Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNUTR0N)

• DOT Name: Amyloid-beta A4 precursor protein-binding family B member 3 (APBB3)
• Synonyms: Protein Fe65-like 2; Fe65L2
• Gene Name: APBB3
• Related Disease:
  Subarachnoid hemorrhage
  Advanced cancer
  Alzheimer disease
  Atrial fibrillation
  Bacteremia
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Endometrial carcinoma
  Hyperaldosteronism
  Neoplasm
  Primary aldosteronism
  Stroke
  Trypanosomiasis
  Cardiovascular disease
  High blood pressure
  Prostate cancer
  Prostate carcinoma
  Asthma
  Heparin-induced thrombocytopenia
  Rectal carcinoma
• UniProt ID: APBB3_HUMAN
• PDB ID: 2DYQ; 2YSC
• Pfam ID: PF00640 ; PF00397
• Sequence:
  MLGKDYMLAIILVNCDDDLWGDHSLEVEAGLPPGWRKIHDAAGTYYWHVPSGSTQWQRPT
  WELGDAEDPGTGTEGIWGLRPPKGRSFSSLESSLDRSNSLSWYGGESYIQSMEPGAKCFA
  VRSLGWVEVPEEDLAPGKSSIAVNNCIQQLAQTRSRSQPPDGAWGEGQNMLMILKKDAMS
  LVNPLDHSLIHCQPLVHIRVWGVGSSKGRDRDFAFVASDKDSCMLKCHVFCCDVPAKAIA
  SALHGLCAQILSERVEVSGDASCCSPDPISPEDLPRQVELLDAVSQAAQKYEALYMGTLP
  VTKAMGMDVLNEAIGTLTARGDRNAWVPTMLSVSDSLMTAHPIQAEASTEEEPLWQCPVR
  LVTFIGVGRDPHTFGLIADLGRQSFQCAAFWCQPHAGGLSEAVQAACMVQYQKCLVASAA
  RGKAWGAQARARLRLKRTSSMDSPGGPLPLPLLKGGVGGAGATPRKRGVFSFLDAFRLKP
  SLLHMP
• Function: May modulate the internalization of amyloid-beta precursor protein.
• Tissue Specificity: Expressed in various tissues, highest expression in brain.

Molecular Interaction Atlas (MIA) of This DOT

21 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Subarachnoid hemorrhage	DISI7I8Y	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[3]
Atrial fibrillation	DIS15W6U	Strong	Biomarker	[4]
Bacteremia	DIS6N9RZ	Strong	Genetic Variation	[5]
Breast cancer	DIS7DPX1	Strong	Biomarker	[6]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[6]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[7]
Endometrial carcinoma	DISXR5CY	Strong	Altered Expression	[8]
Hyperaldosteronism	DIS3WGAL	Strong	Altered Expression	[9]
Neoplasm	DISZKGEW	Strong	Altered Expression	[10]
Primary aldosteronism	DISOEFNH	Strong	Altered Expression	[9]
Stroke	DISX6UHX	Strong	Biomarker	[4]
Trypanosomiasis	DISUBO83	Strong	Genetic Variation	[11]
Cardiovascular disease	DIS2IQDX	moderate	Biomarker	[12]
High blood pressure	DISY2OHH	moderate	Genetic Variation	[13]
Prostate cancer	DISF190Y	Disputed	Biomarker	[14]
Prostate carcinoma	DISMJPLE	Disputed	Biomarker	[14]
Asthma	DISW9QNS	Limited	Biomarker	[15]
Heparin-induced thrombocytopenia	DISAKJKZ	Limited	Biomarker	[16]
Rectal carcinoma	DIS8FRR7	Limited	Biomarker	[17]

5 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 Amyloid-beta A4 precursor protein-binding family B member 3 (APBB3).	[18]
Tretinoin	DM49DUI	Approved	Tretinoin affects the expression of Amyloid-beta A4 precursor protein-binding family B member 3 (APBB3).	[19]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Amyloid-beta A4 precursor protein-binding family B member 3 (APBB3).	[20]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene affects the expression of Amyloid-beta A4 precursor protein-binding family B member 3 (APBB3).	[19]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Amyloid-beta A4 precursor protein-binding family B member 3 (APBB3).	[23]

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 Amyloid-beta A4 precursor protein-binding family B member 3 (APBB3).	[21]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Amyloid-beta A4 precursor protein-binding family B member 3 (APBB3).	[22]

References

• [1] Risk factors predicting a higher grade of subarachnoid haemorrhage in small ruptured intracranial aneurysm (< 5 mm).Neurol Neurochir Pol. 2019;53(4):296-303. doi: 10.5603/PJNNS.a2019.0029. Epub 2019 Aug 9.
• [2] Role of UHRF1 in malignancy and its function as a therapeutic target for molecular docking towards the SRA domain.Int J Biochem Cell Biol. 2019 Sep;114:105558. doi: 10.1016/j.biocel.2019.06.006. Epub 2019 Jun 22.
• [3] Genome structure and chromosomal mapping of the gene for Fe65L2 interacting with Alzheimer's beta-amyloid precursor protein.Biochem Biophys Res Commun. 1999 May 10;258(2):385-9. doi: 10.1006/bbrc.1999.0639.
• [4] Refinement of detecting atrial fibrillation in stroke patients: results from the TRACK-AF Study.Eur J Neurol. 2018 Apr;25(4):631-636. doi: 10.1111/ene.13538. Epub 2018 Feb 13.
• [5] A Core Genome Multilocus Sequence Typing Scheme for Enterococcus faecalis.J Clin Microbiol. 2019 Feb 27;57(3):e01686-18. doi: 10.1128/JCM.01686-18. Print 2019 Mar.
• [6] Identification of new human coding steroid receptor RNA activator isoforms.Biochem Biophys Res Commun. 2003 Feb 7;301(2):509-15. doi: 10.1016/s0006-291x(02)03070-x.
• [7] Altered expression of estrogen receptor coregulators during human breast tumorigenesis.Cancer Res. 2000 Nov 15;60(22):6266-71.
• [8] Long Non-Coding RNAs in Endometrial Carcinoma.Int J Mol Sci. 2015 Nov 4;16(11):26463-72. doi: 10.3390/ijms161125962.
• [9] AN INDIVIDUALIZED APPROACH TO THE EVALUATION AND MANAGEMENT OF PRIMARY ALDOSTERONISM.Endocr Pract. 2017 Jun;23(6):680-689. doi: 10.4158/EP161717.RA. Epub 2017 Mar 23.
• [10] Silencing of SRA1 Regulates ER Expression and Attenuates the Growth of Stromal Cells in Ovarian Endometriosis.Reprod Sci. 2017 Jun;24(6):836-843. doi: 10.1177/1933719116670036. Epub 2016 Sep 30.
• [11] Detection of Trypanosoma brucei rhodesiense in animals from sleeping sickness foci in East Africa using the serum resistance associated (SRA) gene.Acta Trop. 2004 May;90(3):249-54. doi: 10.1016/j.actatropica.2004.01.001.
• [12] Downregulation of lncRNA-SRA participates in the development of cardiovascular disease in type II diabetic patients.Exp Ther Med. 2019 May;17(5):3367-3372. doi: 10.3892/etm.2019.7362. Epub 2019 Mar 7.
• [13] Kidney CLC-K chloride channels inhibitors: structure-based studies and efficacy in hypertension and associated CLC-K polymorphisms.J Hypertens. 2016 May;34(5):981-92. doi: 10.1097/HJH.0000000000000876.
• [14] The SRA protein UHRF1 promotes epigenetic crosstalks and is involved in prostate cancer progression.Oncogene. 2012 Nov 15;31(46):4878-87. doi: 10.1038/onc.2011.641. Epub 2012 Feb 13.
• [15] Exhaled breath temperature in optimally treated asthmatics: severity and underlying mechanisms.J Breath Res. 2018 Feb 20;12(2):026013. doi: 10.1088/1752-7163/aa9d46.
• [16] HIT or miss? A comprehensive contemporary investigation of laboratory tests for heparin induced thrombocytopenia.Pathology. 2018 Jun;50(4):426-436. doi: 10.1016/j.pathol.2017.11.089. Epub 2018 Apr 17.
• [17] Localization of mesenteric lymph node metastases in relation to the level of arterial ligation in rectal cancer surgery.Eur J Surg Oncol. 2019 Jun;45(6):989-994. doi: 10.1016/j.ejso.2019.01.183. Epub 2019 Feb 5.
• [18] 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.
• [19] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [20] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [21] 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.
• [22] 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.
• [23] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.