Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTULZE67)

• DOT Name: Pre-mRNA-splicing factor ISY1 homolog (ISY1)
• Gene Name: ISY1
• UniProt ID: ISY1_HUMAN
• PDB ID: 5YZG; 6FF7; 6ZYM; 7A5P; 8C6J; 8CH6
• Pfam ID: PF06246
• Sequence:
  MARNAEKAMTALARFRQAQLEEGKVKERRPFLASECTELPKAEKWRRQIIGEISKKVAQI
  QNAGLGEFRIRDLNDEINKLLREKGHWEVRIKELGGPDYGKVGPKMLDHEGKEVPGNRGY
  KYFGAAKDLPGVRELFEKEPLPPPRKTRAELMKAIDFEYYGYLDEDDGVIVPLEQEYEKK
  LRAELVEKWKAEREARLARGEKEEEEEEEEEINIYAVTEEESDEEGSQEKGGDDSQQKFI
  AHVPVPSQQEIEEALVRRKKMELLQKYASETLQAQSEEARRLLGY
• Function: Component of the spliceosome C complex required for the selective processing of microRNAs during embryonic stem cell differentiation. Required for the biogenesis of all miRNAs from the pri-miR-17-92 primary transcript except miR-92a. Only required for the biogenesis of miR-290 and miR-96 from the pri-miR-290-295 and pri-miR-96-183 primary transcripts, respectively. Required during the transition of embryonic stem cells (ESCs) from the naive to primed state. By enhancing miRNA biogenesis, promotes exit of ESCs from the naive state to an intermediate state of poised pluripotency, which precedes transition to the primed state. Involved in pre-mRNA splicing as component of the spliceosome.
• KEGG Pathway: Spliceosome (hsa03040)
• Reactome Pathway:
  Transcription-Coupled Nucleotide Excision Repair (TC-NER) (R-HSA-6781827)
  Dual incision in TC-NER (R-HSA-6782135)
  Gap-filling DNA repair synthesis and ligation in TC-NER (R-HSA-6782210)
  mRNA Splicing - Major Pathway (R-HSA-72163)
  Formation of TC-NER Pre-Incision Complex (R-HSA-6781823)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Pre-mRNA-splicing factor ISY1 homolog (ISY1).	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Pre-mRNA-splicing factor ISY1 homolog (ISY1).	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Pre-mRNA-splicing factor ISY1 homolog (ISY1).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Pre-mRNA-splicing factor ISY1 homolog (ISY1).	[4]

References

• [1] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [2] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [3] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.