Details of Drug Off-Target (DOT)

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

• DOT Name: Receptor-transporting protein 4 (RTP4)
• Synonyms: 28 kDa interferon-responsive protein; 3CxxC-type zinc finger protein 4
• Gene Name: RTP4
• Related Disease:
  Influenza
  Breast cancer
  Breast carcinoma
• UniProt ID: RTP4_HUMAN
• Pfam ID: PF13695
• Sequence:
  MVVDFWTWEQTFQELIQEAKPRATWTLKLDGNLQLDCLAQGWKQYQQRAFGWFRCSSCQR
  SWASAQVQILCHTYWEHWTSQGQVRMRLFGQRCQKCSWSQYEMPEFSSDSTMRILSNLVQ
  HILKKYYGNGTRKSPEMPVILEVSLEGSHDTANCEACTLGICGQGLKSCMTKPSKSLLPH
  LKTGNSSPGIGAVYLANQAKNQSAEAKEAKGSGYEKLGPSRDPDPLNICVFILLLVFIVV
  KCFTSE
• Function: Probable chaperone protein which facilitates trafficking and functional cell surface expression of some G-protein coupled receptors (GPCRs). Promotes functional expression of the bitter taste receptor TAS2R16. Also promotes functional expression of the opioid receptor heterodimer OPRD1-OPRM1.
• Tissue Specificity: Expressed in circumvallate papillae and testis.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Influenza	DIS3PNU3	Strong	Biomarker	[1]
Breast cancer	DIS7DPX1	Limited	Altered Expression	[2]
Breast carcinoma	DIS2UE88	Limited	Altered Expression	[2]

9 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 Receptor-transporting protein 4 (RTP4).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Receptor-transporting protein 4 (RTP4).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Receptor-transporting protein 4 (RTP4).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Receptor-transporting protein 4 (RTP4).	[6]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Receptor-transporting protein 4 (RTP4).	[7]
GSK2110183	DMZHB37	Phase 2	GSK2110183 increases the expression of Receptor-transporting protein 4 (RTP4).	[8]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Receptor-transporting protein 4 (RTP4).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Receptor-transporting protein 4 (RTP4).	[11]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Receptor-transporting protein 4 (RTP4).	[12]

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 Receptor-transporting protein 4 (RTP4).	[9]

References

• [1] A host transcriptional signature for presymptomatic detection of infection in humans exposed to influenza H1N1 or H3N2.PLoS One. 2013;8(1):e52198. doi: 10.1371/journal.pone.0052198. Epub 2013 Jan 9.
• [2] Rac-specific guanine nucleotide exchange factor DOCK1 is a critical regulator of HER2-mediated breast cancer metastasis.Proc Natl Acad Sci U S A. 2013 Apr 30;110(18):7434-9. doi: 10.1073/pnas.1213050110. Epub 2013 Apr 16.
• [3] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [4] Cyclosporine A--induced oxidative stress in human renal mesangial cells: a role for ERK 1/2 MAPK signaling. Toxicol Sci. 2012 Mar;126(1):101-13.
• [5] Retinoic acid receptor alpha amplifications and retinoic acid sensitivity in breast cancers. Clin Breast Cancer. 2013 Oct;13(5):401-8.
• [6] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [7] 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.
• [8] Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
• [9] Gene expression and cytosine DNA methylation alterations in induced pluripotent stem-cell-derived human hepatocytes treated with low doses of chemical carcinogens. Arch Toxicol. 2019 Nov;93(11):3335-3344. doi: 10.1007/s00204-019-02569-5. Epub 2019 Sep 25.
• [10] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [11] 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.
• [12] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.