Details of Drug Off-Target (DOT)

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

• DOT Name: Amyloid-beta A4 precursor protein-binding family A member 3 (APBA3)
• Synonyms: Adapter protein X11gamma; Neuron-specific X11L2 protein; Neuronal Munc18-1-interacting protein 3; Mint-3
• Gene Name: APBA3
• Related Disease:
  Advanced cancer
  Alzheimer disease
  Breast cancer
  Breast carcinoma
• UniProt ID: APBA3_HUMAN
• PDB ID: 2YT7; 2YT8; 5UWS
• Pfam ID: PF00595 ; PF00640
• Sequence:
  MDFPTISRSPSGPPAMDLEGPRDILVPSEDLTPDSQWDPMPGGPGSLSRMELDESSLQEL
  VQQFEALPGDLVGPSPGGAPCPLHIATGHGLASQEIADAHGLLSAEAGRDDLLGLLHCEE
  CPPSQTGPEEPLEPAPRLLQPPEDPDEDSDSPEWVEGASAEQEGSRSSSSSPEPWLETVP
  LVTPEEPPAGAQSPETLASYPAPQEVPGPCDHEDLLDGVIFGARYLGSTQLVSERNPPTS
  TRMAQAREAMDRVKAPDGETQPMTEVDLFVSTKRIKVLTADSQEAMMDHALHTISYTADI
  GCVLVLMARRRLARRPAPQDHGRRLYKMLCHVFYAEDAQLIAQAIGQAFAAAYSQFLRES
  GIDPSQVGVHPSPGACHLHNGDLDHFSNSDNCREVHLEKRRGEGLGVALVESGWGSLLPT
  AVIANLLHGGPAERSGALSIGDRLTAINGTSLVGLPLAACQAAVRETKSQTSVTLSIVHC
  PPVTTAIIHRPHAREQLGFCVEDGIICSLLRGGIAERGGIRVGHRIIEINGQSVVATPHA
  RIIELLTEAYGEVHIKTMPAATYRLLTGQEQPVYL
• Function: May modulate processing of the amyloid-beta precursor protein (APP) and hence formation of APP-beta. May enhance the activity of HIF1A in macrophages by inhibiting the activity of HIF1AN.
• Tissue Specificity: Expressed in all tissues examined with lower levels in brain and testis.
• Reactome Pathway: Neurexins and neuroligins (R-HSA-6794361)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Alzheimer disease	DISF8S70	Strong	Biomarker	[2]
Breast cancer	DIS7DPX1	Strong	Biomarker	[3]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Amyloid-beta A4 precursor protein-binding family A member 3 (APBA3).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Amyloid-beta A4 precursor protein-binding family A member 3 (APBA3).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Amyloid-beta A4 precursor protein-binding family A member 3 (APBA3).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Amyloid-beta A4 precursor protein-binding family A member 3 (APBA3).	[7]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Amyloid-beta A4 precursor protein-binding family A member 3 (APBA3).	[8]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Amyloid-beta A4 precursor protein-binding family A member 3 (APBA3).	[7]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Amyloid-beta A4 precursor protein-binding family A member 3 (APBA3).	[9]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Amyloid-beta A4 precursor protein-binding family A member 3 (APBA3).	[10]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Amyloid-beta A4 precursor protein-binding family A member 3 (APBA3).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Amyloid-beta A4 precursor protein-binding family A member 3 (APBA3).	[12]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Amyloid-beta A4 precursor protein-binding family A member 3 (APBA3).	[12]

References

• [1] Control of metastatic niche formation by targeting APBA3/Mint3 in inflammatory monocytes.Proc Natl Acad Sci U S A. 2017 May 30;114(22):E4416-E4424. doi: 10.1073/pnas.1703171114. Epub 2017 May 15.
• [2] Deletion of Mint proteins decreases amyloid production in transgenic mouse models of Alzheimer's disease.J Neurosci. 2008 Dec 31;28(53):14392-400. doi: 10.1523/JNEUROSCI.2481-08.2008.
• [3] Mint3 in bone marrow-derived cells promotes lung metastasis in breast cancer model mice.Biochem Biophys Res Commun. 2017 Aug 26;490(3):688-692. doi: 10.1016/j.bbrc.2017.06.102. Epub 2017 Jun 19.
• [4] 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.
• [5] Effect of all-trans retinoic acid on sodium/iodide symporter expression, radioiodine uptake and gene expression profiles in a human anaplastic thyroid carcinoma cell line. Nucl Med Biol. 2006 Oct;33(7):875-82. doi: 10.1016/j.nucmedbio.2006.07.004.
• [6] 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.
• [7] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [8] 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.
• [9] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [10] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [11] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [12] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.