Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTH4VJL)

DTT Name Histone acetyltransferase KAT6B (KAT6B)
Synonyms KAT6B
Gene Name KAT6B
DTT Type
Literature-reported target
 [1]
BioChemical Class
Acyltransferase
UniProt ID
KAT6B_HUMAN
TTD ID
T98275
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
EC 2.3.1.48
Sequence
MVKLANPLYTEWILEAIQKIKKQKQRPSEERICHAVSTSHGLDKKTVSEQLELSVQDGSV
LKVTNKGLASYKDPDNPGRFSSVKPGTFPKSAKGSRGSCNDLRNVDWNKLLRRAIEGLEE
PNGSSLKNIEKYLRSQSDLTSTTNNPAFQQRLRLGAKRAVNNGRLLKDGPQYRVNYGSLD
GKGAPQYPSAFPSSLPPVSLLPHEKDQPRADPIPICSFCLGTKESNREKKPEELLSCADC
GSSGHPSCLKFCPELTTNVKALRWQCIECKTCSACRVQGRNADNMLFCDSCDRGFHMECC
DPPLSRMPKGMWICQVCRPKKKGRKLLHEKAAQIKRRYAKPIGRPKNKLKQRLLSVTSDE
GSMNAFTGRGSPGRGQKTKVCTTPSSGHAASGKDSSSRLAVTDPTRPGATTKITTTSTYI
SASTLKVNKKTKGLIDGLTKFFTPSPDGRRSRGEIIDFSKHYRPRKKVSQKQSCTSHVLA
TGTTQKLKPPPSSLPPPTPISGQSPSSQKSSTATSSPSPQSSSSQCSVPSLSSLTTNSQL
KALFDGLSHIYTTQGQSRKKGHPSYAPPKRMRRKTELSSTAKSKAHFFGKRDIRSRFISH
SSSSSWGMARGSIFKAIAHFKRTTFLKKHRMLGRLKYKVTPQMGTPSPGKGSLTDGRIKP
DQDDDTEIKINIKQESADVNVIGNKDVVTEEDLDVFKQAQELSWEKIECESGVEDCGRYP
SVIEFGKYEIQTWYSSPYPQEYARLPKLYLCEFCLKYMKSKNILLRHSKKCGWFHPPANE
IYRRKDLSVFEVDGNMSKIYCQNLCLLAKLFLDHKTLYYDVEPFLFYVLTKNDEKGCHLV
GYFSKEKLCQQKYNVSCIMIMPQHQRQGFGRFLIDFSYLLSRREGQAGSPEKPLSDLGRL
SYLAYWKSVILEYLYHHHERHISIKAISRATGMCPHDIATTLQHLHMIDKRDGRFVIIRR
EKLILSHMEKLKTCSRANELDPDSLRWTPILISNAAVSEEEREAEKEAERLMEQASCWEK
EEQEILSTRANSRQSPAKVQSKNKYLHSPESRPVTGERGQLLELSKESSEEEEEEEDEEE
EEEEEEEEEDEEEEEEEEEEEEEENIQSSPPRLTKPQSVAIKRKRPFVLKKKRGRKRRRI
NSSVTTETISETTEVLNEPFDNSDEERPMPQLEPTCEIEVEEDGRKPVLRKAFQHQPGKK
RQTEEEEGKDNHCFKNADPCRNNMNDDSSNLKEGSKDNPEPLKCKQVWPKGTKRGLSKWR
QNKERKTGFKLNLYTPPETPMEPDEQVTVEEQKETSEGKTSPSPIRIEEEVKETGEALLP
QEENRREETCAPVSPNTSPGEKPEDDLIKPEEEEEEEEEEEEEEEEEEGEEEEGGGNVEK
DPDGAKSQEKEEPEISTEKEDSARLDDHEEEEEEDEEPSHNEDHDADDEDDSHMESAEVE
KEELPRESFKEVLENQETFLDLNVQPGHSNPEVLMDCGVDLTASCNSEPKELAGDPEAVP
ESDEEPPPGEQAQKQDQKNSKEVDTEFKEGNPATMEIDSETVQAVQSLTQESSEQDDTFQ
DCAETQEACRSLQNYTRADQSPQIATTLDDCQQSDHSSPVSSVHSHPGQSVRSVNSPSVP
ALENSYAQISPDQSAISVPSLQNMETSPMMDVPSVSDHSQQVVDSGFSDLGSIESTTENY
ENPSSYDSTMGGSICGNGSSQNSCSYSNLTSSSLTQSSCAVTQQMSNISGSCSMLQQTSI
SSPPTCSVKSPQGCVVERPPSSSQQLAQCSMAANFTPPMQLAEIPETSNANIGLYERMGQ
SDFGAGHYPQPSATFSLAKLQQLTNTLIDHSLPYSHSAAVTSYANSASLSTPLSNTGLVQ
LSQSPHSVPGGPQAQATMTPPPNLTPPPMNLPPPLLQRNMAASNIGISHSQRLQTQIASK
GHISMRTKSASLSPAAATHQSQIYGRSQTVAMQGPARTLTMQRGMNMSVNLMPAPAYNVN
SVNMNMNTLNAMNGYSMSQPMMNSGYHSNHGYMNQTPQYPMQMQMGMMGTQPYAQQPMQT
PPHGNMMYTAPGHHGYMNTGMSKQSLNGSYMRR
Function
Functions as histone acetyltransferase and regulates transcription via chromatin remodeling. 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 nonhistone targets. Acetylates 'Lys-131' of ALX1 and acts as its coactivator in the presence of CREBBP. Acetylates SIRT2 and is proposed to indirectly increase the transcriptional activity of TP53 through acetylation and subsequent attenuation ofSIRT2 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. Binds to and may be involved in the transforming capacity of the adenovirus E1A protein. In case of HIV-1 infection, it is recruited by the viral protein Tat. Regulates Tat's transactivating activity and may help inducing chromatin remodeling of proviral genes. 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 CLOCKor 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 (PubMed:10733570, PubMed:11430825, PubMed:11701890, PubMed:12402037, PubMed:12586840, PubMed:12929931, PubMed:14645221, PubMed:15186775, PubMed:15890677, PubMed:16617102, PubMed:16762839, PubMed:18722353,PubMed:18995842, PubMed:23415232, PubMed:23911289, PubMed:23934153, PubMed:8945521). Acetylates XBP1 isoform 2; acetylation increases protein stability of XBP1 isoform 2 and enhances its transcriptional activity.
KEGG Pathway
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 )
Huntington's disease (hsa05016 )
Tuberculosis (hsa05152 )
Hepatitis B (hsa05161 )
Influenza A (hsa05164 )
HTLV-I infection (hsa05166 )
Herpes simplex infection (hsa05168 )
Epstein-Barr virus infection (hsa05169 )
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 )
BMAL1 (R-HSA-1368108 )
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 )
YAP1- and WWTR1 (TAZ)-stimulated gene expression (R-HSA-2032785 )
NOTCH1 Intracellular Domain Regulates Transcription (R-HSA-2122947 )
NOTCH2 intracellular domain regulates transcription (R-HSA-2197563 )
DNA Damage/Telomere Stress Induced Senescence (R-HSA-2559586 )
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 )
Circadian Clock (R-HSA-400253 )
HDR through Single Strand Annealing (SSA) (R-HSA-5685938 )
HDR through Homologous Recombination (HRR) (R-HSA-5685942 )
Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks (R-HSA-5693565 )
Nonhomologous End-Joining (NHEJ) (R-HSA-5693571 )
Processing of DNA double-strand break ends (R-HSA-5693607 )
Presynaptic phase of homologous DNA pairing and strand exchange (R-HSA-5693616 )
Formation of TC-NER Pre-Incision Complex (R-HSA-6781823 )
Dual incision in TC-NER (R-HSA-6782135 )
Gap-filling DNA repair synthesis and ligation in TC-NER (R-HSA-6782210 )
G2/M DNA damage checkpoint (R-HSA-69473 )
RNA Polymerase I Transcription Initiation (R-HSA-73762 )
TRAF3-dependent IRF activation pathway (R-HSA-918233 )
TRAF6 mediated IRF7 activation (R-HSA-933541 )
Factors involved in megakaryocyte development and platelet production (R-HSA-983231 )
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
6 Investigative Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
anacardic acid DMAS5BI Discovery agent N.A. Investigative [2]
C646 DMCOQKH Discovery agent N.A. Investigative [3]
garcinol DM6B9ZG Discovery agent N.A. Investigative [4]
I-CBP112 DMQX3W6 Discovery agent N.A. Investigative [1]
MG149 DM7V58G Discovery agent N.A. Investigative [5]
SGC-CBP30 DMTLRGZ Discovery agent N.A. Investigative [6]
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⏷ Show the Full List of 6 Investigative Drug(s)

References

1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2735).
2 Small molecule modulators of histone acetyltransferase p300. J Biol Chem. 2003 May 23;278(21):19134-40.
3 Virtual ligand screening of the p300/CBP histone acetyltransferase: identification of a selective small molecule inhibitor. Chem Biol. 2010 May 28;17(5):471-82.
4 Polyisoprenylated benzophenone, garcinol, a natural histone acetyltransferase inhibitor, represses chromatin transcription and alters global gene e... J Biol Chem. 2004 Aug 6;279(32):33716-26.
5 6-alkylsalicylates are selective Tip60 inhibitors and target the acetyl-CoA binding site. Eur J Med Chem. 2012 Jan;47(1):337-44.
6 Bromodomains and their pharmacological inhibitors. ChemMedChem. 2014 Mar;9(3):438-64.