Details of Drug Off-Target (DOT)

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

• DOT Name: Disintegrin and metalloproteinase domain-containing protein 21 (ADAM21)
• Synonyms: ADAM 21; EC 3.4.24.-
• Gene Name: ADAM21
• Related Disease:
  Adult T-cell leukemia/lymphoma
  T-cell leukaemia
  Hepatocellular carcinoma
• UniProt ID: ADA21_HUMAN
• EC Number: 3.4.24.-
• Pfam ID: PF08516 ; PF00200 ; PF01562 ; PF01421
• Sequence:
  MAVDGTLVYIRVTLLLLWLGVFLSISGYCQAGPSQHFTSPEVVIPLKVISRGRSAKAPGW
  LSYSLRFGGQKHVVHMRVKKLLVSRHLPVFTYTDDRALLEDQLFIPDDCYYHGYVEAAPE
  SLVVFSACFGGFRGVLKISGLTYEIEPIRHSATFEHLVYKINSNETQFPAMRCGLTEKEV
  ARQQLEFEEAENSALEPKSAGDWWTHAWFLELVVVVNHDFFIYSQSNISKVQEDVFLVVN
  IVDSMYKQLGTYIILIGIEIWNQGNVFPMTSIEQVLNDFSQWKQISLSQLQHDAAHMFIK
  NSLISILGLAYVAGICRPPIDCGVDNFQGDTWSLFANTVAHELGHTLGMQHDEEFCFCGE
  RGCIMNTFRVPAEKFTNCSYADFMKTTLNQGSCLHNPPRLGEIFMLKRCGNGVVEREEQC
  DCGSVQQCEQDACCLLNCTLRPGAACAFGLCCKDCKFMPSGELCRQEVNECDLPEWCNGT
  SHQCPEDRYVQDGIPCSDSAYCYQKRCNNHDQHCREIFGKDAKSASQNCYKEINSQGNRF
  GHCGINGTTYLKCHISDVFCGRVQCENVRDIPLLQDHFTLQHTHINGVTCWGIDYHLRMN
  ISDIGEVKDGTVCGPGKICIHKKCVSLSVLSHVCLPETCNMKGICNNKHHCHCGYGWSPP
  YCQHRGYGGSIDSGPASAKRGVFLPLIVIPSLSVLTFLFTVGLLMYLRQCSGPKETKAHS
  SG
• Function: May be involved in sperm maturation and/or fertilization. May also be involved in epithelia functions associated with establishing and maintaining gradients of ions or nutrients.
• Reactome Pathway: Interaction With Cumulus Cells And The Zona Pellucida (R-HSA-2534343)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult T-cell leukemia/lymphoma	DIS882XU	Strong	Biomarker	[1]
T-cell leukaemia	DISJ6YIF	Strong	Biomarker	[1]
Hepatocellular carcinoma	DIS0J828	moderate	Biomarker	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Disintegrin and metalloproteinase domain-containing protein 21 (ADAM21).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Disintegrin and metalloproteinase domain-containing protein 21 (ADAM21).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Disintegrin and metalloproteinase domain-containing protein 21 (ADAM21).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Disintegrin and metalloproteinase domain-containing protein 21 (ADAM21).	[4]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Disintegrin and metalloproteinase domain-containing protein 21 (ADAM21).	[7]

References

• [1] TCR variable gene involvement in chromosome inversion between 14q11 and 14q24 in adult T-cell leukemia.J Hum Genet. 2006;51(4):326-334. doi: 10.1007/s10038-006-0364-y. Epub 2006 Mar 7.
• [2] Overexpression of a disintegrin and metalloproteinase 21 is associated with motility, metastasis, and poor prognosis in hepatocellular carcinoma.Sci Rep. 2017 Nov 14;7(1):15485. doi: 10.1038/s41598-017-15800-z.
• [3] 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.
• [4] 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.
• [5] 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.
• [6] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [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.