Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9U5OXJ)

• DOT Name: Leukocyte surface antigen CD53 (CD53)
• Synonyms: Cell surface glycoprotein CD53; Tetraspanin-25; Tspan-25; CD antigen CD53
• Gene Name: CD53
• Related Disease:
  Acute myelogenous leukaemia
  Digestive system neuroendocrine tumor, grade 1/2
  Osteoarthritis
  Small lymphocytic lymphoma
  Tuberculosis
  Asthma
• UniProt ID: CD53_HUMAN
• PDB ID: 6WVG
• Pfam ID: PF00335
• Sequence:
  MGMSSLKLLKYVLFFFNLLFWICGCCILGFGIYLLIHNNFGVLFHNLPSLTLGNVFVIVG
  SIIMVVAFLGCMGSIKENKCLLMSFFILLLIILLAEVTLAILLFVYEQKLNEYVAKGLTD
  SIHRYHSDNSTKAAWDSIQSFLQCCGINGTSDWTSGPPASCPSDRKVEGCYAKARLWFHS
  NFLYIGIITICVCVIEVLGMSFALTLNCQIDKTSQTIGL
• Function: Required for efficient formation of myofibers in regenerating muscle at the level of cell fusion. May be involved in growth regulation in hematopoietic cells.
• Tissue Specificity: B-cells, monocytes, macrophages, neutrophils, single (CD4 or CD8) positive thymocytes and peripheral T-cells.
• Reactome Pathway: Neutrophil degranulation (R-HSA-6798695)

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[1]
Digestive system neuroendocrine tumor, grade 1/2	DISDR98B	Strong	Biomarker	[2]
Osteoarthritis	DIS05URM	Strong	Altered Expression	[3]
Small lymphocytic lymphoma	DIS30POX	Strong	Altered Expression	[4]
Tuberculosis	DIS2YIMD	Strong	Altered Expression	[5]
Asthma	DISW9QNS	Limited	Genetic Variation	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the methylation of Leukocyte surface antigen CD53 (CD53).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Leukocyte surface antigen CD53 (CD53).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Leukocyte surface antigen CD53 (CD53).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Leukocyte surface antigen CD53 (CD53).	[9]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Leukocyte surface antigen CD53 (CD53).	[10]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Leukocyte surface antigen CD53 (CD53).	[11]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Leukocyte surface antigen CD53 (CD53).	[12]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Leukocyte surface antigen CD53 (CD53).	[13]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Leukocyte surface antigen CD53 (CD53).	[14]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene increases the expression of Leukocyte surface antigen CD53 (CD53).	[8]

References

• [1] Novel Targeted Nano-Parthenolide Molecule against NF-kB in Acute Myeloid Leukemia.Molecules. 2019 Jun 3;24(11):2103. doi: 10.3390/molecules24112103.
• [2] A precision oncology approach to the pharmacological targeting of mechanistic dependencies in neuroendocrine tumors.Nat Genet. 2018 Jul;50(7):979-989. doi: 10.1038/s41588-018-0138-4. Epub 2018 Jun 18.
• [3] Analysis of differences in the molecular mechanism of rheumatoid arthritis and osteoarthritis based on integration of gene expression profiles.Immunol Lett. 2015 Dec;168(2):246-53. doi: 10.1016/j.imlet.2015.09.011. Epub 2015 Sep 25.
• [4] Aberrant expression of tetraspanin molecules in B-cell chronic lymphoproliferative disorders and its correlation with normal B-cell maturation.Leukemia. 2005 Aug;19(8):1376-83. doi: 10.1038/sj.leu.2403822.
• [5] Pathogen lineage-based genome-wide association study identified CD53 as susceptible locus in tuberculosis.J Hum Genet. 2017 Dec;62(12):1015-1022. doi: 10.1038/jhg.2017.82. Epub 2017 Sep 7.
• [6] CD53, a suppressor of inflammatory cytokine production, is associated with population asthma risk via the functional promoter polymorphism -1560 C>T.Biochim Biophys Acta. 2013 Apr;1830(4):3011-8. doi: 10.1016/j.bbagen.2012.12.030. Epub 2013 Jan 10.
• [7] 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.
• [8] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [9] 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.
• [10] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [11] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [12] Single-cell Transcriptome Mapping Identifies Common and Cell-type Specific Genes Affected by Acute Delta9-tetrahydrocannabinol in Humans. Sci Rep. 2020 Feb 26;10(1):3450. doi: 10.1038/s41598-020-59827-1.
• [13] Gene expression profile of human lymphoid CEM cells sensitive and resistant to glucocorticoid-evoked apoptosis. Genomics. 2003 Jun;81(6):543-55.
• [14] 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.
• [15] 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.