Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT704FQ0)

DOT Name Tripartite motif-containing protein 3 (TRIM3)
Synonyms EC 2.3.2.27; Brain-expressed RING finger protein; RING finger protein 22; RING finger protein 97
Gene Name TRIM3
Related Disease
Arthritis ( )
Brain neoplasm ( )
Breast cancer ( )
Breast carcinoma ( )
Cervical cancer ( )
Cervical carcinoma ( )
Colorectal carcinoma ( )
Esophageal squamous cell carcinoma ( )
Glioma ( )
Hepatocellular carcinoma ( )
Influenza ( )
Parkinson disease ( )
Rheumatoid arthritis ( )
Schizophrenia ( )
Carcinoma of liver and intrahepatic biliary tract ( )
Gastric cancer ( )
Liver cancer ( )
Metastatic malignant neoplasm ( )
Stomach cancer ( )
Advanced cancer ( )
Neoplasm ( )
UniProt ID
TRIM3_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
7O0B; 7QRW; 8AMR
EC Number
2.3.2.27
Pfam ID
PF00630 ; PF01436 ; PF00643 ; PF00097
Sequence
MAKREDSPGPEVQPMDKQFLVCSICLDRYQCPKVLPCLHTFCERCLQNYIPAQSLTLSCP
VCRQTSILPEQGVSALQNNFFISSLMEAMQQAPDGAHDPEDPHPLSVVAGRPLSCPNHEG
KTMEFYCEACETAMCGECRAGEHREHGTVLLRDVVEQHKAALQRQLEAVRGRLPQLSAAI
ALVGGISQQLQERKAEALAQISAAFEDLEQALQQRKQALVSDLETICGAKQKVLQSQLDT
LRQGQEHIGSSCSFAEQALRLGSAPEVLLVRKHMRERLAALAAQAFPERPHENAQLELVL
EVDGLRRSVLNLGALLTTSATAHETVATGEGLRQALVGQPASLTVTTKDKDGRLVRTGSA
ELRAEITGPDGTRLPVPVVDHKNGTYELVYTARTEGELLLSVLLYGQPVRGSPFRVRALR
PGDLPPSPDDVKRRVKSPGGPGSHVRQKAVRRPSSMYSTGGKRKDNPIEDELVFRVGSRG
REKGEFTNLQGVSAASSGRIVVADSNNQCIQVFSNEGQFKFRFGVRGRSPGQLQRPTGVA
VDTNGDIIVADYDNRWVSIFSPEGKFKTKIGAGRLMGPKGVAVDRNGHIIVVDNKSCCVF
TFQPNGKLVGRFGGRGATDRHFAGPHFVAVNNKNEIVVTDFHNHSVKVYSADGEFLFKFG
SHGEGNGQFNAPTGVAVDSNGNIIVADWGNSRIQVFDSSGSFLSYINTSAEPLYGPQGLA
LTSDGHVVVADAGNHCFKAYRYLQ
Function
E3 ubiquitin ligase that plays essential roles in neuronal functions such as regulation of neuronal plasticity, learning, and memory. In addition to its neuronal functions, participates in other biological processes such as innate immunity or cell cycle regulation. Component of the cytoskeleton-associated recycling or transport complex in neurons, polyubiquitinates gamma-actin, thus regulating neuronal plasticity, learning, and memory. Ubiquitinates postsynaptic scaffold GKAP, a neuronal substrate involved in synaptic remodeling and thereby modulates dendritic spine morphology. Positively regulates motility of microtubule-dependent motor protein KIF21B. Induces growth arrest via its RING-dependent E3 ligase activity and ubiquinates CDKN1A. Positively regulates TLR3-mediated signaling by mediating 'Lys-63'-linked polyubiquitination of TLR3. In turn, promotes the recognition and sorting of polyubiquitinated TLR3 by the ESCRT complexes.
Tissue Specificity Expressed in brain, heart, uterus and testis.
Reactome Pathway
Interferon gamma signaling (R-HSA-877300 )

Molecular Interaction Atlas (MIA) of This DOT

21 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Arthritis DIST1YEL Strong Altered Expression [1]
Brain neoplasm DISY3EKS Strong Biomarker [2]
Breast cancer DIS7DPX1 Strong Altered Expression [3]
Breast carcinoma DIS2UE88 Strong Altered Expression [3]
Cervical cancer DISFSHPF Strong Biomarker [4]
Cervical carcinoma DIST4S00 Strong Biomarker [4]
Colorectal carcinoma DIS5PYL0 Strong Biomarker [5]
Esophageal squamous cell carcinoma DIS5N2GV Strong Altered Expression [6]
Glioma DIS5RPEH Strong Altered Expression [2]
Hepatocellular carcinoma DIS0J828 Strong Altered Expression [7]
Influenza DIS3PNU3 Strong Biomarker [8]
Parkinson disease DISQVHKL Strong Biomarker [9]
Rheumatoid arthritis DISTSB4J Strong Altered Expression [1]
Schizophrenia DISSRV2N Strong Altered Expression [10]
Carcinoma of liver and intrahepatic biliary tract DIS8WA0W moderate Altered Expression [7]
Gastric cancer DISXGOUK moderate Biomarker [11]
Liver cancer DISDE4BI moderate Altered Expression [7]
Metastatic malignant neoplasm DIS86UK6 moderate Biomarker [7]
Stomach cancer DISKIJSX moderate Biomarker [11]
Advanced cancer DISAT1Z9 Limited Biomarker [12]
Neoplasm DISZKGEW Limited Genetic Variation [6]
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⏷ Show the Full List of 21 Disease(s)
Molecular Interaction Atlas (MIA) 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
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of Tripartite motif-containing protein 3 (TRIM3). [13]
Estradiol DMUNTE3 Approved Estradiol affects the expression of Tripartite motif-containing protein 3 (TRIM3). [14]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Tripartite motif-containing protein 3 (TRIM3). [15]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide decreases the expression of Tripartite motif-containing protein 3 (TRIM3). [16]
Urethane DM7NSI0 Phase 4 Urethane increases the expression of Tripartite motif-containing protein 3 (TRIM3). [17]
Leflunomide DMR8ONJ Phase 1 Trial Leflunomide decreases the expression of Tripartite motif-containing protein 3 (TRIM3). [18]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Tripartite motif-containing protein 3 (TRIM3). [19]
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⏷ Show the Full List of 7 Drug(s)

References

1 Forkhead box o3a suppresses lipopolysaccharide-stimulated proliferation and inflammation in fibroblast-like synoviocytes through regulating tripartite motif-containing protein 3.J Cell Physiol. 2019 Nov;234(11):20139-20148. doi: 10.1002/jcp.28615. Epub 2019 Apr 13.
2 Human Brat ortholog TRIM3 is a tumor suppressor that regulates asymmetric cell division in glioblastoma.Cancer Res. 2014 Aug 15;74(16):4536-48. doi: 10.1158/0008-5472.CAN-13-3703. Epub 2014 Jun 19.
3 miR-4513 promotes breast cancer progression through targeting TRIM3.Am J Transl Res. 2019 Apr 15;11(4):2431-2438. eCollection 2019.
4 miR-454-3p promotes proliferation and induces apoptosis in human cervical cancer cells by targeting TRIM3.Biochem Biophys Res Commun. 2019 Aug 27;516(3):872-879. doi: 10.1016/j.bbrc.2019.06.126. Epub 2019 Jun 30.
5 TRIM37 promotes epithelialmesenchymal transition in colorectal cancer.Mol Med Rep. 2017 Mar;15(3):1057-1062. doi: 10.3892/mmr.2017.6125. Epub 2017 Jan 16.
6 Targeting TRIM3 deletion-induced tumor-associated lymphangiogenesis prohibits lymphatic metastasis in esophageal squamous cell carcinoma.Oncogene. 2019 Apr;38(15):2736-2749. doi: 10.1038/s41388-018-0621-5. Epub 2018 Dec 12.
7 Tripartite motif-containing 3 (TRIM3) inhibits tumor growth and metastasis of liver cancer.Chin J Cancer. 2017 Sep 26;36(1):77. doi: 10.1186/s40880-017-0240-5.
8 The human potential of a recombinant pandemic influenza vaccine produced in tobacco plants.Hum Vaccin Immunother. 2012 May;8(5):653-61. doi: 10.4161/hv.19503. Epub 2012 May 1.
9 Proteomics and bioinformatics approaches for the identification of plasma biomarkers to detect Parkinson's disease.Exp Ther Med. 2019 Oct;18(4):2833-2842. doi: 10.3892/etm.2019.7888. Epub 2019 Aug 14.
10 Prefrontal cortex shotgun proteome analysis reveals altered calcium homeostasis and immune system imbalance in schizophrenia.Eur Arch Psychiatry Clin Neurosci. 2009 Apr;259(3):151-63. doi: 10.1007/s00406-008-0847-2. Epub 2009 Jan 22.
11 Exosomal TRIM3 is a novel marker and therapy target for gastric cancer.J Exp Clin Cancer Res. 2018 Jul 21;37(1):162. doi: 10.1186/s13046-018-0825-0.
12 Hemoglobins, Hemorphins, and 11p15.5 Chromosomal Region in Cancer Biology and mmunity with Special Emphasis for Brain Tumors.J Neurol Surg A Cent Eur Neurosurg. 2016 May;77(3):247-57. doi: 10.1055/s-0035-1566120. Epub 2016 Mar 2.
13 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
14 Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
15 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.
16 Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
17 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
18 Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
19 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.