Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYJ6EAU)

DOT Name RB-associated KRAB zinc finger protein (RBAK)
Synonyms RB-associated KRAB repressor; hRBaK; Zinc finger protein 769
Gene Name RBAK
Related Disease
Anaplastic large cell lymphoma ( )
Familial hyperaldosteronism type II ( )
Hyperaldosteronism ( )
Non-small-cell lung cancer ( )
Prostate cancer ( )
Prostate carcinoma ( )
UniProt ID
RBAK_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF01352 ; PF00096
Sequence
MNTLQGPVSFKDVAVDFTQEEWQQLDPDEKITYRDVMLENYSHLVSVGYDTTKPNVIIKL
EQGEEPWIMGGEFPCQHSPEAWRVDDLIERIQENEDKHSRQAACINSKTLTEEKENTFSQ
IYMETSLVPSSIIAHNCVSCGKNLESISQLISSDGSYARTKPDECNECGKTYHGEKMCEF
NQNGDTYSHNEENILQKISILEKPFEYNECMEALDNEAVFIAHKRAYIGEKPYEWNDSGP
DFIQMSNFNAYQRSQMEMKPFECSECGKSFCKKSKFIIHQRAHTGEKPYECNVCGKSFSQ
KGTLTVHRRSHLEEKPYKCNECGKTFCQKLHLTQHLRTHSGEKPYECSECGKTFCQKTHL
TLHQRNHSGERPYPCNECGKSFSRKSALSDHQRTHTGEKLYKCNECGKSYYRKSTLITHQ
RTHTGEKPYQCSECGKFFSRVSYLTIHYRSHLEEKPYECNECGKTFNLNSAFIRHRKVHT
EEKSHECSECGKFSQLYLTDHHTAHLEEKPYECNECGKTFLVNSAFDGHQPLPKGEKSYE
CNVCGKLFNELSYYTEHYRSHSEEKPYGCSECGKTFSHNSSLFRHQRVHTGEKPYECYEC
GKFFSQKSYLTIHHRIHSGEKPYECSKCGKVFSRMSNLTVHYRSHSGEKPYECNECGKVF
SQKSYLTVHYRTHSGEKPYECNECGKKFHHRSAFNSHQRIHRRGNMNVLDVENL
Function May repress E2F-dependent transcription. May promote AR-dependent transcription.
Tissue Specificity Expressed in bone, brain, heart, kidney, liver, lung, pancreas and placenta.
KEGG Pathway
Herpes simplex virus 1 infection (hsa05168 )

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Anaplastic large cell lymphoma DISP4D1R Strong Biomarker [1]
Familial hyperaldosteronism type II DISR8EFW Strong Genetic Variation [2]
Hyperaldosteronism DIS3WGAL Strong Genetic Variation [2]
Non-small-cell lung cancer DIS5Y6R9 Strong Biomarker [3]
Prostate cancer DISF190Y Disputed Altered Expression [4]
Prostate carcinoma DISMJPLE Disputed Altered Expression [4]
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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
10 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 RB-associated KRAB zinc finger protein (RBAK). [5]
Doxorubicin DMVP5YE Approved Doxorubicin affects the expression of RB-associated KRAB zinc finger protein (RBAK). [6]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of RB-associated KRAB zinc finger protein (RBAK). [7]
Vorinostat DMWMPD4 Approved Vorinostat decreases the expression of RB-associated KRAB zinc finger protein (RBAK). [8]
Fenretinide DMRD5SP Phase 3 Fenretinide increases the expression of RB-associated KRAB zinc finger protein (RBAK). [9]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of RB-associated KRAB zinc finger protein (RBAK). [11]
Geldanamycin DMS7TC5 Discontinued in Phase 2 Geldanamycin increases the expression of RB-associated KRAB zinc finger protein (RBAK). [12]
Trichostatin A DM9C8NX Investigative Trichostatin A decreases the expression of RB-associated KRAB zinc finger protein (RBAK). [13]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of RB-associated KRAB zinc finger protein (RBAK). [14]
QUERCITRIN DM1DH96 Investigative QUERCITRIN increases the expression of RB-associated KRAB zinc finger protein (RBAK). [15]
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⏷ Show the Full List of 10 Drug(s)
1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
TAK-243 DM4GKV2 Phase 1 TAK-243 increases the sumoylation of RB-associated KRAB zinc finger protein (RBAK). [10]
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References

1 Identification of putative pathogenic microRNA and its downstream targets in anaplastic lymphoma kinase-negative anaplastic large cell lymphoma.Hum Pathol. 2014 Oct;45(10):1995-2005. doi: 10.1016/j.humpath.2014.06.012. Epub 2014 Jun 30.
2 Examination of chromosome 7p22 candidate genes RBaK, PMS2 and GNA12 in familial hyperaldosteronism type II.Clin Exp Pharmacol Physiol. 2008 Apr;35(4):380-5. doi: 10.1111/j.1440-1681.2008.04882.x.
3 RBAK is upregulated in non-small cell lung cancer and promotes cell migration and invasion.Exp Ther Med. 2019 Oct;18(4):2942-2948. doi: 10.3892/etm.2019.7900. Epub 2019 Aug 16.
4 Androgen-induced miR-135a acts as a tumor suppressor through downregulating RBAK and MMP11, and mediates resistance to androgen deprivation therapy.Oncotarget. 2016 Aug 9;7(32):51284-51300. doi: 10.18632/oncotarget.9992.
5 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
6 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.
7 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
8 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.
9 4-HPR modulates gene expression in ovarian cells. Int J Cancer. 2006 Sep 1;119(5):1005-13. doi: 10.1002/ijc.21797.
10 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.
11 Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
12 Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
13 From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
14 Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
15 Molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer. Arch Med Res. 2014 Aug;45(6):445-54.