General Information of Drug Off-Target (DOT) (ID: OT6LIGJP)

DOT Name Mannosyl-oligosaccharide 1,2-alpha-mannosidase IA (MAN1A1)
Synonyms EC 3.2.1.113; Man(9)-alpha-mannosidase; Man9-mannosidase; Mannosidase alpha class 1A member 1; Processing alpha-1,2-mannosidase IA; Alpha-1,2-mannosidase IA
Gene Name MAN1A1
Related Disease
ALG8-congenital disorder of glycosylation ( )
Breast cancer ( )
Breast carcinoma ( )
Congenital disorder of glycosylation ( )
Epithelial ovarian cancer ( )
Gaucher disease ( )
HIV infectious disease ( )
Neoplasm ( )
Ovarian cancer ( )
Ovarian neoplasm ( )
Non-insulin dependent diabetes ( )
UniProt ID
MA1A1_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
MPVGGLLPLFSSPAGGVLGGGLGGGGGRKGSGPAALRLTEKFVLLLVFSAFITLCFGAIF
FLPDSSKLLSGVLFHSSPALQPAADHKPGPGARAEDAAEGRARRREEGAPGDPEAALEDN
LARIRENHERALREAKETLQKLPEEIQRDILLEKKKVAQDQLRDKAPFRGLPPVDFVPPI
GVESREPADAAIREKRAKIKEMMKHAWNNYKGYAWGLNELKPISKGGHSSSLFGNIKGAT
IVDALDTLFIMEMKHEFEEAKSWVEENLDFNVNAEISVFEVNIRFVGGLLSAYYLSGEEI
FRKKAVELGVKLLPAFHTPSGIPWALLNMKSGIGRNWPWASGGSSILAEFGTLHLEFMHL
SHLSGNPIFAEKVMNIRTVLNKLEKPQGLYPNYLNPSSGQWGQHHVSVGGLGDSFYEYLL
KAWLMSDKTDLEAKKMYFDAVQAIETHLIRKSSSGLTYIAEWKGGLLEHKMGHLTCFAGG
MFALGADAAPEGMAQHYLELGAEIARTCHESYNRTFMKLGPEAFRFDGGVEAIATRQNEK
YYILRPEVMETYMYMWRLTHDPKYRKWAWEAVEALENHCRVNGGYSGLRDVYLLHESYDD
VQQSFFLAETLKYLYLIFSDDDLLPLEHWIFNSEAHLLPILPKDKKEVEIREE
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).
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:HS03480-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
ALG8-congenital disorder of glycosylation DISIK17Y Strong Biomarker [1]
Breast cancer DIS7DPX1 Strong Biomarker [2]
Breast carcinoma DIS2UE88 Strong Biomarker [2]
Congenital disorder of glycosylation DIS400QP Strong Biomarker [3]
Epithelial ovarian cancer DIS56MH2 Strong Biomarker [2]
Gaucher disease DISTW5JG Strong Biomarker [4]
HIV infectious disease DISO97HC Strong Altered Expression [5]
Neoplasm DISZKGEW Strong Biomarker [2]
Ovarian cancer DISZJHAP Strong Biomarker [2]
Ovarian neoplasm DISEAFTY Strong Biomarker [2]
Non-insulin dependent diabetes DISK1O5Z Limited Biomarker [6]
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⏷ Show the Full List of 11 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
21 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 Mannosyl-oligosaccharide 1,2-alpha-mannosidase IA (MAN1A1). [7]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Mannosyl-oligosaccharide 1,2-alpha-mannosidase IA (MAN1A1). [8]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Mannosyl-oligosaccharide 1,2-alpha-mannosidase IA (MAN1A1). [9]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Mannosyl-oligosaccharide 1,2-alpha-mannosidase IA (MAN1A1). [10]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Mannosyl-oligosaccharide 1,2-alpha-mannosidase IA (MAN1A1). [11]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Mannosyl-oligosaccharide 1,2-alpha-mannosidase IA (MAN1A1). [12]
Estradiol DMUNTE3 Approved Estradiol decreases the expression of Mannosyl-oligosaccharide 1,2-alpha-mannosidase IA (MAN1A1). [13]
Quercetin DM3NC4M Approved Quercetin decreases the expression of Mannosyl-oligosaccharide 1,2-alpha-mannosidase IA (MAN1A1). [14]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide increases the expression of Mannosyl-oligosaccharide 1,2-alpha-mannosidase IA (MAN1A1). [15]
Vorinostat DMWMPD4 Approved Vorinostat decreases the expression of Mannosyl-oligosaccharide 1,2-alpha-mannosidase IA (MAN1A1). [16]
Fluorouracil DMUM7HZ Approved Fluorouracil increases the expression of Mannosyl-oligosaccharide 1,2-alpha-mannosidase IA (MAN1A1). [17]
Panobinostat DM58WKG Approved Panobinostat increases the expression of Mannosyl-oligosaccharide 1,2-alpha-mannosidase IA (MAN1A1). [18]
Isotretinoin DM4QTBN Approved Isotretinoin increases the expression of Mannosyl-oligosaccharide 1,2-alpha-mannosidase IA (MAN1A1). [19]
Bicalutamide DMZMSPF Approved Bicalutamide increases the expression of Mannosyl-oligosaccharide 1,2-alpha-mannosidase IA (MAN1A1). [20]
Rigosertib DMOSTXF Phase 3 Rigosertib increases the expression of Mannosyl-oligosaccharide 1,2-alpha-mannosidase IA (MAN1A1). [21]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Mannosyl-oligosaccharide 1,2-alpha-mannosidase IA (MAN1A1). [22]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 increases the expression of Mannosyl-oligosaccharide 1,2-alpha-mannosidase IA (MAN1A1). [23]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of Mannosyl-oligosaccharide 1,2-alpha-mannosidase IA (MAN1A1). [24]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of Mannosyl-oligosaccharide 1,2-alpha-mannosidase IA (MAN1A1). [25]
Milchsaure DM462BT Investigative Milchsaure increases the expression of Mannosyl-oligosaccharide 1,2-alpha-mannosidase IA (MAN1A1). [26]
[3H]methyltrienolone DMTSGOW Investigative [3H]methyltrienolone decreases the expression of Mannosyl-oligosaccharide 1,2-alpha-mannosidase IA (MAN1A1). [27]
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⏷ Show the Full List of 21 Drug(s)

References

1 A new case of ALG8 deficiency (CDG Ih).J Inherit Metab Dis. 2009 Dec;32 Suppl 1. doi: 10.1007/s10545-009-1203-z. Epub 2009 Aug 18.
2 Prognostic relevance of the Golgi mannosidase MAN1A1 in ovarian cancer: impact of N-glycosylation on tumour cell aggregation.Br J Cancer. 2019 Nov;121(11):944-953. doi: 10.1038/s41416-019-0607-2. Epub 2019 Oct 29.
3 Novel ALG8 mutations expand the clinical spectrum of congenital disorder of glycosylation type Ih.Mol Genet Metab. 2009 Nov;98(3):305-9. doi: 10.1016/j.ymgme.2009.06.010. Epub 2009 Jun 24.
4 Investigations on therapeutic glucocerebrosidases through paired detection with fluorescent activity-based probes.PLoS One. 2017 Feb 16;12(2):e0170268. doi: 10.1371/journal.pone.0170268. eCollection 2017.
5 Activity of lysosomal exoglycosidases in saliva of patients with HIV infection.Adv Med Sci. 2007;52:186-90.
6 The endoplasmic reticulum in pancreatic beta cells of type 2 diabetes patients.Diabetologia. 2007 Dec;50(12):2486-94. doi: 10.1007/s00125-007-0816-8. Epub 2007 Sep 30.
7 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
8 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
9 Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
10 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
11 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.
12 Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
13 Persistent and non-persistent changes in gene expression result from long-term estrogen exposure of MCF-7 breast cancer cells. J Steroid Biochem Mol Biol. 2011 Feb;123(3-5):140-50.
14 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.
15 Arsenic suppresses gene expression in promyelocytic leukemia cells partly through Sp1 oxidation. Blood. 2005 Jul 1;106(1):304-10.
16 Gene microarray analysis of human renal cell carcinoma: the effects of HDAC inhibition and retinoid treatment. Cancer Biol Ther. 2008 Oct;7(10):1607-18.
17 Pharmacogenomic identification of novel determinants of response to chemotherapy in colon cancer. Cancer Res. 2006 Mar 1;66(5):2765-77.
18 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.
19 Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
20 Microarray analysis of bicalutamide action on telomerase activity, p53 pathway and viability of prostate carcinoma cell lines. J Pharm Pharmacol. 2005 Jan;57(1):83-92.
21 ON 01910.Na is selectively cytotoxic for chronic lymphocytic leukemia cells through a dual mechanism of action involving PI3K/AKT inhibition and induction of oxidative stress. Clin Cancer Res. 2012 Apr 1;18(7):1979-91. doi: 10.1158/1078-0432.CCR-11-2113. Epub 2012 Feb 20.
22 Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
23 Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
24 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.
25 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.
26 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
27 Gene expression signature-based chemical genomic prediction identifies a novel class of HSP90 pathway modulators. Cancer Cell. 2006 Oct;10(4):321-30.