Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT17VT8D)

DOT Name Alpha-mannosidase 2C1 (MAN2C1)
Synonyms EC 3.2.1.24; Alpha mannosidase 6A8B; Alpha-D-mannoside mannohydrolase; Mannosidase alpha class 2C member 1
Gene Name MAN2C1
Related Disease
Breast cancer ( )
Breast carcinoma ( )
Breast neoplasm ( )
Carcinoma of esophagus ( )
Congenital disorder of deglycosylation 2 ( )
Alpha-mannosidosis ( )
Carcinoma ( )
Intellectual disability ( )
Post-traumatic stress disorder ( )
Prostate cancer ( )
Prostate carcinoma ( )
UniProt ID
MA2C1_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
3.2.1.24
Pfam ID
PF09261 ; PF17677 ; PF07748 ; PF01074
Sequence
MAAAPALKHWRTTLERVEKFVSPLYFTDCNLRGRLFGASCPVAVLSSFLTPERLPYQEAV
QRDFRPAQVGDSFGPTWWTCWFRVELTIPEAWVGQEVHLCWESDGEGLVWRDGEPVQGLT
KEGEKTSYVLTDRLGERDPRSLTLYVEVACNGLLGAGKGSMIAAPDPEKMFQLSRAELAV
FHRDVHMLLVDLELLLGIAKGLGKDNQRSFQALYTANQMVNVCDPAQPETFPVAQALASR
FFGQHGGESQHTIHATGHCHIDTAWLWPFKETVRKCARSWVTALQLMERNPEFIFACSQA
QQLEWVKSRYPGLYSRIQEFACRGQFVPVGGTWVEMDGNLPSGEAMVRQFLQGQNFFLQE
FGKMCSEFWLPDTFGYSAQLPQIMHGCGIRRFLTQKLSWNLVNSFPHHTFFWEGLDGSRV
LVHFPPGDSYGMQGSVEEVLKTVANNRDKGRANHSAFLFGFGDGGGGPTQTMLDRLKRLS
NTDGLPRVQLSSPRQLFSALESDSEQLCTWVGELFLELHNGTYTTHAQIKKGNRECERIL
HDVELLSSLALARSAQFLYPAAQLQHLWRLLLLNQFHDVVTGSCIQMVAEEAMCHYEDIR
SHGNTLLSAAAAALCAGEPGPEGLLIVNTLPWKRIEVMALPKPGGAHSLALVTVPSMGYA
PVPPPTSLQPLLPQQPVFVVQETDGSVTLDNGIIRVKLDPTGRLTSLVLVASGREAIAEG
AVGNQFVLFDDVPLYWDAWDVMDYHLETRKPVLGQAGTLAVGTEGGLRGSAWFLLQISPN
SRLSQEVVLDVGCPYVRFHTEVHWHEAHKFLKVEFPARVRSSQATYEIQFGHLQRPTHYN
TSWDWARFEVWAHRWMDLSEHGFGLALLNDCKYGASVRGSILSLSLLRAPKAPDATADTG
RHEFTYALMPHKGSFQDAGVIQAAYSLNFPLLALPAPSPAPATSWSAFSVSSPAVVLETV
KQAESSPQRRSLVLRLYEAHGSHVDCWLHLSLPVQEAILCDLLERPDPAGHLTLRDNRLK
LTFSPFQVLSLLLVLQPPPH
Function Cleaves alpha 1,2-, alpha 1,3-, and alpha 1,6-linked mannose residues on cytoplasmatic free oligosaccharides generated by N-glycoprotein degradation pathways.
KEGG Pathway
Other glycan degradation (hsa00511 )
Reactome Pathway
Lysosomal oligosaccharide catabolism (R-HSA-8853383 )

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Breast cancer DIS7DPX1 Strong Biomarker [1]
Breast carcinoma DIS2UE88 Strong Biomarker [1]
Breast neoplasm DISNGJLM Strong Biomarker [1]
Carcinoma of esophagus DISS6G4D Strong Altered Expression [2]
Congenital disorder of deglycosylation 2 DISCDKYJ Moderate Autosomal recessive [3]
Alpha-mannosidosis DISUIMJH Limited Biomarker [4]
Carcinoma DISH9F1N Limited Biomarker [5]
Intellectual disability DISMBNXP Limited Biomarker [6]
Post-traumatic stress disorder DISHL1EY Limited Posttranslational Modification [7]
Prostate cancer DISF190Y Limited Biomarker [5]
Prostate carcinoma DISMJPLE Limited Biomarker [5]
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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
2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the methylation of Alpha-mannosidase 2C1 (MAN2C1). [8]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Alpha-mannosidase 2C1 (MAN2C1). [17]
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8 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 Alpha-mannosidase 2C1 (MAN2C1). [9]
Doxorubicin DMVP5YE Approved Doxorubicin increases the expression of Alpha-mannosidase 2C1 (MAN2C1). [10]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Alpha-mannosidase 2C1 (MAN2C1). [11]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Alpha-mannosidase 2C1 (MAN2C1). [12]
Quercetin DM3NC4M Approved Quercetin increases the expression of Alpha-mannosidase 2C1 (MAN2C1). [13]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of Alpha-mannosidase 2C1 (MAN2C1). [14]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Alpha-mannosidase 2C1 (MAN2C1). [15]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of Alpha-mannosidase 2C1 (MAN2C1). [16]
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⏷ Show the Full List of 8 Drug(s)

References

1 A transcriptome-wide association study of 229,000 women identifies new candidate susceptibility genes for breast cancer.Nat Genet. 2018 Jul;50(7):968-978. doi: 10.1038/s41588-018-0132-x. Epub 2018 Jun 18.
2 Inhibition of alpha-mannosidase Man2c1 gene expression suppresses growth of esophageal carcinoma cells through mitotic arrest and apoptosis.Cancer Sci. 2008 Dec;99(12):2428-34. doi: 10.1111/j.1349-7006.2008.01019.x. Epub 2008 Nov 19.
3 Impaired catabolism of free oligosaccharides due to MAN2C1 variants causes a neurodevelopmental disorder. Am J Hum Genet. 2022 Feb 3;109(2):345-360. doi: 10.1016/j.ajhg.2021.12.010. Epub 2022 Jan 18.
4 A boy with ring chromosome 15 derived from a t(15q;15q) Robertsonian translocation in the mother: cytogenetic and biochemical findings.Am J Med Genet. 1983 Feb;14(2):307-14. doi: 10.1002/ajmg.1320140211.
5 -Mannosidase 2C1 attenuates PTEN function in prostate cancer cells.Nat Commun. 2011;2:307. doi: 10.1038/ncomms1309.
6 Ancient Haplotypes at the 15q24.2 Microdeletion Region Are Linked to Brain Expression of MAN2C1 and Children's Intelligence.PLoS One. 2016 Jun 29;11(6):e0157739. doi: 10.1371/journal.pone.0157739. eCollection 2016.
7 Gene expression and methylation signatures of MAN2C1 are associated with PTSD.Dis Markers. 2011;30(2-3):111-21. doi: 10.3233/DMA-2011-0750.
8 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.
9 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
10 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.
11 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.
12 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.
13 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.
14 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
15 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.
16 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.
17 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.