Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTC4UAR5)

• DOT Name: Post-GPI attachment to proteins factor 4 (PGAP4)
• Synonyms: Post-GPI attachment to proteins GalNAc transferase 4; Transmembrane protein 246
• Gene Name: PGAP4
• UniProt ID: PGAP4_HUMAN
• Sequence:
  MSTSTSPAAMLLRRLRRLSWGSTAVQLFILTVVTFGLLAPLACHRLLHSYFYLRHWHLNQ
  MSQEFLQQSLKEGEAALHYFEELPSANGSVPIVWQATPRPWLVITIITVDRQPGFHYVLQ
  VVSQFHRLLQQCGPQCEGHQLFLCNVERSVSHFDAKLLSKYVPVANRYEGTEDDYGDDPS
  TNSFEKEKQDYVYCLESSLQTYNPDYVLMVEDDAVPEEQIFPVLEHLLRARFSEPHLRDA
  LYLKLYHPERLQHYINPEPMRILEWVGVGMLLGPLLTWIYMRFASRPGFSWPVMLFFSLY
  SMGLVELVGRHYFLELRRLSPSLYSVVPASQCCTPAMLFPAPAARRTLTYLSQVYCHKGF
  GKDMALYSLLRAKGERAYVVEPNLVKHIGLFSSLRYNFHPSLL
• Function: Golgi-resident glycosylphosphatidylinositol (GPI)-N-acetylgalactosamine transferase involved in the lipid remodeling steps of GPI-anchor maturation. Lipid remodeling steps consist in the generation of 2 saturated fatty chains at the sn-2 position of GPI-anchors proteins. Required for the initial step of GPI-GalNAc biosynthesis, transfers GalNAc to GPI in the Golgi after fatty acid remodeling by PGAP2.

Molecular Interaction Atlas (MIA) of This DOT

4 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 Post-GPI attachment to proteins factor 4 (PGAP4).	[1]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Post-GPI attachment to proteins factor 4 (PGAP4).	[2]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Post-GPI attachment to proteins factor 4 (PGAP4).	[3]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Post-GPI attachment to proteins factor 4 (PGAP4).	[5]

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 Post-GPI attachment to proteins factor 4 (PGAP4).	[4]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] 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.
• [3] 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.
• [4] 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.
• [5] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.