Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLJJ4VT)

• DOT Name: CUGBP Elav-like family member 2 (CELF2)
• Synonyms: CELF-2; Bruno-like protein 3; CUG triplet repeat RNA-binding protein 2; CUG-BP2; CUG-BP- and ETR-3-like factor 2; ELAV-type RNA-binding protein 3; ETR-3; Neuroblastoma apoptosis-related RNA-binding protein; hNAPOR; RNA-binding protein BRUNOL-3
• Gene Name: CELF2
• Related Disease:
  Rheumatoid arthritis
  Adult glioblastoma
  Advanced cancer
  Alzheimer disease
  Arrhythmogenic right ventricular cardiomyopathy
  Autoimmune disease
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Colonic neoplasm
  Developmental and epileptic encephalopathy 97
  DiGeorge syndrome
  Glioblastoma multiforme
  Glioma
  Hypertrophic cardiomyopathy
  Motion sickness
  Myotonic dystrophy
  Neoplasm
  Nervous system disease
  Non-small-cell lung cancer
  Partial deletion of the short arm of chromosome 10
  Prostate cancer
  Prostate neoplasm
  Schizophrenia
  Shprintzen-Goldberg syndrome
  Spinal muscular atrophy
  Stevens-Johnson syndrome
  Systemic lupus erythematosus
  Toxic epidermal necrolysis
  Nasopharyngeal carcinoma
  Undetermined early-onset epileptic encephalopathy
  Adult respiratory distress syndrome
  Colorectal carcinoma
  Complex neurodevelopmental disorder
  Gastric cancer
  Kennedy disease
  Pancreatic cancer
  Pneumonia
  Stomach cancer
• UniProt ID: CELF2_HUMAN
• PDB ID: 2MY7; 2MY8; 4LJM; 4LMZ; 4TLQ; 5M8I
• Pfam ID: PF00076
• Sequence:
  MRCPKSAVTMRNEELLLSNGTANKMNGALDHSDQPDPDAIKMFVGQIPRSWSEKELKELF
  EPYGAVYQINVLRDRSQNPPQSKGCCFVTFYTRKAALEAQNALHNIKTLPGMHHPIQMKP
  ADSEKSNAVEDRKLFIGMVSKKCNENDIRVMFSPFGQIEECRILRGPDGLSRGCAFVTFS
  TRAMAQNAIKAMHQSQTMEGCSSPIVVKFADTQKDKEQRRLQQQLAQQMQQLNTATWGNL
  TGLGGLTPQYLALLQQATSSSNLGAFSGIQQMAGMNALQLQNLATLAAAAAAAQTSATST
  NANPLSTTSSALGALTSPVAASTPNSTAGAAMNSLTSLGTLQGLAGATVGLNNINALAGM
  AALNGGLGATGLTNGTAGTMDALTQAYSGIQQYAAAALPTLYSQSLLQQQSAAGSQKEGP
  EGANLFIYHLPQEFGDQDILQMFMPFGNVISAKVFIDKQTNLSKCFGFVSYDNPVSAQAA
  IQAMNGFQIGMKRLKVQLKRSKNDSKPY
• Function: RNA-binding protein implicated in the regulation of several post-transcriptional events. Involved in pre-mRNA alternative splicing, mRNA translation and stability. 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 TNNT2 in embryonic, but not adult, skeletal muscle. Activates TNNT2 exon 5 inclusion by antagonizing the repressive effect of PTB. Acts both as an activator and as a repressor of a pair of coregulated exons: promotes inclusion of the smooth muscle (SM) exon but exclusion of the non-muscle (NM) exon in actinin pre-mRNAs. Promotes inclusion of exonS 21 and exclusion of exon 5 of the NMDA receptor R1 pre-mRNA. Involved in the apoB RNA editing activity. Increases COX2 mRNA stability and inhibits COX2 mRNA translation in epithelial cells after radiation injury. Modulates the cellular apoptosis program by regulating COX2-mediated prostaglandin E2 (PGE2) expression. Binds to (CUG)n triplet repeats in the 3'-UTR of transcripts such as DMPK. Binds to the muscle-specific splicing enhancer (MSE) intronic sites flanking the TNNT2 alternative exon 5. Binds preferentially to UG-rich sequences, in particular UG repeat and UGUU motifs. Binds to apoB mRNA, specifically to AU-rich sequences located immediately upstream of the edited cytidine. Binds AU-rich sequences in the 3'-UTR of COX2 mRNA. Binds to an intronic RNA element responsible for the silencing of exon 21 splicing. Binds to (CUG)n repeats. May be a specific regulator of miRNA biogenesis. Binds to primary microRNA pri-MIR140 and, with CELF1, negatively regulates the processing to mature miRNA.
• Tissue Specificity: Expressed in frontal cortex. Isoform 1 is expressed in brain and lung. Isoform 2 is expressed in heart, brain, placenta, lung, liver, kidney, skeletal muscle and pancreas. Isoform 4 is expressed in heart, lung, skeletal muscle, kidney and pancreas.

Molecular Interaction Atlas (MIA) of This DOT

39 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Rheumatoid arthritis	DISTSB4J	Definitive	Genetic Variation	[1]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[4]
Arrhythmogenic right ventricular cardiomyopathy	DIS3V2BE	Strong	Genetic Variation	[5]
Autoimmune disease	DISORMTM	Strong	Altered Expression	[6]
Breast cancer	DIS7DPX1	Strong	Posttranslational Modification	[7]
Breast carcinoma	DIS2UE88	Strong	Posttranslational Modification	[7]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[8]
Colonic neoplasm	DISSZ04P	Strong	Altered Expression	[9]
Developmental and epileptic encephalopathy 97	DIS8VCPI	Strong	Autosomal dominant	[10]
DiGeorge syndrome	DIST1RKO	Strong	Genetic Variation	[11]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[2]
Glioma	DIS5RPEH	Strong	Biomarker	[12]
Hypertrophic cardiomyopathy	DISQG2AI	Strong	Altered Expression	[13]
Motion sickness	DISZ2WZW	Strong	Genetic Variation	[14]
Myotonic dystrophy	DISNBEMX	Strong	Biomarker	[15]
Neoplasm	DISZKGEW	Strong	Biomarker	[16]
Nervous system disease	DISJ7GGT	Strong	Biomarker	[17]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[2]
Partial deletion of the short arm of chromosome 10	DISET3W3	Strong	Biomarker	[11]
Prostate cancer	DISF190Y	Strong	Biomarker	[18]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[18]
Schizophrenia	DISSRV2N	Strong	Biomarker	[19]
Shprintzen-Goldberg syndrome	DISQH6P3	Strong	Genetic Variation	[11]
Spinal muscular atrophy	DISTLKOB	Strong	Altered Expression	[20]
Stevens-Johnson syndrome	DISZG4YX	Strong	Biomarker	[21]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[6]
Toxic epidermal necrolysis	DISIWPFR	Strong	Biomarker	[21]
Nasopharyngeal carcinoma	DISAOTQ0	moderate	Genetic Variation	[22]
Undetermined early-onset epileptic encephalopathy	DISISEI2	Supportive	Autosomal dominant	[10]
Adult respiratory distress syndrome	DISIJV47	Limited	Genetic Variation	[23]
Colorectal carcinoma	DIS5PYL0	Limited	Biomarker	[16]
Complex neurodevelopmental disorder	DISB9AFI	Limited	Autosomal dominant	[24]
Gastric cancer	DISXGOUK	Limited	Biomarker	[25]
Kennedy disease	DISXZVM1	Limited	Posttranslational Modification	[26]
Pancreatic cancer	DISJC981	Limited	Altered Expression	[27]
Pneumonia	DIS8EF3M	Limited	Genetic Variation	[23]
Stomach cancer	DISKIJSX	Limited	Biomarker	[25]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Mitoxantrone	DMM39BF	Approved	CUGBP Elav-like family member 2 (CELF2) affects the response to substance of Mitoxantrone.	[44]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of CUGBP Elav-like family member 2 (CELF2).	[28]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of CUGBP Elav-like family member 2 (CELF2).	[34]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of CUGBP Elav-like family member 2 (CELF2).	[40]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of CUGBP Elav-like family member 2 (CELF2).	[29]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of CUGBP Elav-like family member 2 (CELF2).	[30]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of CUGBP Elav-like family member 2 (CELF2).	[31]
Marinol	DM70IK5	Approved	Marinol increases the expression of CUGBP Elav-like family member 2 (CELF2).	[32]
Selenium	DM25CGV	Approved	Selenium decreases the expression of CUGBP Elav-like family member 2 (CELF2).	[33]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of CUGBP Elav-like family member 2 (CELF2).	[35]
Isotretinoin	DM4QTBN	Approved	Isotretinoin increases the expression of CUGBP Elav-like family member 2 (CELF2).	[36]
Menthol	DMG2KW7	Approved	Menthol increases the expression of CUGBP Elav-like family member 2 (CELF2).	[37]
Colchicine	DM2POTE	Approved	Colchicine increases the expression of CUGBP Elav-like family member 2 (CELF2).	[38]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of CUGBP Elav-like family member 2 (CELF2).	[39]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of CUGBP Elav-like family member 2 (CELF2).	[41]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of CUGBP Elav-like family member 2 (CELF2).	[35]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of CUGBP Elav-like family member 2 (CELF2).	[39]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of CUGBP Elav-like family member 2 (CELF2).	[42]
Lithium chloride	DMHYLQ2	Investigative	Lithium chloride decreases the expression of CUGBP Elav-like family member 2 (CELF2).	[43]

References

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