IntAct European Bioinformatics Institute IntAct intact http://www.ebi.ac.uk/ http://www.ebi.ac.uk/intact/query/${ac} EBI-[0-9]+|IA:[0-9]+ INTerAction database (IntAct) provides an open source database and toolkit for the storage, presentation and analysis of molecular interactions. http://www.ebi.ac.uk/intact European Bioinformatics Institute; Wellcome Trust Genome Campus; Hinxton, Cambridge; CB10 1SD; United Kingdom http://www.ebi.ac.uk/intact/ Altered neuregulin 1-erbB4 signaling contributes to NMDA receptor hypofunction in schizophrenia. Altered neuregulin 1-erbB4 signaling contributes to NMDA receptor hypofunction in schizophrenia. Nat. Med. (1078-8956) 2006 imex curation Hahn CG., Wang HY., Cho DS., Talbot K., Gur RE., Berrettini WH., Bakshi K., Kamins J., Borgmann-Winter KE., Siegel SJ., Gallop RJ., Arnold SE. BioCreative - Critical Assessment of Information Extraction systems in Biology Synapse - Interactions of proteins with an established role in the presynapse. Prefrontal cortex tissue slices from schizophrenic and control patients were used in this assay. Slices of tissue were treated or untreated with neuregulin1 (NGR1)(200ng per ml) for 30 minutes before lysis and assay. hahnc@mail.med.upenn.edu 24-JAN-2007: Contacted by JYOTI. Only protein-protein interactions human-brain-cortex Homo sapiens brain cortex brain_cortex Brain cortex [Cerebral cortex; Cerebrum cortex; Cortex; Pallium] anti bait coip anti bait coimmunoprecipitation anti bait coip western blot western blot Immuno blot Immuno blot Hahn CG., Wang HY., Cho DS., Talbot K., Gur RE., Berrettini WH., Bakshi K., Kamins J., Borgmann-Winter KE., Siegel SJ., Gallop RJ., Arnold SE. Prefrontal cortex tissue slices from schizophrenic and control patients were used in this assay. Slices of tissue were treated or untreated with neuregulin1 (NGR1)(200ng per ml) for 30 minutes before lysis and assay. hahn@mail.med.upenn.edu hahnc@mail.med.upenn.edu Accepted 2006-SEP-12 by ORCHARD. Nat. Med. (1078-8956) 2006 Altered neuregulin 1-erbB4 signaling contributes to NMDA receptor hypofunction in schizophrenia. Altered neuregulin 1-erbB4 signaling contributes to NMDA receptor hypofunction in schizophrenia. Nat. Med. (1078-8956) 2006 imex curation Hahn CG., Wang HY., Cho DS., Talbot K., Gur RE., Berrettini WH., Bakshi K., Kamins J., Borgmann-Winter KE., Siegel SJ., Gallop RJ., Arnold SE. BioCreative - Critical Assessment of Information Extraction systems in Biology Synapse - Interactions of proteins with an established role in the presynapse. Prefrontal cortex tissue slices from schizophrenic and control patients were used in this assay. Slices of tissue were treated or untreated with neuregulin1 (NGR1)(200ng per ml) for 30 minutes before lysis and assay. hahnc@mail.med.upenn.edu 24-JAN-2007: Contacted by JYOTI. Only protein-protein interactions human-brain-cortex Homo sapiens brain cortex brain_cortex Brain cortex [Cerebral cortex; Cerebrum cortex; Cortex; Pallium] anti bait coip anti bait coimmunoprecipitation anti bait coip western blot western blot Immuno blot Immuno blot Hahn CG., Wang HY., Cho DS., Talbot K., Gur RE., Berrettini WH., Bakshi K., Kamins J., Borgmann-Winter KE., Siegel SJ., Gallop RJ., Arnold SE. As the treatments of PFC slices differed between hahn-2006-1 and this entry it was decided to have a separate entry for this data. Prefrontal cortex tissue slices from schizophrenic and control patients were used in this assay. Slices of tissue were treated or untreated with the following NMDA (100 micro molar)and glycine (1 micro molar)or neuregulin (NGR1) (200ng per ml) or NMDA and glycine and NGR1 (concentratons as before) before lysis and assay. hahn@mail.med.upenn.edu hahnc@mail.med.upenn.edu Accepted 2006-SEP-15 by ORCHARD. Nat. Med. (1078-8956) 2006 plcb4_human 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 Phosphoinositide phospholipase C-beta-4 Phospholipase C-beta-4 PLCB4 protein protein human Homo sapiens Human MAKPYEFNWQKEVPSFLQEGAVFDRYEEESFVFEPNCLFKVDEFGFFLTWRSEGKEGQVLECSLINSIRSGAIPKDPKILAALEAVGKSENDLEGRIVCVCSGTDLVNISFTYMVAENPEVTKQWVEGLRSIIHNFRANNVSPMTCLKKHWMKLAFMTNTNGKIPVRSITRTFASGKTEKVIFQALKELGLPSGKNDEIEPTAFSYEKFYELTQKICPRTDIEDLFKKINGDKTDYLTVDQLVSFLNEHQRDPRLNEILFPFYDAKRAMQIIEMYEPDEDLKKKGLISSDGFCRYLMSDENAPVFLDRLELYQEMDHPLAHYFISSSHNTYLTGRQFGGKSSVEMYRQVLLAGCRCVELDCWDGKGEDQEPIITHGKAMCTDILFKDVIQAIKETAFVTSEYPVILSFENHCSKYQQYKMSKYCEDLFGDLLLKQALESHPLEPGRALPSPNDLKRKILIKNKRLKPEVEKKQLEALRSMMEAGESASPANILEDDNEEEIESADQEEEAHPEFKFGNELSADDLGHKEAVANSVKKGLVTVEDEQAWMASYKYVGATTNIHPYLSTMINYAQPVKFQGFHVAEERNIHYNMSSFNESVGLGYLKTHAIEFVNYNKRQMSRIYPKGGRVDSSNYMPQIFWNAGCQMVSLNYQTPDLAMQLNQGKFEYNGSCGYLLKPDFMRRPDRTFDPFSETPVDGVIAATCSVQVISGQFLSDKKIGTYVEVDMYGLPTDTIRKEFRTRMVMNNGLNPVYNEESFVFRKVILPDLAVLRIAVYDDNNKLIGQRILPLDGLQAGYRHISLRNEGNKPLSLPTIFCNIVLKTYVPDGFGDIVDALSDPKKFLSITEKRADQMRAMGIETSDIADVPSDTSKNDKKGKANTAKANVTPQSSSELRPTTTAALASGVEAKKGIELIPQVRIEDLKQMKAYLKHLKKQQKELNSLKKKHAKEHSTMQKLHCTQVDKIVAQYDKEKSTHEKILEKAMKKKGGSNCLEMKKETEIKIQTLTSDHKSKVKEIVAQHTKEWSEMINTHSAEEQEIRDLHLSQQCELLKKLLINAHEQQTQQLKLSHDRESKEMRAHQAKISMENSKAISQDKSIKNKAERERRVRELNSSNTKKFLEERKRLAMKQSKEMDQLKKVQLEHLEFLEKQNEQAKEMQQMVKLEAEMDRRPATVV DIP protein Q15147 original sequence version: 167 AB2C8EB99EF57357 erbb4_human Receptor tyrosine-protein kinase erbB-4 ERBB4 HER4 p180erbB4 Proto-oncogene-like protein c-ErbB-4 Tyrosine kinase-type cell surface receptor HER4 protein protein human Homo sapiens Human MKPATGLWVWVSLLVAAGTVQPSDSQSVCAGTENKLSSLSDLEQQYRALRKYYENCEVVMGNLEITSIEHNRDLSFLRSVREVTGYVLVALNQFRYLPLENLRIIRGTKLYEDRYALAIFLNYRKDGNFGLQELGLKNLTEILNGGVYVDQNKFLCYADTIHWQDIVRNPWPSNLTLVSTNGSSGCGRCHKSCTGRCWGPTENHCQTLTRTVCAEQCDGRCYGPYVSDCCHRECAGGCSGPKDTDCFACMNFNDSGACVTQCPQTFVYNPTTFQLEHNFNAKYTYGAFCVKKCPHNFVVDSSSCVRACPSSKMEVEENGIKMCKPCTDICPKACDGIGTGSLMSAQTVDSSNIDKFINCTKINGNLIFLVTGIHGDPYNAIEAIDPEKLNVFRTVREITGFLNIQSWPPNMTDFSVFSNLVTIGGRVLYSGLSLLILKQQGITSLQFQSLKEISAGNIYITDNSNLCYYHTINWTTLFSTINQRIVIRDNRKAENCTAEGMVCNHLCSSDGCWGPGPDQCLSCRRFSRGRICIESCNLYDGEFREFENGSICVECDPQCEKMEDGLLTCHGPGPDNCTKCSHFKDGPNCVEKCPDGLQGANSFIFKYADPDRECHPCHPNCTQGCNGPTSHDCIYYPWTGHSTLPQHARTPLIAAGVIGGLFILVIVGLTFAVYVRRKSIKKKRALRRFLETELVEPLTPSGTAPNQAQLRILKETELKRVKVLGSGAFGTVYKGIWVPEGETVKIPVAIKILNETTGPKANVEFMDEALIMASMDHPHLVRLLGVCLSPTIQLVTQLMPHGCLLEYVHEHKDNIGSQLLLNWCVQIAKGMMYLEERRLVHRDLAARNVLVKSPNHVKITDFGLARLLEGDEKEYNADGGKMPIKWMALECIHYRKFTHQSDVWSYGVTIWELMTFGGKPYDGIPTREIPDLLEKGERLPQPPICTIDVYMVMVKCWMIDADSRPKFKELAAEFSRMARDPQRYLVIQGDDRMKLPSPNDSKFFQNLLDEEDLEDMMDAEEYLVPQAFNIPPPIYTSRARIDSNRSEIGHSPPPAYTPMSGNQFVYRDGGFAAEQGVSVPYRAPTSTIPEAPVAQGATAEIFDDSCCNGTLRKPVAPHVQEDSSTQRYSADPTVFAPERSPRGELDEEGYMTPMRDKPKQEYLNPVEENPFVSRRKNGDLQALDNPEYHNASNGPPKAEDEYVNEPLYLNTFANTLGKAEYLKNNILSMPEKAKKAFDNPDYWNHSLPPRSTLQHPDYLQEYSTKYFYKQNGRIRPIVAENPEYLSEFSLKPGTVLPPPPYRHRNTVV DIP protein Q15303 original sequence version: 163 DIP protein Q15303-1 original sequence version: 92 DIP protein Q15303-1 original sequence version: 127 DIP protein Q15303-1 original sequence version: 96 DIP protein Q15303 original sequence version: 96 5E4AE80985D88761 nmdz1_human Glutamate receptor ionotropic, NMDA 1 N-methyl-D-aspartate receptor subunit NR1 GRIN1 NMDAR1 Glutamate [NMDA] receptor subunit zeta-1 protein protein human Homo sapiens Human MSTMRLLTLALLFSCSVARAACDPKIVNIGAVLSTRKHEQMFREAVNQANKRHGSWKIQLNATSVTHKPNAIQMALSVCEDLISSQVYAILVSHPPTPNDHFTPTPVSYTAGFYRIPVLGLTTRMSIYSDKSIHLSFLRTVPPYSHQSSVWFEMMRVYSWNHIILLVSDDHEGRAAQKRLETLLEERESKAEKVLQFDPGTKNVTALLMEAKELEARVIILSASEDDAATVYRAAAMLNMTGSGYVWLVGEREISGNALRYAPDGILGLQLINGKNESAHISDAVGVVAQAVHELLEKENITDPPRGCVGNTNIWKTGPLFKRVLMSSKYADGVTGRVEFNEDGDRKFANYSIMNLQNRKLVQVGIYNGTHVIPNDRKIIWPGGETEKPRGYQMSTRLKIVTIHQEPFVYVKPTLSDGTCKEEFTVNGDPVKKVICTGPNDTSPGSPRHTVPQCCYGFCIDLLIKLARTMNFTYEVHLVADGKFGTQERVNNSNKKEWNGMMGELLSGQADMIVAPLTINNERAQYIEFSKPFKYQGLTILVKKEIPRSTLDSFMQPFQSTLWLLVGLSVHVVAVMLYLLDRFSPFGRFKVNSEEEEEDALTLSSAMWFSWGVLLNSGIGEGAPRSFSARILGMVWAGFAMIIVASYTANLAAFLVLDRPEERITGINDPRLRNPSDKFIYATVKQSSVDIYFRRQVELSTMYRHMEKHNYESAAEAIQAVRDNKLHAFIWDSAVLEFEASQKCDLVTTGELFFRSGFGIGMRKDSPWKQNVSLSILKSHENGFMEDLDKTWVRYQECDSRSNAPATLTFENMAGVFMLVAGGIVAGIFLIFIEIAYKRHKDARRKQMQLAFAAVNVWRKNLQDRKSGRAEPDPKKKATFRAITSTLASSFKRRRSSKDTSTGGGRGALQNQKDTVLPRRAIEREEGQLQLCSRHRES CDF5402769E530AB erbb2_human Receptor tyrosine-protein kinase erbB-2 p185erbB2 MLN19 Proto-oncogene c-ErbB-2 Tyrosine kinase-type cell surface receptor HER2 Proto-oncogene Neu ERBB2 HER2 NEU NGL Metastatic lymph node gene 19 protein protein protein human Homo sapiens Human MELAALCRWGLLLALLPPGAASTQVCTGTDMKLRLPASPETHLDMLRHLYQGCQVVQGNLELTYLPTNASLSFLQDIQEVQGYVLIAHNQVRQVPLQRLRIVRGTQLFEDNYALAVLDNGDPLNNTTPVTGASPGGLRELQLRSLTEILKGGVLIQRNPQLCYQDTILWKDIFHKNNQLALTLIDTNRSRACHPCSPMCKGSRCWGESSEDCQSLTRTVCAGGCARCKGPLPTDCCHEQCAAGCTGPKHSDCLACLHFNHSGICELHCPALVTYNTDTFESMPNPEGRYTFGASCVTACPYNYLSTDVGSCTLVCPLHNQEVTAEDGTQRCEKCSKPCARVCYGLGMEHLREVRAVTSANIQEFAGCKKIFGSLAFLPESFDGDPASNTAPLQPEQLQVFETLEEITGYLYISAWPDSLPDLSVFQNLQVIRGRILHNGAYSLTLQGLGISWLGLRSLRELGSGLALIHHNTHLCFVHTVPWDQLFRNPHQALLHTANRPEDECVGEGLACHQLCARGHCWGPGPTQCVNCSQFLRGQECVEECRVLQGLPREYVNARHCLPCHPECQPQNGSVTCFGPEADQCVACAHYKDPPFCVARCPSGVKPDLSYMPIWKFPDEEGACQPCPINCTHSCVDLDDKGCPAEQRASPLTSIISAVVGILLVVVLGVVFGILIKRRQQKIRKYTMRRLLQETELVEPLTPSGAMPNQAQMRILKETELRKVKVLGSGAFGTVYKGIWIPDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTSTVQLVTQLMPYGCLLDHVRENRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGKVPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSECRPRFRELVSEFSRMARDPQRFVVIQNEDLGPASPLDSTFYRSLLEDDDMGDLVDAEEYLVPQQGFFCPDPAPGAGGMVHHRHRSSSTRSGGGDLTLGLEPSEEEAPRSPLAPSEGAGSDVFDGDLGMGAAKGLQSLPTHDPSPLQRYSEDPTVPLPSETDGYVAPLTCSPQPEYVNQPDVRPQPPSPREGPLPAARPAGATLERPKTLSPGKNGVVKDVFAFGGAVENPEYLTPQGGAAPQPHPPPAFSPAFDNLYYWDQDPPERGAPPSTFKGTPTAENPEYLGLDVPV DIP protein P04626 original sequence version: 198 DIP protein P04626 original sequence version: 122 DIP protein P04626 original sequence version: 206 DIP protein P04626 original sequence version: 195 DIP protein P04626 original sequence version: 150 DIP protein P04626 original sequence version: 179 DIP protein P04626 original sequence version: 146 DIP protein P04626 original sequence version: 147 39E9DFDA04DCF962 dlg4_human Disks large homolog 4 Postsynaptic density protein 95 Synapse-associated protein 90 DLG4 PSD95 protein protein human Homo sapiens Human MDCLCIVTTKKYRYQDEDTPPLEHSPAHLPNQANSPPVIVNTDTLEAPGYELQVNGTEGEMEYEEITLERGNSGLGFSIAGGTDNPHIGDDPSIFITKIIPGGAAAQDGRLRVNDSILFVNEVDVREVTHSAAVEALKEAGSIVRLYVMRRKPPAEKVMEIKLIKGPKGLGFSIAGGVGNQHIPGDNSIYVTKIIEGGAAHKDGRLQIGDKILAVNSVGLEDVMHEDAVAALKNTYDVVYLKVAKPSNAYLSDSYAPPDITTSYSQHLDNEISHSSYLGTDYPTAMTPTSPRRYSPVAKDLLGEEDIPREPRRIVIHRGSTGLGFNIVGGEDGEGIFISFILAGGPADLSGELRKGDQILSVNGVDLRNASHEQAAIALKNAGQTVTIIAQYKPEEYSRFEAKIHDLREQLMNSSLGSGTASLRSNPKRGFYIRALFDYDKTKDCGFLSQALSFRFGDVLHVIDASDEEWWQARRVHSDSETDDIGFIPSKRRVERREWSRLKAKDWGSSSGSQGREDSVLSYETVTQMEVHYARPIIILGPTKDRANDDLLSEFPDKFGSCVPHTTRPKREYEIDGRDYHFVSSREKMEKDIQAHKFIEAGQYNSHLYGTSVQSVREVAEQGKHCILDVSANAVRRLQAAHLHPIAIFIRPRSLENVLEINKRITEEQARKAFDRATKLEQEFTECFSAIVEGDSFEEIYHKVKRVIEDLSGPYIWVPARERL DIP protein P78352 original sequence version: 162 DIP protein P78352 original sequence version: 122 DIP protein P78352-1 original sequence version: 127 DIP protein P78352 original sequence version: 148 7922D3F220F9A101 erbb4-dlg4 1 4 unspecified role unspecified role bait bait 7 unspecified role unspecified role prey prey physical association physical association Figure 3 Association of erbB4 with PSD-95 is enhanced in the PFC of schizophrenic subjects. The authors note that erbB4 protein interaction with PSD-95 protein is enhanced in schizophrenic subjects. erbb4-nmdar1 1 5 unspecified role unspecified role prey prey 4 unspecified role unspecified role bait bait physical association physical association Supplementary Figure 4 Supplementary Figure 5 Association of erbB4 with NMDAR is enhanced in PFCs of SCZ subjects. The authors note that erbB4 protein interaction with NMDAR protein is enhanced in schizophrenic subjects. nmdar1-plcb4 2 5 unspecified role unspecified role bait bait 3 unspecified role unspecified role prey prey physical association physical association Figure 4 NRG1 treatment attenuated the NMDA-induced enhancement of NMDAR2A tyrosine phosphorylation as well as the recruitment of PIPLC-g1 by NMDAR1. The authors note that NMDAR protein and PLCB4 protein interaction was enhanced by NMDA and glycine treatment. However interaction between the proteins was significantly lower in schizophrenic subjects. Even with the relatively small sample size, NRG1 stimulation significantly attenuated PLCB4 recruitment by NMDAR1 in the schizophrenia group (t(9) = 5.64, P less than 0.001). erbb4-erbb2 1 4 unspecified role unspecified role bait bait 6 unspecified role unspecified role prey prey physical association physical association Supplementary Figure 1 These enhancements were accompanied by parallel increases in the activation of ERK and AKT, downstream signaling molecules, as well as in the formation of erbB4 and erbB2 heterodimers