Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5LPQTR)

DOT Name	Histone acetyltransferase KAT8 (KAT8)
Synonyms	EC 2.3.1.48; Lysine acetyltransferase 8; MOZ, YBF2/SAS3, SAS2 and TIP60 protein 1; MYST-1; hMOF
Gene Name	KAT8
Related Disease	Breast cancer ( ) Melanoma ( ) Non-insulin dependent diabetes ( ) Abdominal aortic aneurysm ( ) Acute myelogenous leukaemia ( ) Adult glioblastoma ( ) Adult respiratory distress syndrome ( ) Advanced cancer ( ) Alzheimer disease ( ) Anxiety ( ) Autism ( ) Brachydactyly type C ( ) Breast carcinoma ( ) Breast neoplasm ( ) Cardiac failure ( ) Clear cell renal carcinoma ( ) Colorectal carcinoma ( ) Congestive heart failure ( ) Cowden disease ( ) Epithelial ovarian cancer ( ) Glioblastoma multiforme ( ) Glioma ( ) Hepatitis C virus infection ( ) Hyperphosphatemia ( ) Hypertrophic cardiomyopathy ( ) Intellectual disability ( ) Kidney neoplasm ( ) leukaemia ( ) Leukemia ( ) Li-Ghorbani-Weisz-Hubshman syndrome ( ) Lung cancer ( ) Lung carcinoma ( ) Medulloblastoma ( ) Metastatic prostate carcinoma ( ) Multiple sclerosis ( ) Non-small-cell lung cancer ( ) Osteoporosis ( ) Ovarian cancer ( ) Ovarian neoplasm ( ) Renal cell carcinoma ( ) Schizophrenia ( ) Bacterial infection ( ) Metastatic malignant neoplasm ( ) Cystinuria ( ) Prostate cancer ( ) Prostate carcinoma ( )
UniProt ID	KAT8_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	2GIV; 2PQ8; 2Y0M; 3QAH; 3TOA; 3TOB; 4DNC; 5H43; 5J8C; 5J8F; 5WCI; 6BA2; 6BA4; 6CT2; 6OIN; 6OIO; 6OIP; 6OIQ; 6OIR; 6OWH; 6OWI; 6PD8; 6PD9; 6PDA; 6PDB; 6PDC; 6PDD; 6PDE; 6PDF; 6PDG; 7CMR
EC Number	2.3.1.48
Pfam ID	PF01853 ; PF11717 ; PF17772
Sequence	MAAQGAAAAVAAGTSGVAGEGEPGPGENAAAEGTAPSPGRVSPPTPARGEPEVTVEIGET YLCRRPDSTWHSAEVIQSRVNDQEGREEFYVHYVGFNRRLDEWVDKNRLALTKTVKDAVQ KNSEKYLSELAEQPERKITRNQKRKHDEINHVQKTYAEMDPTTAALEKEHEAITKVKYVD KIHIGNYEIDAWYFSPFPEDYGKQPKLWLCEYCLKYMKYEKSYRFHLGQCQWRQPPGKEI YRKSNISVYEVDGKDHKIYCQNLCLLAKLFLDHKTLYFDVEPFVFYILTEVDRQGAHIVG YFSKEKESPDGNNVACILTLPPYQRRGYGKFLIAFSYELSKLESTVGSPEKPLSDLGKLS YRSYWSWVLLEILRDFRGTLSIKDLSQMTSITQNDIISTLQSLNMVKYWKGQHVICVTPK LVEEHLKSAQYKKPPITVDSVCLKWAPPKHKQVKLSKK
Function	Histone acetyltransferase which may be involved in transcriptional activation. May influence the function of ATM. As part of the MSL complex it is involved in acetylation of nucleosomal histone H4 producing specifically H4K16ac. As part of the NSL complex it may be involved in acetylation of nucleosomal histone H4 on several lysine residues. That activity is less specific than the one of the MSL complex. Can also acetylate TP53/p53 at 'Lys-120'.
Reactome Pathway	Formation of WDR5-containing histone-modifying complexes (R-HSA-9772755 ) HATs acetylate histones (R-HSA-3214847 )

Molecular Interaction Atlas (MIA) of This DOT

46 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Breast cancer	DIS7DPX1	Definitive	Biomarker	[1]
Melanoma	DIS1RRCY	Definitive	Biomarker	[2]
Non-insulin dependent diabetes	DISK1O5Z	Definitive	Biomarker	[3]
Abdominal aortic aneurysm	DISD06OF	Strong	Biomarker	[4]
Acute myelogenous leukaemia	DISCSPTN	Strong	Altered Expression	[5]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[6]
Adult respiratory distress syndrome	DISIJV47	Strong	Biomarker	[7]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[8]
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[9]
Anxiety	DISIJDBA	Strong	Genetic Variation	[10]
Autism	DISV4V1Z	Strong	Biomarker	[11]
Brachydactyly type C	DISZ8FTZ	Strong	Biomarker	[12]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[1]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[13]
Cardiac failure	DISDC067	Strong	Biomarker	[14]
Clear cell renal carcinoma	DISBXRFJ	Strong	Altered Expression	[15]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[15]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[14]
Cowden disease	DISMYKCE	Strong	Biomarker	[16]
Epithelial ovarian cancer	DIS56MH2	Strong	Altered Expression	[17]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[6]
Glioma	DIS5RPEH	Strong	Altered Expression	[6]
Hepatitis C virus infection	DISQ0M8R	Strong	Altered Expression	[18]
Hyperphosphatemia	DISHW3R3	Strong	Biomarker	[19]
Hypertrophic cardiomyopathy	DISQG2AI	Strong	Biomarker	[14]
Intellectual disability	DISMBNXP	Strong	Genetic Variation	[11]
Kidney neoplasm	DISBNZTN	Strong	Altered Expression	[20]
leukaemia	DISS7D1V	Strong	Biomarker	[5]
Leukemia	DISNAKFL	Strong	Biomarker	[5]
Li-Ghorbani-Weisz-Hubshman syndrome	DIS3RMNZ	Strong	Autosomal dominant	[21]
Lung cancer	DISCM4YA	Strong	Biomarker	[22]
Lung carcinoma	DISTR26C	Strong	Biomarker	[22]
Medulloblastoma	DISZD2ZL	Strong	Altered Expression	[23]
Metastatic prostate carcinoma	DISVBEZ9	Strong	Biomarker	[24]
Multiple sclerosis	DISB2WZI	Strong	Biomarker	[25]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[26]
Osteoporosis	DISF2JE0	Strong	Genetic Variation	[27]
Ovarian cancer	DISZJHAP	Strong	Altered Expression	[17]
Ovarian neoplasm	DISEAFTY	Strong	Altered Expression	[17]
Renal cell carcinoma	DISQZ2X8	Strong	Altered Expression	[15]
Schizophrenia	DISSRV2N	Strong	Biomarker	[28]
Bacterial infection	DIS5QJ9S	moderate	Biomarker	[29]
Metastatic malignant neoplasm	DIS86UK6	moderate	Biomarker	[30]
Cystinuria	DISCU7CO	Limited	Biomarker	[31]
Prostate cancer	DISF190Y	Limited	Genetic Variation	[32]
Prostate carcinoma	DISMJPLE	Limited	Genetic Variation	[32]
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⏷ Show the Full List of 46 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Histone acetyltransferase KAT8 (KAT8) decreases the response to substance of Arsenic.	[40]
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5 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Histone acetyltransferase KAT8 (KAT8).	[33]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Histone acetyltransferase KAT8 (KAT8).	[34]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Histone acetyltransferase KAT8 (KAT8).	[36]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Histone acetyltransferase KAT8 (KAT8).	[38]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Histone acetyltransferase KAT8 (KAT8).	[39]
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4 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Quercetin	DM3NC4M	Approved	Quercetin decreases the phosphorylation of Histone acetyltransferase KAT8 (KAT8).	[35]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Histone acetyltransferase KAT8 (KAT8).	[37]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Histone acetyltransferase KAT8 (KAT8).	[35]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Histone acetyltransferase KAT8 (KAT8).	[35]
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References

1	Enhanced Photodynamic Therapy by Reduced Levels of Intracellular Glutathione Obtained By Employing a Nano-MOF with Cu(II) as the Active Center.Angew Chem Int Ed Engl. 2018 Apr 23;57(18):4891-4896. doi: 10.1002/anie.201710800. Epub 2018 Mar 23.
2	Catalase-like metal-organic framework nanoparticles to enhance radiotherapy in hypoxic cancer and prevent cancer recurrence.Chem Sci. 2019 Apr 25;10(22):5773-5778. doi: 10.1039/c9sc00747d. eCollection 2019 Jun 14.
3	THE ASSOCIATIONS BETWEEN HYPOVITAMINOSIS D, HIGHER PTH LEVELS WITH BONE MINERAL DENSITIES, AND RISK OF THE 10-YEAR PROBABILITY OF MAJOR OSTEOPOROTIC FRACTURES IN CHINESE PATIENTS WITH T2DM.Endocr Pract. 2018 Apr;24(4):334-341. doi: 10.4158/EP-2017-0164.
4	Histone acetylation and histone acetyltransferases show significant alterations in human abdominal aortic aneurysm.Clin Epigenetics. 2016 Jan 13;8:3. doi: 10.1186/s13148-016-0169-6. eCollection 2016.
5	Histone Acetyltransferase Activity of MOF Is Required for MLL-AF9 Leukemogenesis.Cancer Res. 2017 Apr 1;77(7):1753-1762. doi: 10.1158/0008-5472.CAN-16-2374. Epub 2017 Feb 15.
6	MYST1/KAT8 contributes to tumor progression by activating EGFR signaling in glioblastoma cells.Cancer Med. 2019 Dec;8(18):7793-7808. doi: 10.1002/cam4.2639. Epub 2019 Nov 5.
7	Effects of adjunct treatments on end-organ damage and histological injury severity in acute respiratory distress syndrome and multiorgan failure caused by smoke inhalation injury and burns.Burns. 2019 Dec;45(8):1765-1774. doi: 10.1016/j.burns.2019.07.020. Epub 2019 Aug 2.
8	Bimetallic ZrHf-based metal-organic framework embedded with carbon dots: Ultra-sensitive platform for early diagnosis of HER2 and HER2-overexpressed living cancer cells.Biosens Bioelectron. 2019 Jun 1;134:8-15. doi: 10.1016/j.bios.2019.03.043. Epub 2019 Mar 22.
9	Genome-wide meta-analysis identifies new loci and functional pathways influencing Alzheimer's disease risk.Nat Genet. 2019 Mar;51(3):404-413. doi: 10.1038/s41588-018-0311-9. Epub 2019 Jan 7.
10	Meta-analysis of genome-wide association studies for neuroticism in 449,484 individuals identifies novel genetic loci and pathways.Nat Genet. 2018 Jul;50(7):920-927. doi: 10.1038/s41588-018-0151-7. Epub 2018 Jun 25.
11	Lysine acetyltransferase 8 is involved in cerebral development and syndromic intellectual disability. J Clin Invest. 2020 Mar 2;130(3):1431-1445. doi: 10.1172/JCI131145.
12	Building MOF Nanocomposites with Oxidized Graphitic Carbon Nitride Nanospheres: The Effect of Framework Geometry on the Structural Heterogeneity.Molecules. 2019 Dec 11;24(24):4529. doi: 10.3390/molecules24244529.
13	Histone-modifier gene expression profiles are associated with pathological and clinical outcomes in human breast cancer.Anticancer Res. 2011 Dec;31(12):4115-25.
14	MOF Acetyl Transferase Regulates Transcription and Respiration in Mitochondria.Cell. 2016 Oct 20;167(3):722-738.e23. doi: 10.1016/j.cell.2016.09.052.
15	Correlation of low expression of hMOF with clinicopathological features of colorectal carcinoma, gastric cancer and renal cell carcinoma.Int J Oncol. 2014 Apr;44(4):1207-14. doi: 10.3892/ijo.2014.2266. Epub 2014 Jan 21.
16	Homochiral MOF as Circular Dichroism Sensor for Enantioselective Recognition on Nature and Chirality of Unmodified Amino Acids.ACS Appl Mater Interfaces. 2017 Jun 21;9(24):20991-20999. doi: 10.1021/acsami.7b04640. Epub 2017 Jun 6.
17	Expression of hMOF in different ovarian tissues and its effects on ovarian cancer prognosis.Oncol Rep. 2015 Feb;33(2):685-92. doi: 10.3892/or.2014.3649. Epub 2014 Dec 5.
18	A genetic screen identifies interferon- effector genes required to suppress hepatitis C virus replication.Gastroenterology. 2013 Jun;144(7):1438-49, 1449.e1-9. doi: 10.1053/j.gastro.2013.02.026. Epub 2013 Feb 24.
19	Treatment of hyperphosphatemia based on specific interactions between phosphorus and Zr(iv) active centers of nano-MOFs.Chem Sci. 2018 Jul 23;9(38):7483-7487. doi: 10.1039/c8sc02638f. eCollection 2018 Oct 14.
20	Epigenetic change in kidney tumor: downregulation of histone acetyltransferase MYST1 in human renal cell carcinoma.J Exp Clin Cancer Res. 2013 Feb 9;32(1):8. doi: 10.1186/1756-9966-32-8.
21	Histone acetyltransferase KAT8 is essential for mouse oocyte development by regulating reactive oxygen species levels. Development. 2017 Jun 15;144(12):2165-2174. doi: 10.1242/dev.149518. Epub 2017 May 15.
22	Selective Surface Enhanced Raman Scattering for Quantitative Detection of Lung Cancer Biomarkers in Superparticle@MOF Structure.Adv Mater. 2018 Feb;30(5). doi: 10.1002/adma.201702275. Epub 2017 Dec 11.
23	The histone acetyltransferase hMOF is frequently downregulated in primary breast carcinoma and medulloblastoma and constitutes a biomarker for clinical outcome in medulloblastoma.Int J Cancer. 2008 Mar 15;122(6):1207-13. doi: 10.1002/ijc.23283.
24	The aspirin metabolite salicylate inhibits lysine acetyltransferases and MUC1 induced epithelial to mesenchymal transition.Sci Rep. 2017 Jul 17;7(1):5626. doi: 10.1038/s41598-017-06149-4.
25	-Cyclodextrin-metal organic frameworks as efficient microcontainers for encapsulation of leflunomide and acceleration of its transformation into teriflunomide.Carbohydr Polym. 2019 Jul 15;216:224-230. doi: 10.1016/j.carbpol.2019.04.037. Epub 2019 Apr 9.
26	The histone acetylranseferase hMOF acetylates Nrf2 and regulates anti-drug responses in human non-small cell lung cancer.Br J Pharmacol. 2014 Jul;171(13):3196-211. doi: 10.1111/bph.12661.
27	Performance of FRAX in clinical practice according to sex and osteoporosis definitions: the Manitoba BMD registry.Osteoporos Int. 2018 Mar;29(3):759-767. doi: 10.1007/s00198-018-4415-y. Epub 2018 Feb 5.
28	22q11.2 deletion carriers and schizophrenia-associated novel variants.Br J Psychiatry. 2014;204:398-9. doi: 10.1192/bjp.bp.113.138420. Epub 2014 Jan 30.
29	Porous Iron-Carboxylate Metal-Organic Framework: A Novel Bioplatform with Sustained Antibacterial Efficacy and Nontoxicity.ACS Appl Mater Interfaces. 2017 Jun 7;9(22):19248-19257. doi: 10.1021/acsami.7b04810. Epub 2017 May 30.
30	MOF Acetylates the Histone Demethylase LSD1 to Suppress Epithelial-to-Mesenchymal Transition.Cell Rep. 2016 Jun 21;15(12):2665-78. doi: 10.1016/j.celrep.2016.05.050. Epub 2016 Jun 9.
31	A highly selective and sensitive fluorescent sensor based on Tb(3+)-functionalized MOFs to determine arginine in urine: a potential application for the diagnosis of cystinuria.Analyst. 2019 Oct 7;144(19):5875-5881. doi: 10.1039/c9an01204d. Epub 2019 Sep 5.
32	Patients with prostate cancer and androgen deprivation therapy have increased risk of fractures-a study from the fractures and fall injuries in the elderly cohort (FRAILCO).Osteoporos Int. 2019 Jan;30(1):115-125. doi: 10.1007/s00198-018-4722-3. Epub 2018 Oct 15.
33	Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
34	Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
35	Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
36	Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells. Toxicol Appl Pharmacol. 2012 Jun 1;261(2):204-16.
37	Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
38	Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
39	Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
40	Quantitative mass spectrometry reveals the epigenome as a target of arsenic. Chem Biol Interact. 2011 Jun 30;192(1-2):113-7. doi: 10.1016/j.cbi.2010.11.003. Epub 2010 Nov 12.