Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTI95VOO)

• DOT Name: Tubulin beta-3 chain
• Synonyms: Tubulin beta-4 chain; Tubulin beta-III
• Gene Name: TUBB3
• Related Disease:
  Complex cortical dysplasia with other brain malformations 1
  Fibrosis of extraocular muscles, congenital, 3A, with or without extraocular involvement
  Congenital fibrosis of extraocular muscles
  Tubulinopathy-associated dysgyria
• UniProt ID: TBB3_HUMAN
• PDB ID: 5IJ0; 5IJ9; 5JCO; 6E7B; 6S8L; 6WSL; 7LXB; 7M18; 7M20; 7PJF; 7SJ7; 7SJ8; 7SJ9; 7SJA; 7Z6S
• Pfam ID: PF00091 ; PF03953
• Sequence:
  MREIVHIQAGQCGNQIGAKFWEVISDEHGIDPSGNYVGDSDLQLERISVYYNEASSHKYV
  PRAILVDLEPGTMDSVRSGAFGHLFRPDNFIFGQSGAGNNWAKGHYTEGAELVDSVLDVV
  RKECENCDCLQGFQLTHSLGGGTGSGMGTLLISKVREEYPDRIMNTFSVVPSPKVSDTVV
  EPYNATLSIHQLVENTDETYCIDNEALYDICFRTLKLATPTYGDLNHLVSATMSGVTTSL
  RFPGQLNADLRKLAVNMVPFPRLHFFMPGFAPLTARGSQQYRALTVPELTQQMFDAKNMM
  AACDPRHGRYLTVATVFRGRMSMKEVDEQMLAIQSKNSSYFVEWIPNNVKVAVCDIPPRG
  LKMSSTFIGNSTAIQELFKRISEQFTAMFRRKAFLHWYTGEGMDEMEFTEAESNMNDLVS
  EYQQYQDATAEEEGEMYEDDEEESEAQGPK
• 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. TUBB3 plays a critical role in proper axon guidance and maintenance. Binding of NTN1/Netrin-1 to its receptor UNC5C might cause dissociation of UNC5C from polymerized TUBB3 in microtubules and thereby lead to increased microtubule dynamics and axon repulsion. Plays a role in dorsal root ganglion axon projection towards the spinal cord.
• Tissue Specificity: Expression is primarily restricted to central and peripheral nervous system. Greatly increased expression in most cancerous tissues.
• 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

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Complex cortical dysplasia with other brain malformations 1	DISOP2YQ	Strong	Autosomal dominant	[1]
Fibrosis of extraocular muscles, congenital, 3A, with or without extraocular involvement	DISPG5B0	Strong	Autosomal dominant	[2]
Congenital fibrosis of extraocular muscles	DISE84PU	Supportive	Autosomal dominant	[3]
Tubulinopathy-associated dysgyria	DISXIWVG	Supportive	Autosomal dominant	[4]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
PEITC	DMOMN31	Phase 2	Tubulin beta-3 chain affects the binding of PEITC.	[33]

2 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-3 chain.	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Tubulin beta-3 chain.	[22]

30 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-3 chain.	[6]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Tubulin beta-3 chain.	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Tubulin beta-3 chain.	[8]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Tubulin beta-3 chain.	[9]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Tubulin beta-3 chain.	[10]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Tubulin beta-3 chain.	[11]
Carbamazepine	DMZOLBI	Approved	Carbamazepine decreases the expression of Tubulin beta-3 chain.	[12]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Tubulin beta-3 chain.	[13]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Tubulin beta-3 chain.	[14]
Selenium	DM25CGV	Approved	Selenium increases the expression of Tubulin beta-3 chain.	[15]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Tubulin beta-3 chain.	[16]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Tubulin beta-3 chain.	[17]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Tubulin beta-3 chain.	[18]
Alitretinoin	DMME8LH	Approved	Alitretinoin decreases the expression of Tubulin beta-3 chain.	[7]
Sodium phenylbutyrate	DMXLBCQ	Approved	Sodium phenylbutyrate affects the expression of Tubulin beta-3 chain.	[13]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Tubulin beta-3 chain.	[19]
Fenretinide	DMRD5SP	Phase 3	Fenretinide increases the expression of Tubulin beta-3 chain.	[20]
Seocalcitol	DMKL9QO	Phase 3	Seocalcitol increases the expression of Tubulin beta-3 chain.	[21]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Tubulin beta-3 chain.	[15]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Tubulin beta-3 chain.	[23]
AMEP	DMFELMQ	Phase 1	AMEP decreases the expression of Tubulin beta-3 chain.	[24]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Tubulin beta-3 chain.	[25]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Tubulin beta-3 chain.	[26]
UNC0379	DMD1E4J	Preclinical	UNC0379 increases the expression of Tubulin beta-3 chain.	[27]
EMODIN	DMAEDQG	Terminated	EMODIN decreases the expression of Tubulin beta-3 chain.	[28]
WIN-55212-2	DMACBIW	Terminated	WIN-55212-2 decreases the expression of Tubulin beta-3 chain.	[29]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Tubulin beta-3 chain.	[30]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Tubulin beta-3 chain.	[31]
Glyphosate	DM0AFY7	Investigative	Glyphosate decreases the expression of Tubulin beta-3 chain.	[24]
Forskolin	DM6ITNG	Investigative	Forskolin increases the expression of Tubulin beta-3 chain.	[32]

References

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