Details of Drug Off-Target (DOT)

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

• DOT Name: Polyamine deacetylase HDAC10 (HDAC10)
• Synonyms: EC 3.5.1.48; EC 3.5.1.62; Histone deacetylase 10; HD10
• Gene Name: HDAC10
• UniProt ID: HDA10_HUMAN
• EC Number: 3.5.1.48; 3.5.1.62
• Pfam ID: PF00850
• Sequence:
  MGTALVYHEDMTATRLLWDDPECEIERPERLTAALDRLRQRGLEQRCLRLSAREASEEEL
  GLVHSPEYVSLVRETQVLGKEELQALSGQFDAIYFHPSTFHCARLAAGAGLQLVDAVLTG
  AVQNGLALVRPPGHHGQRAAANGFCVFNNVAIAAAHAKQKHGLHRILVVDWDVHHGQGIQ
  YLFEDDPSVLYFSWHRYEHGRFWPFLRESDADAVGRGQGLGFTVNLPWNQVGMGNADYVA
  AFLHLLLPLAFEFDPELVLVSAGFDSAIGDPEGQMQATPECFAHLTQLLQVLAGGRVCAV
  LEGGYHLESLAESVCMTVQTLLGDPAPPLSGPMAPCQSALESIQSARAAQAPHWKSLQQQ
  DVTAVPMSPSSHSPEGRPPPLLPGGPVCKAAASAPSSLLDQPCLCPAPSVRTAVALTTPD
  ITLVLPPDVIQQEASALREETEAWARPHESLAREEALTALGKLLYLLDGMLDGQVNSGIA
  ATPASAAAATLDVAVRRGLSHGAQRLLCVALGQLDRPPDLAHDGRSLWLNIRGKEAAALS
  MFHVSTPLPVMTGGFLSCILGLVLPLAYGFQPDLVLVALGPGHGLQGPHAALLAAMLRGL
  AGGRVLALLEENSTPQLAGILARVLNGEAPPSLGPSSVASPEDVQALMYLRGQLEPQWKM
  LQCHPHLVA
• Function: Polyamine deacetylase (PDAC), which acts preferentially on N(8)-acetylspermidine, and also on acetylcadaverine and acetylputrescine. Exhibits attenuated catalytic activity toward N(1),N(8)-diacetylspermidine and very low activity, if any, toward N(1)-acetylspermidine. Histone deacetylase activity has been observed in vitro. Has also been shown to be involved in MSH2 deacetylation. The physiological relevance of protein/histone deacetylase activity is unclear and could be very weak. May play a role in the promotion of late stages of autophagy, possibly autophagosome-lysosome fusion and/or lysosomal exocytosis in neuroblastoma cells. May play a role in homologous recombination. May promote DNA mismatch repair.
• Tissue Specificity: Widely expressed with high levels in liver and kidney.
• KEGG Pathway:
  Neutrophil extracellular trap formation (hsa04613)
  Alcoholism (hsa05034)
  Viral carcinogenesis (hsa05203)
• Reactome Pathway:
  Constitutive Signaling by NOTCH1 PEST Domain Mutants (R-HSA-2644606)
  Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants (R-HSA-2894862)
  HDACs deacetylate histones (R-HSA-3214815)
  Notch-HLH transcription pathway (R-HSA-350054)
  NOTCH1 Intracellular Domain Regulates Transcription (R-HSA-2122947)

Molecular Interaction Atlas (MIA) of This DOT

6 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Polyamine deacetylase HDAC10 (HDAC10).	[1]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Polyamine deacetylase HDAC10 (HDAC10).	[2]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of Polyamine deacetylase HDAC10 (HDAC10).	[3]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Polyamine deacetylase HDAC10 (HDAC10).	[4]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Polyamine deacetylase HDAC10 (HDAC10).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Polyamine deacetylase HDAC10 (HDAC10).	[7]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Polyamine deacetylase HDAC10 (HDAC10).	[5]

References

• [1] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [2] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [3] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [4] Estrogen receptor alpha (ER)-mediated coregulator binding and gene expression discriminates the toxic ER agonist diethylstilbestrol (DES) from the endogenous ER agonist 17-estradiol (E2). Cell Biol Toxicol. 2020 Oct;36(5):417-435. doi: 10.1007/s10565-020-09516-6. Epub 2020 Feb 22.
• [5] 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.
• [6] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [7] 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.