Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHYX9F3)

• DOT Name: Integrin beta-1-binding protein 2 (ITGB1BP2)
• Synonyms: Melusin
• Gene Name: ITGB1BP2
• Related Disease:
  Cardiac failure
  Congestive heart failure
  Dilated cardiomyopathy
  Dilated cardiomyopathy 1A
  High blood pressure
  Hypertrophic cardiomyopathy
• UniProt ID: ITBP2_HUMAN
• Pfam ID: PF04968 ; PF04969
• Sequence:
  MSLLCRNKGCGQHFDPNTNLPDSCCHHPGVPIFHDALKGWSCCRKRTVDFSEFLNIKGCT
  MGPHCAEKLPEAPQPEGPATSSSLQEQKPLNVIPKSAETLRRERPKSELPLKLLPLNISQ
  ALEMALEQKELDQEPGAGLDSLIRTGSSCQNPGCDAVYQGPESDATPCTYHPGAPRFHEG
  MKSWSCCGIQTLDFGAFLAQPGCRVGRHDWGKQLPASCRHDWHQTDSLVVVTVYGQIPLP
  AFNWVKASQTELHVHIVFDGNRVFQAQMKLWGVINVEQSSVFLMPSRVEISLVKADPGSW
  AQLEHPDALAKKARAGVVLEMDEEESDDSDDDLSWTEEEEEEEAMGE
• Function: May play a role during maturation and/or organization of muscles cells.
• Tissue Specificity: Expressed in skeletal and cardiac muscles but not in other tissues.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cardiac failure	DISDC067	Strong	Genetic Variation	[1]
Congestive heart failure	DIS32MEA	Strong	Genetic Variation	[1]
Dilated cardiomyopathy	DISX608J	Strong	Genetic Variation	[1]
Dilated cardiomyopathy 1A	DIS0RK9Z	Strong	Genetic Variation	[1]
High blood pressure	DISY2OHH	Strong	Genetic Variation	[2]
Hypertrophic cardiomyopathy	DISQG2AI	Strong	Genetic Variation	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Integrin beta-1-binding protein 2 (ITGB1BP2).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Integrin beta-1-binding protein 2 (ITGB1BP2).	[4]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Integrin beta-1-binding protein 2 (ITGB1BP2).	[5]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Integrin beta-1-binding protein 2 (ITGB1BP2).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Integrin beta-1-binding protein 2 (ITGB1BP2).	[8]

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 Integrin beta-1-binding protein 2 (ITGB1BP2).	[6]

References

• [1] Identification of a missense mutation in the melusin-encoding ITGB1BP2 gene in a patient with dilated cardiomyopathy.Gene. 2013 Jan 10;512(2):206-10. doi: 10.1016/j.gene.2012.10.055. Epub 2012 Nov 1.
• [2] Melusin gene (ITGB1BP2) nucleotide variations study in hypertensive and cardiopathic patients.BMC Med Genet. 2009 Dec 17;10:140. doi: 10.1186/1471-2350-10-140.
• [3] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [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] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [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] 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.
• [8] 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.