Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHSBS1B)

• DOT Name: Tumor necrosis factor alpha-induced protein 8-like protein 3 (TNFAIP8L3)
• Synonyms: TNF alpha-induced protein 8-like protein 3; TNFAIP8-like protein 3
• Gene Name: TNFAIP8L3
• Related Disease:
  Adult glioblastoma
  Glioblastoma multiforme
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Ductal breast carcinoma in situ
  Invasive ductal breast carcinoma
  Lung cancer
  Lung carcinoma
  Neoplasm
  Non-small-cell lung cancer
  Nasopharyngeal carcinoma
• UniProt ID: TP8L3_HUMAN
• PDB ID: 4Q9V
• Pfam ID: PF05527
• Sequence:
  MGKPRQNPSTLVSTLCEAEPKGKLWVNGYAGTQGTRDATLQTRLIPLSFHLQRGKGLAAP
  LSALSAPRLPERPADGRVAVDAQPAARSMDSDSGEQSEGEPVTAAGPDVFSSKSLALQAQ
  KKILSKIASKTVANMLIDDTSSEIFDELYKVTKEHTHNKKEAHKIMKDLIKVAIKIGILY
  RNNQFSQEELVIVEKFRKKLNQTAMTIVSFYEVEYTFDRNVLSNLLHECKDLVHELVQRH
  LTPRTHGRINHVFNHFADVEFLSTLYSLDGDCRPNLKRICEGINKLLDEKVL
• Function: Acts as a lipid transfer protein. Preferentially captures and shuttles two lipid second messengers, i.e., phosphatidylinositol 4,5- bisphosphate and phosphatidylinositol 3,4,5-trisphosphate and increases their levels in the plasma membrane. Additionally, may also function as a lipid-presenting protein to enhance the activity of the PI3K-AKT and MEK-ERK pathways. May act as a regulator of tumorigenesis through its activation of phospholipid signaling.
• Tissue Specificity: Widely expressed (at protein level) . Highly expressed in most carcinoma cell lines .
• Reactome Pathway: PI Metabolism (R-HSA-1483255)

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult glioblastoma	DISVP4LU	Definitive	Biomarker	[1]
Glioblastoma multiforme	DISK8246	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Breast cancer	DIS7DPX1	Strong	Biomarker	[2]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[2]
Ductal breast carcinoma in situ	DISLCJY7	Strong	Altered Expression	[2]
Invasive ductal breast carcinoma	DIS43J58	Strong	Altered Expression	[2]
Lung cancer	DISCM4YA	Strong	Biomarker	[3]
Lung carcinoma	DISTR26C	Strong	Biomarker	[3]
Neoplasm	DISZKGEW	Strong	Altered Expression	[3]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[3]
Nasopharyngeal carcinoma	DISAOTQ0	Limited	Altered Expression	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Tumor necrosis factor alpha-induced protein 8-like protein 3 (TNFAIP8L3).	[5]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Tumor necrosis factor alpha-induced protein 8-like protein 3 (TNFAIP8L3).	[6]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Tumor necrosis factor alpha-induced protein 8-like protein 3 (TNFAIP8L3).	[7]
Malathion	DMXZ84M	Approved	Malathion decreases the expression of Tumor necrosis factor alpha-induced protein 8-like protein 3 (TNFAIP8L3).	[8]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Tumor necrosis factor alpha-induced protein 8-like protein 3 (TNFAIP8L3).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Tumor necrosis factor alpha-induced protein 8-like protein 3 (TNFAIP8L3).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Tumor necrosis factor alpha-induced protein 8-like protein 3 (TNFAIP8L3).	[11]

References

• [1] TIPE3 is a regulator of cell apoptosis in glioblastoma.Cancer Lett. 2019 Apr 1;446:1-14. doi: 10.1016/j.canlet.2018.12.019. Epub 2019 Jan 11.
• [2] TIPE3 protein promotes breast cancer metastasis through activating AKT and NF-B signaling pathways.Oncotarget. 2017 Jul 25;8(30):48889-48904. doi: 10.18632/oncotarget.16522.
• [3] TIPE3 differentially modulates proliferation and migration of human non-small-cell lung cancer cells via distinct subcellular location.BMC Cancer. 2018 Mar 6;18(1):260. doi: 10.1186/s12885-018-4177-0.
• [4] TIPE3 hypermethylation correlates with worse prognosis and promotes tumor progression in nasopharyngeal carcinoma.J Exp Clin Cancer Res. 2018 Sep 14;37(1):227. doi: 10.1186/s13046-018-0881-5.
• [5] 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.
• [6] 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.
• [7] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [8] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [11] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.