Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2Y8JFZ)

• DOT Name: RNA ligase 1 (RLIG1)
• Synonyms: EC 6.5.1.3; RNA ligase; Rnl
• Gene Name: RLIG1
• UniProt ID: RLIG1_HUMAN
• EC Number: 6.5.1.3
• Pfam ID: PF17720
• Sequence:
  MKRLGSVQRKMPCVFVTEVKEEPSSKREHQPFKVLATETVSHKALDADIYSAIPTEKVDG
  TCCYVTTYKDQPYLWARLDRKPNKQAEKRFKNFLHSKENPKEFFWNVEEDFKPAPECWIP
  AKETEQINGNPVPDENGHIPGWVPVEKNNKQYCWHSSVVNYEFEIALVLKHHPDDSGLLE
  ISAVPLSDLLEQTLELIGTNINGNPYGLGSKKHPLHLLIPHGAFQIRNLPSLKHNDLVSW
  FEDCKEGKIEGIVWHCSDGCLIKVHRHHLGLCWPIPDTYMNSRPVIINMNLNKCDSAFDI
  KCLFNHFLKIDNQKFVRLKDIIFDV
• Function: Functions as an RNA ligase, in vitro. The ligation reaction entails three nucleotidyl transfer steps. In the first step, the RNA ligase reacts with ATP in the absence of nucleic acid to form a covalent ligase-AMP intermediate and release pyrophosphate. In step 2, the ligase-AMP binds to the nucleic acid and transfers the adenylate to the 5'-PO4 terminus to form an adenylylated intermediate. In step 3, the RNA ligase directs the attack of the 3'-OH on the 5'-phosphoanhydride linkage, resulting in a repaired 3'-5' phosphodiester and release of AMP. Exhibits selectivity for single-stranded RNA substrates and may not have nick-sealing activity on double-stranded DNA-RNA hybrids. May play a role in maintaining RNA integrity under stress conditions, for example in response to reactive oxygen species (ROS).

Molecular Interaction Atlas (MIA) of This DOT

3 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 RNA ligase 1 (RLIG1).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of RNA ligase 1 (RLIG1).	[2]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of RNA ligase 1 (RLIG1).	[5]

2 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 affects the methylation of RNA ligase 1 (RLIG1).	[3]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of RNA ligase 1 (RLIG1).	[4]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [3] 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.
• [4] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [5] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.