Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTMPRLZ5)

DOT Name Four and a half LIM domains protein 3 (FHL3)
Synonyms FHL-3; Skeletal muscle LIM-protein 2; SLIM-2
Gene Name FHL3
Related Disease
Breast cancer ( )
Breast carcinoma ( )
Carcinoma of liver and intrahepatic biliary tract ( )
Colorectal carcinoma ( )
Colorectal neoplasm ( )
Glioma ( )
Griscelli syndrome type 2 ( )
Hereditary hemophagocytic lymphohistiocytosis ( )
Leukopenia ( )
Liver cancer ( )
Thrombocytopenia ( )
Immune system disorder ( )
Lysosomal storage disease ( )
UniProt ID
FHL3_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
1WYH; 2CUQ; 2EHE
Pfam ID
PF00412
Sequence
MSESFDCAKCNESLYGRKYIQTDSGPYCVPCYDNTFANTCAECQQLIGHDSRELFYEDRH
FHEGCFRCCRCQRSLADEPFTCQDSELLCNDCYCSAFSSQCSACGETVMPGSRKLEYGGQ
TWHEHCFLCSGCEQPLGSRSFVPDKGAHYCVPCYENKFAPRCARCSKTLTQGGVTYRDQP
WHRECLVCTGCQTPLAGQQFTSRDEDPYCVACFGELFAPKCSSCKRPIVGLGGGKYVSFE
DRHWHHNCFSCARCSTSLVGQGFVPDGDQVLCQGCSQAGP
Function Recruited by SOX15 to FOXK1 promoters where it acts as a transcriptional coactivator of FOXK1.
Tissue Specificity Expressed only in skeletal muscle.
KEGG Pathway
Cytoskeleton in muscle cells (hsa04820 )

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Breast cancer DIS7DPX1 Strong Biomarker [1]
Breast carcinoma DIS2UE88 Strong Biomarker [1]
Carcinoma of liver and intrahepatic biliary tract DIS8WA0W Strong Biomarker [1]
Colorectal carcinoma DIS5PYL0 Strong Biomarker [2]
Colorectal neoplasm DISR1UCN Strong Biomarker [2]
Glioma DIS5RPEH Strong Altered Expression [3]
Griscelli syndrome type 2 DISDQRBS Strong Biomarker [4]
Hereditary hemophagocytic lymphohistiocytosis DISQP21Z Strong Biomarker [5]
Leukopenia DISJMBMM Strong Biomarker [4]
Liver cancer DISDE4BI Strong Biomarker [1]
Thrombocytopenia DISU61YW Strong Biomarker [6]
Immune system disorder DISAEGPH Limited Genetic Variation [7]
Lysosomal storage disease DIS6QM6U Limited Genetic Variation [8]
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⏷ Show the Full List of 13 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
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 Four and a half LIM domains protein 3 (FHL3). [9]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Four and a half LIM domains protein 3 (FHL3). [10]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of Four and a half LIM domains protein 3 (FHL3). [11]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Four and a half LIM domains protein 3 (FHL3). [12]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Four and a half LIM domains protein 3 (FHL3). [13]
Temozolomide DMKECZD Approved Temozolomide increases the expression of Four and a half LIM domains protein 3 (FHL3). [14]
Testosterone DM7HUNW Approved Testosterone increases the expression of Four and a half LIM domains protein 3 (FHL3). [15]
Fluorouracil DMUM7HZ Approved Fluorouracil increases the expression of Four and a half LIM domains protein 3 (FHL3). [16]
Azathioprine DMMZSXQ Approved Azathioprine increases the expression of Four and a half LIM domains protein 3 (FHL3). [17]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of Four and a half LIM domains protein 3 (FHL3). [18]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Four and a half LIM domains protein 3 (FHL3). [19]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Four and a half LIM domains protein 3 (FHL3). [20]
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⏷ Show the Full List of 12 Drug(s)

References

1 Downregulation and antiproliferative role of FHL3 in breast cancer.IUBMB Life. 2011 Sep;63(9):764-71. doi: 10.1002/iub.502.
2 Discovery of common and rare genetic risk variants for colorectal cancer.Nat Genet. 2019 Jan;51(1):76-87. doi: 10.1038/s41588-018-0286-6. Epub 2018 Dec 3.
3 PCBP2 promotes the development of glioma by regulating FHL3/TGF-/Smad signaling pathway.J Cell Physiol. 2020 Apr;235(4):3280-3291. doi: 10.1002/jcp.29104. Epub 2019 Nov 6.
4 Evidence for defective Rab GTPase-dependent cargo traffic in immune disorders.Exp Cell Res. 2013 Sep 10;319(15):2360-7. doi: 10.1016/j.yexcr.2013.06.012. Epub 2013 Jun 26.
5 Retroviral UNC13D Gene Transfer Restores Cytotoxic Activity of T Cells Derived from Familial Hemophagocytic Lymphohistiocytosis Type 3 Patients In Vitro.Hum Gene Ther. 2019 Aug;30(8):975-984. doi: 10.1089/hum.2019.025. Epub 2019 May 21.
6 Genotype-phenotype study of familial haemophagocytic lymphohistiocytosis type 3.J Med Genet. 2011 May;48(5):343-52. doi: 10.1136/jmg.2010.085456. Epub 2011 Jan 19.
7 A novel Dutch mutation in UNC13D reveals an essential role of the C2B domain in munc13-4 function.Pediatr Blood Cancer. 2012 Apr;58(4):598-605. doi: 10.1002/pbc.23253. Epub 2011 Jul 13.
8 Cross-regulation of defective endolysosome trafficking and enhanced autophagy through TFEB in UNC13D deficiency.Autophagy. 2019 Oct;15(10):1738-1756. doi: 10.1080/15548627.2019.1596475. Epub 2019 Apr 5.
9 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
10 Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
11 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
12 Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
13 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.
14 Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
15 The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
16 Gene expression profiling of breast cancer cells in response to gemcitabine: NF-kappaB pathway activation as a potential mechanism of resistance. Breast Cancer Res Treat. 2007 Apr;102(2):157-72.
17 A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
18 Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
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.
20 Isobaric tags for relative and absolute quantitation-based proteomics analysis of the effect of ginger oil on bisphenol A-induced breast cancer cell proliferation. Oncol Lett. 2021 Feb;21(2):101. doi: 10.3892/ol.2020.12362. Epub 2020 Dec 8.