Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTV90DF7)

• DOT Name: Protein-L-isoaspartate O-methyltransferase domain-containing protein 2 (PCMTD2)
• Gene Name: PCMTD2
• UniProt ID: PCMD2_HUMAN
• Pfam ID: PF01135
• Sequence:
  MGGAVSAGEDNDELIDNLKEAQYIRTELVEQAFRAIDRADYYLEEFKENAYKDLAWKHGN
  IHLSAPCIYSEVMEALDLQPGLSFLNLGSGTGYLSSMVGLILGPFGVNHGVELHSDVIEY
  AKQKLDFFIRTSDSFDKFDFCEPSFVTGNCLEISPDCSQYDRVYCGAGVQKEHEEYMKNL
  LKVGGILVMPLEEKLTKITRTGPSAWETKKILAVSFAPLIQPCHSESGKSRLVQLPPVAV
  RSLQDLARIAIRGTIKKIIHQETVSKNGNGLKNTPRFKRRRVRRRRMETIVFLDKEVFAS
  RISNPSDDNSCEDLEEERREEEEKTPPETKPDPPVNFLRQKVLSLPLPDPLKYYLLYYRE
  K
• Function: May act as a substrate recognition component of an ECS (Elongin BC-CUL5-SOCS-box protein) E3 ubiquitin ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. May bind to the methyltransferase cofactor S-adenosylmethionine (AdoMet) via the N-terminal AdoMet binding motif, but probably does not display methyltransferase activity.

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 Protein-L-isoaspartate O-methyltransferase domain-containing protein 2 (PCMTD2).	[1]

10 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 Protein-L-isoaspartate O-methyltransferase domain-containing protein 2 (PCMTD2).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Protein-L-isoaspartate O-methyltransferase domain-containing protein 2 (PCMTD2).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Protein-L-isoaspartate O-methyltransferase domain-containing protein 2 (PCMTD2).	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Protein-L-isoaspartate O-methyltransferase domain-containing protein 2 (PCMTD2).	[5]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Protein-L-isoaspartate O-methyltransferase domain-containing protein 2 (PCMTD2).	[6]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Protein-L-isoaspartate O-methyltransferase domain-containing protein 2 (PCMTD2).	[7]
GSK2110183	DMZHB37	Phase 2	GSK2110183 increases the expression of Protein-L-isoaspartate O-methyltransferase domain-containing protein 2 (PCMTD2).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Protein-L-isoaspartate O-methyltransferase domain-containing protein 2 (PCMTD2).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Protein-L-isoaspartate O-methyltransferase domain-containing protein 2 (PCMTD2).	[10]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Protein-L-isoaspartate O-methyltransferase domain-containing protein 2 (PCMTD2).	[11]

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] 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.
• [3] 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.
• [4] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [5] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [6] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [7] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [8] Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
• [9] 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.
• [10] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [11] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.