Details of Drug Off-Target (DOT)

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

DOT Name	Transmembrane emp24 domain-containing protein 3 (TMED3)
Synonyms	Membrane protein p24B; p24 family protein gamma-4; p24gamma4; p26
Gene Name	TMED3
Related Disease	Clear cell renal carcinoma ( ) Anemia ( ) Metastatic malignant neoplasm ( ) Retinitis pigmentosa ( ) Colon cancer ( ) Colon carcinoma ( ) Hepatocellular carcinoma ( ) Prostate cancer ( ) Prostate carcinoma ( ) Breast cancer ( ) Breast carcinoma ( )
UniProt ID	TMED3_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
Pfam ID	PF01105
Sequence	MGSTVPRSASVLLLLLLLRRAEQPCGAELTFELPDNAKQCFHEEVEQGVKFSLDYQVITG GHYDVDCYVEDPQGNTIYRETKKQYDSFTYRAEVKGVYQFCFSNEFSTFSHKTVYFDFQV GDEPPILPDMGNRVTALTQMESACVTIHEALKTVIDSQTHYRLREAQDRARAEDLNSRVS YWSVGETIALFVVSFSQVLLLKSFFTEKRPISRAVHS
Function	Potential role in vesicular protein trafficking, mainly in the early secretory pathway. Contributes to the coupled localization of TMED2 and TMED10 in the cis-Golgi network.
Reactome Pathway	COPI-dependent Golgi-to-ER retrograde traffic (R-HSA-6811434 ) COPI-mediated anterograde transport (R-HSA-6807878 )

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Clear cell renal carcinoma	DISBXRFJ	Definitive	Biomarker	[1]
Anemia	DISTVL0C	Strong	Biomarker	[2]
Metastatic malignant neoplasm	DIS86UK6	Strong	Biomarker	[3]
Retinitis pigmentosa	DISCGPY8	Strong	Biomarker	[4]
Colon cancer	DISVC52G	moderate	Biomarker	[1]
Colon carcinoma	DISJYKUO	moderate	Biomarker	[1]
Hepatocellular carcinoma	DIS0J828	moderate	Biomarker	[1]
Prostate cancer	DISF190Y	moderate	Biomarker	[5]
Prostate carcinoma	DISMJPLE	moderate	Biomarker	[5]
Breast cancer	DIS7DPX1	Limited	Biomarker	[3]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[3]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

7 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 Transmembrane emp24 domain-containing protein 3 (TMED3).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Transmembrane emp24 domain-containing protein 3 (TMED3).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Transmembrane emp24 domain-containing protein 3 (TMED3).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Transmembrane emp24 domain-containing protein 3 (TMED3).	[9]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Transmembrane emp24 domain-containing protein 3 (TMED3).	[8]
Azacitidine	DMTA5OE	Approved	Azacitidine increases the expression of Transmembrane emp24 domain-containing protein 3 (TMED3).	[10]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Transmembrane emp24 domain-containing protein 3 (TMED3).	[12]
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1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Transmembrane emp24 domain-containing protein 3 (TMED3).	[11]
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References

1	Prognostic Role of TMED3 in Clear Cell Renal Cell Carcinoma: A Retrospective Multi-Cohort Analysis.Front Genet. 2019 Apr 17;10:355. doi: 10.3389/fgene.2019.00355. eCollection 2019.
2	Enzyme-linked immunosorbent assay and agar gel immunodiffusion assay for diagnosis of equine infectious anemia employing p26 protein fused to the maltose-binding protein.Arch Virol. 2018 Oct;163(10):2871-2875. doi: 10.1007/s00705-018-3923-6. Epub 2018 Jul 7.
3	TMED3 promotes cell proliferation and motility in breast cancer and is negatively modulated by miR-188-3p.Cancer Cell Int. 2019 Mar 29;19:75. doi: 10.1186/s12935-019-0791-4. eCollection 2019.
4	(3R)-5,6,7-trihydroxy-3-isopropyl-3-methylisochroman-1-one ameliorates retinal degeneration in Pde6b(rd10) mice.Cutan Ocul Toxicol. 2018 Sep;37(3):245-251. doi: 10.1080/15569527.2018.1441863. Epub 2018 Mar 15.
5	High-throughput transcriptomic and RNAi analysis identifies AIM1, ERGIC1, TMED3 and TPX2 as potential drug targets in prostate cancer.PLoS One. 2012;7(6):e39801. doi: 10.1371/journal.pone.0039801. Epub 2012 Jun 28.
6	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.
7	Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
8	Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
9	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.
10	The effect of DNA methylation inhibitor 5-Aza-2'-deoxycytidine on human endometrial stromal cells. Hum Reprod. 2010 Nov;25(11):2859-69.
11	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.
12	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.