Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCTI0UW)

• DOT Name: Bone morphogenetic protein 3 (BMP3)
• Synonyms: BMP-3; Bone morphogenetic protein 3A; BMP-3A; Osteogenin
• Gene Name: BMP3
• Related Disease:
  Bone osteosarcoma
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Colorectal neoplasm
  Gastric cancer
  Hepatitis C virus infection
  Myopia
  Neoplasm
  Osteoporosis
  Osteosarcoma
  Pancreatic cancer
  Prostate adenocarcinoma
  Prostate cancer
  Prostate carcinoma
  Schwannoma
  Idiopathic interstitial pneumonia
  Pulmonary fibrosis
  Stomach cancer
• UniProt ID: BMP3_HUMAN
• PDB ID: 2QCQ
• Pfam ID: PF00019
• Sequence:
  MAGASRLLFLWLGCFCVSLAQGERPKPPFPELRKAVPGDRTAGGGPDSELQPQDKVSEHM
  LRLYDRYSTVQAARTPGSLEGGSQPWRPRLLREGNTVRSFRAAAAETLERKGLYIFNLTS
  LTKSENILSATLYFCIGELGNISLSCPVSGGCSHHAQRKHIQIDLSAWTLKFSRNQSQLL
  GHLSVDMAKSHRDIMSWLSKDITQLLRKAKENEEFLIGFNITSKGRQLPKRRLPFPEPYI
  LVYANDAAISEPESVVSSLQGHRNFPTGTVPKWDSHIRAALSIERRKKRSTGVLLPLQNN
  ELPGAEYQYKKDEVWEERKPYKTLQAQAPEKSKNKKKQRKGPHRKSQTLQFDEQTLKKAR
  RKQWIEPRNCARRYLKVDFADIGWSEWIISPKSFDAYYCSGACQFPMPKSLKPSNHATIQ
  SIVRAVGVVPGIPEPCCVPEKMSSLSILFFDENKNVVLKVYPNMTVESCACR
• Function: Growth factor of the TGF-beta superfamily that plays an essential role in developmental process by inducing and patterning early skeletal formation and by negatively regulating bone density. Antagonizes the ability of certain osteogenic BMPs to induce osteoprogenitor differentiation and ossification. Initiates signaling cascades by associating with type II receptor ACVR2B to activate SMAD2-dependent and SMAD-independent signaling cascades including TAK1 and JNK pathways.
• Tissue Specificity: Expressed in adult and fetal cartilage.
• KEGG Pathway: Cytokine-cytokine receptor interaction (hsa04060)

Molecular Interaction Atlas (MIA) of This DOT

19 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bone osteosarcoma	DIST1004	Strong	Altered Expression	[1]
Colon cancer	DISVC52G	Strong	Biomarker	[2]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[2]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[3]
Colorectal neoplasm	DISR1UCN	Strong	Biomarker	[4]
Gastric cancer	DISXGOUK	Strong	Biomarker	[5]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[6]
Myopia	DISK5S60	Strong	Genetic Variation	[7]
Neoplasm	DISZKGEW	Strong	Altered Expression	[2]
Osteoporosis	DISF2JE0	Strong	Biomarker	[8]
Osteosarcoma	DISLQ7E2	Strong	Altered Expression	[1]
Pancreatic cancer	DISJC981	Strong	Genetic Variation	[9]
Prostate adenocarcinoma	DISBZYU8	Strong	Altered Expression	[1]
Prostate cancer	DISF190Y	Strong	Altered Expression	[1]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[1]
Schwannoma	DISTTVLA	Strong	Altered Expression	[10]
Idiopathic interstitial pneumonia	DISH7LPY	Limited	Altered Expression	[11]
Pulmonary fibrosis	DISQKVLA	Limited	Biomarker	[11]
Stomach cancer	DISKIJSX	Limited	Biomarker	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Bone morphogenetic protein 3 (BMP3).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Bone morphogenetic protein 3 (BMP3).	[13]

References

• [1] Sequence and expression of bone morphogenetic protein 3 mRNA in prolonged cultures of fetal rat calvarial osteoblasts and in rat prostate adenocarcinoma PA III cells.DNA Cell Biol. 1995 Mar;14(3):235-9. doi: 10.1089/dna.1995.14.235.
• [2] BMP3 suppresses colon tumorigenesis via ActRIIB/SMAD2-dependent and TAK1/JNK signaling pathways.J Exp Clin Cancer Res. 2019 Oct 28;38(1):428. doi: 10.1186/s13046-019-1435-1.
• [3] A systematic review and quantitative assessment of methylation biomarkers in fecal DNA and colorectal cancer and its precursor, colorectal adenoma.Mutat Res Rev Mutat Res. 2019 Jan-Mar;779:45-57. doi: 10.1016/j.mrrev.2019.01.003. Epub 2019 Jan 16.
• [4] Bone morphogenic protein 3 inactivation is an early and frequent event in colorectal cancer development.Genes Chromosomes Cancer. 2008 Jun;47(6):449-60. doi: 10.1002/gcc.20552.
• [5] 1,25-Dihydroxyvitamin D(3) affects gastric cancer progression by repressing BMP3 promoter methylation.Onco Targets Ther. 2019 Mar 28;12:2343-2353. doi: 10.2147/OTT.S195642. eCollection 2019.
• [6] Up-regulation of proproliferative genes and the ligand/receptor pair placental growth factor and vascular endothelial growth factor receptor 1 in hepatitis C cirrhosis.Liver Int. 2007 Sep;27(7):960-8. doi: 10.1111/j.1478-3231.2007.01542.x.
• [7] Detection and interpretation of shared genetic influences on 42 human traits.Nat Genet. 2016 Jul;48(7):709-17. doi: 10.1038/ng.3570. Epub 2016 May 16.
• [8] BMP3 expression by osteoblast lineage cells is regulated by canonical Wnt signaling.FEBS Open Bio. 2017 Dec 16;8(2):168-176. doi: 10.1002/2211-5463.12347. eCollection 2018 Feb.
• [9] Stool DNA testing for the detection of pancreatic cancer: assessment of methylation marker candidates.Cancer. 2012 May 15;118(10):2623-31. doi: 10.1002/cncr.26558. Epub 2011 Sep 22.
• [10] Transcriptional mRNA of BMP-2, 3, 4 and 5 in trigeminal nerve, benign and malignant peripheral nerve sheath tumors.Histol Histopathol. 2001 Oct;16(4):1013-9. doi: 10.14670/HH-16.1013.
• [11] Reduced expression of BMP3 contributes to the development of pulmonary fibrosis and predicts the unfavorable prognosis in IIP patients.Oncotarget. 2017 Aug 9;8(46):80531-80544. doi: 10.18632/oncotarget.20083. eCollection 2017 Oct 6.
• [12] 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.
• [13] 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.