Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTL90XO8)

• DOT Name: Protein MGARP (MGARP)
• Synonyms: Corneal endothelium-specific protein 1; CESP-1; Hypoxia up-regulated mitochondrial movement regulator protein; Mitochondria-localized glutamic acid-rich protein; Ovary-specific acidic protein
• Gene Name: MGARP
• Related Disease: Rheumatoid arthritis
• UniProt ID: HUMMR_HUMAN
• Pfam ID: PF14962
• Sequence:
  MYLRRAVSKTLALPLRAPPNPAPLGKDASLRRMSSNRFPGSSGSNMIYYLVVGVTVSAGG
  YYAYKTVTSDQAKHTEHKTNLKEKTKAEIHPFQGEKENVAETEKASSEAPEELIVEAEVV
  DAEESPSATVVVIKEASACPGHVEAAPETTAVSAETGPEVTDAAARETTEVNPETTPEVT
  NAALDEAVTIDNDKDTTKNETSDEYAELEEENSPAESESSAGDDLQEEASVGSEAASAQG
• Function: Plays a role in the trafficking of mitochondria along microtubules. Regulates the kinesin-mediated axonal transport of mitochondria to nerve terminals along microtubules during hypoxia. Participates in the translocation of TRAK2/GRIF1 from the cytoplasm to the mitochondrion. Also plays a role in steroidogenesis through maintenance of mitochondrial abundance and morphology. Plays an inhibitory role during neocortex development by regulating mitochondrial morphology, distribution and motility in neocortical neurons.
• Tissue Specificity: Expressed in the brain, adrenal gland and corneal endothelium (CE). Expressed in steroid-producing cells of the ovary and testis (at protein level). Expressed in steroid-producing cells of the ovary and testis. Weakly expressed in placenta. Expressed in corneal endothelial cells.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Rheumatoid arthritis	DISTSB4J	Limited	Biomarker	[1]

14 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 Protein MGARP (MGARP).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Protein MGARP (MGARP).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Protein MGARP (MGARP).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Protein MGARP (MGARP).	[5]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Protein MGARP (MGARP).	[7]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Protein MGARP (MGARP).	[8]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Protein MGARP (MGARP).	[9]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Protein MGARP (MGARP).	[10]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Protein MGARP (MGARP).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Protein MGARP (MGARP).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Protein MGARP (MGARP).	[14]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Protein MGARP (MGARP).	[15]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Protein MGARP (MGARP).	[9]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Protein MGARP (MGARP).	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Protein MGARP (MGARP).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Protein MGARP (MGARP).	[12]

References

• [1] Distinctive gene expression signatures in rheumatoid arthritis synovial tissue fibroblast cells: correlates with disease activity.Genes Immun. 2007 Sep;8(6):480-91. doi: 10.1038/sj.gene.6364400. Epub 2007 Jun 14.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [4] 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.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [7] 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.
• [8] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [9] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [10] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [11] 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.
• [12] 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.
• [13] 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.
• [14] Comparison of transcriptome expression alterations by chronic exposure to low-dose bisphenol A in different subtypes of breast cancer cells. Toxicol Appl Pharmacol. 2019 Dec 15;385:114814. doi: 10.1016/j.taap.2019.114814. Epub 2019 Nov 9.
• [15] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [16] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.