Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUJ2QVA)

• DOT Name: Pleckstrin homology domain-containing family A member 3 (PLEKHA3)
• Synonyms: PH domain-containing family A member 3; Phosphatidylinositol-four-phosphate adapter protein 1; FAPP-1; Phosphoinositol 4-phosphate adapter protein 1
• Gene Name: PLEKHA3
• UniProt ID: PKHA3_HUMAN
• PDB ID: 2KCJ; 2MDX; 3RCP
• Pfam ID: PF00169
• Sequence:
  MEGVLYKWTNYLTGWQPRWFVLDNGILSYYDSQDDVCKGSKGSIKMAVCEIKVHSADNTR
  MELIIPGEQHFYMKAVNAAERQRWLVALGSSKACLTDTRTKKEKEISETSESLKTKMSEL
  RLYCDLLMQQVHTIQEFVHHDENHSSPSAENMNEASSLLSATCNTFITTLEECVKIANAK
  FKPEMFQLHHPDPLVSPVSPSPVQMMKRSVSHPGSCSSERSSHSIKEPVSTLHRLSQRRR
  RTYSDTDSCSDIPLEDPDRPVHCSKNTLNGDLASATIPEESRLMAKKQSESEDTLPSFSS
• Function: Plays a role in regulation of vesicular cargo transport from the trans-Golgi network (TGN) to the plasma membrane. Regulates Golgi phosphatidylinositol 4-phosphate (PtdIns(4)P) levels and activates the PtdIns(4)P phosphatase activity of SACM1L when it binds PtdIns(4)P in 'trans' configuration. Binds preferentially to PtdIns(4)P. Negatively regulates APOB secretion from hepatocytes.
• Tissue Specificity: Widely expressed.
• Reactome Pathway: Synthesis of PIPs at the plasma membrane (R-HSA-1660499)

Molecular Interaction Atlas (MIA) of This DOT

8 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 Pleckstrin homology domain-containing family A member 3 (PLEKHA3).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Pleckstrin homology domain-containing family A member 3 (PLEKHA3).	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Pleckstrin homology domain-containing family A member 3 (PLEKHA3).	[3]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Pleckstrin homology domain-containing family A member 3 (PLEKHA3).	[4]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Pleckstrin homology domain-containing family A member 3 (PLEKHA3).	[5]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Pleckstrin homology domain-containing family A member 3 (PLEKHA3).	[6]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Pleckstrin homology domain-containing family A member 3 (PLEKHA3).	[7]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Pleckstrin homology domain-containing family A member 3 (PLEKHA3).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Pleckstrin homology domain-containing family A member 3 (PLEKHA3).	[8]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] 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.
• [5] 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.
• [6] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [7] 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.
• [8] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [9] 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.