Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZRBZA5)

DOT Name	Metallo-beta-lactamase domain-containing protein 1 (MBLAC1)
Synonyms	EC 3.1.27.-; Endoribonuclease MBLAC1
Gene Name	MBLAC1
Related Disease	Advanced cancer ( )
UniProt ID	MBLC1_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	4V0H
EC Number	3.1.27.-
Pfam ID	PF00753
Sequence	MRTEPLCGASPLLVPGDPYSVVVLLQGYAEPEGVGDAVRADGSVTLVLPQTRGPASSHRE SPRGSGGAEAALEEAARGPILVDTGGPWAREALLGALAGQGVAPGDVTLVVGTHGHSDHI GNLGLFPGAALLVSHDFCLPGGRYLPHGLGEGQPLRLGPGLEVWATPGHGGQRDVSVVVA GTALGTVVVAGDVFERDGDEDSWQALSEDPAAQERSRKRVLVVADVVVPGHGPPFRVLRE ASQPETEGGGNSQQEPVVGDEEPALH
Function	Endoribonuclease that catalyzes the hydrolysis of histone-coding pre-mRNA 3'-end. Involved in histone pre-mRNA processing during the S-phase of the cell cycle, which is required for entering/progressing through S-phase. Cleaves histone pre-mRNA at a major and a minor cleavage site after the 5'-ACCCA-3' and the 5'-ACCCACA-3' sequence, respectively, and located downstream of the stem-loop. May require the presence of the HDE element located at the histone pre-RNA 3'-end to avoid non-specific cleavage.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance		REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
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Molecular Interaction Atlas (MIA)

Jump to Detail Molecular Interaction Atlas of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Metallo-beta-lactamase domain-containing protein 1 (MBLAC1).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Metallo-beta-lactamase domain-containing protein 1 (MBLAC1).	[3]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Metallo-beta-lactamase domain-containing protein 1 (MBLAC1).	[4]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Metallo-beta-lactamase domain-containing protein 1 (MBLAC1).	[5]
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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 Metallo-beta-lactamase domain-containing protein 1 (MBLAC1).	[6]
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References

1	Biosynthesis of histone messenger RNA employs a specific 3' end endonuclease.Elife. 2018 Dec 3;7:e39865. doi: 10.7554/eLife.39865.
2	Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
3	Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
4	CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
5	Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
6	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.