyway. 3E, F are the oligomer not monomer so have added an interaction. IC50s switched round.; Interaction deleted, then realised I didn't have the Ab-AB, which was probably what I was intending to add. Humanin Specifically Interacts with Amyloid-β Oligomers and Counteracts Their in vivo Toxicity. Humanin Specifically Interacts with Amyloid-β Oligomers and Counteracts Their in vivo Toxicity. Journal of Alzheimer's disease : JAD 2016 imex curation Romeo M., Stravalaci M., Beeg M., Rossi A., Fiordaliso F., Corbelli A., Salmona M., Gobbi M., Cagnotto A., Diomede L. Alzheimers - Interactions investigated in the context of Alzheimers disease C.elegans data not added as all whole cell lysate - no purification luisa.diomede@marionegri.it 09-May-2019: Contacted by IntAct-Help. Only protein-protein interactions imex curation in vitro In vitro aggregation aggregation assay aggregation tag fluorescence tag visualisation by fluorescence tag fluorescence Romeo M., Stravalaci M., Beeg M., Rossi A., Fiordaliso F., Corbelli A., Salmona M., Gobbi M., Cagnotto A., Diomede L. Alzheimers - Interactions investigated in the context of Alzheimers disease C.elegans data not added as all whole cell lysate - no purification Aggregation measured by levels of thioflavin T (ThT), a small molecule that gives strong fluorescence upon binding to amyloids. luisa.diomede@marionegri.it Accepted 2019-APR-04 AT 13:28 BST AT 13:28 BST by LIVIAP Journal of Alzheimer's disease : JAD 2016 Only protein-protein interactions imex curation imex curation Again. N/A for chemical synthesis; Exp detail problem as before - with EM data, I tend to assume that if the expert reviewers accept it, its OK for us to. The crystals do look different with the humanin present.; I can't add an exp - prepaswe don't have one for chemical synthese. Purified doesn't work unless we change the definition but I've always regarded ending up with a pure product part of 'chemical synthesis' anyway. 3E, F are the oligomer not monomer so have added an interaction. IC50s switched round.; Interaction deleted, then realised I didn't have the Ab-AB, which was probably what I was intending to add. 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 Humanin Specifically Interacts with Amyloid-β Oligomers and Counteracts Their in vivo Toxicity. Humanin Specifically Interacts with Amyloid-β Oligomers and Counteracts Their in vivo Toxicity. Journal of Alzheimer's disease : JAD 2016 imex curation Romeo M., Stravalaci M., Beeg M., Rossi A., Fiordaliso F., Corbelli A., Salmona M., Gobbi M., Cagnotto A., Diomede L. Alzheimers - Interactions investigated in the context of Alzheimers disease C.elegans data not added as all whole cell lysate - no purification luisa.diomede@marionegri.it 09-May-2019: Contacted by IntAct-Help. Only protein-protein interactions imex curation in vitro In vitro tem transmission electron microscopy tem predetermined predetermined participant predetermined Romeo M., Stravalaci M., Beeg M., Rossi A., Fiordaliso F., Corbelli A., Salmona M., Gobbi M., Cagnotto A., Diomede L. Alzheimers - Interactions investigated in the context of Alzheimers disease C.elegans data not added as all whole cell lysate - no purification luisa.diomede@marionegri.it Accepted 2019-APR-04 AT 13:28 BST AT 13:28 BST by LIVIAP Journal of Alzheimer's disease : JAD 2016 Only protein-protein interactions imex curation imex curation Again. N/A for chemical synthesis; Exp detail problem as before - with EM data, I tend to assume that if the expert reviewers accept it, its OK for us to. The crystals do look different with the humanin present.; I can't add an exp - prepaswe don't have one for chemical synthese. Purified doesn't work unless we change the definition but I've always regarded ending up with a pure product part of 'chemical synthesis' anyway. 3E, F are the oligomer not monomer so have added an interaction. IC50s switched round.; Interaction deleted, then realised I didn't have the Ab-AB, which was probably what I was intending to add. Humanin Specifically Interacts with Amyloid-β Oligomers and Counteracts Their in vivo Toxicity. Humanin Specifically Interacts with Amyloid-β Oligomers and Counteracts Their in vivo Toxicity. Journal of Alzheimer's disease : JAD 2016 imex curation Romeo M., Stravalaci M., Beeg M., Rossi A., Fiordaliso F., Corbelli A., Salmona M., Gobbi M., Cagnotto A., Diomede L. Alzheimers - Interactions investigated in the context of Alzheimers disease C.elegans data not added as all whole cell lysate - no purification luisa.diomede@marionegri.it 09-May-2019: Contacted by IntAct-Help. Only protein-protein interactions imex curation in vitro In vitro aggregation aggregation assay aggregation predetermined predetermined participant predetermined Romeo M., Stravalaci M., Beeg M., Rossi A., Fiordaliso F., Corbelli A., Salmona M., Gobbi M., Cagnotto A., Diomede L. Alzheimers - Interactions investigated in the context of Alzheimers disease C.elegans data not added as all whole cell lysate - no purification luisa.diomede@marionegri.it Accepted 2019-APR-04 AT 13:28 BST AT 13:28 BST by LIVIAP Journal of Alzheimer's disease : JAD 2016 Only protein-protein interactions imex curation imex curation Again. N/A for chemical synthesis; Exp detail problem as before - with EM data, I tend to assume that if the expert reviewers accept it, its OK for us to. The crystals do look different with the humanin present.; I can't add an exp - prepaswe don't have one for chemical synthese. Purified doesn't work unless we change the definition but I've always regarded ending up with a pure product part of 'chemical synthesis' anyway. 3E, F are the oligomer not monomer so have added an interaction. IC50s switched round.; Interaction deleted, then realised I didn't have the Ab-AB, which was probably what I was intending to add. hunin_human Humanin HN Humanin mitochondrial MT-RNR2 protein protein human Homo sapiens Human MAPRGFSCLLLLTSEIDLPVKRRA mint Plays a role as a neuroprotective factor against death induced by multiple different types of familial Alzheimer disease genes and beta amyloid in Alzheimer disease. Induced chemotaxis of mononuclear phagocytes by using FPRL1. Reduced the aggregation and fibrillary formation by suppressing the effect of APP on mononuclear phagocytes and acts by competitively inhibiting the access of FPRL1 to APP. Prevents the translocation of BAX from cytosol to mitochondria 08B9A778EC13B971 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 app-app-116 3 8 unspecified role unspecified role neutral component neutral component chemical synthesis Chemical synthesis (Chemical synthesis) 8 unspecified role unspecified role neutral component neutral component chemical synthesis Chemical synthesis (Chemical synthesis) direct interaction direct interaction Fig. 2 app-app-117 3 7 inhibitor inhibitor neutral component neutral component Q8IVG9:p.Ser14Gly 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 S G Tue Jun 30 19:36:33 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Ser14Gly' chemical synthesis Chemical synthesis (Chemical synthesis) 8 unspecified role unspecified role neutral component neutral component chemical synthesis Chemical synthesis (Chemical synthesis) 8 unspecified role unspecified role neutral component neutral component chemical synthesis Chemical synthesis (Chemical synthesis) direct interaction direct interaction Fig. 2, Table 1 app-mt_rnr2-1 2 7 inhibitor inhibitor prey prey Q8IVG9:p.Ser14Gly 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 S G Tue Jun 30 19:37:32 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Ser14Gly' chemical synthesis Chemical synthesis (Chemical synthesis) 8 unspecified role unspecified role bait bait chemical synthesis Chemical synthesis (Chemical synthesis) direct interaction direct interaction Fig. 3B, 3C app-app-119 1 8 unspecified role unspecified role neutral component neutral component chemical synthesis Chemical synthesis (Chemical synthesis) 8 unspecified role unspecified role neutral component neutral component chemical synthesis Chemical synthesis (Chemical synthesis) direct interaction direct interaction Fig. 4A app-mt_rnr2-2 5 7 unspecified role unspecified role neutral component neutral component Q8IVG9:p.Ser14Gly 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 S G Tue Jun 30 19:06:04 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Ser14Gly' chemical synthesis Chemical synthesis (Chemical synthesis) 8 unspecified role unspecified role neutral component neutral component chemical synthesis Chemical synthesis (Chemical synthesis) direct interaction direct interaction Fig. 4D, 4F app-app-118 5 8 unspecified role unspecified role neutral component neutral component chemical synthesis Chemical synthesis (Chemical synthesis) 8 unspecified role unspecified role neutral component neutral component chemical synthesis Chemical synthesis (Chemical synthesis) direct interaction direct interaction Fig. 4B app-mt_rnr2-3 6 7 unspecified role unspecified role neutral component neutral component Q8IVG9:p.Ser14Gly 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 S G Tue Jun 30 15:56:27 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Ser14Gly' chemical synthesis Chemical synthesis (Chemical synthesis) 8 unspecified role unspecified role neutral component neutral component chemical synthesis Chemical synthesis (Chemical synthesis) direct interaction direct interaction Fig. 5 abeta_42_oligomer_human-mt_rnr2-2 2 7 inhibitor inhibitor prey prey Q8IVG9:p.Ser14Gly 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 S G Tue Jun 30 17:26:15 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Ser14Gly' chemical synthesis Chemical synthesis (Chemical synthesis) 39 unspecified role unspecified role bait bait chemical synthesis Chemical synthesis (Chemical synthesis) direct interaction direct interaction Fig. 3E, 3F app-app-120 6 8 unspecified role unspecified role neutral component neutral component chemical synthesis Chemical synthesis (Chemical synthesis) 8 unspecified role unspecified role neutral component neutral component chemical synthesis Chemical synthesis (Chemical synthesis) direct interaction direct interaction Fig. 5 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 44 46 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