Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTO8XY5A)

• DOT Name: Alpha-taxilin
• Gene Name: TXLNA
• UniProt ID: TXLNA_HUMAN
• Pfam ID: PF09728
• Sequence:
  MKNQDKKNGAAKQSNPKSSPGQPEAGPEGAQERPSQAAPAVEAEGPGSSQAPRKPEGAQA
  RTAQSGALRDVSEELSRQLEDILSTYCVDNNQGGPGEDGAQGEPAEPEDAEKSRTYVARN
  GEPEPTPVVNGEKEPSKGDPNTEEIRQSDEVGDRDHRRPQEKKKAKGLGKEITLLMQTLN
  TLSTPEEKLAALCKKYAELLEEHRNSQKQMKLLQKKQSQLVQEKDHLRGEHSKAVLARSK
  LESLCRELQRHNRSLKEEGVQRAREEEEKRKEVTSHFQVTLNDIQLQMEQHNERNSKLRQ
  ENMELAERLKKLIEQYELREEHIDKVFKHKDLQQQLVDAKLQQAQEMLKEAEERHQREKD
  FLLKEAVESQRMCELMKQQETHLKQQLALYTEKFEEFQNTLSKSSEVFTTFKQEMEKMTK
  KIKKLEKETTMYRSRWESSNKALLEMAEEKTVRDKELEGLQVKIQRLEKLCRALQTERND
  LNKRVQDLSAGGQGSLTDSGPERRPEGPGAQAPSSPRVTEAPCYPGAPSTEASGQTGPQE
  PTSARA
• Function: May be involved in intracellular vesicle traffic and potentially in calcium-dependent exocytosis in neuroendocrine cells.
• Tissue Specificity: Ubiquitous, with much higher expression in heart, kidney, liver and pancreas.
• Reactome Pathway: Other interleukin signaling (R-HSA-449836)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Alpha-taxilin.	[1]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Alpha-taxilin.	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Alpha-taxilin.	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Alpha-taxilin.	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Alpha-taxilin.	[5]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Alpha-taxilin.	[6]
Mifepristone	DMGZQEF	Approved	Mifepristone decreases the expression of Alpha-taxilin.	[7]
Benzatropine	DMF7EXL	Approved	Benzatropine decreases the expression of Alpha-taxilin.	[8]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Alpha-taxilin.	[9]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Alpha-taxilin.	[10]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Alpha-taxilin.	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Alpha-taxilin.	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Alpha-taxilin.	[14]
Aminohippuric acid	DMUN54G	Investigative	Aminohippuric acid affects the expression of Alpha-taxilin.	[15]

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 decreases the phosphorylation of Alpha-taxilin.	[13]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Alpha-taxilin.	[13]

References

• [1] 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.
• [2] 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.
• [3] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [5] 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.
• [6] 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.
• [7] Mifepristone induced progesterone withdrawal reveals novel regulatory pathways in human endometrium. Mol Hum Reprod. 2007 Sep;13(9):641-54.
• [8] Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
• [9] Changes in gene expressions elicited by physiological concentrations of genistein on human endometrial cancer cells. Mol Carcinog. 2006 Oct;45(10):752-63.
• [10] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [11] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [12] 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.
• [13] 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.
• [14] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.
• [15] Cancer-related proteins in serum are altered in workers occupationally exposed to polycyclic aromatic hydrocarbons: a cross-sectional study. Carcinogenesis. 2019 Jul 6;40(6):771-781. doi: 10.1093/carcin/bgz022.