Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0UWPND)

• DOT Name: Pregnancy-specific beta-1-glycoprotein 9 (PSG9)
• Synonyms: PS-beta-G-9; PSBG-9; Pregnancy-specific glycoprotein 9; PS34; Pregnancy-specific beta-1 glycoprotein B; PS-beta-B; Pregnancy-specific beta-1-glycoprotein 11; PS-beta-G-11; PSBG-11; Pregnancy-specific glycoprotein 11; Pregnancy-specific glycoprotein 7; PSG7
• Gene Name: PSG9
• Related Disease:
  Adenoma
  Familial adenomatous polyposis
  Hepatocellular carcinoma
• UniProt ID: PSG9_HUMAN
• Pfam ID: PF13895 ; PF07686
• Sequence:
  MGPLPAPSCTQRITWKGLLLTASLLNFWNPPTTAEVTIEAQPPKVSEGKDVLLLVHNLPQ
  NLPGYFWYKGEMTDLYHYIISYIVDGKIIIYGPAYSGRETVYSNASLLIQNVTRKDAGTY
  TLHIIKRGDETREEIRHFTFTLYLETPKPYISSSNLNPREAMEAVRLICDPETLDASYLW
  WMNGQSLPVTHRLQLSKTNRTLYLFGVTKYIAGPYECEIRNPVSASRSDPVTLNLLPKLP
  IPYITINNLNPRENKDVLAFTCEPKSENYTYIWWLNGQSLPVSPGVKRPIENRILILPSV
  TRNETGPYQCEIRDRYGGLRSNPVILNVLYGPDLPRIYPSFTYYRSGENLDLSCFTESNP
  PAEYFWTINGKFQQSGQKLFIPQITRNHSGLYACSVHNSATGKEISKSMTVKVSGPCHGD
  LTESQS
• Function: Binds to the small latent transforming growth factor-beta complex, consisting of the N-terminal TGFB1 latency-associated peptide (LAP) and the mature form of TGFB1, thereby leading to the activation of TGFB1. The activation of TGFB1 leads to stimulation of naive CD4(+) T-cells to increase FoxP3 expression and to an increase in the number of FoxP3(+) regulatory T-cells. Induces the differentiation of a suppressive CD4(+)LAP(+)FoxP3(-) T-cell subset. Induces the secretion of TGFB1 in macrophages, but not in activated CD4(+) T-cells. May reduce the expression of several pro-inflammatory cytokines and chemokines by CD4(+) T-cells, including IL2 and IL6.
• Reactome Pathway: Cell surface interactions at the vascular wall (R-HSA-202733)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenoma	DIS78ZEV	Strong	Altered Expression	[1]
Familial adenomatous polyposis	DISW53RE	Strong	Biomarker	[1]
Hepatocellular carcinoma	DIS0J828	moderate	Biomarker	[2]

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 Pregnancy-specific beta-1-glycoprotein 9 (PSG9).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Pregnancy-specific beta-1-glycoprotein 9 (PSG9).	[4]
Lucanthone	DMZLBUO	Approved	Lucanthone increases the expression of Pregnancy-specific beta-1-glycoprotein 9 (PSG9).	[6]
SB-431542	DM0YOXQ	Preclinical	SB-431542 increases the expression of Pregnancy-specific beta-1-glycoprotein 9 (PSG9).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Pregnancy-specific beta-1-glycoprotein 9 (PSG9).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Pregnancy-specific beta-1-glycoprotein 9 (PSG9).	[7]

References

• [1] Differential gene expression profile reveals deregulation of pregnancy specific beta1 glycoprotein 9 early during colorectal carcinogenesis.BMC Cancer. 2005 Jun 27;5:66. doi: 10.1186/1471-2407-5-66.
• [2] 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.
• [3] 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.
• [4] 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.
• [5] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [6] Lucanthone is a novel inhibitor of autophagy that induces cathepsin D-mediated apoptosis. J Biol Chem. 2011 Feb 25;286(8):6602-13.
• [7] 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.
• [8] Activin/nodal signaling switches the terminal fate of human embryonic stem cell-derived trophoblasts. J Biol Chem. 2015 Apr 3;290(14):8834-48.