Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTU9V3PE)

• DOT Name: Epididymis-specific alpha-mannosidase (MAN2B2)
• Synonyms: EC 3.2.1.24; Alpha-1,6-mannosidase; Mannosidase alpha class 2B member 2
• Gene Name: MAN2B2
• Related Disease:
  Immunodeficiency
  Stroke
  MAN2B2 deficiency
• UniProt ID: MA2B2_HUMAN
• EC Number: 3.2.1.24
• Pfam ID: PF09261 ; PF07748 ; PF01074
• Sequence:
  MGQLCWLPLLAPLLLLRPPGVQSAGPIRAFVVPHSHMDVGWVYTVQESMRAYAANVYTSV
  VEELARGQQRRFIAVEQEFFRLWWDGVASDQQKYQVRQLLEEGRLEFVIGGQVMHDEAVT
  HLDDQILQLTEGHGFLYETFGIRPQFSWHVDPFGASATTPTLFALAGFNAHLGSRIDYDL
  KAAMQEARGLQFVWRGSPSLSERQEIFTHIMDQYSYCTPSHIPFSNRSGFYWNGVAVFPK
  PPQDGVYPNMSEPVTPANINLYAEALVANVKQRAAWFRTPHVLWPWGCDKQFFNASVQFA
  NMDPLLDHINSHAAELGVSVQYATLGDYFRALHALNVTWRVRDHHDFLPYSTEPFQAWTG
  FYTSRSSLKGLARRASALLYAGESMFTRYLWPAPRGHLDPTWALQQLQQLRWAVSEVQHH
  DAITGTESPKVRDMYATHLASGMLGMRKLMASIVLDELQPQAPMAASSDAGPAGHFASVY
  NPLAWTVTTIVTLTVGFPGVRVTDEAGHPVPSQIQNSTETPSAYDLLILTTIPGLSYRHY
  NIRPTAGAQEGTQEPAATVASTLQFGRRLRRRTSHAGRYLVPVANDCYIVLLDQDTNLMH
  SIWERQSNRTVRVTQEFLEYHVNGDVKQGPISDNYLFTPGKAAVPAWEAVEMEIVAGQLV
  TEIRQYFYRNMTAQNYTYAIRSRLTHVPQGHDGELLCHRIEQEYQAGPLELNREAVLRTS
  TNLNSQQVIYSDNNGYQMQRRPYVSYVNNSIARNYYPMVQSAFMEDGKSRLVLLSERAHG
  ISSQGNGQVEVMLHRRLWNNFDWDLGYNLTLNDTSVVHPVLWLLLGSWSLTTALRQRSAL
  ALQHRPVVLFGDLAGTAPKLPGPQQQEAVTLPPNLHLQILSIPGWRYSSNHTEHSQNLRK
  GHRGEAQADLRRVLLRLYHLYEVGEDPVLSQPVTVNLEAVLQALGSVVAVEERSLTGTWD
  LSMLHRWSWRTGPGRHRGDTTSPSRPPGGPIITVHPKEIRTFFIHFQQQ
• KEGG Pathway: Other glycan degradation (hsa00511)
• Reactome Pathway: Lysosomal oligosaccharide catabolism (R-HSA-8853383)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Immunodeficiency	DIS093I0	Strong	Biomarker	[1]
Stroke	DISX6UHX	Strong	Biomarker	[1]
MAN2B2 deficiency	DISH66SR	Limited	Autosomal recessive	[2]

13 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 Epididymis-specific alpha-mannosidase (MAN2B2).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Epididymis-specific alpha-mannosidase (MAN2B2).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Epididymis-specific alpha-mannosidase (MAN2B2).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Epididymis-specific alpha-mannosidase (MAN2B2).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Epididymis-specific alpha-mannosidase (MAN2B2).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Epididymis-specific alpha-mannosidase (MAN2B2).	[8]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Epididymis-specific alpha-mannosidase (MAN2B2).	[9]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Epididymis-specific alpha-mannosidase (MAN2B2).	[8]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Epididymis-specific alpha-mannosidase (MAN2B2).	[10]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Epididymis-specific alpha-mannosidase (MAN2B2).	[11]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Epididymis-specific alpha-mannosidase (MAN2B2).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the mutagenesis of Epididymis-specific alpha-mannosidase (MAN2B2).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Epididymis-specific alpha-mannosidase (MAN2B2).	[14]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Epididymis-specific alpha-mannosidase (MAN2B2).	[15]

References

• [1] Defining a new immune deficiency syndrome: MAN2B2-CDG.J Allergy Clin Immunol. 2020 Mar;145(3):1008-1011. doi: 10.1016/j.jaci.2019.11.016. Epub 2019 Nov 24.
• [2] 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.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [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] 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.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] 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.
• [9] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [10] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [11] Endometrial receptivity is affected in women with high circulating progesterone levels at the end of the follicular phase: a functional genomics analysis. Hum Reprod. 2011 Jul;26(7):1813-25.
• [12] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [13] Exome-wide mutation profile in benzo[a]pyrene-derived post-stasis and immortal human mammary epithelial cells. Mutat Res Genet Toxicol Environ Mutagen. 2014 Dec;775-776:48-54. doi: 10.1016/j.mrgentox.2014.10.011. Epub 2014 Nov 4.
• [14] 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.
• [15] 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.