Details of Drug Off-Target (DOT)

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

• DOT Name: Serine beta-lactamase-like protein LACTB, mitochondrial (LACTB)
• Synonyms: EC 3.4.-.-
• Gene Name: LACTB
• Related Disease:
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Colorectal carcinoma
  Glioma
  Metastatic malignant neoplasm
  Neoplasm
  Obesity
• UniProt ID: LACTB_HUMAN
• PDB ID: 7ULW; 7V1Y; 7V1Z; 7V21
• EC Number: 3.4.-.-
• Pfam ID: PF00144
• Sequence:
  MYRLMSAVTARAAAPGGLASSCGRRGVHQRAGLPPLGHGWVGGLGLGLGLALGVKLAGGL
  RGAAPAQSPAAPDPEASPLAEPPQEQSLAPWSPQTPAPPCSRCFARAIESSRDLLHRIKD
  EVGAPGIVVGVSVDGKEVWSEGLGYADVENRVPCKPETVMRIASISKSLTMVALAKLWEA
  GKLDLDIPVQHYVPEFPEKEYEGEKVSVTTRLLISHLSGIRHYEKDIKKVKEEKAYKALK
  MMKENVAFEQEKEGKSNEKNDFTKFKTEQENEAKCRNSKPGKKKNDFEQGELYLREKFEN
  SIESLRLFKNDPLFFKPGSQFLYSTFGYTLLAAIVERASGCKYLDYMQKIFHDLDMLTTV
  QEENEPVIYNRARFYVYNKKKRLVNTPYVDNSYKWAGGGFLSTVGDLLKFGNAMLYGYQV
  GLFKNSNENLLPGYLKPETMVMMWTPVPNTEMSWDKEGKYAMAWGVVERKQTYGSCRKQR
  HYASHTGGAVGASSVLLVLPEELDTETINNKVPPRGIIVSIICNMQSVGLNSTALKIALE
  FDKDRSD
• Function: Mitochondrial serine protease that acts as a regulator of mitochondrial lipid metabolism. Acts by decreasing protein levels of PISD, a mitochondrial enzyme that converts phosphatidylserine (PtdSer) to phosphatidylethanolamine (PtdEtn), thereby affecting mitochondrial lipid metabolism. It is unclear whether it acts directly by mediating proteolysis of PISD or by mediating proteolysis of another lipid metabolism protein. Acts as a tumor suppressor that has the ability to inhibit proliferation of multiple types of breast cancer cells: probably by promoting decreased levels of PISD, thereby affecting mitochondrial lipid metabolism.
• Tissue Specificity: Expressed predominantly in skeletal muscle.

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Breast cancer	DIS7DPX1	Strong	Biomarker	[2]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[3]
Glioma	DIS5RPEH	Strong	Biomarker	[2]
Metastatic malignant neoplasm	DIS86UK6	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[3]
Obesity	DIS47Y1K	Strong	Biomarker	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Serine beta-lactamase-like protein LACTB, mitochondrial (LACTB).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Serine beta-lactamase-like protein LACTB, mitochondrial (LACTB).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Serine beta-lactamase-like protein LACTB, mitochondrial (LACTB).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Serine beta-lactamase-like protein LACTB, mitochondrial (LACTB).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Serine beta-lactamase-like protein LACTB, mitochondrial (LACTB).	[9]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Serine beta-lactamase-like protein LACTB, mitochondrial (LACTB).	[10]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Serine beta-lactamase-like protein LACTB, mitochondrial (LACTB).	[11]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Serine beta-lactamase-like protein LACTB, mitochondrial (LACTB).	[12]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Serine beta-lactamase-like protein LACTB, mitochondrial (LACTB).	[13]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Serine beta-lactamase-like protein LACTB, mitochondrial (LACTB).	[9]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Serine beta-lactamase-like protein LACTB, mitochondrial (LACTB).	[14]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Serine beta-lactamase-like protein LACTB, mitochondrial (LACTB).	[15]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Serine beta-lactamase-like protein LACTB, mitochondrial (LACTB).	[14]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Serine beta-lactamase-like protein LACTB, mitochondrial (LACTB).	[14]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Serine beta-lactamase-like protein LACTB, mitochondrial (LACTB).	[17]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Serine beta-lactamase-like protein LACTB, mitochondrial (LACTB).	[10]

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 affects the methylation of Serine beta-lactamase-like protein LACTB, mitochondrial (LACTB).	[16]

References

• [1] Upregulation of miR-374a promotes tumor metastasis and progression by downregulating LACTB and predicts unfavorable prognosis in breast cancer.Cancer Med. 2018 Jul;7(7):3351-3362. doi: 10.1002/cam4.1576. Epub 2018 May 23.
• [2] Overexpression of LACTB, a Mitochondrial Protein That Inhibits Proliferation and Invasion in Glioma Cells.Oncol Res. 2019 Mar 29;27(4):423-429. doi: 10.3727/096504017X15030178624579. Epub 2017 Aug 23.
• [3] LACTB, a novel epigenetic silenced tumor suppressor, inhibits colorectal cancer progression by attenuating MDM2-mediated p53 ubiquitination and degradation.Oncogene. 2018 Oct;37(41):5534-5551. doi: 10.1038/s41388-018-0352-7. Epub 2018 Jun 13.
• [4] Variations in DNA elucidate molecular networks that cause disease.Nature. 2008 Mar 27;452(7186):429-35. doi: 10.1038/nature06757. Epub 2008 Mar 16.
• [5] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [6] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [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] Increased mitochondrial ROS formation by acetaminophen in human hepatic cells is associated with gene expression changes suggesting disruption of the mitochondrial electron transport chain. Toxicol Lett. 2015 Apr 16;234(2):139-50.
• [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] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [11] 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.
• [12] 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.
• [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] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [15] Gingival Stromal Cells as an In Vitro Model: Cannabidiol Modulates Genes Linked With Amyotrophic Lateral Sclerosis. J Cell Biochem. 2017 Apr;118(4):819-828. doi: 10.1002/jcb.25757. Epub 2016 Nov 28.
• [16] 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.
• [17] 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.