Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTX153DQ)

DOT Name Cytoglobin (CYGB)
Synonyms
Histoglobin; HGb; Nitric oxygen dioxygenase CYGB; NOD; EC 1.14.12.-; Nitrite reductase CYGB; EC 1.7.-.-; Pseudoperoxidase CYGB; EC 1.11.1.-; Stellate cell activation-associated protein; Superoxide dismutase CYGB; EC 1.15.1.1
Gene Name CYGB
Related Disease
Glioma ( )
Adult glioblastoma ( )
Advanced cancer ( )
Anemia ( )
Arteriosclerosis ( )
Atherosclerosis ( )
Brain neoplasm ( )
Breast cancer ( )
Breast carcinoma ( )
Carcinoma of liver and intrahepatic biliary tract ( )
Cardiovascular disease ( )
Cholestasis ( )
Colitis ( )
Epithelial ovarian cancer ( )
Esophageal adenocarcinoma ( )
Familial adenomatous polyposis ( )
Glioblastoma multiforme ( )
Head and neck cancer ( )
Head and neck carcinoma ( )
Head-neck squamous cell carcinoma ( )
High blood pressure ( )
Liver cancer ( )
Liver cirrhosis ( )
Lung adenocarcinoma ( )
Lung cancer ( )
Lung carcinoma ( )
Neoplasm ( )
Non-small-cell lung cancer ( )
Ovarian cancer ( )
Ovarian neoplasm ( )
Primary biliary cholangitis ( )
Renal fibrosis ( )
Triple negative breast cancer ( )
Ulcerative colitis ( )
Chronic pancreatitis ( )
Hepatocellular carcinoma ( )
Myocardial ischemia ( )
Nephropathy ( )
Neuroblastoma ( )
Prostate cancer ( )
Prostate carcinoma ( )
Type-1/2 diabetes ( )
Lung neoplasm ( )
Bone osteosarcoma ( )
Glaucoma/ocular hypertension ( )
Osteosarcoma ( )
Retinopathy ( )
UniProt ID
CYGB_HUMAN
3D Structure
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2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
1UMO; 1URV; 1URY; 1UT0; 1UX9; 1V5H; 2DC3; 3AG0; 4B3W
EC Number
1.11.1.-; 1.14.12.-; 1.15.1.1; 1.7.-.-
Pfam ID
PF00042
Sequence
MEKVPGEMEIERRERSEELSEAERKAVQAMWARLYANCEDVGVAILVRFFVNFPSAKQYF
SQFKHMEDPLEMERSPQLRKHACRVMGALNTVVENLHDPDKVSSVLALVGKAHALKHKVE
PVYFKILSGVILEVVAEEFASDFPPETQRAWAKLRGLIYSHVTAAYKEVGWVQQVPNATT
PPATLPSSGP
Function
Probable multifunctional globin with a hexacoordinated heme iron required for the catalysis of various reactions depending on redox condition of the cell as well as oxygen availability. Has a nitric oxide dioxygenase (NOD) activity and is most probably involved in cell-mediated and oxygen-dependent nitric oxide consumption. By scavenging this second messenger may regulate several biological processes including endothelium-mediated vasodilation and vascular tone. Under normoxic conditions functions as a nitric oxide dioxygenase (NOD) but under hypoxic conditions the globin may switch its function to that of a nitrite (NO2) reductase (NiR), generating nitric oxide. Could also have peroxidase and superoxide dismutase activities, detoxifying reactive oxygen species and protecting cells against oxidative stress. Also binds dioxygen with low affinity and could function as an oxygen sensor but has probably no function as a respiratory oxygen carrier.
Tissue Specificity Widely expressed. Highest expression in heart, stomach, bladder and small intestine.
Reactome Pathway
Intracellular oxygen transport (R-HSA-8981607 )
eNOS activation (R-HSA-203615 )

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Glioma DIS5RPEH Definitive Biomarker [1]
Adult glioblastoma DISVP4LU Strong Altered Expression [2]
Advanced cancer DISAT1Z9 Strong Biomarker [3]
Anemia DISTVL0C Strong Biomarker [4]
Arteriosclerosis DISK5QGC Strong Biomarker [5]
Atherosclerosis DISMN9J3 Strong Biomarker [5]
Brain neoplasm DISY3EKS Strong Altered Expression [2]
Breast cancer DIS7DPX1 Strong Altered Expression [6]
Breast carcinoma DIS2UE88 Strong Altered Expression [6]
Carcinoma of liver and intrahepatic biliary tract DIS8WA0W Strong Biomarker [7]
Cardiovascular disease DIS2IQDX Strong Altered Expression [8]
Cholestasis DISDJJWE Strong Biomarker [9]
Colitis DISAF7DD Strong Altered Expression [10]
Epithelial ovarian cancer DIS56MH2 Strong Altered Expression [11]
Esophageal adenocarcinoma DISODWFP Strong Altered Expression [12]
Familial adenomatous polyposis DISW53RE Strong Biomarker [13]
Glioblastoma multiforme DISK8246 Strong Altered Expression [2]
Head and neck cancer DISBPSQZ Strong Posttranslational Modification [14]
Head and neck carcinoma DISOU1DS Strong Posttranslational Modification [14]
Head-neck squamous cell carcinoma DISF7P24 Strong Posttranslational Modification [14]
High blood pressure DISY2OHH Strong Altered Expression [8]
Liver cancer DISDE4BI Strong Biomarker [7]
Liver cirrhosis DIS4G1GX Strong Biomarker [15]
Lung adenocarcinoma DISD51WR Strong Posttranslational Modification [16]
Lung cancer DISCM4YA Strong Biomarker [17]
Lung carcinoma DISTR26C Strong Biomarker [17]
Neoplasm DISZKGEW Strong Biomarker [7]
Non-small-cell lung cancer DIS5Y6R9 Strong Altered Expression [16]
Ovarian cancer DISZJHAP Strong Altered Expression [11]
Ovarian neoplasm DISEAFTY Strong Altered Expression [11]
Primary biliary cholangitis DIS43E0O Strong Biomarker [18]
Renal fibrosis DISMHI3I Strong Biomarker [19]
Triple negative breast cancer DISAMG6N Strong Altered Expression [20]
Ulcerative colitis DIS8K27O Strong Altered Expression [10]
Chronic pancreatitis DISBUOMJ moderate Biomarker [21]
Hepatocellular carcinoma DIS0J828 moderate Biomarker [7]
Myocardial ischemia DISFTVXF moderate Biomarker [22]
Nephropathy DISXWP4P moderate Biomarker [21]
Neuroblastoma DISVZBI4 moderate Altered Expression [23]
Prostate cancer DISF190Y moderate Biomarker [24]
Prostate carcinoma DISMJPLE moderate Biomarker [24]
Type-1/2 diabetes DISIUHAP moderate Biomarker [25]
Lung neoplasm DISVARNB Disputed Altered Expression [2]
Bone osteosarcoma DIST1004 Limited Biomarker [26]
Glaucoma/ocular hypertension DISLBXBY Limited Biomarker [27]
Osteosarcoma DISLQ7E2 Limited Biomarker [26]
Retinopathy DISB4B0F Limited Biomarker [28]
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⏷ Show the Full List of 47 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
1 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 Cytoglobin (CYGB). [29]
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23 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Cytoglobin (CYGB). [30]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Cytoglobin (CYGB). [31]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Cytoglobin (CYGB). [32]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Cytoglobin (CYGB). [33]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of Cytoglobin (CYGB). [34]
Arsenic DMTL2Y1 Approved Arsenic increases the expression of Cytoglobin (CYGB). [35]
Quercetin DM3NC4M Approved Quercetin increases the expression of Cytoglobin (CYGB). [36]
Triclosan DMZUR4N Approved Triclosan increases the expression of Cytoglobin (CYGB). [37]
Decitabine DMQL8XJ Approved Decitabine increases the expression of Cytoglobin (CYGB). [38]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of Cytoglobin (CYGB). [39]
Resveratrol DM3RWXL Phase 3 Resveratrol decreases the expression of Cytoglobin (CYGB). [40]
Epigallocatechin gallate DMCGWBJ Phase 3 Epigallocatechin gallate decreases the expression of Cytoglobin (CYGB). [40]
Guaiacol DMN4E7T Phase 3 Guaiacol decreases the expression of Cytoglobin (CYGB). [40]
Genistein DM0JETC Phase 2/3 Genistein decreases the expression of Cytoglobin (CYGB). [40]
Puerarin DMJIMXH Phase 2 Puerarin decreases the expression of Cytoglobin (CYGB). [40]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of Cytoglobin (CYGB). [41]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Cytoglobin (CYGB). [42]
THAPSIGARGIN DMDMQIE Preclinical THAPSIGARGIN decreases the expression of Cytoglobin (CYGB). [43]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Cytoglobin (CYGB). [44]
chloropicrin DMSGBQA Investigative chloropicrin decreases the expression of Cytoglobin (CYGB). [45]
D-glucose DMMG2TO Investigative D-glucose decreases the expression of Cytoglobin (CYGB). [46]
OXYQUINOLINE DMZVS9Y Investigative OXYQUINOLINE increases the expression of Cytoglobin (CYGB). [36]
Chlorogenic acid DM2Y3P4 Investigative Chlorogenic acid decreases the expression of Cytoglobin (CYGB). [40]
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⏷ Show the Full List of 23 Drug(s)

References

1 Knockdown of cytoglobin expression sensitizes human glioma cells to radiation and oxidative stress.Radiat Res. 2011 Aug;176(2):198-207. doi: 10.1667/rr2517.1. Epub 2011 Jun 1.
2 Old proteins - new locations: myoglobin, haemoglobin, neuroglobin and cytoglobin in solid tumours and cancer cells.Acta Physiol (Oxf). 2011 Jul;202(3):563-81. doi: 10.1111/j.1748-1716.2010.02205.x. Epub 2010 Nov 12.
3 Cytoglobin inhibits migration through PI3K/AKT/mTOR pathway in fibroblast cells.Mol Cell Biochem. 2018 Jan;437(1-2):133-142. doi: 10.1007/s11010-017-3101-2. Epub 2017 Jun 15.
4 A Clinical scoring model to predict mortality in HIV/TB co-infected patients at end stage of AIDS in China: An observational cohort study.Biosci Trends. 2019 May 12;13(2):136-144. doi: 10.5582/bst.2018.01309. Epub 2019 Mar 29.
5 Recombinant Human Cytoglobin Prevents Atherosclerosis by Regulating Lipid Metabolism and Oxidative Stress.J Cardiovasc Pharmacol Ther. 2018 Mar;23(2):162-173. doi: 10.1177/1074248417724870. Epub 2017 Sep 27.
6 The epigenetically downregulated factor CYGB suppresses breast cancer through inhibition of glucose metabolism.J Exp Clin Cancer Res. 2018 Dec 13;37(1):313. doi: 10.1186/s13046-018-0979-9.
7 Cytoglobin ameliorates the stemness of hepatocellular carcinoma via coupling oxidative-nitrosative stress signals.Mol Carcinog. 2019 Mar;58(3):334-343. doi: 10.1002/mc.22931. Epub 2018 Dec 4.
8 Cytoglobin regulates blood pressure and vascular tone through nitric oxide metabolism in the vascular wall.Nat Commun. 2017 Apr 10;8:14807. doi: 10.1038/ncomms14807.
9 Possible Involvement of Nitric Oxide in Enhanced Liver Injury and Fibrogenesis during Cholestasis in Cytoglobin-deficient Mice.Sci Rep. 2017 Feb 3;7:41888. doi: 10.1038/srep41888.
10 Cytoglobin affects tumorigenesis and the expression of ulcerative colitis-associated genes under chemically induced colitis in mice.Sci Rep. 2018 May 2;8(1):6905. doi: 10.1038/s41598-018-24728-x.
11 Expression and biological role of cytoglobin in human ovarian cancer.Tumour Biol. 2014 Jul;35(7):6933-9. doi: 10.1007/s13277-014-1941-x. Epub 2014 Apr 17.
12 Changes in mitochondrial stability during the progression of the Barrett's esophagus disease sequence.BMC Cancer. 2016 Jul 19;16:497. doi: 10.1186/s12885-016-2544-2.
13 Prolonged sampling of spontaneous sputum improves sensitivity of hypermethylation analysis for lung cancer.J Clin Pathol. 2012 Jun;65(6):541-5. doi: 10.1136/jclinpath-2012-200712. Epub 2012 Mar 29.
14 Cytoglobin is upregulated by tumour hypoxia and silenced by promoter hypermethylation in head and neck cancer.Br J Cancer. 2009 Jul 7;101(1):139-44. doi: 10.1038/sj.bjc.6605121.
15 Targeting Keap-1/Nrf-2 pathway and cytoglobin as a potential protective mechanism of diosmin and pentoxifylline against cholestatic liver cirrhosis.Life Sci. 2018 Aug 15;207:50-60. doi: 10.1016/j.lfs.2018.05.048. Epub 2018 May 28.
16 Cytoglobin has bimodal: tumour suppressor and oncogene functions in lung cancer cell lines.Hum Mol Genet. 2013 Aug 15;22(16):3207-17. doi: 10.1093/hmg/ddt174. Epub 2013 Apr 15.
17 Np63 targets cytoglobin to inhibit oxidative stress-induced apoptosis in keratinocytes and lung cancer.Oncogene. 2016 Mar 24;35(12):1493-503. doi: 10.1038/onc.2015.222. Epub 2015 Jun 22.
18 Hepatoprotective effects of diosmin and/or sildenafil against cholestatic liver cirrhosis: The role of Keap-1/Nrf-2 and P(38)-MAPK/NF-B/iNOS signaling pathway.Food Chem Toxicol. 2018 Oct;120:294-304. doi: 10.1016/j.fct.2018.07.027. Epub 2018 Jul 17.
19 Oxidative Stress and Renal Fibrosis: Recent Insights for the Development of Novel Therapeutic Strategies.Front Physiol. 2018 Feb 16;9:105. doi: 10.3389/fphys.2018.00105. eCollection 2018.
20 Putative tumor suppressor cytoglobin promotes aryl hydrocarbon receptor ligand-mediated triple negative breast cancer cell death.J Cell Biochem. 2019 Apr;120(4):6004-6014. doi: 10.1002/jcb.27887. Epub 2018 Nov 18.
21 Cytoglobin/STAP, its unique localization in splanchnic fibroblast-like cells and function in organ fibrogenesis.Lab Invest. 2004 Jan;84(1):91-101. doi: 10.1038/labinvest.3700013.
22 Cytoglobin Promotes Cardiac Progenitor Cell Survival against Oxidative Stress via the Upregulation of the NFB/iNOS Signal Pathway and Nitric Oxide Production.Sci Rep. 2017 Sep 7;7(1):10754. doi: 10.1038/s41598-017-11342-6.
23 Anoxia or oxygen and glucose deprivation in SH-SY5Y cells: a step closer to the unraveling of neuroglobin and cytoglobin functions.Gene. 2007 Aug 15;398(1-2):114-22. doi: 10.1016/j.gene.2007.03.022. Epub 2007 Apr 25.
24 Pathway specific gene expression profiling reveals oxidative stress genes potentially regulated by transcription co-activator LEDGF/p75 in prostate cancer cells.Prostate. 2012 May 1;72(6):597-611. doi: 10.1002/pros.21463. Epub 2011 Jul 27.
25 Cytoglobin: a novel potential gene medicine for fibrosis and cancer therapy.Curr Gene Ther. 2008 Aug;8(4):287-94. doi: 10.2174/156652308785160656.
26 Novel lymphoid enhancer-binding factor 1-cytoglobin axis promotes extravasation of osteosarcoma cells into the lungs.Cancer Sci. 2018 Sep;109(9):2746-2756. doi: 10.1111/cas.13702. Epub 2018 Jul 24.
27 Effect of cytoglobin overexpression on extracellular matrix component synthesis in human tenon fibroblasts.Biol Res. 2019 Apr 16;52(1):23. doi: 10.1186/s40659-019-0229-4.
28 Cytoglobin deficiency potentiates Crb1-mediated retinal degeneration in rd8 mice.Dev Biol. 2020 Feb 15;458(2):141-152. doi: 10.1016/j.ydbio.2019.10.013. Epub 2019 Oct 18.
29 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.
30 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
31 Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
32 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
33 Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
34 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
35 Arsenic alters transcriptional responses to Pseudomonas aeruginosa infection and decreases antimicrobial defense of human airway epithelial cells. Toxicol Appl Pharmacol. 2017 Sep 15;331:154-163.
36 Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
37 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
38 Aryl hydrocarbon receptor ligand 5F 203 induces oxidative stress that triggers DNA damage in human breast cancer cells. Chem Res Toxicol. 2015 May 18;28(5):855-71.
39 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
40 Examining the genomic influence of skin antioxidants in vitro. Mediators Inflamm. 2010;2010.
41 Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
42 Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
43 Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
44 Comparison of transcriptome expression alterations by chronic exposure to low-dose bisphenol A in different subtypes of breast cancer cells. Toxicol Appl Pharmacol. 2019 Dec 15;385:114814. doi: 10.1016/j.taap.2019.114814. Epub 2019 Nov 9.
45 Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
46 Imbalance in the antioxidant defence system and pro-genotoxic status induced by high glucose concentrations: In vitro testing in human liver cells. Toxicol In Vitro. 2020 Dec;69:105001. doi: 10.1016/j.tiv.2020.105001. Epub 2020 Sep 15.