Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTU8VUIG)

• DOT Name: Tubulin polymerization-promoting protein family member 3 (TPPP3)
• Synonyms: TPPP/p20
• Gene Name: TPPP3
• Related Disease:
  Becker muscular dystrophy
  Colorectal carcinoma
  Duchenne muscular dystrophy
  Fatty liver disease
  Glioma
  Malignant soft tissue neoplasm
  Metastatic malignant neoplasm
  Neoplasm
  Neuroblastoma
  Non-small-cell lung cancer
  Sarcoma
  Schizophrenia
• UniProt ID: TPPP3_HUMAN
• PDB ID: 2JRF
• Pfam ID: PF05517
• Sequence:
  MAASTDMAGLEESFRKFAIHGDPKASGQEMNGKNWAKLCKDCKVADGKSVTGTDVDIVFS
  KVKGKSARVINYEEFKKALEELATKRFKGKSKEEAFDAICQLVAGKEPANVGVTKAKTGG
  AVDRLTDTSRYTGSHKERFDESGKGKGIAGRQDILDDSGYVSAYKNAGTYDAKVKK
• Function: Regulator of microtubule dynamic that has microtubule bundling activity. Required for embryo implantation; possibly by regulating beta-catenin. Also required for decidualization via regulation of beta-catenin.
• Tissue Specificity: Expressed in endometrium during the mid-secretory phase (LH + 7) (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Becker muscular dystrophy	DIS5IYHL	Definitive	Biomarker	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[2]
Duchenne muscular dystrophy	DISRQ3NV	Strong	Biomarker	[3]
Fatty liver disease	DIS485QZ	Strong	Altered Expression	[4]
Glioma	DIS5RPEH	Strong	Biomarker	[5]
Malignant soft tissue neoplasm	DISTC6NO	Strong	Biomarker	[6]
Metastatic malignant neoplasm	DIS86UK6	Strong	Biomarker	[7]
Neoplasm	DISZKGEW	Strong	Biomarker	[8]
Neuroblastoma	DISVZBI4	Strong	Altered Expression	[9]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[7]
Sarcoma	DISZDG3U	Strong	Biomarker	[6]
Schizophrenia	DISSRV2N	Strong	Altered Expression	[10]

8 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 Tubulin polymerization-promoting protein family member 3 (TPPP3).	[11]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Tubulin polymerization-promoting protein family member 3 (TPPP3).	[12]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Tubulin polymerization-promoting protein family member 3 (TPPP3).	[13]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Tubulin polymerization-promoting protein family member 3 (TPPP3).	[14]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Tubulin polymerization-promoting protein family member 3 (TPPP3).	[16]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Tubulin polymerization-promoting protein family member 3 (TPPP3).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Tubulin polymerization-promoting protein family member 3 (TPPP3).	[18]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Tubulin polymerization-promoting protein family member 3 (TPPP3).	[19]

1 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 Tubulin polymerization-promoting protein family member 3 (TPPP3).	[15]

References

• [1] A deletion hot spot in the Duchenne muscular dystrophy gene.Genomics. 1988 Feb;2(2):101-8. doi: 10.1016/0888-7543(88)90090-0.
• [2] Knockdown of Tubulin Polymerization Promoting Protein Family Member 3 inhibits cell proliferation and invasion in human colorectal cancer.J Cancer. 2017 Jul 1;8(10):1750-1758. doi: 10.7150/jca.18943. eCollection 2017.
• [3] Identification of Duchenne muscular dystrophy genomic probe P20 constant Taql fragment corresponding to the EcoRV and Mspl polymorphisms.Prenat Diagn. 1991 Jan;11(1):63-7. doi: 10.1002/pd.1970110112.
• [4] Increased Tim-3 expression alleviates liver injury by regulating macrophage activation in MCD-induced NASH mice.Cell Mol Immunol. 2019 Nov;16(11):878-886. doi: 10.1038/s41423-018-0032-0. Epub 2018 May 7.
• [5] Paxilline enhances TRAIL-mediated apoptosis of glioma cells via modulation of c-FLIP, survivin and DR5.Exp Mol Med. 2011 Jan 31;43(1):24-34. doi: 10.3858/emm.2011.43.1.003.
• [6] Cell-type dependent enhancer binding of the EWS/ATF1 fusion gene in clear cell sarcomas.Nat Commun. 2019 Sep 5;10(1):3999. doi: 10.1038/s41467-019-11745-1.
• [7] TPPP3 Promotes Cell Proliferation, Invasion and Tumor Metastasis via STAT3/ Twist1 Pathway in Non-Small-Cell Lung Carcinoma.Cell Physiol Biochem. 2018;50(5):2004-2016. doi: 10.1159/000494892. Epub 2018 Nov 7.
• [8] Inhibition of melanoma metastasis by dual-peptide PLGA NPS.Biopolymers. 2017 Sep;108(5). doi: 10.1002/bip.23029.
• [9] Retinoic acid-induced upregulation of the metalloendopeptidase nardilysin is accelerated by co-expression of the brain-specific protein p42(IP4) (centaurin 1; ADAP1) in neuroblastoma cells.Neurochem Int. 2011 Nov;59(6):936-44. doi: 10.1016/j.neuint.2011.07.004. Epub 2011 Jul 23.
• [10] Prefrontal cortex shotgun proteome analysis reveals altered calcium homeostasis and immune system imbalance in schizophrenia.Eur Arch Psychiatry Clin Neurosci. 2009 Apr;259(3):151-63. doi: 10.1007/s00406-008-0847-2. Epub 2009 Jan 22.
• [11] Evaluation of a human iPSC-derived BBB model for repeated dose toxicity testing with cyclosporine A as model compound. Toxicol In Vitro. 2021 Jun;73:105112. doi: 10.1016/j.tiv.2021.105112. Epub 2021 Feb 22.
• [12] 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.
• [13] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [14] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [15] 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.
• [16] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [17] Inter- and intra-laboratory study to determine the reproducibility of toxicogenomics datasets. Toxicology. 2011 Nov 28;290(1):50-8.
• [18] Proteomics and disease network associations evaluation of environmentally relevant Bisphenol A concentrations in a human 3D neural stem cell model. Front Cell Dev Biol. 2023 Aug 16;11:1236243. doi: 10.3389/fcell.2023.1236243. eCollection 2023.
• [19] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.