Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2EPDFC)

• DOT Name: Amphoterin-induced protein 1 (AMIGO1)
• Synonyms: AMIGO-1; Alivin-2
• Gene Name: AMIGO1
• Related Disease:
  Alzheimer disease
  Schizophrenia
• UniProt ID: AMGO1_HUMAN
• Pfam ID: PF00560 ; PF13855
• Sequence:
  MHPHRDPRGLWLLLPSLSLLLFEVARAGRAVVSCPAACLCASNILSCSKQQLPNVPHSLP
  SYTALLDLSHNNLSRLRAEWTPTRLTQLHSLLLSHNHLNFISSEAFSPVPNLRYLDLSSN
  QLRTLDEFLFSDLQVLEVLLLYNNHIMAVDRCAFDDMAQLQKLYLSQNQISRFPLELVKE
  GAKLPKLTLLDLSSNKLKNLPLPDLQKLPAWIKNGLYLHNNPLNCDCELYQLFSHWQYRQ
  LSSVMDFQEDLYCMNSKKLHNVFNLSFLNCGEYKERAWEAHLGDTLIIKCDTKQQGMTKV
  WVTPSNERVLDEVTNGTVSVSKDGSLLFQQVQVEDGGVYTCYAMGETFNETLSVELKVHN
  FTLHGHHDTLNTAYTTLVGCILSVVLVLIYLYLTPCRCWCRGVEKPSSHQGDSLSSSMLS
  TTPNHDPMAGGDKDDGFDRRVAFLEPAGPGQGQNGKLKPGNTLPVPEATGKGQRRMSDPE
  SVSSVFSDTPIVV
• Function: Promotes growth and fasciculation of neurites from cultured hippocampal neurons. May be involved in fasciculation as well as myelination of developing neural axons. May have a role in regeneration as well as neural plasticity in the adult nervous system. May mediate homophilic as well as heterophilic cell-cell interaction and contribute to signal transduction through its intracellular domain. Assembled with KCNB1 modulates the gating characteristics of the delayed rectifier voltage-dependent potassium channel KCNB1.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[1]
Schizophrenia	DISSRV2N	Strong	Biomarker	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Amphoterin-induced protein 1 (AMIGO1).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Amphoterin-induced protein 1 (AMIGO1).	[11]

10 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 Amphoterin-induced protein 1 (AMIGO1).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Amphoterin-induced protein 1 (AMIGO1).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Amphoterin-induced protein 1 (AMIGO1).	[6]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Amphoterin-induced protein 1 (AMIGO1).	[7]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Amphoterin-induced protein 1 (AMIGO1).	[8]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Amphoterin-induced protein 1 (AMIGO1).	[9]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Amphoterin-induced protein 1 (AMIGO1).	[10]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Amphoterin-induced protein 1 (AMIGO1).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Amphoterin-induced protein 1 (AMIGO1).	[13]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Amphoterin-induced protein 1 (AMIGO1).	[14]

References

• [1] Cholesterol-related genes in Alzheimer's disease.Biochim Biophys Acta. 2010 Aug;1801(8):762-73. doi: 10.1016/j.bbalip.2010.05.009. Epub 2010 May 24.
• [2] AMIGO-Kv2.1 Potassium Channel Complex Is Associated With Schizophrenia-Related Phenotypes.Schizophr Bull. 2016 Jan;42(1):191-201. doi: 10.1093/schbul/sbv105. Epub 2015 Aug 3.
• [3] 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.
• [4] 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.
• [5] 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.
• [6] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [7] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [8] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [11] 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.
• [12] 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.
• [13] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [14] 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.