Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTMKZZU7)

• DOT Name: Homologous recombination OB-fold protein (HROB)
• Gene Name: HROB
• UniProt ID: HROB_HUMAN
• Pfam ID: PF15072
• Sequence:
  MACSLQKLFAVEEEFEDEDFLSAVEDAENRFTGSLPVNAGRLRPVSSRPQETVQAQSSRL
  LLLHPTAPSEALGLPDLDLCLPASSTPSADSRPSCIGAAPLRPVSTSSSWIGNQRRVTVT
  EVLRETARPQSSALHPLLTFESQQQQVGGFEGPEQDEFDKVLASMELEEPGMELECGVSS
  EAIPILPAQQREGSVLAKKARVVDLSGSCQKGPVPAIHKAGIMSAQDESLDPVIQCRTPR
  PPLRPGAVGHLPVPTALTVPTQQLHWEVCPQRSPVQALQPLQAARGTIQSSPQNRFPCQP
  FQSPSSWLSGKAHLPRPRTPNSSCSTPSRTSSGLFPRIPLQPQAPVSSIGSPVGTPKGPQ
  GALQTPIVTNHLVQLVTAASRTPQQPTHPSTRAKTRRFPGPAGILPHQQSGRSLEDIMVS
  APQTPTHGALAKFQTEIVASSQASVEEDFGRGPWLTMKSTLGLDERDPSCFLCTYSIVMV
  LRKQAALKQLPRNKVPNMAVMIKSLTRSTMDASVVFKDPTGEMQGTVHRLLLETCQNELK
  PGSVLLLKQIGVFSPSLRNHYLNVTPNNLVHIYSPDSGDGSFLKPSQPFPKDSGSFQHDV
  AAKPEEGFRTAQNLEAEASPEEELPEADDLDGLLSELPEDFFCGTSS
• Function: DNA-binding protein involved in homologous recombination that acts by recruiting the MCM8-MCM9 helicase complex to sites of DNA damage to promote DNA repair synthesis.

Molecular Interaction Atlas (MIA) of This DOT

12 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Homologous recombination OB-fold protein (HROB).	[1]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Homologous recombination OB-fold protein (HROB).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Homologous recombination OB-fold protein (HROB).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Homologous recombination OB-fold protein (HROB).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Homologous recombination OB-fold protein (HROB).	[5]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Homologous recombination OB-fold protein (HROB).	[6]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Homologous recombination OB-fold protein (HROB).	[6]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Homologous recombination OB-fold protein (HROB).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Homologous recombination OB-fold protein (HROB).	[8]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Homologous recombination OB-fold protein (HROB).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Homologous recombination OB-fold protein (HROB).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Homologous recombination OB-fold protein (HROB).	[12]

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 Homologous recombination OB-fold protein (HROB).	[10]

References

• [1] 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.
• [2] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [3] 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.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [7] Cannabidiol Activates Neuronal Precursor Genes in Human Gingival Mesenchymal Stromal Cells. J Cell Biochem. 2017 Jun;118(6):1531-1546. doi: 10.1002/jcb.25815. Epub 2016 Dec 29.
• [8] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [9] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [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] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.