Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPAIT1O)

• DOT Name: Amphoterin-induced protein 2 (AMIGO2)
• Synonyms: AMIGO-2; Alivin-1; Differentially expressed in gastric adenocarcinomas; DEGA
• Gene Name: AMIGO2
• Related Disease:
  Adenocarcinoma
  Alzheimer disease
  Breast cancer
  Breast carcinoma
  Cleft palate
  Intellectual disability
  Isolated cleft palate
  Multiple sclerosis
  Neoplasm
  Nervous system inflammation
  Parkinson disease
  Myocardial ischemia
  Craniofacial microsomia
  Melanoma
  Metastatic melanoma
• UniProt ID: AMGO2_HUMAN
• Pfam ID: PF00047 ; PF13855
• Sequence:
  MSLRVHTLPTLLGAVVRPGCRELLCLLMITVTVGPGASGVCPTACICATDIVSCTNKNLS
  KVPGNLFRLIKRLDLSYNRIGLLDSEWIPVSFAKLNTLILRHNNITSISTGSFSTTPNLK
  CLDLSSNKLKTVKNAVFQELKVLEVLLLYNNHISYLDPSAFGGLSQLQKLYLSGNFLTQF
  PMDLYVGRFKLAELMFLDVSYNRIPSMPMHHINLVPGKQLRGIYLHGNPFVCDCSLYSLL
  VFWYRRHFSSVMDFKNDYTCRLWSDSRHSRQVLLLQDSFMNCSDSIINGSFRALGFIHEA
  QVGERLMVHCDSKTGNANTDFIWVGPDNRLLEPDKEMENFYVFHNGSLVIESPRFEDAGV
  YSCIAMNKQRLLNETVDVTINVSNFTVSRSHAHEAFNTAFTTLAACVASIVLVLLYLYLT
  PCPCKCKTKRQKNMLHQSNAHSSILSPGPASDASADERKAGAGKRVVFLEPLKDTAAGQN
  GKVRLFPSEAVIAEGILKSTRGKSDSDSVNSVFSDTPFVAST
• Function: Required for depolarization-dependent survival of cultured cerebellar granule neurons. May mediate homophilic as well as heterophilic cell-cell interaction with AMIGO1 or AMIGO3. May contribute to signal transduction through its intracellular domain. May be required for tumorigenesis of a subset of gastric adenocarcinomas.
• Tissue Specificity: Highest levels in breast, ovary, cervix, and uterus. Lower levels in lung, colon, and rectum. Differentially expressed in 56% of thyroid, 57% of pancreatic and 45% of stomach cancers.
• Reactome Pathway:
  RAC3 GTPase cycle (R-HSA-9013423)
  RAC1 GTPase cycle (R-HSA-9013149)

Molecular Interaction Atlas (MIA) of This DOT

15 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenocarcinoma	DIS3IHTY	Strong	Altered Expression	[1]
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[2]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[3]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[3]
Cleft palate	DIS6G5TF	Strong	Biomarker	[4]
Intellectual disability	DISMBNXP	Strong	Biomarker	[4]
Isolated cleft palate	DISV80CD	Strong	Biomarker	[4]
Multiple sclerosis	DISB2WZI	Strong	Biomarker	[5]
Neoplasm	DISZKGEW	Strong	Biomarker	[6]
Nervous system inflammation	DISB3X5A	Strong	Biomarker	[5]
Parkinson disease	DISQVHKL	Strong	Genetic Variation	[2]
Myocardial ischemia	DISFTVXF	moderate	Biomarker	[6]
Craniofacial microsomia	DISYHJ2P	Limited	Autosomal dominant	[7]
Melanoma	DIS1RRCY	Limited	Biomarker	[8]
Metastatic melanoma	DISSL43L	Limited	Biomarker	[8]

24 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 Amphoterin-induced protein 2 (AMIGO2).	[9]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Amphoterin-induced protein 2 (AMIGO2).	[10]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Amphoterin-induced protein 2 (AMIGO2).	[11]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Amphoterin-induced protein 2 (AMIGO2).	[12]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Amphoterin-induced protein 2 (AMIGO2).	[13]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Amphoterin-induced protein 2 (AMIGO2).	[14]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Amphoterin-induced protein 2 (AMIGO2).	[10]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Amphoterin-induced protein 2 (AMIGO2).	[15]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Amphoterin-induced protein 2 (AMIGO2).	[16]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Amphoterin-induced protein 2 (AMIGO2).	[17]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Amphoterin-induced protein 2 (AMIGO2).	[18]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Amphoterin-induced protein 2 (AMIGO2).	[17]
Irinotecan	DMP6SC2	Approved	Irinotecan increases the expression of Amphoterin-induced protein 2 (AMIGO2).	[19]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Amphoterin-induced protein 2 (AMIGO2).	[17]
Dasatinib	DMJV2EK	Approved	Dasatinib increases the expression of Amphoterin-induced protein 2 (AMIGO2).	[20]
Indomethacin	DMSC4A7	Approved	Indomethacin increases the expression of Amphoterin-induced protein 2 (AMIGO2).	[21]
Prednisolone	DMQ8FR2	Approved	Prednisolone decreases the expression of Amphoterin-induced protein 2 (AMIGO2).	[17]
Methylprednisolone	DM4BDON	Approved	Methylprednisolone decreases the expression of Amphoterin-induced protein 2 (AMIGO2).	[17]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Amphoterin-induced protein 2 (AMIGO2).	[22]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Amphoterin-induced protein 2 (AMIGO2).	[24]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Amphoterin-induced protein 2 (AMIGO2).	[25]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Amphoterin-induced protein 2 (AMIGO2).	[26]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Amphoterin-induced protein 2 (AMIGO2).	[27]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Amphoterin-induced protein 2 (AMIGO2).	[28]

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 Amphoterin-induced protein 2 (AMIGO2).	[23]

References

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• [2] Alivin 1, a novel neuronal activity-dependent gene, inhibits apoptosis and promotes survival of cerebellar granule neurons.J Neurosci. 2003 Jul 2;23(13):5887-96. doi: 10.1523/JNEUROSCI.23-13-05887.2003.
• [3] Reporters to mark and eliminate basal or luminal epithelial cells in culture and in vivo.PLoS Biol. 2018 Jun 20;16(6):e2004049. doi: 10.1371/journal.pbio.2004049. eCollection 2018 Jun.
• [4] A de novo 12q13.11 microdeletion in a patient with severe mental retardation, cleft palate, and high myopia.Eur J Med Genet. 2011 Jan-Feb;54(1):94-6. doi: 10.1016/j.ejmg.2010.09.008. Epub 2010 Oct 8.
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• [12] Comparison of base-line and chemical-induced transcriptomic responses in HepaRG and RPTEC/TERT1 cells using TempO-Seq. Arch Toxicol. 2018 Aug;92(8):2517-2531.
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• [15] 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.
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• [18] 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.
• [19] Clinical determinants of response to irinotecan-based therapy derived from cell line models. Clin Cancer Res. 2008 Oct 15;14(20):6647-55.
• [20] 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.
• [21] Mechanisms of indomethacin-induced alterations in the choline phospholipid metabolism of breast cancer cells. Neoplasia. 2006 Sep;8(9):758-71.
• [22] Dose- and time-dependent transcriptional response of Ishikawa cells exposed to genistein. Toxicol Sci. 2016 May;151(1):71-87.
• [23] 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.
• [24] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [25] 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.
• [26] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.
• [27] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [28] Linking site-specific loss of histone acetylation to repression of gene expression by the mycotoxin ochratoxin A. Arch Toxicol. 2018 Feb;92(2):995-1014.