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/ http://www.ebi.ac.uk/ chen-2006a-2 TMP21 is a presenilin complex component that modulates gamma-secretase but not epsilon-secretase activity. human-sh_sy5y Homo sapiens SH-SY5Y cell line sh_sy5y Human neuroblastoma cells anti bait coip anti bait coimmunoprecipitation anti bait coip western blot western blot Immuno blot Immuno blot Chen F., Hasegawa H., Schmitt-Ulms G., Kawarai T., Bohm C., Katayama T., Gu Y., Sanjo N., Glista M., Rogaeva E., Wakutani Y., Pardossi-Piquard R., Ruan X., Tandon A., Checler F., Marambaud P., Hansen K., Westaway D., St George-Hyslop P., Fraser P. p.hyslop@utoronto.ca Nature (0028-0836) 2006 Synapse - Interactions of proteins with an established role in the presynapse. Apoptosis - Interactions involving proteins with a function related to apoptosis BioCreative - Critical Assessment of Information Extraction systems in Biology PS1 complexes were immunoprecipitated from CHAPSO-solubilised membranes of mouse blastocyst-derived cells and components were identified by mass spectrometry. Only protein-protein interactions imex curation chen-2006a-3 TMP21 is a presenilin complex component that modulates gamma-secretase but not epsilon-secretase activity. mouse-brain Mus musculus brain brain Brain [cerebrum] anti bait coip anti bait coimmunoprecipitation anti bait coip western blot western blot Immuno blot Immuno blot Chen F., Hasegawa H., Schmitt-Ulms G., Kawarai T., Bohm C., Katayama T., Gu Y., Sanjo N., Glista M., Rogaeva E., Wakutani Y., Pardossi-Piquard R., Ruan X., Tandon A., Checler F., Marambaud P., Hansen K., Westaway D., St George-Hyslop P., Fraser P. p.hyslop@utoronto.ca Nature (0028-0836) 2006 Synapse - Interactions of proteins with an established role in the presynapse. Apoptosis - Interactions involving proteins with a function related to apoptosis BioCreative - Critical Assessment of Information Extraction systems in Biology PS1 complexes were immunoprecipitated from CHAPSO-solubilised membranes of mouse blastocyst-derived cells and components were identified by mass spectrometry. Only protein-protein interactions imex curation chen-2006a-4 TMP21 is a presenilin complex component that modulates gamma-secretase but not epsilon-secretase activity. 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. anti bait coip anti bait coimmunoprecipitation anti bait coip anti tag western anti tag western blot anti tag western Chen F., Hasegawa H., Schmitt-Ulms G., Kawarai T., Bohm C., Katayama T., Gu Y., Sanjo N., Glista M., Rogaeva E., Wakutani Y., Pardossi-Piquard R., Ruan X., Tandon A., Checler F., Marambaud P., Hansen K., Westaway D., St George-Hyslop P., Fraser P. p.hyslop@utoronto.ca Nature (0028-0836) 2006 Synapse - Interactions of proteins with an established role in the presynapse. Apoptosis - Interactions involving proteins with a function related to apoptosis BioCreative - Critical Assessment of Information Extraction systems in Biology PS1 complexes were immunoprecipitated from CHAPSO-solubilised membranes of mouse blastocyst-derived cells and components were identified by mass spectrometry. Only protein-protein interactions imex curation chen-2006a-1 TMP21 is a presenilin complex component that modulates gamma-secretase but not epsilon-secretase activity. 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. anti bait coip anti bait coimmunoprecipitation anti bait coip western blot western blot Immuno blot Immuno blot Chen F., Hasegawa H., Schmitt-Ulms G., Kawarai T., Bohm C., Katayama T., Gu Y., Sanjo N., Glista M., Rogaeva E., Wakutani Y., Pardossi-Piquard R., Ruan X., Tandon A., Checler F., Marambaud P., Hansen K., Westaway D., St George-Hyslop P., Fraser P. Synapse - Interactions of proteins with an established role in the presynapse. PS1 complexes were immunoprecipitated from CHAPSO-solubilised membranes of mouse blastocyst-derived cells and components were identified by mass spectrometry. p.hyslop@utoronto.ca Nature (0028-0836) 2006 Only protein-protein interactions imex curation Apoptosis - Interactions involving proteins with a function related to apoptosis BioCreative - Critical Assessment of Information Extraction systems in Biology chen-2006a-7 TMP21 is a presenilin complex component that modulates gamma-secretase but not epsilon-secretase activity. mouse-blastocyst Mus musculus blastocyst blastocyst blastocyst anti bait coip anti bait coimmunoprecipitation anti bait coip ms participant Identification by mass spectrometry ms participant Chen F., Hasegawa H., Schmitt-Ulms G., Kawarai T., Bohm C., Katayama T., Gu Y., Sanjo N., Glista M., Rogaeva E., Wakutani Y., Pardossi-Piquard R., Ruan X., Tandon A., Checler F., Marambaud P., Hansen K., Westaway D., St George-Hyslop P., Fraser P. Synapse - Interactions of proteins with an established role in the presynapse. PS1 complexes were immunoprecipitated from CHAPSO-solubilised membranes of mouse blastocyst-derived cells and components were identified by mass spectrometry. p.hyslop@utoronto.ca Nature (0028-0836) 2006 Only protein-protein interactions imex curation Apoptosis - Interactions involving proteins with a function related to apoptosis BioCreative - Critical Assessment of Information Extraction systems in Biology chen-2006a-5 TMP21 is a presenilin complex component that modulates gamma-secretase but not epsilon-secretase activity. 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. cosedimentation cosedimentation western blot western blot Immuno blot Immuno blot Chen F., Hasegawa H., Schmitt-Ulms G., Kawarai T., Bohm C., Katayama T., Gu Y., Sanjo N., Glista M., Rogaeva E., Wakutani Y., Pardossi-Piquard R., Ruan X., Tandon A., Checler F., Marambaud P., Hansen K., Westaway D., St George-Hyslop P., Fraser P. 1 ml of total protein extracts was applied to the top of an 11.0-ml 10�40% (w/v) linear glycerol gradient containing 25 mM HEPES, pH 7.2, 150 mM NaCl, and 0.5% CHAPSO. Gradients were centrifuged for 15 hours at 35,000 rpm and 4 �C using a Beckman SW41 rotor and were collected into 1.0-ml fractions from the top of the centrifugation tube. p.hyslop@utoronto.ca Nature (0028-0836) 2006 Synapse - Interactions of proteins with an established role in the presynapse. Apoptosis - Interactions involving proteins with a function related to apoptosis BioCreative - Critical Assessment of Information Extraction systems in Biology PS1 complexes were immunoprecipitated from CHAPSO-solubilised membranes of mouse blastocyst-derived cells and components were identified by mass spectrometry. Only protein-protein interactions imex curation chen-2006a-6 TMP21 is a presenilin complex component that modulates gamma-secretase but not epsilon-secretase activity. 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. bn-page blue native page bn-page predetermined predetermined participant predetermined Chen F., Hasegawa H., Schmitt-Ulms G., Kawarai T., Bohm C., Katayama T., Gu Y., Sanjo N., Glista M., Rogaeva E., Wakutani Y., Pardossi-Piquard R., Ruan X., Tandon A., Checler F., Marambaud P., Hansen K., Westaway D., St George-Hyslop P., Fraser P. The proteins in CHAPSO-solubilized membrane fractions were separated on a 5-13% Blue Native polyacrylamide gel, followed by a second dimension on a NuPAGE BisTris 4�12% precast 2-D gel (Invitrogen) for SDS-PAGE. p.hyslop@utoronto.ca Nature (0028-0836) 2006 Synapse - Interactions of proteins with an established role in the presynapse. Apoptosis - Interactions involving proteins with a function related to apoptosis BioCreative - Critical Assessment of Information Extraction systems in Biology PS1 complexes were immunoprecipitated from CHAPSO-solubilised membranes of mouse blastocyst-derived cells and components were identified by mass spectrometry. Only protein-protein interactions imex curation psn1_human Presenilin-1 PSEN1 AD3 PS1 PSNL1 Protein S182 protein protein human Homo sapiens Human MTELPAPLSYFQNAQMSEDNHLSNTVRSQNDNRERQEHNDRRSLGHPEPLSNGRPQGNSRQVVEQDEEEDEELTLKYGAKHVIMLFVPVTLCMVVVVATIKSVSFYTRKDGQLIYTPFTEDTETVGQRALHSILNAAIMISVIVVMTILLVVLYKYRCYKVIHAWLIISSLLLLFFFSFIYLGEVFKTYNVAVDYITVALLIWNFGVVGMISIHWKGPLRLQQAYLIMISALMALVFIKYLPEWTAWLILAVISVYDLVAVLCPKGPLRMLVETAQERNETLFPALIYSSTMVWLVNMAEGDPEAQRRVSKNSKYNAESTERESQDTVAENDDGGFSEEWEAQRDSHLGPHRSTPESRAAVQELSSSILAGEDPEERGVKLGLGDFIFYSVLVGKASATASGDWNTTIACFVAILIGLCLTLLLLAIFKKALPALPISITFGLVFYFATDYLVQPFMDQLAFHQFYI tmeda_human Transmembrane emp24 domain-containing protein 10 21 kDa transmembrane-trafficking protein Transmembrane protein Tmp21 Tmp-21-I p24delta S31III125 TMED10 TMP21 p23 p24 family protein delta-1 S31I125 protein protein human Homo sapiens Human MSGLSGPPARRGPFPLALLLLFLLGPRLVLAISFHLPINSRKCLREEIHKDLLVTGAYEISDQSGGAGGLRSHLKITDSAGHILYSKEDATKGKFAFTTEDYDMFEVCFESKGTGRIPDQLVILDMKHGVEAKNYEEIAKVEKLKPLEVELRRLEDLSESIVNDFAYMKKREEEMRDTNESTNTRVLYFSIFSMFCLIGLATWQVFYLRRFFKAKKLIE nica_human Nicastrin NCSTN KIAA0253 UNQ1874/PRO4317 protein protein human Homo sapiens Human MATAGGGSGADPGSRGLLRLLSFCVLLAGLCRGNSVERKIYIPLNKTAPCVRLLNATHQIGCQSSISGDTGVIHVVEKEEDLQWVLTDGPNPPYMVLLESKHFTRDLMEKLKGRTSRIAGLAVSLTKPSPASGFSPSVQCPNDGFGVYSNSYGPEFAHCREIQWNSLGNGLAYEDFSFPIFLLEDENETKVIKQCYQDHNLSQNGSAPTFPLCAMQLFSHMHAVISTATCMRRSSIQSTFSINPEIVCDPLSDYNVWSMLKPINTTGTLKPDDRVVVAATRLDSRSFFWNVAPGAESAVASFVTQLAAAEALQKAPDVTTLPRNVMFVFFQGETFDYIGSSRMVYDMEKGKFPVQLENVDSFVELGQVALRTSLELWMHTDPVSQKNESVRNQVEDLLATLEKSGAGVPAVILRRPNQSQPLPPSSLQRFLRARNISGVVLADHSGAFHNKYYQSIYDTAENINVSYPEWLSPEEDLNFVTDTAKALADVATVLGRALYELAGGTNFSDTVQADPQTVTRLLYGFLIKANNSWFQSILRQDLRSYLGDGPLQHYIAVSSPTNTTYVVQYALANLTGTVVNLTREQCQDPSKVPSENKDLYEYSWVQGPLHSNETDRLPRCVRSTARLARALSPAFELSQWSSTEYSTWTESRWKDIRARIFLIASKELELITLTVGFGILIFSLIVTYCINAKADVLFIAPREPGAVSY pen2_human Gamma-secretase subunit PEN-2 Presenilin enhancer protein 2 PSENEN PEN2 MDS033 protein protein human Homo sapiens Human MNLERVSNEEKLNLCRKYYLGGFAFLPFLWLVNIFWFFREAFLVPAYTEQSQIKGYVWRSAVGFLFWVIVLTSWITIFQIYRPRWGALGDYLSFTIPLGTP psn1_mouse Presenilin-1 Protein S182 Psen1 Ad3h Psnl1 protein protein mouse Mus musculus Mouse MTEIPAPLSYFQNAQMSEDSHSSSAIRSQNDSQERQQQHDRQRLDNPEPISNGRPQSNSRQVVEQDEEEDEELTLKYGAKHVIMLFVPVTLCMVVVVATIKSVSFYTRKDGQLIYTPFTEDTETVGQRALHSILNAAIMISVIVIMTILLVVLYKYRCYKVIHAWLIISSLLLLFFFSFIYLGEVFKTYNVAVDYVTVALLIWNFGVVGMIAIHWKGPLRLQQAYLIMISALMALVFIKYLPEWTAWLILAVISVYDLVAVLCPKGPLRMLVETAQERNETLFPALIYSSTMVWLVNMAEGDPEAQRRVPKNPKYNTQRAERETQDSGSGNDDGGFSEEWEAQRDSHLGPHRSTPESRAAVQELSGSILTSEDPEERGVKLGLGDFIFYSVLVGKASATASGDWNTTIACFVAILIGLCLTLLLLAIFKKALPALPISITFGLVFYFATDYLVQPFMDQLAFHQFYI tmed2_mouse Transmembrane emp24 domain-containing protein 2 Sid 394 Tmed2 Rnp24 Sid394 Membrane protein p24A p24 family protein beta-1 COPI-coated vesicle membrane protein p24 protein protein mouse Mus musculus Mouse MVTLAELLALLAALLATASGYFVSIDAHAEECFFERVTSGTKMGLIFEVAEGGFLDIDVEITGPDNKGIYKGDRESSGKYTFAAHMDGTYKFCFSNRMSTMTPKIVMFTIDIGEAPKGQDMETEAHQNKLEEMINELAVAMTAVKHEQEYMEVRERIHRAINDNTNSRVVLWSFFEALVLVAMTLGQIYYLKRFFEVRRVV nica_mouse Nicastrin Ncstn protein protein mouse Mus musculus Mouse MATTRGGSGPDPGSRGLLLLSFSVVLAGLCGGNSVERKIYIPLNKTAPCVRLLNATHQIGCQSSISGDTGVIHVVEKEEDLKWVLTDGPNPPYMVLLEGKLFTRDVMEKLKGTTSRIAGLAVTLAKPNSTSSFSPSVQCPNDGFGIYSNSYGPEFAHCKKTLWNELGNGLAYEDFSFPIFLLEDENETKVIKQCYQDHNLGQNGSAPSFPLCAMQLFSHMHAVISTATCMRRSFIQSTFSINPEIVCDPLSDYNVWSMLKPINTSVGLEPDVRVVVAATRLDSRSFFWNVAPGAESAVASFVTQLAAAEALHKAPDVTTLSRNVMFVFFQGETFDYIGSSRMVYDMENGKFPVRLENIDSFVELGQVALRTSLDLWMHTDPMSQKNESVKNQVEDLLATLEKSGAGVPEVVLRRLAQSQALPPSSLQRFLRARNISGVVLADHSGSFHNRYYQSIYDTAENINVTYPEWQSPEEDLNFVTDTAKALANVATVLARALYELAGGTNFSSSIQADPQTVTRLLYGFLVRANNSWFQSILKHDLRSYLDDRPLQHYIAVSSPTNTTYVVQYALANLTGKATNLTREQCQDPSKVPNESKDLYEYSWVQGPWNSNRTERLPQCVRSTVRLARALSPAFELSQWSSTEYSTWAESRWKDIQARIFLIASKELEFITLIVGFSTLVFSLIVTYCINAKADVLFVAPREPGAVSY pen2_mouse Gamma-secretase subunit PEN-2 Presenilin enhancer protein 2 Psenen Pen2 protein protein mouse Mus musculus Mouse MNLERVSNEEKLNLCRKYYLGGFAFLPFLWLVNIFWFFREAFLAPAYTEQSQIKGYVWRSAVGFLFWVIILATWITIFQIYRPRWGALGDYLSFTIPLGTP tmed2_human Transmembrane emp24 domain-containing protein 2 TMED2 RNP24 Membrane protein p24A p24 family protein beta-1 p24 protein protein human Homo sapiens Human MVTLAELLVLLAALLATVSGYFVSIDAHAEECFFERVTSGTKMGLIFEVAEGGFLDIDVEITGPDNKGIYKGDRESSGKYTFAAHMDGTYKFCFSNRMSTMTPKIVMFTIDIGEAPKGQDMETEAHQNKLEEMINELAVAMTAVKHEQEYMEVRERIHRAINDNTNSRVVLWSFFEALVLVAMTLGQIYYLKRFFEVRRVV tmed10-psen1-1 507321 N/A 507328 unspecified role unspecified role bait bait N/A 507329 unspecified role unspecified role prey prey physical association physical association false false false Supp. Fig. 1 A tmed10-ncstn 507321 N/A 507329 unspecified role unspecified role prey prey N/A 507330 unspecified role unspecified role bait bait physical association physical association false false false Supp. Fig. 1 A tmed10-psenen 507321 N/A 507331 unspecified role unspecified role bait bait N/A 507329 unspecified role unspecified role prey prey physical association physical association false false false Supp. Fig. 1 A tmed2-psen1 507322 N/A 507332 unspecified role unspecified role bait bait N/A 507333 unspecified role unspecified role prey prey physical association physical association false false false Supp. Fig. 1 A tmed2-ncstn 507322 N/A 507333 unspecified role unspecified role prey prey N/A 507334 unspecified role unspecified role bait bait physical association physical association false false false Supp. Fig. 1 A tmed2-psenen 507322 N/A 507333 unspecified role unspecified role prey prey N/A 507335 unspecified role unspecified role bait bait physical association physical association false false false Supp. Fig. 1 A tmed10-psen1-3 507323 N/A 507328 unspecified role unspecified role bait bait N/A 507329 unspecified role unspecified role prey prey c-terminal flag tag flag tag FLAG-tagged FLAG DYKDDDDKV epitope tag DYKDDDDKV epitope tag FLAG FLAG-tagged c-term range C-terminal range c-term range c-term range C-terminal range c-term range false physical association physical association false false false Supp. Fig. 1 A It is not clear what the species of the flag-tagged TMP21 is, but it is assumed it is human. tmed10-ncstn-2 507323 N/A 507330 unspecified role unspecified role bait bait N/A 507329 unspecified role unspecified role prey prey c-terminal flag tag flag tag FLAG-tagged FLAG DYKDDDDKV epitope tag DYKDDDDKV epitope tag FLAG FLAG-tagged c-term range C-terminal range c-term range c-term range C-terminal range c-term range false physical association physical association false false false Supp. Fig. 1 A It is not clear what the species of the flag-tagged TMP21 is, but it is assumed it is human. tmed10-psenen-2 507323 N/A 507331 unspecified role unspecified role bait bait N/A 507329 unspecified role unspecified role prey prey c-terminal flag tag flag tag FLAG-tagged FLAG DYKDDDDKV epitope tag DYKDDDDKV epitope tag FLAG FLAG-tagged c-term range C-terminal range c-term range c-term range C-terminal range c-term range false physical association physical association false false false Supp. Fig. 1 A It is not clear what the species of the flag-tagged TMP21 is, but it is assumed it is human. tmed10-psen1 507324 N/A 507329 unspecified role unspecified role bait bait N/A 507331 unspecified role unspecified role prey prey N/A 507336 unspecified role unspecified role prey prey N/A 507330 unspecified role unspecified role prey prey N/A 507328 unspecified role unspecified role prey prey association association false false false 1 A TMP21 also coprecipitates with a APH-1 but the authors do not distinguish between APH-1 alpha (Q96BI3) and APH-1 beta (Q8WW43). TMP21 coprecipitates with p24a in this experimet but whereas the other proteins coprecipitated are all part of the same complex, p24a is not. Note there are separate bands for mature nicastrin and immature nicastrin. It is not clear but it seems these interactions take place in HEK-293 cells. tmed10-tmed2 507324 N/A 507329 unspecified role unspecified role bait bait N/A 507336 unspecified role unspecified role prey prey physical association physical association false false false 1 B It is not clear but it seems this interaction is in HEK-293 cells. psen1-ncstn 507325 N/A 507332 unspecified role unspecified role bait bait N/A 507334 unspecified role unspecified role prey prey N/A 507335 unspecified role unspecified role prey prey association association false false false Note APH-1 also cosediments with these proteins but the authors do not distighish between APH-1 alpha and APH-1 beta. The complex was found in wild-type cells and not in PS1-PS2 double knockout cells. tmed10-psen1-4 507326 N/A 507330 unspecified role unspecified role neutral component neutral component N/A 507329 unspecified role unspecified role neutral component neutral component N/A 507331 unspecified role unspecified role neutral component neutral component N/A 507336 unspecified role unspecified role neutral component neutral component N/A 507328 unspecified role unspecified role neutral component neutral component physical association physical association false false false Supp. Fig. 1 B Note APH-1 also cosediments with these proteins but the authors do not distighish between APH-1 alpha and APH-1 beta. tmed10-psen1-5 507327 N/A 507336 unspecified role unspecified role neutral component neutral component N/A 507331 unspecified role unspecified role neutral component neutral component N/A 507329 unspecified role unspecified role neutral component neutral component N/A 507330 unspecified role unspecified role neutral component neutral component N/A 507328 unspecified role unspecified role neutral component neutral component physical association physical association false false false Supp. Fig. 1 C Note APH-1 also comigrates with these proteins but the authors do not distighish between APH-1 alpha and APH-1 beta. In both PS1/PS2 double knockout cells and in pen-2 knock-down cells, TMP21 is destabilized from the ~660 kDa complex (<5% of signal intensity), and instead, TMP21 is predominantly localized with the ~150 kDa nicastrin:aph-1 complex and in a 30 kDa complex.