Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGIY43B)

• DOT Name: E3 ubiquitin-protein ligase RNFT2 (RNFT2)
• Synonyms: RING finger and transmembrane domain-containing protein 2; Transmembrane protein 118
• Gene Name: RNFT2
• Related Disease: Alzheimer disease
• UniProt ID: RNFT2_HUMAN
• Pfam ID: PF13639
• Sequence:
  MWLFTVNQVLRKMQRRHSSNTDNIPPERNRSQALSSEASVDEGGVFESLKAEAASPPALF
  SGLSGSLPTSSFPSSLVLGSSAGGGDVFIQMPASREEGGGRGEGGAYHHRQPHHHFHHGG
  HRGGSLLQHVGGDHRGHSEEGGDEQPGTPAPALSELKAVICWLQKGLPFILILLAKLCFQ
  HKLGIAVCIGMASTFAYANSTLREQVSLKEKRSVLVILWILAFLAGNTLYVLYTFSSQQL
  YNSLIFLKPNLEMLDFFDLLWIVGIADFVLKYITIALKCLIVALPKIILAVKSKGKFYLV
  IEELSQLFRSLVPIQLWYKYIMGDDSSNSYFLGGVLIVLYSLCKSFDICGRVGGVRKALK
  LLCTSQNYGVRATGQQCTEAGDICAICQAEFREPLILLCQHVFCEECLCLWLDRERTCPL
  CRSVAVDTLRCWKDGATSAHFQVY
• Function: E3 ubiquitin-protein ligase that negatively regulates IL3-dependent cellular responses through IL3RA ubiquitination and degradation by the proteasome, having an anti-inflammatory effect.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[1]

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 E3 ubiquitin-protein ligase RNFT2 (RNFT2).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of E3 ubiquitin-protein ligase RNFT2 (RNFT2).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of E3 ubiquitin-protein ligase RNFT2 (RNFT2).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of E3 ubiquitin-protein ligase RNFT2 (RNFT2).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of E3 ubiquitin-protein ligase RNFT2 (RNFT2).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of E3 ubiquitin-protein ligase RNFT2 (RNFT2).	[8]
Marinol	DM70IK5	Approved	Marinol increases the expression of E3 ubiquitin-protein ligase RNFT2 (RNFT2).	[9]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of E3 ubiquitin-protein ligase RNFT2 (RNFT2).	[10]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of E3 ubiquitin-protein ligase RNFT2 (RNFT2).	[11]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of E3 ubiquitin-protein ligase RNFT2 (RNFT2).	[12]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of E3 ubiquitin-protein ligase RNFT2 (RNFT2).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of E3 ubiquitin-protein ligase RNFT2 (RNFT2).	[14]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of E3 ubiquitin-protein ligase RNFT2 (RNFT2).	[15]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of E3 ubiquitin-protein ligase RNFT2 (RNFT2).	[17]

2 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 E3 ubiquitin-protein ligase RNFT2 (RNFT2).	[7]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of E3 ubiquitin-protein ligase RNFT2 (RNFT2).	[16]

References

• [1] Identification of molecular correlations of RBM8A with autophagy in Alzheimer's disease.Aging (Albany NY). 2019 Dec 9;11(23):11673-11685. doi: 10.18632/aging.102571. Epub 2019 Dec 9.
• [2] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [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] 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.
• [9] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [10] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [12] Gene expression profiling in Ishikawa cells: a fingerprint for estrogen active compounds. Toxicol Appl Pharmacol. 2009 Apr 1;236(1):85-96.
• [13] The molecular basis of genistein-induced mitotic arrest and exit of self-renewal in embryonal carcinoma and primary cancer cell lines. BMC Med Genomics. 2008 Oct 10;1:49.
• [14] 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.
• [15] MCM5 as a target of BET inhibitors in thyroid cancer cells. Endocr Relat Cancer. 2016 Apr;23(4):335-47. doi: 10.1530/ERC-15-0322. Epub 2016 Feb 24.
• [16] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [17] 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.