Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVXEF85)

• DOT Name: MAM domain-containing glycosylphosphatidylinositol anchor protein 1 (MDGA1)
• Synonyms: GPI and MAM protein; GPIM; Glycosylphosphatidylinositol-MAM; MAM domain-containing protein 3
• Gene Name: MDGA1
• Related Disease:
  Bipolar disorder
  Schizophrenia
  Neoplasm
• UniProt ID: MDGA1_HUMAN
• PDB ID: 5V5V; 5V5W; 5XEQ
• Pfam ID: PF07679 ; PF13927 ; PF00629
• Sequence:
  MEVTCLLLLALIPFHCRGQGVYAPAQAQIVHAGQACVVKEDNISERVYTIREGDTLMLQC
  LVTGHPRPQVRWTKTAGSASDKFQETSVFNETLRIERIARTQGGRYYCKAENGVGVPAIK
  SIRVDVQYLDEPMLTVHQTVSDVRGNFYQEKTVFLRCTVNSNPPARFIWKRGSDTLSHSQ
  DNGVDIYEPLYTQGETKVLKLKNLRPQDYASYTCQVSVRNVCGIPDKAITFRLTNTTAPP
  ALKLSVNETLVVNPGENVTVQCLLTGGDPLPQLQWSHGPGPLPLGALAQGGTLSIPSVQA
  RDSGYYNCTATNNVGNPAKKTVNLLVRSMKNATFQITPDVIKESENIQLGQDLKLSCHVD
  AVPQEKVTYQWFKNGKPARMSKRLLVTRNDPELPAVTSSLELIDLHFSDYGTYLCMASFP
  GAPVPDLSVEVNISSETVPPTISVPKGRAVVTVREGSPAELQCEVRGKPRPPVLWSRVDK
  EAALLPSGLPLEETPDGKLRLERVSRDMSGTYRCQTARYNGFNVRPREAQVQLNVQFPPE
  VEPSSQDVRQALGRPVLLRCSLLRGSPQRIASAVWRFKGQLLPPPPVVPAAAEAPDHAEL
  RLDAVTRDSSGSYECSVSNDVGSAACLFQVSAKAYSPEFYFDTPNPTRSHKLSKNYSYVL
  QWTQREPDAVDPVLNYRLSIRQLNQHNAVVKAIPVRRVEKGQLLEYILTDLRVPHSYEVR
  LTPYTTFGAGDMASRIIHYTEPINSPNLSDNTCHFEDEKICGYTQDLTDNFDWTRQNALT
  QNPKRSPNTGPPTDISGTPEGYYMFIETSRPRELGDRARLVSPLYNASAKFYCVSFFYHM
  YGKHIGSLNLLVRSRNKGALDTHAWSLSGNKGNVWQQAHVPISPSGPFQIIFEGVRGPGY
  LGDIAIDDVTLKKGECPRKQTDPNKVVVMPGSGAPCQSSPQLWGPMAIFLLALQR
• Function: Required for radial migration of cortical neurons in the superficial layer of the neocortex. Plays a role in the formation or maintenance of inhibitory synapses. May function by inhibiting the activity of NLGN2.
• Tissue Specificity: Has been found in brain, heart, skeletal muscle and kidney. Found to be overexpressed in tumor tissues.
• Reactome Pathway: Post-translational modification (R-HSA-163125)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bipolar disorder	DISAM7J2	Definitive	Biomarker	[1]
Schizophrenia	DISSRV2N	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Limited	Altered Expression	[2]

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 MAM domain-containing glycosylphosphatidylinositol anchor protein 1 (MDGA1).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of MAM domain-containing glycosylphosphatidylinositol anchor protein 1 (MDGA1).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of MAM domain-containing glycosylphosphatidylinositol anchor protein 1 (MDGA1).	[5]
Dasatinib	DMJV2EK	Approved	Dasatinib increases the expression of MAM domain-containing glycosylphosphatidylinositol anchor protein 1 (MDGA1).	[6]
GSK2110183	DMZHB37	Phase 2	GSK2110183 increases the expression of MAM domain-containing glycosylphosphatidylinositol anchor protein 1 (MDGA1).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of MAM domain-containing glycosylphosphatidylinositol anchor protein 1 (MDGA1).	[9]

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 MAM domain-containing glycosylphosphatidylinositol anchor protein 1 (MDGA1).	[8]

References

• [1] MDGA1-deficiency attenuates prepulse inhibition with alterations of dopamine and serotonin metabolism: An ex vivo HPLC-ECD analysis.Neurosci Lett. 2020 Jan 18;716:134677. doi: 10.1016/j.neulet.2019.134677. Epub 2019 Dec 5.
• [2] Genomic organization of a novel glycosylphosphatidylinositol MAM gene expressed in human tissues and tumors.Oncogene. 2002 May 2;21(19):3089-94. doi: 10.1038/sj.onc.1205383.
• [3] 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.
• [4] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [5] RNA sequence analysis of inducible pluripotent stem cell-derived cardiomyocytes reveals altered expression of DNA damage and cell cycle genes in response to doxorubicin. Toxicol Appl Pharmacol. 2018 Oct 1;356:44-53.
• [6] Dasatinib reverses cancer-associated fibroblasts (CAFs) from primary lung carcinomas to a phenotype comparable to that of normal fibroblasts. Mol Cancer. 2010 Jun 27;9:168.
• [7] Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
• [8] 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.
• [9] 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.