Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1SLUZH)

• DOT Name: Tumor necrosis factor-inducible gene 6 protein (TNFAIP6)
• Synonyms: EC 3.1.1.-; Hyaluronate-binding protein; TNF-stimulated gene 6 protein; TSG-6; Tumor necrosis factor alpha-induced protein 6; TNF alpha-induced protein 6
• Gene Name: TNFAIP6
• Related Disease:
  Allergic contact dermatitis
  Intervertebral disc degeneration
  Abdominal aortic aneurysm
  Acute liver failure
  Acute myocardial infarction
  Alzheimer disease
  Aortic valve disorder
  Arteriosclerosis
  Atherosclerosis
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Bronchopulmonary dysplasia
  Cardiovascular disease
  Cerebral cavernous malformation
  Cerebral infarction
  Clear cell renal carcinoma
  Coronary heart disease
  Crohn disease
  Cutaneous mastocytosis
  Hepatitis C virus infection
  Inflammatory bowel disease
  Influenza
  Interstitial cystitis
  Juvenile idiopathic arthritis
  Keloid
  Knee osteoarthritis
  Myocardial infarction
  Neoplasm
  Non-insulin dependent diabetes
  Osteoarthritis
  Prostate neoplasm
  Pulmonary disease
  Skin disease
  Ulcerative colitis
  Carcinoma
  Epstein barr virus infection
  Transitional cell carcinoma
  Urothelial carcinoma
  Type-1 diabetes
  Arthritis
  Colitis
• UniProt ID: TSG6_HUMAN
• PDB ID: 1O7B; 1O7C; 2N40; 2PF5; 2WNO
• EC Number: 3.1.1.-
• Pfam ID: PF00431 ; PF00193
• Sequence:
  MIILIYLFLLLWEDTQGWGFKDGIFHNSIWLERAAGVYHREARSGKYKLTYAEAKAVCEF
  EGGHLATYKQLEAARKIGFHVCAAGWMAKGRVGYPIVKPGPNCGFGKTGIIDYGIRLNRS
  ERWDAYCYNPHAKECGGVFTDPKQIFKSPGFPNEYEDNQICYWHIRLKYGQRIHLSFLDF
  DLEDDPGCLADYVEIYDSYDDVHGFVGRYCGDELPDDIISTGNVMTLKFLSDASVTAGGF
  QIKYVAMDPVSKSSQGKNTSTTSTGNKNFLAGRFSHL
• Function: Major regulator of extracellular matrix organization during tissue remodeling. Catalyzes the transfer of a heavy chain (HC) from inter-alpha-inhibitor (I-alpha-I) complex to hyaluronan. Cleaves the ester bond between the C-terminus of the HC and GalNAc residue of the chondroitin sulfate chain in I-alpha-I complex followed by transesterification of the HC to hyaluronan. In the process, potentiates the antiprotease function of I-alpha-I complex through release of free bikunin. Acts as a catalyst in the formation of hyaluronan-HC oligomers and hyaluronan-rich matrix surrounding the cumulus cell-oocyte complex, a necessary step for oocyte fertilization. Assembles hyaluronan in pericellular matrices that serve as platforms for receptor clustering and signaling. Enables binding of hyaluronan deposited on the surface of macrophages to LYVE1 on lymphatic endothelium and facilitates macrophage extravasation. Alters hyaluronan binding to functionally latent CD44 on vascular endothelium, switching CD44 into an active state that supports leukocyte rolling. Modulates the interaction of chemokines with extracellular matrix components and proteoglycans on endothelial cell surface, likely preventing chemokine gradient formation. In a negative feedback mechanism, may limit excessive neutrophil recruitment at inflammatory sites by antagonizing the association of CXCL8 with glycosaminoglycans on vascular endothelium. Has a role in osteogenesis and bone remodeling. Inhibits BMP2-dependent differentiation of mesenchymal stem cell to osteoblasts. Protects against bone erosion during inflammation by inhibiting TNFSF11/RANKL-dependent osteoclast activation.
• Tissue Specificity: Expressed in airway epithelium and submucosal gland (at protein level). Colocalizes with bikunin at the ciliary border. Present in bronchoalveolar lavage fluid (at protein level) . Expressed in mesenchymal stem cells . Found in the synovial fluid of patients with rheumatoid arthritis.
• Reactome Pathway: Neutrophil degranulation (R-HSA-6798695)

Molecular Interaction Atlas (MIA) of This DOT

42 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Allergic contact dermatitis	DISFFVF9	Definitive	Biomarker	[1]
Intervertebral disc degeneration	DISG3AIM	Definitive	Biomarker	[2]
Abdominal aortic aneurysm	DISD06OF	Strong	Altered Expression	[3]
Acute liver failure	DIS5EZKX	Strong	Biomarker	[4]
Acute myocardial infarction	DISE3HTG	Strong	Biomarker	[5]
Alzheimer disease	DISF8S70	Strong	Biomarker	[6]
Aortic valve disorder	DISKLYD7	Strong	Biomarker	[7]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[5]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[5]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[8]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[8]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[8]
Bronchopulmonary dysplasia	DISO0BY5	Strong	Altered Expression	[9]
Cardiovascular disease	DIS2IQDX	Strong	Biomarker	[5]
Cerebral cavernous malformation	DISLKNYA	Strong	Biomarker	[10]
Cerebral infarction	DISR1WNP	Strong	Biomarker	[5]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[11]
Coronary heart disease	DIS5OIP1	Strong	Biomarker	[5]
Crohn disease	DIS2C5Q8	Strong	Biomarker	[12]
Cutaneous mastocytosis	DISLBZEF	Strong	Genetic Variation	[4]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[13]
Inflammatory bowel disease	DISGN23E	Strong	Biomarker	[14]
Influenza	DIS3PNU3	Strong	Biomarker	[15]
Interstitial cystitis	DIS7CAJA	Strong	Biomarker	[16]
Juvenile idiopathic arthritis	DISQZGBV	Strong	Biomarker	[17]
Keloid	DISV09JY	Strong	Biomarker	[18]
Knee osteoarthritis	DISLSNBJ	Strong	Altered Expression	[19]
Myocardial infarction	DIS655KI	Strong	Altered Expression	[20]
Neoplasm	DISZKGEW	Strong	Altered Expression	[8]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Genetic Variation	[21]
Osteoarthritis	DIS05URM	Strong	Biomarker	[22]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[23]
Pulmonary disease	DIS6060I	Strong	Biomarker	[24]
Skin disease	DISDW8R6	Strong	Biomarker	[25]
Ulcerative colitis	DIS8K27O	Strong	Altered Expression	[26]
Carcinoma	DISH9F1N	moderate	Altered Expression	[27]
Epstein barr virus infection	DISOO0WT	moderate	Altered Expression	[28]
Transitional cell carcinoma	DISWVVDR	moderate	Biomarker	[27]
Urothelial carcinoma	DISRTNTN	moderate	Biomarker	[27]
Type-1 diabetes	DIS7HLUB	Disputed	Biomarker	[2]
Arthritis	DIST1YEL	Limited	Biomarker	[29]
Colitis	DISAF7DD	Limited	Biomarker	[30]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Beta-D-Glucose	DM5IHYP	Investigative	Tumor necrosis factor-inducible gene 6 protein (TNFAIP6) decreases the response to substance of Beta-D-Glucose.	[58]
Fmet-leu-phe	DMQ391A	Investigative	Tumor necrosis factor-inducible gene 6 protein (TNFAIP6) decreases the response to substance of Fmet-leu-phe.	[58]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Tumor necrosis factor-inducible gene 6 protein (TNFAIP6).	[31]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Tumor necrosis factor-inducible gene 6 protein (TNFAIP6).	[32]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Tumor necrosis factor-inducible gene 6 protein (TNFAIP6).	[33]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Tumor necrosis factor-inducible gene 6 protein (TNFAIP6).	[34]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Tumor necrosis factor-inducible gene 6 protein (TNFAIP6).	[35]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Tumor necrosis factor-inducible gene 6 protein (TNFAIP6).	[36]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of Tumor necrosis factor-inducible gene 6 protein (TNFAIP6).	[25]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Tumor necrosis factor-inducible gene 6 protein (TNFAIP6).	[38]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Tumor necrosis factor-inducible gene 6 protein (TNFAIP6).	[39]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Tumor necrosis factor-inducible gene 6 protein (TNFAIP6).	[40]
Selenium	DM25CGV	Approved	Selenium increases the expression of Tumor necrosis factor-inducible gene 6 protein (TNFAIP6).	[41]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Tumor necrosis factor-inducible gene 6 protein (TNFAIP6).	[42]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Tumor necrosis factor-inducible gene 6 protein (TNFAIP6).	[43]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Tumor necrosis factor-inducible gene 6 protein (TNFAIP6).	[44]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Tumor necrosis factor-inducible gene 6 protein (TNFAIP6).	[45]
Aspirin	DM672AH	Approved	Aspirin decreases the expression of Tumor necrosis factor-inducible gene 6 protein (TNFAIP6).	[31]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of Tumor necrosis factor-inducible gene 6 protein (TNFAIP6).	[46]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate decreases the expression of Tumor necrosis factor-inducible gene 6 protein (TNFAIP6).	[47]
Malathion	DMXZ84M	Approved	Malathion increases the expression of Tumor necrosis factor-inducible gene 6 protein (TNFAIP6).	[48]
Menthol	DMG2KW7	Approved	Menthol decreases the expression of Tumor necrosis factor-inducible gene 6 protein (TNFAIP6).	[49]
Pioglitazone	DMKJ485	Approved	Pioglitazone increases the expression of Tumor necrosis factor-inducible gene 6 protein (TNFAIP6).	[31]
Isoproterenol	DMK7MEY	Approved	Isoproterenol decreases the expression of Tumor necrosis factor-inducible gene 6 protein (TNFAIP6).	[31]
Nevirapine	DM6HX9B	Approved	Nevirapine increases the expression of Tumor necrosis factor-inducible gene 6 protein (TNFAIP6).	[31]
Clavulanate	DM2FGRT	Approved	Clavulanate increases the expression of Tumor necrosis factor-inducible gene 6 protein (TNFAIP6).	[31]
Flutamide	DMK0O7U	Approved	Flutamide increases the expression of Tumor necrosis factor-inducible gene 6 protein (TNFAIP6).	[31]
Amodiaquine	DME4RA8	Approved	Amodiaquine decreases the expression of Tumor necrosis factor-inducible gene 6 protein (TNFAIP6).	[31]
Dobutamine	DMD1B8Z	Approved	Dobutamine decreases the expression of Tumor necrosis factor-inducible gene 6 protein (TNFAIP6).	[31]
Zafirlukast	DMHNQOG	Approved	Zafirlukast decreases the expression of Tumor necrosis factor-inducible gene 6 protein (TNFAIP6).	[31]
Entacapone	DMLBVKQ	Approved	Entacapone decreases the expression of Tumor necrosis factor-inducible gene 6 protein (TNFAIP6).	[31]
Trazodone	DMK1GBJ	Approved	Trazodone increases the expression of Tumor necrosis factor-inducible gene 6 protein (TNFAIP6).	[31]
Fludrocortisone	DMUDIR8	Approved	Fludrocortisone decreases the expression of Tumor necrosis factor-inducible gene 6 protein (TNFAIP6).	[31]
Trihexyphenidyl	DMB19L8	Approved	Trihexyphenidyl increases the expression of Tumor necrosis factor-inducible gene 6 protein (TNFAIP6).	[31]
Procyclidine	DMHFJDT	Approved	Procyclidine increases the expression of Tumor necrosis factor-inducible gene 6 protein (TNFAIP6).	[31]
Levofloxacin	DMS60RB	Approved	Levofloxacin decreases the expression of Tumor necrosis factor-inducible gene 6 protein (TNFAIP6).	[31]
Alpidem	DMN7Y9K	Approved	Alpidem decreases the expression of Tumor necrosis factor-inducible gene 6 protein (TNFAIP6).	[31]
Pirprofen	DMMOFHT	Approved	Pirprofen increases the expression of Tumor necrosis factor-inducible gene 6 protein (TNFAIP6).	[31]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Tumor necrosis factor-inducible gene 6 protein (TNFAIP6).	[50]
DNCB	DMDTVYC	Phase 2	DNCB increases the expression of Tumor necrosis factor-inducible gene 6 protein (TNFAIP6).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Tumor necrosis factor-inducible gene 6 protein (TNFAIP6).	[52]
Eugenol	DM7US1H	Patented	Eugenol increases the expression of Tumor necrosis factor-inducible gene 6 protein (TNFAIP6).	[1]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Tumor necrosis factor-inducible gene 6 protein (TNFAIP6).	[53]
SB 203580	DMAET6F	Terminated	SB 203580 decreases the expression of Tumor necrosis factor-inducible gene 6 protein (TNFAIP6).	[42]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Tumor necrosis factor-inducible gene 6 protein (TNFAIP6).	[54]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Tumor necrosis factor-inducible gene 6 protein (TNFAIP6).	[44]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Tumor necrosis factor-inducible gene 6 protein (TNFAIP6).	[55]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of Tumor necrosis factor-inducible gene 6 protein (TNFAIP6).	[56]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine increases the expression of Tumor necrosis factor-inducible gene 6 protein (TNFAIP6).	[57]
benzyl bromide	DM857X2	Investigative	benzyl bromide increases the expression of Tumor necrosis factor-inducible gene 6 protein (TNFAIP6).	[47]

References

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