Target Information

Target General Information

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Target ID

T98275 (Former ID: TTDI01825)

Target Name

Histone acetyltransferase KAT6B (KAT6B)

Synonyms

KAT6B

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Gene Name

KAT6B

Target Type

Literature-reported target

[1]

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.

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BioChemical Class

Acyltransferase

UniProt ID

KAT6B_HUMAN

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

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3D Structure

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AlphaFold

Cell-based Target Expression Variations

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Cell-based Target Expression Variations

Cell-based Target Expression Variations Info

Different Human System Profiles of Target	Top
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 Tissue Distribution of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues. The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects (Nat Rev Drug Discov, 20: 64-81, 2021). 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 Tissue Distribution Biological Network Descriptors

Different Human System Profiles of Target

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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 Tissue Distribution of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.

The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects (Nat Rev Drug Discov, 20: 64-81, 2021).

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 Tissue Distribution

Biological Network Descriptors

Protein Name	Pfam ID	Percentage of Identity (%)	E value
Sterile alpha motif domain-containing protein 1 (SAMD1)	PF00536	40.000 (26/65)	3.47E-08
Lysine N-methyltransferase 3B (NSD1)	PF17907 ; PF17982 ; PF00855 ; PF00856 More >>	27.049 (33/122)	2.00E-03
E3 ubiquitin-protein ligase Jade-2 (JADE2)	PF10513 ; PF13831 ; PF13832 More >>	33.333 (16/48)	2.00E-03
Bromodomain and PHD finger containing 1 (BRPF1)	PF00439 ; PF10513 ; PF13831 ; PF00855 ; PF13832 More >>	36.735 (18/49)	3.00E-03
Bromodomain and PHD finger containing 3 (BRPF3)	PF00439 ; PF10513 ; PF13831 ; PF00855 ; PF13832 More >>	34.783 (16/46)	3.00E-03


Note: If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.

Degree	4	Degree centrality	4.30E-04	Betweenness centrality	4.29E-08
Closeness centrality	1.88E-01	Radiality	1.32E+01	Clustering coefficient	5.00E-01
Neighborhood connectivity	6.00E+00	Topological coefficient	5.00E-01	Eccentricity	12
Download	Click to Download the Full PPI Network of This Target

Drug Property Profile of Target

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(1) Molecular Weight (mw) based Drug Clustering

(2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering

(3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering

(4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering

(5) Rotatable Bond Count (rotbonds) based Drug Clustering

(6) Topological Polar Surface Area (polararea) based Drug Clustering

"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 Affiliated Biological Pathways		Top
KEGG Pathway	[+] 25 KEGG Pathways	+
1	cAMP signaling pathway
2	HIF-1 signaling pathway
3	FoxO signaling pathway
4	Cell cycle
5	Wnt signaling pathway
6	Notch signaling pathway
7	TGF-beta signaling pathway
8	Adherens junction
9	Jak-STAT signaling pathway
10	Long-term potentiation
11	Melanogenesis
12	Thyroid hormone signaling pathway
13	Glucagon signaling pathway
14	Huntington's disease
15	Tuberculosis
16	Hepatitis B
17	Influenza A
18	HTLV-I infection
19	Herpes simplex infection
20	Epstein-Barr virus infection
21	Pathways in cancer
22	Viral carcinogenesis
23	MicroRNAs in cancer
24	Renal cell carcinoma
25	Prostate cancer
Reactome	[+] 32 Reactome Pathways	+
1	Regulation of gene expression by Hypoxia-inducible Factor
2	RORA activates gene expression
3	BMAL1:CLOCK,NPAS2 activates circadian gene expression
4	Polo-like kinase mediated events
5	Pre-NOTCH Transcription and Translation
6	PPARA activates gene expression
7	Formation of the beta-catenin:TCF transactivating complex
8	YAP1- and WWTR1 (TAZ)-stimulated gene expression
9	NOTCH1 Intracellular Domain Regulates Transcription
10	NOTCH2 intracellular domain regulates transcription
11	DNA Damage/Telomere Stress Induced Senescence
12	Constitutive Signaling by NOTCH1 PEST Domain Mutants
13	Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants
14	LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production
15	HATs acetylate histones
16	Attenuation phase
17	Transcriptional regulation of white adipocyte differentiation
18	Circadian Clock
19	HDR through Single Strand Annealing (SSA)
20	HDR through Homologous Recombination (HRR)
21	Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks
22	Nonhomologous End-Joining (NHEJ)
23	Processing of DNA double-strand break ends
24	Presynaptic phase of homologous DNA pairing and strand exchange
25	Formation of TC-NER Pre-Incision Complex
26	Dual incision in TC-NER
27	Gap-filling DNA repair synthesis and ligation in TC-NER
28	G2/M DNA damage checkpoint
29	RNA Polymerase I Transcription Initiation
30	TRAF3-dependent IRF activation pathway
31	TRAF6 mediated IRF7 activation
32	Factors involved in megakaryocyte development and platelet production
WikiPathways	[+] 25 WikiPathways	+
1	SIDS Susceptibility Pathways
2	Notch Signaling Pathway
3	TGF Beta Signaling Pathway
4	Wnt Signaling Pathway and Pluripotency
5	IL-4 Signaling Pathway
6	TGF beta Signaling Pathway
7	Kit receptor signaling pathway
8	Nuclear Receptors Meta-Pathway
9	Aryl Hydrocarbon Receptor Pathway
10	Regulation of Lipid Metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha)
11	Cytosolic sensors of pathogen-associated DNA
12	Pre-NOTCH Expression and Processing
13	Transcriptional Regulation of White Adipocyte Differentiation
14	Regulation of Hypoxia-inducible Factor (HIF) by Oxygen
15	Signaling by NOTCH1
16	Signaling by NOTCH2
17	Aryl Hydrocarbon Receptor
18	Integrated Pancreatic Cancer Pathway
19	Signaling Pathways in Glioblastoma
20	Integrated Breast Cancer Pathway
21	RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways
22	Factors involved in megakaryocyte development and platelet production
23	Circadian Clock
24	Cell Cycle
25	Androgen receptor signaling pathway

References

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REF 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).

REF 2

Small molecule modulators of histone acetyltransferase p300. J Biol Chem. 2003 May 23;278(21):19134-40.

REF 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.

REF 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.

REF 5

6-alkylsalicylates are selective Tip60 inhibitors and target the acetyl-CoA binding site. Eur J Med Chem. 2012 Jan;47(1):337-44.

REF 6

Bromodomains and their pharmacological inhibitors. ChemMedChem. 2014 Mar;9(3):438-64.

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