Details of Drug Off-Target (DOT)

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

• DOT Name: Hemogen (HEMGN)
• Synonyms: Erythroid differentiation-associated gene protein; EDAG-1; Hemopoietic gene protein; Negative differentiation regulator protein
• Gene Name: HEMGN
• Related Disease:
  Acute erythroid leukemia
  leukaemia
  Acute leukaemia
  Diabetic retinopathy
  Leukemia
  Non-insulin dependent diabetes
  Thyroid gland carcinoma
  Thyroid tumor
  X-linked reticulate pigmentary disorder
  Type-1/2 diabetes
  Neoplasm
  Deafness dystonia syndrome
  Retinopathy
• UniProt ID: HEMGN_HUMAN
• Sequence:
  MDLGKDQSHLKHHQTPDPHQEENHSPEVIGTWSLRNRELLRKRKAEVHEKETSQWLFGEQ
  KKRKQQRTGKGNRRGRKRQQNTELKVEPQPQIEKEIVEKALAPIEKKTEPPGSITKVFPS
  VASPQKVVPEEHFSEICQESNIYQENFSEYQEIAVQNHSSETCQHVSEPEDLSPKMYQEI
  SVLQDNSSKICQDMKEPEDNSPNTCQVISVIQDHPFKMYQDMAKREDLAPKMCQEAAVPK
  ILPCPTSEDTADLAGCSLQAYPKPDVPKGYILDTDQNPAEPEEYNETDQGIAETEGLFPK
  IQEIAEPKDLSTKTHQESAEPKYLPHKTCNEIIVPKAPSHKTIQETPHSEDYSIEINQET
  PGSEKYSPETYQEIPGLEEYSPEIYQETSQLEEYSPEIYQETPGPEDLSTETYKNKDVPK
  ECFPEPHQETGGPQGQDPKAHQEDAKDAYTFPQEMKEKPKEEPGIPAILNESHPENDVYS
  YVLF
• Function: Regulates the proliferation and differentiation of hematopoietic cells. Overexpression block the TPA-induced megakaryocytic differentiation in the K562 cell model. May also prevent cell apoptosis through the activation of the nuclear factor-kappa B (NF-kB).
• Tissue Specificity: Expressed in hematopoietic precursor cells, thyroid and spermatids (at protein level). Expressed in bone marrow, testis, thymus. Expressed in prostate cancer and ovarian cancer. Also expressed in thymus and thyroid tumors, non-Hodgkin lymphoma, various leukemia cell lines, peripheral blood mononuclear cells (PBMCs) and bone marrow mononuclear cells (BMMCs) of patients with leukemia.

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute erythroid leukemia	DISZFC1O	Definitive	Altered Expression	[1]
leukaemia	DISS7D1V	Definitive	Altered Expression	[2]
Acute leukaemia	DISDQFDI	Strong	Altered Expression	[3]
Diabetic retinopathy	DISHGUJM	Strong	Biomarker	[4]
Leukemia	DISNAKFL	Strong	Altered Expression	[2]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Genetic Variation	[5]
Thyroid gland carcinoma	DISMNGZ0	Strong	Biomarker	[6]
Thyroid tumor	DISLVKMD	Strong	Biomarker	[2]
X-linked reticulate pigmentary disorder	DIS0RB5A	Strong	Biomarker	[7]
Type-1/2 diabetes	DISIUHAP	moderate	Biomarker	[8]
Neoplasm	DISZKGEW	Disputed	Biomarker	[9]
Deafness dystonia syndrome	DIS0480U	Limited	Genetic Variation	[10]
Retinopathy	DISB4B0F	Limited	Genetic Variation	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Hemogen (HEMGN).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Hemogen (HEMGN).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Hemogen (HEMGN).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Hemogen (HEMGN).	[15]

References

• [1] Down-regulation of EDAG expression by retrovirus-mediated small interfering RNA inhibits the growth and IL-8 production of leukemia cells.Oncol Rep. 2007 Sep;18(3):659-64.
• [2] EDAG-1 promotes proliferation and invasion of human thyroid cancer cells by activating MAPK/Erk and AKT signal pathways.Cancer Biol Ther. 2016 Apr 2;17(4):414-21. doi: 10.1080/15384047.2016.1156259. Epub 2016 Mar 2.
• [3] The GATA site-dependent hemogen promoter is transcriptionally regulated by GATA1 in hematopoietic and leukemia cells.Leukemia. 2006 Mar;20(3):417-25. doi: 10.1038/sj.leu.2404105.
• [4] RNA-Seq Revealed Novel Non-proliferative Retinopathy Specific Circulating MiRNAs in T2DM Patients.Front Genet. 2019 Jun 4;10:531. doi: 10.3389/fgene.2019.00531. eCollection 2019.
• [5] Pros and cons of gastric bypass surgery in individuals with obesity and type 2 diabetes: nationwide, matched, observational cohort study.BMJ Open. 2019 Jan 15;9(1):e023882. doi: 10.1136/bmjopen-2018-023882.
• [6] Embryonic develop-associated gene 1 is overexpressed and acts as a tumor promoter in thyroid carcinoma.Biomed Pharmacother. 2016 Jul;81:86-92. doi: 10.1016/j.biopha.2016.03.052. Epub 2016 Apr 9.
• [7] Plasma metabolomic profiling of proliferative diabetic retinopathy.Nutr Metab (Lond). 2019 May 28;16:37. doi: 10.1186/s12986-019-0358-3. eCollection 2019.
• [8] Correlation between Cystatin C and retinopathy of type-two diabetes mellitus patients.J Biol Regul Homeost Agents. 2017 Jan-Mar;31(1):99-103.
• [9] Divergent Hemogen genes of teleosts and mammals share conserved roles in erythropoiesis: analysis using transgenic and mutant zebrafish.Biol Open. 2018 Aug 28;7(8):bio035576. doi: 10.1242/bio.035576.
• [10] Prognostic factors in patients with mesial temporal lobe epilepsy.Epilepsia. 2009 Jan;50 Suppl 1:41-4. doi: 10.1111/j.1528-1167.2008.01969.x.
• [11] Detection of Subclinical Diabetic Retinopathy by Fine Structure Analysis of Retinal Images.J Ophthalmol. 2019 Jul 4;2019:5171965. doi: 10.1155/2019/5171965. eCollection 2019.
• [12] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [13] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [14] 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.
• [15] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.