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/ sollis-2016-1 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. bret bioluminescence resonance energy transfer BRET LRET LRET BRET bret tag visualisation tag visualisation Sollis E., Graham SA., Vino A., Froehlich H., Vreeburg M., Dimitropoulou D., Gilissen C., Pfundt R., Rappold GA., Brunner HG., Deriziotis P., Fisher SE. Rare diseases - Interactions investigated in the context of Rare genetic disease The cells/cell line used for BRET is not mentioned in this publication but Refs 18 + 19 use 293 cells, so it has been assumed these were used in this publication also. elagia.derizioti@mpi.nl, simon.fisher@mpi.nl Human molecular genetics 2016 imex curation Only protein-protein interactions imex curation sollis-2016-2 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. confocal microscopy confocal microscopy tag fluorescence tag visualisation by fluorescence tag fluorescence Sollis E., Graham SA., Vino A., Froehlich H., Vreeburg M., Dimitropoulou D., Gilissen C., Pfundt R., Rappold GA., Brunner HG., Deriziotis P., Fisher SE. Rare diseases - Interactions investigated in the context of Rare genetic disease elagia.derizioti@mpi.nl, simon.fisher@mpi.nl Human molecular genetics 2016 imex curation Only protein-protein interactions imex curation foxp1_human Forkhead box protein P1 FOXP1 Mac-1-regulated forkhead HSPC215 protein protein human Homo sapiens Human MMQESGTETKSNGSAIQNGSGGSNHLLECGGLREGRSNGETPAVDIGAADLAHAQQQQQQALQVARQLLLQQQQQQQVSGLKSPKRNDKQPALQVPVSVAMMTPQVITPQQMQQILQQQVLSPQQLQVLLQQQQALMLQQQQLQEFYKKQQEQLQLQLLQQQHAGKQPKEQQQVATQQLAFQQQLLQMQQLQQQHLLSLQRQGLLTIQPGQPALPLQPLAQGMIPTELQQLWKEVTSAHTAEETTGNNHSSLDLTTTCVSSSAPSKTSLIMNPHASTNGQLSVHTPKRESLSHEEHPHSHPLYGHGVCKWPGCEAVCEDFQSFLKHLNSEHALDDRSTAQCRVQMQVVQQLELQLAKDKERLQAMMTHLHVKSTEPKAAPQPLNLVSSVTLSKSASEASPQSLPHTPTTPTAPLTPVTQGPSVITTTSMHTVGPIRRRYSDKYNVPISSADIAQNQEFYKNAEVRPPFTYASLIRQAILESPEKQLTLNEIYNWFTRMFAYFRRNAATWKNAVRHNLSLHKCFVRVENVKGAVWTVDEVEFQKRRPQKISGNPSLIKNMQSSHAYCTPLNAALQASMAENSIPLYTTASMGNPTLGNLASAIREELNGAMEHTNSNESDSSPGRSPMQAVHPVHVKEEPLDPEEAEGPLSLVTTANHSPDFDHDRDYEDEPVNEDME foxp2_human Forkhead box protein P2 CAG repeat protein 44 Trinucleotide repeat-containing gene 10 protein FOXP2 CAGH44 TNRC10 protein protein human Homo sapiens Human MMQESATETISNSSMNQNGMSTLSSQLDAGSRDGRSSGDTSSEVSTVELLHLQQQQALQAARQLLLQQQTSGLKSPKSSDKQRPLQVPVSVAMMTPQVITPQQMQQILQQQVLSPQQLQALLQQQQAVMLQQQQLQEFYKKQQEQLHLQLLQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQHPGKQAKEQQQQQQQQQQLAAQQLVFQQQLLQMQQLQQQQHLLSLQRQGLISIPPGQAALPVQSLPQAGLSPAEIQQLWKEVTGVHSMEDNGIKHGGLDLTTNNSSSTTSSNTSKASPPITHHSIVNGQSSVLSARRDSSSHEETGASHTLYGHGVCKWPGCESICEDFGQFLKHLNNEHALDDRSTAQCRVQMQVVQQLEIQLSKERERLQAMMTHLHMRPSEPKPSPKPLNLVSSVTMSKNMLETSPQSLPQTPTTPTAPVTPITQGPSVITPASVPNVGAIRRRHSDKYNIPMSSEIAPNYEFYKNADVRPPFTYATLIRQAIMESSDRQLTLNEIYSWFTRTFAYFRRNAATWKNAVRHNLSLHKCFVRVENVKGAVWTVDEVEYQKRRSQKITGSPTLVKNIPTSLGYGAALNASLQAALAESSLPLLSNPGLINNASSGLLQAVHEDLNGSLDHIDSNGNSSPGCSPQPHIHSIHVKEEPVIAEDEDCPMSLVTTANHSPELEDDREIEEEPLSEDLE foxp1-1 3316432 N/A 3316434 unspecified role unspecified role fluorescence accept fluorescence acceptor fluorescence accept c-terminal region p.ala339serfsTer4 variant required to bind necessary binding region required to bind certain certain sequence position certain c-term range C-terminal range c-term range false As given by the p.ala339serfsTer4 variant. This variant lacks the 339-C tem region and has three residues (SPM) added instead. region required to bind necessary binding region required to bind certain certain sequence position certain certain certain sequence position certain false Q9H334:p.Gln76[2] 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 Q9H334:p.Ile107Thr 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 Q9H334:p.Pro215Ala mutation decreasing strength mutation decreasing interaction strength mutation decreasing strength certain certain sequence position certain certain certain sequence position certain false Q9H334:p.Asn570Ser 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 Q9H334:p.Asn597Thr 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 Q9H334:p.Arg465Gly mutation decreasing strength mutation decreasing interaction strength mutation decreasing strength certain certain sequence position certain certain certain sequence position certain false Q9H334:p.Arg514Cys mutation decreasing strength mutation decreasing interaction strength mutation decreasing strength certain certain sequence position certain certain certain sequence position certain false Q9H334:p.Trp534Arg mutation disrupting strength mutation disrupting interaction strength mutation disrupting strength certain certain sequence position certain certain certain sequence position certain false n_terminus yfp tag yellow fluorescent protein tag YFP yellow fluorescent protein yellow fluorescent protein YFP yfp tag n-term range n-terminal range n-term range n-term range n-terminal range n-term range false N/A 3316434 unspecified role unspecified role fluorescence donor fluorescence donor n_terminus renilla luciferase renilla luciferase protein tag renilla luciferase n-term range n-terminal range n-term range n-term range n-terminal range n-term range false proximity proximity close-contact colocalization neighbourhood interaction false false false figure 5A, Supp fig 1, 4A, Table 4 The A339SfsX4 mutation has a single base insertion (+A relative to mRNA) in FOXP1, introducing a frameshift and premature stop codon. It does not bind to WT FOXP1. foxp2-foxp1-2 3316432 N/A 3316434 unspecified role unspecified role fluorescence accept fluorescence acceptor fluorescence accept c-terminal region p.ala339serfsTer4 variant required to bind necessary binding region required to bind certain certain sequence position certain c-term range C-terminal range c-term range false As given by the p.ala339serfsTer4 variant. This variant lacks the 339-C tem region and has three residues (SPM) added instead. region required to bind necessary binding region required to bind certain certain sequence position certain certain certain sequence position certain false Q9H334:p.Arg465Gly 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 Q9H334:p.Arg514Cys mutation decreasing strength mutation decreasing interaction strength mutation decreasing strength certain certain sequence position certain certain certain sequence position certain false Q9H334:p.Trp534Arg mutation decreasing strength mutation decreasing interaction strength mutation decreasing strength certain certain sequence position certain certain certain sequence position certain false n_terminus yfp tag yellow fluorescent protein tag YFP yellow fluorescent protein yellow fluorescent protein YFP yfp tag n-term range n-terminal range n-term range n-term range n-terminal range n-term range false Q9H334:p.Asn597Thr 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 Q9H334:p.Gln76[2] 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 Q9H334:p.Ile107Thr mutation disrupting strength mutation disrupting interaction strength mutation disrupting strength certain certain sequence position certain certain certain sequence position certain false Q9H334:p.Pro215Ala mutation decreasing strength mutation decreasing interaction strength mutation decreasing strength certain certain sequence position certain certain certain sequence position certain false Q9H334:p.Asn570Ser 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 N/A 3316435 unspecified role unspecified role fluorescence donor fluorescence donor n_terminus renilla luciferase renilla luciferase protein tag renilla luciferase n-term range n-terminal range n-term range n-term range n-terminal range n-term range false proximity proximity close-contact colocalization neighbourhood interaction false false false figure 6A, Supp fig 5A, Table 4 The A339SfsX4 mutation has a single base insertion (+A relative to mRNA) in FOXP1, introducing a frameshift and premature stop codon. It does not bind to WT FOXP1. foxp1-4 3316432 N/A 3316434 unspecified role unspecified role fluorescence donor fluorescence donor c-terminal region p.ala339serfsTer4 variant required to bind necessary binding region required to bind certain certain sequence position certain c-term range C-terminal range c-term range false As given by the p.ala339serfsTer4 variant. This variant lacks the 339-C tem region and has three residues (SPM) added instead. region required to bind necessary binding region required to bind certain certain sequence position certain certain certain sequence position certain false Q9H334:p.Arg465Gly mutation increasing strength mutation increasing interaction strength mutation increasing strength certain certain sequence position certain certain certain sequence position certain false Q9H334:p.Arg514Cys mutation decreasing strength mutation decreasing interaction strength mutation decreasing strength certain certain sequence position certain certain certain sequence position certain false Q9H334:p.Trp534Arg mutation disrupting strength mutation disrupting interaction strength mutation disrupting strength certain certain sequence position certain certain certain sequence position certain false n_terminus renilla luciferase renilla luciferase protein tag renilla luciferase n-term range n-terminal range n-term range n-term range n-terminal range n-term range false Q9H334:p.Gln76[2] 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 Q9H334:p.Ile107Thr 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 Q9H334:p.Pro215Ala mutation decreasing strength mutation decreasing interaction strength mutation decreasing strength certain certain sequence position certain certain certain sequence position certain false Q9H334:p.Asn570Ser 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 Q9H334:p.Asn597Thr 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 N/A 3316434 unspecified role unspecified role fluorescence accept fluorescence acceptor fluorescence accept Q9H334:p.Gln76[2] 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 Q9H334:p.Ile107Thr mutation increasing strength mutation increasing interaction strength mutation increasing strength certain certain sequence position certain certain certain sequence position certain false Q9H334:p.Pro215Ala mutation decreasing strength mutation decreasing interaction strength mutation decreasing strength certain certain sequence position certain certain certain sequence position certain false Q9H334:p.Asn570Ser 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 Q9H334:p.Asn597Thr 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 c-terminal region p.ala339serfsTer4 variant required to bind necessary binding region required to bind certain certain sequence position certain c-term range C-terminal range c-term range false As given by the p.ala339serfsTer4 variant. This variant lacks the 339-C tem region and has three residues (SPM) added instead. region required to bind necessary binding region required to bind certain certain sequence position certain certain certain sequence position certain false Q9H334:p.Arg465Gly mutation increasing strength mutation increasing interaction strength mutation increasing strength certain certain sequence position certain certain certain sequence position certain false Q9H334:p.Arg514Cys mutation decreasing strength mutation decreasing interaction strength mutation decreasing strength certain certain sequence position certain certain certain sequence position certain false Q9H334:p.Trp534Arg mutation disrupting strength mutation disrupting interaction strength mutation disrupting strength certain certain sequence position certain certain certain sequence position certain false n_terminus yfp tag yellow fluorescent protein tag YFP yellow fluorescent protein yellow fluorescent protein YFP yfp tag n-term range n-terminal range n-term range n-term range n-terminal range n-term range false proximity proximity close-contact colocalization neighbourhood interaction false false false Supp fig 1, 3C The A339SfsX4 mutation has a single base insertion (+A relative to mRNA) in FOXP1, introducing a frameshift and premature stop codon. It does not bind to WT FOXP1. foxp1-3 3316433 N/A 3316434 unspecified role unspecified role neutral component neutral component region required to bind necessary binding region required to bind certain certain sequence position certain certain certain sequence position certain false Q9H334:p.Arg465Gly mutation decreasing strength mutation decreasing interaction strength mutation decreasing strength certain certain sequence position certain certain certain sequence position certain false Q9H334:p.Arg514Cys mutation decreasing strength mutation decreasing interaction strength mutation decreasing strength certain certain sequence position certain certain certain sequence position certain false Q9H334:p.Trp534Arg mutation disrupting strength mutation disrupting interaction strength mutation disrupting strength certain certain sequence position certain certain certain sequence position certain false n_terminus yfp tag yellow fluorescent protein tag YFP yellow fluorescent protein yellow fluorescent protein YFP yfp tag n-term range n-terminal range n-term range n-term range n-terminal range n-term range false c-terminal region p.ala339serfsTer4 variant required to bind necessary binding region required to bind certain certain sequence position certain c-term range C-terminal range c-term range false N/A 3316434 unspecified role unspecified role neutral component neutral component n_terminus mcherry mcherry fluorescent protein tag mcherry n-term range n-terminal range n-term range n-term range n-terminal range n-term range false colocalization colocalization false false false figure 5B, Supp figure 4B The A339SfsX4 mutation has a single base insertion (+A relative to mRNA) in FOXP1, introducing a frameshift and premature stop codon. It does not bind to WT FOXP1. When co-expressed with WT FOXP1 or FOXP2 proteins, the p.R465G and p.R514C variants led to mislocalization of the WT proteins in nuclear aggregates and with the p.Y439* variant resulted in translocation of the WT proteins into cytoplasmic aggregates. For Supplementary Figure 4 it is stated that "all variants were able to self-associate and to interact with WT FOXP1 and FOXP2". foxp1-foxp1-1 3316433 N/A 3316434 unspecified role unspecified role neutral component neutral component c-terminal region p.ala339serfsTer4 variant required to bind necessary binding region required to bind certain certain sequence position certain c-term range C-terminal range c-term range false As given by the p.ala339serfsTer4 variant. This variant lacks the 339-C tem region and has three residues (SPM) added instead. region required to bind necessary binding region required to bind certain certain sequence position certain certain certain sequence position certain false Q9H334:p.Arg465Gly mutation decreasing strength mutation decreasing interaction strength mutation decreasing strength certain certain sequence position certain certain certain sequence position certain false Q9H334:p.Arg514Cys mutation decreasing strength mutation decreasing interaction strength mutation decreasing strength certain certain sequence position certain certain certain sequence position certain false Q9H334:p.Trp534Arg mutation disrupting strength mutation disrupting interaction strength mutation disrupting strength certain certain sequence position certain certain certain sequence position certain false n_terminus yfp tag yellow fluorescent protein tag YFP yellow fluorescent protein yellow fluorescent protein YFP yfp tag n-term range n-terminal range n-term range n-term range n-terminal range n-term range false N/A 3316435 unspecified role unspecified role neutral component neutral component n_terminus mcherry mcherry fluorescent protein tag mcherry n-term range n-terminal range n-term range n-term range n-terminal range n-term range false colocalization colocalization false false false figure 6B The A339SfsX4 mutation has a single base insertion (+A relative to mRNA) in FOXP1, introducing a frameshift and premature stop codon. It does not bind to WT FOXP1. When co-expressed with WT FOXP1 or FOXP2 proteins, the p.R465G and p.R514C variants led to mislocalization of the WT proteins in nuclear aggregates and with the p.Y439* variant resulted in translocation of the WT proteins into cytoplasmic aggregates. For Supplementary Figure 5 it is stated that "all variants were able to self-associate and to interact with WT FOXP1 and FOXP2".