Property Summary

NCBI Gene PubMed Count 58
PubMed Score 1175.19
PubTator Score 159.71

Knowledge Summary


No data available



Accession Q8WWM9 Q541Y7 Q8N2X5
Symbols HGB


PANTHER Protein Class (1)


1UMO   1URV   1URY   1UT0   1UX9   1V5H   2DC3   3AG0   4B3W  

  Ortholog (1)

Species Source Disease
Chimp OMA EggNOG

Gene RIF (53)

26928591 Propose a bipartite lipid binding model that rationalizes the modes of interactions of cytoglobin with phospholipids, the effects on structural re-arrangements and the peroxidase activity of the hemoprotein.
26339645 This review provides an overview of the proposed role of cytoglobin and explores its potential functional role as a biomarker for cancer and other diseases
26096935 DeltaNp63-CYGB axis is also present in lung and breast cancer cell lines, indicating that CYGB-mediated ROS-scavenging activity may also have a role in epithelial tumours
25665792 Cygb, expressed in hepatic stellate cells during liver fibrosis, plays role in cancer development with nonalcoholic steatohepatitis.
25601563 The cysteine redox state of the monomer controls histidine dissociation rate constants and hence extrinsic ligand binding in human cytoglobin.
25327890 The monomeric cytoglobin protein with an internal disulfide bond between the two cysteine residues Cys38 and Cys83, interacts with lipids to induce a change in haem co-ordination.
25269893 Cygb stabilizes p53 by inhibiting its ubiquitination and elicit cell cycle arrest in DNA damaged cells.
24816917 This review outlines the current understanding of Cygb's involvement in tumor hypoxia and discusses its role in tumorigenesis.
24737588 Our data provides evidence that cytoglobin regulates the ovarian cancer cell proliferation and invasion.
24632414 Protein multimerization may be a mechanism that triggers physiological functions of human cytoglobin.
24296877 Cytoglobin is expressed in hepatic stellate cells, but not in myofibroblasts, in normal and fibrotic human liver, so it thus a useful marker to distinguish these cells.
24037220 Molecular dynamics studies of four cytoglobinCO models indicated that the distal E7 residue was a crucial influence on the dynamics of cytoglobinCO in terms of loop fluctuations, cavity rearrangement, and slight heme motion.
24008134 Reduction of the internal disulfide bond between Cys 38 and 83 switches the ligand migration pathway in cytoglobin.
23835959 Ngb and Cygb are expressed in the solitary tract nucleus and in the carotid body, and may have roles in the processing of cardiovascular and respiratory reflex inputs
23728617 Treatment of human primary astrocytes with HIV-1 Vpr downregulates expression of eleven genes, BNIP3, CYGB, DUOX2, DUSP1, FOXM1, GAPDH, HPRT1, MT3, MTL5, PTGS2, and SCARA3
23710929 Reduction of Cygb by cellular reductants enables Cygb to efficiently regulate nitric oxide metabolism in the vascular wall in an oxygen-dependent manner.
23591990 Results show that CYGB revealed Tumor Suppressor Gene properties in normoxia but promoted tumourigenic potential of the cells exposed to stress, suggesting a bimodal function in lung tumourigenesis.
23308092 A substantial change in both protein dynamics and inner cavities is observed upon transition from the CO-liganded to the pentacoordinated and bis-histidyl hexacoordinated species, which could be exploited as a signalling state.
23160832 Report cytoglobin expression in human brain.
22896706 Cygb-mediated nitrite reduction can play an important role in NO generation and soluble guanylyl cyclase activation under hypoxic conditions
22750003 This suggests that Cytoglobin is likely not important for global neuronal protection following ischemia and the role of Cytoglobin in relation to endogenous neuroprotection remains unresolved.
22577939 Coexistence of Cygb with efficient reductants in tissues allows Cygb to function as an oxygen-dependent regulator of nitric oxide (NO) decay. A related kinetic model predicts the NO consumption rate.
22359545 normal physiological concentrations of cytoglobin do not offer cytoprotection from reactive oxygen species
22344671 RHBDF2 and CYGB may play distinctive roles in ovarian cancer and could be added to the growing roster of chromosome 17 genes implicated in this disease.
22025306 Cytoglobin, a protein that can be induced in response to oxidative stress, is elevated in most atrophic foci in adenocarcinoma of the prostate, suggesting hypoxic, and/or oxidative damage.
21674044 Caenorhabditis elegans globin GLB-26 (expressed from gene T22C1.2) has been studied in comparison with human neuroglobin (Ngb) and cytoglobin (Cygb) for its electron transfer properties
21631290 knockdown of cytoglobin expression can sensitize human glioma cells to oxidative stress
21171964 Binding of ferric cytoglobin to lipids and their subsequent transformation may be integral to the physiological function of cytoglobin, generating cell signalling lipid molecules under an oxidative environment.
20553503 Cytoglobin displays biphasic kinetics after the photolysis of CO, as a result of competition with an internal protein ligand, the E7 distal histidine.
20511233 Cygb has a nitric-oxide dioxygenase function and ascorbate and cytochrome b(5) have roles as reductants
19568272 CYGB gene is regulated by both promoter methylation and tumour hypoxia in HNSCC and that increased expression of this gene correlates with clincopathological measures of a tumour's biological aggression.
19147491 cytoglobin contributes to cell-mediated NO dioxygenation and represents an important NO sink in the vascular wall.
19001220 Neuroglobin and cytoglobin are colocalized within human retinal neurons and retinal pigment epithelium but not within glial cells.
18794132 Data constitute the first direct functional evidence for CYGB, the newest member of the globin family, as a tumor suppressor gene.
18353768 A role for cytoglobin in cytoprotection of neuronal cells from oxidative-related damage.
17936249 hypoxia responsive elements (HREs) at positions -141, -144 and -448 were essential for activation of CYGB expression under hypoxic conditions. The binding of hypoxia inducible factor protein to the HREs was confirmed.
16797742 Pomoter elements of human CYGB gene are located between -1113 to -10 relative to the translation start site.
16699195 The structure of a new crystal form of cytoglobin reveals a new dimerization arrangement of cytoglobin.
16698880 Results provide the first evidence to suggest the implication of CYGB in the pathogenesis of non-small cell lung cancer.
16510494 We now show that cytoglobin gene expression in oesophageal biopsies from tylotic patients is dramatically reduced by approximately 70% compared with normal oesophagus. Furthermore, both alleles are equally repressed
16449996 Cytoglobin is a novel candidate tumour suppressor gene highly methylated in upper aero-digestive tract squamous cancer
16201751 analysis of the proximal and distal histidine environment of cytoglobin and neuroglobin
15819897 molecular characterization of human and Drosophila cytoglobulins and neuroglobulins
15299006 oxygen binding in human neuroglobin and cytoglobin is allosterically regulated and temperature-dependent
15165856 reporting of X-ray crystallographic structure
15095869 Results describe the crystal structure of cytoglobin, which displays heme hexa-coordination.
15052627 hereditary neuralgic amyotrophy is not caused by point mutations of cytoglobin
14660570 differential expression of cytoglobin argues against a general respiratory function of this molecule, but rather indicates a connective tissue-specific function
14530264 results suggest a novel mechanism for the regulation of oxygen binding; contact with an appropriate electron donor would provoke the release of oxygen. Hence the oxygen affinity would be directly linked to the redox state of the cell.
12718557 characterization of the heme environmental structure of this protein, a fourth globin in humans
12359339 cloned, deduced amino acid sequence and expressed in diseased liver tissue where stellate cells were present
11919282 vertebrate myoglobins are in fact a specialized intracellular globin that evolved in adaptation to the special needs of muscle cells
11893755 A ubiquitously expressed human hexacoordinate hemoglobin

AA Sequence


Text Mined References (59)

PMID Year Title
26928591 2016 Peroxidase activation of cytoglobin by anionic phospholipids: Mechanisms and consequences.
26339645 2015 Cytoglobin as a Biomarker in Cancer: Potential Perspective for Diagnosis and Management.
26096935 2016 ?Np63 targets cytoglobin to inhibit oxidative stress-induced apoptosis in keratinocytes and lung cancer.
25665792 2015 Cytoglobin deficiency promotes liver cancer development from hepatosteatosis through activation of the oxidative stress pathway.
25601563 2015 Coupling of disulfide bond and distal histidine dissociation in human ferrous cytoglobin regulates ligand binding.
25416956 2014 A proteome-scale map of the human interactome network.
25327890 2015 Cytoglobin ligand binding regulated by changing haem-co-ordination in response to intramolecular disulfide bond formation and lipid interaction.
25269893 2014 DNA damage induced activation of Cygb stabilizes p53 and mediates G1 arrest.
24816917 2014 Cytoglobin in tumor hypoxia: novel insights into cancer suppression.
24737588 2014 Expression and biological role of cytoglobin in human ovarian cancer.
24632414 2014 Disulfide bonds regulate binding of exogenous ligand to human cytoglobin.
24296877 2014 Cytoglobin is expressed in hepatic stellate cells, but not in myofibroblasts, in normal and fibrotic human liver.
24037220 2013 Effects of distal mutation on the dynamic properties of carboxycytoglobin: a molecular dynamics simulation study.
24008134 2013 Reduction of the internal disulfide bond between Cys 38 and 83 switches the ligand migration pathway in cytoglobin.
23835959 2013 Cytoglobin and neuroglobin in the human brainstem and carotid body.
23710929 2013 Differences in oxygen-dependent nitric oxide metabolism by cytoglobin and myoglobin account for their differing functional roles.
23591990 2013 Cytoglobin has bimodal: tumour suppressor and oncogene functions in lung cancer cell lines.
23308092 2013 CO rebinding kinetics and molecular dynamics simulations highlight dynamic regulation of internal cavities in human cytoglobin.
23160832 2013 Neuroglobin and cytoglobin expression in the human brain.
22896706 2012 Characterization of the mechanism and magnitude of cytoglobin-mediated nitrite reduction and nitric oxide generation under anaerobic conditions.
22750003 2012 Effect of permanent middle cerebral artery occlusion on Cytoglobin expression in the mouse brain.
22577939 2012 Characterization of the function of cytoglobin as an oxygen-dependent regulator of nitric oxide concentration.
22359545 2012 Protection from intracellular oxidative stress by cytoglobin in normal and cancerous oesophageal cells.
22344671 2012 Chromosome 17q25 genes, RHBDF2 and CYGB, in ovarian cancer.
22025306 2012 Gene expression profiles and differential cytoglobin expression in atrophy and adenocarcinoma of the prostate.
21674044 2011 Electron transfer function versus oxygen delivery: a comparative study for several hexacoordinated globins across the animal kingdom.
21631290 2011 Knockdown of cytoglobin expression sensitizes human glioma cells to radiation and oxidative stress.
21171964 2011 Lipid binding to cytoglobin leads to a change in haem co-ordination: a role for cytoglobin in lipid signalling of oxidative stress.
20553503 2010 Cytoglobin conformations and disulfide bond formation.
20511233 2010 Nitric-oxide dioxygenase function of human cytoglobin with cellular reductants and in rat hepatocytes.
19568272 2009 Cytoglobin is upregulated by tumour hypoxia and silenced by promoter hypermethylation in head and neck cancer.
19147491 2009 Cytoglobin is expressed in the vasculature and regulates cell respiration and proliferation via nitric oxide dioxygenation.
19001220 2008 Patterns of distribution of oxygen-binding globins, neuroglobin and cytoglobin in human retina.
18794132 2008 Cytoglobin, the newest member of the globin family, functions as a tumor suppressor gene.
18353768 2008 Cellular protection from oxidative DNA damage by over-expression of the novel globin cytoglobin in vitro.
17936249 2007 Study of the hypoxia-dependent regulation of human CYGB gene.
16797742 2006 Characterization of human cytoglobin gene promoter region.
16699195 2006 High-resolution structure of human cytoglobin: identification of extra N- and C-termini and a new dimerization mode.
16698880 2006 Frequent genetic and epigenetic abnormalities contribute to the deregulation of cytoglobin in non-small cell lung cancer.
16510494 2006 Down-regulation of the cytoglobin gene, located on 17q25, in tylosis with oesophageal cancer (TOC): evidence for trans-allele repression.
16449996 2006 Promoter methylation of P16, RARbeta, E-cadherin, cyclin A1 and cytoglobin in oral cancer: quantitative evaluation using pyrosequencing.
16201751 2005 Structural characterization of the proximal and distal histidine environment of cytoglobin and neuroglobin.
15819897 2005 Hyperthermal stability of neuroglobin and cytoglobin.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15299006 2004 Allosteric regulation and temperature dependence of oxygen binding in human neuroglobin and cytoglobin. Molecular mechanisms and physiological significance.
15165856 2004 Structural basis of human cytoglobin for ligand binding.
15095869 2004 Crystal structure of cytoglobin: the fourth globin type discovered in man displays heme hexa-coordination.
15052627 2004 Genomic organization and mutation analysis of three candidate genes for hereditary neuralgic amyotrophy.
15044115 2004 Mapping protein matrix cavities in human cytoglobin through Xe atom binding.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
14660570 2004 Cytoglobin is a respiratory protein in connective tissue and neurons, which is up-regulated by hypoxia.
14530264 2003 The redox state of the cell regulates the ligand binding affinity of human neuroglobin and cytoglobin.
12796507 2003 A globin in the nucleus!
12718557 2003 Characterization of the heme environmental structure of cytoglobin, a fourth globin in humans.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12359339 2002 Characterization of human stellate cell activation-associated protein and its expression in human liver.
11919282 2002 Cytoglobin: a novel globin type ubiquitously expressed in vertebrate tissues.
11893755 2002 A ubiquitously expressed human hexacoordinate hemoglobin.
11320098 2001 Characterization of a stellate cell activation-associated protein (STAP) with peroxidase activity found in rat hepatic stellate cells.