Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2PZLLL)

• DOT Name: Tubulin-specific chaperone cofactor E-like protein (TBCEL)
• Synonyms: EL; Leucine-rich repeat-containing protein 35
• Gene Name: TBCEL
• Related Disease:
  Brachydactyly
  Neuroblastoma
  Retinoblastoma
  Adenocarcinoma
  Neoplasm
• UniProt ID: TBCEL_HUMAN
• Pfam ID: PF14580 ; PF14560
• Sequence:
  MDQPSGRSFMQVLCEKYSPENFPYRRGPGMGVHVPATPQGSPMKDRLNLPSVLVLNSCGI
  TCAGDEKEIAAFCAHVSELDLSDNKLEDWHEVSKIVSNVPQLEFLNLSSNPLNLSVLERT
  CAGSFSGVRKLVLNNSKASWETVHMILQELPDLEELFLCLNDYETVSCPSICCHSLKLLH
  ITDNNLQDWTEIRKLGVMFPSLDTLVLANNHLNAIEEPDDSLARLFPNLRSISLHKSGLQ
  SWEDIDKLNSFPKLEEVRLLGIPLLQPYTTEERRKLVIARLPSVSKLNGSVVTDGEREDS
  ERFFIRYYVDVPQEEVPFRYHELITKYGKLEPLAEVDLRPQSSAKVEVHFNDQVEEMSIR
  LDQTVAELKKQLKTLVQLPTSNMLLYYFDHEAPFGPEEMKYSSRALHSFGIRDGDKIYVE
  SKTK
• Function: Acts as a regulator of tubulin stability.
• Tissue Specificity: Abundantly expressed in testis, but is also present in several tissues at a much lower level.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Brachydactyly	DIS2533F	Strong	Genetic Variation	[1]
Neuroblastoma	DISVZBI4	Strong	Biomarker	[2]
Retinoblastoma	DISVPNPB	Strong	Biomarker	[2]
Adenocarcinoma	DIS3IHTY	moderate	Altered Expression	[3]
Neoplasm	DISZKGEW	Limited	Altered Expression	[4]

5 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-specific chaperone cofactor E-like protein (TBCEL).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Tubulin-specific chaperone cofactor E-like protein (TBCEL).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Tubulin-specific chaperone cofactor E-like protein (TBCEL).	[7]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Tubulin-specific chaperone cofactor E-like protein (TBCEL).	[10]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Tubulin-specific chaperone cofactor E-like protein (TBCEL).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Tubulin-specific chaperone cofactor E-like protein (TBCEL).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Tubulin-specific chaperone cofactor E-like protein (TBCEL).	[9]

References

• [1] Spondyloperipheral dysplasia is caused by truncating mutations in the C-propeptide of COL2A1. Am J Med Genet A. 2004 Aug 30;129A(2):144-8. doi: 10.1002/ajmg.a.30222.
• [2] Disabled-1 alternative splicing in human fetal retina and neural tumors.PLoS One. 2011;6(12):e28579. doi: 10.1371/journal.pone.0028579. Epub 2011 Dec 6.
• [3] Antibody GD3G7 selected against embryonic glycosaminoglycans defines chondroitin sulfate-E domains highly up-regulated in ovarian cancer and involved in vascular endothelial growth factor binding.Am J Pathol. 2007 Oct;171(4):1324-33. doi: 10.2353/ajpath.2007.070111. Epub 2007 Aug 23.
• [4] A spontaneous sarcoma dependent on host tumor-specific immune lymphocytes.Bioessays. 1989 Dec;11(6):181-5. doi: 10.1002/bies.950110606.
• [5] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [6] 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.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [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] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [11] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.