Details of Drug Off-Target (DOT)

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

DOT Name Bromodomain and WD repeat-containing protein 1 (BRWD1)
Synonyms WD repeat-containing protein 9
Gene Name BRWD1
Related Disease
Ulcerative colitis ( )
Primary ciliary dyskinesia ( )
Agammaglobulinemia ( )
Ankylosing spondylitis ( )
Ciliary dyskinesia, primary, 51 ( )
Oligospermia ( )
UniProt ID
BRWD1_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
3Q2E
Pfam ID
PF00439 ; PF00400
Sequence
MAEPSSARRPVPLIESELYFLIARYLSAGPCRRAAQVLVQELEQYQLLPKRLDWEGNEHN
RSYEELVLSNKHVAPDHLLQICQRIGPMLDKEIPPSISRVTSLLGAGRQSLLRTAKDCRH
TVWKGSAFAALHRGRPPEMPVNYGSPPNLVEIHRGKQLTGCSTFSTAFPGTMYQHIKMHR
RILGHLSAVYCVAFDRTGHRIFTGSDDCLVKIWSTHNGRLLSTLRGHSAEISDMAVNYEN
TMIAAGSCDKIIRVWCLRTCAPVAVLQGHTGSITSLQFSPMAKGSQRYMVSTGADGTVCF
WQWDLESLKFSPRPLKFTEKPRPGVQMLCSSFSVGGMFLATGSTDHVIRMYFLGFEAPEK
IAELESHTDKVDSIQFCNNGDRFLSGSRDGTARIWRFEQLEWRSILLDMATRISGDLSSE
EERFMKPKVTMIAWNQNDSIVVTAVNDHVLKVWNSYTGQLLHNLMGHADEVFVLETHPFD
SRIMLSAGHDGSIFIWDITKGTKMKHYFNMIEGQGHGAVFDCKFSQDGQHFACTDSHGHL
LIFGFGCSKPYEKIPDQMFFHTDYRPLIRDSNNYVLDEQTQQAPHLMPPPFLVDVDGNPH
PTKYQRLVPGRENSADEHLIPQLGYVATSDGEVIEQIISLQTNDNDERSPESSILDGMIR
QLQQQQDQRMGADQDTIPRGLSNGEETPRRGFRRLSLDIQSPPNIGLRRSGQVEGVRQMH
QNAPRSQIATERDLQAWKRRVVVPEVPLGIFRKLEDFRLEKGEEERNLYIIGRKRKTLQL
SHKSDSVVLVSQSRQRTCRRKYPNYGRRNRSWRELSSGNESSSSVRHETSCDQSEGSGSS
EEDEWRSDRKSESYSESSSDSSSRYSDWTADAGINLQPPLRTSCRRRITRFCSSSEDEIS
TENLSPPKRRRKRKKENKPKKENLRRMTPAELANMEHLYEFHPPVWITDTTLRKSPFVPQ
MGDEVIYFRQGHEAYIEAVRRNNIYELNPNKEPWRKMDLRDQELVKIVGIRYEVGPPTLC
CLKLAFIDPATGKLMDKSFSIRYHDMPDVIDFLVLRQFYDEARQRNWQSCDRFRSIIDDA
WWFGTVLSQEPYQPQYPDSHFQCYIVRWDNTEIEKLSPWDMEPIPDNVDPPEELGASISV
TTDELEKLLYKPQAGEWGQKSRDEECDRIISGIDQLLNLDIAAAFAGPVDLCTYPKYCTV
VAYPTDLYTIRMRLVNRFYRRLSALVWEVRYIEHNARTFNEPESVIARSAKKITDQLLKF
IKNQHCTNISELSNTSENDEQNAEDLDDSDLPKTSSGRRRVHDGKKSIRATNYVESNWKK
QCKELVNLIFQCEDSEPFRQPVDLVEYPDYRDIIDTPMDFGTVRETLDAGNYDSPLEFCK
DIRLIFSNAKAYTPNKRSKIYSMTLRLSALFEEKMKKISSDFKIGQKFNEKLRRSQRFKQ
RQNCKGDSQPNKSIRNLKPKRLKSQTKIIPELVGSPTQSTSSRTAYLGTHKTSAGISSGV
TSGDSSDSAESSERRKRNRPITNGSTLSESEVEDSLATSLSSSASSSSEESKESSRARES
SSRSGLSRSSNLRVTRTRAAQRKTGPVSLANGCGRKATRKRVYLSDSDNNSLETGEILKA
RAGNNRKVLRKCAAVAANKIKLMSDVEENSSSESVCSGRKLPHRNASAVARKKLLHNSED
EQSLKSEIEEEELKDENQLLPVSSSHTAQSNVDESENRDSESESDLRVARKNWHANGYKS
HTPAPSKTKFLKIESSEEDSKSHDSDHACNRTAGPSTSVQKLKAESISEEADSEPGRSGG
RKYNTFHKNASFFKKTKILSDSEDSESEEQDREDGKCHKMEMNPISGNLNCDPIAMSQCS
SDHGCETDLDSDDDKIEKPNNFMKDSASQDNGLSRKISRKRVCSSDSDSSLQVVKKSSKA
RTGLLRITRRCAATAANKIKLMSDVEDVSLENVHTRSKNGRKKPLHLACTTAKKKLSDCE
GSVHCEVPSEQYACEGKPPDPDSEGSTKVLSQALNGDSDSEDMLNSEHKHRHTNIHKIDA
PSKRKSSSVTSSGEDSKSHIPGSETDRTFSSESTLAQKATAENNFEVELNYGLRRWNGRR
LRTYGKAPFSKTKVIHDSQETAEKEVKRKRSHPELENVKISETTGNSKFRPDTSSKSSDL
GSVTESDIDCTDNTKTKRRKTKGKAKVVRKEFVPRDREPNTKVRTCMHNQKDAVQMPSET
LKAKMVPEKVPRRCATVAANKIKIMSNLKETISGPENVWIRKSSRKLPHRNASAAAKKKL
LNVYKEDDTTINSESEKELEDINRKMLFLRGFRSWKENAQ
Function May be a transcriptional activator. May be involved in chromatin remodeling. Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the control of cell shape.
Tissue Specificity Ubiquitously expressed . Expressed in respiratory epithelial cells and testis spermatozoa.
Reactome Pathway
Chromatin modifying enzymes (R-HSA-3247509 )
Interleukin-7 signaling (R-HSA-1266695 )

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Ulcerative colitis DIS8K27O Strong Biomarker [1]
Primary ciliary dyskinesia DISOBC7V Disputed Autosomal recessive [2]
Agammaglobulinemia DISXMS80 Limited Autosomal dominant [2]
Ankylosing spondylitis DISRC6IR Limited Genetic Variation [3]
Ciliary dyskinesia, primary, 51 DIS5ZYNG Limited Autosomal recessive [4]
Oligospermia DIS6YJF3 Limited Biomarker [5]
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⏷ Show the Full List of 6 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
4 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the methylation of Bromodomain and WD repeat-containing protein 1 (BRWD1). [6]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 decreases the phosphorylation of Bromodomain and WD repeat-containing protein 1 (BRWD1). [15]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Bromodomain and WD repeat-containing protein 1 (BRWD1). [16]
Coumarin DM0N8ZM Investigative Coumarin decreases the phosphorylation of Bromodomain and WD repeat-containing protein 1 (BRWD1). [15]
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9 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Bromodomain and WD repeat-containing protein 1 (BRWD1). [7]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Bromodomain and WD repeat-containing protein 1 (BRWD1). [8]
Estradiol DMUNTE3 Approved Estradiol decreases the expression of Bromodomain and WD repeat-containing protein 1 (BRWD1). [9]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide increases the expression of Bromodomain and WD repeat-containing protein 1 (BRWD1). [10]
Folic acid DMEMBJC Approved Folic acid decreases the expression of Bromodomain and WD repeat-containing protein 1 (BRWD1). [11]
Clorgyline DMCEUJD Approved Clorgyline increases the expression of Bromodomain and WD repeat-containing protein 1 (BRWD1). [12]
SNDX-275 DMH7W9X Phase 3 SNDX-275 decreases the expression of Bromodomain and WD repeat-containing protein 1 (BRWD1). [13]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Bromodomain and WD repeat-containing protein 1 (BRWD1). [14]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of Bromodomain and WD repeat-containing protein 1 (BRWD1). [17]
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⏷ Show the Full List of 9 Drug(s)

References

1 Genome wide association (GWA) predictors of anti-TNFalpha therapeutic responsiveness in pediatric inflammatory bowel disease.Inflamm Bowel Dis. 2010 Aug;16(8):1357-66. doi: 10.1002/ibd.21174.
2 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.
3 Association of variants in 21q22 with ankylosing spondylitis in the Chinese Guangxi Zhuang population.Rheumatol Int. 2014 Sep;34(9):1251-5. doi: 10.1007/s00296-014-2973-7. Epub 2014 Mar 19.
4 A human ciliopathy reveals essential functions for NEK10 in airway mucociliary clearance. Nat Med. 2020 Feb;26(2):244-251. doi: 10.1038/s41591-019-0730-x. Epub 2020 Jan 20.
5 The dual bromodomain and WD repeat-containing mouse protein BRWD1 is required for normal spermiogenesis and the oocyte-embryo transition.Dev Biol. 2008 May 1;317(1):72-82. doi: 10.1016/j.ydbio.2008.02.018. Epub 2008 Feb 21.
6 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.
7 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
8 Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
9 Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
10 Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
11 Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
12 Anti-oncogenic and pro-differentiation effects of clorgyline, a monoamine oxidase A inhibitor, on high grade prostate cancer cells. BMC Med Genomics. 2009 Aug 20;2:55. doi: 10.1186/1755-8794-2-55.
13 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.
14 Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
15 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.
16 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.
17 Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.