Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6BBXPD)

• DOT Name: POU domain, class 3, transcription factor 3 (POU3F3)
• Synonyms: Brain-specific homeobox/POU domain protein 1; Brain-1; Brn-1; Octamer-binding protein 8; Oct-8; Octamer-binding transcription factor 8; OTF-8
• Gene Name: POU3F3
• Related Disease:
  Intellectual disability, autosomal dominant 40
  Cerebral cavernous malformation
  Cervical cancer
  Cervical carcinoma
  Esophageal squamous cell carcinoma
  Glioma
  Intellectual disability
  Neurodevelopmental disorder
  Prostate carcinoma
  Snijders blok-fisher syndrome
  Triple negative breast cancer
  Lung cancer
  Metastatic malignant neoplasm
  Neoplasm
  Small-cell lung cancer
  Advanced cancer
  Creatine transporter deficiency
  Hepatocellular carcinoma
  Nasopharyngeal carcinoma
  Osteoarthritis
• UniProt ID: PO3F3_HUMAN
• Pfam ID: PF00046 ; PF00157
• Sequence:
  MATAASNPYLPGNSLLAAGSIVHSDAAGAGGGGGGGGGGGGGGAGGGGGGMQPGSAAVTS
  GAYRGDPSSVKMVQSDFMQGAMAASNGGHMLSHAHQWVTALPHAAAAAAAAAAAAVEASS
  PWSGSAVGMAGSPQQPPQPPPPPPQGPDVKGGAGRDDLHAGTALHHRGPPHLGPPPPPPH
  QGHPGGWGAAAAAAAAAAAAAAAAHLPSMAGGQQPPPQSLLYSQPGGFTVNGMLSAPPGP
  GGGGGGAGGGAQSLVHPGLVRGDTPELAEHHHHHHHHAHPHPPHPHHAQGPPHHGGGGGG
  AGPGLNSHDPHSDEDTPTSDDLEQFAKQFKQRRIKLGFTQADVGLALGTLYGNVFSQTTI
  CRFEALQLSFKNMCKLKPLLNKWLEEADSSTGSPTSIDKIAAQGRKRKKRTSIEVSVKGA
  LESHFLKCPKPSAQEITNLADSLQLEKEVVRVWFCNRRQKEKRMTPPGIQQQTPDDVYSQ
  VGTVSADTPPPHHGLQTSVQ
• Function: Transcription factor that acts synergistically with SOX11 and SOX4. Plays a role in neuronal development. Is implicated in an enhancer activity at the embryonic met-mesencephalic junction; the enhancer element contains the octamer motif (5'-ATTTGCAT-3').
• Tissue Specificity: Brain.

Molecular Interaction Atlas (MIA) of This DOT

20 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Intellectual disability, autosomal dominant 40	DISAI0IH	Definitive	Autosomal dominant	[1]
Cerebral cavernous malformation	DISLKNYA	Strong	Biomarker	[2]
Cervical cancer	DISFSHPF	Strong	Biomarker	[3]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[3]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[4]
Glioma	DIS5RPEH	Strong	Biomarker	[5]
Intellectual disability	DISMBNXP	Strong	Biomarker	[6]
Neurodevelopmental disorder	DIS372XH	Strong	Genetic Variation	[1]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[7]
Snijders blok-fisher syndrome	DISN3WH0	Strong	Autosomal dominant	[8]
Triple negative breast cancer	DISAMG6N	Strong	Biomarker	[9]
Lung cancer	DISCM4YA	moderate	Biomarker	[10]
Metastatic malignant neoplasm	DIS86UK6	moderate	Altered Expression	[11]
Neoplasm	DISZKGEW	moderate	Altered Expression	[11]
Small-cell lung cancer	DISK3LZD	moderate	Biomarker	[10]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[9]
Creatine transporter deficiency	DIS8FWNV	Limited	Biomarker	[12]
Hepatocellular carcinoma	DIS0J828	Limited	Altered Expression	[13]
Nasopharyngeal carcinoma	DISAOTQ0	Limited	Biomarker	[11]
Osteoarthritis	DIS05URM	Limited	Biomarker	[14]

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 POU domain, class 3, transcription factor 3 (POU3F3).	[15]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of POU domain, class 3, transcription factor 3 (POU3F3).	[18]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of POU domain, class 3, transcription factor 3 (POU3F3).	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of POU domain, class 3, transcription factor 3 (POU3F3).	[16]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of POU domain, class 3, transcription factor 3 (POU3F3).	[17]

References

• [1] De Novo Variants Disturbing the Transactivation Capacity of POU3F3 Cause a Characteristic Neurodevelopmental Disorder. Am J Hum Genet. 2019 Aug 1;105(2):403-412. doi: 10.1016/j.ajhg.2019.06.007. Epub 2019 Jul 11.
• [2] CCM-3 Promotes C.elegans Germline Development by Regulating Vesicle Trafficking Cytokinesis and Polarity.Curr Biol. 2017 Mar 20;27(6):868-876. doi: 10.1016/j.cub.2017.02.028. Epub 2017 Mar 9.
• [3] SP1-mediated long noncoding RNA POU3F3 accelerates the cervical cancer through miR-127-5p/FOXD1.Biomed Pharmacother. 2019 Sep;117:109133. doi: 10.1016/j.biopha.2019.109133. Epub 2019 Jun 25.
• [4] Upregulation of the long noncoding RNA TUG1 promotes proliferation and migration of esophageal squamous cell carcinoma.Tumour Biol. 2015 Mar;36(3):1643-51. doi: 10.1007/s13277-014-2763-6. Epub 2014 Oct 31.
• [5] Glioma cells promote angiogenesis through the release of exosomes containing long non-coding RNA POU3F3.Eur Rev Med Pharmacol Sci. 2017 Mar;21(5):959-972.
• [6] A de novo POU3F3 Deletion in a Boy with Intellectual Disability and Dysmorphic Features.Mol Syndromol. 2014 Jan;5(1):32-5. doi: 10.1159/000356060. Epub 2013 Nov 2.
• [7] Long noncoding RNA POU3F3 promotes cancer cell proliferation in prostate carcinoma by upregulating rho-associated protein kinase 1.J Cell Biochem. 2019 May;120(5):8195-8200. doi: 10.1002/jcb.28101. Epub 2018 Nov 26.
• [8] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [9] LncRNA POU3F3 promotes proliferation and inhibits apoptosis of cancer cells in triple-negative breast cancer by inactivating caspase 9.Biosci Biotechnol Biochem. 2019 Jun;83(6):1117-1123. doi: 10.1080/09168451.2019.1588097. Epub 2019 Mar 7.
• [10] Class III/IV POU transcription factors expressed in small cell lung cancer cells are involved in proneural/neuroendocrine differentiation.Pathol Int. 2014 Sep;64(9):415-22. doi: 10.1111/pin.12198.
• [11] LncRNA POU3F3 promotes cancer cell migration and invasion in nasopharyngeal carcinoma by up-regulating TGF-1.Biosci Rep. 2019 Jan 25;39(1):BSR20181632. doi: 10.1042/BSR20181632. Print 2019 Jan 31.
• [12] Contiguous deletion of SLC6A8 and BAP31 in a patient with severe dystonia and sensorineural deafness.Mol Genet Metab. 2012 May;106(1):43-7. doi: 10.1016/j.ymgme.2012.02.018. Epub 2012 Mar 5.
• [13] Linc-POU3F3 is overexpressed in hepatocellular carcinoma and regulates cell proliferation, migration and invasion.Biomed Pharmacother. 2018 Sep;105:683-689. doi: 10.1016/j.biopha.2018.06.006. Epub 2018 Jun 12.
• [14] Distinctive gene expression signatures in rheumatoid arthritis synovial tissue fibroblast cells: correlates with disease activity.Genes Immun. 2007 Sep;8(6):480-91. doi: 10.1038/sj.gene.6364400. Epub 2007 Jun 14.
• [15] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [16] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [17] 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.
• [18] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [19] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.