Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTW8DN50)

• DOT Name: Target of Nesh-SH3 (ABI3BP)
• Synonyms: Tarsh; ABI gene family member 3-binding protein; Nesh-binding protein; NeshBP
• Gene Name: ABI3BP
• Related Disease:
  Advanced cancer
  Carcinoma
  Gallbladder cancer
  Gallbladder carcinoma
  Lung neoplasm
  Major depressive disorder
  Neoplasm
  Non-insulin dependent diabetes
  Thyroid cancer
  Thyroid gland carcinoma
  Thyroid tumor
  Acute myelogenous leukaemia
  Pulmonary emphysema
  Endometriosis
  Angioedema
  Urticaria
• UniProt ID: TARSH_HUMAN
• Pfam ID: PF00041 ; PF21731
• Sequence:
  MLSSLGCLLLCGSITLALGNAQKLPKGKRPNLKVHINTTSDSILLKFLRPSPNVKLEGLL
  LGYGSNVSPNQYFPLPAEGKFTEAIVDAEPKYLIVVRPAPPPSQKKSCSGKTRSRKPLQL
  VVGTLTPSSVFLSWGFLINPHHDWTLPSHCPNDRFYTIRYREKDKEKKWIFQICPATETI
  VENLKPNTVYEFGVKDNVEGGIWSKIFNHKTVVGSKKVNGKIQSTYDQDHTVPAYVPRKL
  IPITIIKQVIQNVTHKDSAKSPEKAPLGGVILVHLIIPGLNETTVKLPASLMFEISDALK
  TQLAKNETLALPAESKTPEVEKISARPTTVTPETVPRSTKPTTSSALDVSETTLASSEKP
  WIVPTAKISEDSKVLQPQTATYDVFSSPTTSDEPEISDSYTATSDRILDSIPPKTSRTLE
  QPRATLAPSETPFVPQKLEIFTSPEMQPTTPAPQQTTSIPSTPKRRPRPKPPRTKPERTT
  SAGTITPKISKSPEPTWTTPAPGKTQFISLKPKIPLSPEVTHTKPAPKQTPRAPPKPKTS
  PRPRIPQTQPVPKVPQRVTAKPKTSPSPEVSYTTPAPKDVLLPHKPYPEVSQSEPAPLET
  RGIPFIPMISPSPSQEELQTTLEETDQSTQEPFTTKIPRTTELAKTTQAPHRFYTTVRPR
  TSDKPHIRPGVKQAPRPSGADRNVSVDSTHPTKKPGTRRPPLPPRPTHPRRKPLPPNNVT
  GKPGSAGIISSGPITTPPLRSTPRPTGTPLERIETDIKQPTVPASGEELENITDFSSSPT
  RETDPLGKPRFKGPHVRYIQKPDNSPCSITDSVKRFPKEEATEGNATSPPQNPPTNLTVV
  TVEGCPSFVILDWEKPLNDTVTEYEVISRENGSFSGKNKSIQMTNQTFSTVENLKPNTSY
  EFQVKPKNPLGEGPVSNTVAFSTESADPRVSEPVSAGRDAIWTERPFNSDSYSECKGKQY
  VKRTWYKKFVGVQLCNSLRYKIYLSDSLTGKFYNIGDQRGHGEDHCQFVDSFLDGRTGQQ
  LTSDQLPIKEGYFRAVRQEPVQFGEIGGHTQINYVQWYECGTTIPGKW
• Tissue Specificity: Expressed in brain, heart, lung, liver, pancreas kidney and placenta.

Molecular Interaction Atlas (MIA) of This DOT

16 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Carcinoma	DISH9F1N	Strong	Altered Expression	[2]
Gallbladder cancer	DISXJUAF	Strong	Altered Expression	[1]
Gallbladder carcinoma	DISD6ACL	Strong	Altered Expression	[1]
Lung neoplasm	DISVARNB	Strong	Altered Expression	[3]
Major depressive disorder	DIS4CL3X	Strong	Biomarker	[4]
Neoplasm	DISZKGEW	Strong	Biomarker	[5]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Genetic Variation	[6]
Thyroid cancer	DIS3VLDH	Strong	Biomarker	[7]
Thyroid gland carcinoma	DISMNGZ0	Strong	Biomarker	[7]
Thyroid tumor	DISLVKMD	Strong	Altered Expression	[2]
Acute myelogenous leukaemia	DISCSPTN	moderate	Genetic Variation	[8]
Pulmonary emphysema	DIS5M7HZ	moderate	Biomarker	[9]
Endometriosis	DISX1AG8	Disputed	Biomarker	[10]
Angioedema	DIS90QDN	Limited	Genetic Variation	[11]
Urticaria	DIS9WQAI	Limited	Genetic Variation	[11]

14 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 Target of Nesh-SH3 (ABI3BP).	[12]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Target of Nesh-SH3 (ABI3BP).	[13]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Target of Nesh-SH3 (ABI3BP).	[14]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Target of Nesh-SH3 (ABI3BP).	[15]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Target of Nesh-SH3 (ABI3BP).	[16]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Target of Nesh-SH3 (ABI3BP).	[17]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Target of Nesh-SH3 (ABI3BP).	[18]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Target of Nesh-SH3 (ABI3BP).	[19]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Target of Nesh-SH3 (ABI3BP).	[10]
Fenofibrate	DMFKXDY	Approved	Fenofibrate decreases the expression of Target of Nesh-SH3 (ABI3BP).	[21]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Target of Nesh-SH3 (ABI3BP).	[23]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Target of Nesh-SH3 (ABI3BP).	[12]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Target of Nesh-SH3 (ABI3BP).	[24]
Nitrobenzanthrone	DMN6L70	Investigative	Nitrobenzanthrone increases the expression of Target of Nesh-SH3 (ABI3BP).	[25]

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 decreases the methylation of Target of Nesh-SH3 (ABI3BP).	[22]

References

• [1] Long noncoding RNA MALAT1 potentiates growth and inhibits senescence by antagonizing ABI3BP in gallbladder cancer cells.J Exp Clin Cancer Res. 2019 Jun 7;38(1):244. doi: 10.1186/s13046-019-1237-5.
• [2] ABI3 ectopic expression reduces in vitro and in vivo cell growth properties while inducing senescence.BMC Cancer. 2011 Jan 11;11:11. doi: 10.1186/1471-2407-11-11.
• [3] Cancer-associated loss of TARSH gene expression in human primary lung cancer.J Cancer Res Clin Oncol. 2006 Jan;132(1):28-34. doi: 10.1007/s00432-005-0032-1. Epub 2005 Oct 4.
• [4] Genome-wide association study of suicide attempts in mood disorder patients.Am J Psychiatry. 2010 Dec;167(12):1499-507. doi: 10.1176/appi.ajp.2010.10040541. Epub 2010 Nov 1.
• [5] Implication of p53-dependent cellular senescence related gene, TARSH in tumor suppression.Biochem Biophys Res Commun. 2009 Mar 20;380(4):807-12. doi: 10.1016/j.bbrc.2009.01.171. Epub 2009 Feb 4.
• [6] Genome-wide association study of coronary artery calcified atherosclerotic plaque in African Americans with type 2 diabetes.BMC Genet. 2017 Dec 8;18(1):105. doi: 10.1186/s12863-017-0572-9.
• [7] Re-expression of ABI3-binding protein suppresses thyroid tumor growth by promoting senescence and inhibiting invasion.Endocr Relat Cancer. 2008 Sep;15(3):787-99. doi: 10.1677/ERC-08-0079. Epub 2008 Jun 17.
• [8] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [9] Variable Susceptibility to Cigarette Smoke-Induced Emphysema in 34 Inbred Strains of Mice Implicates Abi3bp in Emphysema Susceptibility.Am J Respir Cell Mol Biol. 2017 Sep;57(3):367-375. doi: 10.1165/rcmb.2016-0220OC.
• [10] Unique transcriptome, pathways, and networks in the human endometrial fibroblast response to progesterone in endometriosis. Biol Reprod. 2011 Apr;84(4):801-15.
• [11] Genome-wide association study in NSAID-induced acute urticaria/angioedema in Spanish and Han Chinese populations.Pharmacogenomics. 2013 Nov;14(15):1857-69. doi: 10.2217/pgs.13.166.
• [12] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [13] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [14] 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.
• [15] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [16] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [17] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [18] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [19] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [20] Unique transcriptome, pathways, and networks in the human endometrial fibroblast response to progesterone in endometriosis. Biol Reprod. 2011 Apr;84(4):801-15.
• [21] Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
• [22] 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.
• [23] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.
• [24] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [25] 3-Nitrobenzanthrone promotes malignant transformation in human lung epithelial cells through the epiregulin-signaling pathway. Cell Biol Toxicol. 2022 Oct;38(5):865-887. doi: 10.1007/s10565-021-09612-1. Epub 2021 May 25.