Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTEUQ2MI)

• DOT Name: Reticulophagy regulator 3 (RETREG3)
• Gene Name: RETREG3
• Related Disease:
  Colon cancer
  Colorectal adenocarcinoma
  Colorectal cancer
  Colorectal cancer, susceptibility to, 1
  Colorectal cancer, susceptibility to, 10
  Colorectal cancer, susceptibility to, 12
  Colorectal carcinoma
  Colorectal neoplasm
  Endometrium neoplasm
• UniProt ID: RETR3_HUMAN
• Sequence:
  MAEAEGVPTTPGPASGSTFRGRRDVSGSWERDQQVEAAQRALVEVLGPYEPLLSRVQAAL
  VWERPARSALWCLGLNAAFWFFALTSLRLVFLLAFGLMIIVCIDQWKNKIWPEIKVPRPD
  ALDNESWGFVHPRLLSVPELCHHVAEVWVSGTIFIRNVLLFKKQNPGKFCLLSCGILTFL
  AVLGRYVPGLLLSYLMLVTVMMWPLAVYHRLWDRAYVRLKPALQRLDFSVRGYMMSKQRE
  RQLRRRALHPERAMDNHSDSEEELAAFCPQLDDSTVARELAITDSEHSDAEVSCTDNGTF
  NLSRGQTPLTEGSEDLDGHSDPEESFARDLPDFPSINMDPAGLDDEDDTSIGMPSLMYRS
  PPGAEEPQAPPASRDEAALPELLLGALPVGSNLTSNLASLVSQGMIQLALSGASQPGPSG
  APAQRATRGFLRSPSSDLDTDAEGDDFELLDQSELSQLDPASSRSH
• 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. Promotes ER membrane curvature and ER tubulation required for subsequent ER fragmentation and engulfment into autophagosomes. Required for collagen quality control in a LIR motif-dependent manner. Mediates NRF1-enhanced neurite outgrowth.

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colon cancer	DISVC52G	Strong	Genetic Variation	[1]
Colorectal adenocarcinoma	DISPQOUB	Strong	Genetic Variation	[1]
Colorectal cancer	DISNH7P9	Strong	Genetic Variation	[1]
Colorectal cancer, susceptibility to, 1	DISZ794C	Strong	Genetic Variation	[1]
Colorectal cancer, susceptibility to, 10	DISQXMYM	Strong	Genetic Variation	[1]
Colorectal cancer, susceptibility to, 12	DIS4FXJX	Strong	Genetic Variation	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[1]
Colorectal neoplasm	DISR1UCN	Strong	Genetic Variation	[1]
Endometrium neoplasm	DIS6OS2L	Strong	Genetic Variation	[1]

12 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 Reticulophagy regulator 3 (RETREG3).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Reticulophagy regulator 3 (RETREG3).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Reticulophagy regulator 3 (RETREG3).	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Reticulophagy regulator 3 (RETREG3).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Reticulophagy regulator 3 (RETREG3).	[6]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Reticulophagy regulator 3 (RETREG3).	[8]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Reticulophagy regulator 3 (RETREG3).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Reticulophagy regulator 3 (RETREG3).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Reticulophagy regulator 3 (RETREG3).	[12]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Reticulophagy regulator 3 (RETREG3).	[13]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Reticulophagy regulator 3 (RETREG3).	[14]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Reticulophagy regulator 3 (RETREG3).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Reticulophagy regulator 3 (RETREG3).	[7]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Reticulophagy regulator 3 (RETREG3).	[11]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Reticulophagy regulator 3 (RETREG3).	[11]

References

• [1] Meta-analysis of genome-wide association studies identifies common susceptibility polymorphisms for colorectal and endometrial cancer near SH2B3 and TSHZ1.Sci Rep. 2015 Dec 1;5:17369. doi: 10.1038/srep17369.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [5] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [6] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [7] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [8] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] 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.
• [11] 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.
• [12] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
• [13] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [14] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [15] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.