{{Short description|Mammalian protein found in Homo sapiens}} {{Infobox_gene}} '''Cytoglobin''' is the protein product of '''CYGB''', a human and mammalian gene.<ref name="entrez"/>
Cytoglobin is a globin molecule ubiquitously expressed in all tissues and most notably utilized in marine mammals. It was discovered in 2001<ref>{{cite journal | vauthors = Kawada N, Kristensen DB, Asahina K, Nakatani K, Minamiyama Y, Seki S, Yoshizato K | title = Characterization of a stellate cell activation-associated protein (STAP) with peroxidase activity found in rat hepatic stellate cells | journal = The Journal of Biological Chemistry | volume = 276 | issue = 27 | pages = 25318–23 | date = Jul 2001 | pmid = 11320098 | doi = 10.1074/jbc.M102630200 | doi-access = free }}</ref> in hepatic stellate cells during liver fibrosis. Thus, it was originally called "stellate cell activated protein" or STAP.<ref>{{Cite journal |last1=Pesce |first1=Alessandra |last2=Bolognesi |first2=Martino |last3=Bocedi |first3=Alessio |last4=Ascenzi |first4=Paolo |last5=Dewilde |first5=Sylvia |last6=Moens |first6=Luc |last7=Hankeln |first7=Thomas |last8=Burmester |first8=Thorsten |date=December 2002 |title=Neuroglobin and cytoglobin: Fresh blood for the vertebrate globin family |url=https://www.embopress.org/doi/10.1093/embo-reports/kvf248 |journal=EMBO Reports |language=en |volume=3 |issue=12 |pages=1146–1151 |doi=10.1093/embo-reports/kvf248 |issn=1469-221X |pmc=1308314 |pmid=12475928}}</ref> It received its current name in 2002.<ref>{{cite journal | vauthors = Burmester T, Ebner B, Weich B, Hankeln T | title = Cytoglobin: a novel globin type ubiquitously expressed in vertebrate tissues | journal = Molecular Biology and Evolution | volume = 19 | issue = 4 | pages = 416–21 | date = Apr 2002 | pmid = 11919282 | doi = 10.1093/oxfordjournals.molbev.a004096 | doi-access = free }}</ref> 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.<ref name="sciencedaily">{{cite web | title = Why Diving Marine Mammals Resist Brain Damage from Low Oxygen| url= https://www.sciencedaily.com/releases/2007/12/071218192033.htm | work = ScienceDaily | date = 20 December 2007 }}</ref>
== 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.<ref name="entrez">{{cite web | title = Entrez Gene: CYGB cytoglobin| url = https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=114757 }}</ref><ref name="Trent_2002">{{cite journal | vauthors = Trent JT, Hargrove MS | title = A ubiquitously expressed human hexacoordinate hemoglobin | journal = The Journal of Biological Chemistry | volume = 277 | issue = 22 | pages = 19538–45 | date = May 2002 | pmid = 11893755 | doi = 10.1074/jbc.M201934200 | doi-access = free }}</ref>
== 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.<ref name=":0">{{Cite journal |last1=Keller |first1=T. C. Stevenson |last2=Lechauve |first2=Christophe |last3=Keller |first3=Alexander S. |last4=Brooks |first4=Steven |last5=Weiss |first5=Mitchell J. |last6=Columbus |first6=Linda |last7=Ackerman |first7=Hans |last8=Cortese-Krott |first8=Miriam M. |last9=Isakson |first9=Brant E. |date=2022-04-01 |title=The role of globins in cardiovascular physiology |journal=Physiological Reviews |language=en |volume=102 |issue=2 |pages=859–892 |doi=10.1152/physrev.00037.2020 |issn=0031-9333 |pmc=8799389 |pmid=34486392}}</ref>
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.<ref name=":1">{{Cite journal |last1=Hankeln |first1=Thomas |last2=Ebner |first2=Bettina |last3=Fuchs |first3=Christine |last4=Gerlach |first4=Frank |last5=Haberkamp |first5=Mark |last6=Laufs |first6=Tilmann L. |last7=Roesner |first7=Anja |last8=Schmidt |first8=Marc |last9=Weich |first9=Bettina |last10=Wystub |first10=Sylvia |last11=Saaler-Reinhardt |first11=Sigrid |last12=Reuss |first12=Stefan |last13=Bolognesi |first13=Martino |last14=Sanctis |first14=Daniele De |last15=Marden |first15=Michael C. |date=2005-01-01 |title=Neuroglobin and cytoglobin in search of their role in the vertebrate globin family |url=https://www.sciencedirect.com/science/article/abs/pii/S0162013404003514 |journal=Journal of Inorganic Biochemistry |series=Heme-diatomic interactions, Part 1 |volume=99 |issue=1 |pages=110–119 |doi=10.1016/j.jinorgbio.2004.11.009 |pmid=15598495 |issn=0162-0134|url-access=subscription }}</ref> left|thumb|400x400px|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.<ref name=":0" />
== 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.<ref name="pmid24296877">{{cite journal | vauthors = 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 | title = Cytoglobin is expressed in hepatic stellate cells, but not in myofibroblasts, in normal and fibrotic human liver | journal = Laboratory Investigation | volume = 94 | issue = 2 | pages = 192–207 | date = Feb 2014 | pmid = 24296877 | doi = 10.1038/labinvest.2013.135 | doi-access = free }}</ref>
== References == {{reflist}}
== Further reading == {{refbegin | 2}} * {{cite journal | vauthors = Kawada N, Kristensen DB, Asahina K, Nakatani K, Minamiyama Y, Seki S, Yoshizato K | title = Characterization of a stellate cell activation-associated protein (STAP) with peroxidase activity found in rat hepatic stellate cells | journal = The Journal of Biological Chemistry | volume = 276 | issue = 27 | pages = 25318–23 | date = Jul 2001 | pmid = 11320098 | doi = 10.1074/jbc.M102630200 | doi-access = free }} * {{cite journal | vauthors = Burmester T, Ebner B, Weich B, Hankeln T | title = Cytoglobin: a novel globin type ubiquitously expressed in vertebrate tissues | journal = Molecular Biology and Evolution | volume = 19 | issue = 4 | pages = 416–21 | date = Apr 2002 | pmid = 11919282 | doi = 10.1093/oxfordjournals.molbev.a004096 | doi-access = free }} * {{cite journal | vauthors = Asahina K, Kawada N, Kristensen DB, Nakatani K, Seki S, Shiokawa M, Tateno C, Obara M, Yoshizato K | title = Characterization of human stellate cell activation-associated protein and its expression in human liver | journal = Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression | volume = 1577 | issue = 3 | pages = 471–5 | date = Sep 2002 | pmid = 12359339 | doi = 10.1016/s0167-4781(02)00477-3 }} * {{cite journal | vauthors = Sawai H, Kawada N, Yoshizato K, Nakajima H, Aono S, Shiro Y | title = Characterization of the heme environmental structure of cytoglobin, a fourth globin in humans | journal = Biochemistry | volume = 42 | issue = 17 | pages = 5133–42 | date = May 2003 | pmid = 12718557 | doi = 10.1021/bi027067e }} * {{cite journal | vauthors = Geuens E, Brouns I, Flamez D, Dewilde S, Timmermans JP, Moens L | title = A globin in the nucleus! | journal = The Journal of Biological Chemistry | volume = 278 | issue = 33 | pages = 30417–20 | date = Aug 2003 | pmid = 12796507 | doi = 10.1074/jbc.C300203200 | doi-access = free }} * {{cite journal | vauthors = Hamdane D, Kiger L, Dewilde S, Green BN, Pesce A, Uzan J, Burmester T, Hankeln T, Bolognesi M, Moens L, Marden MC | title = The redox state of the cell regulates the ligand binding affinity of human neuroglobin and cytoglobin | journal = The Journal of Biological Chemistry | volume = 278 | issue = 51 | pages = 51713–21 | date = Dec 2003 | pmid = 14530264 | doi = 10.1074/jbc.M309396200 | doi-access = free }} * {{cite journal | vauthors = Schmidt M, Gerlach F, Avivi A, Laufs T, Wystub S, Simpson JC, Nevo E, Saaler-Reinhardt S, Reuss S, Hankeln T, Burmester T | title = Cytoglobin is a respiratory protein in connective tissue and neurons, which is up-regulated by hypoxia | journal = The Journal of Biological Chemistry | volume = 279 | issue = 9 | pages = 8063–9 | date = Feb 2004 | pmid = 14660570 | doi = 10.1074/jbc.M310540200 | doi-access = free }} * {{cite journal | vauthors = Hünermund G, Schirmacher A, Ringelstein B, Young P, Watts GD, Meuleman J, Nelis E, Chance PF, Timmerman V, Stögbauer F, Kuhlenbäumer G | title = Genomic organization and mutation analysis of three candidate genes for hereditary neuralgic amyotrophy | journal = Muscle & Nerve | volume = 29 | issue = 4 | pages = 601–4 | date = Apr 2004 | pmid = 15052627 | doi = 10.1002/mus.20009 | s2cid = 39945876 }} * {{cite journal | vauthors = de Sanctis D, Dewilde S, Pesce A, Moens L, Ascenzi P, Hankeln T, Burmester T, Bolognesi M | title = Crystal structure of cytoglobin: the fourth globin type discovered in man displays heme hexa-coordination | journal = Journal of Molecular Biology | volume = 336 | issue = 4 | pages = 917–27 | date = Feb 2004 | pmid = 15095869 | doi = 10.1016/j.jmb.2003.12.063 | s2cid = 21144924 }} * {{cite journal | vauthors = Sugimoto H, Makino M, Sawai H, Kawada N, Yoshizato K, Shiro Y | title = Structural basis of human cytoglobin for ligand binding | journal = Journal of Molecular Biology | volume = 339 | issue = 4 | pages = 873–85 | date = Jun 2004 | pmid = 15165856 | doi = 10.1016/j.jmb.2004.04.024 }} * {{cite journal | vauthors = Fago A, Hundahl C, Dewilde S, Gilany K, Moens L, Weber RE | title = Allosteric regulation and temperature dependence of oxygen binding in human neuroglobin and cytoglobin. Molecular mechanisms and physiological significance | journal = The Journal of Biological Chemistry | volume = 279 | issue = 43 | pages = 44417–26 | date = Oct 2004 | pmid = 15299006 | doi = 10.1074/jbc.M407126200 | doi-access = free }} * {{cite journal | vauthors = Hamdane D, Kiger L, Dewilde S, Uzan J, Burmester T, Hankeln T, Moens L, Marden MC | title = Hyperthermal stability of neuroglobin and cytoglobin | journal = The FEBS Journal | volume = 272 | issue = 8 | pages = 2076–84 | date = Apr 2005 | pmid = 15819897 | doi = 10.1111/j.1742-4658.2005.04635.x | s2cid = 13377138 | doi-access = free }} * {{cite journal | vauthors = Sawai H, Makino M, Mizutani Y, Ohta T, Sugimoto H, Uno T, Kawada N, Yoshizato K, Kitagawa T, Shiro Y | title = Structural characterization of the proximal and distal histidine environment of cytoglobin and neuroglobin | journal = Biochemistry | volume = 44 | issue = 40 | pages = 13257–65 | date = Oct 2005 | pmid = 16201751 | doi = 10.1021/bi050997o }} * {{cite journal | vauthors = Shaw RJ, Liloglou T, Rogers SN, Brown JS, Vaughan ED, Lowe D, Field JK, Risk JM | title = Promoter methylation of P16, RARbeta, E-cadherin, cyclin A1 and cytoglobin in oral cancer: quantitative evaluation using pyrosequencing | journal = British Journal of Cancer | volume = 94 | issue = 4 | pages = 561–8 | date = Feb 2006 | pmid = 16449996 | pmc = 2361183 | doi = 10.1038/sj.bjc.6602972 }} * {{cite journal | vauthors = McRonald FE, Liloglou T, Xinarianos G, Hill L, Rowbottom L, Langan JE, Ellis A, Shaw JM, Field JK, Risk JM | title = Down-regulation of the cytoglobin gene, located on 17q25, in tylosis with oesophageal cancer (TOC): evidence for trans-allele repression | journal = Human Molecular Genetics | volume = 15 | issue = 8 | pages = 1271–7 | date = Apr 2006 | pmid = 16510494 | doi = 10.1093/hmg/ddl042 | doi-access = free }} * {{cite journal | vauthors = Xinarianos G, McRonald FE, Risk JM, Bowers NL, Nikolaidis G, Field JK, Liloglou T | title = Frequent genetic and epigenetic abnormalities contribute to the deregulation of cytoglobin in non-small cell lung cancer | journal = Human Molecular Genetics | volume = 15 | issue = 13 | pages = 2038–44 | date = Jul 2006 | pmid = 16698880 | doi = 10.1093/hmg/ddl128 | doi-access = free }} {{refend}}
== External links == * {{MeshName|cytoglobin}}
{{PDB Gallery|geneid=114757}} {{Hemeproteins}}
Category:Hemoproteins