The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

NGB  -  neuroglobin

Homo sapiens

Synonyms: Neuroglobin
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of NGB

  • Neuroglobin and cytoglobin overexpression protects human SH-SY5Y neuroblastoma cells against oxidative stress-induced cell death [1].
  • Present evidence points to an important role of neuroglobin in neuronal oxygen homeostasis and hypoxia protection, though other functions are still conceivable [2].
  • CO binding reactions initiated by rapid mixing are measured for four plant hexacoordinate hemoglobins, human neuroglobin and cytoglobin, and Synechocystis hemoglobin [3].
  • Because both intracellular cystatin C and the amyloidogenic variant of cystatin C form dimers, Ngb may modulate the intracellular transport (or secretion) of cystatin C to protect against neuronal death under conditions of oxidative stress and/or it may have a role in the development of neurodegenerative diseases [4].
  • Structurally homologous hexacoordinate hemoglobins (hxHbs) are also found in animals (neuroglobin and cytoglobin) and some cyanobacteria, where they are thought to play a role in free radical scavenging or ligand sensing [5].

High impact information on NGB

  • The human neuroglobin gene (NGB), located on chromosome 14q24, has a unique exon-intron structure [6].
  • We have also discovered a second, unique Myg isoform, distinct from neuroglobin, which is expressed exclusively in the neural tissue but whose transcript expression was unaffected by environmental hypoxia [7].
  • Here we report that, like hemoglobin and myoglobin, neuroglobin expression can also be induced by hemin [8].
  • These results provide evidence for regulation of neuroglobin expression by at least 2 signal transduction pathways [8].
  • The histidine binding affinity is 100-fold lower than in neuroglobin [9].

Chemical compound and disease context of NGB

  • A triple mutant (replacing three Cys residues) of human neuroglobin (151 amino acids) has been expressed in Escherichia coli, purified and crystallized in two crystal forms, the best of which diffracts to 1.95 A resolution using synchrotron radiation [10].
  • While neuroglobin mRNA expression was significantly enhanced in cell culture after severe prolonged hypoxia (0-1% O2 for 24 h), we did not find any significant increases in neuroglobin mRNA levels in the rat brain after transient global ischemia [11].

Biological context of NGB


Anatomical context of NGB


Associations of NGB with chemical compounds

  • NGB shows both alkaline and acid Bohr effects (pH-dependent O2 affinity) and temperature-dependent enthalpy of oxygenation [16].
  • Structural characterization of the proximal and distal histidine environment of cytoglobin and neuroglobin [17].
  • Picosecond time-resolved resonance Raman (ps-TR3) spectroscopy of transient five-coordinate heme species produced by the photolysis of carbon monoxide (CO) adducts of Cgb and Ngb showed Fe-His stretching (nu(Fe-His)) bands at 229 and 221 cm(-1), respectively [17].
  • Moreover, flash photolysis experiments at high temperatures reveal that Ngb remains functional at 90 degrees C. Human Ngb may have a disulfide bond in the CD loop region; reduction of the disulfide bond increases the affinity of the iron atom for the distal (E7) histidine, and leads to a 3 degrees C increase in the T(m) for ferrous Ngb [18].
  • There are three cysteine residues in human neuroglobin; those at positions CD7 and D5 are sufficiently close to form an internal disulfide bond [19].

Physical interactions of NGB


Other interactions of NGB

  • These structural characteristics of Cgb and Ngb are discussed in relation to their ligand binding and physiological properties [17].
  • Both, neuroglobin and cytoglobin are structurally similar to myoglobin, although they contain distinct cavities that may be instrumental in ligand binding [2].
  • The interaction of Ngb with flotillin-1 was confirmed by glutathione S-transferase pull-down experiments [20].
  • p53-mediated apoptosis, neuroglobin overexpression, and globin deposits in a patient with hereditary ferritinopathy [21].
  • By surface plasmon resonance, we found that ferric Ngb, which is generated spontaneously as a result of the rapid autoxidation, binds exclusively to the GDP-bound form of the alpha subunit of heterotrimeric G protein (Galphai) [22].

Analytical, diagnostic and therapeutic context of NGB

  • Furthermore, it was demonstrated that NGB was extensively expressed in rat brain by using in situ hybridization and the immunohistochemical technique [15].
  • Amino acid residues in the ligand binding pocket of human neuroglobin have been identified by site-directed mutagenesis and their properties investigated by resonance Raman and flash photolysis methods [23].
  • Globin X displays the highest identity scores with neuroglobin (approximately 26% to 35%), although it is not a neuronal protein, as revealed by RT-PCR experiments on goldfish RNA from various tissues [24].
  • Both the ferrous and ferric forms of wild-type neuroglobin are found to be hexacoordinated with axial ligation of the F8-His and E7-His [25].
  • PURPOSE: In this preliminary study we sought to determine the effect of instituting nocturnal bladder emptying (NBE) in children with neurogenic (NGB) or nonneurogenic neurogenic bladder (NNGNGB) in whom urinary tract deterioration developed despite optimal daytime clean intermittent catheterization (CIC) and urotropic medications [26].


  1. Neuroglobin and cytoglobin overexpression protects human SH-SY5Y neuroblastoma cells against oxidative stress-induced cell death. Fordel, E., Thijs, L., Martinet, W., Lenjou, M., Laufs, T., Van Bockstaele, D., Moens, L., Dewilde, S. Neurosci. Lett. (2006) [Pubmed]
  2. Neuroglobin and cytoglobin in search of their role in the vertebrate globin family. Hankeln, T., Ebner, B., Fuchs, C., Gerlach, F., Haberkamp, M., Laufs, T.L., Roesner, A., Schmidt, M., Weich, B., Wystub, S., Saaler-Reinhardt, S., Reuss, S., Bolognesi, M., De Sanctis, D., Marden, M.C., Kiger, L., Moens, L., Dewilde, S., Nevo, E., Avivi, A., Weber, R.E., Fago, A., Burmester, T. J. Inorg. Biochem. (2005) [Pubmed]
  3. Slow ligand binding kinetics dominate ferrous hexacoordinate hemoglobin reactivities and reveal differences between plants and other species. Smagghe, B.J., Sarath, G., Ross, E., Hilbert, J.L., Hargrove, M.S. Biochemistry (2006) [Pubmed]
  4. Association of human neuroglobin with cystatin C, a cysteine proteinase inhibitor. Wakasugi, K., Nakano, T., Morishima, I. Biochemistry (2004) [Pubmed]
  5. Role of phenylalanine B10 in plant nonsymbiotic hemoglobins. Smagghe, B.J., Kundu, S., Hoy, J.A., Halder, P., Weiland, T.R., Savage, A., Venugopal, A., Goodman, M., Premer, S., Hargrove, M.S. Biochemistry (2006) [Pubmed]
  6. A vertebrate globin expressed in the brain. Burmester, T., Weich, B., Reinhardt, S., Hankeln, T. Nature (2000) [Pubmed]
  7. Hypoxia-inducible myoglobin expression in nonmuscle tissues. Fraser, J., de Mello, L.V., Ward, D., Rees, H.H., Williams, D.R., Fang, Y., Brass, A., Gracey, A.Y., Cossins, A.R. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  8. Hemin induces neuroglobin expression in neural cells. Zhu, Y., Sun, Y., Jin, K., Greenberg, D.A. Blood (2002) [Pubmed]
  9. The nerve hemoglobin of the bivalve mollusc Spisula solidissima: molecular cloning, ligand binding studies, and phylogenetic analysis. Dewilde, S., Ebner, B., Vinck, E., Gilany, K., Hankeln, T., Burmester, T., Kreiling, J., Reinisch, C., Vanfleteren, J.R., Kiger, L., Marden, M.C., Hundahl, C., Fago, A., Van Doorslaer, S., Moens, L. J. Biol. Chem. (2006) [Pubmed]
  10. Human neuroglobin: crystals and preliminary X-ray diffraction analysis. Pesce, A., Nardini, M., Dewilde, S., Ascenzi, P., Burmester, T., Hankeln, T., Moens, L., Bolognesi, M. Acta Crystallogr. D Biol. Crystallogr. (2002) [Pubmed]
  11. Neuroglobin mRNA expression after transient global brain ischemia and prolonged hypoxia in cell culture. Schmidt-Kastner, R., Haberkamp, M., Schmitz, C., Hankeln, T., Burmester, T. Brain Res. (2006) [Pubmed]
  12. Neuroglobin and cytoglobin. Fresh blood for the vertebrate globin family. Pesce, A., Bolognesi, M., Bocedi, A., Ascenzi, P., Dewilde, S., Moens, L., Hankeln, T., Burmester, T. EMBO Rep. (2002) [Pubmed]
  13. Reversible hexa- to penta-coordination of the heme Fe atom modulates ligand binding properties of neuroglobin and cytoglobin. Pesce, A., De Sanctis, D., Nardini, M., Dewilde, S., Moens, L., Hankeln, T., Burmester, T., Ascenzi, P., Bolognesi, M. IUBMB Life (2004) [Pubmed]
  14. The cellular and subcellular localization of neuroglobin and cytoglobin -- a clue to their function? Hankeln, T., Wystub, S., Laufs, T., Schmidt, M., Gerlach, F., Saaler-Reinhardt, S., Reuss, S., Burmester, T. IUBMB Life (2004) [Pubmed]
  15. Full-length cDNA cloning of human neuroglobin and tissue expression of rat neuroglobin. Zhang, C., Wang, C., Deng, M., Li, L., Wang, H., Fan, M., Xu, W., Meng, F., Qian, L., He, F. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  16. Allosteric regulation and temperature dependence of oxygen binding in human neuroglobin and cytoglobin. Molecular mechanisms and physiological significance. Fago, A., Hundahl, C., Dewilde, S., Gilany, K., Moens, L., Weber, R.E. J. Biol. Chem. (2004) [Pubmed]
  17. Structural characterization of the proximal and distal histidine environment of cytoglobin and neuroglobin. Sawai, H., Makino, M., Mizutani, Y., Ohta, T., Sugimoto, H., Uno, T., Kawada, N., Yoshizato, K., Kitagawa, T., Shiro, Y. Biochemistry (2005) [Pubmed]
  18. Hyperthermal stability of neuroglobin and cytoglobin. Hamdane, D., Kiger, L., Dewilde, S., Uzan, J., Burmester, T., Hankeln, T., Moens, L., Marden, M.C. FEBS J. (2005) [Pubmed]
  19. The redox state of the cell regulates the ligand binding affinity of human neuroglobin and cytoglobin. Hamdane, D., Kiger, L., Dewilde, S., Green, B.N., Pesce, A., Uzan, J., Burmester, T., Hankeln, T., Bolognesi, M., Moens, L., Marden, M.C. J. Biol. Chem. (2003) [Pubmed]
  20. Human neuroglobin interacts with flotillin-1, a lipid raft microdomain-associated protein. Wakasugi, K., Nakano, T., Kitatsuji, C., Morishima, I. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  21. p53-mediated apoptosis, neuroglobin overexpression, and globin deposits in a patient with hereditary ferritinopathy. Powers, J.M. J. Neuropathol. Exp. Neurol. (2006) [Pubmed]
  22. Oxidized human neuroglobin acts as a heterotrimeric Galpha protein guanine nucleotide dissociation inhibitor. Wakasugi, K., Nakano, T., Morishima, I. J. Biol. Chem. (2003) [Pubmed]
  23. Residues in the distal heme pocket of neuroglobin. Implications for the multiple ligand binding steps. Uno, T., Ryu, D., Tsutsumi, H., Tomisugi, Y., Ishikawa, Y., Wilkinson, A.J., Sato, H., Hayashi, T. J. Biol. Chem. (2004) [Pubmed]
  24. A globin gene of ancient evolutionary origin in lower vertebrates: evidence for two distinct globin families in animals. Roesner, A., Fuchs, C., Hankeln, T., Burmester, T. Mol. Biol. Evol. (2005) [Pubmed]
  25. Temperature dependence of NO binding modes in human neuroglobin. Trandafir, F., Van Doorslaer, S., Dewilde, S., Moens, L. Biochim. Biophys. Acta (2004) [Pubmed]
  26. Nocturnal bladder emptying: a simple technique for reversing urinary tract deterioration in children with neurogenic bladder. Koff, S.A., Gigax, M.R., Jayanthi, V.R. J. Urol. (2005) [Pubmed]
WikiGenes - Universities