Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGWL4U4)

• DOT Name: RING finger protein 44 (RNF44)
• Gene Name: RNF44
• Related Disease:
  Melanoma
  Neoplasm
• UniProt ID: RNF44_HUMAN
• Pfam ID: PF13639
• Sequence:
  MRPWALAVTRWPPSAPVGQRRFSAGPGSTPGQLWGSPGLEGPLASPPARDERLPSQQPPS
  RPPHLPVEERRASAPAGGSPRMLHPATQQSPFMVDLHEQVHQGPVPLSYTVTTVTTQGFP
  LPTGQHIPGCSAQQLPACSVMFSGQHYPLCCLPPPLIQACTMQQLPVPYQAYPHLISSDH
  YILHPPPPAPPPQPTHMAPLGQFVSLQTQHPRMPLQRLDNDVDLRGDQPSLGSFTYSTSA
  PGPALSPSVPLHYLPHDPLHQELSFGVPYSHMMPRRLSTQRYRLQQPLPPPPPPPPPPPY
  YPSFLPYFLSMLPMSPTAMGPTISLDLDVDDVEMENYEALLNLAERLGDAKPRGLTKADI
  EQLPSYRFNPDSHQSEQTLCVVCFSDFEARQLLRVLPCNHEFHTKCVDKWLKANRTCPIC
  RADASEVPREAE

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Melanoma	DIS1RRCY	Limited	Altered Expression	[1]
Neoplasm	DISZKGEW	Limited	Altered Expression	[1]

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 RING finger protein 44 (RNF44).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of RING finger protein 44 (RNF44).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of RING finger protein 44 (RNF44).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of RING finger protein 44 (RNF44).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of RING finger protein 44 (RNF44).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of RING finger protein 44 (RNF44).	[7]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of RING finger protein 44 (RNF44).	[9]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of RING finger protein 44 (RNF44).	[10]
Menadione	DMSJDTY	Approved	Menadione affects the expression of RING finger protein 44 (RNF44).	[11]

3 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 RING finger protein 44 (RNF44).	[8]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of RING finger protein 44 (RNF44).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of RING finger protein 44 (RNF44).	[13]

References

• [1] Degradation of AMPK-1 sensitizes BRAF inhibitor-resistant melanoma cells to arginine deprivation.Mol Oncol. 2017 Dec;11(12):1806-1825. doi: 10.1002/1878-0261.12151. Epub 2017 Nov 16.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [4] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [5] 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.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [8] 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.
• [9] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [10] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [11] 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.
• [12] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [13] 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.