Details of Drug Off-Target (DOT)

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

DOT Name Tubulin polymerization-promoting protein (TPPP)
Synonyms TPPP; EC 3.6.5.-; 25 kDa brain-specific protein; TPPP/p25; p24; p25-alpha
Gene Name TPPP
Related Disease
Adult T-cell leukemia/lymphoma ( )
Advanced cancer ( )
Amyotrophic lateral sclerosis ( )
Autosomal dominant optic atrophy, classic form ( )
Barrett esophagus ( )
Bladder cancer ( )
Chorioamnionitis ( )
Chronic fatigue syndrome ( )
Clear cell renal carcinoma ( )
Colon carcinoma ( )
Cytomegalovirus infection ( )
Esophageal adenocarcinoma ( )
Glioma ( )
Huntington disease ( )
Hypospadias ( )
Immunodeficiency ( )
Influenza ( )
Insomnia ( )
Latent tuberculosis infection ( )
Leukemia ( )
Lymphoma ( )
Mental disorder ( )
Motor neurone disease ( )
Neoplasm ( )
Parkinson disease ( )
Prion disease ( )
Progressive multifocal leukoencephalopathy ( )
Prostate cancer ( )
Prostate carcinoma ( )
Pulmonary disease ( )
Renal cell carcinoma ( )
Schizophrenia ( )
Sjogren syndrome ( )
Status epilepticus seizure ( )
T-cell leukaemia ( )
Tuberculosis ( )
Urinary bladder cancer ( )
Urinary bladder neoplasm ( )
Urticaria ( )
Vibrio cholerae infection ( )
Frontotemporal dementia ( )
Neuroblastoma ( )
Stroke ( )
Amyloidosis ( )
Lewy body dementia ( )
Malaria ( )
Mood disorder ( )
Nervous system disease ( )
Psychotic disorder ( )
Rheumatoid arthritis ( )
UniProt ID
TPPP_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
EC Number
3.6.5.-
Pfam ID
PF05517
Sequence
MADKAKPAKAANRTPPKSPGDPSKDRAAKRLSLESEGAGEGAAASPELSALEEAFRRFAV
HGDARATGREMHGKNWSKLCKDCQVIDGRNVTVTDVDIVFSKIKGKSCRTITFEQFQEAL
EELAKKRFKDKSSEEAVREVHRLIEGKAPIISGVTKAISSPTVSRLTDTTKFTGSHKERF
DPSGKGKGKAGRVDLVDESGYVSGYKHAGTYDQKVQGGK
Function
Regulator of microtubule dynamics that plays a key role in myelination by promoting elongation of the myelin sheath. Acts as a microtubule nucleation factor in oligodendrocytes: specifically localizes to the postsynaptic Golgi apparatus region, also named Golgi outpost, and promotes microtubule nucleation, an important step for elongation of the myelin sheath. Required for both uniform polarized growth of distal microtubules as well as directing the branching of proximal processes. Shows magnesium-dependent GTPase activity; the role of the GTPase activity is unclear. In addition to microtubule nucleation activity, also involved in microtubule bundling and stabilization of existing microtubules, thereby maintaining the integrity of the microtubule network. Regulates microtubule dynamics by promoting tubulin acetylation: acts by inhibiting the tubulin deacetylase activity of HDAC6. Also regulates cell migration: phosphorylation by ROCK1 inhibits interaction with HDAC6, resulting in decreased acetylation of tubulin and increased cell motility. Plays a role in cell proliferation by regulating the G1/S-phase transition. Involved in astral microtubule organization and mitotic spindle orientation during early stage of mitosis; this process is regulated by phosphorylation by LIMK2.
Tissue Specificity Widely expressed.

Molecular Interaction Atlas (MIA) of This DOT

50 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Adult T-cell leukemia/lymphoma DIS882XU Strong Biomarker [1]
Advanced cancer DISAT1Z9 Strong Biomarker [2]
Amyotrophic lateral sclerosis DISF7HVM Strong Biomarker [3]
Autosomal dominant optic atrophy, classic form DISXUAV9 Strong Altered Expression [4]
Barrett esophagus DIS416Y7 Strong Genetic Variation [5]
Bladder cancer DISUHNM0 Strong Biomarker [6]
Chorioamnionitis DISL1D9U Strong Altered Expression [7]
Chronic fatigue syndrome DIS34WJ5 Strong Biomarker [8]
Clear cell renal carcinoma DISBXRFJ Strong Genetic Variation [9]
Colon carcinoma DISJYKUO Strong Biomarker [10]
Cytomegalovirus infection DISCEMGC Strong Altered Expression [11]
Esophageal adenocarcinoma DISODWFP Strong Genetic Variation [5]
Glioma DIS5RPEH Strong Altered Expression [2]
Huntington disease DISQPLA4 Strong Altered Expression [12]
Hypospadias DIS48CCP Strong Biomarker [13]
Immunodeficiency DIS093I0 Strong Biomarker [14]
Influenza DIS3PNU3 Strong Biomarker [15]
Insomnia DIS0AFR7 Strong Biomarker [16]
Latent tuberculosis infection DIS6R1EH Strong Biomarker [17]
Leukemia DISNAKFL Strong Biomarker [18]
Lymphoma DISN6V4S Strong Biomarker [19]
Mental disorder DIS3J5R8 Strong Biomarker [20]
Motor neurone disease DISUHWUI Strong Biomarker [21]
Neoplasm DISZKGEW Strong Biomarker [22]
Parkinson disease DISQVHKL Strong Biomarker [23]
Prion disease DISOUMB0 Strong Biomarker [24]
Progressive multifocal leukoencephalopathy DISX02WS Strong Biomarker [25]
Prostate cancer DISF190Y Strong Biomarker [26]
Prostate carcinoma DISMJPLE Strong Biomarker [26]
Pulmonary disease DIS6060I Strong Altered Expression [27]
Renal cell carcinoma DISQZ2X8 Strong Genetic Variation [9]
Schizophrenia DISSRV2N Strong Biomarker [20]
Sjogren syndrome DISUBX7H Strong Biomarker [28]
Status epilepticus seizure DISY3BIC Strong Biomarker [29]
T-cell leukaemia DISJ6YIF Strong Biomarker [1]
Tuberculosis DIS2YIMD Strong Biomarker [17]
Urinary bladder cancer DISDV4T7 Strong Biomarker [6]
Urinary bladder neoplasm DIS7HACE Strong Biomarker [6]
Urticaria DIS9WQAI Strong Altered Expression [30]
Vibrio cholerae infection DISW7E3U Strong Biomarker [31]
Frontotemporal dementia DISKYHXL moderate Genetic Variation [32]
Neuroblastoma DISVZBI4 moderate Genetic Variation [33]
Stroke DISX6UHX moderate Biomarker [34]
Amyloidosis DISHTAI2 Limited Biomarker [35]
Lewy body dementia DISAE66J Limited Biomarker [35]
Malaria DISQ9Y50 Limited Biomarker [36]
Mood disorder DISLVMWO Limited Altered Expression [37]
Nervous system disease DISJ7GGT Limited Altered Expression [38]
Psychotic disorder DIS4UQOT Limited Biomarker [37]
Rheumatoid arthritis DISTSB4J Limited Altered Expression [39]
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⏷ Show the Full List of 50 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
3 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the methylation of Tubulin polymerization-promoting protein (TPPP). [40]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Tubulin polymerization-promoting protein (TPPP). [46]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the methylation of Tubulin polymerization-promoting protein (TPPP). [48]
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7 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Tubulin polymerization-promoting protein (TPPP). [41]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Tubulin polymerization-promoting protein (TPPP). [42]
Niclosamide DMJAGXQ Approved Niclosamide increases the expression of Tubulin polymerization-promoting protein (TPPP). [43]
Irinotecan DMP6SC2 Approved Irinotecan increases the expression of Tubulin polymerization-promoting protein (TPPP). [44]
Urethane DM7NSI0 Phase 4 Urethane increases the expression of Tubulin polymerization-promoting protein (TPPP). [45]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 increases the expression of Tubulin polymerization-promoting protein (TPPP). [47]
Trichostatin A DM9C8NX Investigative Trichostatin A affects the expression of Tubulin polymerization-promoting protein (TPPP). [49]
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⏷ Show the Full List of 7 Drug(s)

References

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23 Pharmacological targeting of -synuclein and TPPP/p25 in Parkinson's disease: challenges and opportunities in a Nutshell.FEBS Lett. 2019 Jul;593(13):1641-1653. doi: 10.1002/1873-3468.13464. Epub 2019 Jun 11.
24 Molecular interaction of TPPP with PrP antagonized the CytoPrP-induced disruption of microtubule structures and cytotoxicity.PLoS One. 2011;6(8):e23079. doi: 10.1371/journal.pone.0023079. Epub 2011 Aug 12.
25 Detection of HIV-1 Tat and JCV capsid protein, VP1, in AIDS brain with progressive multifocal leukoencephalopathy.J Neurovirol. 2000 Jun;6(3):221-8. doi: 10.3109/13550280009015824.
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