Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTGH73N)

DTT Name Histone acetyltransferase p300 (EP300)
Synonyms p300 HAT; Protein propionyltransferase p300; P300; Histone crotonyltransferase p300; Histone butyryltransferase p300; E1Aassociated protein p300; E1A-associated protein p300
Gene Name EP300
DTT Type
Clinical trial target
 [1]
BioChemical Class
Acyltransferase
UniProt ID
EP300_HUMAN
TTD ID
T25956
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
EC Number
EC 2.3.1.48
Sequence
MAENVVEPGPPSAKRPKLSSPALSASASDGTDFGSLFDLEHDLPDELINSTELGLTNGGD
INQLQTSLGMVQDAASKHKQLSELLRSGSSPNLNMGVGGPGQVMASQAQQSSPGLGLINS
MVKSPMTQAGLTSPNMGMGTSGPNQGPTQSTGMMNSPVNQPAMGMNTGMNAGMNPGMLAA
GNGQGIMPNQVMNGSIGAGRGRQNMQYPNPGMGSAGNLLTEPLQQGSPQMGGQTGLRGPQ
PLKMGMMNNPNPYGSPYTQNPGQQIGASGLGLQIQTKTVLSNNLSPFAMDKKAVPGGGMP
NMGQQPAPQVQQPGLVTPVAQGMGSGAHTADPEKRKLIQQQLVLLLHAHKCQRREQANGE
VRQCNLPHCRTMKNVLNHMTHCQSGKSCQVAHCASSRQIISHWKNCTRHDCPVCLPLKNA
GDKRNQQPILTGAPVGLGNPSSLGVGQQSAPNLSTVSQIDPSSIERAYAALGLPYQVNQM
PTQPQVQAKNQQNQQPGQSPQGMRPMSNMSASPMGVNGGVGVQTPSLLSDSMLHSAINSQ
NPMMSENASVPSLGPMPTAAQPSTTGIRKQWHEDITQDLRNHLVHKLVQAIFPTPDPAAL
KDRRMENLVAYARKVEGDMYESANNRAEYYHLLAEKIYKIQKELEEKRRTRLQKQNMLPN
AAGMVPVSMNPGPNMGQPQPGMTSNGPLPDPSMIRGSVPNQMMPRITPQSGLNQFGQMSM
AQPPIVPRQTPPLQHHGQLAQPGALNPPMGYGPRMQQPSNQGQFLPQTQFPSQGMNVTNI
PLAPSSGQAPVSQAQMSSSSCPVNSPIMPPGSQGSHIHCPQLPQPALHQNSPSPVPSRTP
TPHHTPPSIGAQQPPATTIPAPVPTPPAMPPGPQSQALHPPPRQTPTPPTTQLPQQVQPS
LPAAPSADQPQQQPRSQQSTAASVPTPTAPLLPPQPATPLSQPAVSIEGQVSNPPSTSST
EVNSQAIAEKQPSQEVKMEAKMEVDQPEPADTQPEDISESKVEDCKMESTETEERSTELK
TEIKEEEDQPSTSATQSSPAPGQSKKKIFKPEELRQALMPTLEALYRQDPESLPFRQPVD
PQLLGIPDYFDIVKSPMDLSTIKRKLDTGQYQEPWQYVDDIWLMFNNAWLYNRKTSRVYK
YCSKLSEVFEQEIDPVMQSLGYCCGRKLEFSPQTLCCYGKQLCTIPRDATYYSYQNRYHF
CEKCFNEIQGESVSLGDDPSQPQTTINKEQFSKRKNDTLDPELFVECTECGRKMHQICVL
HHEIIWPAGFVCDGCLKKSARTRKENKFSAKRLPSTRLGTFLENRVNDFLRRQNHPESGE
VTVRVVHASDKTVEVKPGMKARFVDSGEMAESFPYRTKALFAFEEIDGVDLCFFGMHVQE
YGSDCPPPNQRRVYISYLDSVHFFRPKCLRTAVYHEILIGYLEYVKKLGYTTGHIWACPP
SEGDDYIFHCHPPDQKIPKPKRLQEWYKKMLDKAVSERIVHDYKDIFKQATEDRLTSAKE
LPYFEGDFWPNVLEESIKELEQEEEERKREENTSNESTDVTKGDSKNAKKKNNKKTSKNK
SSLSRGNKKKPGMPNVSNDLSQKLYATMEKHKEVFFVIRLIAGPAANSLPPIVDPDPLIP
CDLMDGRDAFLTLARDKHLEFSSLRRAQWSTMCMLVELHTQSQDRFVYTCNECKHHVETR
WHCTVCEDYDLCITCYNTKNHDHKMEKLGLGLDDESNNQQAAATQSPGDSRRLSIQRCIQ
SLVHACQCRNANCSLPSCQKMKRVVQHTKGCKRKTNGGCPICKQLIALCCYHAKHCQENK
CPVPFCLNIKQKLRQQQLQHRLQQAQMLRRRMASMQRTGVVGQQQGLPSPTPATPTTPTG
QQPTTPQTPQPTSQPQPTPPNSMPPYLPRTQAAGPVSQGKAAGQVTPPTPPQTAQPPLPG
PPPAAVEMAMQIQRAAETQRQMAHVQIFQRPIQHQMPPMTPMAPMGMNPPPMTRGPSGHL
EPGMGPTGMQQQPPWSQGGLPQPQQLQSGMPRPAMMSVAQHGQPLNMAPQPGLGQVGISP
LKPGTVSQQALQNLLRTLRSPSSPLQQQQVLSILHANPQLLAAFIKQRAAKYANSNPQPI
PGQPGMPQGQPGLQPPTMPGQQGVHSNPAMQNMNPMQAGVQRAGLPQQQPQQQLQPPMGG
MSPQAQQMNMNHNTMPSQFRDILRRQQMMQQQQQQGAGPGIGPGMANHNQFQQPQGVGYP
PQQQQRMQHHMQQMQQGNMGQIGQLPQALGAEAGASLQAYQQRLLQQQMGSPVQPNPMSP
QQHMLPNQAQSPHLQGQQIPNSLSNQVRSPQPVPSPRPQSQPPHSSPSPRMQPQPSPHHV
SPQTSSPHPGLVAAQANPMEQGHFASPDQNSMLSQLASNPGMANLHGASATDLGLSTDNS
DLNSNLSQSTLDIH
Function
Acetylates all four core histones in nucleosomes. Histone acetylation gives an epigenetic tag for transcriptional activation. Mediates cAMP-gene regulation by binding specifically to phosphorylated CREB protein. Mediates acetylation of histone H3 at 'Lys-122' (H3K122ac), a modification that localizes at the surface of the histone octamer and stimulates transcription, possibly by promoting nucleosome instability. Mediates acetylation of histone H3 at 'Lys-27' (H3K27ac). Also functions as acetyltransferase for non-histone targets, such as ALX1, HDAC1, PRMT1 or SIRT2. Acetylates 'Lys-131' of ALX1 and acts as its coactivator. Acetylates SIRT2 and is proposed to indirectly increase the transcriptional activity of TP53 through acetylation and subsequent attenuation of SIRT2 deacetylase function. Acetylates HDAC1 leading to its inactivation and modulation of transcription. Acts as a TFAP2A-mediated transcriptional coactivator in presence of CITED2. Plays a role as a coactivator of NEUROD1-dependent transcription of the secretin and p21 genes and controls terminal differentiation of cells in the intestinal epithelium. Promotes cardiac myocyte enlargement. Can also mediate transcriptional repression. Acetylates FOXO1 and enhances its transcriptional activity. Acetylates BCL6 wich disrupts its ability to recruit histone deacetylases and hinders its transcriptional repressor activity. Participates in CLOCK or NPAS2-regulated rhythmic gene transcription; exhibits a circadian association with CLOCK or NPAS2, correlating with increase in PER1/2 mRNA and histone H3 acetylation on the PER1/2 promoter. Acetylates MTA1 at 'Lys-626' which is essential for its transcriptional coactivator activity. Acetylates XBP1 isoform 2; acetylation increases protein stability of XBP1 isoform 2 and enhances its transcriptional activity. Acetylates PCNA; acetylation promotes removal of chromatin-bound PCNA and its degradation during nucleotide excision repair (NER). Acetylates MEF2D. Acetylates and stabilizes ZBTB7B protein by antagonizing ubiquitin conjugation and degragation, this mechanism may be involved in CD4/CD8 lineage differentiation. In addition to protein acetyltransferase, can use different acyl-CoA substrates, such as (2E)-butenoyl-CoA (crotonyl-CoA), butanoyl-CoA (butyryl-CoA) or propanoyl-CoA (propionyl-CoA), and is able to mediate protein crotonylation, butyrylation or propionylation, respectively. Acts as a histone crotonyltransferase; crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. Histone crotonyltransferase activity is dependent on the concentration of (2E)-butenoyl-CoA (crotonyl-CoA) substrate and such activity is weak when (E)-but-2-enoyl-CoA (crotonyl-CoA) concentration is low. Also acts as a histone butyryltransferase; butyrylation marks active promoters. Functions as a transcriptional coactivator for SMAD4 in the TGF-beta signaling pathway. Acetylates PCK1 and promotes PCK1 anaplerotic activity. Functions as histone acetyltransferase and regulates transcription via chromatin remodeling.
KEGG Pathway
Viral life cycle - HIV-1 (hsa03250 )
cAMP signaling pathway (hsa04024 )
HIF-1 signaling pathway (hsa04066 )
FoxO signaling pathway (hsa04068 )
Cell cycle (hsa04110 )
Wnt signaling pathway (hsa04310 )
Notch signaling pathway (hsa04330 )
TGF-beta signaling pathway (hsa04350 )
Adherens junction (hsa04520 )
JAK-STAT signaling pathway (hsa04630 )
Long-term potentiation (hsa04720 )
Melanogenesis (hsa04916 )
Thyroid hormone signaling pathway (hsa04919 )
Glucagon signaling pathway (hsa04922 )
Growth hormone synthesis, secretion and action (hsa04935 )
Huntington disease (hsa05016 )
Tuberculosis (hsa05152 )
Hepatitis B (hsa05161 )
Influenza A (hsa05164 )
Human papillomavirus infection (hsa05165 )
Human T-cell leukemia virus 1 infection (hsa05166 )
Kaposi sarcoma-associated herpesvirus infection (hsa05167 )
Pathways in cancer (hsa05200 )
Viral carcinogenesis (hsa05203 )
MicroRNAs in cancer (hsa05206 )
Renal cell carcinoma (hsa05211 )
Prostate cancer (hsa05215 )
Reactome Pathway
RORA activates gene expression (R-HSA-1368082 )
Polo-like kinase mediated events (R-HSA-156711 )
Pre-NOTCH Transcription and Translation (R-HSA-1912408 )
PPARA activates gene expression (R-HSA-1989781 )
Formation of the beta-catenin (R-HSA-201722 )
Regulation of gene expression in late stage (branching morphogenesis) pancreatic bud precursor cells (R-HSA-210744 )
NOTCH1 Intracellular Domain Regulates Transcription (R-HSA-2122947 )
NOTCH2 intracellular domain regulates transcription (R-HSA-2197563 )
Constitutive Signaling by NOTCH1 PEST Domain Mutants (R-HSA-2644606 )
Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants (R-HSA-2894862 )
LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production (R-HSA-3134973 )
HATs acetylate histones (R-HSA-3214847 )
Attenuation phase (R-HSA-3371568 )
Transcriptional regulation of white adipocyte differentiation (R-HSA-381340 )
SUMOylation of transcription cofactors (R-HSA-3899300 )
Circadian Clock (R-HSA-400253 )
B-WICH complex positively regulates rRNA expression (R-HSA-5250924 )
Activation of anterior HOX genes in hindbrain development during early embryogenesis (R-HSA-5617472 )
CD209 (DC-SIGN) signaling (R-HSA-5621575 )
Metalloprotease DUBs (R-HSA-5689901 )
Formation of TC-NER Pre-Incision Complex (R-HSA-6781823 )
Transcription-Coupled Nucleotide Excision Repair (TC-NER) (R-HSA-6781827 )
Dual incision in TC-NER (R-HSA-6782135 )
Gap-filling DNA repair synthesis and ligation in TC-NER (R-HSA-6782210 )
TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest (R-HSA-6804114 )
Regulation of TP53 Activity through Acetylation (R-HSA-6804758 )
Regulation of TP53 Activity through Methylation (R-HSA-6804760 )
PI5P Regulates TP53 Acetylation (R-HSA-6811555 )
Activation of the TFAP2 (AP-2) family of transcription factors (R-HSA-8866907 )
RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function (R-HSA-8936459 )
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known (R-HSA-8939243 )
RUNX3 regulates NOTCH signaling (R-HSA-8941856 )
Regulation of RUNX3 expression and activity (R-HSA-8941858 )
RUNX3 regulates p14-ARF (R-HSA-8951936 )
NOTCH3 Intracellular Domain Regulates Transcription (R-HSA-9013508 )
NOTCH4 Intracellular Domain Regulates Transcription (R-HSA-9013695 )
Estrogen-dependent gene expression (R-HSA-9018519 )
NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux (R-HSA-9029569 )
NGF-stimulated transcription (R-HSA-9031628 )
TRAF3-dependent IRF activation pathway (R-HSA-918233 )
TRAF6 mediated IRF7 activation (R-HSA-933541 )
FOXO-mediated transcription of cell death genes (R-HSA-9614657 )
Transcriptional regulation of granulopoiesis (R-HSA-9616222 )
Regulation of FOXO transcriptional activity by acetylation (R-HSA-9617629 )
STAT3 nuclear events downstream of ALK signaling (R-HSA-9701898 )
Heme signaling (R-HSA-9707616 )
Nuclear events mediated by NFE2L2 (R-HSA-9759194 )
Regulation of gene expression by Hypoxia-inducible Factor (R-HSA-1234158 )

Molecular Interaction Atlas (MIA) of This DTT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DTT
2 Clinical Trial Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
CCS1477 DM9UZM1 Solid tumour/cancer 2A00-2F9Z Phase 1/2 [2]
FT-7051 DMCK3OI Prostate cancer 2C82.0 Phase 1 [3]
------------------------------------------------------------------------------------

References

1 Tumour suppressor EP300, a modulator of paclitaxel resistance and stemness, is downregulated in metaplastic breast cancer. Breast Cancer Res Treat. 2017 Jun;163(3):461-474.
2 Targeting the p300/CBP Axis in Lethal Prostate Cancer. Cancer Discov. 2021 May;11(5):1118-1137.
3 Clinical pipeline report, company report or official report of FORMA Therapeutics.