Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXTU37H)

• DOT Name: TANK-binding kinase 1-binding protein 1 (TBKBP1)
• Synonyms: TBK1-binding protein 1
• Gene Name: TBKBP1
• Related Disease:
  Lung cancer
  Lung carcinoma
  Ankylosing spondylitis
• UniProt ID: TBKB1_HUMAN
• Pfam ID: PF12845
• Sequence:
  MESMFEDDISILTQEALGPSEVWLDSPGDPSLGGDMCSASHFALITAYGDIKERLGGLER
  ENATLRRRLKVYEIKYPLISDFGEEHGFSLYEIKDGSLLEVEKVSLQQRLNQFQHELQKN
  KEQEEQLGEMIQAYEKLCVEKSDLETELREMRALVETHLRQICGLEQQLRQQQGLQDAAF
  SNLSPPPAPAPPCTDLDLHYLALRGGSGLSHAGWPGSTPSVSDLERRRLEEALEAAQGEA
  RGAQLREEQLQAECERLQGELKQLQETRAQDLASNQSERDMAWVKRVGDDQVNLALAYTE
  LTEELGRLRELSSLQGRILRTLLQEQARSGGQRHSPLSQRHSPAPQCPSPSPPARAAPPC
  PPCQSPVPQRRSPVPPCPSPQQRRSPASPSCPSPVPQRRSPVPPSCQSPSPQRRSPVPPS
  CPAPQPRPPPPPPPGERTLAERAYAKPPSHHVKAGFQGRRSYSELAEGAAYAGASPPWLQ
  AEAATLPKPRAYGSELYGPGRPLSPRRAFEGIRLRFEKQPSEEDEWAVPTSPPSPEVGTI
  RCASFCAGFPIPESPAATAYAHAEHAQSWPSINLLMETVGSDIRSCPLCQLGFPVGYPDD
  ALIKHIDSHLENSKI
• Function: Adapter protein which constitutively binds TBK1 and IKBKE playing a role in antiviral innate immunity.
• Tissue Specificity: Detected in leukocytes, lung, placenta, small intestine, liver, kidney, spleen, muscle, heart, brain and at low levels in thymus.
• KEGG Pathway: RIG-I-like receptor sig.ling pathway (hsa04622)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Lung cancer	DISCM4YA	Strong	Biomarker	[1]
Lung carcinoma	DISTR26C	Strong	Biomarker	[1]
Ankylosing spondylitis	DISRC6IR	moderate	Biomarker	[2]

2 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 TANK-binding kinase 1-binding protein 1 (TBKBP1).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of TANK-binding kinase 1-binding protein 1 (TBKBP1).	[9]

8 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 TANK-binding kinase 1-binding protein 1 (TBKBP1).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of TANK-binding kinase 1-binding protein 1 (TBKBP1).	[5]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of TANK-binding kinase 1-binding protein 1 (TBKBP1).	[6]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of TANK-binding kinase 1-binding protein 1 (TBKBP1).	[7]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of TANK-binding kinase 1-binding protein 1 (TBKBP1).	[8]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene decreases the expression of TANK-binding kinase 1-binding protein 1 (TBKBP1).	[4]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of TANK-binding kinase 1-binding protein 1 (TBKBP1).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of TANK-binding kinase 1-binding protein 1 (TBKBP1).	[11]

References

• [1] TBKBP1 and TBK1 form a growth factor signalling axis mediating immunosuppression and tumourigenesis.Nat Cell Biol. 2019 Dec;21(12):1604-1614. doi: 10.1038/s41556-019-0429-8. Epub 2019 Dec 2.
• [2] Analysis of 47 Non-MHC Ankylosing Spondylitis Susceptibility Loci Regarding Associated Variants across Whites and Han Chinese.J Rheumatol. 2020 May 1;47(5):674-681. doi: 10.3899/jrheum.190184. Epub 2019 Sep 15.
• [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] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [5] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [6] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [7] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [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] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [11] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.