Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTX1R7O1)

• DOT Name: Erythroid transcription factor (GATA1)
• Synonyms: Eryf1; GATA-binding factor 1; GATA-1; GF-1; NF-E1 DNA-binding protein
• Gene Name: GATA1
• Related Disease:
  GATA1-Related X-Linked Cytopenia
  Lung adenocarcinoma
  Myelodysplastic syndrome
  Prostate carcinoma
  Acute erythroid leukemia
  Acute monocytic leukemia
  Anemia
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Carcinoma
  Childhood acute megakaryoblastic leukemia
  Clear cell renal carcinoma
  Congenital dyserythropoietic anemia
  Diamond-Blackfan anemia 6
  Inherited bleeding disorder, platelet-type
  Myeloid leukaemia
  Myeloproliferative neoplasm
  Polycythemia vera
  Prostate cancer
  Thalassemia
  Thrombocytopenia 1
  Thrombocytopenia, X-linked, with or without dyserythropoietic anemia
  Tubular aggregate myopathy
  Wilms tumor
  Acute leukaemia
  Asthma
  Beta-thalassemia-X-linked thrombocytopenia syndrome
  Childhood myelodysplastic syndrome
  Rheumatoid arthritis
  Cutaneous porphyria
  Diamond-Blackfan anemia
  Thrombocytopenia with congenital dyserythropoietic anemia
  X-linked dyserythropoetic anemia with abnormal platelets and neutropenia
  Hematologic disease
  Plasma cell myeloma
  Plasma cell neoplasm
  Abetalipoproteinemia
  Acute lymphocytic leukaemia
  Advanced cancer
  Blast phase chronic myelogenous leukemia, BCR-ABL1 positive
  Childhood acute lymphoblastic leukemia
  Myelofibrosis
  Pancreatic cancer
  Pancreatitis
  Primary myelofibrosis
• UniProt ID: GATA1_HUMAN
• PDB ID: 6G0Q
• Pfam ID: PF00320
• Sequence:
  MEFPGLGSLGTSEPLPQFVDPALVSSTPESGVFFPSGPEGLDAAASSTAPSTATAAAAAL
  AYYRDAEAYRHSPVFQVYPLLNCMEGIPGGSPYAGWAYGKTGLYPASTVCPTREDSPPQA
  VEDLDGKGSTSFLETLKTERLSPDLLTLGPALPSSLPVPNSAYGGPDFSSTFFSPTGSPL
  NSAAYSSPKLRGTLPLPPCEARECVNCGATATPLWRRDRTGHYLCNACGLYHKMNGQNRP
  LIRPKKRLIVSKRAGTQCTNCQTTTTTLWRRNASGDPVCNACGLYYKLHQVNRPLTMRKD
  GIQTRNRKASGKGKKKRGSSLGGTGAAEGPAGGFMVVAGGSGSGNCGEVASGLTLGPPGT
  AHLYQGLGPVVLSGPVSHLMPFPGPLLGSPTGSFPTGPMPPTTSTTVVAPLSS
• Function: Transcriptional activator or repressor which serves as a general switch factor for erythroid development. It binds to DNA sites with the consensus sequence 5'-[AT]GATA[AG]-3' within regulatory regions of globin genes and of other genes expressed in erythroid cells. Activates the transcription of genes involved in erythroid differentiation of K562 erythroleukemia cells, including HBB, HBG1/2, ALAS2 and HMBS.
• Tissue Specificity: Erythrocytes.
• Reactome Pathway:
  RUNX1 regulates transcription of genes involved in differentiation of HSCs (R-HSA-8939236)
  Factors involved in megakaryocyte development and platelet production (R-HSA-983231)
  RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function (R-HSA-8936459)

Molecular Interaction Atlas (MIA) of This DOT

46 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
GATA1-Related X-Linked Cytopenia	DISCRY6M	Definitive	X-linked	[1]
Lung adenocarcinoma	DISD51WR	Definitive	Altered Expression	[2]
Myelodysplastic syndrome	DISYHNUI	Definitive	Biomarker	[3]
Prostate carcinoma	DISMJPLE	Definitive	Altered Expression	[4]
Acute erythroid leukemia	DISZFC1O	Strong	Altered Expression	[5]
Acute monocytic leukemia	DIS28NEL	Strong	Genetic Variation	[6]
Anemia	DISTVL0C	Strong	Biomarker	[7]
Breast cancer	DIS7DPX1	Strong	Biomarker	[8]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[8]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[8]
Carcinoma	DISH9F1N	Strong	Altered Expression	[9]
Childhood acute megakaryoblastic leukemia	DIS5VZDR	Strong	Genetic Variation	[10]
Clear cell renal carcinoma	DISBXRFJ	Strong	Altered Expression	[11]
Congenital dyserythropoietic anemia	DIS6FAT6	Strong	Biomarker	[12]
Diamond-Blackfan anemia 6	DIS4FKKF	Strong	GermlineCausalMutation	[13]
Inherited bleeding disorder, platelet-type	DISIUNXT	Strong	Genetic Variation	[14]
Myeloid leukaemia	DISMN944	Strong	Biomarker	[15]
Myeloproliferative neoplasm	DIS5KAPA	Strong	Altered Expression	[16]
Polycythemia vera	DISB5FPO	Strong	Biomarker	[17]
Prostate cancer	DISF190Y	Strong	Altered Expression	[4]
Thalassemia	DIS76XZB	Strong	Genetic Variation	[18]
Thrombocytopenia 1	DISTC3AW	Strong	Genetic Variation	[19]
Thrombocytopenia, X-linked, with or without dyserythropoietic anemia	DIS1BZF4	Strong	X-linked	[14]
Tubular aggregate myopathy	DISC11WH	Strong	Genetic Variation	[20]
Wilms tumor	DISB6T16	Strong	Biomarker	[21]
Acute leukaemia	DISDQFDI	moderate	Altered Expression	[5]
Asthma	DISW9QNS	moderate	Altered Expression	[22]
Beta-thalassemia-X-linked thrombocytopenia syndrome	DISNM782	Moderate	X-linked	[23]
Childhood myelodysplastic syndrome	DISMN80I	moderate	Biomarker	[3]
Rheumatoid arthritis	DISTSB4J	moderate	Biomarker	[24]
Cutaneous porphyria	DISUQTL2	Supportive	Autosomal recessive	[25]
Diamond-Blackfan anemia	DISI2SNW	Supportive	Autosomal dominant	[13]
Thrombocytopenia with congenital dyserythropoietic anemia	DIS9NMM4	Supportive	X-linked	[26]
X-linked dyserythropoetic anemia with abnormal platelets and neutropenia	DISL8N09	Supportive	X-linked	[27]
Hematologic disease	DIS9XD9A	Disputed	Altered Expression	[28]
Plasma cell myeloma	DIS0DFZ0	Disputed	Altered Expression	[29]
Plasma cell neoplasm	DIS2PJJM	Disputed	Altered Expression	[29]
Abetalipoproteinemia	DISMSS7T	Limited	Genetic Variation	[30]
Acute lymphocytic leukaemia	DISPX75S	Limited	Biomarker	[5]
Advanced cancer	DISAT1Z9	Limited	Altered Expression	[8]
Blast phase chronic myelogenous leukemia, BCR-ABL1 positive	DIS3KLUX	Limited	Genetic Variation	[31]
Childhood acute lymphoblastic leukemia	DISJ5D6U	Limited	Altered Expression	[32]
Myelofibrosis	DISIMP21	Limited	Genetic Variation	[33]
Pancreatic cancer	DISJC981	Limited	Altered Expression	[34]
Pancreatitis	DIS0IJEF	Limited	Biomarker	[35]
Primary myelofibrosis	DIS6L0CN	Limited	Genetic Variation	[33]

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 Erythroid transcription factor (GATA1).	[36]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Erythroid transcription factor (GATA1).	[45]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Erythroid transcription factor (GATA1).	[37]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Erythroid transcription factor (GATA1).	[38]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Erythroid transcription factor (GATA1).	[39]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Erythroid transcription factor (GATA1).	[40]
Zidovudine	DM4KI7O	Approved	Zidovudine decreases the expression of Erythroid transcription factor (GATA1).	[41]
Pomalidomide	DMTGBAX	Approved	Pomalidomide decreases the expression of Erythroid transcription factor (GATA1).	[42]
Aclarubicin	DMLFZHD	Approved	Aclarubicin increases the expression of Erythroid transcription factor (GATA1).	[43]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the activity of Erythroid transcription factor (GATA1).	[44]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Erythroid transcription factor (GATA1).	[46]
Butanoic acid	DMTAJP7	Investigative	Butanoic acid increases the expression of Erythroid transcription factor (GATA1).	[43]
Protoporphyrin IX	DMWYE7A	Investigative	Protoporphyrin IX increases the expression of Erythroid transcription factor (GATA1).	[40]
Catechol	DML0YEK	Investigative	Catechol increases the expression of Erythroid transcription factor (GATA1).	[47]
Chebulinic acid	DMR8HKC	Investigative	Chebulinic acid decreases the expression of Erythroid transcription factor (GATA1).	[48]

References

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