Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3MEGIU)

• DOT Name: Endoplasmic reticulum-Golgi intermediate compartment protein 2 (ERGIC2)
• Gene Name: ERGIC2
• Related Disease:
  Adenoma
  Colitis
  Paroxysmal nocturnal haemoglobinuria
  Prostate cancer
  Prostate carcinoma
  Uterine serous carcinoma
  Treacher-Collins syndrome
  Prostate neoplasm
• UniProt ID: ERGI2_HUMAN
• Pfam ID: PF07970 ; PF13850
• Sequence:
  MRRLNRKKTLSLVKELDAFPKVPESYVETSASGGTVSLIAFTTMALLTIMEFSVYQDTWM
  KYEYEVDKDFSSKLRINIDITVAMKCQYVGADVLDLAETMVASADGLVYEPTVFDLSPQQ
  KEWQRMLQLIQSRLQEEHSLQDVIFKSAFKSTSTALPPREDDSSQSPNACRIHGHLYVNK
  VAGNFHITVGKAIPHPRGHAHLAALVNHESYNFSHRIDHLSFGELVPAIINPLDGTEKIA
  IDHNQMFQYFITVVPTKLHTYKISADTHQFSVTERERIINHAAGSHGVSGIFMKYDLSSL
  MVTVTEEHMPFWQFFVRLCGIVGGIFSTTGMLHGIGKFIVEIICCRFRLGSYKPVNSVPF
  EDGHTDNHLPLLENNTH
• Function: Possible role in transport between endoplasmic reticulum and Golgi.
• Tissue Specificity: Ubiquitously expressed.

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenoma	DIS78ZEV	Strong	Biomarker	[1]
Colitis	DISAF7DD	Strong	Altered Expression	[2]
Paroxysmal nocturnal haemoglobinuria	DISBHMYH	Strong	Biomarker	[3]
Prostate cancer	DISF190Y	Strong	Biomarker	[4]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[4]
Uterine serous carcinoma	DISAW5MD	Strong	Biomarker	[5]
Treacher-Collins syndrome	DIS2GXZ1	moderate	Altered Expression	[6]
Prostate neoplasm	DISHDKGQ	Limited	Altered Expression	[4]

1 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-Golgi intermediate compartment protein 2 (ERGIC2).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Endoplasmic reticulum-Golgi intermediate compartment protein 2 (ERGIC2).	[8]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Endoplasmic reticulum-Golgi intermediate compartment protein 2 (ERGIC2).	[9]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Endoplasmic reticulum-Golgi intermediate compartment protein 2 (ERGIC2).	[10]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Endoplasmic reticulum-Golgi intermediate compartment protein 2 (ERGIC2).	[11]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Endoplasmic reticulum-Golgi intermediate compartment protein 2 (ERGIC2).	[12]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Endoplasmic reticulum-Golgi intermediate compartment protein 2 (ERGIC2).	[13]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Endoplasmic reticulum-Golgi intermediate compartment protein 2 (ERGIC2).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Endoplasmic reticulum-Golgi intermediate compartment protein 2 (ERGIC2).	[15]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Endoplasmic reticulum-Golgi intermediate compartment protein 2 (ERGIC2).	[16]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Endoplasmic reticulum-Golgi intermediate compartment protein 2 (ERGIC2).	[17]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Endoplasmic reticulum-Golgi intermediate compartment protein 2 (ERGIC2).	[18]
CH-223191	DMMJZYC	Investigative	CH-223191 decreases the expression of Endoplasmic reticulum-Golgi intermediate compartment protein 2 (ERGIC2).	[19]

References

• [1] Expression of pituitary homeo box 1 (Ptx1) in human non-neoplastic pituitaries and pituitary adenomas.Mod Pathol. 2000 Oct;13(10):1097-108. doi: 10.1038/modpathol.3880204.
• [2] Nitric Oxide Is Involved in Activation of Toll-Like Receptor 4 Signaling through Tyrosine Nitration of Src Homology Protein Tyrosine Phosphatase 2 in Murine Dextran Sulfate-Induced Colitis.Biol Pharm Bull. 2018;41(12):1843-1852. doi: 10.1248/bpb.b18-00558.
• [3] Monocyte antigen CD14 is a phospholipid anchored membrane protein.Blood. 1989 Jan;73(1):284-9.
• [4] PTX1(ERGIC2)-VP22 fusion protein upregulates interferon-beta in prostate cancer cell line PC-3.DNA Cell Biol. 2006 Sep;25(9):523-9. doi: 10.1089/dna.2006.25.523.
• [5] Metabolomic analysis of uterine serous carcinoma with acquired resistance to paclitaxel.Oncotarget. 2018 Aug 10;9(62):31985-31998. doi: 10.18632/oncotarget.25868. eCollection 2018 Aug 10.
• [6] Human and murine PTX1/Ptx1 gene maps to the region for Treacher Collins syndrome.Mamm Genome. 1997;8(11):841-5. doi: 10.1007/s003359900589.
• [7] 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.
• [8] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [9] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [10] 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.
• [11] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [12] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [13] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [14] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [15] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [16] 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.
• [17] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [18] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [19] Adaptive changes in global gene expression profile of lung carcinoma A549 cells acutely exposed to distinct types of AhR ligands. Toxicol Lett. 2018 Aug;292:162-174.