Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTONRBL7)

• DOT Name: Tubulin alpha chain-like 3
• Synonyms: EC 3.6.5.-
• Gene Name: TUBAL3
• Related Disease: Complex neurodevelopmental disorder
• UniProt ID: TBAL3_HUMAN
• EC Number: 3.6.5.-
• Pfam ID: PF00091 ; PF03953
• Sequence:
  MRECLSIHIGQAGIQIGDACWELYCLEHGIQPNGVVLDTQQDQLENAKMEHTNASFDTFF
  CETRAGKHVPRALFVDLEPTVIDGIRTGQHRSLFHPEQLLSGKEDAANNYARGRYSVGSE
  VIDLVLERTRKLAEQCGGLQGFLIFRSFGGGTGSGFTSLLMERLTGEYSRKTKLEFSVYP
  APRISTAVVEPYNSVLTTHSTTEHTDCTFMVDNEAVYDICHRKLGVECPSHASINRLVVQ
  VVSSITASLRFEGPLNVDLIEFQTNLVPYPRIHFPMTAFAPIVSADKAYHEQFSVSDITT
  ACFESSNQLVKCDPRLGKYMACCLLYRGDVVPKEVNAAIAATKSRHSVQFVDWCPTGFKV
  GINNRPPTVMPGGDLAKVHRSICMLSNTTAIVEAWARLDHKFDLMYAKRAFLHWYLREGM
  EEAEFLEAREDLAALERDYEEVAQSF
• 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:
  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)
  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)
  Cilium Assembly (R-HSA-5617833)
  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

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Complex neurodevelopmental disorder	DISB9AFI	Limited	Autosomal recessive	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Tubulin alpha chain-like 3.	[2]
Clozapine	DMFC71L	Approved	Clozapine increases the expression of Tubulin alpha chain-like 3.	[3]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate increases the expression of Tubulin alpha chain-like 3.	[4]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the expression of Tubulin alpha chain-like 3.	[4]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Tubulin alpha chain-like 3.	[6]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Tubulin alpha chain-like 3.	[7]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Tubulin alpha chain-like 3.	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Tubulin alpha chain-like 3.	[5]

References

• [1] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [2] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [3] Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
• [4] Comparative proteomics reveals concordant and discordant biochemical effects of caffeine versus epigallocatechin-3-gallate in human endothelial cells. Toxicol Appl Pharmacol. 2019 Sep 1;378:114621. doi: 10.1016/j.taap.2019.114621. Epub 2019 Jun 10.
• [5] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [6] Comparison of transcriptome expression alterations by chronic exposure to low-dose bisphenol A in different subtypes of breast cancer cells. Toxicol Appl Pharmacol. 2019 Dec 15;385:114814. doi: 10.1016/j.taap.2019.114814. Epub 2019 Nov 9.
• [7] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.
• [8] Probiotic Bacillus subtilis CW14 reduces disruption of the epithelial barrier and toxicity of ochratoxin A to Caco-2?cells. Food Chem Toxicol. 2019 Apr;126:25-33. doi: 10.1016/j.fct.2019.02.009. Epub 2019 Feb 11.