GPMDB0025372OtherHosp F, et al.InstrumentNot AvailableNot availableHomo_sapiens_viruses, Human_femalematthias.selbach@mdc-berlin.de25959826http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32320018160http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32320018120http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32320018142http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32320018121http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32320018143http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32320018140http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32320018141http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32320018119http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32320018157http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32320018135http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32320018158http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32320018136http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32320018133http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32320018155http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32320018134http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32320018156http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32320018139http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32320018137http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32320018159http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32320018138http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32320018150http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32320018153http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32320018131http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32320018154http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32320018151http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32320018130http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32320018152http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32320018124http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32320018146http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32320018125http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32320018147http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32320018144http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32320018122http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32320018123http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32320018145http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32320018128http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32320018129http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32320018126http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32320018148http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32320018149http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32320018127Max Delbrueck Center for Molecular Medicine, et al.Not availableGPMDBSeveral proteins have been linked to neurodegenerative disorders (NDDs), but their molecular function is not completely understood. Here, we used quantitative interaction proteomics to identify binding partners of Amyloid beta precursor protein (APP) and Presenilin-1 (PSEN1) for Alzheimer's disease (AD), Huntingtin (HTT) for Huntington's disease, Parkin (PARK2) for Parkinson's disease, and Ataxin-1 (ATXN1) for spinocerebellar ataxia type 1. Our network reveals common signatures of protein degradation and misfolding and recapitulates known biology. Toxicity modifier screens and comparison to genome-wide association studies show that interaction partners are significantly linked to disease phenotypes in vivo. Direct comparison of wild-type proteins and disease-associated variants identified binders involved in pathogenesis, highlighting the value of differential interactome mapping. Finally, we show that the mitochondrial protein LRPPRC interacts preferentially with an early-onset AD variant of APP. This interaction appears to induce mitochondrial dysfunction, which is an early phenotype of AD.Quantitative interaction proteomics of neurodegenerative disease proteins.Hosp Fabian F,Vossfeldt Hannes H,Heinig Matthias M,Vasiljevic Djordje D,Arumughan Anup A,Wyler Emanuel E,Genetic and Environmental Risk for Alzheimer’s Disease GERAD1 Consortium,Landthaler Markus M,Hubner Norbert N,Wanker Erich E EE,Lannfelt Lars L,Ingelsson Martin M,Lalowski Maciej M,Voigt Aaron A,Selbach Matthias M,Hosp Fabian F,Vossfeldt Hannes H,Heinig Matthias M,Vasiljevic Djordje D,Arumughan Anup A,Wyler Emanuel E,Landthaler Markus M,Hubner Norbert N,Wanker Erich E EE,Lannfelt Lars L,Ingelsson Martin M,Lalowski Maciej M,Voigt Aaron A,Selbach Matthias M,Hosp Fabian F, Vossfeldt Hannes H, Heinig Matthias M, Vasiljevic Djordje D, Arumughan Anup A, Wyler Emanuel E, Landthaler Markus M, Hubner Norbert N, Wanker Erich E EE, Lannfelt Lars L, Ingelsson Martin M, Lalowski Maciej M, Voigt Aaron A, Selbach Matthias MProtein Gene Products, Neurodegenerative Diseases, Gene., Gene Proteins, polypeptide, count in organism, count, Protein, Gene Products, Proteins, number, quantitative, proteins, "Neurodegenerative disease" EXACT [NCI2004_11_17:C4802], presence, central nervous system degenerative disorder, presence or absence in organismAmyloid intracellular domain 57, APP, Amyloid intracellular domain 59, ABETA, Atxn1, C85907, Spinocerebellar Ataxia Type 1 Protein, Rab interactor activity, Ad3h, P3(40), PARK2, number, Ataxin 1, A4, Sert, Gm10786, Gene, CTFgamma, betaApp, Amyloid intracellular domain 50, presence, AI323329, Abpp, Atxn-1 Protein, AID(59), AAA, Cvap, Prkn, AG, Beta-amyloid protein 42, cerebral vascular amyloid peptide, APP-C57, APP-C59, Beta-amyloid protein 40, SERT1, Park, Gene Products, alzheimer disease amyloid protein, 5-HTT, protease nexin-II, SERT, ENSMUSG00000074917, amyloidogenic glycoprotein, AID(50), S182 Protein, human disease, Ag, SCA1, Ataxin 1 Protein, Sca1, PreA4, cell, ligand, Rep-3, 2900016G23Rik, ATX1, Atx1, S-APP-beta, proteins, Gamma-CTF(59), Substance, LPRS2, Amyloid, Alzheimer disease amyloid A4 protein homolog, N-APP, AID(57), Gamma-secretase C-terminal fragment 50, OCD1, Atxn-1, Gamma-secretase C-terminal fragment 57, 5HTT, Gamma-secretase C-terminal fragment 59, AD1, Rep3, AD3, Abeta, Homo sapiens disease, APPI, molecular function, C80, REP, C83, Ataxin-1, data, SCA1 Protein, Amyloidogenic glycoprotein, AICD-50, rEP3b, S-APP-alpha, rEP3a, E030013M08Rik, PS1, Proteins, Ataxin-1 Protein, D13Em1, Atxn1 Protein, Gamma-CTF(57), hSERT, Cell, S182, Gamma-CTF(50), polypeptide, Amyloid Fibrils, C99, APP-C99, Rab escort protein activity, count in organism, 5-HTTLPR, count, Adap, IT15, Protein, Diseases, AICD-57, AICD-59, Cerebral vascular amyloid peptide, PRKN, PS-1, P3(42), PN-II, D6S504E., Amyloid Substance, HTT, Htt, Soluble APP-beta, alzheimer disease amyloid A4 protein homolog, PDJ, Alzheimer disease amyloid protein, Protease nexin-II, AR-JP, Protein Gene Products, C31, Gene Proteins, Fibrils, FAD, EP3, Atxn 1 Protein, Soluble APP-alpha, Beta-APP42, PN2, Presenilin 1, quantitative, Beta-APP40, D6S504E, HD, CVAP, presence or absence in organism, ABPPProtein Gene Products, Neurodegenerative Diseases, Gene., Gene Proteins, polypeptide, count in organism, count, Protein, Gene Products, Proteins, number, quantitative, proteins, "Neurodegenerative disease" EXACT [NCI2004_11_17:C4802], presence, central nervous system degenerative disorder, presence or absence in organismAmyloid intracellular domain 57, APP, Genome-Wide Association, Amyloid intracellular domain 59, ABETA, C85907, Presenile Alzheimer Dementia, Parkinson's disease, ALZHEIMERS DIS, Ad3h, Huntington chorea, Early Onset, Parkinson's disease NOS, Whole Genome Association Study, Ataxin 1, A4, Sert, CTFgamma, protein breakdown, Chronic progressive chorea, HD - Huntington chorea, Amyloid intracellular domain 50, AI323329, IDIOPATHIC PARKINSON DIS, Alzheimer's disease, Abpp, AAA, Cvap, Huntington's chorea (disorder), dysfunctional, AD, unspecified, AG, Huntington's disease pathway, Beta-amyloid protein 42, cerebral vascular amyloid peptide, Beta-amyloid protein 40, SERT1, Park, 5-HTT, SERT, amyloidogenic glycoprotein, AID(50), S182 Protein, protein degradation, Presenile Alzheimer, GWA Study, LATE ONSET ALZHEIMER DIS, human disease, Ag, SCA1, Parkinsons disease, Sca1, Parkinson disease, DAT - Dementia Alzheimer's type, Parkinson's disease (disorder), ATX1, Atx1, proteins, Substance, LPRS2, Amyloid, Genome-Wide Association Studies, Alzheimer disease amyloid A4 protein homolog, N-APP, Gamma-secretase C-terminal fragment 50, Atxn-1, Gamma-secretase C-terminal fragment 57, AD - Alzheimer's disease, 5HTT, Gamma-secretase C-terminal fragment 59, Alzheimer Type Dementia, HUNTINGTON'S CHOREA, AD1, AD3, Abeta, Homo sapiens disease, ALZHEIMER DIS EARLY ONSET, Parkinson syndrome, APPI, Presenile, associated, C80, Alzheimers disease, C83, Huntington's, Parkinson's syndrome, Lsfc, Ataxin-1, Senile, Parkinsons, SCA1 Protein, sporadic Alzheimer's disease, AICD-50, S-APP-alpha, Acute Confusional Senile Dementia, PS1, PARKINSON DIS, Mitochondrial Protein, PARKINSON DIS IDIOPATHIC, Atxn1 Protein, Gamma-CTF(57), Genome-Wide, Alzheimer's Dementia, partial functionality, Alzheimer Type, Amyloid Fibrils, C99, Juvenile-Onset, Idiopathic Parkinson's Disease, LSFC, count, Genome Wide Association Study, Lewy Body Parkinson Disease, IT15, LATE ONSET HUNTINGTON DIS, Lrp130, Diseases, AICD-57, margin of safety, precocious, NOS, Whole Genome Association Analysis, Gp130, AICD-59, Dementia, Cerebral vascular amyloid peptide, PRKN, PS-1, Mitochondrial, Amyloid Substance, Alzheimers, GP130, HTT, Htt, Alzheimer, HUNTINGTON DIS, Dementias, alzheimer disease amyloid A4 protein homolog, PDJ, Alzheimer disease amyloid protein, lacks function of type, Protease nexin-II, LRP130, early, low functionality, Alzheimer's, C76645, Phenotypes, Lrp157, multicellular organismal protein catabolic process, DMDA, FAD, Senile Dementia, JUVENILE HUNTINGTON DIS, paralysis agitans, PARKINSONS DIS IDIOPATHIC, Atxn 1 Protein, Presenilin 1, Alzheimer's Disease, Association Study, HD, PARKINSONS DIS LEWY BODY, Dementia of the Alzheimer's type, Atxn1, Chronic Progressive Hereditary Chorea (Huntington), advanced, Spinocerebellar Ataxia Type 1 Protein, P3(40), Lewy Body, PARK2, Genome Wide Association Analysis, number, Gm10786, Gene, impaired, betaApp, Focal Onset, presence, TYPE, Atxn-1 Protein, unspecified (disorder), AID(59), DAGA4, ALZHEIMER DIS, Prkn, Huntington disease, GWA Studies, [X]Dementia in Alzheimer's disease, APP-C57, APP-C59, Gene Products, alzheimer disease amyloid protein, Studies, protease nexin-II, HUNTINGTON DIS AKINETIC RIGID VARIANT, ENSMUSG00000074917, Chronic progressive hereditary chorea, MAM, SCG3, Akinetic Rigid Variant, Ataxin 1 Protein, pheromone catabolism, PreA4, ligand, Akinetic Rigid Variant of Huntington Disease, dysfunction, GWA, 2900016G23Rik, S-APP-beta, JUVENILE ONSET HUNTINGTON DIS, Gamma-CTF(59), IDIOPATHIC PARKINSONS DIS, protein catabolism, Idiopathic PD, FOCAL ONSET ALZHEIMERS DIS, Genome Wide Association Scan, Parkinson's, Study, AID(57), OCD1, Idiopathic, Alzheimer Disease, Parkinson Disease, Parkinsonism, PARKINSONS DIS, CLONE-23970, toxic potential, Alzheimer's disease (disorder), molecular function, Alzheimers Dementia, HC - Huntington chorea, Huntington Disease, Alzheimer Senile Dementia, Disease, Primary Parkinsonism, Chorea, Amyloidogenic glycoprotein, E030013M08Rik, Proteins, Phenotypes., Paralysis agitans, Ataxin-1 Protein, Primary, hSERT, S182, Primary Senile Degenerative Dementia, Idiopathic Parkinson Disease, LGMD2C, LEWY BODY PARKINSON DIS, Gamma-CTF(50), [X]Dementia in Alzheimer's disease (disorder), polypeptide, APP-C99, count in organism, 5-HTTLPR, Juvenile Huntington Disease, Parkinson's Disease, Adap, Protein, 3110001K13Rik, P3(42), pheromone catabolic process, PN-II, DMDA1, Huntington, Dementia in Alzheimer's disease, HUNTINGTONS DIS, Alzheimer's Disease Pathway, Huntington's chorea, Soluble APP-beta, Alzheimer Dementia, AR-JP, Genome Wide Association Studies, Lewy Body Parkinson's Disease, Protein Gene Products, C31, Parkinsonian disorder, Gene Proteins, having decreased function, Fibrils, Late Onset, Parkinson's disease NOS (disorder), Huntington's disease, Dementia in Alzheimer's disease (disorder), SCARMD2, Soluble APP-alpha, Association Studies, virulence, Beta-APP42, PN2, quantitative, Beta-APP40, variable, D6S504E, CVAP, presence or absence in organism, ABPP250372http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32320018141dbgap_ncbi~0patentfamilies~0rfam~0merops~0complex-portal~0uniprot~0wormbaseparasite~0embl-covid19~0reactome~0emdb~0wgs_masters~0ebiweb_resources~0opentargets_genetics~0biomodels_all~0ipd-mhc~0ebiweb_teams~0taxonomy~0genome_assembly~0sc-experiments~0ebiweb_people~0enzymeportal_enzymes~0ipd-nhkir~0cellosaurus~0pdbe~0chebi~0patentproteins~0interpro7~0uniref~0chembl~0pdbekb~0gpcrdb~0hgnc~0sc-genes~0rhea~0ebiweb_training~0alphafold~0imgt-hla~0patentnucleotides~0ensemblroot~0eva_studies~0non-coding~0europepmc~0pubmed~1identifiers_registry~0pdbechem~0hpa-covid19~0eva-variants-covid19~0biosamples~0gwas_catalog~0biotools~0tls_masters~0mesh~0coding~0sra~0opentargets~0efo~0embl-pathogen~0intact~367project~0pride~1human_diseases~0geo_datasets~0embl~0treefam~0uniparc~0ols~0dgva~0intenz~0go~0tsa_masters~0biosamples-covid19~0ebiweb_corporate~0omim~0lrg~0earlycause-molecular-sequences~0ipd-kir~0empiar~0rnacentral~0orcid_data_claims~0gpmdb~2lineage-covid19~0metagenomics~0pfam~0pride archive~1varsite~00Resource Reanalysis0.00.00.00771128932757557050.01.0falseQuantitative interaction proteomics of neurodegenerative disease proteins.Data from ProteomeXchange, PXD ID: PXD001942. File: 20130829_Orbi6_FaHo_SA_NN_SWEvsEV_Rep3_01.mzml. Published as part of Cell Rep. 2015 May 19;11(7):1134-46 . From the Abstract: {{i}} Several proteins have been linked to neurodegenerative disorders (NDDs), but their molecular function is not completely understood. Here, we used quantitative interaction proteomics to identify binding partners of Amyloid beta precursor protein (APP) and Presenilin-1 (PSEN1) for Alzheimer"s disease (AD), Huntingtin (HTT) for Huntington"s disease, Parkin (PARK2) for Parkinson"s disease, and Ataxin-1 (ATXN1) for spinocerebellar ataxia type 1 ... {{/i}}2015-09-23GPM3232001814125959826PXD001942PXD001942