Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6KXSXD)

• DOT Name: FAST kinase domain-containing protein 4 (TBRG4)
• Synonyms: Cell cycle progression restoration protein 2; Cell cycle progression protein 2; Protein TBRG4; Transforming growth factor beta regulator 4
• Gene Name: TBRG4
• Related Disease: Advanced cancer
• UniProt ID: FAKD4_HUMAN
• Pfam ID: PF06743 ; PF08368 ; PF08373
• Sequence:
  MAAHLVKRCTCLLREAARQAPAMAPVGRLRLAWVAHKTLTSSATSPISHLPGSLMEPVEK
  ERASTPYIEKQVDHLIKKATRPEELLELLGGSHDLDSNQAAMVLIRLSHLLSEKPEDKGL
  LIQDAHFHQLLCLLNSQIASVWHGTLSKLLGSLYALGIPKASKELQSVEQEVRWRMRKLK
  YKHLAFLAESCATLSQEQHSQELLAELLTHLERRWTEIEDSHTLVTVMMKVGHLSEPLMN
  RLEDKCLELVEHFGPNELRKVLVMLAAQSRRSVPLLRAISYHLVQKPFSLTKDVLLDVAY
  AYGKLSFHQTQVSQRLATDLLSLMPSLTSGEVAHCAKSFALLKWLSLPLFEAFAQHVLNR
  AQDITLPHLCSVLLAFARLNFHPDQEDQFFSLVHEKLGSELPGLEPALQVDLVWALCVLQ
  QAREAELQAVLHPEFHIQFLGGKSQKDQNTFQKLLHINATALLEYPEYSGPLLPASAVAP
  GPSALDRKVTPLQKELQETLKGLLGSADKGSLEVATQYGWVLDAEVLLDSDGEFLPVRDF
  VAPHLAQPTGSQSPPPGSKRLAFLRWEFPNFNSRSKDLLGRFVLARRHIVAAGFLIVDVP
  FYEWLELKSEWQKGAYLKDKMRKAVAEELAK
• Function: Plays a role in processing of mitochondrial RNA precursors and in stabilization of a subset of mature mitochondrial RNA species, such as MT-CO1, MT-CO2, MT-CYB, MT-CO3, MT-ND3, MT-ND5 and MT-ATP8/6. May play a role in cell cycle progression.
• Tissue Specificity: Ubiquitously expressed . Expression detected in spleen, thymus, testis, ovary, colon, heart, smooth muscle, kidney, brain, lung, liver and white adipose tissue with highest expression in smooth muscle .
• Reactome Pathway: FASTK family proteins regulate processing and stability of mitochondrial RNAs (R-HSA-9837092)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]

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 FAST kinase domain-containing protein 4 (TBRG4).	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of FAST kinase domain-containing protein 4 (TBRG4).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of FAST kinase domain-containing protein 4 (TBRG4).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of FAST kinase domain-containing protein 4 (TBRG4).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of FAST kinase domain-containing protein 4 (TBRG4).	[6]
BRN-3548355	DM4KXT0	Investigative	BRN-3548355 decreases the expression of FAST kinase domain-containing protein 4 (TBRG4).	[7]

References

• [1] Knockdown of TBRG4 affects tumorigenesis in human H1299 lung cancer cells by regulating DDIT3, CAV1 and RRM2.Oncol Lett. 2018 Jan;15(1):121-128. doi: 10.3892/ol.2017.7328. Epub 2017 Nov 2.
• [2] 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.
• [3] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [4] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [5] 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.
• [6] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [7] Gene expression profiles in HPV-immortalized human cervical cells treated with the nicotine-derived carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. Chem Biol Interact. 2009 Feb 12;177(3):173-80. doi: 10.1016/j.cbi.2008.10.051. Epub 2008 Nov 6.