Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTG1LU87)

• DOT Name: D-dopachrome decarboxylase-like protein (DDTL)
• Synonyms: EC 4.1.1.-; D-dopachrome tautomerase-like protein
• Gene Name: DDTL
• Related Disease:
  Dowling-Degos disease
  Schizophrenia
• UniProt ID: DDTL_HUMAN
• EC Number: 4.1.1.-
• Pfam ID: PF01187
• Sequence:
  MPFLELDTNLPANRVPAGLEKRLCAAAASILGKPADRVNVTVRPGLAMALSGSTEPCAQL
  SISSIGVVGTAEDNRSHSAHFFEFLTKELALGQDRFPTVLSTSPAAHGGPRCPGEIIEGK
  KSCLNEEALFIYFI
• Function: May have lyase activity.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Dowling-Degos disease	DISGTTEP	Strong	Genetic Variation	[1]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[2]

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 D-dopachrome decarboxylase-like protein (DDTL).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of D-dopachrome decarboxylase-like protein (DDTL).	[4]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of D-dopachrome decarboxylase-like protein (DDTL).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of D-dopachrome decarboxylase-like protein (DDTL).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of D-dopachrome decarboxylase-like protein (DDTL).	[7]

References

• [1] Associations between DDT and egg parameters of the House Sparrow Passer domesticus from the Thohoyandou area of South Africa.Chemosphere. 2018 May;198:249-256. doi: 10.1016/j.chemosphere.2018.01.125. Epub 2018 Feb 6.
• [2] Associations of common copy number variants in glutathione S-transferase mu 1 and D-dopachrome tautomerase-like protein genes with risk of schizophrenia in a Japanese population.Am J Med Genet B Neuropsychiatr Genet. 2015 Oct;168(7):630-6. doi: 10.1002/ajmg.b.32347. Epub 2015 Jul 14.
• [3] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [4] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [5] Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
• [6] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [7] 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.