Cytoglobin Explained

Cytoglobin is the protein product of CYGB, a human and mammalian gene.

Cytoglobin is a globin molecule ubiquitously expressed in all tissues and most notably utilized in marine mammals. It was discovered in 2001^[1] and named cytoglobin in 2002.^[2] It is thought to protect against hypoxia. The predicted function of cytoglobin is the transfer of oxygen from arterial blood to the brain.^[3]

Function

Cytoglobin is a ubiquitously expressed hexacoordinate hemoglobin that may facilitate diffusion of oxygen through tissues, scavenge nitric oxide or reactive oxygen species, or serve a protective function during oxidative stress.^{[4] [5]}

Applications

CYGB expression can be used as a specific marker with which hepatic stellate cells can be distinguished from portal myofibroblasts in the damaged human liver.^[6]

Further reading

• Kawada N, Kristensen DB, Asahina K, Nakatani K, Minamiyama Y, Seki S, Yoshizato K . Characterization of a stellate cell activation-associated protein (STAP) with peroxidase activity found in rat hepatic stellate cells . The Journal of Biological Chemistry . 276 . 27 . 25318–23 . Jul 2001 . 11320098 . 10.1074/jbc.M102630200 . free .
• Burmester T, Ebner B, Weich B, Hankeln T . Cytoglobin: a novel globin type ubiquitously expressed in vertebrate tissues . Molecular Biology and Evolution . 19 . 4 . 416–21 . Apr 2002 . 11919282 . 10.1093/oxfordjournals.molbev.a004096 . free .
• Asahina K, Kawada N, Kristensen DB, Nakatani K, Seki S, Shiokawa M, Tateno C, Obara M, Yoshizato K . Characterization of human stellate cell activation-associated protein and its expression in human liver . Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression . 1577 . 3 . 471–5 . Sep 2002 . 12359339 . 10.1016/s0167-4781(02)00477-3 .
• Sawai H, Kawada N, Yoshizato K, Nakajima H, Aono S, Shiro Y . Characterization of the heme environmental structure of cytoglobin, a fourth globin in humans . Biochemistry . 42 . 17 . 5133–42 . May 2003 . 12718557 . 10.1021/bi027067e .
• Geuens E, Brouns I, Flamez D, Dewilde S, Timmermans JP, Moens L . A globin in the nucleus! . The Journal of Biological Chemistry . 278 . 33 . 30417–20 . Aug 2003 . 12796507 . 10.1074/jbc.C300203200 . free .
• Hamdane D, Kiger L, Dewilde S, Green BN, Pesce A, Uzan J, Burmester T, Hankeln T, Bolognesi M, Moens L, Marden MC . The redox state of the cell regulates the ligand binding affinity of human neuroglobin and cytoglobin . The Journal of Biological Chemistry . 278 . 51 . 51713–21 . Dec 2003 . 14530264 . 10.1074/jbc.M309396200 . free .
• Schmidt M, Gerlach F, Avivi A, Laufs T, Wystub S, Simpson JC, Nevo E, Saaler-Reinhardt S, Reuss S, Hankeln T, Burmester T . Cytoglobin is a respiratory protein in connective tissue and neurons, which is up-regulated by hypoxia . The Journal of Biological Chemistry . 279 . 9 . 8063–9 . Feb 2004 . 14660570 . 10.1074/jbc.M310540200 . free .
• Hünermund G, Schirmacher A, Ringelstein B, Young P, Watts GD, Meuleman J, Nelis E, Chance PF, Timmerman V, Stögbauer F, Kuhlenbäumer G . Genomic organization and mutation analysis of three candidate genes for hereditary neuralgic amyotrophy . Muscle & Nerve . 29 . 4 . 601–4 . Apr 2004 . 15052627 . 10.1002/mus.20009 . 39945876 .
• de Sanctis D, Dewilde S, Pesce A, Moens L, Ascenzi P, Hankeln T, Burmester T, Bolognesi M . Crystal structure of cytoglobin: the fourth globin type discovered in man displays heme hexa-coordination . Journal of Molecular Biology . 336 . 4 . 917–27 . Feb 2004 . 15095869 . 10.1016/j.jmb.2003.12.063 . 21144924 .
• Sugimoto H, Makino M, Sawai H, Kawada N, Yoshizato K, Shiro Y . Structural basis of human cytoglobin for ligand binding . Journal of Molecular Biology . 339 . 4 . 873–85 . Jun 2004 . 15165856 . 10.1016/j.jmb.2004.04.024 .
• Fago A, Hundahl C, Dewilde S, Gilany K, Moens L, Weber RE . Allosteric regulation and temperature dependence of oxygen binding in human neuroglobin and cytoglobin. Molecular mechanisms and physiological significance . The Journal of Biological Chemistry . 279 . 43 . 44417–26 . Oct 2004 . 15299006 . 10.1074/jbc.M407126200 . free .
• Hamdane D, Kiger L, Dewilde S, Uzan J, Burmester T, Hankeln T, Moens L, Marden MC . Hyperthermal stability of neuroglobin and cytoglobin . The FEBS Journal . 272 . 8 . 2076–84 . Apr 2005 . 15819897 . 10.1111/j.1742-4658.2005.04635.x . 13377138 . free .
• Sawai H, Makino M, Mizutani Y, Ohta T, Sugimoto H, Uno T, Kawada N, Yoshizato K, Kitagawa T, Shiro Y . Structural characterization of the proximal and distal histidine environment of cytoglobin and neuroglobin . Biochemistry . 44 . 40 . 13257–65 . Oct 2005 . 16201751 . 10.1021/bi050997o .
• Shaw RJ, Liloglou T, Rogers SN, Brown JS, Vaughan ED, Lowe D, Field JK, Risk JM . Promoter methylation of P16, RARbeta, E-cadherin, cyclin A1 and cytoglobin in oral cancer: quantitative evaluation using pyrosequencing . British Journal of Cancer . 94 . 4 . 561–8 . Feb 2006 . 16449996 . 2361183 . 10.1038/sj.bjc.6602972 .
• McRonald FE, Liloglou T, Xinarianos G, Hill L, Rowbottom L, Langan JE, Ellis A, Shaw JM, Field JK, Risk JM . Down-regulation of the cytoglobin gene, located on 17q25, in tylosis with oesophageal cancer (TOC): evidence for trans-allele repression . Human Molecular Genetics . 15 . 8 . 1271–7 . Apr 2006 . 16510494 . 10.1093/hmg/ddl042 . free .
• Xinarianos G, McRonald FE, Risk JM, Bowers NL, Nikolaidis G, Field JK, Liloglou T . Frequent genetic and epigenetic abnormalities contribute to the deregulation of cytoglobin in non-small cell lung cancer . Human Molecular Genetics . 15 . 13 . 2038–44 . Jul 2006 . 16698880 . 10.1093/hmg/ddl128 . free .

Notes and References

1. Kawada N, Kristensen DB, Asahina K, Nakatani K, Minamiyama Y, Seki S, Yoshizato K . Characterization of a stellate cell activation-associated protein (STAP) with peroxidase activity found in rat hepatic stellate cells . The Journal of Biological Chemistry . 276 . 27 . 25318–23 . Jul 2001 . 11320098 . 10.1074/jbc.M102630200 . free .
2. Burmester T, Ebner B, Weich B, Hankeln T . Cytoglobin: a novel globin type ubiquitously expressed in vertebrate tissues . Molecular Biology and Evolution . 19 . 4 . 416–21 . Apr 2002 . 11919282 . 10.1093/oxfordjournals.molbev.a004096 . free .
3. Web site: Why Diving Marine Mammals Resist Brain Damage from Low Oxygen. ScienceDaily . 20 December 2007 .
4. Web site: Entrez Gene: CYGB cytoglobin.
5. Trent JT, Hargrove MS . A ubiquitously expressed human hexacoordinate hemoglobin . The Journal of Biological Chemistry . 277 . 22 . 19538–45 . May 2002 . 11893755 . 10.1074/jbc.M201934200 . free .
6. Motoyama H, Komiya T, Thuy le TT, Tamori A, Enomoto M, Morikawa H, Iwai S, Uchida-Kobayashi S, Fujii H, Hagihara A, Kawamura E, Murakami Y, Yoshizato K, Kawada N . Cytoglobin is expressed in hepatic stellate cells, but not in myofibroblasts, in normal and fibrotic human liver . Laboratory Investigation . 94 . 2 . 192–207 . Feb 2014 . 24296877 . 10.1038/labinvest.2013.135 . free .