Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5CJTMK)

• DOT Name: Reticulophagy regulator 2 (RETREG2)
• Gene Name: RETREG2
• Related Disease:
  Advanced cancer
  Lung cancer
  Lung carcinoma
  Schizophrenia
• UniProt ID: RETR2_HUMAN
• PDB ID: 6EWC
• Sequence:
  MASGGGGGNTGAGGGPGMGLSLGLGLGLSLGMSEATSEAEEEAATAEAVGRLATTLWLRL
  RGWEAVLAAAQRLLVWEKPLHSLVTAAALNGLFWLLSSSSLRPFFLLSVSLLAYFLLDLW
  QPRFLPDVSASSPEEPHSDSEGAGSGARPHLLSVPELCRYLAESWLTFQIHLQELLQYKR
  QNPAQFCVRVCSGCAVLAVLGHYVPGIMISYIVLLSILLWPLVVYHELIQRMYTRLEPLL
  MQLDYSMKAEANALHHKHDKRKRQGKNAPPGGDEPLAETESESEAELAGFSPVVDVKKTA
  LALAITDSELSDEEASILESGGFSVSRATTPQLTDVSEDLDQQSLPSEPEETLSRDLGEG
  EEGELAPPEDLLGRPQALSRQALDSEEEEEDVAAKETLLRLSSPLHFVNTHFNGAGSPPD
  GVKCSPGGPVETLSPETVSGGLTALPGTLSPPLCLVGSDPAPSPSILPPVPQDSPQPLPA
  PEEEEALTTEDFELLDQGELEQLNAELGLEPETPPKPPDAPPLGPDIHSLVQSDQEAQAV
  AEP
• Function: Endoplasmic reticulum (ER)-anchored autophagy regulator which exists in an inactive state under basal conditions but is activated following cellular stress. When activated, induces ER fragmentation and mediates ER delivery into lysosomes through sequestration into autophagosomes via interaction with ATG8 family proteins. Required for collagen quality control in a LIR motif-independent manner.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Lung cancer	DISCM4YA	Strong	Biomarker	[2]
Lung carcinoma	DISTR26C	Strong	Biomarker	[2]
Schizophrenia	DISSRV2N	Strong	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Reticulophagy regulator 2 (RETREG2).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Reticulophagy regulator 2 (RETREG2).	[5]
Selenium	DM25CGV	Approved	Selenium increases the expression of Reticulophagy regulator 2 (RETREG2).	[6]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Reticulophagy regulator 2 (RETREG2).	[7]
APR-246	DMNFADH	Phase 2	APR-246 affects the expression of Reticulophagy regulator 2 (RETREG2).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Reticulophagy regulator 2 (RETREG2).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Reticulophagy regulator 2 (RETREG2).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Reticulophagy regulator 2 (RETREG2).	[10]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Reticulophagy regulator 2 (RETREG2).	[10]

References

• [1] Cancer-secreted hsa-miR-940 induces an osteoblastic phenotype in the bone metastatic microenvironment via targeting ARHGAP1 and FAM134A.Proc Natl Acad Sci U S A. 2018 Feb 27;115(9):2204-2209. doi: 10.1073/pnas.1717363115. Epub 2018 Feb 12.
• [2] MAG-2 promotes invasion, mobility and adherence capability of lung cancer cells by MMP-2, CD44 and intracellular calcium in vitro.Oncol Rep. 2009 Mar;21(3):697-706.
• [3] Genome-wide association study of schizophrenia using microsatellite markers in the Japanese population. Psychiatr Genet. 2013 Jun;23(3):117-23.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [6] 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.
• [7] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [8] Mutant p53 reactivation by PRIMA-1MET induces multiple signaling pathways converging on apoptosis. Oncogene. 2010 Mar 4;29(9):1329-38. doi: 10.1038/onc.2009.425. Epub 2009 Nov 30.
• [9] 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.
• [10] 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.
• [11] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.