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/ froese-2015-3 in vitro In vitro bn-page blue native page bn-page weight by comassie molecular weight estimation by coomasie staining weight by comassie Froese DS., Kopec J., Fitzpatrick F., Schuller M., McCorvie TJ., Chalk R., Plessl T., Fettelschoss V., Fowler B., Baumgartner MR., Yue WW. Rare diseases - Interactions investigated in the context of Rare genetic disease matthias.baumgartner@kispi.uzh.ch The Journal of biological chemistry 2015 Only protein-protein interactions imex curation imex curation froese-2015-1 in vitro In vitro molecular sieving molecular sieving Gel Filtration Size Exclusion Chromatography Size Exclusion Chromatography Gel Filtration Sizing column weight identificat confirmation by molecular weight weight identificat Froese DS., Kopec J., Fitzpatrick F., Schuller M., McCorvie TJ., Chalk R., Plessl T., Fettelschoss V., Fowler B., Baumgartner MR., Yue WW. Rare diseases - Interactions investigated in the context of Rare genetic disease MMACHC-MMADHC complex was initially purified by affinity chromotography matthias.baumgartner@kispi.uzh.ch The Journal of biological chemistry 2015 Only protein-protein interactions imex curation imex curation froese-2015-2 in vitro In vitro ms of complexes mass spectrometry studies of complexes ms of complexes weight identificat confirmation by molecular weight weight identificat Froese DS., Kopec J., Fitzpatrick F., Schuller M., McCorvie TJ., Chalk R., Plessl T., Fettelschoss V., Fowler B., Baumgartner MR., Yue WW. Rare diseases - Interactions investigated in the context of Rare genetic disease matthias.baumgartner@kispi.uzh.ch The Journal of biological chemistry 2015 Only protein-protein interactions imex curation imex curation froese-2015-4 in vitro In vitro saxs x ray scattering saxs predetermined predetermined participant predetermined Froese DS., Kopec J., Fitzpatrick F., Schuller M., McCorvie TJ., Chalk R., Plessl T., Fettelschoss V., Fowler B., Baumgartner MR., Yue WW. Rare diseases - Interactions investigated in the context of Rare genetic disease matthias.baumgartner@kispi.uzh.ch The Journal of biological chemistry 2015 Only protein-protein interactions imex curation imex curation glutathione glutathione gamma-L-Glutamyl-L-cysteinyl-glycine 5-L-Glutamyl-L-cysteinylglycine Glutathione Glutathione-SH GSH N-(N-gamma-L-Glutamyl-L-cysteinyl)glycine Reduced glutathione L-gamma-glutamyl-L-cysteinylglycine small molecule small molecule chemical synthesis Chemical synthesis (Chemical synthesis) methylcobalamin methylcobalamin CO-METHYLCOBALAMIN MeCbl mecobalamin methylcob(III)alamin Methylcobalamin methylcobalamin Coalpha-[alpha-(5,6-dimethylbenzimidazolyl)]-Cobeta-methylcobamide small molecule small molecule chemical synthesis Chemical synthesis (Chemical synthesis) mmad_human Cobalamin trafficking protein CblD Methylmalonic aciduria and homocystinuria type D protein, mitochondrial HSPC161 My011 MMADHC C2orf25 CL25022 CblD protein protein human Homo sapiens Human MANVLCNRARLVSYLPGFCSLVKRVVNPKAFSTAGSSGSDESHVAAAPPDICSRTVWPDETMGPFGPQDQRFQLPGNIGFDCHLNGTASQKKSLVHKTLPDVLAEPLSSERHEFVMAQYVNEFQGNDAPVEQEINSAETYFESARVECAIQTCPELLRKDFESLFPEVANGKLMILTVTQKTKNDMTVWSEEVEIEREVLLEKFINGAKEICYALRAEGYWADFIDPSSGLAFFGPYTNNTLFETDERYRHLGFSVDDLGCCKVIRHSLWGTHVVVGSIFTNATPDSHIMKKLSGN mmac_human Cyanocobalamin reductase / alkylcobalamin dealkylase MMACHC CblC Cyanocobalamin reductase (cyanide-eliminating) Alkylcobalamin:glutathione S-alkyltransferase Methylmalonic aciduria and homocystinuria type C protein protein protein human Homo sapiens Human MEPKVAELKQKIEDTLCPFGFEVYPFQVAWYNELLPPAFHLPLPGPTLAFLVLSTPAMFDRALKPFLQSCHLRMLTDPVDQCVAYHLGRVRESLPELQIEIIADYEVHPNRRPKILAQTAAHVAGAAYYYQRQDVEADPWGNQRISGVCIHPRFGGWFAIRGVVLLPGIEVPDLPPRKPHDCVPTRADRIALLEGFNFHWRDWTYRDAVTPQERYSEEQKAYFSTPPAQRLALLGLAQPSEKPSSPSPDLPFTTPAPKKPGNPSRARSWLSPRVSPPASPGP mmad_mouse Cobalamin trafficking protein CblD Methylmalonic aciduria and homocystinuria type D homolog, mitochondrial Mmadhc CblD protein protein mouse Mus musculus Mouse MAHVLCNRARLVSYLPGFCSLVKRVINPRAFSTAGSSGSDESHVATAPPDICSRTVWPDETMGPFGPQDQRFQLPGNIGFDCHLNGTASQKKSQAHKTLPDVLAEPLSTERHEFVMAQYVNEFQDSDAPVEQEINSAETYFESAKVECAIQTCPELLRRDFESLFPEVANSKLMILTVTQKTENDMTVWSEEVEVEREVLLEKFISGAKEICYALRAEGYWADFIDPSSGVAFFGPYTNNTLFETDERYRHLGFSVDDLGCCKVIRHSLWGTHVVVGSIFTNATADSSIMRKLSGN glutathione-methylcobalamin-1 3587903 N/A 3587907 cofactor cofactor coenzyme neutral component neutral component purified purified chemical synthesis Chemical synthesis (Chemical synthesis) N/A 3587908 cofactor cofactor coenzyme neutral component neutral component purified purified chemical synthesis Chemical synthesis (Chemical synthesis) N/A 3587909 unspecified role unspecified role neutral component neutral component purified purified region sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain false Q9H3L0:p.Thr182Asn mutation decreasing strength mutation decreasing interaction strength mutation decreasing strength certain certain sequence position certain certain certain sequence position certain false Q9H3L0:p.Met186Ala 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 false Q9H3L0:p.Trp189Ala mutation decreasing strength mutation decreasing interaction strength mutation decreasing strength certain certain sequence position certain certain certain sequence position certain false Q9H3L0:p.Asp226Ala 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 false Q9H3L0:p.Leu259Pro 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 false region his tag his tag Hexa-His-tag 6-His-tag Histidine-tag Hexa-His-tag Histidine-tag 6-His-tag n-term range n-terminal range n-term range n-term range n-terminal range n-term range false ecoli Escherichia coli (strain K12) Stoichiometry: 1.0 N/A 3587910 unspecified role unspecified role neutral component neutral component purified purified Q9Y4U1:p.Arg161Gln mutation decreasing strength mutation decreasing interaction strength mutation decreasing strength certain certain sequence position certain certain certain sequence position certain false p.Pro109_Arg111del mutation disrupting strength mutation disrupting interaction strength mutation disrupting strength certain certain sequence position certain certain certain sequence position certain false ecoli Escherichia coli (strain K12) Stoichiometry: 1.0 direct interaction direct interaction false false false Figure 5d, 1a, 1b, 1c, 1d glutathione-methylcobalamin-3 3587903 N/A 3587908 cofactor cofactor coenzyme neutral component neutral component purified purified chemical synthesis Chemical synthesis (Chemical synthesis) N/A 3587907 cofactor cofactor coenzyme neutral component neutral component purified purified chemical synthesis Chemical synthesis (Chemical synthesis) N/A 3587911 unspecified role unspecified role neutral component neutral component purified purified region sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain false region his tag his tag Hexa-His-tag 6-His-tag Histidine-tag Hexa-His-tag Histidine-tag 6-His-tag n-term range n-terminal range n-term range n-term range n-terminal range n-term range false ecoli Escherichia coli (strain K12) N/A 3587910 unspecified role unspecified role neutral component neutral component purified purified ecoli Escherichia coli (strain K12) direct interaction direct interaction false false false Figure 1f mmachc-mmadhc-1 3587904 N/A 3587908 cofactor cofactor coenzyme neutral component neutral component purified purified chemical synthesis Chemical synthesis (Chemical synthesis) N/A 3587907 cofactor cofactor coenzyme neutral component neutral component purified purified chemical synthesis Chemical synthesis (Chemical synthesis) N/A 3587911 unspecified role unspecified role neutral component neutral component purified purified region sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain false region his tag his tag Hexa-His-tag 6-His-tag Histidine-tag Hexa-His-tag Histidine-tag 6-His-tag n-term range n-terminal range n-term range n-term range n-terminal range n-term range false ecoli Escherichia coli (strain K12) N/A 3587910 unspecified role unspecified role neutral component neutral component purified purified region sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain false ecoli Escherichia coli (strain K12) direct interaction direct interaction false false false Figure 1d mmachc-mmadhc-2 3587905 N/A 3587907 cofactor cofactor coenzyme neutral component neutral component purified purified chemical synthesis Chemical synthesis (Chemical synthesis) N/A 3587908 cofactor cofactor coenzyme neutral component neutral component purified purified chemical synthesis Chemical synthesis (Chemical synthesis) N/A 3587909 unspecified role unspecified role neutral component neutral component purified purified region sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain false region his tag his tag Hexa-His-tag 6-His-tag Histidine-tag Hexa-His-tag Histidine-tag 6-His-tag n-term range n-terminal range n-term range n-term range n-terminal range n-term range false ecoli Escherichia coli (strain K12) Stoichiometry: 1.0 N/A 3587910 unspecified role unspecified role neutral component neutral component purified purified ecoli Escherichia coli (strain K12) Stoichiometry: 1.0 direct interaction direct interaction false false false Figure 1g glutathione-methylcobalamin-2 3587906 N/A 3587908 cofactor cofactor coenzyme neutral component neutral component purified purified chemical synthesis Chemical synthesis (Chemical synthesis) N/A 3587907 cofactor cofactor coenzyme neutral component neutral component purified purified chemical synthesis Chemical synthesis (Chemical synthesis) N/A 3587911 unspecified role unspecified role neutral component neutral component purified purified region sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain false ecoli Escherichia coli (strain K12) Stoichiometry: 1.0 N/A 3587910 unspecified role unspecified role neutral component neutral component purified purified region sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain false ecoli Escherichia coli (strain K12) Stoichiometry: 1.0 direct interaction direct interaction false false false Figure 6a, 6b, 6c