Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQWZ1UO)

• DOT Name: Protein FAM83D (FAM83D)
• Synonyms: Spindle protein CHICA
• Gene Name: FAM83D
• UniProt ID: FA83D_HUMAN
• PDB ID: 5E0L; 5E0M
• Pfam ID: PF07894
• Sequence:
  MALLSEGLDEVPAACLSPCGPPNPTELFSESRRLALEELVAGGPEAFAAFLRRERLARFL
  NPDEVHAILRAAERPGEEGAAAAAAAEDSFGSSHDCSSGTYFPEQSDLEPPLLELGWPAF
  YQGAYRGATRVETHFQPRGAGEGGPYGCKDALRQQLRSAREVIAVVMDVFTDIDIFRDLQ
  EICRKQGVAVYILLDQALLSQFLDMCMDLKVHPEQEKLMTVRTITGNIYYARSGTKIIGK
  VHEKFTLIDGIRVATGSYSFTWTDGKLNSSNLVILSGQVVEHFDLEFRILYAQSKPISPK
  LLSHFQSSNKFDHLTNRKPQSKELTLGNLLRMRLARLSSTPRKADLDPEMPAEGKAERKP
  HDCESSTVSEEDYFSSHRDELQSRKAIDAATQTEPGEEMPGLSVSEVGTQTSITTACAGT
  QTAVITRIASSQTTIWSRSTTTQTDMDENILFPRGTQSTEGSPVSKMSVSRSSSLKSSSS
  VSSQGSVASSTGSPASIRTTDFHNPGYPKYLGTPHLELYLSDSLRNLNKERQFHFAGIRS
  RLNHMLAMLSRRTLFTENHLGLHSGNFSRVNLLAVRDVALYPSYQ
• Function: Through the degradation of FBXW7, may act indirectly on the expression and downstream signaling of MTOR, JUN and MYC. May play also a role in cell proliferation through activation of the ERK1/ERK2 signaling cascade. May also be important for proper chromosome congression and alignment during mitosis through its interaction with KIF22.
• Tissue Specificity: Expressed in the testis.

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Temozolomide	DMKECZD	Approved	Protein FAM83D (FAM83D) decreases the response to substance of Temozolomide.	[27]

3 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Protein FAM83D (FAM83D).	[1]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Protein FAM83D (FAM83D).	[8]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Protein FAM83D (FAM83D).	[23]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Protein FAM83D (FAM83D).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Protein FAM83D (FAM83D).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Protein FAM83D (FAM83D).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protein FAM83D (FAM83D).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Protein FAM83D (FAM83D).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Protein FAM83D (FAM83D).	[7]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Protein FAM83D (FAM83D).	[9]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Protein FAM83D (FAM83D).	[10]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Protein FAM83D (FAM83D).	[10]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Protein FAM83D (FAM83D).	[11]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Protein FAM83D (FAM83D).	[12]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of Protein FAM83D (FAM83D).	[13]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Protein FAM83D (FAM83D).	[14]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Protein FAM83D (FAM83D).	[15]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Protein FAM83D (FAM83D).	[16]
Palbociclib	DMD7L94	Approved	Palbociclib decreases the expression of Protein FAM83D (FAM83D).	[17]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Protein FAM83D (FAM83D).	[18]
GSK2110183	DMZHB37	Phase 2	GSK2110183 decreases the expression of Protein FAM83D (FAM83D).	[19]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Protein FAM83D (FAM83D).	[20]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Protein FAM83D (FAM83D).	[21]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Protein FAM83D (FAM83D).	[22]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Protein FAM83D (FAM83D).	[24]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Protein FAM83D (FAM83D).	[25]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Protein FAM83D (FAM83D).	[26]

References

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• [7] 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.
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• [10] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [11] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [12] 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.
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• [15] In vitro effects of aldehydes present in tobacco smoke on gene expression in human lung alveolar epithelial cells. Toxicol In Vitro. 2013 Apr;27(3):1072-81.
• [16] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [17] Cdk4/6 inhibition induces epithelial-mesenchymal transition and enhances invasiveness in pancreatic cancer cells. Mol Cancer Ther. 2012 Oct;11(10):2138-48. doi: 10.1158/1535-7163.MCT-12-0562. Epub 2012 Aug 6.
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• [19] Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
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• [21] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [22] 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.
• [23] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [24] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [25] 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.
• [26] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [27] Inhibition of FAM83D displays antitumor effects in glioblastoma via down-regulation of the AKT/Wnt/-catenin pathway. Environ Toxicol. 2022 Jun;37(6):1343-1356. doi: 10.1002/tox.23488. Epub 2022 Feb 12.