Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0CBZ6F)

• DOT Name: Dystrophia myotonica WD repeat-containing protein (DMWD)
• Synonyms: Dystrophia myotonica-containing WD repeat motif protein; Protein 59; Protein DMR-N9
• Gene Name: DMWD
• Related Disease:
  Chronic obstructive pulmonary disease
  Male infertility
  Oligospermia
  Myotonic dystrophy
• UniProt ID: DMWD_HUMAN
• Pfam ID: PF00400
• Sequence:
  MAAGGAEGGSGPGAAMGDCAEIKSQFRTREGFYKLLPGDGAARRSGPASAQTPVPPQPPQ
  PPPGPASASGPGAAGPASSPPPAGPGPGPALPAVRLSLVRLGEPDSAGAGEPPATPAGLG
  SGGDRVCFNLGRELYFYPGCCRRGSQRSIDLNKPIDKRIYKGTQPTCHDFNQFTAATETI
  SLLVGFSAGQVQYLDLIKKDTSKLFNEERLIDKTKVTYLKWLPESESLFLASHASGHLYL
  YNVSHPCASAPPQYSLLKQGEGFSVYAAKSKAPRNPLAKWAVGEGPLNEFAFSPDGRHLA
  CVSQDGCLRVFHFDSMLLRGLMKSYFGGLLCVCWSPDGRYVVTGGEDDLVTVWSFTEGRV
  VARGHGHKSWVNAVAFDPYTTRAEEAATAAGADGERSGEEEEEEPEAAGTGSAGGAPLSP
  LPKAGSITYRFGSAGQDTQFCLWDLTEDVLYPHPPLARTRTLPGTPGTTPPAASSSRGGE
  PGPGPLPRSLSRSNSLPHPAGGGKAGGPGVAAEPGTPFSIGRFATLTLQERRDRGAEKEH
  KRYHSLGNISRGGSGGSGSGGEKPSGPVPRSRLDPAKVLGTALCPRIHEVPLLEPLVCKK
  IAQERLTVLLFLEDCIITACQEGLICTWARPGKAFTDEETEAQTGEGSWPRSPSKSVVEG
  ISSQPGNSPSGTVV
• Function: Regulator of the deubiquitinating USP12/DMWD/WDR48 complex. Functions as a cofactor that promotes USP12 enzymatic activity.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Chronic obstructive pulmonary disease	DISQCIRF	Strong	Genetic Variation	[1]
Male infertility	DISY3YZZ	Strong	Genetic Variation	[2]
Oligospermia	DIS6YJF3	Strong	Genetic Variation	[2]
Myotonic dystrophy	DISNBEMX	Limited	Genetic Variation	[3]

4 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 Dystrophia myotonica WD repeat-containing protein (DMWD).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Dystrophia myotonica WD repeat-containing protein (DMWD).	[12]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Dystrophia myotonica WD repeat-containing protein (DMWD).	[14]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Dystrophia myotonica WD repeat-containing protein (DMWD).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Dystrophia myotonica WD repeat-containing protein (DMWD).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Dystrophia myotonica WD repeat-containing protein (DMWD).	[6]
Marinol	DM70IK5	Approved	Marinol increases the expression of Dystrophia myotonica WD repeat-containing protein (DMWD).	[7]
Selenium	DM25CGV	Approved	Selenium increases the expression of Dystrophia myotonica WD repeat-containing protein (DMWD).	[8]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of Dystrophia myotonica WD repeat-containing protein (DMWD).	[9]
Irinotecan	DMP6SC2	Approved	Irinotecan increases the expression of Dystrophia myotonica WD repeat-containing protein (DMWD).	[10]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Dystrophia myotonica WD repeat-containing protein (DMWD).	[11]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Dystrophia myotonica WD repeat-containing protein (DMWD).	[13]
PMID27336223-Compound-5	DM6E50A	Patented	PMID27336223-Compound-5 decreases the expression of Dystrophia myotonica WD repeat-containing protein (DMWD).	[9]

References

• [1] Genetic landscape of chronic obstructive pulmonary disease identifies heterogeneous cell-type and phenotype associations.Nat Genet. 2019 Mar;51(3):494-505. doi: 10.1038/s41588-018-0342-2. Epub 2019 Feb 25.
• [2] Searching for candidate genes for male infertility.Asian J Androl. 2003 Jun;5(2):137-47.
• [3] Myotonic dystrophy is associated with a reduced level of RNA from the DMWD allele adjacent to the expanded repeat.Hum Mol Genet. 1999 Aug;8(8):1491-7. doi: 10.1093/hmg/8.8.1491.
• [4] 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.
• [5] Cyclosporine A--induced oxidative stress in human renal mesangial cells: a role for ERK 1/2 MAPK signaling. Toxicol Sci. 2012 Mar;126(1):101-13.
• [6] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [7] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [8] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [9] PPARgamma controls CD1d expression by turning on retinoic acid synthesis in developing human dendritic cells. J Exp Med. 2006 Oct 2;203(10):2351-62.
• [10] In vitro and in vivo irinotecan-induced changes in expression profiles of cell cycle and apoptosis-associated genes in acute myeloid leukemia cells. Mol Cancer Ther. 2005 Jun;4(6):885-900.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [12] 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.
• [13] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [14] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.