Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTD7EDR8)

• DOT Name: SEC14-like protein 4 (SEC14L4)
• Synonyms: Tocopherol-associated protein 3
• Gene Name: SEC14L4
• UniProt ID: S14L4_HUMAN
• PDB ID: 4TLG
• Pfam ID: PF00650 ; PF03765
• Sequence:
  MSSRVGDLSPQQQEALARFRENLQDLLPILPNADDYFLLRWLRARNFDLQKSEDMLRRHM
  EFRKQQDLDNIVTWQPPEVIQLYDSGGLCGYDYEGCPVYFNIIGSLDPKGLLLSASKQDM
  IRKRIKVCELLLHECELQTQKLGRKIEMALMVFDMEGLSLKHLWKPAVEVYQQFFSILEA
  NYPETLKNLIVIRAPKLFPVAFNLVKSFMSEETRRKIVILGDNWKQELTKFISPDQLPVE
  FGGTMTDPDGNPKCLTKINYGGEVPKSYYLCEQVRLQYEHTRSVGRGSSLQVENEILFPG
  CVLRWQFASDGGDIGFGVFLKTKMGEQQSAREMTEVLPSQRYNAHMVPEDGSLTCLQAGV
  YVLRFDNTYSRMHAKKLSYTVEVLLPDKASEETLQSLKAMRPSPTQ
• Function: Probable hydrophobic ligand-binding protein; may play a role in the transport of hydrophobic ligands like tocopherol, squalene and phospholipids.

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of SEC14-like protein 4 (SEC14L4).	[1]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of SEC14-like protein 4 (SEC14L4).	[2]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of SEC14-like protein 4 (SEC14L4).	[4]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of SEC14-like protein 4 (SEC14L4).	[6]

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 SEC14-like protein 4 (SEC14L4).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of SEC14-like protein 4 (SEC14L4).	[5]

References

• [1] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [2] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [3] 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.
• [4] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [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] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.