Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5O61XL)

• DOT Name: Beta-mannosidase (MANBA)
• Synonyms: EC 3.2.1.25; Lysosomal beta A mannosidase; Mannanase; Mannase
• Gene Name: MANBA
• Related Disease: Beta-mannosidosis
• UniProt ID: MANBA_HUMAN
• EC Number: 3.2.1.25
• Pfam ID: PF02836 ; PF17753 ; PF17786
• Sequence:
  MRLHLLLLLALCGAGTTAAELSYSLRGNWSICNGNGSLELPGAVPGCVHSALFQQGLIQD
  SYYRFNDLNYRWVSLDNWTYSKEFKIPFEISKWQKVNLILEGVDTVSKILFNEVTIGETD
  NMFNRYSFDITNVVRDVNSIELRFQSAVLYAAQQSKAHTRYQVPPDCPPLVQKGECHVNF
  VRKEQCSFSWDWGPSFPTQGIWKDVRIEAYNICHLNYFTFSPIYDKSAQEWNLEIESTFD
  VVSSKPVGGQVIVAIPKLQTQQTYSIELQPGKRIVELFVNISKNITVETWWPHGHGNQTG
  YNMTVLFELDGGLNIEKSAKVYFRTVELIEEPIKGSPGLSFYFKINGFPIFLKGSNWIPA
  DSFQDRVTSELLRLLLQSVVDANMNTLRVWGGGIYEQDEFYELCDELGIMVWQDFMFACA
  LYPTDQGFLDSVTAEVAYQIKRLKSHPSIIIWSGNNENEEALMMNWYHISFTDRPIYIKD
  YVTLYVKNIRELVLAGDKSRPFITSSPTNGAETVAEAWVSQNPNSNYFGDVHFYDYISDC
  WNWKVFPKARFASEYGYQSWPSFSTLEKVSSTEDWSFNSKFSLHRQHHEGGNKQMLYQAG
  LHFKLPQSTDPLRTFKDTIYLTQVMQAQCVKTETEFYRRSRSEIVDQQGHTMGALYWQLN
  DIWQAPSWASLEYGGKWKMLHYFAQNFFAPLLPVGFENENTFYIYGVSDLHSDYSMTLSV
  RVHTWSSLEPVCSRVTERFVMKGGEAVCLYEEPVSELLRRCGNCTRESCVVSFYLSADHE
  LLSPTNYHFLSSPKEAVGLCKAQITAIISQQGDIFVFDLETSAVAPFVWLDVGSIPGRFS
  DNGFLMTEKTRTILFYPWEPTSKNELEQSFHVTSLTDIY
• Function: Exoglycosidase that cleaves the single beta-linked mannose residue from the non-reducing end of all N-linked glycoprotein oligosaccharides.
• Tissue Specificity: Ubiquitous. Detected in pancreas, kidney and placenta, ands at lower levels in liver, lung, brain, heart and muscle.
• KEGG Pathway:
  Other glycan degradation (hsa00511)
  Lysosome (hsa04142)
• Reactome Pathway:
  Lysosomal oligosaccharide catabolism (R-HSA-8853383)
  Neutrophil degranulation (R-HSA-6798695)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Beta-mannosidosis	DISN0CYD	Definitive	Autosomal recessive	[1]

11 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 Beta-mannosidase (MANBA).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Beta-mannosidase (MANBA).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Beta-mannosidase (MANBA).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Beta-mannosidase (MANBA).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Beta-mannosidase (MANBA).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Beta-mannosidase (MANBA).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin increases the expression of Beta-mannosidase (MANBA).	[8]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Beta-mannosidase (MANBA).	[7]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Beta-mannosidase (MANBA).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Beta-mannosidase (MANBA).	[11]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Beta-mannosidase (MANBA).	[12]

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 Beta-mannosidase (MANBA).	[10]

References

• [1] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [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] 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.
• [5] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] 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.
• [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] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [11] 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.
• [12] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.