Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPV0J0C)

DOT Name	POU domain, class 2, transcription factor 2 (POU2F2)
Synonyms	Lymphoid-restricted immunoglobulin octamer-binding protein NF-A2; Octamer-binding protein 2; Oct-2; Octamer-binding transcription factor 2; OTF-2
Gene Name	POU2F2
Related Disease	B-cell lymphoma ( ) B-cell neoplasm ( ) Classic Hodgkin lymphoma ( ) AIDS-related lymphoma ( ) Burkitt lymphoma ( ) Cervical Intraepithelial neoplasia ( ) Cholangiocarcinoma ( ) Chronic kidney disease ( ) Clear cell renal carcinoma ( ) Colorectal carcinoma ( ) Digestive system neuroendocrine tumor, grade 1/2 ( ) Essential hypertension ( ) Familial prostate carcinoma ( ) Lung adenocarcinoma ( ) Mediastinal large B-cell lymphoma ( ) Neoplasm ( ) Plasma cell myeloma ( ) Prostate cancer, hereditary, 1 ( ) Renal cell carcinoma ( ) Rheumatoid arthritis ( ) Small lymphocytic lymphoma ( ) Splenic marginal zone lymphoma ( ) Advanced cancer ( ) Cerebrotendinous xanthomatosis ( ) Gastric cancer ( ) Metastatic malignant neoplasm ( ) Nasopharyngeal carcinoma ( ) Stomach cancer ( ) Adult lymphoma ( ) Extranodal NK/T-cell Lymphoma ( ) Lymphoma ( ) Pediatric lymphoma ( ) Epstein barr virus infection ( ) Follicular lymphoma ( ) Kaposi sarcoma ( ) Non-insulin dependent diabetes ( ) Retinopathy ( ) Spinocerebellar ataxia type 3 ( ) Type-1/2 diabetes ( ) Waldenstrom macroglobulinemia ( )
UniProt ID	PO2F2_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	1HDP
Pfam ID	PF00046 ; PF00157
Sequence	MVHSSMGAPEIRMSKPLEAEKQGLDSPSEHTDTERNGPDTNHQNPQNKTSPFSVSPTGPS TKIKAEDPSGDSAPAAPLPPQPAQPHLPQAQLMLTGSQLAGDIQQLLQLQQLVLVPGHHL QPPAQFLLPQAQQSQPGLLPTPNLFQLPQQTQGALLTSQPRAGLPTQAVTRPTLPDPHLS HPQPPKCLEPPSHPEEPSDLEELEQFARTFKQRRIKLGFTQGDVGLAMGKLYGNDFSQTT ISRFEALNLSFKNMCKLKPLLEKWLNDAETMSVDSSLPSPNQLSSPSLGFDGLPGRRRKK RTSIETNVRFALEKSFLANQKPTSEEILLIAEQLHMEKEVIRVWFCNRRQKEKRINPCSA APMLPSPGKPASYSPHMVTPQGGAGTLPLSQASSSLSTTVTTLSSAVGTLHPSRTAGGGG GGGGAAPPLNSIPSVTPPPPATTNSTNPSPQGSHSAIGLSGLNPSTGPGLWWNPAPYQP
Function	Transcription factor that specifically binds to the octamer motif (5'-ATTTGCAT-3'). Regulates IL6 expression in B cells with POU2AF1. Regulates transcription in a number of tissues in addition to activating immunoglobulin gene expression. Modulates transcription transactivation by NR3C1, AR and PGR ; [Isoform 5]: Activates the U2 small nuclear RNA (snRNA) promoter.
Tissue Specificity	Isoform 3 is B-cell specific. Isoform 5 is expressed in B-cells and the immunoglobulin-expressing T-cell line MOLT-4, but not in the T-cell line BW5147.
KEGG Pathway	Herpes simplex virus 1 infection (hsa05168 ) Lipid and atherosclerosis (hsa05417 )
Reactome Pathway	RNA polymerase II transcribes snRNA genes (R-HSA-6807505 )

Molecular Interaction Atlas (MIA) of This DOT

40 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
B-cell lymphoma	DISIH1YQ	Definitive	Altered Expression	[1]
B-cell neoplasm	DISVY326	Definitive	Biomarker	[2]
Classic Hodgkin lymphoma	DISV1LU6	Definitive	Altered Expression	[3]
AIDS-related lymphoma	DISSLRAU	Strong	Altered Expression	[4]
Burkitt lymphoma	DIS9D5XU	Strong	Altered Expression	[5]
Cervical Intraepithelial neoplasia	DISXP757	Strong	Altered Expression	[6]
Cholangiocarcinoma	DIS71F6X	Strong	Biomarker	[7]
Chronic kidney disease	DISW82R7	Strong	Biomarker	[8]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[9]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[10]
Digestive system neuroendocrine tumor, grade 1/2	DISDR98B	Strong	Biomarker	[11]
Essential hypertension	DIS7WI98	Strong	Biomarker	[12]
Familial prostate carcinoma	DISL9KNO	Strong	Biomarker	[13]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[14]
Mediastinal large B-cell lymphoma	DISAUA10	Strong	Biomarker	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[15]
Plasma cell myeloma	DIS0DFZ0	Strong	Biomarker	[16]
Prostate cancer, hereditary, 1	DISE2P4L	Strong	Biomarker	[13]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[9]
Rheumatoid arthritis	DISTSB4J	Strong	Altered Expression	[17]
Small lymphocytic lymphoma	DIS30POX	Strong	Altered Expression	[18]
Splenic marginal zone lymphoma	DISCGTZY	Strong	Biomarker	[19]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[20]
Cerebrotendinous xanthomatosis	DIST9FNK	moderate	Biomarker	[21]
Gastric cancer	DISXGOUK	moderate	Biomarker	[22]
Metastatic malignant neoplasm	DIS86UK6	moderate	Biomarker	[22]
Nasopharyngeal carcinoma	DISAOTQ0	moderate	Altered Expression	[23]
Stomach cancer	DISKIJSX	moderate	Biomarker	[22]
Adult lymphoma	DISK8IZR	Disputed	Biomarker	[24]
Extranodal NK/T-cell Lymphoma	DIS72GCL	Disputed	Biomarker	[25]
Lymphoma	DISN6V4S	Disputed	Biomarker	[24]
Pediatric lymphoma	DIS51BK2	Disputed	Biomarker	[24]
Epstein barr virus infection	DISOO0WT	Limited	Biomarker	[26]
Follicular lymphoma	DISVEUR6	Limited	Genetic Variation	[27]
Kaposi sarcoma	DISC1H1Z	Limited	Altered Expression	[4]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Genetic Variation	[28]
Retinopathy	DISB4B0F	Limited	Biomarker	[29]
Spinocerebellar ataxia type 3	DISQBQID	Limited	Biomarker	[30]
Type-1/2 diabetes	DISIUHAP	Limited	Biomarker	[31]
Waldenstrom macroglobulinemia	DIS9O23I	Limited	Altered Expression	[32]
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⏷ Show the Full List of 40 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

2 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 2, transcription factor 2 (POU2F2).	[33]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of POU domain, class 2, transcription factor 2 (POU2F2).	[37]
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5 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of POU domain, class 2, transcription factor 2 (POU2F2).	[34]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of POU domain, class 2, transcription factor 2 (POU2F2).	[35]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of POU domain, class 2, transcription factor 2 (POU2F2).	[36]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of POU domain, class 2, transcription factor 2 (POU2F2).	[38]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of POU domain, class 2, transcription factor 2 (POU2F2).	[39]
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References

1	An unusual case of Epstein-Barr virus-positive large B-cell lymphoma lacking various B-cell markers.Diagn Pathol. 2017 Jan 31;12(1):15. doi: 10.1186/s13000-017-0606-7.
2	J chain and myocyte enhancer factor 2B are useful in differentiating classical Hodgkin lymphoma from nodular lymphocyte predominant Hodgkin lymphoma and primary mediastinal large B-cell lymphoma.Hum Pathol. 2017 Oct;68:47-53. doi: 10.1016/j.humpath.2017.08.015. Epub 2017 Aug 26.
3	Alterations of loci encoding PU.1, BOB1, and OCT2 transcription regulators do not correlate with their suppressed expression in Hodgkin lymphoma.Cancer Genet Cytogenet. 2005 Apr 15;158(2):167-71. doi: 10.1016/j.cancergencyto.2004.09.005.
4	Role of defective Oct-2 and OCA-B expression in immunoglobulin production and Kaposi's sarcoma-associated herpesvirus lytic reactivation in primary effusion lymphoma.J Virol. 2009 May;83(9):4308-15. doi: 10.1128/JVI.02196-08. Epub 2009 Feb 18.
5	NF-kappa B and Oct-2 synergize to activate the human 3' Igh hs4 enhancer in B cells.J Immunol. 2004 Jan 15;172(2):1054-64. doi: 10.4049/jimmunol.172.2.1054.
6	Involvement of organic cation transporter 2 in the metformin-associated increased lactate levels caused by contrast-induced nephropathy.Biomed Pharmacother. 2018 Oct;106:1760-1766. doi: 10.1016/j.biopha.2018.07.068. Epub 2018 Jul 31.
7	Network analyses-based identification of circular ribonucleic acid-related pathways in intrahepatic cholangiocarcinoma.Tumour Biol. 2018 Sep;40(9):1010428318795761. doi: 10.1177/1010428318795761.
8	The Effect of Uremic Solutes on the Organic Cation Transporter 2.J Pharm Sci. 2017 Sep;106(9):2551-2557. doi: 10.1016/j.xphs.2017.04.076. Epub 2017 May 5.
9	Upregulation of miR-489-3p and miR-630 inhibits oxaliplatin uptake in renal cell carcinoma by targeting OCT2.Acta Pharm Sin B. 2019 Sep;9(5):1008-1020. doi: 10.1016/j.apsb.2019.01.002. Epub 2019 Jan 8.
10	Src family kinase inhibitor Saracatinib (AZD0530) impairs oxaliplatin uptake in colorectal cancer cells and blocks organic cation transporters. Cancer Res. 2010 Jul 15;70(14):5931-41.
11	A precision oncology approach to the pharmacological targeting of mechanistic dependencies in neuroendocrine tumors.Nat Genet. 2018 Jul;50(7):979-989. doi: 10.1038/s41588-018-0138-4. Epub 2018 Jun 18.
12	Lower prevalence of the OCT2 Ser270 allele in patients with essential hypertension.Clin Exp Hypertens. 2006 Oct;28(7):645-53. doi: 10.1080/10641960600946411.
13	Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci.Nat Genet. 2018 Jul;50(7):928-936. doi: 10.1038/s41588-018-0142-8. Epub 2018 Jun 11.
14	Genome-wide analyses of long noncoding RNA expression profiles in lung adenocarcinoma.Sci Rep. 2017 Nov 10;7(1):15331. doi: 10.1038/s41598-017-15712-y.
15	Methylomes of renal cell lines and tumors or metastases differ significantly with impact on pharmacogenes. Sci Rep. 2016 Jul 20;6:29930.
16	In silico analysis identifies CRISP3 as a potential peripheral blood biomarker for multiple myeloma: From data modeling to validation with RT-PCR.Oncol Lett. 2018 Apr;15(4):5167-5174. doi: 10.3892/ol.2018.7969. Epub 2018 Feb 6.
17	Key role of organic cation transporter 2 for the nephrotoxicity effect of triptolide in rheumatoid arthritis.Int Immunopharmacol. 2019 Dec;77:105959. doi: 10.1016/j.intimp.2019.105959. Epub 2019 Oct 20.
18	Expression of B cell-associated transcription factors in B-cell precursor acute lymphoblastic leukemia cells: association with PU.1 expression, phenotype, and immunogenotype.Int J Hematol. 2000 Jun;71(4):372-8.
19	Classical Hodgkin lymphoma concurrently evolving in a patient with marginal zone B-cell lymphoma of the spleen.Ann Diagn Pathol. 2008 Jun;12(3):212-6. doi: 10.1016/j.anndiagpath.2006.12.005. Epub 2007 Sep 14.
20	Epigenetic activation of the drug transporter OCT2 sensitizes renal cell carcinoma to oxaliplatin. Sci Transl Med. 2016 Jul 20;8(348):348ra97.
21	Cerebrotendinous xanthomatosis patients with and without parkinsonism: clinical characteristics and neuroimaging findings.Mov Disord. 2010 Mar 15;25(4):452-8. doi: 10.1002/mds.22979.
22	POU2F2-oriented network promotes human gastric cancer metastasis.Gut. 2016 Sep;65(9):1427-38. doi: 10.1136/gutjnl-2014-308932. Epub 2015 May 27.
23	The B-cell specific transcription factor, Oct-2, promotes Epstein-Barr virus latency by inhibiting the viral immediate-early protein, BZLF1.PLoS Pathog. 2012 Feb;8(2):e1002516. doi: 10.1371/journal.ppat.1002516. Epub 2012 Feb 9.
24	Oct transcription factors mediate t(14;18) lymphoma cell survival by directly regulating bcl-2 expression.Oncogene. 2006 Feb 9;25(6):888-98. doi: 10.1038/sj.onc.1209127.
25	Aberrant antigenic expression in extranodal NK/T-cell lymphoma: a multi-parameter study from Thailand.Diagn Pathol. 2011 Aug 25;6:79. doi: 10.1186/1746-1596-6-79.
26	American Registry of Pathology Expert Opinions: Immunohistochemical evaluation of classic Hodgkin lymphoma.Ann Diagn Pathol. 2019 Apr;39:105-110. doi: 10.1016/j.anndiagpath.2019.02.001. Epub 2019 Feb 6.
27	Mutations in linker histone genes HIST1H1 B, C, D, and E; OCT2 (POU2F2); IRF8; and ARID1A underlying the pathogenesis of follicular lymphoma.Blood. 2014 Mar 6;123(10):1487-98. doi: 10.1182/blood-2013-05-500264. Epub 2014 Jan 16.
28	Single nucleotide polymorphisms in the intergenic region between metformin transporter OCT2 and OCT3 coding genes are associated with short-term response to metformin monotherapy in type 2 diabetes mellitus patients.Eur J Endocrinol. 2016 Dec;175(6):531-540. doi: 10.1530/EJE-16-0347. Epub 2016 Sep 8.
29	OPTICAL COHERENCE TOMOGRAPHY 2: Diagnostic Tool to Study Peripheral Vitreoretinal Pathologies.Retina. 2019 Feb;39(2):415-421. doi: 10.1097/IAE.0000000000001953.
30	Dopamine transporter concentration is reduced in asymptomatic Machado-Joseph disease gene carriers.J Nucl Med. 2002 Feb;43(2):153-9.
31	The role of organic cation transporter 2 inhibitor cimetidine, experimental diabetes mellitus and metformin on gabapentin pharmacokinetics in rats.Life Sci. 2018 May 1;200:63-68. doi: 10.1016/j.lfs.2018.03.012. Epub 2018 Mar 15.
32	Transcriptional repression of plasma cell differentiation is orchestrated by aberrant over-expression of the ETS factor SPIB in Waldenstrm macroglobulinaemia.Br J Haematol. 2014 Sep;166(5):677-89. doi: 10.1111/bjh.12936. Epub 2014 May 7.
33	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.
34	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.
35	Omeprazole protects against cisplatin-induced nephrotoxicity by alleviating oxidative stress, inflammation, and transporter-mediated cisplatin accumulation in rats and HK-2?cells. Chem Biol Interact. 2019 Jan 5;297:130-140. doi: 10.1016/j.cbi.2018.11.008. Epub 2018 Nov 16.
36	Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
37	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.
38	Identification of a novel BET bromodomain inhibitor-sensitive, gene regulatory circuit that controls Rituximab response and tumour growth in aggressive lymphoid cancers. EMBO Mol Med. 2013 Aug;5(8):1180-95. doi: 10.1002/emmm.201202034. Epub 2013 Jul 4.
39	Regulation of chromatin assembly and cell transformation by formaldehyde exposure in human cells. Environ Health Perspect. 2017 Sep 21;125(9):097019.