Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJ3OLC8)

• DOT Name: Rhomboid domain-containing protein 3 (RHBDD3)
• Gene Name: RHBDD3
• Related Disease:
  Colorectal neoplasm
  Drug dependence
  Pituitary adenoma
  Substance abuse
  Substance dependence
• UniProt ID: RHBD3_HUMAN
• Pfam ID: PF01694 ; PF00627
• Sequence:
  MHARGPHGQLSPALPLASSVLMLLMSTLWLVGAGPGLVLAPELLLDPWQVHRLLTHALGH
  TALPGLLLSLLLLPTVGWQQECHLGTLRFLHASALLALASGLLAVLLAGLGLSSAAGSCG
  YMPVHLAMLAGEGHRPRRPRGALPPWLSPWLLLALTPLLSSEPPFLQLLCGLLAGLAYAA
  GAFRWLEPSERRLQVLQEGVLCRTLAGCWPLRLLATPGSLAELPVTHPAGVRPPIPGPPY
  VASPDLWSHWEDSALPPPSLRPVQPTWEGSSEAGLDWAGASFSPGTPMWAALDEQMLQEG
  IQASLLDGPAQEPQSAPWLSKSSVSSLRLQQLERMGFPTEQAVVALAATGRVEGAVSLLV
  GGQVGTETLVTHGKGGPAHSEGPGPP

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colorectal neoplasm	DISR1UCN	Strong	Altered Expression	[1]
Drug dependence	DIS9IXRC	Strong	Biomarker	[2]
Pituitary adenoma	DISJ5R1X	Strong	Genetic Variation	[3]
Substance abuse	DIS327VW	Strong	Biomarker	[2]
Substance dependence	DISDRAAR	Strong	Biomarker	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Rhomboid domain-containing protein 3 (RHBDD3).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Rhomboid domain-containing protein 3 (RHBDD3).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Rhomboid domain-containing protein 3 (RHBDD3).	[6]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Rhomboid domain-containing protein 3 (RHBDD3).	[8]
Selenium	DM25CGV	Approved	Selenium increases the expression of Rhomboid domain-containing protein 3 (RHBDD3).	[9]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Rhomboid domain-containing protein 3 (RHBDD3).	[10]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene decreases the expression of Rhomboid domain-containing protein 3 (RHBDD3).	[5]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Rhomboid domain-containing protein 3 (RHBDD3).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Rhomboid domain-containing protein 3 (RHBDD3).	[7]

References

• [1] Primary colorectal tumors fail to express the proapoptotic mediator PTAG and its reexpression augments drug-induced apoptosis.Genes Chromosomes Cancer. 2007 Feb;46(2):202-12. doi: 10.1002/gcc.20401.
• [2] Genome wide association for addiction: replicated results and comparisons of two analytic approaches.PLoS One. 2010 Jan 21;5(1):e8832. doi: 10.1371/journal.pone.0008832.
• [3] The role of epigenetic modification in tumorigenesis and progression of pituitary adenomas: a systematic review of the literature.PLoS One. 2013 Dec 18;8(12):e82619. doi: 10.1371/journal.pone.0082619. eCollection 2013.
• [4] 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.
• [5] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [6] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [7] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [8] 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.
• [9] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [10] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [11] 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.