Details of Drug Off-Target (DOT)

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

• DOT Name: ADAMTS-like protein 5 (ADAMTSL5)
• Synonyms: ADAMTSL-5; Thrombospondin type-1 domain-containing protein 6
• Gene Name: ADAMTSL5
• Related Disease:
  Psoriasis
  Acute lymphocytic leukaemia
  Childhood acute lymphoblastic leukemia
• UniProt ID: ATL5_HUMAN
• Pfam ID: PF19236 ; PF05986 ; PF01759 ; PF00090
• Sequence:
  MGKLRPGRVEWLASGHTERPHLFQNLLLFLWALLNCGLGVSAQGPGEWTPWVSWTRCSSS
  CGRGVSVRSRRCLRLPGEEPCWGDSHEYRLCQLPDCPPGAVPFRDLQCALYNGRPVLGTQ
  KTYQWVPFHGAPNQCDLNCLAEGHAFYHSFGRVLDGTACSPGAQGVCVAGRCLSAGCDGL
  LGSGALEDRCGRCGGANDSCLFVQRVFRDAGAFAGYWNVTLIPEGARHIRVEHRSRNHLA
  LMGGDGRYVLNGHWVVSPPGTYEAAGTHVVYTRDTGPQETLQAAGPTSHDLLLQVLLQEP
  NPGIEFEFWLPRERYSPFQARVQALGWPLRQPQPRGVEPQPPAAPAVTPAQTPTLAPDPC
  PPCPDTRGRAHRLLHYCGSDFVFQARVLGHHHQAQETRYEVRIQLVYKNRSPLRAREYVW
  APGHCPCPMLAPHRDYLMAVQRLVSPDGTQDQLLLPHAGYARPWSPAEDSRIRLTARRCP
  G
• Function: May play a role in modulation of fibrillin microfibrils in the extracellular matrix (ECM).
• Reactome Pathway:
  O-glycosylation of TSR domain-containing proteins (R-HSA-5173214)
  Defective B3GALTL causes PpS (R-HSA-5083635)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Psoriasis	DIS59VMN	Definitive	Biomarker	[1]
Acute lymphocytic leukaemia	DISPX75S	Strong	Biomarker	[2]
Childhood acute lymphoblastic leukemia	DISJ5D6U	Strong	Posttranslational Modification	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of ADAMTS-like protein 5 (ADAMTSL5).	[3]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of ADAMTS-like protein 5 (ADAMTSL5).	[4]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of ADAMTS-like protein 5 (ADAMTSL5).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of ADAMTS-like protein 5 (ADAMTSL5).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of ADAMTS-like protein 5 (ADAMTSL5).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of ADAMTS-like protein 5 (ADAMTSL5).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of ADAMTS-like protein 5 (ADAMTSL5).	[7]

References

• [1] Adaptive and Innate Immunity in Psoriasis and Other Inflammatory Disorders.Front Immunol. 2019 Jul 26;10:1764. doi: 10.3389/fimmu.2019.01764. eCollection 2019.
• [2] ADAMTSL5 and CDH11: putative epigenetic markers for therapeutic resistance in acute lymphoblastic leukemia.Hematology. 2017 Aug;22(7):386-391. doi: 10.1080/10245332.2017.1299417. Epub 2017 Mar 15.
• [3] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [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] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [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] 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.
• [8] 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.
• [9] Cultured human peripheral blood mononuclear cells alter their gene expression when challenged with endocrine-disrupting chemicals. Toxicology. 2013 Jan 7;303:17-24.