Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGP7D5Y)

• DOT Name: Trans-acting T-cell-specific transcription factor GATA-3 (GATA3)
• Synonyms: GATA-binding factor 3
• Gene Name: GATA3
• Related Disease: Hypoparathyroidism-deafness-renal disease syndrome
• UniProt ID: GATA3_HUMAN
• PDB ID: 4HC7; 4HC9; 4HCA
• Pfam ID: PF00320
• Sequence:
  MEVTADQPRWVSHHHPAVLNGQHPDTHHPGLSHSYMDAAQYPLPEEVDVLFNIDGQGNHV
  PPYYGNSVRATVQRYPPTHHGSQVCRPPLLHGSLPWLDGGKALGSHHTASPWNLSPFSKT
  SIHHGSPGPLSVYPPASSSSLSGGHASPHLFTFPPTPPKDVSPDPSLSTPGSAGSARQDE
  KECLKYQVPLPDSMKLESSHSRGSMTALGGASSSTHHPITTYPPYVPEYSSGLFPPSSLL
  GGSPTGFGCKSRPKARSSTGRECVNCGATSTPLWRRDGTGHYLCNACGLYHKMNGQNRPL
  IKPKRRLSAARRAGTSCANCQTTTTTLWRRNANGDPVCNACGLYYKLHNINRPLTMKKEG
  IQTRNRKMSSKSKKCKKVHDSLEDFPKNSSFNPAALSRHMSSLSHISPFSHSSHMLTTPT
  PMHPPSSLSFGPHHPSSMVTAMG
• Function: Transcriptional activator which binds to the enhancer of the T-cell receptor alpha and delta genes. Binds to the consensus sequence 5'-AGATAG-3'. Required for the T-helper 2 (Th2) differentiation process following immune and inflammatory responses. Positively regulates ASB2 expression. Coordinates macrophage transcriptional activation and UCP2-dependent metabolic reprogramming in response to IL33. Upon tissue injury, acts downstream of IL33 signaling to drive differentiation of inflammation-resolving alternatively activated macrophages.
• Tissue Specificity: T-cells and endothelial cells.
• KEGG Pathway:
  Th1 and Th2 cell differentiation (hsa04658)
  Th17 cell differentiation (hsa04659)
  Parathyroid hormone synthesis, secretion and action (hsa04928)
  Inflammatory bowel disease (hsa05321)
• Reactome Pathway:
  Interleukin-4 and Interleukin-13 signaling (R-HSA-6785807)
  RUNX1 regulates transcription of genes involved in differentiation of HSCs (R-HSA-8939236)
  Estrogen-dependent gene expression (R-HSA-9018519)
  Factors involved in megakaryocyte development and platelet production (R-HSA-983231)
  Ub-specific processing proteases (R-HSA-5689880)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hypoparathyroidism-deafness-renal disease syndrome	DISRCBP9	Definitive	Autosomal dominant	[1]

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 Trans-acting T-cell-specific transcription factor GATA-3 (GATA3).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Trans-acting T-cell-specific transcription factor GATA-3 (GATA3).	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Trans-acting T-cell-specific transcription factor GATA-3 (GATA3).	[3]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Trans-acting T-cell-specific transcription factor GATA-3 (GATA3).	[4]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Trans-acting T-cell-specific transcription factor GATA-3 (GATA3).	[5]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Trans-acting T-cell-specific transcription factor GATA-3 (GATA3).	[6]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Trans-acting T-cell-specific transcription factor GATA-3 (GATA3).	[7]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Trans-acting T-cell-specific transcription factor GATA-3 (GATA3).	[8]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Trans-acting T-cell-specific transcription factor GATA-3 (GATA3).	[9]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Trans-acting T-cell-specific transcription factor GATA-3 (GATA3).	[10]
Marinol	DM70IK5	Approved	Marinol increases the expression of Trans-acting T-cell-specific transcription factor GATA-3 (GATA3).	[11]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Trans-acting T-cell-specific transcription factor GATA-3 (GATA3).	[7]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Trans-acting T-cell-specific transcription factor GATA-3 (GATA3).	[12]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of Trans-acting T-cell-specific transcription factor GATA-3 (GATA3).	[13]
Lindane	DMB8CNL	Approved	Lindane increases the expression of Trans-acting T-cell-specific transcription factor GATA-3 (GATA3).	[14]
Rofecoxib	DM3P5DA	Approved	Rofecoxib decreases the expression of Trans-acting T-cell-specific transcription factor GATA-3 (GATA3).	[15]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Trans-acting T-cell-specific transcription factor GATA-3 (GATA3).	[7]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Trans-acting T-cell-specific transcription factor GATA-3 (GATA3).	[7]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Trans-acting T-cell-specific transcription factor GATA-3 (GATA3).	[17]
Clioquinol	DM746BZ	Withdrawn from market	Clioquinol decreases the expression of Trans-acting T-cell-specific transcription factor GATA-3 (GATA3).	[18]
PD-153035	DM7KJTI	Discontinued in Phase 1	PD-153035 decreases the expression of Trans-acting T-cell-specific transcription factor GATA-3 (GATA3).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Trans-acting T-cell-specific transcription factor GATA-3 (GATA3).	[4]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Trans-acting T-cell-specific transcription factor GATA-3 (GATA3).	[19]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Trans-acting T-cell-specific transcription factor GATA-3 (GATA3).	[20]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine increases the expression of Trans-acting T-cell-specific transcription factor GATA-3 (GATA3).	[21]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	4-hydroxy-2-nonenal decreases the expression of Trans-acting T-cell-specific transcription factor GATA-3 (GATA3).	[22]
BRN-3548355	DM4KXT0	Investigative	BRN-3548355 increases the expression of Trans-acting T-cell-specific transcription factor GATA-3 (GATA3).	[23]

References

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