Details of Drug Off-Target (DOT)

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

• DOT Name: Endoplasmic reticulum resident protein 29 (ERP29)
• Synonyms: ERp29; Endoplasmic reticulum resident protein 28; ERp28; Endoplasmic reticulum resident protein 31; ERp31
• Gene Name: ERP29
• Related Disease:
  Lung adenocarcinoma
  Bone osteosarcoma
  Breast cancer
  Breast neoplasm
  Carcinoma
  Colorectal carcinoma
  Hepatocellular carcinoma
  Neoplasm
  Osteosarcoma
  Prostate cancer
  Prostate neoplasm
  Skin cancer
  Gastric cancer
  Nasopharyngeal carcinoma
  Stomach cancer
  Type-1/2 diabetes
  Advanced cancer
  Breast carcinoma
  Intrahepatic cholestasis of pregnancy
• UniProt ID: ERP29_HUMAN
• PDB ID: 2QC7; 5V8Z; 5V90
• Pfam ID: PF07749 ; PF07912
• Sequence:
  MAAAVPRAAFLSPLLPLLLGFLLLSAPHGGSGLHTKGALPLDTVTFYKVIPKSKFVLVKF
  DTQYPYGEKQDEFKRLAENSASSDDLLVAEVGISDYGDKLNMELSEKYKLDKESYPVFYL
  FRDGDFENPVPYTGAVKVGAIQRWLKGQGVYLGMPGCLPVYDALAGEFIRASGVEARQAL
  LKQGQDNLSSVKETQKKWAEQYLKIMGKILDQGEDFPASEMTRIARLIEKNKMSDGKKEE
  LQKSLNILTAFQKKGAEKEEL
• Function: Does not seem to be a disulfide isomerase. Plays an important role in the processing of secretory proteins within the endoplasmic reticulum (ER), possibly by participating in the folding of proteins in the ER.
• Tissue Specificity: Ubiquitous. Mostly expressed in secretory tissues.
• KEGG Pathway: Protein processing in endoplasmic reticulum (hsa04141)

Molecular Interaction Atlas (MIA) of This DOT

19 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Lung adenocarcinoma	DISD51WR	Definitive	Biomarker	[1]
Bone osteosarcoma	DIST1004	Strong	Altered Expression	[2]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[3]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[4]
Carcinoma	DISH9F1N	Strong	Altered Expression	[5]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[6]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[7]
Neoplasm	DISZKGEW	Strong	Biomarker	[2]
Osteosarcoma	DISLQ7E2	Strong	Altered Expression	[2]
Prostate cancer	DISF190Y	Strong	Biomarker	[8]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[8]
Skin cancer	DISTM18U	Strong	Biomarker	[5]
Gastric cancer	DISXGOUK	moderate	Biomarker	[9]
Nasopharyngeal carcinoma	DISAOTQ0	moderate	Biomarker	[10]
Stomach cancer	DISKIJSX	moderate	Biomarker	[9]
Type-1/2 diabetes	DISIUHAP	Disputed	Biomarker	[7]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[2]
Breast carcinoma	DIS2UE88	Limited	Altered Expression	[3]
Intrahepatic cholestasis of pregnancy	DISMHS5F	Limited	Biomarker	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Endoplasmic reticulum resident protein 29 (ERP29).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Endoplasmic reticulum resident protein 29 (ERP29).	[20]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Endoplasmic reticulum resident protein 29 (ERP29).	[13]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Endoplasmic reticulum resident protein 29 (ERP29).	[14]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Endoplasmic reticulum resident protein 29 (ERP29).	[15]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Endoplasmic reticulum resident protein 29 (ERP29).	[16]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Endoplasmic reticulum resident protein 29 (ERP29).	[17]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Endoplasmic reticulum resident protein 29 (ERP29).	[18]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Endoplasmic reticulum resident protein 29 (ERP29).	[19]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Endoplasmic reticulum resident protein 29 (ERP29).	[21]

References

• [1] ERp29 downregulation enhances lung adenocarcinoma cell chemosensitivity to gemcitabine by upregulating HSP27 phosphorylation.Exp Ther Med. 2019 Jan;17(1):817-823. doi: 10.3892/etm.2018.7040. Epub 2018 Nov 30.
• [2] Endoplasmic reticulum protein 29 (ERp29) as a novel prognostic marker and tumor suppressor in osteosarcoma.J Bone Oncol. 2019 Mar 19;16:100233. doi: 10.1016/j.jbo.2019.100233. eCollection 2019 Jun.
• [3] miR-205-5p downregulation decreases gemcitabine sensitivity of breast cancer cells via ERp29 upregulation.Exp Ther Med. 2019 Nov;18(5):3525-3533. doi: 10.3892/etm.2019.7962. Epub 2019 Aug 30.
• [4] ERp29, an endoplasmic reticulum secretion factor is involved in the growth of breast tumor xenografts.Mol Carcinog. 2008 Nov;47(11):886-92. doi: 10.1002/mc.20444.
• [5] Expression of ERp29, an endoplasmic reticulum secretion factor in basal-cell carcinoma.Am J Dermatopathol. 2006 Oct;28(5):410-2. doi: 10.1097/01.dad.0000211521.49810.ac.
• [6] ERp29 counteracts the suppression of malignancy mediated by endoplasmic reticulum stress and promotes the metastasis of colorectal cancer.Oncol Rep. 2019 Mar;41(3):1603-1615. doi: 10.3892/or.2018.6943. Epub 2018 Dec 19.
• [7] High glucose regulates ERp29 in hepatocellular carcinoma by LncRNA MEG3-miRNA 483-3p pathway.Life Sci. 2019 Sep 1;232:116602. doi: 10.1016/j.lfs.2019.116602. Epub 2019 Jun 26.
• [8] Identification of genes potentially involved in the acquisition of androgen-independent and metastatic tumor growth in an autochthonous genetically engineered mouse prostate cancer model.Prostate. 2007 Jan 1;67(1):83-106. doi: 10.1002/pros.20505.
• [9] ERp29 controls invasion and metastasis of gastric carcinoma by inhibition of epithelial-mesenchymal transition via PI3K/Aktsignaling pathway.BMC Cancer. 2017 Sep 6;17(1):626. doi: 10.1186/s12885-017-3613-x.
• [10] Inhibiting ERp29 expression enhances radiosensitivity in human nasopharyngeal carcinoma cell lines.Med Oncol. 2012 Jun;29(2):721-8. doi: 10.1007/s12032-011-9929-5. Epub 2011 Apr 11.
• [11] ERp29 inhibition attenuates TCA toxicity via affecting p38/p53- dependent pathway in human trophoblast HTR-8/SVeno cells.Arch Biochem Biophys. 2019 Nov 15;676:108125. doi: 10.1016/j.abb.2019.108125. Epub 2019 Oct 3.
• [12] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [13] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [14] 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.
• [15] Nucleophosmin in the pathogenesis of arsenic-related bladder carcinogenesis revealed by quantitative proteomics. Toxicol Appl Pharmacol. 2010 Jan 15;242(2):126-35. doi: 10.1016/j.taap.2009.09.016. Epub 2009 Oct 7.
• [16] Identification of biomarkers for the initiation of apoptosis in human preneoplastic colonocytes by proteome analysis. Int J Cancer. 2004 Mar 20;109(2):220-9. doi: 10.1002/ijc.11692.
• [17] Proteomic identification of differentially expressed proteins associated with the multiple drug resistance in methotrexate-resistant human breast cancer cells. Int J Oncol. 2014 Jul;45(1):448-58.
• [18] Proteomic analysis of antiproliferative effects by treatment of 5-fluorouracil in cervical cancer cells. DNA Cell Biol. 2004 Nov;23(11):769-76.
• [19] Effects of acute ethanol treatment on NCCIT cells and NCCIT cell-derived embryoid bodies (EBs). Toxicol In Vitro. 2010 Sep;24(6):1696-704. doi: 10.1016/j.tiv.2010.05.017. Epub 2010 May 26.
• [20] 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.
• [21] 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.