Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2QPWQJ)

DOT Name	Bleomycin hydrolase (BLMH)
Synonyms	BH; BLM hydrolase; BMH; EC 3.4.22.40
Gene Name	BLMH
UniProt ID	BLMH_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	1CB5; 2CB5; 7V5L; 7V5S; 7V5T; 7XF9
EC Number	3.4.22.40
Pfam ID	PF03051
Sequence	MSSSGLNSEKVAALIQKLNSDPQFVLAQNVGTTHDLLDICLKRATVQRAQHVFQHAVPQE GKPITNQKSSGRCWIFSCLNVMRLPFMKKLNIEEFEFSQSYLFFWDKVERCYFFLSAFVD TAQRKEPEDGRLVQFLLMNPANDGGQWDMLVNIVEKYGVIPKKCFPESYTTEATRRMNDI LNHKMREFCIRLRNLVHSGATKGEISATQDVMMEEIFRVVCICLGNPPETFTWEYRDKDK NYQKIGPITPLEFYREHVKPLFNMEDKICLVNDPRPQHKYNKLYTVEYLSNMVGGRKTLY NNQPIDFLKKMVAASIKDGEAVWFGCDVGKHFNSKLGLSDMNLYDHELVFGVSLKNMNKA ERLTFGESLMTHAMTFTAVSEKDDQDGAFTKWRVENSWGEDHGHKGYLCMTDEWFSEYVY EVVVDRKHVPEEVLAVLEQEPIILPAWDPMGALAE
Function	The normal physiological role of BLM hydrolase is unknown, but it catalyzes the inactivation of the antitumor drug BLM (a glycopeptide) by hydrolyzing the carboxamide bond of its B-aminoalaninamide moiety thus protecting normal and malignant cells from BLM toxicity.
Reactome Pathway	Antigen processing (R-HSA-983168 )

Molecular Interaction Atlas (MIA) of This DOT

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Bleomycin	DMNER5S	Approved	Bleomycin hydrolase (BLMH) affects the response to substance of Bleomycin.	[11]
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10 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 Bleomycin hydrolase (BLMH).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Bleomycin hydrolase (BLMH).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Bleomycin hydrolase (BLMH).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Bleomycin hydrolase (BLMH).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Bleomycin hydrolase (BLMH).	[5]
Phenobarbital	DMXZOCG	Approved	Phenobarbital decreases the expression of Bleomycin hydrolase (BLMH).	[6]
Aspirin	DM672AH	Approved	Aspirin decreases the expression of Bleomycin hydrolase (BLMH).	[7]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene decreases the expression of Bleomycin hydrolase (BLMH).	[2]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Bleomycin hydrolase (BLMH).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Bleomycin hydrolase (BLMH).	[10]
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⏷ Show the Full List of 10 Drug(s)

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 Bleomycin hydrolase (BLMH).	[8]
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References

1	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.
2	Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
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	Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
5	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.
6	Dose- and time-dependent effects of phenobarbital on gene expression profiling in human hepatoma HepaRG cells. Toxicol Appl Pharmacol. 2009 Feb 1;234(3):345-60.
7	DNA array analysis of the effects of aspirin on colon cancer cells: involvement of Rac1. Carcinogenesis. 2004 Jul;25(7):1293-8.
8	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.
9	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.
10	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.
11	Genetic polymorphisms of DNA repair and xenobiotic-metabolizing enzymes: role in mutagen sensitivity. Carcinogenesis. 2002 Jun;23(6):1003-8. doi: 10.1093/carcin/23.6.1003.