Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTP45WK)

• DOT Name: CUGBP Elav-like family member 3 (CELF3)
• Synonyms: CELF-3; Bruno-like protein 1; CAG repeat protein 4; CUG-BP- and ETR-3-like factor 3; ELAV-type RNA-binding protein 1; ETR-1; Expanded repeat domain protein CAG/CTG 4; RNA-binding protein BRUNOL-1; Trinucleotide repeat-containing gene 4 protein
• Gene Name: CELF3
• Related Disease: Colorectal carcinoma
• UniProt ID: CELF3_HUMAN
• PDB ID: 2DNO
• Pfam ID: PF00076
• Sequence:
  MKEPDAIKLFVGQIPRHLEEKDLKPIFEQFGRIFELTVIKDKYTGLHKGCAFLTYCARDS
  ALKAQSALHEQKTLPGMNRPIQVKPADSESRGEDRKLFVGMLGKQQTDEDVRKMFEPFGT
  IDECTVLRGPDGTSKGCAFVKFQTHAEAQAAINTLHSSRTLPGASSSLVVKFADTEKERG
  LRRMQQVATQLGMFSPIALQFGAYSAYTQALMQQQAALVAAHSAYLSPMATMAAVQMQHM
  AAINANGLIATPITPSSGTSTPPAIAATPVSAIPAALGVNGYSPVPTQPTGQPAPDALYP
  NGVHPYPAQSPAAPVDPLQQAYAGMQHYTAAYPAAYSLVAPAFPQPPALVAQQPPPPPQQ
  QQQQQQQQQQQQQREGPDGCNIFIYHLPQEFTDSEILQMFVPFGHVISAKVFVDRATNQS
  KCFGFVSFDNPASAQAAIQAMNGFQIGMKRLKVQLKRPKDANRPY
• Function: RNA-binding protein involved in the regulation of pre-mRNA alternative splicing. Mediates exon inclusion and/or exclusion in pre-mRNA that are subject to tissue-specific and developmentally regulated alternative splicing. Specifically activates exon 5 inclusion of cardiac isoforms of TNNT2 during heart remodeling at the juvenile to adult transition. Activates the splicing of MAPT/Tau exon 10. Binds to muscle-specific splicing enhancer (MSE) intronic sites flanking the alternative exon 5 of TNNT2 pre-mRNA.
• Tissue Specificity: Expressed in brain.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of CUGBP Elav-like family member 3 (CELF3).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of CUGBP Elav-like family member 3 (CELF3).	[3]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of CUGBP Elav-like family member 3 (CELF3).	[4]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of CUGBP Elav-like family member 3 (CELF3).	[5]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of CUGBP Elav-like family member 3 (CELF3).	[6]
Cytarabine	DMZD5QR	Approved	Cytarabine increases the expression of CUGBP Elav-like family member 3 (CELF3).	[7]

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 CUGBP Elav-like family member 3 (CELF3).	[8]

References

• [1] Integrative analysis of significant RNA-binding proteins in colorectal cancer metastasis.J Cell Biochem. 2018 Dec;119(12):9730-9741. doi: 10.1002/jcb.27290. Epub 2018 Aug 21.
• [2] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [3] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [4] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [5] 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.
• [6] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [7] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [8] 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.