Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTW0SIUY)

DOT Name	Neuroglobin (NGB)
Synonyms	Nitrite reductase; EC 1.7.-.-
Gene Name	NGB
Related Disease	Cognitive impairment ( ) Glioma ( ) Nervous system disease ( ) Acute myocardial infarction ( ) Adult glioblastoma ( ) Advanced cancer ( ) Alzheimer disease ( ) Amyloidosis ( ) Arteriosclerosis ( ) Brain neoplasm ( ) Cerebral infarction ( ) Encephalitis ( ) Glioblastoma multiforme ( ) Hepatocellular carcinoma ( ) Huntington disease ( ) Myocardial infarction ( ) Myocardial ischemia ( ) Neoplasm ( ) Neuroferritinopathy ( ) Obstructive sleep apnea ( ) Primary aldosteronism ( ) Retinitis pigmentosa ( ) Stroke ( ) Subarachnoid hemorrhage ( ) Bacterial infection ( ) High blood pressure ( ) Adenocarcinoma ( ) Amyotrophic lateral sclerosis ( ) Atherosclerosis ( ) Breast cancer ( ) Breast carcinoma ( ) Glaucoma/ocular hypertension ( ) Neuroblastoma ( ) Non-small-cell lung cancer ( ) Squamous cell carcinoma ( )
UniProt ID	NGB_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	1OJ6; 4MPM; 7VQG; 8GRZ
EC Number	1.7.-.-
Pfam ID	PF00042
Sequence	MERPEPELIRQSWRAVSRSPLEHGTVLFARLFALEPDLLPLFQYNCRQFSSPEDCLSSPE FLDHIRKVMLVIDAAVTNVEDLSSLEEYLASLGRKHRAVGVKLSSFSTVGESLLYMLEKC LGPAFTPATRAAWSQLYGAVVQAMSRGWDGE
Function	Monomeric globin with a bis-histidyl six-coordinate heme-iron atom through which it can bind dioxygen, carbon monoxide and nitric oxide. Could help transport oxygen and increase its availability to the metabolically active neuronal tissues, though its low quantity in tissues as well as its high affinity for dioxygen, which may limit its oxygen-releasing ability, argue against it. The ferrous/deoxygenated form exhibits a nitrite reductase activity and it could produce nitric oxide which in turn inhibits cellular respiration in response to hypoxia. In its ferrous/deoxygenated state, it may also exhibit GDI (Guanine nucleotide Dissociation Inhibitor) activity toward heterotrimeric G-alpha proteins, thereby regulating signal transduction to facilitate neuroprotective responses in the wake of hypoxia and associated oxidative stress.
Tissue Specificity	Predominantly expressed in brain, the strongest expression is seen in the frontal lobe, the subthalamic nucleus and the thalamus.
Reactome Pathway	Intracellular oxygen transport (R-HSA-8981607 )

Molecular Interaction Atlas (MIA) of This DOT

35 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Cognitive impairment	DISH2ERD	Definitive	Biomarker	[1]
Glioma	DIS5RPEH	Definitive	Biomarker	[2]
Nervous system disease	DISJ7GGT	Definitive	Biomarker	[3]
Acute myocardial infarction	DISE3HTG	Strong	Altered Expression	[4]
Adult glioblastoma	DISVP4LU	Strong	Altered Expression	[5]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[6]
Alzheimer disease	DISF8S70	Strong	Altered Expression	[7]
Amyloidosis	DISHTAI2	Strong	Biomarker	[8]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[4]
Brain neoplasm	DISY3EKS	Strong	Altered Expression	[9]
Cerebral infarction	DISR1WNP	Strong	Biomarker	[10]
Encephalitis	DISLD1RL	Strong	Biomarker	[11]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[5]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[12]
Huntington disease	DISQPLA4	Strong	Biomarker	[13]
Myocardial infarction	DIS655KI	Strong	Biomarker	[4]
Myocardial ischemia	DISFTVXF	Strong	Altered Expression	[4]
Neoplasm	DISZKGEW	Strong	Biomarker	[14]
Neuroferritinopathy	DIS0E4F3	Strong	Altered Expression	[15]
Obstructive sleep apnea	DIS0SVD1	Strong	Biomarker	[16]
Primary aldosteronism	DISOEFNH	Strong	Biomarker	[16]
Retinitis pigmentosa	DISCGPY8	Strong	Altered Expression	[17]
Stroke	DISX6UHX	Strong	Biomarker	[3]
Subarachnoid hemorrhage	DISI7I8Y	Strong	Altered Expression	[18]
Bacterial infection	DIS5QJ9S	moderate	Altered Expression	[19]
High blood pressure	DISY2OHH	moderate	Genetic Variation	[20]
Adenocarcinoma	DIS3IHTY	Limited	Altered Expression	[21]
Amyotrophic lateral sclerosis	DISF7HVM	Limited	Biomarker	[22]
Atherosclerosis	DISMN9J3	Limited	Biomarker	[4]
Breast cancer	DIS7DPX1	Limited	Altered Expression	[23]
Breast carcinoma	DIS2UE88	Limited	Altered Expression	[23]
Glaucoma/ocular hypertension	DISLBXBY	Limited	Biomarker	[24]
Neuroblastoma	DISVZBI4	Limited	Altered Expression	[25]
Non-small-cell lung cancer	DIS5Y6R9	Limited	Posttranslational Modification	[21]
Squamous cell carcinoma	DISQVIFL	Limited	Altered Expression	[21]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

3 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 Neuroglobin (NGB).	[26]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Neuroglobin (NGB).	[27]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Neuroglobin (NGB).	[28]
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References

1	Cognitive Deficits Are Attenuated in Neuroglobin Overexpressing Mice Exposed to a Model of Obstructive Sleep Apnea.Front Neurol. 2018 Jun 5;9:426. doi: 10.3389/fneur.2018.00426. eCollection 2018.
2	Neuroglobin promotes the proliferation and suppresses the apoptosis of glioma cells by activating the PI3K/AKT pathway.Mol Med Rep. 2018 Feb;17(2):2757-2763. doi: 10.3892/mmr.2017.8132. Epub 2017 Nov 22.
3	Neuroglobin promotes neurogenesis through Wnt signaling pathway.Cell Death Dis. 2018 Sep 20;9(10):945. doi: 10.1038/s41419-018-1007-x.
4	Cytoprotective effects of transgenic neuroglobin overexpression in an acute and chronic mouse model of ischemic heart disease.Heart Vessels. 2018 Jan;33(1):80-88. doi: 10.1007/s00380-017-1065-5. Epub 2017 Nov 2.
5	Neuroglobin functions as a prognostic marker and promotes the tumor growth of glioma via suppressing apoptosis.Biomed Pharmacother. 2017 Apr;88:173-180. doi: 10.1016/j.biopha.2017.01.029. Epub 2017 Jan 17.
6	Neuroglobin As Key Mediator in the 17-Estradiol-Induced Antioxidant Cell Response to Oxidative Stress.Antioxid Redox Signal. 2020 Feb 1;32(4):217-227. doi: 10.1089/ars.2019.7870.
7	Neuroglobin Expression in the Brain: a Story of Tissue Homeostasis Preservation.Mol Neurobiol. 2019 Mar;56(3):2101-2122. doi: 10.1007/s12035-018-1212-8. Epub 2018 Jul 10.
8	Amyloid-25-35 Upregulates Endogenous Neuroprotectant Neuroglobin via NFB Activation in vitro.J Alzheimers Dis. 2018;64(4):1163-1174. doi: 10.3233/JAD-180163.
9	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.
10	Neuroglobin mediates neuroprotection of hypoxic postconditioning against transient global cerebral ischemia in rats through preserving the activity of Na(+)/K(+) ATPases.Cell Death Dis. 2018 May 25;9(6):635. doi: 10.1038/s41419-018-0656-0.
11	[Expression of neuroglobin in rats with brain injury induced by LPS].Zhonghua Shao Shang Za Zhi. 2009 Jun;25(3):222-6.
12	Neuroglobin, a novel intracellular hexa-coordinated globin, functions as a tumor suppressor in hepatocellular carcinoma via Raf/MAPK/Erk.Mol Pharmacol. 2013 May;83(5):1109-19. doi: 10.1124/mol.112.083634. Epub 2013 Mar 11.
13	Localization of neuroglobin in the brain of R6/2 mouse model of Huntington's disease.Neurol Sci. 2018 Feb;39(2):275-285. doi: 10.1007/s10072-017-3168-2. Epub 2017 Nov 3.
14	Neuroglobin: A Novel Player in the Oxidative Stress Response of Cancer Cells.Oxid Med Cell Longev. 2019 Jul 1;2019:6315034. doi: 10.1155/2019/6315034. eCollection 2019.
15	p53-mediated apoptosis, neuroglobin overexpression, and globin deposits in a patient with hereditary ferritinopathy.J Neuropathol Exp Neurol. 2006 Jul;65(7):716-21. doi: 10.1097/01.jnen.0000228200.27539.19.
16	Neuroglobin correlates with cryptochrome-1 in obstructive sleep apnea with primary aldosteronism.PLoS One. 2018 Sep 20;13(9):e0204390. doi: 10.1371/journal.pone.0204390. eCollection 2018.
17	Hemin supports the survival of photoreceptors injured by N-Methyl-N-nitrosourea: The contributory role of neuroglobin in photoreceptor degeneration.Brain Res. 2018 Jan 1;1678:47-55. doi: 10.1016/j.brainres.2017.10.007. Epub 2017 Oct 13.
18	Recombinant neuroglobin ameliorates early brain injury after subarachnoid hemorrhage via inhibiting the activation of mitochondria apoptotic pathway.Neurochem Int. 2018 Jan;112:219-226. doi: 10.1016/j.neuint.2017.07.012. Epub 2017 Jul 31.
19	Identification of neuroglobin as a novel player in anti-bacterial responses in amphioxus.Dev Comp Immunol. 2017 Dec;77:157-165. doi: 10.1016/j.dci.2017.08.004. Epub 2017 Aug 10.
20	Five-coordinate H64Q neuroglobin as a ligand-trap antidote for carbon monoxide poisoning.Sci Transl Med. 2016 Dec 7;8(368):368ra173. doi: 10.1126/scitranslmed.aah6571.
21	Neuroglobin and myoglobin in non-small cell lung cancer: expression, regulation and prognosis.Lung Cancer. 2011 Dec;74(3):411-8. doi: 10.1016/j.lungcan.2011.05.001. Epub 2011 Jun 2.
22	Non-Methylation-Linked Mechanism of REST-Induced Neuroglobin Expression Impacts Mitochondrial Phenotypes in a Mouse Model of Amyotrophic Lateral Sclerosis.Neuroscience. 2019 Aug 1;412:233-247. doi: 10.1016/j.neuroscience.2019.05.039. Epub 2019 May 31.
23	Dissecting the 17-estradiol pathways necessary for neuroglobin anti-apoptotic activity in breast cancer.J Cell Physiol. 2018 Jul;233(7):5087-5103. doi: 10.1002/jcp.26378. Epub 2018 Jan 19.
24	Neuroglobin Can Prevent or Reverse Glaucomatous Progression in DBA/2J Mice.Mol Ther Methods Clin Dev. 2017 Apr 27;5:200-220. doi: 10.1016/j.omtm.2017.04.008. eCollection 2017 Jun 16.
25	Neuroglobin overexpression plays a pivotal role in neuroprotection through mitochondrial raft-like microdomains in neuroblastoma SK-N-BE2 cells.Mol Cell Neurosci. 2018 Apr;88:167-176. doi: 10.1016/j.mcn.2018.01.007. Epub 2018 Jan 31.
26	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.
27	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.
28	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.