Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNQKNL3)

• DOT Name: EARP and GARP complex-interacting protein 1 (EIPR1)
• Synonyms: Endosome-associated recycling protein-interacting protein; Golgi-associated retrograde protein-interacting protein; Tumor-suppressing STF cDNA 1 protein; Tumor-suppressing subchromosomal transferable fragment candidate gene 1 protein
• Gene Name: EIPR1
• Related Disease:
  Drug dependence
  Insulinoma
  Substance abuse
  Substance dependence
  Ocular infection
  Breast cancer
  Breast carcinoma
• UniProt ID: EIPR1_HUMAN
• Pfam ID: PF00400
• Sequence:
  MEDDAPVIYGLEFQARALTPQTAETDAIRFLVGTQSLKYDNQIHIIDFDDENNIINKNVL
  LHQAGEIWHISASPADRGVLTTCYNRTSDSKVLTCAAVWRMPKELESGSHESPDDSSSTA
  QTLELLCHLDNTAHGNMACVVWEPMGDGKKIISLADNHILLWDLQESSSQAVLASSASLE
  GKGQLKFTSGRWSPHHNCTQVATANDTTLRGWDTRSMSQIYCIENAHGQLVRDLDFNPNK
  QYYLASCGDDCKVKFWDTRNVTEPVKTLEEHSHWVWNVRYNHSHDQLVLTGSSDSRVILS
  NMVSISSEPFGHLVDDDDISDQEDHRSEEKSKEPLQDNVIATYEEHEDSVYAVDWSSADP
  WLFASLSYDGRLVINRVPRALKYHILL
• Function: Acts as a component of endosomal retrieval machinery that is involved in protein transport from early endosomes to either recycling endosomes or the trans-Golgi network. Mediates the recruitment of Golgi-associated retrograde protein (GARP) complex to the trans-Golgi network and controls early endosome-to-Golgi transport of internalized protein. Promotes the recycling of internalized transferrin receptor (TFRC) to the plasma membrane through interaction with endosome-associated recycling protein (EARP) complex. Controls proper insulin distribution and secretion, and retention of cargo in mature dense core vesicles. Required for the stability of the endosome-associated retrograde protein (EARP) complex subunits and for proper localization and association of EARP with membranes.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Drug dependence	DIS9IXRC	Strong	Biomarker	[1]
Insulinoma	DISIU1JS	Strong	Biomarker	[2]
Substance abuse	DIS327VW	Strong	Biomarker	[1]
Substance dependence	DISDRAAR	Strong	Biomarker	[1]
Ocular infection	DISTTJES	moderate	Biomarker	[3]
Breast cancer	DIS7DPX1	Limited	Biomarker	[4]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of EARP and GARP complex-interacting protein 1 (EIPR1).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of EARP and GARP complex-interacting protein 1 (EIPR1).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of EARP and GARP complex-interacting protein 1 (EIPR1).	[8]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of EARP and GARP complex-interacting protein 1 (EIPR1).	[9]
GALLICACID	DM6Y3A0	Investigative	GALLICACID decreases the expression of EARP and GARP complex-interacting protein 1 (EIPR1).	[12]

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 EARP and GARP complex-interacting protein 1 (EIPR1).	[7]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of EARP and GARP complex-interacting protein 1 (EIPR1).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of EARP and GARP complex-interacting protein 1 (EIPR1).	[11]

References

• [1] Genome wide association for addiction: replicated results and comparisons of two analytic approaches.PLoS One. 2010 Jan 21;5(1):e8832. doi: 10.1371/journal.pone.0008832.
• [2] EIPR1 controls dense-core vesicle cargo retention and EARP complex localization in insulin-secreting cells.Mol Biol Cell. 2020 Jan 1;31(1):59-79. doi: 10.1091/mbc.E18-07-0469. Epub 2019 Nov 13.
• [3] Evaluation of biofilm-specific antimicrobial resistance genes in Pseudomonas aeruginosa isolates in Farabi Hospital.J Med Microbiol. 2017 Jul;66(7):905-909. doi: 10.1099/jmm.0.000521. Epub 2017 Jul 19.
• [4] Runx2 induces bone osteolysis by transcriptional suppression of TSSC1.Biochem Biophys Res Commun. 2013 Sep 6;438(4):635-9. doi: 10.1016/j.bbrc.2013.07.131. Epub 2013 Aug 8.
• [5] The thioxotriazole copper(II) complex A0 induces endoplasmic reticulum stress and paraptotic death in human cancer cells. J Biol Chem. 2009 Sep 4;284(36):24306-19.
• [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 signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [9] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [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] 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.
• [12] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.