Recombinant Human Neuroglobin (NGB)

Function

Monomeric globin with a bis-histidyl six-coordinate heme-iron atom through which it can bind dioxygen, carbon monoxide and nitric oxide (PubMed:11473128, PubMed:12962627, PubMed:24699645). 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 (PubMed:11473128, PubMed:12860983, PubMed:12962627, PubMed:24699645). 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 (PubMed:21296891). 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 (PubMed:12860983, PubMed:18302932)

Subcellular Location

Cytoplasm, cytosol; Mitochondrion matrix

Tissue Specificity

Predominantly expressed in brain, the strongest expression is seen in the frontal lobe, the subthalamic nucleus and the thalamus

Subunit

Monomer (PubMed:11029004). Homodimer and homotetramer; disulfide-linked. Mainly monomeric but also detected as part of homodimers and homotetramers (By similarity). Interacts with 14-3-3 proteins; regulates the phosphorylation of NGB (PubMed:21965683). Could interact (ferrous form) with G-alpha(i) proteins (GTP-bound form) (PubMed:12860983)

• Burmester T. et al. A vertebrate globin expressed in the brain. — Nature (2000)
• Zhang C.G. et al. Full-length cDNA cloning of human neuroglobin and tissue expression of rat neuroglobin. — Biochem. Biophys. Res. Commun. (2002)
• Heilig R. et al. The DNA sequence and analysis of human chromosome 14. — Nature (2003)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Dewilde S. et al. Biochemical characterization and ligand binding properties of neuroglobin, a novel member of the globin family. — J. Biol. Chem. (2001)
• Wakasugi K. et al. Oxidized human neuroglobin acts as a heterotrimeric Galpha protein guanine nucleotide dissociation inhibitor. — J. Biol. Chem. (2003)
• Hamdane D. et al. Coupling of the heme and an internal disulfide bond in human neuroglobin. — Micron (2004)
• Watanabe S. et al. Neuroprotective function of human neuroglobin is correlated with its guanine nucleotide dissociation inhibitor activity. — Biochem. Biophys. Res. Commun. (2008)