Details of Drug Off-Target (DOT)

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

• DOT Name: Amphiphysin (AMPH)
• Gene Name: AMPH
• Related Disease:
  Bone osteosarcoma
  Breast cancer
  Breast carcinoma
  Osteosarcoma
  Advanced cancer
  Alzheimer disease
  Attention deficit hyperactivity disorder
  Autoimmune disease
  Autoimmune disorder of the nervous system
  Bipolar disorder
  Centronuclear myopathy
  Congenital structural myopathy
  Facial nerve disorder
  Lung cancer
  Lung carcinoma
  Lung neoplasm
  Melanoma
  Myopathy
  Myotonic dystrophy
  Non-small-cell lung cancer
  Polyneuropathy
  Encephalitis
  Gastrointestinal stromal tumour
  Amyotrophic lateral sclerosis
  Autosomal recessive centronuclear myopathy
  Cognitive impairment
  Follicular lymphoma
  Myopathy, centronuclear, 2
  Neoplasm
  Neoplasm of esophagus
• UniProt ID: AMPH_HUMAN
• PDB ID: 1KY7; 1UTC; 3SOG; 4ATM; 5M5S; 5M61
• Pfam ID: PF03114
• Sequence:
  MADIKTGIFAKNVQKRLNRAQEKVLQKLGKADETKDEQFEEYVQNFKRQEAEGTRLQREL
  RGYLAAIKGMQEASMKLTESLHEVYEPDWYGREDVKMVGEKCDVLWEDFHQKLVDGSLLT
  LDTYLGQFPDIKNRIAKRSRKLVDYDSARHHLEALQSSKRKDESRISKAEEEFQKAQKVF
  EEFNVDLQEELPSLWSRRVGFYVNTFKNVSSLEAKFHKEIAVLCHKLYEVMTKLGDQHAD
  KAFTIQGAPSDSGPLRIAKTPSPPEEPSPLPSPTASPNHTLAPASPAPARPRSPSQTRKG
  PPVPPLPKVTPTKELQQENIISFFEDNFVPEISVTTPSQNEVPEVKKEETLLDLDFDPFK
  PEVTPAGSAGVTHSPMSQTLPWDLWTTSTDLVQPASGGSFNGFTQPQDTSLFTMQTDQSM
  ICNLAESEQAPPTEPKAEEPLAAVTPAVGLDLGMDTRAEEPVEEAVIIPGADADAAVGTL
  VSAAEGAPGEEAEAEKATVPAGEGVSLEEAKIGTETTEGAESAQPEAEELEATVPQEKVI
  PSVVIEPASNHEEEGENEITIGAEPKETTEDAAPPGPTSETPELATEQKPIQDPQPTPSA
  PAMGAADQLASAREASQELPPGFLYKVETLHDFEAANSDELTLQRGDVVLVVPSDSEADQ
  DAGWLVGVKESDWLQYRDLATYKGLFPENFTRRLD
• Function: May participate in mechanisms of regulated exocytosis in synapses and certain endocrine cell types. May control the properties of the membrane associated cytoskeleton.
• Tissue Specificity: Neurons, certain endocrine cell types and spermatocytes.
• KEGG Pathway:
  Endocytosis (hsa04144)
  Fc gamma R-mediated phagocytosis (hsa04666)
• Reactome Pathway: Clathrin-mediated endocytosis (R-HSA-8856828)

Molecular Interaction Atlas (MIA) of This DOT

30 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bone osteosarcoma	DIST1004	Definitive	Biomarker	[1]
Breast cancer	DIS7DPX1	Definitive	Biomarker	[2]
Breast carcinoma	DIS2UE88	Definitive	Biomarker	[2]
Osteosarcoma	DISLQ7E2	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[4]
Attention deficit hyperactivity disorder	DISL8MX9	Strong	Biomarker	[5]
Autoimmune disease	DISORMTM	Strong	Biomarker	[6]
Autoimmune disorder of the nervous system	DIS7OIK6	Strong	Biomarker	[7]
Bipolar disorder	DISAM7J2	Strong	Biomarker	[8]
Centronuclear myopathy	DISXBEJO	Strong	Biomarker	[9]
Congenital structural myopathy	DISZ9JP4	Strong	Biomarker	[9]
Facial nerve disorder	DISD2U0E	Strong	Genetic Variation	[6]
Lung cancer	DISCM4YA	Strong	Biomarker	[2]
Lung carcinoma	DISTR26C	Strong	Biomarker	[2]
Lung neoplasm	DISVARNB	Strong	Biomarker	[10]
Melanoma	DIS1RRCY	Strong	Biomarker	[2]
Myopathy	DISOWG27	Strong	Genetic Variation	[11]
Myotonic dystrophy	DISNBEMX	Strong	Biomarker	[12]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[13]
Polyneuropathy	DISB9G3W	Strong	Biomarker	[6]
Encephalitis	DISLD1RL	moderate	Biomarker	[14]
Gastrointestinal stromal tumour	DIS6TJYS	moderate	Biomarker	[15]
Amyotrophic lateral sclerosis	DISF7HVM	Limited	Genetic Variation	[16]
Autosomal recessive centronuclear myopathy	DIS4ZI6X	Limited	Genetic Variation	[17]
Cognitive impairment	DISH2ERD	Limited	Biomarker	[18]
Follicular lymphoma	DISVEUR6	Limited	Biomarker	[19]
Myopathy, centronuclear, 2	DIS7NCZX	Limited	Genetic Variation	[17]
Neoplasm	DISZKGEW	Limited	Biomarker	[2]
Neoplasm of esophagus	DISOLKAQ	Limited	Genetic Variation	[20]

12 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 Amphiphysin (AMPH).	[21]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Amphiphysin (AMPH).	[22]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Amphiphysin (AMPH).	[23]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Amphiphysin (AMPH).	[24]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Amphiphysin (AMPH).	[25]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Amphiphysin (AMPH).	[26]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Amphiphysin (AMPH).	[27]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Amphiphysin (AMPH).	[28]
Ethanol	DMDRQZU	Approved	Ethanol decreases the expression of Amphiphysin (AMPH).	[29]
Heroin diacetylmorphine	DMDBWHY	Approved	Heroin diacetylmorphine decreases the expression of Amphiphysin (AMPH).	[30]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Amphiphysin (AMPH).	[33]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	4-hydroxy-2-nonenal decreases the expression of Amphiphysin (AMPH).	[25]

2 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 increases the methylation of Amphiphysin (AMPH).	[31]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Amphiphysin (AMPH).	[32]

References

• [1] AMPH-1 As A Critical Tumor Suppressor That Inhibits Osteosarcoma Progression.Cancer Manag Res. 2019 Nov 25;11:9913-9919. doi: 10.2147/CMAR.S220544. eCollection 2019.
• [2] AMPH-1 is a tumor suppressor of lung cancer by inhibiting Ras-Raf-MEK-ERK signal pathway.Lasers Med Sci. 2019 Apr;34(3):473-478. doi: 10.1007/s10103-018-2616-4. Epub 2018 Aug 24.
• [3] Expression of amphiphysin I, an autoantigen of paraneoplastic neurological syndromes, in breast cancer.Mol Med. 1998 Jan;4(1):29-39.
• [4] Gene expression variance in hippocampal tissue of temporal lobe epilepsy patients corresponds to differential memory performance.Neurobiol Dis. 2016 Feb;86:121-30. doi: 10.1016/j.nbd.2015.11.011. Epub 2015 Nov 26.
• [5] Early-Onset Efficacy and Safety Pilot Study of Amphetamine Extended-Release Oral Suspension in the Treatment of Children with Attention-Deficit/Hyperactivity Disorder.J Child Adolesc Psychopharmacol. 2019 Feb;29(1):2-8. doi: 10.1089/cap.2018.0078. Epub 2018 Dec 21.
• [6] Amphiphysin-IgG autoimmune neuropathy: A recognizable clinicopathologic syndrome.Neurology. 2019 Nov 12;93(20):e1873-e1880. doi: 10.1212/WNL.0000000000008472. Epub 2019 Oct 17.
• [7] Primary structure of human amphiphysin, the dominant autoantigen of paraneoplastic stiff-man syndrome, and mapping of its gene (AMPH) to chromosome 7p13-p14.Hum Mol Genet. 1995 Feb;4(2):265-8. doi: 10.1093/hmg/4.2.265.
• [8] The role of neurotrophic factors in manic-, anxious- and depressive-like behaviors induced by amphetamine sensitization: Implications to the animal model of bipolar disorder.J Affect Disord. 2019 Feb 15;245:1106-1113. doi: 10.1016/j.jad.2018.10.370. Epub 2018 Nov 29.
• [9] Amphiphysin 2 modulation rescues myotubular myopathy and prevents focal adhesion defects in mice.Sci Transl Med. 2019 Mar 20;11(484):eaav1866. doi: 10.1126/scitranslmed.aav1866.
• [10] Antiamphiphysin-positive stiff-person syndrome associated with small cell lung cancer.Mov Disord. 2006 Aug;21(8):1285-7. doi: 10.1002/mds.20910.
• [11] Amphiphysin 2 Orchestrates Nucleus Positioning and Shape by Linking the Nuclear Envelope to the Actin and Microtubule Cytoskeleton.Dev Cell. 2015 Oct 26;35(2):186-98. doi: 10.1016/j.devcel.2015.09.018.
• [12] N-WASP is required for Amphiphysin-2/BIN1-dependent nuclear positioning and triad organization in skeletal muscle and is involved in the pathophysiology of centronuclear myopathy.EMBO Mol Med. 2014 Nov;6(11):1455-75. doi: 10.15252/emmm.201404436.
• [13] miR-425 regulates cell proliferation, migration and apoptosis by targeting AMPH-1 in non-small-cell lung cancer.Pathol Res Pract. 2019 Dec;215(12):152705. doi: 10.1016/j.prp.2019.152705. Epub 2019 Oct 23.
• [14] Paraneoplastic autoimmune movement disorders.Parkinsonism Relat Disord. 2017 Nov;44:106-109. doi: 10.1016/j.parkreldis.2017.08.017. Epub 2017 Oct 13.
• [15] Gastrointestinal stromal tumors regularly express synaptic vesicle proteins: evidence of a neuroendocrine phenotype.Endocr Relat Cancer. 2007 Sep;14(3):853-63. doi: 10.1677/ERC-06-0014.
• [16] Exocytosis regulates trafficking of GABA and glycine heterotransporters in spinal cord glutamatergic synapses: a mechanism for the excessive heterotransporter-induced release of glutamate in experimental amyotrophic lateral sclerosis.Neurobiol Dis. 2015 Feb;74:314-24. doi: 10.1016/j.nbd.2014.12.004. Epub 2014 Dec 10.
• [17] Case report of intrafamilial variability in autosomal recessive centronuclear myopathy associated to a novel BIN1 stop mutation.Orphanet J Rare Dis. 2010 Dec 3;5:35. doi: 10.1186/1750-1172-5-35.
• [18] Decreased synaptic vesicle recycling efficiency and cognitive deficits in amphiphysin 1 knockout mice.Neuron. 2002 Feb 28;33(5):789-804. doi: 10.1016/s0896-6273(02)00601-3.
• [19] DNA hypermethylation accompanied by transcriptional repression in follicular lymphoma.Genes Chromosomes Cancer. 2009 Sep;48(9):828-41. doi: 10.1002/gcc.20687.
• [20] Genome-wide association analyses of esophageal squamous cell carcinoma in Chinese identify multiple susceptibility loci and gene-environment interactions.Nat Genet. 2012 Oct;44(10):1090-7. doi: 10.1038/ng.2411. Epub 2012 Sep 9.
• [21] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [22] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [23] 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.
• [24] 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.
• [25] Microarray analysis of H2O2-, HNE-, or tBH-treated ARPE-19 cells. Free Radic Biol Med. 2002 Nov 15;33(10):1419-32.
• [26] 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.
• [27] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [28] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [29] Effects of acute ethanol treatment on NCCIT cells and NCCIT cell-derived embryoid bodies (EBs). Toxicol In Vitro. 2010 Sep;24(6):1696-704. doi: 10.1016/j.tiv.2010.05.017. Epub 2010 May 26.
• [30] Distinctive profiles of gene expression in the human nucleus accumbens associated with cocaine and heroin abuse. Neuropsychopharmacology. 2006 Oct;31(10):2304-12. doi: 10.1038/sj.npp.1301089. Epub 2006 May 3.
• [31] 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.
• [32] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [33] 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.