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/ The R882H DNMT3A Mutation Associated with AML Dominantly Inhibits Wild-Type DNMT3A by Blocking Its Ability to Form Active Tetramers. The R882H DNMT3A Mutation Associated with AML Dominantly Inhibits Wild-Type DNMT3A by Blocking Its Ability to Form Active Tetramers. Cancer Cell (1535-6108) 2014 imex curation Russler-Germain D.A., Spencer D.H., Young M.A., Lamprecht T.L., Miller C.A., Fulton R., Meyer M.R., Erdmann-Gilmore P., Townsend R.R., Wilson R.K., Ley T.J. Cancer - Interactions investigated in the context of cancer methylation reactions using pcDNA3.1 have not been included as a) dont know which variety of pcDNA3.1 was used - and it is an artificial construct, which we dont curate... timley@wustl.edu 21-Jul-2014: Contacted by IntAct-Help. Only protein-protein interactions human-293t Homo sapiens 293 cells transformed with SV40 large T antigen 293t 293 cells expressing SV40 large T antigen. The original designation of this cell line was 293tsA1609neo. It is not in Cabri,ATCC or HyperCLDB. molecular sieving molecular sieving Gel Filtration Size Exclusion Chromatography Size Exclusion Chromatography Gel Filtration Sizing column predetermined predetermined participant predetermined Russler-Germain D.A., Spencer D.H., Young M.A., Lamprecht T.L., Miller C.A., Fulton R., Meyer M.R., Erdmann-Gilmore P., Townsend R.R., Wilson R.K., Ley T.J. Cancer - Interactions investigated in the context of cancer methylation reactions using pcDNA3.1 have not been included as a) dont know which variety of pcDNA3.1 was used - and it is an artificial construct, which we dont curate... timley@wustl.edu Accepted 2014-JUN-06 by ORCHARD Cancer Cell (1535-6108) 2014 Only protein-protein interactions imex curation The R882H DNMT3A Mutation Associated with AML Dominantly Inhibits Wild-Type DNMT3A by Blocking Its Ability to Form Active Tetramers. The R882H DNMT3A Mutation Associated with AML Dominantly Inhibits Wild-Type DNMT3A by Blocking Its Ability to Form Active Tetramers. Cancer Cell (1535-6108) 2014 imex curation Russler-Germain D.A., Spencer D.H., Young M.A., Lamprecht T.L., Miller C.A., Fulton R., Meyer M.R., Erdmann-Gilmore P., Townsend R.R., Wilson R.K., Ley T.J. Cancer - Interactions investigated in the context of cancer methylation reactions using pcDNA3.1 have not been included as a) dont know which variety of pcDNA3.1 was used - and it is an artificial construct, which we dont curate... timley@wustl.edu 21-Jul-2014: Contacted by IntAct-Help. Only protein-protein interactions in vitro In vitro molecular sieving molecular sieving Gel Filtration Size Exclusion Chromatography Size Exclusion Chromatography Gel Filtration Sizing column predetermined predetermined participant predetermined Russler-Germain D.A., Spencer D.H., Young M.A., Lamprecht T.L., Miller C.A., Fulton R., Meyer M.R., Erdmann-Gilmore P., Townsend R.R., Wilson R.K., Ley T.J. Cancer - Interactions investigated in the context of cancer methylation reactions using pcDNA3.1 have not been included as a) dont know which variety of pcDNA3.1 was used - and it is an artificial construct, which we dont curate... timley@wustl.edu Accepted 2014-JUN-06 by ORCHARD Cancer Cell (1535-6108) 2014 Only protein-protein interactions imex curation dnm3a_human DNA (cytosine-5)-methyltransferase 3A DNMT3A DNA methyltransferase HsaIIIA Cysteine methyltransferase DNMT3A protein protein human Homo sapiens Human MPAMPSSGPGDTSSSAAEREEDRKDGEEQEEPRGKEERQEPSTTARKVGRPGRKRKHPPVESGDTPKDPAVISKSPSMAQDSGASELLPNGDLEKRSEPQPEEGSPAGGQKGGAPAEGEGAAETLPEASRAVENGCCTPKEGRGAPAEAGKEQKETNIESMKMEGSRGRLRGGLGWESSLRQRPMPRLTFQAGDPYYISKRKRDEWLARWKREAEKKAKVIAGMNAVEENQGPGESQKVEEASPPAVQQPTDPASPTVATTPEPVGSDAGDKNATKAGDDEPEYEDGRGFGIGELVWGKLRGFSWWPGRIVSWWMTGRSRAAEGTRWVMWFGDGKFSVVCVEKLMPLSSFCSAFHQATYNKQPMYRKAIYEVLQVASSRAGKLFPVCHDSDESDTAKAVEVQNKPMIEWALGGFQPSGPKGLEPPEEEKNPYKEVYTDMWVEPEAAAYAPPPPAKKPRKSTAEKPKVKEIIDERTRERLVYEVRQKCRNIEDICISCGSLNVTLEHPLFVGGMCQNCKNCFLECAYQYDDDGYQSYCTICCGGREVLMCGNNNCCRCFCVECVDLLVGPGAAQAAIKEDPWNCYMCGHKGTYGLLRRREDWPSRLQMFFANNHDQEFDPPKVYPPVPAEKRKPIRVLSLFDGIATGLLVLKDLGIQVDRYIASEVCEDSITVGMVRHQGKIMYVGDVRSVTQKHIQEWGPFDLVIGGSPCNDLSIVNPARKGLYEGTGRLFFEFYRLLHDARPKEGDDRPFFWLFENVVAMGVSDKRDISRFLESNPVMIDAKEVSAAHRARYFWGNLPGMNRPLASTVNDKLELQECLEHGRIAKFSKVRTITTRSNSIKQGKDQHFPVFMNEKEDILWCTEMERVFGFPVHYTDVSNMSRLARQRLLGRSWSVPVIRHLFAPLKEYFACV DIP protein Q9Y6K1 original sequence version: 134 DIP protein Q9Y6K1-1 original sequence version: 88 DIP protein Q9Y6K1 original sequence version: 88 DIP protein Q9Y6K1-1 original sequence version: 135 BD1FF7C5B4F54A33 dnmt3a-dnmt3a 2 3 unspecified role unspecified role neutral component neutral component n_terminus 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 c_terminus 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 Q9Y6K1:p.Arg882His mutation decreasing mutation decreasing interaction hotspot hotspot mutation decreasing certain certain sequence position certain certain certain sequence position certain R H Wed May 02 19:41:49 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'arg882his' Tue Jun 30 20:04:41 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Arg882His' human-293t Homo sapiens 293 cells transformed with SV40 large T antigen 293t 293 cells expressing SV40 large T antigen. The original designation of this cell line was 293tsA1609neo. It is not in Cabri,ATCC or HyperCLDB. 3 unspecified role unspecified role neutral component neutral component n_terminus 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 c_terminus 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 Q9Y6K1:p.Arg882His mutation decreasing mutation decreasing interaction hotspot hotspot mutation decreasing certain certain sequence position certain certain certain sequence position certain R H Wed May 02 16:05:15 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'arg882his' Tue Jun 30 16:32:56 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Arg882His' human-293t Homo sapiens 293 cells transformed with SV40 large T antigen 293t 293 cells expressing SV40 large T antigen. The original designation of this cell line was 293tsA1609neo. It is not in Cabri,ATCC or HyperCLDB. direct interaction direct interaction 7A Two populations of full-length WT DNMT3A oligomers were identified: a macro-oligomer peak with a mean molecular weight of ∼800 kDa (i.e., eight or more DNMT3A molecules) and a tetramer peak of DNMT3A molecules. dnmt3a-dnmt3a-1 2 3 unspecified role unspecified role neutral component neutral component n_terminus 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 c_terminus 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 Q9Y6K1:p.Arg882His mutation disrupting mutation disrupting interaction mutation disrupting certain certain sequence position certain certain certain sequence position certain R H Wed May 02 19:14:59 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'arg882his' Tue Jun 30 19:00:04 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Arg882His' human-293t Homo sapiens 293 cells transformed with SV40 large T antigen 293t 293 cells expressing SV40 large T antigen. The original designation of this cell line was 293tsA1609neo. It is not in Cabri,ATCC or HyperCLDB. direct interaction direct interaction 7Ai Two populations of full-length WT DNMT3A oligomers were identified: a macro-oligomer peak with a mean molecular weight of ∼800 kDa (i.e., eight or more DNMT3A molecules) and a tetramer peak of DNMT3A molecules. dnmt3a-dnmt3a-2 2 3 unspecified role unspecified role neutral component neutral component Q9Y6K1:p.Arg882His mutation decreasing mutation decreasing interaction hotspot hotspot mutation decreasing certain certain sequence position certain certain certain sequence position certain R H Wed May 02 18:00:04 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'arg882his' Tue Jun 30 20:07:35 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Arg882His' n_terminus 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 c_terminus 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 human-293t Homo sapiens 293 cells transformed with SV40 large T antigen 293t 293 cells expressing SV40 large T antigen. The original designation of this cell line was 293tsA1609neo. It is not in Cabri,ATCC or HyperCLDB. 3 unspecified role unspecified role neutral component neutral component n_terminus 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 c_terminus 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 human-293t Homo sapiens 293 cells transformed with SV40 large T antigen 293t 293 cells expressing SV40 large T antigen. The original designation of this cell line was 293tsA1609neo. It is not in Cabri,ATCC or HyperCLDB. direct interaction direct interaction 7Aii In vitro mixed WT and R882H DNMT3A exhibited a distribution of oligomers corresponding to the expected average of the WT and R882H curves for both tetramer and higher order oligomers. dnmt3a-dnmt3a-3 1 3 unspecified role unspecified role neutral component neutral component c_terminus 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 n_terminus 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 3 unspecified role unspecified role neutral component neutral component c_terminus 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 n_terminus 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 Q9Y6K1:p.Arg882His mutation mutation certain certain sequence position certain certain certain sequence position certain R H Wed May 02 15:49:24 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'arg882his' Tue Jun 30 18:34:10 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Arg882His' physical association physical association 7Aii All species (WT, R882H, as well as in vivo and in vitro mixed WT and R882H DNMT3A) were able to form macro-oligomers. In vivo expressed WT and R882H DNMT3A (copurified) complexes exhibited a pattern of oligomerization identical to R882H DNMT3A alone - no tetramer forms.