Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQEBL0W)

• DOT Name: Calcium-binding protein 39-like (CAB39L)
• Synonyms: Antigen MLAA-34; MO25beta; Mo25-like protein
• Gene Name: CAB39L
• Related Disease:
  Acute monocytic leukemia
  Adult acute monocytic leukemia
  Endometriosis
  leukaemia
  Leukemia
  Parkinson disease
  Gastric cancer
  Neoplasm
  Stomach cancer
• UniProt ID: CB39L_HUMAN
• PDB ID: 3ZHP
• Pfam ID: PF08569
• Sequence:
  MKKMPLFSKSHKNPAEIVKILKDNLAILEKQDKKTDKASEEVSKSLQAMKEILCGTNEKE
  PPTEAVAQLAQELYSSGLLVTLIADLQLIDFEGKKDVTQIFNNILRRQIGTRSPTVEYIS
  AHPHILFMLLKGYEAPQIALRCGIMLRECIRHEPLAKIILFSNQFRDFFKYVELSTFDIA
  SDAFATFKDLLTRHKVLVADFLEQNYDTIFEDYEKLLQSENYVTKRQSLKLLGELILDRH
  NFAIMTKYISKPENLKLMMNLLRDKSPNIQFEAFHVFKVFVASPHKTQPIVEILLKNQPK
  LIEFLSSFQKERTDDEQFADEKNYLIKQIRDLKKTAP
• Function: Component of a complex that binds and activates STK11/LKB1. In the complex, required to stabilize the interaction between CAB39/MO25 (CAB39/MO25alpha or CAB39L/MO25beta) and STK11/LKB1.
• KEGG Pathway:
  mTOR sig.ling pathway (hsa04150)
  AMPK sig.ling pathway (hsa04152)
• Reactome Pathway: Energy dependent regulation of mTOR by LKB1-AMPK (R-HSA-380972)

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute monocytic leukemia	DIS28NEL	Strong	Genetic Variation	[1]
Adult acute monocytic leukemia	DISG6BLX	Strong	Genetic Variation	[1]
Endometriosis	DISX1AG8	Strong	Biomarker	[2]
leukaemia	DISS7D1V	Strong	Genetic Variation	[1]
Leukemia	DISNAKFL	Strong	Genetic Variation	[1]
Parkinson disease	DISQVHKL	Strong	Genetic Variation	[3]
Gastric cancer	DISXGOUK	moderate	Biomarker	[4]
Neoplasm	DISZKGEW	moderate	Biomarker	[4]
Stomach cancer	DISKIJSX	moderate	Biomarker	[4]

16 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 Calcium-binding protein 39-like (CAB39L).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Calcium-binding protein 39-like (CAB39L).	[6]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Calcium-binding protein 39-like (CAB39L).	[7]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Calcium-binding protein 39-like (CAB39L).	[8]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Calcium-binding protein 39-like (CAB39L).	[9]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Calcium-binding protein 39-like (CAB39L).	[9]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Calcium-binding protein 39-like (CAB39L).	[10]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Calcium-binding protein 39-like (CAB39L).	[11]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Calcium-binding protein 39-like (CAB39L).	[12]
PEITC	DMOMN31	Phase 2	PEITC increases the expression of Calcium-binding protein 39-like (CAB39L).	[13]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Calcium-binding protein 39-like (CAB39L).	[15]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Calcium-binding protein 39-like (CAB39L).	[16]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Calcium-binding protein 39-like (CAB39L).	[17]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Calcium-binding protein 39-like (CAB39L).	[18]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID increases the expression of Calcium-binding protein 39-like (CAB39L).	[19]
2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE	DMNQL17	Investigative	2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE decreases the expression of Calcium-binding protein 39-like (CAB39L).	[20]

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 affects the methylation of Calcium-binding protein 39-like (CAB39L).	[14]

References

• [1] Leukemia-associated gene MLAA-34 reduces arsenic trioxide-induced apoptosis in HeLa cells via activation of the Wnt/-catenin signaling pathway.PLoS One. 2017 Oct 23;12(10):e0186868. doi: 10.1371/journal.pone.0186868. eCollection 2017.
• [2] Genome-wide enrichment analysis between endometriosis and obesity-related traits reveals novel susceptibility loci.Hum Mol Genet. 2015 Feb 15;24(4):1185-99. doi: 10.1093/hmg/ddu516. Epub 2014 Oct 8.
• [3] A meta-analysis of genome-wide association studies identifies 17 new Parkinson's disease risk loci.Nat Genet. 2017 Oct;49(10):1511-1516. doi: 10.1038/ng.3955. Epub 2017 Sep 11.
• [4] CAB39L elicited an anti-Warburg effect via a LKB1-AMPK-PGC1 axis to inhibit gastric tumorigenesis.Oncogene. 2018 Dec;37(50):6383-6398. doi: 10.1038/s41388-018-0402-1. Epub 2018 Jul 27.
• [5] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [6] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [7] Persistent and non-persistent changes in gene expression result from long-term estrogen exposure of MCF-7 breast cancer cells. J Steroid Biochem Mol Biol. 2011 Feb;123(3-5):140-50.
• [8] Gene expression profile induced by arsenic trioxide in chronic lymphocytic leukemia cells reveals a central role for heme oxygenase-1 in apoptosis and regulation of matrix metalloproteinase-9. Oncotarget. 2016 Dec 13;7(50):83359-83377.
• [9] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [10] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [11] 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.
• [12] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [13] Phenethyl isothiocyanate alters the gene expression and the levels of protein associated with cell cycle regulation in human glioblastoma GBM 8401 cells. Environ Toxicol. 2017 Jan;32(1):176-187.
• [14] 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.
• [15] Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 2013 Mar;3(3):308-23.
• [16] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [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.
• [18] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
• [19] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.
• [20] Preferential induction of the AhR gene battery in HepaRG cells after a single or repeated exposure to heterocyclic aromatic amines. Toxicol Appl Pharmacol. 2010 Nov 15;249(1):91-100.