Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRZVI77)

• DOT Name: Disintegrin and metalloproteinase domain-containing protein 33 (ADAM33)
• Synonyms: ADAM 33; EC 3.4.24.-
• Gene Name: ADAM33
• UniProt ID: ADA33_HUMAN
• PDB ID: 1R54; 1R55
• EC Number: 3.4.24.-
• Pfam ID: PF08516 ; PF00200 ; PF01562 ; PF01421
• Sequence:
  MGWRPRRARGTPLLLLLLLLLLWPVPGAGVLQGHIPGQPVTPHWVLDGQPWRTVSLEEPV
  SKPDMGLVALEAEGQELLLELEKNHRLLAPGYIETHYGPDGQPVVLAPNHTDHCHYQGRV
  RGFPDSWVVLCTCSGMSGLITLSRNASYYLRPWPPRGSKDFSTHEIFRMEQLLTWKGTCG
  HRDPGNKAGMTSLPGGPQSRGRREARRTRKYLELYIVADHTLFLTRHRNLNHTKQRLLEV
  ANYVDQLLRTLDIQVALTGLEVWTERDRSRVTQDANATLWAFLQWRRGLWAQRPHDSAQL
  LTGRAFQGATVGLAPVEGMCRAESSGGVSTDHSELPIGAAATMAHEIGHSLGLSHDPDGC
  CVEAAAESGGCVMAAATGHPFPRVFSACSRRQLRAFFRKGGGACLSNAPDPGLPVPPALC
  GNGFVEAGEECDCGPGQECRDLCCFAHNCSLRPGAQCAHGDCCVRCLLKPAGALCRQAMG
  DCDLPEFCTGTSSHCPPDVYLLDGSPCARGSGYCWDGACPTLEQQCQQLWGPGSHPAPEA
  CFQVVNSAGDAHGNCGQDSEGHFLPCAGRDALCGKLQCQGGKPSLLAPHMVPVDSTVHLD
  GQEVTCRGALALPSAQLDLLGLGLVEPGTQCGPRMVCQSRRCRKNAFQELQRCLTACHSH
  GVCNSNHNCHCAPGWAPPFCDKPGFGGSMDSGPVQAENHDTFLLAMLLSVLLPLLPGAGL
  AWCCYRLPGAHLQRCSWGCRRDPACSGPKDGPHRDHPLGGVHPMELGPTATGQPWPLDPE
  NSHEPSSHPEKPLPAVSPDPQADQVQMPRSCLW
• Tissue Specificity: Expressed in all tissues, except liver, with high expression in placenta, lung, spleen and veins.
• Reactome Pathway: Regulation of CDH11 function (R-HSA-9762292)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Aspirin	DM672AH	Approved	Disintegrin and metalloproteinase domain-containing protein 33 (ADAM33) affects the response to substance of Aspirin.	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Disintegrin and metalloproteinase domain-containing protein 33 (ADAM33).	[1]
Decitabine	DMQL8XJ	Approved	Decitabine decreases the methylation of Disintegrin and metalloproteinase domain-containing protein 33 (ADAM33).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Disintegrin and metalloproteinase domain-containing protein 33 (ADAM33).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Disintegrin and metalloproteinase domain-containing protein 33 (ADAM33).	[2]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Disintegrin and metalloproteinase domain-containing protein 33 (ADAM33).	[3]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Disintegrin and metalloproteinase domain-containing protein 33 (ADAM33).	[4]
Liraglutide	DM3FXPS	Approved	Liraglutide increases the expression of Disintegrin and metalloproteinase domain-containing protein 33 (ADAM33).	[5]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Disintegrin and metalloproteinase domain-containing protein 33 (ADAM33).	[7]

References

• [1] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [2] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [3] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [4] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [5] Antitumoral activity of liraglutide, a new DNMT inhibitor in breast cancer cells in vitro and in vivo. Chem Biol Interact. 2021 Nov 1;349:109641. doi: 10.1016/j.cbi.2021.109641. Epub 2021 Sep 14.
• [6] 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.
• [7] 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.
• [8] ADAM33 polymorphisms are associated with aspirin-intolerant asthma in the Japanese population. J Hum Genet. 2007;52(1):66-72. doi: 10.1007/s10038-006-0081-6. Epub 2006 Oct 24.