Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTSAE5UE)

DOT Name TNFAIP3-interacting protein 3 (TNIP3)
Synonyms A20-binding inhibitor of NF-kappa-B activation 3; ABIN-3; Listeria-induced gene protein
Gene Name TNIP3
Related Disease
Breast cancer ( )
Breast carcinoma ( )
Depression ( )
Listeriosis ( )
Major depressive disorder ( )
Kaposi sarcoma ( )
Rheumatoid arthritis ( )
UniProt ID
TNIP3_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF16516
Sequence
MAHFVQGTSRMIAAESSTEHKECAEPSTRKNLMNSLEQKIRCLEKQRKELLEVNQQWDQQ
FRSMKELYERKVAELKTKLDAAERFLSTREKDPHQRQRKDDRQREDDRQRDLTRDRLQRE
EKEKERLNEELHELKEENKLLKGKNTLANKEKEHYECEIKRLNKALQDALNIKCSFSEDC
LRKSRVEFCHEEMRTEMEVLKQQVQIYEEDFKKERSDRERLNQEKEELQQINETSQSQLN
RLNSQIKACQMEKEKLEKQLKQMYCPPCNCGLVFHLQDPWVPTGPGAVQKQREHPPDYQW
YALDQLPPDVQHKANGLSSVKKVHP
Function
Binds to zinc finger protein TNFAIP3 and inhibits NF-kappa-B activation induced by tumor necrosis factor, Toll-like receptor 4 (TLR4), interleukin-1 and 12-O-tetradecanoylphorbol-13-acetate. Overexpression inhibits NF-kappa-B-dependent gene expression in response to lipopolysaccharide at a level downstream of TRAF6 and upstream of IKBKB. NF-kappa-B inhibition is independent of TNFAIP3 binding.
Tissue Specificity
Highly expressed in lung, lymph node, thymus and fetal liver. Expressed at lower levels in bone marrow, brain, kidney, spleen, leukocytes and tonsils. Could be detected in heart, salivary gland, adrenal gland, pancreas, ovary and fetal brain. High levels detected in liver, colon, small intestine, muscle, stomach, testis, placenta, thyroid, uterus, prostate, skin and PBL.
Reactome Pathway
Ovarian tumor domain proteases (R-HSA-5689896 )

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Breast cancer DIS7DPX1 Strong Genetic Variation [1]
Breast carcinoma DIS2UE88 Strong Genetic Variation [1]
Depression DIS3XJ69 Strong Biomarker [2]
Listeriosis DISKMQBM Strong Biomarker [3]
Major depressive disorder DIS4CL3X Strong Altered Expression [2]
Kaposi sarcoma DISC1H1Z Limited Altered Expression [4]
Rheumatoid arthritis DISTSB4J Limited Biomarker [5]
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⏷ Show the Full List of 7 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
5 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of TNFAIP3-interacting protein 3 (TNIP3). [6]
Temozolomide DMKECZD Approved Temozolomide decreases the expression of TNFAIP3-interacting protein 3 (TNIP3). [7]
Zoledronate DMIXC7G Approved Zoledronate increases the expression of TNFAIP3-interacting protein 3 (TNIP3). [8]
Malathion DMXZ84M Approved Malathion increases the expression of TNFAIP3-interacting protein 3 (TNIP3). [9]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of TNFAIP3-interacting protein 3 (TNIP3). [10]
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References

1 A genome-wide scan for breast cancer risk haplotypes among African American women.PLoS One. 2013;8(2):e57298. doi: 10.1371/journal.pone.0057298. Epub 2013 Feb 28.
2 Elevated TNIP3 mRNA Expression in TNF--Secreting Cells from Patients with Major Depressive Disorder.Neuroimmunomodulation. 2019;26(3):153-158. doi: 10.1159/000501083. Epub 2019 Jul 15.
3 Two novel genes FIND and LIND differentially expressed in deactivated and Listeria-infected human macrophages.Immunogenetics. 2001 Mar;53(2):105-13. doi: 10.1007/s002510100306.
4 A20/TNFAIP3 inhibits NF-B activation induced by the Kaposi's sarcoma-associated herpesvirus vFLIP oncoprotein.Oncogene. 2013 Mar 7;32(10):1223-32. doi: 10.1038/onc.2012.145. Epub 2012 Apr 23.
5 A pro-inflammatory role for A20 and ABIN family proteins in human fibroblast-like synoviocytes in rheumatoid arthritis.Immunol Lett. 2012 Jan 30;141(2):246-53. doi: 10.1016/j.imlet.2011.10.011. Epub 2011 Nov 9.
6 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
7 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.
8 Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
9 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.
10 Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.