Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTONT0CN)

• DOT Name: Piercer of microtubule wall 1 protein (PIERCE1)
• Synonyms: Pierce1; UPF0691 protein C9orf116; p53-induced expression in RB-null cells protein 1
• Gene Name: PIERCE1
• UniProt ID: PIRC1_HUMAN
• PDB ID: 7UNG; 8J07
• Pfam ID: PF14892
• Sequence:
  MAEECPRACAEPVAPKATAPPERTSDYYRVSADLPGRFNNPGWFRGYRTQKAVSVYRTSN
  QAYGSRAPTVHEMPKVFYPNSNKFSQQLAAGGMFRNNTLNVYLEKSIVTGPDNCITSCDR
  LNFHPSYNINRPSICD
• Function: Microtubule inner protein involved in the attachment of outer dynein arms (ODAs) to dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is required for motile cilia beating. Functions at the initial step of left-right asymmetry specification of the visceral organs.
• Tissue Specificity: Expressed in airway epithelial cells.

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 Piercer of microtubule wall 1 protein (PIERCE1).	[1]

9 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 Piercer of microtubule wall 1 protein (PIERCE1).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Piercer of microtubule wall 1 protein (PIERCE1).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Piercer of microtubule wall 1 protein (PIERCE1).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Piercer of microtubule wall 1 protein (PIERCE1).	[5]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Piercer of microtubule wall 1 protein (PIERCE1).	[6]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol decreases the expression of Piercer of microtubule wall 1 protein (PIERCE1).	[7]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Piercer of microtubule wall 1 protein (PIERCE1).	[8]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Piercer of microtubule wall 1 protein (PIERCE1).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Piercer of microtubule wall 1 protein (PIERCE1).	[10]

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] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] 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.
• [7] The genomic response of a human uterine endometrial adenocarcinoma cell line to 17alpha-ethynyl estradiol. Toxicol Sci. 2009 Jan;107(1):40-55.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [10] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.