Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1GMBOX)

• DOT Name: Tektin-4 (TEKT4)
• Gene Name: TEKT4
• Related Disease:
  Thyroid gland papillary carcinoma
  Breast cancer
  Breast carcinoma
• UniProt ID: TEKT4_HUMAN
• PDB ID: 7UNG
• Pfam ID: PF03148
• Sequence:
  MAQTVPPCELPCKEYDVARNTGAYTSSGLATASFRTSKYLLEEWFQNCYARYHQAFADRD
  QSERQRHESQQLATETQALAQRTQQDSTRTVGERLQDTHSWKSELQREMEALAAETNLLL
  AQKQRLERALDATEVPFSITTDNLQCRERREHPNLVRDHVETELLKEAELIRNIQELLKR
  TIMQAVSQIRLNREHKETCEMDWSDKMEAYNIDETCGRHHSQSTEVQAHPYSTTFQESAS
  TPETRAKFTQDNLCRAQRERLASANLRVLVDCILRDTSEDLRLQCDAVNLAFGRRCEELE
  DARYKLHHHLHKTLREITDQEHNVAALKQAIKDKEAPLHVAQTRLYLRSHRPNMELCRDA
  AQFRLLSEVEELNMSLTALREKLLEAEQSLRNLEDIHMSLEKDIAAMTNSLFIDRQKCMA
  HRTRYPTILQLAGYQ
• Function: Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia and flagellar axoneme. Forms filamentous polymers in the walls of ciliary and flagellar microtubules. Contributes to normal sperm motility.
• Tissue Specificity: Strongly expressed in spermatozoa. Also detected at low levels in pancreas. Expressed in airway epithelial cells .

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Thyroid gland papillary carcinoma	DIS48YMM	Definitive	Biomarker	[1]
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[2]
Breast carcinoma	DIS2UE88	Limited	Genetic Variation	[2]

1 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 Tektin-4 (TEKT4).	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Tektin-4 (TEKT4).	[4]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Tektin-4 (TEKT4).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Tektin-4 (TEKT4).	[6]

References

• [1] TEKT4 Promotes Papillary Thyroid Cancer Cell Proliferation, Colony Formation, and Metastasis through Activating PI3K/Akt Pathway.Endocr Pathol. 2018 Dec;29(4):310-316. doi: 10.1007/s12022-018-9549-0.
• [2] Enriched variations in TEKT4 and breast cancer resistance to paclitaxel.Nat Commun. 2014 May 13;5:3802. doi: 10.1038/ncomms4802.
• [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] 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.
• [5] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [6] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.