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/ Regulation of p53 activity through lysine methylation. Regulation of p53 activity through lysine methylation. Nature (0028-0836) 2004 imex curation Chuikov S., Kurash JK., Wilson JR., Xiao B., Justin N., Ivanov GS., McKinney K., Tempst P., Prives C., Gamblin SJ., Barlev NA., Reinberg D. Apoptosis - Interactions involving proteins with a function related to apoptosis Cancer - Interactions investigated in the context of cancer Chromatin - Epigenetic interactions resulting in chromatin modulation reinbedf@UMDNJ.EDU,nbarlev@tufts-nemc.org davet Only protein-protein interactions in vitro In vitro x-ray diffraction x-ray crystallography X-ray X-ray x-ray diffraction predetermined predetermined participant predetermined Chuikov S., Kurash JK., Wilson JR., Xiao B., Justin N., Ivanov GS., McKinney K., Tempst P., Prives C., Gamblin SJ., Barlev NA., Reinberg D. Apoptosis - Interactions involving proteins with a function related to apoptosis reinbedf@UMDNJ.EDU,nbarlev@tufts-nemc.org Accepted 2007-AUG-17 by DAVET. Nature (0028-0836) 2004 davet Only protein-protein interactions imex curation Regulation of p53 activity through lysine methylation. Regulation of p53 activity through lysine methylation. Nature (0028-0836) 2004 imex curation Chuikov S., Kurash JK., Wilson JR., Xiao B., Justin N., Ivanov GS., McKinney K., Tempst P., Prives C., Gamblin SJ., Barlev NA., Reinberg D. Apoptosis - Interactions involving proteins with a function related to apoptosis Cancer - Interactions investigated in the context of cancer Chromatin - Epigenetic interactions resulting in chromatin modulation reinbedf@UMDNJ.EDU,nbarlev@tufts-nemc.org davet Only protein-protein interactions in vitro In vitro enzymatic study enzymatic study predetermined predetermined participant predetermined Chuikov S., Kurash JK., Wilson JR., Xiao B., Justin N., Ivanov GS., McKinney K., Tempst P., Prives C., Gamblin SJ., Barlev NA., Reinberg D. Apoptosis - Interactions involving proteins with a function related to apoptosis Mehtyl transferase activity studied. reinbedf@UMDNJ.EDU,nbarlev@tufts-nemc.org Accepted 2007-AUG-17 by DAVET. Nature (0028-0836) 2004 davet Only protein-protein interactions imex curation Regulation of p53 activity through lysine methylation. Regulation of p53 activity through lysine methylation. Nature (0028-0836) 2004 imex curation Chuikov S., Kurash JK., Wilson JR., Xiao B., Justin N., Ivanov GS., McKinney K., Tempst P., Prives C., Gamblin SJ., Barlev NA., Reinberg D. Apoptosis - Interactions involving proteins with a function related to apoptosis Cancer - Interactions investigated in the context of cancer Chromatin - Epigenetic interactions resulting in chromatin modulation reinbedf@UMDNJ.EDU,nbarlev@tufts-nemc.org davet Only protein-protein interactions in vitro In vitro competition binding competition binding predetermined predetermined participant predetermined Chuikov S., Kurash JK., Wilson JR., Xiao B., Justin N., Ivanov GS., McKinney K., Tempst P., Prives C., Gamblin SJ., Barlev NA., Reinberg D. Apoptosis - Interactions involving proteins with a function related to apoptosis The affinity of Set9 for putative peptide substrates derived from the sequences of either the H3 tail or p53 was determined by competition binding studies against an N-terminal dansyl labelled H3 peptide - ARTKQTARKY. reinbedf@UMDNJ.EDU,nbarlev@tufts-nemc.org Accepted 2007-AUG-17 by DAVET. Nature (0028-0836) 2004 davet Only protein-protein interactions imex curation setd7_human Histone-lysine N-methyltransferase SETD7 SETD7 KIAA1717 SET7 KMT7 SET9 Histone H3-K4 methyltransferase SETD7 SET domain-containing protein 7 SET7/9 Lysine N-methyltransferase 7 protein protein human Homo sapiens Human MDSDDEMVEEAVEGHLDDDGLPHGFCTVTYSSTDRFEGNFVHGEKNGRGKFFFFDGSTLEGYYVDDALQGQGVYTYEDGGVLQGTYVDGELNGPAQEYDTDGRLIFKGQYKDNIRHGVCWIYYPDGGSLVGEVNEDGEMTGEKIAYVYPDERTALYGKFIDGEMIEGKLATLMSTEEGRPHFELMPGNSVYHFDKSTSSCISTNALLPDPYESERVYVAESLISSAGEGLFSKVAVGPNTVMSFYNGVRITHQEVDSRDWALNGNTLSLDEETVIDVPEPYNHVSKYCASLGHKANHSFTPNCIYDMFVHPRFGPIKCIRTLRAVEADEELTVAYGYDHSPPGKSGPEAPEWYQVELKAFQATQQK DIP protein Q8WTS6 original sequence version: 46 DIP protein Q8WTS6 original sequence version: 89 DIP protein Q8WTS6 original sequence version: 106 DIP protein Q8WTS6 original sequence version: 120 DIP protein Q8WTS6 original sequence version: 121 DIP protein Q8WTS6 original sequence version: 114 DIP protein Q8WTS6 original sequence version: 95 73A1217079E3BA13 h31_mouse Histone H3.1 H3c1 H3c10 H3c11 H3c8 H3.1-221 H3.1-291 H3.1-I H3a H3g H3h H3i Hist1h3a Hist1h3g Hist1h3h Hist1h3i protein protein mouse Mus musculus Mouse MARTKQTARKSTGGKAPRKQLATKAARKSAPATGGVKKPHRYRPGTVALREIRRYQKSTELLIRKLPFQRLVREIAQDFKTDLRFQSSAVMALQEACEAYLVGLFEDTNLCAIHAKRVTIMPKDIQLARRIRGERA 9B89008EA50A0EF6 s-adenosyl-l-homocysteine S-adenosyl-l-homocysteine small molecule small molecule chemical synthesis Chemical synthesis (Chemical synthesis) p53_human Cellular tumor antigen p53 TP53 P53 Tumor suppressor p53 Phosphoprotein p53 Antigen NY-CO-13 protein protein human Homo sapiens Human MEEPQSDPSVEPPLSQETFSDLWKLLPENNVLSPLPSQAMDDLMLSPDDIEQWFTEDPGPDEAPRMPEAAPPVAPAPAAPTPAAPAPAPSWPLSSSVPSQKTYQGSYGFRLGFLHSGTAKSVTCTYSPALNKMFCQLAKTCPVQLWVDSTPPPGTRVRAMAIYKQSQHMTEVVRRCPHHERCSDSDGLAPPQHLIRVEGNLRVEYLDDRNTFRHSVVVPYEPPEVGSDCTTIHYNYMCNSSCMGGMNRRPILTIITLEDSSGNLLGRNSFEVRVCACPGRDRRTEEENLRKKGEPHHELPPGSTKRALPNNTSSSPQPKKKPLDGEYFTLQIRGRERFEMFRELNEALELKDAQAGKEPGGSRAHSSHLKSKKGQSTSRHKKLMFKTEGPDSD DIP protein P04637 original sequence version: 121 DIP protein P04637 original sequence version: 115 DIP protein P04637-1 original sequence version: 224 DIP protein P04637 original sequence version: 117 DIP protein P04637-1 original sequence version: 226 DIP protein P04637 original sequence version: 226 DIP protein P04637 original sequence version: 212 DIP protein P04637 original sequence version: 220 DIP protein P04637-1 original sequence version: 220 DIP protein P04637-1 original sequence version: 145 DIP protein P04637 original sequence version: 146 DIP protein P04637 original sequence version: 145 DIP protein P04637 original sequence version: 166 DIP protein P04637-1 original sequence version: 166 DIP protein P04637 original sequence version: 169 DIP protein P04637 original sequence version: 177 DIP protein P04637 original sequence version: 175 DIP protein P04637-1 original sequence version: 175 DIP protein P04637-1 original sequence version: 172 DIP protein P04637-1 original sequence version: 169 DIP protein P04637 original sequence version: 170 DIP protein P04637 original sequence version: 172 DIP protein P04637-1 original sequence version: 194 DIP protein P04637 original sequence version: 196 DIP protein P04637 original sequence version: 185 DIP protein P04637-1 original sequence version: 191 DIP protein P04637 original sequence version: 191 DIP protein P04637 original sequence version: 180 DIP protein P04637-1 original sequence version: 197 DIP protein P04637 original sequence version: 183 DIP protein P04637-1 original sequence version: 183 DIP protein P04637-1 original sequence version: 185 DIP protein P04637 original sequence version: 199 DIP protein P04637 original sequence version: 201 DIP protein P04637 original sequence version: 189 DIP protein P04637 original sequence version: 235 DIP protein P04637 original sequence version: 230 DIP protein P04637 original sequence version: 234 DIP protein P04637-1 original sequence version: 234 DIP protein P04637-1 original sequence version: 235 DIP protein P04637 original sequence version: 239 DIP protein P04637-1 original sequence version: 212 DIP protein P04637-1 original sequence version: 213 DIP protein P04637 original sequence version: 213 DIP protein P04637 original sequence version: 206 DIP protein P04637-1 original sequence version: 188 DIP protein P04637-1 original sequence version: 228 DIP protein P04637 original sequence version: 208 DIP protein P04637 original sequence version: 240 DIP protein P04637-1 original sequence version: 240 DIP protein P04637 original sequence version: 204 DIP protein P04637-1 original sequence version: 204 DIP protein P04637-1 original sequence version: 209 DIP protein P04637-1 original sequence version: 203 DIP protein P04637 original sequence version: 221 DIP protein P04637-1 original sequence version: 152 DIP protein P04637 original sequence version: 217 DIP protein P04637-1 original sequence version: 140 DIP protein P04637 original sequence version: 215 DIP protein P04637 original sequence version: 214 DIP protein P04637-1 original sequence version: 182 DIP protein P04637 original sequence version: 182 DIP protein P04637 original sequence version: 188 DIP protein P04637 original sequence version: 192 DIP protein P04637-1 original sequence version: 192 DIP protein P04637 original sequence version: 218 DIP protein P04637-1 original sequence version: 218 AD5C149FD8106131 set7-tp53 1 6 unspecified role unspecified role neutral component neutral component 7 unspecified role unspecified role neutral component neutral component region sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain lys371 melys methylated lysine MeLys certain certain sequence position certain certain certain sequence position certain chemical synthesis Chemical synthesis (Chemical synthesis) 4 unspecified role unspecified role neutral component neutral component region gst tag glutathione s tranferase tag glutathione S-tranferase tag glutathione S-tranferase tag gst tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined region sufficient to bind sufficient binding region sufficient to bind undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined [EBI-1270256]Certain and ragged-n-terminus positions must always be strictly superior to 0 and inferior or equal to the protein sequence length. Actual positions : 367-367, sequence length 366 [EBI-1270256]108-367 ecoli Escherichia coli (strain K12) direct interaction direct interaction working 18.4%, free 22.3% 1.75 A We next determined the structure of Set9 in complex with a mono-methylated p53 peptide and cofactor product AdoHcy. Figure 2, Table T1 The p53 peptide has a n-terminal Cys not seen in the UniprotKB entry. set9-p53 2 4 enzyme enzyme unspecified role unspecified role region gst tag glutathione s tranferase tag glutathione S-tranferase tag glutathione S-tranferase tag gst tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined region sufficient to bind sufficient binding region sufficient to bind undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined [EBI-1270287]Certain and ragged-n-terminus positions must always be strictly superior to 0 and inferior or equal to the protein sequence length. Actual positions : 367-367, sequence length 366 [EBI-1270287]108-367 ecoli Escherichia coli (strain K12) 7 enzyme target enzyme target substrate substrate unspecified role unspecified role P04637:p.Lys372Arg mutation decreasing mutation decreasing interaction hotspot hotspot mutation decreasing certain certain sequence position certain certain certain sequence position certain K R Wed May 02 14:42:48 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'lys372arg' Tue Jun 30 19:57:03 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Lys372Arg' region sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain region gst tag glutathione s tranferase tag glutathione S-tranferase tag glutathione S-tranferase tag gst tag c-term range C-terminal range c-term range c-term range C-terminal range c-term range ecoli Escherichia coli (strain K12) direct interaction direct interaction Figure 1a, 1c, 1e Methylated GST p53 lys 372 Set9 methylated the tumour suppressor protein p53 in vitro set9-h3 2 5 enzyme target enzyme target substrate substrate unspecified role unspecified role n terminal gst tag glutathione s tranferase tag glutathione S-tranferase tag glutathione S-tranferase tag gst tag certain certain sequence position certain certain certain sequence position certain ecoli Escherichia coli (strain K12) 4 enzyme enzyme unspecified role unspecified role region sufficient to bind sufficient binding region sufficient to bind undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined [EBI-1270344]Certain and ragged-n-terminus positions must always be strictly superior to 0 and inferior or equal to the protein sequence length. Actual positions : 367-367, sequence length 366 [EBI-1270344]108-367 region gst tag glutathione s tranferase tag glutathione S-tranferase tag glutathione S-tranferase tag gst tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined ecoli Escherichia coli (strain K12) direct interaction direct interaction Figure 1a Methylated GST H3 set9-p53-1 2 4 enzyme enzyme unspecified role unspecified role region sufficient to bind sufficient binding region sufficient to bind undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined [EBI-1270360]Certain and ragged-n-terminus positions must always be strictly superior to 0 and inferior or equal to the protein sequence length. Actual positions : 367-367, sequence length 366 [EBI-1270360]108-367 region gst tag glutathione s tranferase tag glutathione S-tranferase tag glutathione S-tranferase tag gst tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined ecoli Escherichia coli (strain K12) 7 enzyme target enzyme target substrate substrate unspecified role unspecified role region sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain P04637:p.Lys372Arg mutation decreasing mutation decreasing interaction hotspot hotspot mutation decreasing certain certain sequence position certain certain certain sequence position certain K R Wed May 02 15:30:04 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'lys372arg' Tue Jun 30 20:10:58 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Lys372Arg' chemical synthesis Chemical synthesis (Chemical synthesis) direct interaction direct interaction Figure 1d, S1 Monomethylated p53 peptide at lys 372 We found that Set9 methylated lysine 372 set9-p53-2 3 4 enzyme enzyme unspecified role unspecified role region gst tag glutathione s tranferase tag glutathione S-tranferase tag glutathione S-tranferase tag gst tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined region sufficient to bind sufficient binding region sufficient to bind undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined [EBI-1270392]Certain and ragged-n-terminus positions must always be strictly superior to 0 and inferior or equal to the protein sequence length. Actual positions : 367-367, sequence length 366 [EBI-1270392]108-367 ecoli Escherichia coli (strain K12) 7 enzyme target enzyme target substrate substrate unspecified role unspecified role region sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain chemical synthesis Chemical synthesis (Chemical synthesis) direct interaction direct interaction Figure 2b The affinity of Set9 for putative peptide substrates derived from the sequences of either the H3 tail or p53 was determined by competition binding studies against an N-terminal dansyl-labelled H3 10-mer peptide set9-h3-1 3 5 enzyme target enzyme target substrate substrate unspecified role unspecified role n terminal sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain chemical synthesis Chemical synthesis (Chemical synthesis) 4 enzyme enzyme unspecified role unspecified role region gst tag glutathione s tranferase tag glutathione S-tranferase tag glutathione S-tranferase tag gst tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined region sufficient to bind sufficient binding region sufficient to bind undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined [EBI-1270400]Certain and ragged-n-terminus positions must always be strictly superior to 0 and inferior or equal to the protein sequence length. Actual positions : 367-367, sequence length 366 [EBI-1270400]108-367 ecoli Escherichia coli (strain K12) direct interaction direct interaction Figure 2b The affinity of Set9 for putative peptide substrates derived from the sequences of either the H3 tail or p53 was determined by competition binding studies against an N-terminal dansyl-labelled H3 10-mer peptide