Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTF5LO98)

• DOT Name: PCI domain-containing protein 2 (PCID2)
• Synonyms: CSN12-like protein
• Gene Name: PCID2
• UniProt ID: PCID2_HUMAN
• PDB ID: 3T5X
• Pfam ID: PF01399
• Sequence:
  MAHITINQYLQQVYEAIDSRDGASCAELVSFKHPHVANPRLQMASPEEKCQQVLEPPYDE
  MFAAHLRCTYAVGNHDFIEAYKCQTVIVQSFLRAFQAHKEENWALPVMYAVALDLRVFAN
  NADQQLVKKGKSKVGDMLEKAAELLMSCFRVCASDTRAGIEDSKKWGMLFLVNQLFKIYF
  KINKLHLCKPLIRAIDSSNLKDDYSTAQRVTYKYYVGRKAMFDSDFKQAEEYLSFAFEHC
  HRSSQKNKRMILIYLLPVKMLLGHMPTVELLKKYHLMQFAEVTRAVSEGNLLLLHEALAK
  HEAFFIRCGIFLILEKLKIITYRNLFKKVYLLLKTHQLSLDAFLVALKFMQVEDVDIDEV
  QCILANLIYMGHVKGYISHQHQKLVVSKQNPFPPLSTVC
• Function: Required for B-cell survival through the regulation of the expression of cell-cycle checkpoint MAD2L1 protein during B cell differentiation. As a component of the TREX-2 complex, involved in the export of mRNAs to the cytoplasm through the nuclear pores. Binds and stabilizes BRCA2 and is thus involved in the control of R-loop-associated DNA damage and transcription-associated genomic instability. Blocks the activity of the SRCAP chromatin remodeling complex by interacting with SRCAP complex member ZNHIT1 and inhibiting its interaction with the complex. This prevents the deposition of histone variant H2AZ1/H2A.Z at the nucleosomes of key lymphoid fate regulator genes which suppresses their expression and restricts lymphoid lineage commitment.

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of PCI domain-containing protein 2 (PCID2).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of PCI domain-containing protein 2 (PCID2).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of PCI domain-containing protein 2 (PCID2).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of PCI domain-containing protein 2 (PCID2).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of PCI domain-containing protein 2 (PCID2).	[4]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of PCI domain-containing protein 2 (PCID2).	[5]
Marinol	DM70IK5	Approved	Marinol decreases the expression of PCI domain-containing protein 2 (PCID2).	[6]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of PCI domain-containing protein 2 (PCID2).	[7]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of PCI domain-containing protein 2 (PCID2).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of PCI domain-containing protein 2 (PCID2).	[10]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of PCI domain-containing protein 2 (PCID2).	[11]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of PCI domain-containing protein 2 (PCID2).	[12]

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] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [3] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [4] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [5] 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.
• [6] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [7] Cannabidiol Activates Neuronal Precursor Genes in Human Gingival Mesenchymal Stromal Cells. J Cell Biochem. 2017 Jun;118(6):1531-1546. doi: 10.1002/jcb.25815. Epub 2016 Dec 29.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] 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.
• [10] Bisphenol A Exposure Changes the Transcriptomic and Proteomic Dynamics of Human Retinoblastoma Y79 Cells. Genes (Basel). 2021 Feb 11;12(2):264. doi: 10.3390/genes12020264.
• [11] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [12] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.