Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWDBVZ4)

• DOT Name: Tubulin alpha-4A chain
• Synonyms: EC 3.6.5.-; Alpha-tubulin 1; Testis-specific alpha-tubulin; Tubulin H2-alpha; Tubulin alpha-1 chain
• Gene Name: TUBA4A
• Related Disease:
  Amyotrophic lateral sclerosis type 22
  Autosomal dominant macrothrombocytopenia
• UniProt ID: TBA4A_HUMAN
• EC Number: 3.6.5.-
• Pfam ID: PF00091 ; PF03953
• Sequence:
  MRECISVHVGQAGVQMGNACWELYCLEHGIQPDGQMPSDKTIGGGDDSFTTFFCETGAGK
  HVPRAVFVDLEPTVIDEIRNGPYRQLFHPEQLITGKEDAANNYARGHYTIGKEIIDPVLD
  RIRKLSDQCTGLQGFLVFHSFGGGTGSGFTSLLMERLSVDYGKKSKLEFSIYPAPQVSTA
  VVEPYNSILTTHTTLEHSDCAFMVDNEAIYDICRRNLDIERPTYTNLNRLISQIVSSITA
  SLRFDGALNVDLTEFQTNLVPYPRIHFPLATYAPVISAEKAYHEQLSVAEITNACFEPAN
  QMVKCDPRHGKYMACCLLYRGDVVPKDVNAAIAAIKTKRSIQFVDWCPTGFKVGINYQPP
  TVVPGGDLAKVQRAVCMLSNTTAIAEAWARLDHKFDLMYAKRAFVHWYVGEGMEEGEFSE
  AREDMAALEKDYEEVGIDSYEDEDEGEE
• 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.
• KEGG Pathway:
  Phagosome (hsa04145)
  Apoptosis (hsa04210)
  Tight junction (hsa04530)
  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:
  Translocation of SLC2A4 (GLUT4) to the plasma membrane (R-HSA-1445148)
  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)
  Regulation of PLK1 Activity at G2/M Transition (R-HSA-2565942)
  HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand (R-HSA-3371497)
  Loss of Nlp from mitotic centrosomes (R-HSA-380259)
  Recruitment of mitotic centrosome proteins and complexes (R-HSA-380270)
  Loss of proteins required for interphase microtubule organization from the centrosome (R-HSA-380284)
  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)
  Anchoring of the basal body to the plasma membrane (R-HSA-5620912)
  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)
  AURKA Activation by TPX2 (R-HSA-8854518)
  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)
  Platelet degranulation (R-HSA-114608)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Amyotrophic lateral sclerosis type 22	DISACI32	Moderate	Autosomal dominant	[1]
Autosomal dominant macrothrombocytopenia	DISUTMSW	Limited	Autosomal dominant	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PEITC	DMOMN31	Phase 2	Tubulin alpha-4A chain affects the binding of PEITC.	[29]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Tubulin alpha-4A chain.	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Tubulin alpha-4A chain.	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Tubulin alpha-4A chain.	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Tubulin alpha-4A chain.	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Tubulin alpha-4A chain.	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Tubulin alpha-4A chain.	[7]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Tubulin alpha-4A chain.	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Tubulin alpha-4A chain.	[9]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Tubulin alpha-4A chain.	[11]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Tubulin alpha-4A chain.	[12]
Selenium	DM25CGV	Approved	Selenium increases the expression of Tubulin alpha-4A chain.	[13]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Tubulin alpha-4A chain.	[14]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Tubulin alpha-4A chain.	[15]
Etoposide	DMNH3PG	Approved	Etoposide increases the expression of Tubulin alpha-4A chain.	[16]
Nicotine	DMWX5CO	Approved	Nicotine decreases the expression of Tubulin alpha-4A chain.	[17]
Cocaine	DMSOX7I	Approved	Cocaine decreases the expression of Tubulin alpha-4A chain.	[18]
Cyclophosphamide	DM4O2Z7	Approved	Cyclophosphamide increases the expression of Tubulin alpha-4A chain.	[16]
Dactinomycin	DM2YGNW	Approved	Dactinomycin increases the expression of Tubulin alpha-4A chain.	[16]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene affects the expression of Tubulin alpha-4A chain.	[19]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Tubulin alpha-4A chain.	[20]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Tubulin alpha-4A chain.	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Tubulin alpha-4A chain.	[21]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Tubulin alpha-4A chain.	[22]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Tubulin alpha-4A chain.	[24]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Tubulin alpha-4A chain.	[25]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Tubulin alpha-4A chain.	[26]
Resorcinol	DMM37C0	Investigative	Resorcinol increases the expression of Tubulin alpha-4A chain.	[27]
CH-223191	DMMJZYC	Investigative	CH-223191 decreases the expression of Tubulin alpha-4A chain.	[28]

2 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 alpha-4A chain.	[10]
PMID29671355-Compound-23	DMUBOEX	Patented	PMID29671355-Compound-23 increases the acetylation of Tubulin alpha-4A chain.	[23]

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