Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTO5WT78)

• DOT Name: ELMO domain-containing protein 2 (ELMOD2)
• Gene Name: ELMOD2
• Related Disease:
  Pulmonary fibrosis
  Pulmonary disease
• UniProt ID: ELMD2_HUMAN
• Pfam ID: PF04727
• Sequence:
  MFISLWEFFYGHFFRFWMKWLLRQMTGKCELQRIFDTYVGAQRTHRIENSLTYSKNKVLQ
  KATHVVQSEVDKYVDDIMKEKNINPEKDASFKICMKMCLLQITGYKQLYLDVESVRKRPY
  DSDNLQHEELLMKLWNLLMPTKKLNARISKQWAEIGFQGDDPKTDFRGMGILGLINLVYF
  SENYTSEAHQILSRSNHPKLGYSYAIVGINLTEMAYSLLKSEALKFHLYNLVPGIPTMEH
  FHQFYCYLVYEFDKFWFEEEPESIMYFNLYREKFHEKIKGLLLDCNVALTLKV
• Function: Acts as a GTPase-activating protein (GAP) toward guanine nucleotide exchange factors like ARL2, ARL3, ARF1 and ARF6, but not for GTPases outside the Arf family. Regulates IFN-related antiviral responses.
• Tissue Specificity: Alveolar cells (morphologically type II cells) and alveolar macrophages (at protein level). Expressed in brain, colon, heart, kidney, liver, lung, muscle, placenta, small intestine, spleen, stomach and testis. In lung it is expressed in alveolar macrophages and alveolar walls.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Pulmonary fibrosis	DISQKVLA	Strong	Biomarker	[1]
Pulmonary disease	DIS6060I	Limited	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of ELMO domain-containing protein 2 (ELMOD2).	[2]

7 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of ELMO domain-containing protein 2 (ELMOD2).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of ELMO domain-containing protein 2 (ELMOD2).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of ELMO domain-containing protein 2 (ELMOD2).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of ELMO domain-containing protein 2 (ELMOD2).	[6]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of ELMO domain-containing protein 2 (ELMOD2).	[7]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of ELMO domain-containing protein 2 (ELMOD2).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the mutagenesis of ELMO domain-containing protein 2 (ELMOD2).	[10]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB affects the binding of ELMO domain-containing protein 2 (ELMOD2).	[9]

References

• [1] ELMOD2 is a candidate gene for familial idiopathic pulmonary fibrosis.Am J Hum Genet. 2006 Jul;79(1):149-54. doi: 10.1086/504639. Epub 2006 May 9.
• [2] 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.
• [3] 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.
• [4] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] 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.
• [7] 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.
• [8] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [9] Proteomic analysis of the cellular response to a potent sensitiser unveils the dynamics of haptenation in living cells. Toxicology. 2020 Dec 1;445:152603. doi: 10.1016/j.tox.2020.152603. Epub 2020 Sep 28.
• [10] 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.