Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGS53SC)

• DOT Name: AP-5 complex subunit sigma-1 (AP5S1)
• Synonyms: Adaptor-related protein complex 5 sigma subunit; Sigma5
• Gene Name: AP5S1
• UniProt ID: AP5S1_HUMAN
• Pfam ID: PF15001
• Sequence:
  MVHAFLIHTLRAPNTEDTGLCRVLYSCVFGAEKSPDDPRPHGAERDRLLRKEQILAVARQ
  VESMCRLQQQASGRPPMDLQPQSSDEQVPLHEAPRGAFRLAAENPFQEPRTVVWLGVLSL
  GFALVLDAHENLLLAEGTLRLLTRLLLDHLRLLAPSTSLLLRADRIEGILTRFLPHGQLL
  FLNDQFVQGLEKEFSAAWPR
• Function: As part of AP-5, a probable fifth adaptor protein complex it may be involved in endosomal transport. According to PubMed:20613862, it is required for efficient homologous recombination DNA double-strand break repair.

Molecular Interaction Atlas (MIA) of This DOT

10 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 AP-5 complex subunit sigma-1 (AP5S1).	[1]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of AP-5 complex subunit sigma-1 (AP5S1).	[2]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of AP-5 complex subunit sigma-1 (AP5S1).	[3]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of AP-5 complex subunit sigma-1 (AP5S1).	[4]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of AP-5 complex subunit sigma-1 (AP5S1).	[4]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of AP-5 complex subunit sigma-1 (AP5S1).	[4]
2-deoxyglucose	DMIAHVU	Approved	2-deoxyglucose increases the expression of AP-5 complex subunit sigma-1 (AP5S1).	[4]
Pracinostat	DMTD7AB	Phase 3	Pracinostat decreases the expression of AP-5 complex subunit sigma-1 (AP5S1).	[4]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of AP-5 complex subunit sigma-1 (AP5S1).	[6]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of AP-5 complex subunit sigma-1 (AP5S1).	[4]

1 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 increases the methylation of AP-5 complex subunit sigma-1 (AP5S1).	[5]

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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [3] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [4] Development and validation of the TGx-HDACi transcriptomic biomarker to detect histone deacetylase inhibitors in human TK6 cells. Arch Toxicol. 2021 May;95(5):1631-1645. doi: 10.1007/s00204-021-03014-2. Epub 2021 Mar 26.
• [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.