Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6JU3I9)

• DOT Name: D-aspartate oxidase (DDO)
• Synonyms: DASOX; DASPO; DDO; EC 1.4.3.1
• Gene Name: DDO
• UniProt ID: OXDD_HUMAN
• PDB ID: 6RKF
• EC Number: 1.4.3.1
• Pfam ID: PF01266
• Sequence:
  MDTARIAVVGAGVVGLSTAVCISKLVPRCSVTIISDKFTPDTTSDVAAGMLIPHTYPDTP
  IHTQKQWFRETFNHLFAIANSAEAGDAGVHLVSGWQIFQSTPTEEVPFWADVVLGFRKMT
  EAELKKFPQYVFGQAFTTLKCECPAYLPWLEKRIKGSGGWTLTRRIEDLWELHPSFDIVV
  NCSGLGSRQLAGDSKIFPVRGQVLQVQAPWVEHFIRDGSGLTYIYPGTSHVTLGGTRQKG
  DWNLSPDAENSREILSRCCALEPSLHGACNIREKVGLRPYRPGVRLQTELLARDGQRLPV
  VHHYGHGSGGISVHWGTALEAARLVSECVHALRTPIPKSNL
• Function: Selectively catalyzes the oxidative deamination of acidic amino acids. Suppresses the level of D-aspartate in the brain, an amino acid that can act as an agonist for glutamate receptors. Protects the organism from the toxicity of D-amino acids. May also function in the intestine.
• Tissue Specificity: Expressed in epithelial cells of the proximal nephron tubules in the renal cortex (at protein level) . In the brain, expressed in the frontal, temporal, and occipital lobes of the cortex, hippocampus, striatum, diencephalon, brainstem, cerebellum, spinal cord, plexus choroiderus and ependyma (at protein level) . Expression is increased in the prefrontal cortex of schizophrenic patients . Levels are normal in the superior frontal gyrus of patients with Alzheimer's disease .
• KEGG Pathway:
  Alanine, aspartate and glutamate metabolism (hsa00250)
  D-Amino acid metabolism (hsa00470)
  Metabolic pathways (hsa01100)
  Peroxisome (hsa04146)
• Reactome Pathway:
  Peroxisomal protein import (R-HSA-9033241)
  Glyoxylate metabolism and glycine degradation (R-HSA-389661)

Molecular Interaction Atlas (MIA) of This DOT

4 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-aspartate oxidase (DDO).	[1]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of D-aspartate oxidase (DDO).	[2]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of D-aspartate oxidase (DDO).	[3]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of D-aspartate oxidase (DDO).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of D-aspartate oxidase (DDO).	[4]

References

• [1] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [2] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [3] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [4] 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.
• [5] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.