General Information of Drug Off-Target (DOT) (ID: OTRP8R4W)

DOT Name Formin-like protein 3 (FMNL3)
Synonyms Formin homology 2 domain-containing protein 3; WW domain-binding protein 3; WBP-3
Gene Name FMNL3
Related Disease
Advanced cancer ( )
Esophageal squamous cell carcinoma ( )
Colorectal carcinoma ( )
Nasopharyngeal carcinoma ( )
Neoplasm ( )
UniProt ID
FMNL3_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF06367 ; PF06371 ; PF02181
Sequence
MGNLESAEGVPGEPPSVPLLLPPGKMPMPEPCELEERFALVLSSMNLPPDKARLLRQYDN
EKKWDLICDQERFQVKNPPHTYIQKLQSFLDPSVTRKKFRRRVQESTKVLRELEISLRTN
HIGWVREFLNDENKGLDVLVDYLSFAQCSVMFDFEGLESGDDGAFDKLRSWSRSIEDLQP
PSALSAPFTNSLARSARQSVLRYSTLPGRRALKNSRLVSQKDDVHVCILCLRAIMNYQYG
FNLVMSHPHAVNEIALSLNNKNPRTKALVLELLAAVCLVRGGHEIILAAFDNFKEVCKEL
HRFEKLMEYFRNEDSNIDFMVACMQFINIVVHSVEDMNFRVHLQYEFTKLGLEEFLQKSR
HTESEKLQVQIQAYLDNVFDVGGLLEDAETKNVALEKVEELEEHVSHLTEKLLDLENENM
MRVAELEKQLLQREKELESIKETYENTSHQVHTLRRLIKEKEEAFQRRCHLEPNVRGLES
VDSEALARVGPAELSEGMPPSDLDLLAPAPPPEEVLPLPPPPAPPLPPPPPPLPDKCPPA
PPLPGAAPSVVLTVGLSAIRIKKPIKTKFRLPVFNWTALKPNQISGTVFSELDDEKILED
LDLDKFEELFKTKAQGPALDLICSKNKTAQKAASKVTLLEANRAKNLAITLRKAGRSAEE
ICRAIHTFDLQTLPVDFVECLMRFLPTEAEVKLLRQYERERQPLEELAAEDRFMLLFSKV
ERLTQRMAGMAFLGNFQDNLQMLTPQLNAIIAASASVKSSQKLKQMLEIILALGNYMNSS
KRGAVYGFKLQSLDLLLDTKSTDRKMTLLHFIALTVKEKYPDLANFWHELHFVEKAAAVS
LENVLLDVKELGRGMELIRRECSIHDNSVLRNFLSTNEGKLDKLQRDAKTAEEAYNAVVR
YFGESPKTTPPSVFFPVFVRFIRSYKEAEQENEARKKQEEVMREKQLAQEAKKLDAKTPS
QRNKWQQQELIAELRRRQAKEHRPVYEGKDGTIEDIITVLKSVPFTARTAKRGSRFFCDA
AHHDESNC
Function
Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the control of cell shape and migration. Required for developmental angiogenesis. In this process, required for microtubule reorganization and for efficient endothelial cell elongation. In quiescent endothelial cells, triggers rearrangement of the actin cytoskeleton, but does not alter microtubule alignement.
Tissue Specificity Expressed in endothelial cells.
KEGG Pathway
Cytoskeleton in muscle cells (hsa04820 )
Reactome Pathway
RHOA GTPase cycle (R-HSA-8980692 )
RHOC GTPase cycle (R-HSA-9013106 )
CDC42 GTPase cycle (R-HSA-9013148 )
RHOJ GTPase cycle (R-HSA-9013409 )
RHO GTPases Activate Formins (R-HSA-5663220 )

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Advanced cancer DISAT1Z9 Strong Altered Expression [1]
Esophageal squamous cell carcinoma DIS5N2GV Strong Altered Expression [2]
Colorectal carcinoma DIS5PYL0 moderate Altered Expression [3]
Nasopharyngeal carcinoma DISAOTQ0 Limited Altered Expression [4]
Neoplasm DISZKGEW Limited Biomarker [1]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
8 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate affects the expression of Formin-like protein 3 (FMNL3). [5]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Formin-like protein 3 (FMNL3). [6]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Formin-like protein 3 (FMNL3). [7]
Temozolomide DMKECZD Approved Temozolomide decreases the expression of Formin-like protein 3 (FMNL3). [9]
Zoledronate DMIXC7G Approved Zoledronate increases the expression of Formin-like protein 3 (FMNL3). [10]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Formin-like protein 3 (FMNL3). [11]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Formin-like protein 3 (FMNL3). [12]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of Formin-like protein 3 (FMNL3). [13]
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⏷ Show the Full List of 8 Drug(s)
1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Arsenic DMTL2Y1 Approved Arsenic affects the methylation of Formin-like protein 3 (FMNL3). [8]
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References

1 High expression of FMNL3 associates with cancer cell migration, invasion, and unfavorable prognosis in tongue squamous cell carcinoma.J Oral Pathol Med. 2019 Jul;48(6):459-467. doi: 10.1111/jop.12857. Epub 2019 Apr 25.
2 MicroRNA-127 is a tumor suppressor in human esophageal squamous cell carcinoma through the regulation of oncogene FMNL3.Eur J Pharmacol. 2016 Nov 15;791:603-610. doi: 10.1016/j.ejphar.2016.09.025. Epub 2016 Sep 17.
3 Formin-like 3 regulates RhoC/FAK pathway and actin assembly to promote cell invasion in colorectal carcinoma.World J Gastroenterol. 2018 Sep 14;24(34):3884-3897. doi: 10.3748/wjg.v24.i34.3884.
4 High FMNL3 expression promotes nasopharyngeal carcinoma cell metastasis: role in TGF-1-induced epithelia-to-mesenchymal transition.Sci Rep. 2017 Feb 15;7:42507. doi: 10.1038/srep42507.
5 Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
6 Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
7 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
8 Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
9 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.
10 Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
11 Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
12 Comprehensive transcriptome profiling of BET inhibitor-treated HepG2 cells. PLoS One. 2022 Apr 29;17(4):e0266966. doi: 10.1371/journal.pone.0266966. eCollection 2022.
13 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.