Details of Drug Off-Target (DOT)

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

• DOT Name: GA-binding protein subunit beta-1 (GABPB1)
• Synonyms: GABP subunit beta-1; GABPB-1; GABP subunit beta-2; GABPB-2; Nuclear respiratory factor 2; Transcription factor E4TF1-47; Transcription factor E4TF1-53
• Gene Name: GABPB1
• Related Disease:
  Hepatocellular carcinoma
  Adult glioblastoma
  Advanced cancer
  Clear cell renal carcinoma
  Glioblastoma multiforme
  Kidney cancer
  Neoplasm
  Non-insulin dependent diabetes
  Obesity
  Renal carcinoma
  Renal cell carcinoma
• UniProt ID: GABP1_HUMAN
• Pfam ID: PF12796
• Sequence:
  MSLVDLGKKLLEAARAGQDDEVRILMANGAPFTTDWLGTSPLHLAAQYGHYSTTEVLLRA
  GVSRDARTKVDRTPLHMAASEGHASIVEVLLKHGADVNAKDMLKMTALHWATEHNHQEVV
  ELLIKYGADVHTQSKFCKTAFDISIDNGNEDLAEILQIAMQNQINTNPESPDTVTIHAAT
  PQFIIGPGGVVNLTGLVSSENSSKATDETGVSAVQFGNSSTSVLATLAALAEASAPLSNS
  SETPVVATEEVVTAESVDGAIQQVVSSGGQQVITIVTDGIQLGNLHSIPTSGIGQPIIVT
  MPDGQQVLTVPATDIAEETVISEEPPAKRQCIEIIENRVESAEIEEREALQKQLDEANRE
  AQKYRQQLLKKEQEAEAYRQKLEAMTRLQTNKEAV
• Function: Transcription factor capable of interacting with purine rich repeats (GA repeats). Acts as a master regulator of nuclear-encoded mitochondrial genes; (Microbial infection) Necessary for the expression of the Adenovirus E4 gene.
• Reactome Pathway: Transcriptional activation of mitochondrial biogenesis (R-HSA-2151201)

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatocellular carcinoma	DIS0J828	Definitive	Biomarker	[1]
Adult glioblastoma	DISVP4LU	moderate	Biomarker	[2]
Advanced cancer	DISAT1Z9	moderate	Altered Expression	[2]
Clear cell renal carcinoma	DISBXRFJ	moderate	Biomarker	[3]
Glioblastoma multiforme	DISK8246	moderate	Biomarker	[2]
Kidney cancer	DISBIPKM	moderate	Altered Expression	[3]
Neoplasm	DISZKGEW	moderate	Altered Expression	[2]
Non-insulin dependent diabetes	DISK1O5Z	moderate	Genetic Variation	[4]
Obesity	DIS47Y1K	moderate	Genetic Variation	[4]
Renal carcinoma	DISER9XT	moderate	Altered Expression	[3]
Renal cell carcinoma	DISQZ2X8	moderate	Biomarker	[3]

14 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 GA-binding protein subunit beta-1 (GABPB1).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of GA-binding protein subunit beta-1 (GABPB1).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of GA-binding protein subunit beta-1 (GABPB1).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of GA-binding protein subunit beta-1 (GABPB1).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of GA-binding protein subunit beta-1 (GABPB1).	[9]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of GA-binding protein subunit beta-1 (GABPB1).	[5]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of GA-binding protein subunit beta-1 (GABPB1).	[9]
Seocalcitol	DMKL9QO	Phase 3	Seocalcitol decreases the expression of GA-binding protein subunit beta-1 (GABPB1).	[10]
GSK2110183	DMZHB37	Phase 2	GSK2110183 decreases the expression of GA-binding protein subunit beta-1 (GABPB1).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of GA-binding protein subunit beta-1 (GABPB1).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of GA-binding protein subunit beta-1 (GABPB1).	[14]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of GA-binding protein subunit beta-1 (GABPB1).	[15]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of GA-binding protein subunit beta-1 (GABPB1).	[16]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of GA-binding protein subunit beta-1 (GABPB1).	[17]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of GA-binding protein subunit beta-1 (GABPB1).	[12]

References

• [1] LncRNA GABPB1-AS1 and GABPB1 regulate oxidative stress during erastin-induced ferroptosis in HepG2 hepatocellular carcinoma cells.Sci Rep. 2019 Nov 7;9(1):16185. doi: 10.1038/s41598-019-52837-8.
• [2] GABPA is a master regulator of luminal identity and restrains aggressive diseases in bladder cancer.Cell Death Differ. 2020 Jun;27(6):1862-1877. doi: 10.1038/s41418-019-0466-7. Epub 2019 Dec 4.
• [3] Knockdown of GA-binding protein subunit 1 inhibits cell proliferation via p21 induction in renal cell carcinoma.Int J Oncol. 2018 Aug;53(2):886-894. doi: 10.3892/ijo.2018.4411. Epub 2018 May 17.
• [4] Association of SNP rs7181866 in the nuclear respiratory factor-2 beta subunit encoding GABPB1 gene with obesity and type-2 diabetes mellitus in South Indian population.Int J Biol Macromol. 2019 Jul 1;132:606-614. doi: 10.1016/j.ijbiomac.2019.03.125. Epub 2019 Mar 20.
• [5] A genomic approach to predict synergistic combinations for breast cancer treatment. Pharmacogenomics J. 2013 Feb;13(1):94-104. doi: 10.1038/tpj.2011.48. Epub 2011 Nov 15.
• [6] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [7] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [8] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [9] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [10] Expression profiling in squamous carcinoma cells reveals pleiotropic effects of vitamin D3 analog EB1089 signaling on cell proliferation, differentiation, and immune system regulation. Mol Endocrinol. 2002 Jun;16(6):1243-56.
• [11] Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
• [12] 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.
• [13] 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.
• [14] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [15] 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.
• [16] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [17] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.