Details of Drug Off-Target (DOT)

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

DOT Name	Tubulin alpha-1A chain
Synonyms	EC 3.6.5.-; Alpha-tubulin 3; Tubulin B-alpha-1; Tubulin alpha-3 chain
Gene Name	TUBA1A
Related Disease	Intellectual disability, autosomal dominant 40 ( ) Lissencephaly due to TUBA1A mutation ( ) Tubulinopathy ( ) Tubulinopathy-associated dysgyria ( )
UniProt ID	TBA1A_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	5JCO; 6J8F; 6WSL; 7C1M; 7UN1; 7UNG; 8J07
EC Number	3.6.5.-
Pfam ID	PF00091 ; PF03953
Sequence	MRECISIHVGQAGVQIGNACWELYCLEHGIQPDGQMPSDKTIGGGDDSFNTFFSETGAGK HVPRAVFVDLEPTVIDEVRTGTYRQLFHPEQLITGKEDAANNYARGHYTIGKEIIDLVLD RIRKLADQCTGLQGFLVFHSFGGGTGSGFTSLLMERLSVDYGKKSKLEFSIYPAPQVSTA VVEPYNSILTTHTTLEHSDCAFMVDNEAIYDICRRNLDIERPTYTNLNRLIGQIVSSITA SLRFDGALNVDLTEFQTNLVPYPRIHFPLATYAPVISAEKAYHEQLSVAEITNACFEPAN QMVKCDPRHGKYMACCLLYRGDVVPKDVNAAIATIKTKRTIQFVDWCPTGFKVGINYQPP TVVPGGDLAKVQRAVCMLSNTTAIAEAWARLDHKFDLMYAKRAFVHWYVGEGMEEGEFSE AREDMAALEKDYEEVGVDSVEGEGEEEGEEY
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	Expressed at a high level in fetal brain.
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	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 ) 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
Intellectual disability, autosomal dominant 40	DISAI0IH	Definitive	Autosomal dominant	[1]
Lissencephaly due to TUBA1A mutation	DIS1GSO6	Definitive	Autosomal dominant	[2]
Tubulinopathy	DISB3627	Definitive	Autosomal dominant	[3]
Tubulinopathy-associated dysgyria	DISXIWVG	Supportive	Autosomal dominant	[4]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
PEITC	DMOMN31	Phase 2	Tubulin alpha-1A chain affects the binding of PEITC.	[36]
Sulforaphane	DMQY3L0	Investigative	Tubulin alpha-1A chain affects the binding of Sulforaphane.	[36]
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33 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Tubulin alpha-1A chain.	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Tubulin alpha-1A chain.	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Tubulin alpha-1A chain.	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Tubulin alpha-1A chain.	[8]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Tubulin alpha-1A chain.	[9]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Tubulin alpha-1A chain.	[10]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Tubulin alpha-1A chain.	[12]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Tubulin alpha-1A chain.	[13]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Tubulin alpha-1A chain.	[14]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Tubulin alpha-1A chain.	[15]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Tubulin alpha-1A chain.	[16]
Menadione	DMSJDTY	Approved	Menadione decreases the expression of Tubulin alpha-1A chain.	[13]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Tubulin alpha-1A chain.	[17]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Tubulin alpha-1A chain.	[18]
Aspirin	DM672AH	Approved	Aspirin decreases the expression of Tubulin alpha-1A chain.	[19]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Tubulin alpha-1A chain.	[15]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Tubulin alpha-1A chain.	[20]
Etretinate	DM2CZFA	Approved	Etretinate decreases the expression of Tubulin alpha-1A chain.	[22]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Tubulin alpha-1A chain.	[23]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Tubulin alpha-1A chain.	[25]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Tubulin alpha-1A chain.	[26]
AMEP	DMFELMQ	Phase 1	AMEP decreases the expression of Tubulin alpha-1A chain.	[27]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Tubulin alpha-1A chain.	[28]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Tubulin alpha-1A chain.	[29]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Tubulin alpha-1A chain.	[30]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Tubulin alpha-1A chain.	[31]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Tubulin alpha-1A chain.	[17]
chloropicrin	DMSGBQA	Investigative	chloropicrin affects the expression of Tubulin alpha-1A chain.	[32]
Glyphosate	DM0AFY7	Investigative	Glyphosate decreases the expression of Tubulin alpha-1A chain.	[27]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of Tubulin alpha-1A chain.	[33]
OXYQUINOLINE	DMZVS9Y	Investigative	OXYQUINOLINE decreases the expression of Tubulin alpha-1A chain.	[12]
AHPN	DM8G6O4	Investigative	AHPN decreases the expression of Tubulin alpha-1A chain.	[34]
Cordycepin	DM72Y01	Investigative	Cordycepin decreases the expression of Tubulin alpha-1A chain.	[35]
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⏷ Show the Full List of 33 Drug(s)

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic increases the ubiquitination of Tubulin alpha-1A chain.	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Tubulin alpha-1A chain.	[24]
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1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Dihydroartemisinin	DMBXVMZ	Approved	Dihydroartemisinin affects the binding of Tubulin alpha-1A chain.	[21]
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