Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTU4IFBU)

• DOT Name: Endoribonuclease LACTB2 (LACTB2)
• Synonyms: EC 3.1.27.-; Beta-lactamase-like protein 2
• Gene Name: LACTB2
• Related Disease: Colorectal carcinoma
• UniProt ID: LACB2_HUMAN
• PDB ID: 4AD9
• EC Number: 3.1.27.-
• Pfam ID: PF17778 ; PF00753
• Sequence:
  MAAVLQRVERLSNRVVRVLGCNPGPMTLQGTNTYLVGTGPRRILIDTGEPAIPEYISCLK
  QALTEFNTAIQEIVVTHWHRDHSGGIGDICKSINNDTTYCIKKLPRNPQREEIIGNGEQQ
  YVYLKDGDVIKTEGATLRVLYTPGHTDDHMALLLEEENAIFSGDCILGEGTTVFEDLYDY
  MNSLKELLKIKADIIYPGHGPVIHNAEAKIQQYISHRNIREQQILTLFRENFEKSFTVME
  LVKIIYKNTPENLHEMAKHNLLLHLKKLEKEGKIFSNTDPDKKWKAHL
• Function: Endoribonuclease; cleaves preferentially 3' to purine-pyrimidine dinucleotide motifs in single-stranded RNA. The cleavage product contains a free 3' -OH group. Has no activity with double-stranded RNA or DNA. Required for normal mitochondrial function and cell viability.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[1]

1 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 Endoribonuclease LACTB2 (LACTB2).	[2]

17 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 Endoribonuclease LACTB2 (LACTB2).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Endoribonuclease LACTB2 (LACTB2).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Endoribonuclease LACTB2 (LACTB2).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Endoribonuclease LACTB2 (LACTB2).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Endoribonuclease LACTB2 (LACTB2).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Endoribonuclease LACTB2 (LACTB2).	[8]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Endoribonuclease LACTB2 (LACTB2).	[9]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Endoribonuclease LACTB2 (LACTB2).	[10]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Endoribonuclease LACTB2 (LACTB2).	[11]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Endoribonuclease LACTB2 (LACTB2).	[12]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Endoribonuclease LACTB2 (LACTB2).	[13]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Endoribonuclease LACTB2 (LACTB2).	[14]
Clozapine	DMFC71L	Approved	Clozapine increases the expression of Endoribonuclease LACTB2 (LACTB2).	[15]
Benzatropine	DMF7EXL	Approved	Benzatropine increases the expression of Endoribonuclease LACTB2 (LACTB2).	[15]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Endoribonuclease LACTB2 (LACTB2).	[16]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Endoribonuclease LACTB2 (LACTB2).	[3]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Endoribonuclease LACTB2 (LACTB2).	[17]

References

• [1] Disruption of NCOA2 by recurrent fusion with LACTB2 in colorectal cancer.Oncogene. 2016 Jan 14;35(2):187-95. doi: 10.1038/onc.2015.72. Epub 2015 Mar 30.
• [2] 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.
• [3] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [4] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [5] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [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] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [9] 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.
• [10] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [11] 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.
• [12] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [13] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [14] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [15] Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
• [16] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [17] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.