Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBG61YZ)

• DOT Name: Actin-associated protein FAM107A (FAM107A)
• Synonyms: Down-regulated in renal cell carcinoma 1; Protein TU3A
• Gene Name: FAM107A
• Related Disease:
  Cognitive impairment
  Adult glioblastoma
  Bladder cancer
  Clear cell renal carcinoma
  Glioblastoma multiforme
  Lung cancer
  Lung carcinoma
  Multiple sclerosis
  Neuroblastoma
  Non-small-cell lung cancer
  Ulcerative colitis
  Urinary bladder cancer
  Urinary bladder neoplasm
  Advanced cancer
  Autoimmune disease
  Immune system disorder
  Laryngeal squamous cell carcinoma
  Rheumatoid arthritis
  Autism spectrum disorder
  Glioma
  Malignant glioma
  Mixed glioma
  Renal cell carcinoma
• UniProt ID: F107A_HUMAN
• Pfam ID: PF06625
• Sequence:
  MYSEIQRERADIGGLMARPEYREWNPELIKPKKLLNPVKASRSHQELHRELLMNHRRGLG
  VDSKPELQRVLEHRRRNQLIKKKKEELEAKRLQCPFEQELLRRQQRLNQLEKPPEKEEDH
  APEFIKVRENLRRIATLTSEEREL
• Function: Stress-inducible actin-binding protein that plays a role in synaptic and cognitive functions by modulating actin filamentous (F-actin) dynamics. Mediates polymerization of globular actin to F-actin. Also binds to, stabilizes and bundles F-actin. Involved in synaptic function by regulating neurite outgrowth in an actin-dependent manner and for the acquisition of hippocampus-dependent cognitive function, such as learning and long-term memory. Plays a role in the actin and microtubule cytoskeleton organization; negatively regulates focal adhesion (FA) assembly promoting malignant glial cell migration in an actin-, microtubule- and MAP1A-dependent manner. Also involved in neuroblastoma G1/S phase cell cycle progression and cell proliferation inhibition by stimulating ubiquitination of NF-kappa-B subunit RELA and NF-kappa-B degradation in a COMMD1- and actin-dependent manner. May play a role in tumor development.
• Tissue Specificity: Widely expressed . Expressed in neurons . Expressed in malignant glial tumors . Expression is reduced or absent in a number of cancer cell lines .

Molecular Interaction Atlas (MIA) of This DOT

23 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cognitive impairment	DISH2ERD	Definitive	Altered Expression	[1]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[2]
Bladder cancer	DISUHNM0	Strong	Biomarker	[3]
Clear cell renal carcinoma	DISBXRFJ	Strong	Posttranslational Modification	[4]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[2]
Lung cancer	DISCM4YA	Strong	Altered Expression	[5]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[5]
Multiple sclerosis	DISB2WZI	Strong	Genetic Variation	[6]
Neuroblastoma	DISVZBI4	Strong	Biomarker	[7]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[8]
Ulcerative colitis	DIS8K27O	Strong	Biomarker	[9]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[3]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[3]
Advanced cancer	DISAT1Z9	moderate	Altered Expression	[10]
Autoimmune disease	DISORMTM	moderate	Genetic Variation	[11]
Immune system disorder	DISAEGPH	moderate	Genetic Variation	[11]
Laryngeal squamous cell carcinoma	DIS9UUVF	moderate	Posttranslational Modification	[12]
Rheumatoid arthritis	DISTSB4J	moderate	Genetic Variation	[13]
Autism spectrum disorder	DISXK8NV	Limited	Altered Expression	[14]
Glioma	DIS5RPEH	Limited	Biomarker	[15]
Malignant glioma	DISFXKOV	Limited	Biomarker	[15]
Mixed glioma	DIS64UY3	Limited	Biomarker	[15]
Renal cell carcinoma	DISQZ2X8	Limited	Posttranslational Modification	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Actin-associated protein FAM107A (FAM107A).	[16]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Actin-associated protein FAM107A (FAM107A).	[17]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Actin-associated protein FAM107A (FAM107A).	[18]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Actin-associated protein FAM107A (FAM107A).	[19]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Actin-associated protein FAM107A (FAM107A).	[16]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Actin-associated protein FAM107A (FAM107A).	[20]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Actin-associated protein FAM107A (FAM107A).	[18]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Actin-associated protein FAM107A (FAM107A).	[21]
Selenium	DM25CGV	Approved	Selenium increases the expression of Actin-associated protein FAM107A (FAM107A).	[22]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Actin-associated protein FAM107A (FAM107A).	[23]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Actin-associated protein FAM107A (FAM107A).	[24]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Actin-associated protein FAM107A (FAM107A).	[25]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Actin-associated protein FAM107A (FAM107A).	[24]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Actin-associated protein FAM107A (FAM107A).	[24]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Actin-associated protein FAM107A (FAM107A).	[22]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Actin-associated protein FAM107A (FAM107A).	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Actin-associated protein FAM107A (FAM107A).	[26]

References

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• [2] DRR1 promotes glioblastoma cell invasion and epithelial-mesenchymal transition via regulating AKT activation.Cancer Lett. 2018 Jun 1;423:86-94. doi: 10.1016/j.canlet.2018.03.015. Epub 2018 Mar 13.
• [3] Diagnostic value of combined IQGAP3/BMP4 and IQGAP3/FAM107A expression ratios in urinary cell-free DNA for discriminating bladder cancer from hematuria.Urol Oncol. 2019 Jan;37(1):86-96. doi: 10.1016/j.urolonc.2018.10.023. Epub 2018 Nov 13.
• [4] Methylation-associated silencing of TU3A in human cancers.Int J Oncol. 2008 Oct;33(4):893-9.
• [5] Induction of tumor inhibition and apoptosis by a candidate tumor suppressor gene DRR1 on 3p21.1.Oncol Rep. 2009 Nov;22(5):1069-75.
• [6] Genome-wide meta-analysis identifies novel multiple sclerosis susceptibility loci.Ann Neurol. 2011 Dec;70(6):897-912. doi: 10.1002/ana.22609.
• [7] A novel nuclear complex of DRR1, F-actin and COMMD1 involved in NF-B degradation and cell growth suppression in neuroblastoma.Oncogene. 2017 Oct 12;36(41):5745-5756. doi: 10.1038/onc.2017.181. Epub 2017 Jun 12.
• [8] Decreased FAM107A Expression in Patients with Non-small Cell Lung Cancer.Adv Exp Med Biol. 2015;852:39-48. doi: 10.1007/5584_2014_109.
• [9] Identifying candidate genes for discrimination of ulcerative colitis and Crohn's disease.Mol Biol Rep. 2014 Oct;41(10):6349-55. doi: 10.1007/s11033-014-3469-y. Epub 2014 Sep 3.
• [10] DRR1 is expressed in the developing nervous system and downregulated during neuroblastoma carcinogenesis.Biochem Biophys Res Commun. 2010 Apr 9;394(3):829-35. doi: 10.1016/j.bbrc.2010.03.085. Epub 2010 Mar 16.
• [11] Meta-analysis of genome-wide association studies in celiac disease and rheumatoid arthritis identifies fourteen non-HLA shared loci.PLoS Genet. 2011 Feb;7(2):e1002004. doi: 10.1371/journal.pgen.1002004. Epub 2011 Feb 24.
• [12] Combined deletion and DNA methylation result in silencing of FAM107A gene in laryngeal tumors.Sci Rep. 2017 Jul 14;7(1):5386. doi: 10.1038/s41598-017-05857-1.
• [13] Meta-analysis identifies nine new loci associated with rheumatoid arthritis in the Japanese population.Nat Genet. 2012 Mar 25;44(5):511-6. doi: 10.1038/ng.2231.
• [14] Genes and Pathways Regulated by Androgens in Human Neural Cells, Potential Candidates for the Male Excess in Autism Spectrum Disorder.Biol Psychiatry. 2018 Aug 15;84(4):239-252. doi: 10.1016/j.biopsych.2018.01.002. Epub 2018 Jan 9.
• [15] Identification of novel genes associated with astrocytoma progression using suppression subtractive hybridization and real-time reverse transcription-polymerase chain reaction.Int J Cancer. 2006 Nov 15;119(10):2330-8. doi: 10.1002/ijc.22108.
• [16] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [17] 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.
• [18] 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.
• [19] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [20] 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.
• [21] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [22] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [23] Progesterone regulation of implantation-related genes: new insights into the role of oestrogen. Cell Mol Life Sci. 2007 Apr;64(7-8):1009-32.
• [24] Gene expression profiling in Ishikawa cells: a fingerprint for estrogen active compounds. Toxicol Appl Pharmacol. 2009 Apr 1;236(1):85-96.
• [25] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [26] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.