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/ Two catalytic domains are required for protein deacetylation. Two catalytic domains are required for protein deacetylation. J. Biol. Chem. (0021-9258) 2006 imex curation Zhang Y., Gilquin B., Khochbin S., Matthias P. BioCreative - Critical Assessment of Information Extraction systems in Biology Chromatin - Epigenetic interactions resulting in chromatin modulation patrick.matthias@fmi.ch 24-JAN-2007: Contacted by JYOTI. Only protein-protein interactions in vitro In vitro enzymatic study enzymatic study predetermined predetermined participant predetermined Zhang Y., Gilquin B., Khochbin S., Matthias P. BioCreative - Critical Assessment of Information Extraction systems in Biology patrick.matthias@fmi.ch Accepted 2006-SEP-13 by JYOTI. J. Biol. Chem. (0021-9258) 2006 Only protein-protein interactions imex curation h4_peptide Histone h4 n terminal peptide. peptide peptide polypeptide oligopeptide oligopeptide polypeptide in vitro In vitro SGRGKGGKGLGKGGAKRHRKVLR Similar to P62806 An amino acid sequence which is not represented in UniProt A GSGS linker with lysyl biotin was linked to the peptide at the C terminal end. 09EA0849703A8A96 hdac6_mouse Histone deacetylase 6 Histone deacetylase mHDA2 Hdac6 Tubulin-lysine deacetylase HDAC6 protein protein mouse Mus musculus Mouse MTSTGQDSSTRQRKSRHNPQSPLQESSATLKRGGKKCAVPHSSPNLAEVKKKGKMKKLSQPAEEDLVVGLQGLDLNPETRVPVGTGLVFDEQLNDFHCLWDDSFPESPERLHAIREQLILEGLLGRCVSFQARFAEKEELMLVHSLEYIDLMETTQYMNEGELRVLAETYDSVYLHPNSYSCACLATGSVLRLVDALMGAEIRNGMAVIRPPGHHAQHNLMDGYCMFNHLAVAARYAQKKHRIQRVLIVDWDVHHGQGTQFIFDQDPSVLYFSIHRYEHGRFWPHLKASNWSTIGFGQGQGYTINVPWNQTGMRDADYIAAFLHILLPVASEFQPQLVLVAAGFDALHGDPKGEMAATPAGFAHLTHLLMGLAGGKLILSLEGGYNLRALAKGVSASLHTLLGDPCPMLESCVVPCASAQTSIYCTLEALEPFWEVLERSVETQEEDEVEEAVLEEEEEEGGWEATALPMDTWPLLQNRTGLVYDEKMMSHCNLWDNHHPETPQRILRIMCHLEEVGLAARCLILPARPALDSELLTCHSAEYVEHLRTTEKMKTRDLHREGANFDSIYICPSTFACAKLATGAACRLVEAVLSGEVLNGIAVVRPPGHHAEPNAACGFCFFNSVAVAARHAQIIAGRALRILIVDWDVHHGNGTQHIFEDDPSVLYVSLHRYDRGTFFPMGDEGASSQVGRDAGIGFTVNVPWNGPRMGDADYLAAWHRLVLPIAYEFNPELVLISAGFDAAQGDPLGGCQVTPEGYAHLTHLLMGLAGGRIILILEGGYNLASISESMAACTHSLLGDPPPQLTLLRPPQSGALVSISEVIQVHRKYWRSLRLMKMEDKEECSSSRLVIKKLPPTASPVSAKEMTTPKGKVPEESVRKTIAALPGKESTLGQAKSKMAKAVLAQGQSSEQAAKGTTLDLATSKETVGGATTDLWASAAAPENFPNQTTSVEALGETEPTPPASHTNKQTTGASPLQGVTAQQSLQLGVLSTLELSREAEEAHDSEEGLLGEAAGGQDMNSLMLTQGFGDFNTQDVFYAVTPLSWCPHLMAVCPIPAAGLDVSQPCKTCGTVQENWVCLTCYQVYCSRYVNAHMVCHHEASEHPLVLSCVDLSTWCYVCQAYVHHEDLQDVKNAAHQNKFGEDMPHSH DIP protein Q9Z2V5 original sequence version: 131 D5F73BA3F79AF520 hdac6-h4 1 2 enzyme target enzyme target substrate substrate unspecified role unspecified role region ac1res monoacetylated residue Acetyl Acetylation (N terminus, N epsilon of Lysine, O of Serine) (Ac) Acetylation Ac1Res undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined chemical synthesis Chemical synthesis (Chemical synthesis) 3 enzyme enzyme unspecified role unspecified role region ha tag ha tag YPYDVPDYA epitope tag YPYDVPDYA epitope tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined Q9Z2V5:p.[Asp250Asn;Asp252Asn;His254Val;His255Val] HD1m mutation disrupting mutation disrupting interaction mutation disrupting mutation analysis mutation analysis certain certain sequence position certain certain certain sequence position certain D N certain certain sequence position certain certain certain sequence position certain D N certain certain sequence position certain certain certain sequence position certain H V certain certain sequence position certain certain certain sequence position certain H V Wed May 02 16:16:35 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'asp250asn,asp252asn,his254val,his255val' Tue Jun 30 15:51:37 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.[Asp250Asn;Asp252Asn;His254Val;His255Val]' Q9Z2V5:p.[Asp648Asn;His650Val;His651Val] HD2m mutation disrupting mutation disrupting interaction mutation disrupting mutation analysis mutation analysis certain certain sequence position certain certain certain sequence position certain D N certain certain sequence position certain certain certain sequence position certain H V certain certain sequence position certain certain certain sequence position certain H V Wed May 02 15:26:02 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'asp648asn,his650val,his651val' Tue Jun 30 19:50:10 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.[Asp648Asn;His650Val;His651Val]' Q9Z2V5:p.Leu798Ala mutation disrupting mutation disrupting interaction mutation disrupting mutation analysis mutation analysis certain certain sequence position certain certain certain sequence position certain L A Wed May 02 16:50:21 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'leu798ala' Tue Jun 30 20:07:48 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Leu798Ala' Q9Z2V5:p.Leu402Ala mutation decreasing mutation decreasing interaction hotspot hotspot mutation decreasing mutation analysis mutation analysis certain certain sequence position certain certain certain sequence position certain L A Wed May 02 16:19:17 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'leu402ala' Tue Jun 30 20:16:11 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Leu402Ala' 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. enzymatic reaction enzymatic reaction Biochemical reaction Biochemical reaction 1 A, B point mutations in the catalytic core of both hdac domains (HD1/2m) completely abolished the HDAC and the TDAC activities of HDAC-6. Surprisingly, mutating either of the hdac catalytic cores (HD1m or HD2m) also destroyed the whole activity on both substrates. This suggests that the cooperation between the two hdac catalytic cores is critical for the deacetylation reaction mediated by HDAC-6. Interestingly, the mutations in the presumed substrate recognition region (7) led to somewhat different effects on enzymatic activities. The mutation in the second substrate recognition site (L798A) completely inactivated the catalytic activity on both peptides, whereas the mutation of the corresponding region in the first hdac domain (L402A) retained partial activity The exact histone H4 peptide used could not be determined but the tail peptide is conserved and so this peptide is used as a reference. These results suggest that cooperation between the two HDAC6 catalytic cores is needed for enzyme activity. Deacetylated H4 tail. hdac6-h4-1 1 2 enzyme target enzyme target substrate substrate unspecified role unspecified role region ac1res monoacetylated residue Acetyl Acetylation (N terminus, N epsilon of Lysine, O of Serine) (Ac) Acetylation Ac1Res undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined chemical synthesis Chemical synthesis (Chemical synthesis) 3 enzyme enzyme unspecified role unspecified role Q9Z2V5:p.[Asp250Asn;Asp252Asn;His254Val;His255Val] mutation decreasing mutation decreasing interaction hotspot hotspot mutation decreasing mutation analysis mutation analysis certain certain sequence position certain certain certain sequence position certain D N certain certain sequence position certain certain certain sequence position certain D N certain certain sequence position certain certain certain sequence position certain H V certain certain sequence position certain certain certain sequence position certain H V Wed May 02 18:29:50 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'asp250asn,asp252asn,his254val,his255val' Tue Jun 30 16:17:42 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.[Asp250Asn;Asp252Asn;His254Val;His255Val]' Q9Z2V5:p.[Asp648Asn;His650Val;His651Val] mutation decreasing mutation decreasing interaction hotspot hotspot mutation decreasing mutation analysis mutation analysis certain certain sequence position certain certain certain sequence position certain D N certain certain sequence position certain certain certain sequence position certain H V certain certain sequence position certain certain certain sequence position certain H V Wed May 02 18:09:57 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'asp648asn,his650val,his651val' Tue Jun 30 18:48:32 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.[Asp648Asn;His650Val;His651Val]' 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 enzymatic reaction enzymatic reaction Biochemical reaction Biochemical reaction 1 A, C The exact histone H4 peptide used could not be determined but the tail peptide is conserved and so this peptide is used as a reference. His6-tagged HDAC-6 proteins could be purified as single protein and equal amount of wild type and mutant proteins were used for activity assays (Fig. 1C, left panel). As shown in Fig. 1C, right panel, the HDAC and TDAC activity of HDAC-6 is intrinsic and requires both intact catalytic cores. The HDAC6 was expressed in insect cells but the exact cell type is not specified. These results suggest that cooperation between the two HDAC6 catalytic cores is needed for efficient enzyme activity. Deacetylated histone H4 tail.