Cytoglobin

Template:Short description An Error has occurred retrieving Wikidata item for infobox 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 in hepatic stellate cells during liver fibrosis. Thus, it was originally called "stellate cell activated protein" or STAP. It received its current name in 2002. It is thought to help in the distribution and storage of oxygen as well as protect against hypoxia by scavenging reactive oxygen species . The predicted function of cytoglobin is the facilitation of oxygen among tissues that don't express myoglobin.

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.

Structure

Cytoglobin has 30-40% sequence homology with myoglobin, and has a similar oxygen binding affinity. One of the major differences is the presence of a 20 amino acids extension at both the n and c terminus.

Cytoglobin is a hexacoordinate heme protein. The heme iron in coordinated with histidine residues on both sides, HisF8 and HisE7. The HisE7 is considered to be an "endogenous ligand." In order for oxygen or another gaseous ligand to bind, the HisE7 must dissociate from the iron, making the binding kinetics relatively slow.

Diagram of how the heme group in cytoglobin interacts with the surrounding amino acids of the globin protein. Normally, the iron is coordinated with histidine residues on both sides. The HisE7 must be dissociated in order for oxygen to bind.

In an oxidizing environment, a disulfide bond between Cys38 and Cys83 of the protein forms and causes a conformational change to move HisE7 out of the way, allowing oxygen to bind. Thus, oxygen binding is dependent on the redox state of the tissue.

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.

Further reading

• Kawada N, Kristensen DB, Asahina K, Nakatani K, Minamiyama Y, Seki S, Yoshizato K (Jul 2001). "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. doi:10.1074/jbc.M102630200. PMID 11320098.
• Burmester T, Ebner B, Weich B, Hankeln T (Apr 2002). "Cytoglobin: a novel globin type ubiquitously expressed in vertebrate tissues". Molecular Biology and Evolution. 19 (4): 416–21. doi:10.1093/oxfordjournals.molbev.a004096. PMID 11919282.
• Asahina K, Kawada N, Kristensen DB, Nakatani K, Seki S, Shiokawa M, Tateno C, Obara M, Yoshizato K (Sep 2002). "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. doi:10.1016/s0167-4781(02)00477-3. PMID 12359339.
• Sawai H, Kawada N, Yoshizato K, Nakajima H, Aono S, Shiro Y (May 2003). "Characterization of the heme environmental structure of cytoglobin, a fourth globin in humans". Biochemistry. 42 (17): 5133–42. doi:10.1021/bi027067e. PMID 12718557.
• Geuens E, Brouns I, Flamez D, Dewilde S, Timmermans JP, Moens L (Aug 2003). "A globin in the nucleus!". The Journal of Biological Chemistry. 278 (33): 30417–20. doi:10.1074/jbc.C300203200. PMID 12796507.
• Hamdane D, Kiger L, Dewilde S, Green BN, Pesce A, Uzan J, Burmester T, Hankeln T, Bolognesi M, Moens L, Marden MC (Dec 2003). "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. doi:10.1074/jbc.M309396200. PMID 14530264.
• Schmidt M, Gerlach F, Avivi A, Laufs T, Wystub S, Simpson JC, Nevo E, Saaler-Reinhardt S, Reuss S, Hankeln T, Burmester T (Feb 2004). "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. doi:10.1074/jbc.M310540200. PMID 14660570.
• Hünermund G, Schirmacher A, Ringelstein B, Young P, Watts GD, Meuleman J, Nelis E, Chance PF, Timmerman V, Stögbauer F, Kuhlenbäumer G (Apr 2004). "Genomic organization and mutation analysis of three candidate genes for hereditary neuralgic amyotrophy". Muscle & Nerve. 29 (4): 601–4. doi:10.1002/mus.20009. PMID 15052627. S2CID 39945876.
• de Sanctis D, Dewilde S, Pesce A, Moens L, Ascenzi P, Hankeln T, Burmester T, Bolognesi M (Feb 2004). "Crystal structure of cytoglobin: the fourth globin type discovered in man displays heme hexa-coordination". Journal of Molecular Biology. 336 (4): 917–27. doi:10.1016/j.jmb.2003.12.063. PMID 15095869. S2CID 21144924.
• Sugimoto H, Makino M, Sawai H, Kawada N, Yoshizato K, Shiro Y (Jun 2004). "Structural basis of human cytoglobin for ligand binding". Journal of Molecular Biology. 339 (4): 873–85. doi:10.1016/j.jmb.2004.04.024. PMID 15165856.
• Fago A, Hundahl C, Dewilde S, Gilany K, Moens L, Weber RE (Oct 2004). "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. doi:10.1074/jbc.M407126200. PMID 15299006.
• Hamdane D, Kiger L, Dewilde S, Uzan J, Burmester T, Hankeln T, Moens L, Marden MC (Apr 2005). "Hyperthermal stability of neuroglobin and cytoglobin". The FEBS Journal. 272 (8): 2076–84. doi:10.1111/j.1742-4658.2005.04635.x. PMID 15819897. S2CID 13377138.
• Sawai H, Makino M, Mizutani Y, Ohta T, Sugimoto H, Uno T, Kawada N, Yoshizato K, Kitagawa T, Shiro Y (Oct 2005). "Structural characterization of the proximal and distal histidine environment of cytoglobin and neuroglobin". Biochemistry. 44 (40): 13257–65. doi:10.1021/bi050997o. PMID 16201751.
• Shaw RJ, Liloglou T, Rogers SN, Brown JS, Vaughan ED, Lowe D, Field JK, Risk JM (Feb 2006). "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. doi:10.1038/sj.bjc.6602972. PMC 2361183. PMID 16449996.
• McRonald FE, Liloglou T, Xinarianos G, Hill L, Rowbottom L, Langan JE, Ellis A, Shaw JM, Field JK, Risk JM (Apr 2006). "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. doi:10.1093/hmg/ddl042. PMID 16510494.
• Xinarianos G, McRonald FE, Risk JM, Bowers NL, Nikolaidis G, Field JK, Liloglou T (Jul 2006). "Frequent genetic and epigenetic abnormalities contribute to the deregulation of cytoglobin in non-small cell lung cancer". Human Molecular Genetics. 15 (13): 2038–44. doi:10.1093/hmg/ddl128. PMID 16698880.

External links

• cytoglobin at the U.S. National Library of Medicine Medical Subject Headings (MeSH)