Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHEC6AK)

• DOT Name: Homocysteine-responsive endoplasmic reticulum-resident ubiquitin-like domain member 2 protein (HERPUD2)
• Gene Name: HERPUD2
• Related Disease: Juvenile idiopathic arthritis
• UniProt ID: HERP2_HUMAN
• PDB ID: 2KDB
• Pfam ID: PF00240
• Sequence:
  MDQSGMEIPVTLIIKAPNQKYSDQTISCFLNWTVGKLKTHLSNVYPSKPLTKDQRLVYSG
  RLLPDHLQLKDILRKQDEYHMVHLVCTSRTPPSSPKSSTNRESHEALASSSNSSSDHSGS
  TTPSSGQETLSLAVGSSSEGLRQRTLPQAQTDQAQSHQFPYVMQGNVDNQFPGQAAPPGF
  PVYPAFSPLQMLWWQQMYAHQYYMQYQAAVSAQATSNVNPTQPTTSQPLNLAHVPGEEPP
  PAPNLVAQENRPMNENVQMNAQGGPVLNEEDFNRDWLDWMYTFSRAAILLSIVYFYSSFS
  RFIMVMGAMLLVYLHQAGWFPFRQEGGHQQAPNNNAEVNNDGQNANNLELEEMERLMDDG
  LEDESGEDGGEDASAIQRPGLMASAWSFITTFFTSLIPEGPPQVAN
• Function: Could be involved in the unfolded protein response (UPR) pathway.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Juvenile idiopathic arthritis	DISQZGBV	Strong	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Homocysteine-responsive endoplasmic reticulum-resident ubiquitin-like domain member 2 protein (HERPUD2).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Homocysteine-responsive endoplasmic reticulum-resident ubiquitin-like domain member 2 protein (HERPUD2).	[3]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Homocysteine-responsive endoplasmic reticulum-resident ubiquitin-like domain member 2 protein (HERPUD2).	[4]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Homocysteine-responsive endoplasmic reticulum-resident ubiquitin-like domain member 2 protein (HERPUD2).	[5]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Homocysteine-responsive endoplasmic reticulum-resident ubiquitin-like domain member 2 protein (HERPUD2).	[6]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Homocysteine-responsive endoplasmic reticulum-resident ubiquitin-like domain member 2 protein (HERPUD2).	[8]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Homocysteine-responsive endoplasmic reticulum-resident ubiquitin-like domain member 2 protein (HERPUD2).	[9]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Homocysteine-responsive endoplasmic reticulum-resident ubiquitin-like domain member 2 protein (HERPUD2).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Homocysteine-responsive endoplasmic reticulum-resident ubiquitin-like domain member 2 protein (HERPUD2).	[7]

References

• [1] Gene expression signatures in polyarticular juvenile idiopathic arthritis demonstrate disease heterogeneity and offer a molecular classification of disease subsets.Arthritis Rheum. 2009 Jul;60(7):2113-23. doi: 10.1002/art.24534.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] 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.
• [4] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [5] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [6] 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.
• [7] 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.
• [8] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [9] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [10] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.