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/ fox-2019-4 in vitro In vitro saxs x ray scattering saxs predetermined predetermined participant predetermined Fox NG., Yu X., Feng X., Bailey HJ., Martelli A., Nabhan JF., Strain-Damerell C., Bulawa C., Yue WW., Han S. Rare diseases - Interactions investigated in the context of Rare genetic disease wyatt.yue@sgc.ox.ac.uk,seungil.han@pfizer.com Nature communications 2019 Only protein-protein interactions imex curation imex curation fox-2019-1 in vitro In vitro 3d-em-single electron microscopy 3D single particle reconstruction 3D-EM-single predetermined predetermined participant predetermined Fox NG., Yu X., Feng X., Bailey HJ., Martelli A., Nabhan JF., Strain-Damerell C., Bulawa C., Yue WW., Han S. Rare diseases - Interactions investigated in the context of Rare genetic disease Suppl. Fig. 2 co-purification experiments were not captured as two participants were his-tagged, could not infer which one could be the bait wyatt.yue@sgc.ox.ac.uk,seungil.han@pfizer.com Nature communications 2019 Only protein-protein interactions imex curation imex curation fox-2019-2 in vitro In vitro bio-layer interferometry bio-layer interferometry bli bli predetermined predetermined participant predetermined Fox NG., Yu X., Feng X., Bailey HJ., Martelli A., Nabhan JF., Strain-Damerell C., Bulawa C., Yue WW., Han S. Rare diseases - Interactions investigated in the context of Rare genetic disease wyatt.yue@sgc.ox.ac.uk,seungil.han@pfizer.com Nature communications 2019 Only protein-protein interactions imex curation imex curation fox-2019-3 in vitro In vitro dsc differential scanning calorimetry dsc predetermined predetermined participant predetermined Fox NG., Yu X., Feng X., Bailey HJ., Martelli A., Nabhan JF., Strain-Damerell C., Bulawa C., Yue WW., Han S. Rare diseases - Interactions investigated in the context of Rare genetic disease wyatt.yue@sgc.ox.ac.uk,seungil.han@pfizer.com Nature communications 2019 Only protein-protein interactions imex curation imex curation a0a437hbf4_ecolx Acyl carrier protein acpP DQL48_09575 protein protein ecolx Escherichia coli MSTIEERVKKIIGEQLGVKQEEVTNNASFVEDLGADSLDTVELVMALEEEFDTEIPDEEAEKITTVQAAIDYINGH The sequence has been withdrawn from uniprot. iscu_human Iron-sulfur cluster assembly enzyme ISCU, mitochondrial NifU-like N-terminal domain-containing protein ISCU NIFUN NifU-like protein protein protein human Homo sapiens Human MAAAGAFRLRRAASALLLRSPRLPARELSAPARLYHKKVVDHYENPRNVGSLDKTSKNVGTGLVGAPACGDVMKLQIQVDEKGKIVDARFKTFGCGSAIASSSLATEWVKGKTVEEALTIKNTDIAKELCLPPVKLHCSMLAEDAIKAALADYKLKQEPKKGEAEKK frda_human Frataxin, mitochondrial Friedreich ataxia protein FXN FRDA X25 protein protein human Homo sapiens Human MWTLGRRAVAGLLASPSPAQAQTLTRVPRPAELAPLCGRRGLRTDIDATCTPRRASSNQRGLNQIWNVKKQSVYLMNLRKSGTLGHPGSLDETTYERLAEETLDSLAEFFEDLADKPYTFEDYDVSFGSGVLTVKLGGDLGTYVINKQTPNKQIWLSSPSSGPKRYDWTGKNWVYSHDGVSLHELLAAELTKALKTKLDLSSLAYSGKDA lyrm4_human LYR motif-containing protein 4 LYRM4 C6orf149 ISD11 CGI-203 protein protein human Homo sapiens Human MAASSRAQVLSLYRAMLRESKRFSAYNYRTYAVRRIRDAFRENKNVKDPVEIQTLVNKAKRDLGVIRRQVHIGQLYSTDKLIIENRDMPRT zinc(2+) zinc(2+) small molecule small molecule chemical synthesis Chemical synthesis (Chemical synthesis) s-dodecanoyl-4'-phosphopantetheine S-dodecanoyl-4'-phosphopantetheine dodecanoyl-4'-phosphopantetheine lauroyl-4-phosphopantetheine S-dodecanoyl-D-pantetheine 4'-phosphate S-lauroyl-4-phosphopantetheine S-lauroyl-D-pantetheine 4'-phosphate S-[2-({N-[(2R)-2-hydroxy-3,3-dimethyl-4-(phosphonooxy)butanoyl]-beta-alanyl}amino)ethyl] dodecanethioate small molecule small molecule chemical synthesis Chemical synthesis (Chemical synthesis) pyridoxal 5'-phosphate pyridoxal 5'-phosphate 3-hydroxy-2-methyl-5-[(phosphonooxy)methyl]-4-pyridinecarboxaldehyde 3-hydroxy-5-(hydroxymethyl)-2-methylisonicotinaldehyde 5-phosphate codecarboxylase Phosphoric acid mono-(4-formyl-5-hydroxy-6-methyl-pyridin-3-ylmethyl) ester pyridoxal 5-monophosphoric acid ester pyridoxal 5'-(dihydrogen phosphate) Pyridoxal 5'-phosphate Pyridoxal 5-phosphate Pyridoxal phosphate PYRIDOXAL-5'-PHOSPHATE (4-formyl-5-hydroxy-6-methylpyridin-3-yl)methyl dihydrogen phosphate small molecule small molecule chemical synthesis Chemical synthesis (Chemical synthesis) NGVDGCNFYWLIFO-UHFFFAOYSA-N nfs1_human Cysteine desulfurase, mitochondrial NFS1 NIFS HUSSY-08 protein protein human Homo sapiens Human MLLRAAWRRAAVAVTAAPGPKPAAPTRGLRLRVGDRAPQSAVPADTAAAPEVGPVLRPLYMDVQATTPLDPRVLDAMLPYLINYYGNPHSRTHAYGWESEAAMERARQQVASLIGADPREIIFTSGATESNNIAIKGVARFYRSRKKHLITTQTEHKCVLDSCRSLEAEGFQVTYLPVQKSGIIDLKELEAAIQPDTSLVSVMTVNNEIGVKQPIAEIGRICSSRKVYFHTDAAQAVGKIPLDVNDMKIDLMSISGHKIYGPKGVGAIYIRRRPRVRVEALQSGGGQERGMRSGTVPTPLVVGLGAACEVAQQEMEYDHKRISKLSERLIQNIMKSLPDVVMNGDPKHHYPGCINLSFAYVEGESLLMALKDVALSSGSACTSASLEPSYVLRAIGTDEDLAHSSIRFGIGRFTTEEEVDYTVEKCIQHVKRLREMSPLWEMVQDGIDLKSIKWTQH q9y697-2 Cysteine desulfurase, mitochondrial NFS1 NIFS HUSSY-08 protein protein human Homo sapiens Human MDVQATTPLDPRVLDAMLPYLINYYGNPHSRTHAYGWESEAAMERARQQVASLIGADPREIIFTSGATESNNIAIKGVARFYRSRKKHLITTQTEHKCVLDSCRSLEAEGFQVTYLPVQKSGIIDLKELEAAIQPDTSLVSVMTVNNEIGVKQPIAEIGRICSSRKVYFHTDAAQAVGKIPLDVNDMKIDLMSISGHKIYGPKGVGAIYIRRRPRVRVEALQSGGGQERGMRSGTVPTPLVVGLGAACEVAQQEMEYDHKRISKLSERLIQNIMKSLPDVVMNGDPKHHYPGCINLSFAYVEGESLLMALKDVALSSGSACTSASLEPSYVLRAIGTDEDLAHSSIRFGIGRFTTEEEVDYTVEKCIQHVKRLREMSPLWEMVQDGIDLKSIKWTQH acpp-fxn-2 3581997 N/A 3582001 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) N/A 3582002 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) N/A 3582003 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) N/A 3582004 unspecified role unspecified role neutral component neutral component purified purified region his tag his tag Hexa-His-tag 6-His-tag Histidine-tag Hexa-His-tag Histidine-tag 6-His-tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined false ecoli Escherichia coli (strain K12) N/A 3582005 unspecified role unspecified role neutral component neutral component purified purified chemical synthesis Chemical synthesis (Chemical synthesis) N/A 3582006 unspecified role unspecified role neutral component neutral component purified purified chemical synthesis Chemical synthesis (Chemical synthesis) N/A 3582007 unspecified role unspecified role neutral component neutral component purified purified chemical synthesis Chemical synthesis (Chemical synthesis) N/A 3582008 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) physical association physical association false false false Supplementary Table 4, Supplementary Figure 7 0.99 Å acpp-fxn-3 3581997 N/A 3582001 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) N/A 3582002 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) N/A 3582004 unspecified role unspecified role neutral component neutral component purified purified region his tag his tag Hexa-His-tag 6-His-tag Histidine-tag Hexa-His-tag Histidine-tag 6-His-tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined false ecoli Escherichia coli (strain K12) N/A 3582005 unspecified role unspecified role neutral component neutral component purified purified chemical synthesis Chemical synthesis (Chemical synthesis) N/A 3582006 unspecified role unspecified role neutral component neutral component purified purified chemical synthesis Chemical synthesis (Chemical synthesis) N/A 3582007 unspecified role unspecified role neutral component neutral component purified purified chemical synthesis Chemical synthesis (Chemical synthesis) N/A 3582008 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) physical association physical association false false false Supplementary Table 4, Supplementary Figure 7 acpp-fxn-1 3581998 N/A 3582001 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 binding region binding-associated region binding region certain certain sequence position certain certain certain sequence position certain false ISD11 binding region binding region binding-associated region binding region undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined false ecoli Escherichia coli (strain K12) Stoichiometry: 1.0 N/A 3582002 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 Zn2+ binding region binding region binding-associated region binding region undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined false FXN binding region binding region binding-associated region binding region undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined false ecoli Escherichia coli (strain K12) Stoichiometry: 1.0 N/A 3582003 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 NFS1 binding region binding region binding-associated region binding region undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined false ISCU binding region binding region binding-associated region binding region undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined false ecoli Escherichia coli (strain K12) Stoichiometry: 1.0 N/A 3582004 unspecified role unspecified role neutral component neutral component purified purified region his tag his tag Hexa-His-tag 6-His-tag Histidine-tag Hexa-His-tag Histidine-tag 6-His-tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined false region sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain false ACP binding region binding region binding-associated region binding region undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined false NFS1 binding region binding region binding-associated region binding region undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined false ecoli Escherichia coli (strain K12) Stoichiometry: 1.0 N/A 3582009 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 4'PP binding region binding region binding-associated region binding region certain certain sequence position certain certain certain sequence position certain false FXN binding region binding region binding-associated region binding region undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined false ISD11 binding region binding region binding-associated region binding region undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined false NFS1 binding region binding region binding-associated region binding region undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined false ecoli Escherichia coli (strain K12) Stoichiometry: 1.0 N/A 3582006 unspecified role unspecified role neutral component neutral component purified purified acyl chain binding region binding region binding-associated region binding region undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined false chemical synthesis Chemical synthesis (Chemical synthesis) Stoichiometry: 1.0 N/A 3582005 unspecified role unspecified role neutral component neutral component purified purified ISCU binding region binding region binding-associated region binding region undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined false chemical synthesis Chemical synthesis (Chemical synthesis) Stoichiometry: 1.0 N/A 3582007 unspecified role unspecified role neutral component neutral component purified purified NFS1 binding region binding region binding-associated region binding region undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined false chemical synthesis Chemical synthesis (Chemical synthesis) Stoichiometry: 1.0 N/A 3582005 unspecified role unspecified role neutral component neutral component purified purified ISCU binding region binding region binding-associated region binding region undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined false chemical synthesis Chemical synthesis (Chemical synthesis) Stoichiometry: 1.0 N/A 3582006 unspecified role unspecified role neutral component neutral component purified purified acyl chain binding region binding region binding-associated region binding region undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined false chemical synthesis Chemical synthesis (Chemical synthesis) Stoichiometry: 1.0 N/A 3582007 unspecified role unspecified role neutral component neutral component purified purified NFS1 binding region binding region binding-associated region binding region undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined false chemical synthesis Chemical synthesis (Chemical synthesis) Stoichiometry: 1.0 N/A 3582001 unspecified role unspecified role neutral component neutral component purified purified ISD11 binding region binding region binding-associated region binding region undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined false region sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain false region binding region binding-associated region binding region certain certain sequence position certain certain certain sequence position certain false ecoli Escherichia coli (strain K12) Stoichiometry: 1.0 N/A 3582002 unspecified role unspecified role neutral component neutral component purified purified FXN binding region binding region binding-associated region binding region undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined false region sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain false Zn2+ binding region binding region binding-associated region binding region undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined false ecoli Escherichia coli (strain K12) Stoichiometry: 1.0 N/A 3582003 unspecified role unspecified role neutral component neutral component purified purified ISCU binding region binding region binding-associated region binding region undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined false region sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain false NFS1 binding region binding region binding-associated region binding region undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined false ecoli Escherichia coli (strain K12) Stoichiometry: 1.0 N/A 3582004 unspecified role unspecified role neutral component neutral component purified purified ACP binding region binding region binding-associated region binding region undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined false 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 undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined false NFS1 binding region binding region binding-associated region binding region undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined false ecoli Escherichia coli (strain K12) Stoichiometry: 1.0 N/A 3582009 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 4'PP binding region binding region binding-associated region binding region certain certain sequence position certain certain certain sequence position certain false FXN binding region binding region binding-associated region binding region undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined false ISD11 binding region binding region binding-associated region binding region undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined false NFS1 binding region binding region binding-associated region binding region undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined false ecoli Escherichia coli (strain K12) Stoichiometry: 1.0 3582048 3582044 3582052 3582040 3582065 3582056 3582067 3582043 3582069 3582039 3582075 3582061 3582079 3582063 3582081 3582077 3582083 3582057 3582085 3582073 3582088 3582058 3582091 3582071 3582092 3582047 3582093 3582053 3582094 3582059 physical association physical association false false false Supplementary Table 1, Fig. 1a, b, Supplementary Figure 4 3.2Å More specifically, the interaction detection method is Cryo-EM with 3D refinement iscu-acpp-1 3581999 N/A 3582008 unspecified role unspecified role prey prey 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) N/A 3582004 unspecified role unspecified role prey prey purified purified ecoli Escherichia coli (strain K12) N/A 3582001 unspecified role unspecified role prey prey purified purified ecoli Escherichia coli (strain K12) N/A 3582002 unspecified role unspecified role bait bait purified purified region sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain false region biotin tag biotin tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined false ecoli Escherichia coli (strain K12) N/A 3582003 unspecified role unspecified role prey prey purified purified region sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain false Q16595:p.Asp124Ala mutation decreasing strength mutation decreasing interaction strength mutation decreasing strength certain certain sequence position certain certain certain sequence position certain false Q16595:p.Asn146Lys mutation disrupting strength mutation disrupting interaction strength mutation disrupting strength certain certain sequence position certain certain certain sequence position certain false Q16595:p.Asn151Ala mutation decreasing strength mutation decreasing interaction strength mutation decreasing strength certain certain sequence position certain certain certain sequence position certain false Q16595:p.Trp155Arg mutation disrupting strength mutation disrupting interaction strength mutation disrupting strength certain certain sequence position certain certain certain sequence position certain false Q16595:p.Pro163Gly mutation decreasing strength mutation decreasing interaction strength mutation decreasing strength certain certain sequence position certain certain certain sequence position certain false Q16595:p.Arg165Cys 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) physical association physical association false false false 3581999 Table 1, Supplementary Figure 1d Impact of FXN mutations is on the whole of SDAU complex (NFS1-ISD11-ACP-ISCU); SDAU is not a functional complex without FXN so we couldn't have the possibility of generating a complex portal identifier so as to be taken as a participant fxn-nfs1-2 3582000 N/A 3582008 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: 2.0 N/A 3582003 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 p.Asp124Ala mutation with complex effect mutation with complex effect certain certain sequence position certain certain certain sequence position certain false p.Asn146Lys mutation with complex effect mutation with complex effect certain certain sequence position certain certain certain sequence position certain false p.Asn151Ala mutation with complex effect mutation with complex effect certain certain sequence position certain certain certain sequence position certain false p.Trp155Arg mutation with complex effect mutation with complex effect certain certain sequence position certain certain certain sequence position certain false p.Pro163Gly mutation with complex effect mutation with complex effect certain certain sequence position certain certain certain sequence position certain false p.Arg165Cys mutation with complex effect mutation with complex effect certain certain sequence position certain certain certain sequence position certain false ecoli Escherichia coli (strain K12) Stoichiometry: 2.0 direct interaction direct interaction false false false 3582000 Table 1 From the given melting temperature of the individual mutations, it is not possible to infer effects of the mutations. The difference in melting point can tell us about the overall stability of the interaction, but very little detail is available on the binding site