Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBF0X8R)

• DOT Name: Tubulin-specific chaperone C (TBCC)
• Synonyms: Tubulin-folding cofactor C; CFC
• Gene Name: TBCC
• Related Disease:
  Neoplasm
  Breast carcinoma
  Costello syndrome
  Myelodysplastic syndrome
  Psoriasis
  Acute myelogenous leukaemia
  Congenital heart disease
• UniProt ID: TBCC_HUMAN
• PDB ID: 2L3L; 2YUH
• Pfam ID: PF07986 ; PF16752
• Sequence:
  MESVSCSAAAVRTGDMESQRDLSLVPERLQRREQERQLEVERRKQKRQNQEVEKENSHFF
  VATFVRERAAVEELLERAESVERLEEAASRLQGLQKLINDSVFFLAAYDLRQGQEALARL
  QAALAERRRGLQPKKRFAFKTRGKDAASSTKVDAAPGIPPAVESIQDSPLPKKAEGDLGP
  SWVCGFSNLESQVLEKRASELHQRDVLLTELSNCTVRLYGNPNTLRLTKAHSCKLLCGPV
  STSVFLEDCSDCVLAVACQQLRIHSTKDTRIFLQVTSRAIVEDCSGIQFAPYTWSYPEID
  KDFESSGLDRSKNNWNDVDDFNWLARDMASPNWSILPEEERNIQWD
• Function: Tubulin-folding protein; involved in the final step of the tubulin folding pathway.
• Tissue Specificity: Expressed in the retina. Expressed in the rod and cone photoreceptors, extending from the inner segments (IS), through the outer nuclear layer (ONL) and into the synapses in the outer plexiform layer (OPL). Strongly expressed to the photoreceptor connecting cilium at the tips of the IS (at protein level).
• Reactome Pathway: Post-chaperonin tubulin folding pathway (R-HSA-389977)

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Definitive	Altered Expression	[1]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[2]
Costello syndrome	DISXVJH3	Strong	Biomarker	[3]
Myelodysplastic syndrome	DISYHNUI	Strong	Biomarker	[4]
Psoriasis	DIS59VMN	Strong	Genetic Variation	[5]
Acute myelogenous leukaemia	DISCSPTN	Limited	Biomarker	[6]
Congenital heart disease	DISQBA23	Limited	Genetic Variation	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Tubulin-specific chaperone C (TBCC).	[8]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Tubulin-specific chaperone C (TBCC).	[9]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Tubulin-specific chaperone C (TBCC).	[10]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Tubulin-specific chaperone C (TBCC).	[11]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Tubulin-specific chaperone C (TBCC).	[12]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Tubulin-specific chaperone C (TBCC).	[13]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Tubulin-specific chaperone C (TBCC).	[14]
Irinotecan	DMP6SC2	Approved	Irinotecan increases the expression of Tubulin-specific chaperone C (TBCC).	[15]
Urethane	DM7NSI0	Phase 4	Urethane affects the expression of Tubulin-specific chaperone C (TBCC).	[16]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Tubulin-specific chaperone C (TBCC).	[18]
EMODIN	DMAEDQG	Terminated	EMODIN decreases the expression of Tubulin-specific chaperone C (TBCC).	[19]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Tubulin-specific chaperone C (TBCC).	[20]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone increases the expression of Tubulin-specific chaperone C (TBCC).	[21]
CH-223191	DMMJZYC	Investigative	CH-223191 decreases the expression of Tubulin-specific chaperone C (TBCC).	[22]

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 affects the methylation of Tubulin-specific chaperone C (TBCC).	[17]

References

• [1] MicroRNA-1251-5p Promotes Carcinogenesis and Autophagy via Targeting the Tumor Suppressor TBCC in Ovarian Cancer Cells.Mol Ther. 2019 Sep 4;27(9):1653-1664. doi: 10.1016/j.ymthe.2019.06.005. Epub 2019 Jun 14.
• [2] Cripto-1 overexpression leads to enhanced invasiveness and resistance to anoikis in human MCF-7 breast cancer cells.J Cell Physiol. 2004 Jan;198(1):31-9. doi: 10.1002/jcp.10375.
• [3] Prenatal findings in cardio-facio-cutaneous syndrome.Am J Med Genet A. 2016 Feb;170A(2):441-445. doi: 10.1002/ajmg.a.37420. Epub 2015 Oct 22.
• [4] Reduction in multi-lineage and erythroid progenitors distinguishes myelodysplastic syndromes from non-malignant cytopenias.Leuk Res. 2009 Dec;33(12):1636-42. doi: 10.1016/j.leukres.2009.03.019. Epub 2009 May 2.
• [5] The mRNA expression and promoter methylation status of the p16 gene in colony-forming cells with high proliferative potential in patients with psoriasis.Clin Exp Dermatol. 2007 Nov;32(6):702-8. doi: 10.1111/j.1365-2230.2007.02458.x. Epub 2007 May 17.
• [6] Expression of beta-catenin by acute myeloid leukemia cells predicts enhanced clonogenic capacities and poor prognosis.Leukemia. 2006 Jul;20(7):1211-6. doi: 10.1038/sj.leu.2404239. Epub 2006 May 11.
• [7] Mutations in the EGF-CFC gene cryptic are an infrequent cause of congenital heart disease.Pediatr Cardiol. 2006 Nov-Dec;27(6):695-8. doi: 10.1007/s00246-006-1082-0. Epub 2006 Oct 27.
• [8] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [9] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [10] 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.
• [11] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [12] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [13] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [14] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [15] In vitro and in vivo irinotecan-induced changes in expression profiles of cell cycle and apoptosis-associated genes in acute myeloid leukemia cells. Mol Cancer Ther. 2005 Jun;4(6):885-900.
• [16] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [17] 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.
• [18] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [19] Gene expression alteration during redox-dependent enhancement of arsenic cytotoxicity by emodin in HeLa cells. Cell Res. 2005 Jul;15(7):511-22.
• [20] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [21] Evaluation of an in vitro model of androgen ablation and identification of the androgen responsive proteome in LNCaP cells. Proteomics. 2007 Jan;7(1):47-63.
• [22] Adaptive changes in global gene expression profile of lung carcinoma A549 cells acutely exposed to distinct types of AhR ligands. Toxicol Lett. 2018 Aug;292:162-174.