Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOO6WHL)

DOT Name POU domain class 2-associating factor 1 (POU2AF1)
Synonyms B-cell-specific coactivator OBF-1; BOB-1; OCA-B; OCT-binding factor 1
Gene Name POU2AF1
Related Disease
Advanced cancer ( )
Arthritis ( )
Autoimmune disease ( )
B-cell lymphoma ( )
Classic Hodgkin lymphoma ( )
Common variable immunodeficiency ( )
Follicular lymphoma ( )
Lung adenocarcinoma ( )
Lymphoma ( )
Lymphoproliferative syndrome ( )
Obstructive sleep apnea ( )
Plasma cell myeloma ( )
Progressive multifocal leukoencephalopathy ( )
Pulmonary fibrosis ( )
Seminoma ( )
Small lymphocytic lymphoma ( )
Gastrointestinal stromal tumour ( )
Primary biliary cholangitis ( )
Multiple sclerosis ( )
Adult lymphoma ( )
Agammaglobulinemia ( )
AIDS-related lymphoma ( )
Kaposi sarcoma ( )
Nervous system inflammation ( )
Pediatric lymphoma ( )
Rheumatoid arthritis ( )
Waldenstrom macroglobulinemia ( )
UniProt ID
OBF1_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
1CQT
Pfam ID
PF09310
Sequence
MLWQKPTAPEQAPAPARPYQGVRVKEPVKELLRRKRGHASSGAAPAPTAVVLPHQPLATY
TTVGPSCLDMEGSVSAVTEEAALCAGWLSQPTPATLQPLAPWTPYTEYVPHEAVSCPYSA
DMYVQPVCPSYTVVGPSSVLTYASPPLITNVTTRSSATPAVGPPLEGPEHQAPLTYFPWP
QPLSTLPTSTLQYQPPAPALPGPQFVQLPISIPEPVLQDMEDPRRAASSLTIDKLLLEEE
DSDAYALNHTLSVEGF
Function
Transcriptional coactivator that specifically associates with either POU2F1/OCT1 or POU2F2/OCT2. It boosts the POU2F1/OCT1 mediated promoter activity and to a lesser extent, that of POU2F2/OCT2. It recognizes the POU domains of POU2F1/OCT1 and POU2F2/OCT2. It is essential for the response of B-cells to antigens and required for the formation of germinal centers. Regulates IL6 expression in B cells as POU2F2/OCT2 coactivator.
Tissue Specificity B-cell specific . Detected in mainly in spleen, but also in thymus, periphral blood leukocyte and small intestine .

Molecular Interaction Atlas (MIA) of This DOT

27 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Advanced cancer DISAT1Z9 Strong Biomarker [1]
Arthritis DIST1YEL Strong Biomarker [2]
Autoimmune disease DISORMTM Strong Biomarker [3]
B-cell lymphoma DISIH1YQ Strong Altered Expression [4]
Classic Hodgkin lymphoma DISV1LU6 Strong Genetic Variation [5]
Common variable immunodeficiency DISHE7JQ Strong Biomarker [6]
Follicular lymphoma DISVEUR6 Strong Altered Expression [4]
Lung adenocarcinoma DISD51WR Strong Biomarker [7]
Lymphoma DISN6V4S Strong Genetic Variation [8]
Lymphoproliferative syndrome DISMVL8O Strong Biomarker [9]
Obstructive sleep apnea DIS0SVD1 Strong Altered Expression [10]
Plasma cell myeloma DIS0DFZ0 Strong Altered Expression [1]
Progressive multifocal leukoencephalopathy DISX02WS Strong Altered Expression [11]
Pulmonary fibrosis DISQKVLA Strong Biomarker [12]
Seminoma DIS3J8LJ Strong Altered Expression [13]
Small lymphocytic lymphoma DIS30POX Strong Altered Expression [14]
Gastrointestinal stromal tumour DIS6TJYS moderate Biomarker [15]
Primary biliary cholangitis DIS43E0O moderate Genetic Variation [16]
Multiple sclerosis DISB2WZI Disputed Biomarker [17]
Adult lymphoma DISK8IZR Limited Genetic Variation [8]
Agammaglobulinemia DISXMS80 Limited Autosomal recessive [18]
AIDS-related lymphoma DISSLRAU Limited Altered Expression [19]
Kaposi sarcoma DISC1H1Z Limited Altered Expression [19]
Nervous system inflammation DISB3X5A Limited Biomarker [3]
Pediatric lymphoma DIS51BK2 Limited Genetic Variation [8]
Rheumatoid arthritis DISTSB4J Limited Biomarker [2]
Waldenstrom macroglobulinemia DIS9O23I Limited Altered Expression [20]
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⏷ Show the Full List of 27 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
1 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-associating factor 1 (POU2AF1). [21]
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12 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 POU domain class 2-associating factor 1 (POU2AF1). [22]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of POU domain class 2-associating factor 1 (POU2AF1). [23]
Arsenic DMTL2Y1 Approved Arsenic decreases the expression of POU domain class 2-associating factor 1 (POU2AF1). [24]
Quercetin DM3NC4M Approved Quercetin decreases the expression of POU domain class 2-associating factor 1 (POU2AF1). [25]
Calcitriol DM8ZVJ7 Approved Calcitriol decreases the expression of POU domain class 2-associating factor 1 (POU2AF1). [23]
Testosterone DM7HUNW Approved Testosterone decreases the expression of POU domain class 2-associating factor 1 (POU2AF1). [26]
Nicotine DMWX5CO Approved Nicotine decreases the expression of POU domain class 2-associating factor 1 (POU2AF1). [27]
OTX-015 DMI8RG1 Phase 1/2 OTX-015 decreases the expression of POU domain class 2-associating factor 1 (POU2AF1). [28]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of POU domain class 2-associating factor 1 (POU2AF1). [27]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of POU domain class 2-associating factor 1 (POU2AF1). [29]
Leflunomide DMR8ONJ Phase 1 Trial Leflunomide increases the expression of POU domain class 2-associating factor 1 (POU2AF1). [30]
Mivebresib DMCPF90 Phase 1 Mivebresib decreases the expression of POU domain class 2-associating factor 1 (POU2AF1). [28]
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⏷ Show the Full List of 12 Drug(s)

References

1 TCR-based therapy for multiple myeloma and other B-cell malignancies targeting intracellular transcription factor BOB1.Blood. 2017 Mar 9;129(10):1284-1295. doi: 10.1182/blood-2016-09-737536. Epub 2017 Jan 4.
2 Evaluation of SUMO1 and POU2AF1 in whole blood from rheumatoid arthritis patients and at risk relatives.Int J Immunogenet. 2019 Apr;46(2):59-66. doi: 10.1111/iji.12414. Epub 2019 Jan 25.
3 Bob1 enhances RORt-mediated IL-17A expression in Th17cells through interaction with RORt.Biochem Biophys Res Commun. 2019 Jul 5;514(4):1167-1171. doi: 10.1016/j.bbrc.2019.05.057. Epub 2019 May 15.
4 Unraveling transformation of follicular lymphoma to diffuse large B-cell lymphoma.PLoS One. 2019 Feb 25;14(2):e0212813. doi: 10.1371/journal.pone.0212813. eCollection 2019.
5 Genome-wide association study implicates immune dysfunction in the development of Hodgkin lymphoma.Blood. 2018 Nov 8;132(19):2040-2052. doi: 10.1182/blood-2018-06-855296. Epub 2018 Sep 7.
6 Evaluation of CARMA1/CARD11 and Bob1 as candidate genes in common variable immunodeficiency.J Investig Allergol Clin Immunol. 2011;21(5):348-53.
7 AGR2-mediated lung adenocarcinoma metastasis novel mechanism network through repression with interferon coupling cytoskeleton to steroid metabolism-dependent humoral immune response.Cell Immunol. 2014 Jul;290(1):102-6. doi: 10.1016/j.cellimm.2014.05.008. Epub 2014 Jun 11.
8 Germline variation in the 3'-untranslated region of the POU2AF1 gene is associated with susceptibility to lymphoma.Mol Carcinog. 2017 Aug;56(8):1945-1952. doi: 10.1002/mc.22652. Epub 2017 Apr 19.
9 Heterogeneity of breakpoints at the transcriptional co-activator gene, BOB-1, in lymphoproliferative disease.Leukemia. 1996 Sep;10(9):1492-6.
10 High frequency of Bob1(lo) T follicular helper cells in florid reactive follicular hyperplasia.Immunol Lett. 2017 Nov;191:23-30. doi: 10.1016/j.imlet.2017.07.012. Epub 2017 Jul 26.
11 MiR-126: a novel route for natalizumab action?.Mult Scler. 2014 Sep;20(10):1363-70. doi: 10.1177/1352458514524998. Epub 2014 Mar 5.
12 Transcriptional regulatory model of fibrosis progression in the human lung.JCI Insight. 2019 Nov 14;4(22):e131597. doi: 10.1172/jci.insight.131597.
13 Novel germ cell markers characterize testicular seminoma and fetal testis.Mol Hum Reprod. 2007 Oct;13(10):721-7. doi: 10.1093/molehr/gam059. Epub 2007 Sep 4.
14 Identification of a potential role for POU2AF1 and BTG4 in the deletion of 11q23 in chronic lymphocytic leukemia.Genes Chromosomes Cancer. 2005 May;43(1):1-10. doi: 10.1002/gcc.20159.
15 Identification of key genes related to high-risk gastrointestinal stromal tumors using bioinformatics analysis.J Cancer Res Ther. 2018;14(Supplement):S243-S247. doi: 10.4103/0973-1482.207068.
16 Genome-wide association studies identify PRKCB as a novel genetic susceptibility locus for primary biliary cholangitis in the Japanese population.Hum Mol Genet. 2017 Feb 1;26(3):650-659. doi: 10.1093/hmg/ddw406.
17 Linkage disequilibrium screening for multiple sclerosis implicates JAG1 and POU2AF1 as susceptibility genes in Europeans.J Neuroimmunol. 2006 Oct;179(1-2):108-16. doi: 10.1016/j.jneuroim.2006.06.003. Epub 2006 Aug 24.
18 Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
19 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.
20 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.
21 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.
22 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
23 Comparison of the gene expression profiles of monocytic versus granulocytic lineages of HL-60 leukemia cell differentiation by DNA microarray analysis. Life Sci. 2003 Aug 15;73(13):1705-19. doi: 10.1016/s0024-3205(03)00515-0.
24 Inorganic arsenic exposure promotes malignant progression by HDAC6-mediated down-regulation of HTRA1. J Appl Toxicol. 2023 Aug;43(8):1214-1224. doi: 10.1002/jat.4457. Epub 2023 Mar 11.
25 Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
26 The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
27 Effects of tobacco compounds on gene expression in fetal lung fibroblasts. Environ Toxicol. 2008 Aug;23(4):423-34.
28 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.
29 Discovery and characterization of super-enhancer-associated dependencies in diffuse large B cell lymphoma. Cancer Cell. 2013 Dec 9;24(6):777-90. doi: 10.1016/j.ccr.2013.11.003.
30 Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.