Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1997IN)

• DOT Name: Bone morphogenetic protein 8A (BMP8A)
• Synonyms: BMP-8A
• Gene Name: BMP8A
• Related Disease:
  Thyroid cancer
  Thyroid gland carcinoma
  Thyroid tumor
  Male infertility
  Peripheral arterial disease
  Ankylosing spondylitis
  Chronic obstructive pulmonary disease
• UniProt ID: BMP8A_HUMAN
• Pfam ID: PF00019 ; PF00688
• Sequence:
  MAARPGPLWLLGLTLCALGGGGPGLRPPPGCPQRRLGARERRDVQREILAVLGLPGRPRP
  RAPPAASRLPASAPLFMLDLYHAMAGDDDEDGAPAEQRLGRADLVMSFVNMVERDRALGH
  QEPHWKEFRFDLTQIPAGEAVTAAEFRIYKVPSIHLLNRTLHVSMFQVVQEQSNRESDLF
  FLDLQTLRAGDEGWLVLDVTAASDCWLLKRHKDLGLRLYVETEDGHSVDPGLAGLLGQRA
  PRSQQPFVVTFFRASPSPIRTPRAVRPLRRRQPKKSNELPQANRLPGIFDDVRGSHGRQV
  CRRHELYVSFQDLGWLDWVIAPQGYSAYYCEGECSFPLDSCMNATNHAILQSLVHLMKPN
  AVPKACCAPTKLSATSVLYYDSSNNVILRKHRNMVVKACGCH
• Function: Induces cartilage and bone formation. May be the osteoinductive factor responsible for the phenomenon of epithelial osteogenesis. Plays a role in calcium regulation and bone homeostasis. Signaling protein involved in regulation of thermogenesis and energy balance. Proposed to increase the peripheral response of brown adipose tissue (BAT) to adrenergic stimulation while acting centrally in the hypothalamus to increase sympathetic output to BAT; Growth factor of the TGF-beta superfamily that plays important role in various biological processes, including spermatogenesis, osteogenesis, steroidogenesis as well as regulation of energy balance. Initiates the canonical BMP signaling cascade by associating with type I receptor BMPR1A and type II receptor BMPR2. Once all three components are bound together in a complex at the cell surface, BMPR2 phosphorylates and activates BMPR1A. In turn, BMPR1A propagates signal by phosphorylating SMAD1/5/8 that travel to the nucleus and act as activators and repressors of transcription of target genes. In addition, activates the SMAD2/3 pathway.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  TGF-beta sig.ling pathway (hsa04350)
  Hippo sig.ling pathway (hsa04390)
  Thermogenesis (hsa04714)

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Thyroid cancer	DIS3VLDH	Definitive	Altered Expression	[1]
Thyroid gland carcinoma	DISMNGZ0	Definitive	Altered Expression	[1]
Thyroid tumor	DISLVKMD	Definitive	Altered Expression	[1]
Male infertility	DISY3YZZ	Strong	Biomarker	[2]
Peripheral arterial disease	DIS78WFB	Strong	Biomarker	[3]
Ankylosing spondylitis	DISRC6IR	Limited	Altered Expression	[4]
Chronic obstructive pulmonary disease	DISQCIRF	Limited	Genetic Variation	[5]

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 Bone morphogenetic protein 8A (BMP8A).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Bone morphogenetic protein 8A (BMP8A).	[10]

4 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Bone morphogenetic protein 8A (BMP8A).	[7]
Irinotecan	DMP6SC2	Approved	Irinotecan increases the expression of Bone morphogenetic protein 8A (BMP8A).	[8]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Bone morphogenetic protein 8A (BMP8A).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Bone morphogenetic protein 8A (BMP8A).	[11]

References

• [1] Serous BMP8A has Clinical Significance in the Ultrasonic Diagnosis of Thyroid Cancer and Promotes Thyroid Cancer Cell Progression.Endocr Metab Immune Disord Drug Targets. 2020;20(4):591-598. doi: 10.2174/1871530319666191018170022.
• [2] BMP8A sustains spermatogenesis by activating both SMAD1/5/8 and SMAD2/3 in spermatogonia.Sci Signal. 2017 May 2;10(477):eaal1910. doi: 10.1126/scisignal.aal1910.
• [3] Genetic Variants in the Bone Morphogenic Protein Gene Family Modify the Association between Residential Exposure to Traffic and Peripheral Arterial Disease.PLoS One. 2016 Apr 15;11(4):e0152670. doi: 10.1371/journal.pone.0152670. eCollection 2016.
• [4] Association study of copy number variation in BMP8A gene with the risk of ankylosing spondylitis in Iranian population.J Cell Biochem. 2019 May;120(5):8359-8365. doi: 10.1002/jcb.28120. Epub 2018 Nov 28.
• [5] Genetic overlap of chronic obstructive pulmonary disease and cardiovascular disease-related traits: a large-scale genome-wide cross-trait analysis.Respir Res. 2019 Apr 2;20(1):64. doi: 10.1186/s12931-019-1036-8.
• [6] 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.
• [7] Integrated assessment by multiple gene expression analysis of quercetin bioactivity on anticancer-related mechanisms in colon cancer cells in vitro. Eur J Nutr. 2005 Mar;44(3):143-56. doi: 10.1007/s00394-004-0503-1. Epub 2004 Apr 30.
• [8] In vitro and in vivo irinotecan-induced changes in expression profiles of cell cycle and apoptosis-associated genes in acute myeloid leukemia cells. Mol Cancer Ther. 2005 Jun;4(6):885-900.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [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] Comparison of transcriptome expression alterations by chronic exposure to low-dose bisphenol A in different subtypes of breast cancer cells. Toxicol Appl Pharmacol. 2019 Dec 15;385:114814. doi: 10.1016/j.taap.2019.114814. Epub 2019 Nov 9.