Target Information
| Target General Information | Top | |||||
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| Target ID |
T16902
(Former ID: TTDI00174)
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| Target Name |
Histone acetyltransferase KAT2B (KAT2B)
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| Synonyms |
Spermidine acetyltransferase KAT2B; PCAF; P300/CBP-associated factor; P/CAF; Lysine acetyltransferase 2B; Histone acetyltransferase PCAF; Histone acetylase PCAF
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| Gene Name |
KAT2B
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| Target Type |
Literature-reported target
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[1] | ||||
| Function |
Has significant histone acetyltransferase activity with core histones (H3 and H4), and also with nucleosome core particles. Also acetylates non-histone proteins, such as ACLY, PLK4 and TBX5. Inhibits cell-cycle progression and counteracts the mitogenic activity of the adenoviral oncoprotein E1A. Acts as a circadian transcriptional coactivator which enhances the activity of the circadian transcriptional activators: NPAS2-ARNTL/BMAL1 and CLOCK-ARNTL/BMAL1 heterodimers. Involved in heart and limb development by mediating acetylation of TBX5, acetylation regulating nucleocytoplasmic shuttling of TBX5. Acts as a negative regulator of centrosome amplification by mediating acetylation of PLK4. Also acetylates spermidine. Functions as a histone acetyltransferase (HAT) to promote transcriptional activation.
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| BioChemical Class |
Acyltransferase
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| UniProt ID | ||||||
| EC Number |
EC 2.3.1.48
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| Sequence |
MSEAGGAGPGGCGAGAGAGAGPGALPPQPAALPPAPPQGSPCAAAAGGSGACGPATAVAA
AGTAEGPGGGGSARIAVKKAQLRSAPRAKKLEKLGVYSACKAEESCKCNGWKNPNPSPTP PRADLQQIIVSLTESCRSCSHALAAHVSHLENVSEEEMNRLLGIVLDVEYLFTCVHKEED ADTKQVYFYLFKLLRKSILQRGKPVVEGSLEKKPPFEKPSIEQGVNNFVQYKFSHLPAKE RQTIVELAKMFLNRINYWHLEAPSQRRLRSPNDDISGYKENYTRWLCYCNVPQFCDSLPR YETTQVFGRTLLRSVFTVMRRQLLEQARQEKDKLPLEKRTLILTHFPKFLSMLEEEVYSQ NSPIWDQDFLSASSRTSQLGIQTVINPPPVAGTISYNSTSSSLEQPNAGSSSPACKASSG LEANPGEKRKMTDSHVLEEAKKPRVMGDIPMELINEVMSTITDPAAMLGPETNFLSAHSA RDEAARLEERRGVIEFHVVGNSLNQKPNKKILMWLVGLQNVFSHQLPRMPKEYITRLVFD PKHKTLALIKDGRVIGGICFRMFPSQGFTEIVFCAVTSNEQVKGYGTHLMNHLKEYHIKH DILNFLTYADEYAIGYFKKQGFSKEIKIPKTKYVGYIKDYEGATLMGCELNPRIPYTEFS VIIKKQKEIIKKLIERKQAQIRKVYPGLSCFKDGVRQIPIESIPGIRETGWKPSGKEKSK EPRDPDQLYSTLKSILQQVKSHQSAWPFMEPVKRTEAPGYYEVIRFPMDLKTMSERLKNR YYVSKKLFMADLQRVFTNCKEYNPPESEYYKCANILEKFFFSKIKEAGLIDK Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| HIT2.0 ID | T20TPU | |||||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: Coenzyme A | Ligand Info | |||||
| Structure Description | CRYSTAL STRUCTURE OF THE PCAF/COENZYME-A COMPLEX | PDB:1CM0 | ||||
| Method | X-ray diffraction | Resolution | 2.30 Å | Mutation | No | [6] |
| PDB Sequence |
KVIEFHVVGN
501 SLNQKPNKKI511 LMWLVGLQNV521 FSHQLPRMPK531 EYITRLVFDP541 KHKTLALIKD 551 GRVIGGICFR561 MFPSQGFTEI571 VFCAVTSNEQ581 VKGYGTHLMN591 HLKEYHIKHD 601 ILNFLTYADE611 YAIGYFKKQG621 FSKEIKIPKT631 KYVGYIKDYE641 GATLMGCELN 651 PR
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GLN525
3.349
LEU526
3.710
CYS574
2.333
ALA575
3.334
VAL576
2.853
GLU580
4.709
GLN581
3.137
VAL582
2.354
LYS583
3.375
GLY584
2.923
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: 3-methyl-2-[[(3~{R})-1-methylpiperidin-3-yl]amino]-5~{H}-pyrrolo[3,2-d]pyrimidin-4-one | Ligand Info | |||||
| Structure Description | Crystal structure of the human PCAF bromodomain in complex with compound 12 | PDB:6J3O | ||||
| Method | X-ray diffraction | Resolution | 2.11 Å | Mutation | No | [7] |
| PDB Sequence |
DQLYSTLKSI
735 LQQVKSHQSA745 WPFMEPVKRT755 EAPGYYEVIR765 FPMDLKTMSE775 RLKNRYYVSK 785 KLFMADLQRV795 FTNCKEYNPP805 ESEYYKCANI815 LEKFFFSKIK825 EAGLID |
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| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Human Pathway Affiliation
Biological Network Descriptors
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There is no similarity protein (E value < 0.005) for this target
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| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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| Viral life cycle - HIV-1 | hsa03250 | Affiliated Target |
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| Class: Genetic Information Processing => Information processing in viruses | Pathway Hierarchy | ||
| Notch signaling pathway | hsa04330 | Affiliated Target |
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| Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
| Thyroid hormone signaling pathway | hsa04919 | Affiliated Target |
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| Class: Organismal Systems => Endocrine system | Pathway Hierarchy | ||
| Degree | 59 | Degree centrality | 6.34E-03 | Betweenness centrality | 2.70E-03 |
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| Closeness centrality | 2.57E-01 | Radiality | 1.44E+01 | Clustering coefficient | 2.01E-01 |
| Neighborhood connectivity | 4.62E+01 | Topological coefficient | 4.69E-02 | Eccentricity | 11 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Regulators | Top | |||||
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| Target-regulating microRNAs | ||||||
| Target-interacting Proteins | ||||||
| References | Top | |||||
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| REF 1 | Specific inhibition of p300-HAT alters global gene expression and represses HIV replication. Chem Biol. 2007 Jun;14(6):645-57. | |||||
| REF 2 | 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: 2737). | |||||
| REF 3 | 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. | |||||
| REF 4 | Design, synthesis, and biological evaluation of a small-molecule inhibitor of the histone acetyltransferase Gcn5. Angew Chem Int Ed Engl. 2004 Jul 26;43(30):3974-6. | |||||
| REF 5 | Selective small molecules blocking HIV-1 Tat and coactivator PCAF association. J Am Chem Soc. 2005 Mar 2;127(8):2376-7. | |||||
| REF 6 | Crystal structure of the histone acetyltransferase domain of the human PCAF transcriptional regulator bound to coenzyme A. EMBO J. 1999 Jul 1;18(13):3521-32. | |||||
| REF 7 | Discovery of Pyrrolo[3,2- d]pyrimidin-4-one Derivatives as a New Class of Potent and Cell-Active Inhibitors of P300/CBP-Associated Factor Bromodomain. J Med Chem. 2019 May 9;62(9):4526-4542. | |||||
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