Details of Drug Off-Target (DOT)

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

DOT Name Hemoglobin subunit zeta (HBZ)
Synonyms HBAZ; Hemoglobin zeta chain; Zeta-globin
Gene Name HBZ
Related Disease
Adult T-cell leukemia/lymphoma ( )
T-cell leukaemia ( )
Acute erythroid leukemia ( )
Adult lymphoma ( )
Advanced cancer ( )
Beta thalassemia ( )
Bone disease ( )
Congenital anemia ( )
Hemoglobin H disease ( )
Herpes simplex infection ( )
Lymphoma ( )
Lymphoproliferative syndrome ( )
Neoplasm ( )
Pediatric lymphoma ( )
Thalassemia ( )
Leukemia ( )
Human T-lymphotropic virus 1 infectious disease ( )
Hemoglobinopathy ( )
Spastic paralysis ( )
UniProt ID
HBAZ_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
1JEB; 3W4U
Pfam ID
PF00042
Sequence
MSLTKTERTIIVSMWAKISTQADTIGTETLERLFLSHPQTKTYFPHFDLHPGSAQLRAHG
SKVVAAVGDAVKSIDDIGGALSKLSELHAYILRVDPVNFKLLSHCLLVTLAARFPADFTA
EAHAAWDKFLSVVSSVLTEKYR
Function The zeta chain is an alpha-type chain of mammalian embryonic hemoglobin.
Tissue Specificity Detected in fetal erythrocytes (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

19 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Adult T-cell leukemia/lymphoma DIS882XU Definitive Biomarker [1]
T-cell leukaemia DISJ6YIF Definitive Altered Expression [2]
Acute erythroid leukemia DISZFC1O Strong Altered Expression [3]
Adult lymphoma DISK8IZR Strong Altered Expression [4]
Advanced cancer DISAT1Z9 Strong Biomarker [5]
Beta thalassemia DIS5RCQK Strong Biomarker [6]
Bone disease DISE1F82 Strong Biomarker [7]
Congenital anemia DISTW0J6 Strong Biomarker [8]
Hemoglobin H disease DISHFWO5 Strong Biomarker [9]
Herpes simplex infection DISL1SAV Strong Biomarker [10]
Lymphoma DISN6V4S Strong Altered Expression [4]
Lymphoproliferative syndrome DISMVL8O Strong Biomarker [1]
Neoplasm DISZKGEW Strong Biomarker [11]
Pediatric lymphoma DIS51BK2 Strong Altered Expression [4]
Thalassemia DIS76XZB Strong Biomarker [12]
Leukemia DISNAKFL moderate Biomarker [13]
Human T-lymphotropic virus 1 infectious disease DISN5C4M Disputed Biomarker [1]
Hemoglobinopathy DISCT4GX Limited Biomarker [12]
Spastic paralysis DISVQ6I2 Limited Biomarker [14]
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⏷ Show the Full List of 19 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
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 Hemoglobin subunit zeta (HBZ). [15]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Hemoglobin subunit zeta (HBZ). [18]
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3 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide increases the expression of Hemoglobin subunit zeta (HBZ). [16]
SNDX-275 DMH7W9X Phase 3 SNDX-275 decreases the expression of Hemoglobin subunit zeta (HBZ). [17]
Butanoic acid DMTAJP7 Investigative Butanoic acid increases the expression of Hemoglobin subunit zeta (HBZ). [16]
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References

1 HTLV-1 viral oncogene HBZ drives bone destruction in adult T cell leukemia.JCI Insight. 2019 Oct 3;4(19):e128713. doi: 10.1172/jci.insight.128713.
2 Novel Interactions between the Human T-Cell Leukemia Virus Type 1 Antisense Protein HBZ and the SWI/SNF Chromatin Remodeling Family: Implications for Viral Life Cycle.J Virol. 2019 Jul 30;93(16):e00412-19. doi: 10.1128/JVI.00412-19. Print 2019 Aug 15.
3 Identification of a major positive regulatory element located 5' to the human zeta-globin gene.Blood. 1995 May 1;85(9):2587-97.
4 The TP53-Induced Glycolysis and Apoptosis Regulator mediates cooperation between HTLV-1 p30(II) and the retroviral oncoproteins Tax and HBZ and is highly expressed in an in vivo xenograft model of HTLV-1-induced lymphoma.Virology. 2018 Jul;520:39-58. doi: 10.1016/j.virol.2018.05.007. Epub 2018 May 26.
5 Role of the HTLV-1 viral factors in the induction of apoptosis.Biomed Pharmacother. 2017 Jan;85:334-347. doi: 10.1016/j.biopha.2016.11.034. Epub 2016 Nov 23.
6 Screening for co-existence of -thalassemia in -thalassemia and in HbE heterozygotes via an enzyme-linked immunosorbent assay for Hb Bart's and embryonic -globin chain.Int J Hematol. 2012 Apr;95(4):386-93. doi: 10.1007/s12185-012-1039-4. Epub 2012 Mar 23.
7 HTLV-1 viral oncogene HBZ induces osteolytic bone disease in transgenic mice.Oncotarget. 2017 Aug 27;8(41):69250-69263. doi: 10.18632/oncotarget.20565. eCollection 2017 Sep 19.
8 Expression of embryonic zeta-globin and epsilon-globin chains in a 10-year-old girl with congenital anemia.Blood. 1993 Mar 15;81(6):1636-40.
9 Prenatal diagnosis of Chinese homozygous alpha-thalassaemia 1 and haemoglobin H disease by analysis of alpha- and phi zeta-globin genes in chorionic villi and amniocytes.Prenat Diagn. 1989 Oct;9(10):715-25. doi: 10.1002/pd.1970091007.
10 HTLV-1 bZIP factor impairs cell-mediated immunity by suppressing production of Th1 cytokines.Blood. 2012 Jan 12;119(2):434-44. doi: 10.1182/blood-2011-05-357459. Epub 2011 Nov 28.
11 Characterization of novel Bovine Leukemia Virus (BLV) antisense transcripts by deep sequencing reveals constitutive expression in tumors and transcriptional interaction with viral microRNAs.Retrovirology. 2016 May 3;13(1):33. doi: 10.1186/s12977-016-0267-8.
12 Screening of (-SEA) -thalassaemia using an immunochromatographic strip assay for the -globin chain in a population with a high prevalence and heterogeneity of haemoglobinopathies.J Clin Pathol. 2017 Jan;70(1):63-68. doi: 10.1136/jclinpath-2016-203765. Epub 2016 Jun 16.
13 Novel interactions between the HTLV antisense proteins HBZ and APH-2 and the NFAR protein family: Implications for the HTLV lifecycles.Virology. 2016 Jul;494:129-42. doi: 10.1016/j.virol.2016.04.012. Epub 2016 Apr 22.
14 The effect of HTLV-1 virulence factors (HBZ, Tax, proviral load), HLA class I and plasma neopterin on manifestation of HTLV-1 associated myelopathy tropical spastic paraparesis.Virus Res. 2017 Jan 15;228:1-6. doi: 10.1016/j.virusres.2016.11.009. Epub 2016 Nov 12.
15 Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
16 MS4A3-HSP27 target pathway reveals potential for haematopoietic disorder treatment in alimentary toxic aleukia. Cell Biol Toxicol. 2023 Feb;39(1):201-216. doi: 10.1007/s10565-021-09639-4. Epub 2021 Sep 28.
17 Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
18 Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.