Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCFNW3L)

• DOT Name: Pregnancy-specific beta-1-glycoprotein 4 (PSG4)
• Synonyms: PS-beta-G-4; PSBG-4; Pregnancy-specific glycoprotein 4; Pregnancy-specific beta-1-glycoprotein 9; PS-beta-G-9; PSBG-9; Pregnancy-specific glycoprotein 9
• Gene Name: PSG4
• Related Disease: Hepatocellular carcinoma
• UniProt ID: PSG4_HUMAN
• Pfam ID: PF13895 ; PF13927 ; PF07686
• Sequence:
  MGPLSAPPCTQRITWKGVLLTASLLNFWNPPTTAQVTIEAQPPKVSEGKDVLLLVHNLPQ
  NLAGYIWYKGQMTYLYHYITSYVVDGQRIIYGPAYSGRERVYSNASLLIQNVTQEDAGSY
  TLHIIKRRDGTGGVTGHFTFTLHLETPKPSISSSNLNPREAMEAVILTCDPATPAASYQW
  WMNGQSLPMTHRLQLSKTNRTLFIFGVTKYIAGPYECEIRNPVSASRSDPVTLNLLPKLS
  KPYITINNLNPRENKDVLTFTCEPKSKNYTYIWWLNGQSLPVSPRVKRPIENRILILPNV
  TRNETGPYQCEIRDRYGGIRSDPVTLNVLYGPDLPSIYPSFTYYRSGENLYLSCFAESNP
  RAQYSWTINGKFQLSGQKLSIPQITTKHSGLYACSVRNSATGKESSKSITVKVSDWILP
• Reactome Pathway: Cell surface interactions at the vascular wall (R-HSA-202733)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[1]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Pregnancy-specific beta-1-glycoprotein 4 (PSG4) affects the response to substance of Doxorubicin.	[8]

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 Pregnancy-specific beta-1-glycoprotein 4 (PSG4).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Pregnancy-specific beta-1-glycoprotein 4 (PSG4).	[3]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Pregnancy-specific beta-1-glycoprotein 4 (PSG4).	[4]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Pregnancy-specific beta-1-glycoprotein 4 (PSG4).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Pregnancy-specific beta-1-glycoprotein 4 (PSG4).	[7]

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 increases the methylation of Pregnancy-specific beta-1-glycoprotein 4 (PSG4).	[6]

References

• [1] Post-surgical resection prognostic value of combined OPN, MMP7, and PSG9 plasma biomarkers in hepatocellular carcinoma.Front Med. 2019 Apr;13(2):250-258. doi: 10.1007/s11684-018-0632-1. Epub 2018 May 16.
• [2] 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.
• [3] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [4] Effects of progesterone treatment on expression of genes involved in uterine quiescence. Reprod Sci. 2011 Aug;18(8):781-97.
• [5] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [6] 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.
• [7] 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.
• [8] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.