Details of Drug Off-Target (DOT)

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

• DOT Name: Metallophosphoesterase 1 (MPPE1)
• Synonyms: EC 3.1.-.-; Post-GPI attachment to proteins factor 5
• Gene Name: MPPE1
• Related Disease:
  Malaria
  Bipolar disorder
  Bronchopulmonary dysplasia
  Hepatitis B virus infection
  Myelodysplastic syndrome
  Neoplasm
  Sleep disorder
  Influenza
  Pneumonia
  Pneumonitis
  Advanced cancer
  Hepatitis
  Melanoma
• UniProt ID: MPPE1_HUMAN
• EC Number: 3.1.-.-
• Pfam ID: PF00149
• Sequence:
  MAMIELGFGRQNFHPLKRKSSLLLKLIAVVFAVLLFCEFLIYYLAIFQCNWPEVKTTASD
  GEQTTREPVLKAMFLADTHLLGEFLGHWLDKLRREWQMERAFQTALWLLQPEVVFILGDI
  FDEGKWSTPEAWADDVERFQKMFRHPSHVQLKVVAGNHDIGFHYEMNTYKVERFEKVFSS
  ERLFSWKGINFVMVNSVALNGDGCGICSETEAELIEVSHRLNCSREARGSSRCGPGPLLP
  TSAPVLLQHYPLYRRSDANCSGEDAAPAEERDIPFKENYDVLSREASQKLLWWLQPRLVL
  SGHTHSACEVHHGGRVPELSVPSFSWRNRNNPSFIMGSITPTDYTLSKCYLPREDVVLII
  YCGVVGFLVVLTLTHFGLLASPFLSGLNLLGKRKTR
• Function: Metallophosphoesterase required for transport of GPI-anchor proteins from the endoplasmic reticulum to the Golgi. Acts in lipid remodeling steps of GPI-anchor maturation by mediating the removal of a side-chain ethanolamine-phosphate (EtNP) from the second Man (Man2) of the GPI intermediate, an essential step for efficient transport of GPI-anchor proteins.
• Tissue Specificity: Expressed in brain.
• KEGG Pathway:
  Glycosylphosphatidylinositol (GPI)-anchor biosynthesis (hsa00563)
  Metabolic pathways (hsa01100)

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Malaria	DISQ9Y50	Definitive	Biomarker	[1]
Bipolar disorder	DISAM7J2	Strong	Biomarker	[2]
Bronchopulmonary dysplasia	DISO0BY5	Strong	Genetic Variation	[2]
Hepatitis B virus infection	DISLQ2XY	Strong	Biomarker	[3]
Myelodysplastic syndrome	DISYHNUI	Strong	Biomarker	[4]
Neoplasm	DISZKGEW	Strong	Biomarker	[5]
Sleep disorder	DIS3JP1U	Strong	Genetic Variation	[6]
Influenza	DIS3PNU3	moderate	Biomarker	[7]
Pneumonia	DIS8EF3M	moderate	Biomarker	[7]
Pneumonitis	DIS88E0K	moderate	Biomarker	[7]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[8]
Hepatitis	DISXXX35	Limited	Biomarker	[9]
Melanoma	DIS1RRCY	Limited	Biomarker	[10]

6 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 Metallophosphoesterase 1 (MPPE1).	[11]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Metallophosphoesterase 1 (MPPE1).	[12]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Metallophosphoesterase 1 (MPPE1).	[13]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Metallophosphoesterase 1 (MPPE1).	[14]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Metallophosphoesterase 1 (MPPE1).	[15]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Metallophosphoesterase 1 (MPPE1).	[17]

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 decreases the methylation of Metallophosphoesterase 1 (MPPE1).	[16]

References

• [1] Profiling MHC II immunopeptidome of blood-stage malaria reveals that cDC1 control the functionality of parasite-specific CD4 T cells.EMBO Mol Med. 2017 Nov;9(11):1605-1621. doi: 10.15252/emmm.201708123.
• [2] Association between polymorphisms in the metallophosphoesterase (MPPE1) gene and bipolar disorder.Am J Med Genet B Neuropsychiatr Genet. 2010 Apr 5;153B(3):830-6. doi: 10.1002/ajmg.b.31042.
• [3] Circulating and Hepatic BDCA1+, BDCA2+, and BDCA3+ Dendritic Cells Are Differentially Subverted in Patients With Chronic HBV Infection.Front Immunol. 2019 Feb 4;10:112. doi: 10.3389/fimmu.2019.00112. eCollection 2019.
• [4] Costimulatory Molecules and Immune Checkpoints Are Differentially Expressed on Different Subsets of Dendritic Cells.Front Immunol. 2019 Jun 11;10:1325. doi: 10.3389/fimmu.2019.01325. eCollection 2019.
• [5] Effective cancer immunotherapy by natural mouse conventional type-1 dendritic cells bearing dead tumor antigen.J Immunother Cancer. 2019 Apr 8;7(1):100. doi: 10.1186/s40425-019-0565-5.
• [6] Sleep in individuals with Cri du Chat syndrome: a comparative study.J Intellect Disabil Res. 2009 Aug;53(8):704-15. doi: 10.1111/j.1365-2788.2009.01184.x. Epub 2009 Jun 8.
• [7] Type 1 Conventional CD103(+) Dendritic Cells Control Effector CD8(+) T Cell Migration, Survival, and Memory Responses During Influenza Infection.Front Immunol. 2018 Dec 21;9:3043. doi: 10.3389/fimmu.2018.03043. eCollection 2018.
• [8] Are Conventional Type 1 Dendritic Cells Critical for Protective Antitumor Immunity and How?.Front Immunol. 2019 Feb 12;10:9. doi: 10.3389/fimmu.2019.00009. eCollection 2019.
• [9] Characterization of Antigen-Presenting Cell Subsets in Human Liver-Draining Lymph Nodes.Front Immunol. 2019 Mar 14;10:441. doi: 10.3389/fimmu.2019.00441. eCollection 2019.
• [10] Differential chemokine receptor expression and usage by pre-cDC1 and pre-cDC2.Immunol Cell Biol. 2018 Nov;96(10):1131-1139. doi: 10.1111/imcb.12186. Epub 2018 Jul 20.
• [11] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [12] 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.
• [13] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [14] 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.
• [15] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [16] 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.
• [17] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.