Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT514IKQ)

• DOT Name: Hemoglobin subunit beta (HBB)
• Synonyms: Beta-globin; Hemoglobin beta chain
• Gene Name: HBB
• Related Disease:
  Beta thalassemia
  Beta-thalassemia HBB/LCRB
  Dominant beta-thalassemia
  Hemoglobin M disease
  Obsolete sickle cell disease and related diseases
  Erythrocytosis, familial, 6
  Heinz body anemia
  Sickle-cell anaemia
  Beta-thalassemia intermedia
  Beta-thalassemia major
  Delta-beta-thalassemia
  Hemoglobin C disease
  Hemoglobin C-beta-thalassemia syndrome
  Hemoglobin E disease
  Hemoglobin E-beta-thalassemia syndrome
  Hereditary persistence of fetal hemoglobin-beta-thalassemia syndrome
  Hereditary persistence of fetal hemoglobin-sickle cell disease syndrome
  Sickle cell-beta-thalassemia disease syndrome
  Sickle cell-hemoglobin c disease syndrome
  Sickle cell-hemoglobin d disease syndrome
  Sickle cell-hemoglobin E disease syndrome
• UniProt ID: HBB_HUMAN
• PDB ID: 1A00 ; 1A01 ; 1A0U ; 1A0Z ; 1A3N ; 1A3O ; 1ABW ; 1ABY ; 1AJ9 ; 1B86 ; 1BAB ; 1BBB ; 1BIJ ; 1BUW ; 1BZ0 ; 1BZ1 ; 1BZZ ; 1C7B ; 1C7C ; 1C7D ; 1CBL ; 1CBM ; 1CH4 ; 1CLS ; 1CMY ; 1COH ; 1DKE ; 1DXT ; 1DXU ; 1DXV ; 1FN3 ; 1G9V ; 1GBU ; 1GBV ; 1GLI ; 1GZX ; 1HAB ; 1HAC ; 1HBA ; 1HBB ; 1HBS ; 1HCO ; 1HDB ; 1HGA ; 1HGB ; 1HGC ; 1HHO ; 1IRD ; 1J3Y ; 1J3Z ; 1J40 ; 1J41 ; 1J7S ; 1J7W ; 1J7Y ; 1JY7 ; 1K0Y ; 1K1K ; 1KD2 ; 1LFL ; 1LFQ ; 1LFT ; 1LFV ; 1LFY ; 1LFZ ; 1LJW ; 1M9P ; 1MKO ; 1NEJ ; 1NIH ; 1NQP ; 1O1I ; 1O1J ; 1O1K ; 1O1L ; 1O1M ; 1O1N ; 1O1O ; 1O1P ; 1QI8 ; 1QSH ; 1QSI ; 1QXD ; 1QXE ; 1R1X ; 1R1Y ; 1RPS ; 1RQ3 ; 1RQ4 ; 1RQA ; 1RVW ; 1SDK ; 1SDL ; 1THB ; 1UIW ; 1VWT ; 1XXT ; 1XY0 ; 1XYE ; 1XZ2 ; 1XZ4 ; 1XZ5 ; 1XZ7 ; 1XZU ; 1XZV ; 1Y09 ; 1Y0A ; 1Y0C ; 1Y0D ; 1Y0T ; 1Y0W ; 1Y22 ; 1Y2Z ; 1Y31 ; 1Y35 ; 1Y45 ; 1Y46 ; 1Y4B ; 1Y4F ; 1Y4G ; 1Y4P ; 1Y4Q ; 1Y4R ; 1Y4V ; 1Y5F ; 1Y5J ; 1Y5K ; 1Y7C ; 1Y7D ; 1Y7G ; 1Y7Z ; 1Y83 ; 1Y85 ; 1Y8W ; 1YDZ ; 1YE0 ; 1YE1 ; 1YE2 ; 1YEN ; 1YEO ; 1YEQ ; 1YEU ; 1YEV ; 1YFF ; 1YG5 ; 1YGD ; 1YGF ; 1YH9 ; 1YHE ; 1YHR ; 1YIE ; 1YIH ; 1YVQ ; 1YVT ; 1YZI ; 2D5Z ; 2D60 ; 2DN1 ; 2DN2 ; 2DN3 ; 2DXM ; 2H35 ; 2HBC ; 2HBD ; 2HBE ; 2HBF ; 2HBS ; 2HCO ; 2HHB ; 2HHD ; 2HHE ; 2M6Z ; 2W6V ; 2W72 ; 2YRS ; 3B75 ; 3D17 ; 3D7O ; 3DUT ; 3HHB ; 3HXN ; 3IC0 ; 3IC2 ; 3KMF ; 3NL7 ; 3NMM ; 3ODQ ; 3ONZ ; 3OO4 ; 3OO5 ; 3P5Q ; 3QJB ; 3QJC ; 3QJD ; 3QJE ; 3R5I ; 3S65 ; 3S66 ; 3SZK ; 3W4U ; 3WCP ; 3WHM ; 4FC3 ; 4HHB ; 4IJ2 ; 4L7Y ; 4M4A ; 4M4B ; 4MQC ; 4MQG ; 4MQH ; 4MQI ; 4N7N ; 4N7O ; 4N7P ; 4N8T ; 4NI0 ; 4NI1 ; 4ROL ; 4ROM ; 4WJG ; 4X0L ; 4XS0 ; 5E29 ; 5E6E ; 5E83 ; 5EE4 ; 5HU6 ; 5HY8 ; 5JDO ; 5KDQ ; 5KSI ; 5KSJ ; 5NI1 ; 5SW7 ; 5U3I ; 5UCU ; 5UFJ ; 5URC ; 5VMM ; 5WOG ; 5WOH ; 5X2R ; 5X2S ; 5X2T ; 5X2U ; 6BB5 ; 6BNR ; 6BWP ; 6BWU ; 6DI4 ; 6FQF ; 6HAL ; 6HBW ; 6HK2 ; 6KA9 ; 6KAE ; 6KAH ; 6KAI ; 6KAO ; 6KAP ; 6KAQ ; 6KAR ; 6KAS ; 6KAT ; 6KAU ; 6KAV ; 6KYE ; 6L5V ; 6L5W ; 6L5X ; 6L5Y ; 6LCW ; 6LCX ; 6NBC ; 6NBD ; 6NQ5 ; 6TB2 ; 6XD9 ; 6XDT ; 6XE7 ; 7AET ; 7AEU ; 7AEV ; 7CUE ; 7DY3 ; 7DY4 ; 7JJQ ; 7JXZ ; 7JY0 ; 7JY1 ; 7JY3 ; 7K4M ; 7PCF ; 7PCH ; 7PCQ ; 7UD7 ; 7UD8 ; 7UF6 ; 7UF7 ; 7UVB ; 7VDE ; 7XGY ; 8DOV ; 8EGI ; 8FDK ; 8FDL ; 8FDM ; 8FDN
• Pfam ID: PF00042
• Sequence:
  MVHLTPEEKSAVTALWGKVNVDEVGGEALGRLLVVYPWTQRFFESFGDLSTPDAVMGNPK
  VKAHGKKVLGAFSDGLAHLDNLKGTFATLSELHCDKLHVDPENFRLLGNVLVCVLAHHFG
  KEFTPPVQAAYQKVVAGVANALAHKYH
• Function: Involved in oxygen transport from the lung to the various peripheral tissues; LVV-hemorphin-7 potentiates the activity of bradykinin, causing a decrease in blood pressure.; [Spinorphin]: Functions as an endogenous inhibitor of enkephalin-degrading enzymes such as DPP3, and as a selective antagonist of the P2RX3 receptor which is involved in pain signaling, these properties implicate it as a regulator of pain and inflammation.
• Tissue Specificity: Red blood cells.
• KEGG Pathway:
  African trypanosomiasis (hsa05143)
  Malaria (hsa05144)
• Reactome Pathway:
  Erythrocytes take up oxygen and release carbon dioxide (R-HSA-1247673)
  Scavenging of heme from plasma (R-HSA-2168880)
  Neutrophil degranulation (R-HSA-6798695)
  Chaperone Mediated Autophagy (R-HSA-9613829)
  Late endosomal microautophagy (R-HSA-9615710)
  Cytoprotection by HMOX1 (R-HSA-9707564)
  Heme signaling (R-HSA-9707616)
  Factors involved in megakaryocyte development and platelet production (R-HSA-983231)
  Erythrocytes take up carbon dioxide and release oxygen (R-HSA-1237044)

Molecular Interaction Atlas (MIA) of This DOT

21 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Beta thalassemia	DIS5RCQK	Definitive	Autosomal recessive	[1]
Beta-thalassemia HBB/LCRB	DISOIXFU	Definitive	Autosomal recessive	[1]
Dominant beta-thalassemia	DISQS5PK	Definitive	Autosomal dominant	[1]
Hemoglobin M disease	DISGMVWE	Definitive	Autosomal dominant	[1]
Obsolete sickle cell disease and related diseases	DISKXKSF	Definitive	Autosomal recessive	[1]
Erythrocytosis, familial, 6	DIS3TBBA	Strong	Autosomal dominant	[2]
Heinz body anemia	DISVMFK6	Strong	Autosomal dominant	[3]
Sickle-cell anaemia	DIS5YNZB	Strong	Autosomal recessive	[4]
Beta-thalassemia intermedia	DISYQ0NL	Supportive	Autosomal recessive	[5]
Beta-thalassemia major	DISW06BV	Supportive	Autosomal recessive	[5]
Delta-beta-thalassemia	DIS6CWYR	Supportive	Autosomal recessive	[6]
Hemoglobin C disease	DISPVNTG	Supportive	Autosomal recessive	[5]
Hemoglobin C-beta-thalassemia syndrome	DISL5FCO	Supportive	Autosomal recessive	[5]
Hemoglobin E disease	DIS5OW63	Supportive	Autosomal recessive	[5]
Hemoglobin E-beta-thalassemia syndrome	DIST2GQ9	Supportive	Autosomal recessive	[5]
Hereditary persistence of fetal hemoglobin-beta-thalassemia syndrome	DISD21FA	Supportive	Autosomal dominant	[7]
Hereditary persistence of fetal hemoglobin-sickle cell disease syndrome	DISK38J4	Supportive	Autosomal recessive	[4]
Sickle cell-beta-thalassemia disease syndrome	DIS2VWX2	Supportive	Autosomal recessive	[4]
Sickle cell-hemoglobin c disease syndrome	DISX4EOQ	Supportive	Autosomal recessive	[4]
Sickle cell-hemoglobin d disease syndrome	DIS47FK6	Supportive	Autosomal recessive	[4]
Sickle cell-hemoglobin E disease syndrome	DISKV1JQ	Supportive	Autosomal recessive	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE	DMNQL17	Investigative	Hemoglobin subunit beta (HBB) affects the response to substance of 2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE.	[29]

14 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 Hemoglobin subunit beta (HBB).	[8]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide affects the expression of Hemoglobin subunit beta (HBB).	[9]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Hemoglobin subunit beta (HBB).	[10]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Hemoglobin subunit beta (HBB).	[11]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil affects the splicing of Hemoglobin subunit beta (HBB).	[12]
Zidovudine	DM4KI7O	Approved	Zidovudine decreases the expression of Hemoglobin subunit beta (HBB).	[14]
Capecitabine	DMTS85L	Approved	Capecitabine decreases the expression of Hemoglobin subunit beta (HBB).	[15]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Hemoglobin subunit beta (HBB).	[19]
Coprexa	DMA0WEK	Phase 3	Coprexa increases the expression of Hemoglobin subunit beta (HBB).	[20]
SB-431542	DM0YOXQ	Preclinical	SB-431542 increases the expression of Hemoglobin subunit beta (HBB).	[23]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Hemoglobin subunit beta (HBB).	[24]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Hemoglobin subunit beta (HBB).	[25]
Protoporphyrin IX	DMWYE7A	Investigative	Protoporphyrin IX increases the expression of Hemoglobin subunit beta (HBB).	[27]
Catechol	DML0YEK	Investigative	Catechol increases the expression of Hemoglobin subunit beta (HBB).	[28]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the methylation of Hemoglobin subunit beta (HBB).	[13]
Phenol	DM1QSM3	Phase 2/3	Phenol increases the methylation of Hemoglobin subunit beta (HBB).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Hemoglobin subunit beta (HBB).	[22]

4 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Flucloxacillin	DMNUWST	Approved	Flucloxacillin affects the binding of Hemoglobin subunit beta (HBB).	[16]
Ibrutinib	DMHZCPO	Approved	Ibrutinib affects the binding of Hemoglobin subunit beta (HBB).	[17]
Voxelotor	DMCS6M5	Approved	Voxelotor affects the binding of Hemoglobin subunit beta (HBB).	[18]
D-glucose	DMMG2TO	Investigative	D-glucose affects the binding of Hemoglobin subunit beta (HBB).	[26]

2 Drug(s) Affected the Biochemical Pathways of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB increases the metabolism of Hemoglobin subunit beta (HBB).	[21]
cinnamaldehyde	DMZDUXG	Investigative	cinnamaldehyde increases the metabolism of Hemoglobin subunit beta (HBB).	[21]

References

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