Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTITCN3Q)

DOT Name Mannosyl-oligosaccharide 1,2-alpha-mannosidase IB (MAN1A2)
Synonyms EC 3.2.1.113; Mannosidase alpha class 1A member 2; Processing alpha-1,2-mannosidase IB; Alpha-1,2-mannosidase IB
Gene Name MAN1A2
Related Disease
Hepatocellular carcinoma ( )
UniProt ID
MA1A2_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
3.2.1.113
Pfam ID
PF01532
Sequence
MTTPALLPLSGRRIPPLNLGPPSFPHHRATLRLSEKFILLLILSAFITLCFGAFFFLPDS
SKHKRFDLGLEDVLIPHVDAGKGAKNPGVFLIHGPDEHRHREEEERLRNKIRADHEKALE
EAKEKLRKSREEIRAEIQTEKNKVVQEMKIKENKPLPPVPIPNLVGIRGGDPEDNDIREK
REKIKEMMKHAWDNYRTYGWGHNELRPIARKGHSPNIFGSSQMGATIVDALDTLYIMGLH
DEFLDGQRWIEDNLDFSVNSEVSVFEVNIRFIGGLLAAYYLSGEEIFKIKAVQLAEKLLP
AFNTPTGIPWAMVNLKSGVGRNWGWASAGSSILAEFGTLHMEFIHLSYLTGDLTYYKKVM
HIRKLLQKMDRPNGLYPNYLNPRTGRWGQYHTSVGGLGDSFYEYLLKAWLMSDKTDHEAR
KMYDDAIEAIEKHLIKKSRGGLTFIGEWKNGHLEKKMGHLACFAGGMFALGADGSRADKA
GHYLELGAEIARTCHESYDRTALKLGPESFKFDGAVEAVAVRQAEKYYILRPEVIETYWY
LWRFTHDPRYRQWGWEAALAIEKYCRVNGGFSGVKDVYSSTPTHDDVQQSFFLAETLKYL
YLLFSGDDLLPLDHWVFNTEAHPLPVLHLANTTLSGNPAVR
Function Involved in the maturation of Asn-linked oligosaccharides. Progressively trim alpha-1,2-linked mannose residues from Man(9)GlcNAc(2) to produce Man(5)GlcNAc(2).
Tissue Specificity Highest levels of expression in placenta and testis.
KEGG Pathway
N-Glycan biosynthesis (hsa00510 )
Various types of N-glycan biosynthesis (hsa00513 )
Metabolic pathways (hsa01100 )
Protein processing in endoplasmic reticulum (hsa04141 )
Reactome Pathway
Progressive trimming of alpha-1,2-linked mannose residues from Man9/8/7GlcNAc2 to produce Man5GlcNAc2 (R-HSA-964827 )
Intra-Golgi traffic (R-HSA-6811438 )
BioCyc Pathway
MetaCyc:HS05846-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Hepatocellular carcinoma DIS0J828 Strong Altered Expression [1]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
2 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 Mannosyl-oligosaccharide 1,2-alpha-mannosidase IB (MAN1A2). [2]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Mannosyl-oligosaccharide 1,2-alpha-mannosidase IB (MAN1A2). [13]
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15 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Mannosyl-oligosaccharide 1,2-alpha-mannosidase IB (MAN1A2). [3]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Mannosyl-oligosaccharide 1,2-alpha-mannosidase IB (MAN1A2). [4]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Mannosyl-oligosaccharide 1,2-alpha-mannosidase IB (MAN1A2). [5]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Mannosyl-oligosaccharide 1,2-alpha-mannosidase IB (MAN1A2). [6]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Mannosyl-oligosaccharide 1,2-alpha-mannosidase IB (MAN1A2). [7]
Quercetin DM3NC4M Approved Quercetin decreases the expression of Mannosyl-oligosaccharide 1,2-alpha-mannosidase IB (MAN1A2). [8]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide increases the expression of Mannosyl-oligosaccharide 1,2-alpha-mannosidase IB (MAN1A2). [9]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide decreases the expression of Mannosyl-oligosaccharide 1,2-alpha-mannosidase IB (MAN1A2). [10]
Rosiglitazone DMILWZR Approved Rosiglitazone decreases the expression of Mannosyl-oligosaccharide 1,2-alpha-mannosidase IB (MAN1A2). [6]
Cidofovir DMA13GD Approved Cidofovir decreases the expression of Mannosyl-oligosaccharide 1,2-alpha-mannosidase IB (MAN1A2). [6]
Urethane DM7NSI0 Phase 4 Urethane increases the expression of Mannosyl-oligosaccharide 1,2-alpha-mannosidase IB (MAN1A2). [11]
Phenol DM1QSM3 Phase 2/3 Phenol decreases the expression of Mannosyl-oligosaccharide 1,2-alpha-mannosidase IB (MAN1A2). [12]
Geldanamycin DMS7TC5 Discontinued in Phase 2 Geldanamycin increases the expression of Mannosyl-oligosaccharide 1,2-alpha-mannosidase IB (MAN1A2). [14]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of Mannosyl-oligosaccharide 1,2-alpha-mannosidase IB (MAN1A2). [15]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of Mannosyl-oligosaccharide 1,2-alpha-mannosidase IB (MAN1A2). [16]
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⏷ Show the Full List of 15 Drug(s)

References

1 Hepatitis B virus upregulates host expression of -1,2-mannosidases via the PPAR pathway.World J Gastroenterol. 2016 Nov 21;22(43):9534-9543. doi: 10.3748/wjg.v22.i43.9534.
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 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
4 Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
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 Transcriptomics hit the target: monitoring of ligand-activated and stress response pathways for chemical testing. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):7-18.
7 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.
8 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.
9 Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
10 Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
11 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
12 Classification of heavy-metal toxicity by human DNA microarray analysis. Environ Sci Technol. 2007 May 15;41(10):3769-74.
13 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.
14 Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
15 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.
16 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.