Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBQ2C1J)

• DOT Name: Actin-binding Rho-activating protein (ABRA)
• Synonyms: Striated muscle activator of Rho-dependent signaling; STARS
• Gene Name: ABRA
• Related Disease:
  Dilated cardiomyopathy
  Dilated cardiomyopathy 1A
• UniProt ID: ABRA_HUMAN
• Pfam ID: PF14705
• Sequence:
  MAPGEKESGEGPAKSALRKIRTATLVISLARGWQQWANENSIRQAQEPTGWLPGGTQDSP
  QAPKPITPPTSHQKAQSAPKSPPRLPEGHGDGQSSEKAPEVSHIKKKEVSKTVVSKTYER
  GGDVSHLSHRYERDAGVLEPGQPENDIDRILHSHGSPTRRRKCANLVSELTKGWRVMEQE
  EPTWRSDSVDTEDSGYGGEAEERPEQDGVQVAVVRIKRPLPSQVNRFTEKLNCKAQQKYS
  PVGNLKGRWQQWADEHIQSQKLNPFSEEFDYELAMSTRLHKGDEGYGRPKEGTKTAERAK
  RAEEHIYREMMDMCFIICTMARHRRDGKIQVTFGDLFDRYVRISDKVVGILMRARKHGLV
  DFEGEMLWQGRDDHVVITLLK
• Function: Acts as an activator of serum response factor (SRF)-dependent transcription possibly by inducing nuclear translocation of MKL1 or MKL2 and through a mechanism requiring Rho-actin signaling.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Dilated cardiomyopathy	DISX608J	Limited	Biomarker	[1]
Dilated cardiomyopathy 1A	DIS0RK9Z	Limited	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Actin-binding Rho-activating protein (ABRA).	[2]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Actin-binding Rho-activating protein (ABRA).	[3]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Actin-binding Rho-activating protein (ABRA).	[4]
Etoposide	DMNH3PG	Approved	Etoposide increases the expression of Actin-binding Rho-activating protein (ABRA).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Actin-binding Rho-activating protein (ABRA).	[6]

References

• [1] Transcriptional analysis of doxorubicin-induced cardiotoxicity.Am J Physiol Heart Circ Physiol. 2006 Mar;290(3):H1098-102. doi: 10.1152/ajpheart.00832.2005. Epub 2005 Oct 21.
• [2] 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.
• [3] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [4] 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.
• [5] Cell death mechanisms of the anti-cancer drug etoposide on human cardiomyocytes isolated from pluripotent stem cells. Arch Toxicol. 2018 Apr;92(4):1507-1524.
• [6] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.