Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKDED8A)

• DOT Name: Luc7-like protein 3 (LUC7L3)
• Synonyms: Cisplatin resistance-associated-overexpressed protein; Luc7A; Okadaic acid-inducible phosphoprotein OA48-18; cAMP regulatory element-associated protein 1; CRE-associated protein 1; CREAP-1
• Gene Name: LUC7L3
• Related Disease:
  Chronic renal failure
  Hyperglycemia
  Advanced cancer
  Cardiac failure
  Central retinal vein occlusion
  Chromosomal disorder
  Colon cancer
  Colorectal adenoma
  Colorectal carcinoma
  Congestive heart failure
  Non-alcoholic fatty liver disease
  Obesity
  Cardiac arrest
  Head and neck carcinoma
  Nasopharyngeal carcinoma
  Rhabdomyosarcoma
  Ventricular fibrillation
  Ventricular tachycardia
  Neoplasm
• UniProt ID: LC7L3_HUMAN
• Pfam ID: PF03194
• Sequence:
  MISAAQLLDELMGRDRNLAPDEKRSNVRWDHESVCKYYLCGFCPAELFTNTRSDLGPCEK
  IHDENLRKQYEKSSRFMKVGYERDFLRYLQSLLAEVERRIRRGHARLALSQNQQSSGAAG
  PTGKNEEKIQVLTDKIDVLLQQIEELGSEGKVEEAQGMMKLVEQLKEERELLRSTTSTIE
  SFAAQEKQMEVCEVCGAFLIVGDAQSRVDDHLMGKQHMGYAKIKATVEELKEKLRKRTEE
  PDRDERLKKEKQEREEREKEREREREERERKRRREEEEREKERARDRERRKRSRSRSRHS
  SRTSDRRCSRSRDHKRSRSRERRRSRSRDRRRSRSHDRSERKHRSRSRDRRRSKSRDRKS
  YKHRSKSRDREQDRKSKEKEKRGSDDKKSSVKSGSREKQSEDTNTESKESDTKNEVNGTS
  EDIKSEGDTQSN
• Function: Binds cAMP regulatory element DNA sequence. May play a role in RNA splicing.
• Tissue Specificity: Widely expressed. Highest levels in heart, brain, pancreas, thymus, ovary, small intestine and peripheral blood leukocytes, as well as cerebellum, putamen and pituitary gland. Lowest levels in lung, liver and kidney. Also expressed in fetal tissues, including brain, heart, kidney, thymus and lung.
• Reactome Pathway: mRNA Splicing - Major Pathway (R-HSA-72163)

Molecular Interaction Atlas (MIA) of This DOT

19 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Chronic renal failure	DISGG7K6	Definitive	Genetic Variation	[1]
Hyperglycemia	DIS0BZB5	Definitive	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[3]
Cardiac failure	DISDC067	Strong	Biomarker	[4]
Central retinal vein occlusion	DIS5ICKE	Strong	Biomarker	[5]
Chromosomal disorder	DISM5BB5	Strong	Biomarker	[6]
Colon cancer	DISVC52G	Strong	Altered Expression	[7]
Colorectal adenoma	DISTSVHM	Strong	Biomarker	[3]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[8]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[4]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Biomarker	[3]
Obesity	DIS47Y1K	Strong	Biomarker	[9]
Cardiac arrest	DIS9DIA4	moderate	Biomarker	[10]
Head and neck carcinoma	DISOU1DS	moderate	Biomarker	[11]
Nasopharyngeal carcinoma	DISAOTQ0	moderate	Biomarker	[11]
Rhabdomyosarcoma	DISNR7MS	moderate	Biomarker	[12]
Ventricular fibrillation	DIS7IN76	moderate	Biomarker	[10]
Ventricular tachycardia	DISIBXJ3	moderate	Genetic Variation	[10]
Neoplasm	DISZKGEW	Limited	Genetic Variation	[13]

13 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 Luc7-like protein 3 (LUC7L3).	[14]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Luc7-like protein 3 (LUC7L3).	[15]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Luc7-like protein 3 (LUC7L3).	[16]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Luc7-like protein 3 (LUC7L3).	[17]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Luc7-like protein 3 (LUC7L3).	[18]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Luc7-like protein 3 (LUC7L3).	[19]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Luc7-like protein 3 (LUC7L3).	[20]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Luc7-like protein 3 (LUC7L3).	[21]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Luc7-like protein 3 (LUC7L3).	[19]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Luc7-like protein 3 (LUC7L3).	[23]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Luc7-like protein 3 (LUC7L3).	[26]
Resorcinol	DMM37C0	Investigative	Resorcinol increases the expression of Luc7-like protein 3 (LUC7L3).	[27]
Arachidonic acid	DMUOQZD	Investigative	Arachidonic acid decreases the expression of Luc7-like protein 3 (LUC7L3).	[28]

4 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 affects the methylation of Luc7-like protein 3 (LUC7L3).	[22]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Luc7-like protein 3 (LUC7L3).	[24]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Luc7-like protein 3 (LUC7L3).	[25]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Luc7-like protein 3 (LUC7L3).	[25]

References

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• [16] 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.
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• [18] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [19] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [20] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
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• [24] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
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