Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTV8N39)

• DOT Name: Tubulin beta-2A chain
• Synonyms: Tubulin beta class IIa
• Gene Name: TUBB2A
• Related Disease:
  Complex cortical dysplasia with other brain malformations 5
  Tubulinopathy
• UniProt ID: TBB2A_HUMAN
• PDB ID: 7NVN
• Pfam ID: PF00091 ; PF03953
• Sequence:
  MREIVHIQAGQCGNQIGAKFWEVISDEHGIDPTGSYHGDSDLQLERINVYYNEAAGNKYV
  PRAILVDLEPGTMDSVRSGPFGQIFRPDNFVFGQSGAGNNWAKGHYTEGAELVDSVLDVV
  RKESESCDCLQGFQLTHSLGGGTGSGMGTLLISKIREEYPDRIMNTFSVMPSPKVSDTVV
  EPYNATLSVHQLVENTDETYSIDNEALYDICFRTLKLTTPTYGDLNHLVSATMSGVTTCL
  RFPGQLNADLRKLAVNMVPFPRLHFFMPGFAPLTSRGSQQYRALTVPELTQQMFDSKNMM
  AACDPRHGRYLTVAAIFRGRMSMKEVDEQMLNVQNKNSSYFVEWIPNNVKTAVCDIPPRG
  LKMSATFIGNSTAIQELFKRISEQFTAMFRRKAFLHWYTGEGMDEMEFTEAESNMNDLVS
  EYQQYQDATADEQGEFEEEEGEDEA
• Function: Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin.
• Tissue Specificity: High expression in brain, where it represents 30% of all beta-tubulins.
• KEGG Pathway:
  Phagosome (hsa04145)
  Gap junction (hsa04540)
  Motor proteins (hsa04814)
  Alzheimer disease (hsa05010)
  Parkinson disease (hsa05012)
  Amyotrophic lateral sclerosis (hsa05014)
  Huntington disease (hsa05016)
  Prion disease (hsa05020)
  Pathways of neurodegeneration - multiple diseases (hsa05022)
  Pathogenic Escherichia coli infection (hsa05130)
  Salmonella infection (hsa05132)
• Reactome Pathway:
  Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane (R-HSA-190840)
  Gap junction assembly (R-HSA-190861)
  MHC class II antigen presentation (R-HSA-2132295)
  Separation of Sister Chromatids (R-HSA-2467813)
  Resolution of Sister Chromatid Cohesion (R-HSA-2500257)
  HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand (R-HSA-3371497)
  Recruitment of NuMA to mitotic centrosomes (R-HSA-380320)
  Prefoldin mediated transfer of substrate to CCT/TriC (R-HSA-389957)
  Formation of tubulin folding intermediates by CCT/TriC (R-HSA-389960)
  Post-chaperonin tubulin folding pathway (R-HSA-389977)
  Recycling pathway of L1 (R-HSA-437239)
  Hedgehog 'off' state (R-HSA-5610787)
  Cilium Assembly (R-HSA-5617833)
  Intraflagellar transport (R-HSA-5620924)
  RHO GTPases activate IQGAPs (R-HSA-5626467)
  RHO GTPases Activate Formins (R-HSA-5663220)
  COPI-mediated anterograde transport (R-HSA-6807878)
  COPI-dependent Golgi-to-ER retrograde traffic (R-HSA-6811434)
  COPI-independent Golgi-to-ER retrograde traffic (R-HSA-6811436)
  Mitotic Prometaphase (R-HSA-68877)
  The role of GTSE1 in G2/M progression after G2 checkpoint (R-HSA-8852276)
  Carboxyterminal post-translational modifications of tubulin (R-HSA-8955332)
  HCMV Early Events (R-HSA-9609690)
  Assembly and cell surface presentation of NMDA receptors (R-HSA-9609736)
  Activation of AMPK downstream of NMDARs (R-HSA-9619483)
  Aggrephagy (R-HSA-9646399)
  EML4 and NUDC in mitotic spindle formation (R-HSA-9648025)
  Sealing of the nuclear envelope (NE) by ESCRT-III (R-HSA-9668328)
  Kinesins (R-HSA-983189)
  PKR-mediated signaling (R-HSA-9833482)
  Translocation of SLC2A4 (GLUT4) to the plasma membrane (R-HSA-1445148)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Complex cortical dysplasia with other brain malformations 5	DISQZQ69	Definitive	Autosomal dominant	[1]
Tubulinopathy	DISB3627	Definitive	Autosomal dominant	[2]

This DOT Affected the Drug Response of 3 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Tubulin beta-2A chain affects the response to substance of Cisplatin.	[24]
Arsenic	DMTL2Y1	Approved	Tubulin beta-2A chain increases the response to substance of Arsenic.	[25]
PEITC	DMOMN31	Phase 2	Tubulin beta-2A chain affects the binding of PEITC.	[26]

1 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 beta-2A chain.	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Tubulin beta-2A chain.	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Tubulin beta-2A chain.	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Tubulin beta-2A chain.	[6]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Tubulin beta-2A chain.	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Tubulin beta-2A chain.	[8]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Tubulin beta-2A chain.	[9]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Tubulin beta-2A chain.	[10]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Tubulin beta-2A chain.	[11]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Tubulin beta-2A chain.	[12]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Tubulin beta-2A chain.	[13]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Tubulin beta-2A chain.	[14]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Tubulin beta-2A chain.	[15]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of Tubulin beta-2A chain.	[16]
Testosterone Undecanoate	DMZO10Y	Approved	Testosterone Undecanoate increases the expression of Tubulin beta-2A chain.	[17]
Bleomycin	DMNER5S	Approved	Bleomycin decreases the expression of Tubulin beta-2A chain.	[12]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Tubulin beta-2A chain.	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Tubulin beta-2A chain.	[18]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Tubulin beta-2A chain.	[19]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Tubulin beta-2A chain.	[20]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Tubulin beta-2A chain.	[21]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Tubulin beta-2A chain.	[22]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Tubulin beta-2A chain.	[23]

References

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