Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTI3WA6X)

DOT Name Tubulin polymerization-promoting protein family member 2 (TPPP2)
Synonyms Protein p25-beta; TPPP/p18
Gene Name TPPP2
Related Disease
Angelman syndrome ( )
Meningioma ( )
Non-insulin dependent diabetes ( )
Acute leukaemia ( )
Acute lymphocytic leukaemia ( )
Adult lymphoma ( )
Advanced cancer ( )
Bone osteosarcoma ( )
Breast neoplasm ( )
Childhood acute lymphoblastic leukemia ( )
Chromosomal disorder ( )
Depression ( )
Hepatitis B virus infection ( )
Hepatocellular carcinoma ( )
Hyperparathyroidism ( )
Lassa fever ( )
Lung cancer ( )
Lymphoma ( )
Lymphoma, non-Hodgkin, familial ( )
Malignant soft tissue neoplasm ( )
Melanoma ( )
Myelodysplastic syndrome ( )
Non-hodgkin lymphoma ( )
Non-small-cell lung cancer ( )
Osteosarcoma ( )
Pediatric lymphoma ( )
Psoriatic arthritis ( )
Retinoblastoma ( )
Sarcoma ( )
Status epilepticus seizure ( )
Viral hemorrhagic fever ( )
Arterial tortuosity syndrome ( )
Breast cancer ( )
Breast carcinoma ( )
Neuroendocrine neoplasm ( )
Familial medullary thyroid carcinoma ( )
Neuroblastoma ( )
Plasma cell myeloma ( )
UniProt ID
TPPP2_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF05517
Sequence
MASEAEKTFHRFAAFGESSSSGTEMNNKNFSKLCKDCGIMDGKTVTSTDVDIVFSKVKAK
NARTITFQQFKEAVKELGQKRFKGKSPDEVLENIYGLMEGKDPATTGATKATTVGAVDRL
TDTSKYTGTHKERFDESGKGKGIAGREEMTDNTGYVSGYKGSGTYDKKTK
Function Probable regulator of microtubule dynamics required for sperm motility (Probable). In contrast to other members of the family, has no microtubule bundling activity.
Tissue Specificity Expressed in spermatids . Detected in liver cancer (at protein level) .

Molecular Interaction Atlas (MIA) of This DOT

38 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Angelman syndrome DIS4QVXO Definitive Biomarker [1]
Meningioma DISPT4TG Definitive Genetic Variation [2]
Non-insulin dependent diabetes DISK1O5Z Definitive Genetic Variation [3]
Acute leukaemia DISDQFDI Strong Altered Expression [4]
Acute lymphocytic leukaemia DISPX75S Strong Genetic Variation [4]
Adult lymphoma DISK8IZR Strong Biomarker [5]
Advanced cancer DISAT1Z9 Strong Biomarker [6]
Bone osteosarcoma DIST1004 Strong Biomarker [7]
Breast neoplasm DISNGJLM Strong Biomarker [8]
Childhood acute lymphoblastic leukemia DISJ5D6U Strong Genetic Variation [4]
Chromosomal disorder DISM5BB5 Strong Biomarker [9]
Depression DIS3XJ69 Strong Genetic Variation [10]
Hepatitis B virus infection DISLQ2XY Strong Biomarker [11]
Hepatocellular carcinoma DIS0J828 Strong Altered Expression [11]
Hyperparathyroidism DIS4FVAT Strong Altered Expression [12]
Lassa fever DISKFYGZ Strong Biomarker [13]
Lung cancer DISCM4YA Strong Biomarker [14]
Lymphoma DISN6V4S Strong Biomarker [5]
Lymphoma, non-Hodgkin, familial DISCXYIZ Strong Biomarker [15]
Malignant soft tissue neoplasm DISTC6NO Strong Genetic Variation [7]
Melanoma DIS1RRCY Strong Biomarker [16]
Myelodysplastic syndrome DISYHNUI Strong Biomarker [17]
Non-hodgkin lymphoma DISS2Y8A Strong Biomarker [15]
Non-small-cell lung cancer DIS5Y6R9 Strong Genetic Variation [18]
Osteosarcoma DISLQ7E2 Strong Genetic Variation [7]
Pediatric lymphoma DIS51BK2 Strong Biomarker [5]
Psoriatic arthritis DISLWTG2 Strong Biomarker [19]
Retinoblastoma DISVPNPB Strong Biomarker [20]
Sarcoma DISZDG3U Strong Genetic Variation [7]
Status epilepticus seizure DISY3BIC Strong Genetic Variation [21]
Viral hemorrhagic fever DISQEBTU Strong Genetic Variation [22]
Arterial tortuosity syndrome DISWG36B moderate Biomarker [23]
Breast cancer DIS7DPX1 moderate Biomarker [24]
Breast carcinoma DIS2UE88 moderate Biomarker [24]
Neuroendocrine neoplasm DISNPLOO moderate Altered Expression [25]
Familial medullary thyroid carcinoma DIS01PWX Limited Biomarker [26]
Neuroblastoma DISVZBI4 Limited Biomarker [27]
Plasma cell myeloma DIS0DFZ0 Limited Biomarker [28]
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⏷ Show the Full List of 38 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
2 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Tubulin polymerization-promoting protein family member 2 (TPPP2). [29]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Tubulin polymerization-promoting protein family member 2 (TPPP2). [31]
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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 2 (TPPP2). [30]
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References

1 UBE3A-mediated p18/LAMTOR1 ubiquitination and degradation regulate mTORC1 activity and synaptic plasticity.Elife. 2018 Jul 18;7:e37993. doi: 10.7554/eLife.37993.
2 Molecular analysis of alterations of the p18INK4c gene in human meningiomas.Neuropathol Appl Neurobiol. 2000 Feb;26(1):67-75. doi: 10.1046/j.1365-2990.2000.00219.x.
3 Whole-exome sequencing in maya indigenous families: variant in PPP1R3A is associated with type 2 diabetes. Mol Genet Genomics. 2018 Oct;293(5):1205-1216. doi: 10.1007/s00438-018-1453-2. Epub 2018 Jun 11.
4 Homozygous deletions of cyclin-dependent kinase inhibitor genes, p16(INK4A) and p18, in childhood T cell lineage acute lymphoblastic leukemias.Leukemia. 1996 Feb;10(2):255-60.
5 Analysis of the novel cyclin-dependent kinase 4 and 6 inhibitor gene p18 in lymphoma and leukemia cell lines.Leuk Res. 1996 Feb;20(2):197-200. doi: 10.1016/0145-2126(95)00137-9.
6 Host Tumor Suppressor p18(INK4c) Functions as a Potent Cell-Intrinsic Inhibitor of Murine Gammaherpesvirus 68 Reactivation and Pathogenesis.J Virol. 2018 Feb 26;92(6):e01604-17. doi: 10.1128/JVI.01604-17. Print 2018 Mar 15.
7 Alterations of the p15, p16,and p18 genes in osteosarcoma.Cancer Genet Cytogenet. 1996 Feb;86(2):136-42. doi: 10.1016/0165-4608(95)00216-2.
8 A p18 mutant defective in CDK6 binding in human breast cancer cells.Cancer Res. 1996 Oct 15;56(20):4586-9.
9 Absence of cyclin-dependent kinase inhibitor p27 or p18 increases efficiency of iPSC generation without induction of iPSC genomic instability.Cell Death Dis. 2019 Mar 20;10(4):271. doi: 10.1038/s41419-019-1502-8.
10 Reliability and Validity of a Material Resources Scale and Its Association With Depression Among Young Men Who Have Sex With Men: The P18 Cohort Study.Am J Mens Health. 2018 Sep;12(5):1384-1397. doi: 10.1177/1557988316651206. Epub 2016 May 25.
11 Elevation of highly up-regulated in liver cancer (HULC) by hepatitis B virus X protein promotes hepatoma cell proliferation via down-regulating p18.J Biol Chem. 2012 Jul 27;287(31):26302-11. doi: 10.1074/jbc.M112.342113. Epub 2012 Jun 8.
12 Reduced p18INK4c, p21CIP1/WAF1 and p27KIP1 mRNA levels in tumours of primary and secondary hyperparathyroidism.Clin Endocrinol (Oxf). 2004 Mar;60(3):389-93. doi: 10.1111/j.1365-2265.2004.01995.x.
13 Characterization of virulence-associated determinants in the envelope glycoprotein of Pichinde virus.Virology. 2012 Nov 10;433(1):97-103. doi: 10.1016/j.virol.2012.07.009. Epub 2012 Aug 9.
14 Intragenic mutations of the p16(INK4), p15(INK4B) and p18 genes in primary non-small-cell lung cancers.Int J Cancer. 1996 Mar 15;65(6):734-9. doi: 10.1002/(SICI)1097-0215(19960315)65:6<734::AID-IJC4>3.0.CO;2-#.
15 Deletion of cyclin-dependent kinase 4 inhibitor genes P15 and P16 in non-Hodgkin's lymphoma.Blood. 1995 Oct 15;86(8):2900-5.
16 Screening of germline mutations in the CDK4, CDKN2C and TP53 genes in familial melanoma: a clinic-based population study.Int J Cancer. 1998 Sep 25;78(1):13-5. doi: 10.1002/(sici)1097-0215(19980925)78:1<13::aid-ijc3>3.0.co;2-#.
17 Hematopathological alterations of major tumor suppressor cascade, vital cell cycle inhibitors and hematopoietic niche components in experimental myelodysplasia.Chem Biol Interact. 2017 Aug 1;273:1-10. doi: 10.1016/j.cbi.2017.05.014. Epub 2017 May 23.
18 Potentially functional polymorphisms in cell cycle genes and the survival of non-small cell lung cancer in a Chinese population.Lung Cancer. 2011 Jul;73(1):32-7. doi: 10.1016/j.lungcan.2010.11.001. Epub 2010 Dec 9.
19 "Invivo self-assembled" nanoprobes for optimizing autophagy-mediated chemotherapy.Biomaterials. 2017 Oct;141:199-209. doi: 10.1016/j.biomaterials.2017.06.042. Epub 2017 Jun 30.
20 The effect of miR-340 over-expression on cell-cycle-related genes in triple-negative breast cancer cells.Eur J Cancer Care (Engl). 2017 Nov;26(6). doi: 10.1111/ecc.12496. Epub 2016 May 27.
21 Interaction of GABA(A) and GABA(B) antagonists after status epilepticus in immature rats.Epilepsy Behav. 2020 Jan;102:106683. doi: 10.1016/j.yebeh.2019.106683. Epub 2019 Nov 21.
22 Cytokine patterns in a comparative model of arenavirus haemorrhagic fever in guinea pigs.J Gen Virol. 2008 Oct;89(Pt 10):2569-2579. doi: 10.1099/vir.0.2008/002048-0.
23 Oxygen-Induced Retinopathy and Choroidopathy: In Vivo Longitudinal Observation of Vascular Changes Using OCTA.Invest Ophthalmol Vis Sci. 2018 Aug 1;59(10):3932-3942. doi: 10.1167/iovs.18-24320.
24 Indolo-pyrido-isoquinolin based alkaloid inhibits growth, invasion and migration of breast cancer cells via activation ofp53-miR34a axis.Mol Oncol. 2016 Aug;10(7):1118-32. doi: 10.1016/j.molonc.2016.04.003. Epub 2016 May 20.
25 A gene that encodes for a leukemia-associated phosphoprotein (p18) maps to chromosome bands 1p35-36.1.Genes Chromosomes Cancer. 1990 Jul;2(2):125-9. doi: 10.1002/gcc.2870020208.
26 Synergistic effect of oncogenic RET and loss of p18 on medullary thyroid carcinoma development.Cancer Res. 2008 Mar 1;68(5):1329-37. doi: 10.1158/0008-5472.CAN-07-5754.
27 The p16 and p18 tumor suppressor genes in neuroblastoma: implications for drug resistance.Cancer Lett. 1996 Jul 12;104(2):183-92. doi: 10.1016/0304-3835(96)04250-4.
28 Frequent inactivation of the cyclin-dependent kinase inhibitor p18 by homozygous deletion in multiple myeloma cell lines: ectopic p18 expression inhibits growth and induces apoptosis.Leukemia. 2002 Jan;16(1):127-34. doi: 10.1038/sj.leu.2402328.
29 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
30 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.
31 Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.