Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRZQJV9)

• DOT Name: Protein SLX4IP (SLX4IP)
• Synonyms: SLX4-interacting protein
• Gene Name: SLX4IP
• Related Disease:
  Osteosarcoma
  Acute lymphocytic leukaemia
  Childhood acute lymphoblastic leukemia
• UniProt ID: SLX4I_HUMAN
• Pfam ID: PF15744
• Sequence:
  MASKKFAVKCGNFAVLVDLHILPQGSNKDTSWFSEQKKEEVCLLLKETIDSRVQEYLEVR
  KQHRPSNAEFTRSNPLSLKGYGFQITAYFLKRGIRLRCIRSTQNAELCVFPDRFVVCVSQ
  LAFSRDLLASQNEDLTERVLHGVSDYFAECAESSLPPSAKLRRNALKEIVKRTETKSSVT
  SKSQTRRDTVETSSDSVIAEIARRRNDGQASSSPPSESMGQAKDSIKAAESHWGLPVQKL
  EKVNQTQPEDTSGQQKPHPGERLKTGLLSRSPVCSCESASPCPKQSPRVAKTQQKRRNCS
  SAEDFDHHGRVSLGSDRLVPREIIVEKSKAVRVLPASELSDPGLLLKQDLAKTTSKEELH
  VLESLSSRHLMKNNPGQAQQTGLATNTERLSTIQNSPTKKRKKYERGH

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Osteosarcoma	DISLQ7E2	Definitive	Biomarker	[1]
Acute lymphocytic leukaemia	DISPX75S	Strong	Genetic Variation	[2]
Childhood acute lymphoblastic leukemia	DISJ5D6U	Strong	Genetic Variation	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Protein SLX4IP (SLX4IP).	[3]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Protein SLX4IP (SLX4IP).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Protein SLX4IP (SLX4IP).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 affects the sumoylation of Protein SLX4IP (SLX4IP).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Protein SLX4IP (SLX4IP).	[7]

References

• [1] SLX4IP Antagonizes Promiscuous BLM Activity during ALT Maintenance.Mol Cell. 2019 Oct 3;76(1):27-43.e11. doi: 10.1016/j.molcel.2019.07.010. Epub 2019 Aug 22.
• [2] Frequent and sex-biased deletion of SLX4IP by illegitimate V(D)J-mediated recombination in childhood acute lymphoblastic leukemia.Hum Mol Genet. 2014 Feb 1;23(3):590-601. doi: 10.1093/hmg/ddt447. Epub 2013 Sep 17.
• [3] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [4] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [5] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [6] 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.
• [7] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.