Details of Drug Off-Target (DOT)

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

• DOT Name: TNFAIP3-interacting protein 1 (TNIP1)
• Synonyms: A20-binding inhibitor of NF-kappa-B activation 1; ABIN-1; HIV-1 Nef-interacting protein; Nef-associated factor 1; Naf1; Nip40-1; Virion-associated nuclear shuttling protein; VAN; hVAN
• Gene Name: TNIP1
• Related Disease:
  Myasthenia gravis
  Amyotrophic lateral sclerosis
  Arthritis
  Asthma
  Atopic dermatitis
  B-cell lymphoma
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Carcinoma of esophagus
  Depression
  Esophageal cancer
  Glioma
  Glomerulonephritis
  Haematological malignancy
  Immune system disorder
  Inflammatory bowel disease
  Lymphoma, non-Hodgkin, familial
  Multiple sclerosis
  Myositis disease
  Neoplasm
  Neoplasm of esophagus
  Non-hodgkin lymphoma
  Palmoplantar pustulosis
  Prostate cancer
  Prostate carcinoma
  Psoriatic arthritis
  Rheumatoid arthritis
  Skin disease
  Stomach cancer
  Type-1/2 diabetes
  Autoimmune disease
  Chronic renal failure
  End-stage renal disease
  Endocarditis
  Pancreatic cancer
  Chronic hepatitis B virus infection
  Clear cell renal carcinoma
  Coronary heart disease
  Crohn disease
  Hepatitis B virus infection
  Hepatocellular carcinoma
  Kaposi sarcoma
  Lupus nephritis
  Malignant pleural mesothelioma
  Neuroblastoma
  Renal cell carcinoma
  Sclerosing cholangitis
  Ulcerative colitis
• UniProt ID: TNIP1_HUMAN
• PDB ID: 7EAL; 7EAO; 7EB9
• Sequence:
  MEGRGPYRIYDPGGSVPSGEASAAFERLVKENSRLKEKMQGIKMLGELLEESQMEATRLR
  QKAEELVKDNELLPPPSPSLGSFDPLAELTGKDSNVTASPTAPACPSDKPAPVQKPPSSG
  TSSEFEVVTPEEQNSPESSSHANAMALGPLPREDGNLMLHLQRLETTLSVCAEEPDHGQL
  FTHLGRMALEFNRLASKVHKNEQRTSILQTLCEQLRKENEALKAKLDKGLEQRDQAAERL
  REENLELKKLLMSNGNKEGASGRPGSPKMEGTGKKAVAGQQQASVTAGKVPEVVALGAAE
  KKVKMLEQQRSELLEVNKQWDQHFRSMKQQYEQKITELRQKLADLQKQVTDLEAEREQKQ
  RDFDRKLLLAKSKIEMEETDKEQLTAEAKELRQKVKYLQDQLSPLTRQREYQEKEIQRLN
  KALEEALSIQTPPSSPPTAFGSPEGAGALLRKQELVTQNELLKQQVKIFEEDFQRERSDR
  ERMNEEKEELKKQVEKLQAQVTLSNAQLKAFKDEEKAREALRQQKRKAKASGERYHVEPH
  PEHLCGAYPYAYPPMPAMVPHHGFEDWSQIRYPPPPMAMEHPPPLPNSRLFHLPEYTWRL
  PCGGVRNPNQSSQVMDPPTARPTEPESPKNDREGPQ
• Function: Inhibits NF-kappa-B activation and TNF-induced NF-kappa-B-dependent gene expression by regulating TAX1BP1 and A20/TNFAIP3-mediated deubiquitination of IKBKG; proposed to link A20/TNFAIP3 to ubiquitinated IKBKG. Involved in regulation of EGF-induced ERK1/ERK2 signaling pathway; blocks MAPK3/MAPK1 nuclear translocation and MAPK1-dependent transcription. Increases cell surface CD4(T4) antigen expression. Involved in the anti-inflammatory response of macrophages and positively regulates TLR-induced activation of CEBPB. Involved in the prevention of autoimmunity; this function implicates binding to polyubiquitin. Involved in leukocyte integrin activation during inflammation; this function is mediated by association with SELPLG and dependent on phosphorylation by SRC-family kinases. Interacts with HIV-1 matrix protein and is packaged into virions and overexpression can inhibit viral replication. May regulate matrix nuclear localization, both nuclear import of PIC (Preintegration complex) and export of GAG polyprotein and viral genomic RNA during virion production. In case of infection, promotes association of IKBKG with Shigella flexneri E3 ubiquitin-protein ligase ipah9.8 p which in turn promotes polyubiquitination of IKBKG leading to its proteasome-dependent degradation and thus is perturbing NF-kappa-B activation during bacterial infection.
• Tissue Specificity: Ubiquitous. Strongly expressed in peripheral blood lymphocytes, spleen and skeletal muscle, and is weakly expressed in the brain. In peripheral blood mononucleocytes, isoform 4 is mainly expressed and isoform 1 and isoform 7 are almost not expressed. Expression of isoform 1 and isoform 7 increases in leukemic cells.
• KEGG Pathway: Shigellosis (hsa05131)
• Reactome Pathway: Ovarian tumor domain proteases (R-HSA-5689896)

Molecular Interaction Atlas (MIA) of This DOT

49 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Myasthenia gravis	DISELRCI	Definitive	Genetic Variation	[1]
Amyotrophic lateral sclerosis	DISF7HVM	Strong	Genetic Variation	[2]
Arthritis	DIST1YEL	Strong	Genetic Variation	[3]
Asthma	DISW9QNS	Strong	Biomarker	[4]
Atopic dermatitis	DISTCP41	Strong	Genetic Variation	[5]
B-cell lymphoma	DISIH1YQ	Strong	Biomarker	[6]
Breast cancer	DIS7DPX1	Strong	Biomarker	[7]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[7]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[8]
Carcinoma of esophagus	DISS6G4D	Strong	Genetic Variation	[9]
Depression	DIS3XJ69	Strong	Altered Expression	[10]
Esophageal cancer	DISGB2VN	Strong	Genetic Variation	[9]
Glioma	DIS5RPEH	Strong	Altered Expression	[11]
Glomerulonephritis	DISPZIQ3	Strong	Biomarker	[12]
Haematological malignancy	DISCDP7W	Strong	Genetic Variation	[13]
Immune system disorder	DISAEGPH	Strong	Biomarker	[11]
Inflammatory bowel disease	DISGN23E	Strong	Biomarker	[14]
Lymphoma, non-Hodgkin, familial	DISCXYIZ	Strong	Altered Expression	[15]
Multiple sclerosis	DISB2WZI	Strong	Genetic Variation	[16]
Myositis disease	DISCIXF0	Strong	Genetic Variation	[17]
Neoplasm	DISZKGEW	Strong	Biomarker	[18]
Neoplasm of esophagus	DISOLKAQ	Strong	Genetic Variation	[9]
Non-hodgkin lymphoma	DISS2Y8A	Strong	Altered Expression	[15]
Palmoplantar pustulosis	DISCNSWD	Strong	Biomarker	[19]
Prostate cancer	DISF190Y	Strong	Altered Expression	[20]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[20]
Psoriatic arthritis	DISLWTG2	Strong	Genetic Variation	[21]
Rheumatoid arthritis	DISTSB4J	Strong	Genetic Variation	[17]
Skin disease	DISDW8R6	Strong	Biomarker	[22]
Stomach cancer	DISKIJSX	Strong	Genetic Variation	[23]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[24]
Autoimmune disease	DISORMTM	moderate	Altered Expression	[25]
Chronic renal failure	DISGG7K6	moderate	Genetic Variation	[26]
End-stage renal disease	DISXA7GG	moderate	Genetic Variation	[26]
Endocarditis	DISBU610	moderate	Biomarker	[27]
Pancreatic cancer	DISJC981	moderate	Biomarker	[28]
Chronic hepatitis B virus infection	DISHL4NT	Limited	Genetic Variation	[29]
Clear cell renal carcinoma	DISBXRFJ	Limited	Biomarker	[30]
Coronary heart disease	DIS5OIP1	Limited	Genetic Variation	[31]
Crohn disease	DIS2C5Q8	Limited	Genetic Variation	[32]
Hepatitis B virus infection	DISLQ2XY	Limited	Genetic Variation	[29]
Hepatocellular carcinoma	DIS0J828	Limited	Altered Expression	[33]
Kaposi sarcoma	DISC1H1Z	Limited	Altered Expression	[34]
Lupus nephritis	DISCVGPZ	Limited	Genetic Variation	[26]
Malignant pleural mesothelioma	DIST2R60	Limited	Biomarker	[35]
Neuroblastoma	DISVZBI4	Limited	Biomarker	[18]
Renal cell carcinoma	DISQZ2X8	Limited	Biomarker	[30]
Sclerosing cholangitis	DIS7GZNB	Limited	Genetic Variation	[32]
Ulcerative colitis	DIS8K27O	Limited	Genetic Variation	[32]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	TNFAIP3-interacting protein 1 (TNIP1) affects the response to substance of Methotrexate.	[53]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of TNFAIP3-interacting protein 1 (TNIP1).	[36]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of TNFAIP3-interacting protein 1 (TNIP1).	[37]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of TNFAIP3-interacting protein 1 (TNIP1).	[38]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of TNFAIP3-interacting protein 1 (TNIP1).	[39]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of TNFAIP3-interacting protein 1 (TNIP1).	[40]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of TNFAIP3-interacting protein 1 (TNIP1).	[41]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of TNFAIP3-interacting protein 1 (TNIP1).	[42]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of TNFAIP3-interacting protein 1 (TNIP1).	[43]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of TNFAIP3-interacting protein 1 (TNIP1).	[44]
Plicamycin	DM7C8YV	Approved	Plicamycin decreases the expression of TNFAIP3-interacting protein 1 (TNIP1).	[45]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of TNFAIP3-interacting protein 1 (TNIP1).	[46]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of TNFAIP3-interacting protein 1 (TNIP1).	[48]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of TNFAIP3-interacting protein 1 (TNIP1).	[49]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of TNFAIP3-interacting protein 1 (TNIP1).	[51]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine increases the expression of TNFAIP3-interacting protein 1 (TNIP1).	[52]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of TNFAIP3-interacting protein 1 (TNIP1).	[47]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of TNFAIP3-interacting protein 1 (TNIP1).	[50]

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