Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5THLYG)

• DOT Name: Protein transport protein Sec61 subunit alpha isoform 2 (SEC61A2)
• Synonyms: Sec61 alpha-2
• Gene Name: SEC61A2
• UniProt ID: S61A2_HUMAN
• Pfam ID: PF10559 ; PF00344
• Sequence:
  MGIKFLEVIKPFCAVLPEIQKPERKIQFREKVLWTAITLFIFLVCCQIPLFGIMSSDSAD
  PFYWMRVILASNRGTLMELGISPIVTSGLIMQLLAGAKIIEVGDTPKDRALFNGAQKLFG
  MIITIGQAIVYVMTGMYGDPAEMGAGICLLIIIQLFVAGLIVLLLDELLQKGYGLGSGIS
  LFIATNICETIVWKAFSPTTINTGRGTEFEGAVIALFHLLATRTDKVRALREAFYRQNLP
  NLMNLIATVFVFAVVIYFQGFRVDLPIKSARYRGQYSSYPIKLFYTSNIPIILQSALVSN
  LYVISQMLSVRFSGNFLVNLLGQWADVSGGGPARSYPVGGLCYYLSPPESMGAIFEDPVH
  VVVYIIFMLGSCAFFSKTWIEVSGSSAKDVAKQLKEQQMVMRGHRDTSMVHELNRYIPTA
  AAFGGLCIGALSVLADFLGAIGSGTGILLAVTIIYQYFEIFVKEQAEVGGMGALFF
• Function: Component of SEC61 channel-forming translocon complex that mediates transport of signal peptide-containing precursor polypeptides across the endoplasmic reticulum (ER). Forms a ribosome receptor and a gated pore in the ER membrane, both functions required for cotranslational translocation of nascent polypeptides.
• KEGG Pathway:
  Protein export (hsa03060)
  Protein processing in endoplasmic reticulum (hsa04141)
  Phagosome (hsa04145)
  Vibrio cholerae infection (hsa05110)
• Reactome Pathway:
  SRP-dependent cotranslational protein targeting to membrane (R-HSA-1799339)
  ER-Phagosome pathway (R-HSA-1236974)

Molecular Interaction Atlas (MIA) of This DOT

6 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 Protein transport protein Sec61 subunit alpha isoform 2 (SEC61A2).	[1]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Protein transport protein Sec61 subunit alpha isoform 2 (SEC61A2).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protein transport protein Sec61 subunit alpha isoform 2 (SEC61A2).	[3]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Protein transport protein Sec61 subunit alpha isoform 2 (SEC61A2).	[4]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Protein transport protein Sec61 subunit alpha isoform 2 (SEC61A2).	[5]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Protein transport protein Sec61 subunit alpha isoform 2 (SEC61A2).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Protein transport protein Sec61 subunit alpha isoform 2 (SEC61A2).	[6]

References

• [1] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [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] 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.
• [4] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [5] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [6] 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.
• [7] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.