Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3S6W4Q)

• DOT Name: Activin receptor type-2A (ACVR2A)
• Synonyms: EC 2.7.11.30; Activin receptor type IIA; ACTR-IIA; ACTRIIA
• Gene Name: ACVR2A
• UniProt ID: AVR2A_HUMAN
• PDB ID: 3Q4T; 3SOC; 4ASX; 5NH3; 7U5P
• EC Number: 2.7.11.30
• Pfam ID: PF01064 ; PF00069
• Sequence:
  MGAAAKLAFAVFLISCSSGAILGRSETQECLFFNANWEKDRTNQTGVEPCYGDKDKRRHC
  FATWKNISGSIEIVKQGCWLDDINCYDRTDCVEKKDSPEVYFCCCEGNMCNEKFSYFPEM
  EVTQPTSNPVTPKPPYYNILLYSLVPLMLIAGIVICAFWVYRHHKMAYPPVLVPTQDPGP
  PPPSPLLGLKPLQLLEVKARGRFGCVWKAQLLNEYVAVKIFPIQDKQSWQNEYEVYSLPG
  MKHENILQFIGAEKRGTSVDVDLWLITAFHEKGSLSDFLKANVVSWNELCHIAETMARGL
  AYLHEDIPGLKDGHKPAISHRDIKSKNVLLKNNLTACIADFGLALKFEAGKSAGDTHGQV
  GTRRYMAPEVLEGAINFQRDAFLRIDMYAMGLVLWELASRCTAADGPVDEYMLPFEEEIG
  QHPSLEDMQEVVVHKKKRPVLRDYWQKHAGMAMLCETIEECWDHDAEARLSAGCVGERIT
  QMQRLTNIITTEDIVTVVTMVTNVDFPPKESSL
• Function: On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators. Receptor for activin A, activin B and inhibin A. Mediates induction of adipogenesis by GDF6.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  TGF-beta sig.ling pathway (hsa04350)
  Sig.ling pathways regulating pluripotency of stem cells (hsa04550)
  Fluid shear stress and atherosclerosis (hsa05418)
• Reactome Pathway:
  Regulation of signaling by NODAL (R-HSA-1433617)
  Signaling by Activin (R-HSA-1502540)
  Signaling by BMP (R-HSA-201451)
  Signaling by NODAL (R-HSA-1181150)

Molecular Interaction Atlas (MIA) of This DOT

10 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 Activin receptor type-2A (ACVR2A).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Activin receptor type-2A (ACVR2A).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Activin receptor type-2A (ACVR2A).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Activin receptor type-2A (ACVR2A).	[4]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of Activin receptor type-2A (ACVR2A).	[5]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Activin receptor type-2A (ACVR2A).	[6]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Activin receptor type-2A (ACVR2A).	[7]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Activin receptor type-2A (ACVR2A).	[8]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Activin receptor type-2A (ACVR2A).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Activin receptor type-2A (ACVR2A).	[11]

2 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 affects the methylation of Activin receptor type-2A (ACVR2A).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Activin receptor type-2A (ACVR2A).	[12]

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] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [4] 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.
• [5] Prenatal arsenic exposure and shifts in the newborn proteome: interindividual differences in tumor necrosis factor (TNF)-responsive signaling. Toxicol Sci. 2014 Jun;139(2):328-37. doi: 10.1093/toxsci/kfu053. Epub 2014 Mar 27.
• [6] 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.
• [7] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [10] 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.
• [11] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [12] Expression and DNA methylation changes in human breast epithelial cells after bisphenol A exposure. Int J Oncol. 2012 Jul;41(1):369-77.