Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4K7KON)

• DOT Name: Isthmin-2 (ISM2)
• Synonyms: Thrombospondin and AMOP domain-containing isthmin-like protein 1; Thrombospondin type-1 domain-containing protein 3
• Gene Name: ISM2
• Related Disease:
  Arrhythmogenic right ventricular cardiomyopathy
  Carcinoma
  Cardiomyopathy
• UniProt ID: ISM2_HUMAN
• Pfam ID: PF03782 ; PF00090
• Sequence:
  MRALRDRAGLLLCVLLLAALLEAALGLPVKKPRLRGPRPGSLTRLAEVSASPDPRPLKEE
  EEAPLLPRTHLQAEPHQHGCWTVTEPAAMTPGNATPPRTPEVTPLRLELQKLPGLANTTL
  STPNPDTQASASPDPRPLREEEEARLLPRTHLQAELHQHGCWTVTEPAALTPGNATPPRT
  QEVTPLLLELQKLPELVHATLSTPNPDNQVTIKVVEDPQAEVSIDLLAEPSNPPPQDTLS
  WLPALWSFLWGDYKGEEKDRAPGEKGEEKEEDEDYPSEDIEGEDQEDKEEDEEEQALWFN
  GTTDNWDQGWLAPGDWVFKDSVSYDYEPQKEWSPWSPCSGNCSTGKQQRTRPCGYGCTAT
  ETRTCDLPSCPGTEDKDTLGLPSEEWKLLARNATDMHDQDVDSCEKWLNCKSDFLIKYLS
  QMLRDLPSCPCAYPLEAMDSPVSLQDEHQGRSFRWRDASGPRERLDIYQPTARFCLRSML
  SGESSTLAAQHCCYDEDSRLLTRGKGAGMPNLISTDFSPKLHFKFDTTPWILCKGDWSRL
  HAVLPPNNGRACTDNPLEEEYLAQLQEAKEY
• Tissue Specificity: Expressed at high levels in the placenta and at moderate levels in the pancreas, kidney, heart, liver, lung, brain and skeletal muscle.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Arrhythmogenic right ventricular cardiomyopathy	DIS3V2BE	Strong	Altered Expression	[1]
Carcinoma	DISH9F1N	Strong	Biomarker	[2]
Cardiomyopathy	DISUPZRG	Strong	Altered Expression	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Isthmin-2 (ISM2).	[3]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Isthmin-2 (ISM2).	[3]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Isthmin-2 (ISM2).	[4]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Isthmin-2 (ISM2).	[5]
Pioglitazone	DMKJ485	Approved	Pioglitazone increases the expression of Isthmin-2 (ISM2).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Isthmin-2 (ISM2).	[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 Isthmin-2 (ISM2).	[7]

References

• [1] TAIL1: an isthmin-like gene, containing type 1 thrombospondin-repeat and AMOP domain, mapped to ARVD1 critical region.Gene. 2004 Jun 23;335:101-8. doi: 10.1016/j.gene.2004.03.008.
• [2] Pancreatic carcinoma in carriers of a specific 19 base pair deletion of CDKN2A/p16 (p16-leiden).Clin Cancer Res. 2003 Sep 1;9(10 Pt 1):3598-605.
• [3] 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.
• [4] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [5] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [6] Peroxisome proliferator activated receptor gamma (PPAR-gama) ligand pioglitazone regulated gene networks in term human primary trophoblast cells. Reprod Toxicol. 2018 Oct;81:99-107.
• [7] 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.
• [8] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.