Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHZGAC4)

• DOT Name: Tubulin-folding cofactor B (TBCB)
• Synonyms: Cytoskeleton-associated protein 1; Cytoskeleton-associated protein CKAPI; Tubulin-specific chaperone B
• Gene Name: TBCB
• Related Disease:
  Schizophrenia
  Amyotrophic lateral sclerosis
• UniProt ID: TBCB_HUMAN
• Pfam ID: PF01302 ; PF14560
• Sequence:
  MEVTGVSAPTVTVFISSSLNTFRSEKRYSRSLTIAEFKCKLELLVGSPASCMELELYGVD
  DKFYSKLDQEDALLGSYPVDDGCRIHVIDHSGARLGEYEDVSRVEKYTISQEAYDQRQDT
  VRSFLKRSKLGRYNEEERAQQEAEAAQRLAEEKAQASSIPVGSRCEVRAAGQSPRRGTVM
  YVGLTDFKPGYWIGVRYDEPLGKNDGSVNGKRYFECQAKYGAFVKPAVVTVGDFPEEDYG
  LDEI
• Function: Binds to alpha-tubulin folding intermediates after their interaction with cytosolic chaperonin in the pathway leading from newly synthesized tubulin to properly folded heterodimer. Involved in regulation of tubulin heterodimer dissociation. May function as a negative regulator of axonal growth.
• Tissue Specificity: Found in most tissues.
• Reactome Pathway: Post-chaperonin tubulin folding pathway (R-HSA-389977)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Schizophrenia	DISSRV2N	Strong	Altered Expression	[1]
Amyotrophic lateral sclerosis	DISF7HVM	Limited	Biomarker	[2]

3 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-folding cofactor B (TBCB).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Tubulin-folding cofactor B (TBCB).	[9]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Tubulin-folding cofactor B (TBCB).	[10]

8 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-folding cofactor B (TBCB).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Tubulin-folding cofactor B (TBCB).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Tubulin-folding cofactor B (TBCB).	[6]
Selenium	DM25CGV	Approved	Selenium increases the expression of Tubulin-folding cofactor B (TBCB).	[7]
Benzatropine	DMF7EXL	Approved	Benzatropine decreases the expression of Tubulin-folding cofactor B (TBCB).	[8]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Tubulin-folding cofactor B (TBCB).	[7]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Tubulin-folding cofactor B (TBCB).	[11]
GALLICACID	DM6Y3A0	Investigative	GALLICACID decreases the expression of Tubulin-folding cofactor B (TBCB).	[12]

References

• [1] Prefrontal cortex shotgun proteome analysis reveals altered calcium homeostasis and immune system imbalance in schizophrenia.Eur Arch Psychiatry Clin Neurosci. 2009 Apr;259(3):151-63. doi: 10.1007/s00406-008-0847-2. Epub 2009 Jan 22.
• [2] Dysregulation of a novel miR-1825/TBCB/TUBA4A pathway in sporadic and familial ALS.Cell Mol Life Sci. 2018 Dec;75(23):4301-4319. doi: 10.1007/s00018-018-2873-1. Epub 2018 Jul 20.
• [3] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [4] Cyclosporine A--induced oxidative stress in human renal mesangial cells: a role for ERK 1/2 MAPK signaling. Toxicol Sci. 2012 Mar;126(1):101-13.
• [5] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [6] 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.
• [7] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [8] 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.
• [9] 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.
• [10] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [11] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
• [12] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.