Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZTHVS2)

• DOT Name: Zinc phosphodiesterase ELAC protein 1 (ELAC1)
• Synonyms: EC 3.1.26.11; Deleted in Ma29; ElaC homolog protein 1; Ribonuclease Z 1; RNase Z 1; tRNA 3 endonuclease 1; tRNase Z 1
• Gene Name: ELAC1
• UniProt ID: RNZ1_HUMAN
• PDB ID: 3ZWF
• EC Number: 3.1.26.11
• Pfam ID: PF00753
• Sequence:
  MSMDVTFLGTGAAYPSPTRGASAVVLRCEGECWLFDCGEGTQTQLMKSQLKAGRITKIFI
  THLHGDHFFGLPGLLCTISLQSGSMVSKQPIEIYGPVGLRDFIWRTMELSHTELVFHYVV
  HELVPTADQCPAEELKEFAHVNRADSPPKEEQGRTILLDSEENSYLLFDDEQFVVKAFRL
  FHRIPSFGFSVVEKKRPGKLNAQKLKDLGVPPGPAYGKLKNGISVVLENGVTISPQDVLK
  KPIVGRKICILGDCSGVVGDGGVKLCFEADLLIHEATLDDAQMDKAKEHGHSTPQMAATF
  AKLCRAKRLVLTHFSQRYKPVALAREGETDGIAELKKQAESVLDLQEVTLAEDFMVISIP
  IKK
• Function: Zinc phosphodiesterase, which displays some tRNA 3'-processing endonuclease activity. Specifically involved in tRNA repair: acts downstream of the ribosome-associated quality control (RQC) pathway by removing a 2',3'-cyclic phosphate from tRNAs following cleavage by ANKZF1. tRNAs are then processed by TRNT1.
• Tissue Specificity: Widely expressed . Expressed in heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas .

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Zinc phosphodiesterase ELAC protein 1 (ELAC1).	[1]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Zinc phosphodiesterase ELAC protein 1 (ELAC1).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Zinc phosphodiesterase ELAC protein 1 (ELAC1).	[3]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Zinc phosphodiesterase ELAC protein 1 (ELAC1).	[5]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Zinc phosphodiesterase ELAC protein 1 (ELAC1).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Zinc phosphodiesterase ELAC protein 1 (ELAC1).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Zinc phosphodiesterase ELAC protein 1 (ELAC1).	[6]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [3] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [4] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [5] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [6] 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.
• [7] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.