Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBGDG8C)

• DOT Name: Pleckstrin homology domain-containing family F member 2 (PLEKHF2)
• Synonyms: PH domain-containing family F member 2; Endoplasmic reticulum-associated apoptosis-involved protein containing PH and FYVE domains; EAPF; PH and FYVE domain-containing protein 2; Phafin-2; Phafin2; Zinc finger FYVE domain-containing protein 18
• Gene Name: PLEKHF2
• UniProt ID: PKHF2_HUMAN
• Pfam ID: PF01363 ; PF00169
• Sequence:
  MVDRLANSEANTRRISIVENCFGAAGQPLTIPGRVLIGEGVLTKLCRKKPKARQFFLFND
  ILVYGNIVIQKKKYNKQHIIPLENVTIDSIKDEGDLRNGWLIKTPTKSFAVYAATATEKS
  EWMNHINKCVTDLLSKSGKTPSNEHAAVWVPDSEATVCMRCQKAKFTPVNRRHHCRKCGF
  VVCGPCSEKRFLLPSQSSKPVRICDFCYDLLSAGDMATCQPARSDSYSQSLKSPLNDMSD
  DDDDDDSSD
• Function: May play a role in early endosome fusion upstream of RAB5, hence regulating receptor trafficking and fluid-phase transport. Enhances cellular sensitivity to TNF-induced apoptosis.
• Tissue Specificity: Expressed in placenta, ovary and small intestine, as well as in heart and pancreas. Also expressed in peripheral blood mononuclear cells and dendritic cells.

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Pleckstrin homology domain-containing family F member 2 (PLEKHF2).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Pleckstrin homology domain-containing family F member 2 (PLEKHF2).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Pleckstrin homology domain-containing family F member 2 (PLEKHF2).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Pleckstrin homology domain-containing family F member 2 (PLEKHF2).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Pleckstrin homology domain-containing family F member 2 (PLEKHF2).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Pleckstrin homology domain-containing family F member 2 (PLEKHF2).	[6]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Pleckstrin homology domain-containing family F member 2 (PLEKHF2).	[7]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Pleckstrin homology domain-containing family F member 2 (PLEKHF2).	[8]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the expression of Pleckstrin homology domain-containing family F member 2 (PLEKHF2).	[7]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Pleckstrin homology domain-containing family F member 2 (PLEKHF2).	[7]
Mestranol	DMG3F94	Approved	Mestranol decreases the expression of Pleckstrin homology domain-containing family F member 2 (PLEKHF2).	[7]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Pleckstrin homology domain-containing family F member 2 (PLEKHF2).	[9]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Pleckstrin homology domain-containing family F member 2 (PLEKHF2).	[7]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Pleckstrin homology domain-containing family F member 2 (PLEKHF2).	[10]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Pleckstrin homology domain-containing family F member 2 (PLEKHF2).	[12]
HEXESTROL	DM9AGWQ	Withdrawn from market	HEXESTROL decreases the expression of Pleckstrin homology domain-containing family F member 2 (PLEKHF2).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Pleckstrin homology domain-containing family F member 2 (PLEKHF2).	[13]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Pleckstrin homology domain-containing family F member 2 (PLEKHF2).	[14]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Pleckstrin homology domain-containing family F member 2 (PLEKHF2).	[15]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Pleckstrin homology domain-containing family F member 2 (PLEKHF2).	[16]

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 decreases the methylation of Pleckstrin homology domain-containing family F member 2 (PLEKHF2).	[11]

References

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• [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.
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• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [7] Moving toward integrating gene expression profiling into high-throughput testing: a gene expression biomarker accurately predicts estrogen receptor alpha modulation in a microarray compendium. Toxicol Sci. 2016 May;151(1):88-103.
• [8] 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.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [11] 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.
• [12] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [13] Isobaric tags for relative and absolute quantitation-based proteomics analysis of the effect of ginger oil on bisphenol A-induced breast cancer cell proliferation. Oncol Lett. 2021 Feb;21(2):101. doi: 10.3892/ol.2020.12362. Epub 2020 Dec 8.
• [14] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [15] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [16] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.