Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT15CSR0)

• DOT Name: Phosphatidylinositol glycan anchor biosynthesis class U protein (PIGU)
• Synonyms: Cell division cycle protein 91-like 1; Protein CDC91-like 1; GPI transamidase component PIG-U
• Gene Name: PIGU
• Related Disease: Glycosylphosphatidylinositol biosynthesis defect 21
• UniProt ID: PIGU_HUMAN
• PDB ID: 7W72; 7WLD; 8IMX; 8IMY
• Pfam ID: PF06728
• Sequence:
  MAAPLVLVLVVAVTVRAALFRSSLAEFISERVEVVSPLSSWKRVVEGLSLLDLGVSPYSG
  AVFHETPLIIYLFHFLIDYAELVFMITDALTAIALYFAIQDFNKVVFKKQKLLLELDQYA
  PDVAELIRTPMEMRYIPLKVALFYLLNPYTILSCVAKSTCAINNTLIAFFILTTIKGSAF
  LSAIFLALATYQSLYPLTLFVPGLLYLLQRQYIPVKMKSKAFWIFSWEYAMMYVGSLVVI
  ICLSFFLLSSWDFIPAVYGFILSVPDLTPNIGLFWYFFAEMFEHFSLFFVCVFQINVFFY
  TIPLAIKLKEHPIFFMFIQIAVIAIFKSYPTVGDVALYMAFFPVWNHLYRFLRNIFVLTC
  IIIVCSLLFPVLWHLWIYAGSANSNFFYAITLTFNVGQILLISDYFYAFLRREYYLTHGL
  YLTAKDGTEAMLVLK
• Function: Component of the GPI transamidase complex, necessary for transfer of GPI to proteins. May be involved in the recognition of either the GPI attachment signal or the lipid portion of GPI.
• KEGG Pathway:
  Glycosylphosphatidylinositol (GPI)-anchor biosynthesis (hsa00563)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Attachment of GPI anchor to uPAR (R-HSA-162791)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Glycosylphosphatidylinositol biosynthesis defect 21	DIS7IMDC	Strong	Autosomal recessive	[1]

5 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 Phosphatidylinositol glycan anchor biosynthesis class U protein (PIGU).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Phosphatidylinositol glycan anchor biosynthesis class U protein (PIGU).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Phosphatidylinositol glycan anchor biosynthesis class U protein (PIGU).	[4]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Phosphatidylinositol glycan anchor biosynthesis class U protein (PIGU).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Phosphatidylinositol glycan anchor biosynthesis class U protein (PIGU).	[6]

References

• [1] Mutations in GPAA1, Encoding a GPI Transamidase Complex Protein, Cause Developmental Delay, Epilepsy, Cerebellar Atrophy, and Osteopenia. Am J Hum Genet. 2017 Nov 2;101(5):856-865. doi: 10.1016/j.ajhg.2017.09.020.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] 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.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [6] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.