View source for ETHE1

{{Short description|Protein-coding gene in the species Homo sapiens}}
{{cs1 config|name-list-style=vanc}}{{Infobox_gene}}
'''Protein ETHE1, mitochondrial''', also known as "ethylmalonic encephalopathy 1 protein" and "per sulfide dioxygenase", is a [[protein]] that in humans is encoded by the ''ETHE1'' [[gene]] located on chromosome 19.<ref name="entrez">{{cite web | title = Entrez Gene: ETHE1 ethylmalonic encephalopathy 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=23474}}</ref>

== Structure ==

The human ETHE1 [[gene]] consists of 7 exons and encodes for a protein that is approximately 27 kDa in size.

== Function ==

This gene encodes a protein that is expressed mainly in the gastrointestinal tract, but also in several other tissues such as the liver and the thyroid.<ref name="entrez" />

The ETHE1 protein is thought to localize primarily to the [[mitochondrial matrix]]<ref name="ReferenceA">{{cite journal |vauthors=Tiranti V, Viscomi C, Hildebrandt T, Di Meo I, Mineri R, Tiveron C, Levitt MD, Prelle A, Fagiolari G, Rimoldi M, Zeviani M |title=Loss of ETHE1, a mitochondrial dioxygenase, causes fatal sulfide toxicity in ethylmalonic encephalopathy |journal=Nat. Med. |volume=15 |issue=2 |pages=200–5 |year=2009 |pmid=19136963 |doi=10.1038/nm.1907 |hdl=11577/3321438 |s2cid=5970257 }}</ref><ref name="ReferenceB">{{cite journal |vauthors=Tiranti V, D'Adamo P, Briem E, Ferrari G, Mineri R, Lamantea E, Mandel H, Balestri P, Garcia-Silva MT, Vollmer B, Rinaldo P, Hahn SH, Leonard J, Rahman S, Dionisi-Vici C, Garavaglia B, Gasparini P, Zeviani M |title=Ethylmalonic encephalopathy is caused by mutations in ETHE1, a gene encoding a mitochondrial matrix protein |journal=Am. J. Hum. Genet. |volume=74 |issue=2 |pages=239–52 |year=2004 |pmid=14732903 |pmc=1181922 |doi=10.1086/381653 }}</ref> and functions as a [[sulfur dioxygenase]].  Sulfur deoxygenates are proteins that function in [[sulfur metabolism]]. The ETHE1 protein is thought to catalyze the following reaction:

: [[sulfur]] + O<sub>2</sub> + H<sub>2</sub>O <math>\rightleftharpoons</math> [[sulfite]] + 2 H<sup>+</sup> (overall reaction)
: (1a) [[glutathione]] + sulfur <math>\rightleftharpoons</math> S-sulfanylglutathione (glutathione persulfide, spontaneous reaction)
: (1b) S-sulfanylglutathione + O<sub>2</sub> + H<sub>2</sub>O <math>\rightleftharpoons</math> glutathione + sulfite + 2 H<sup>+</sup><ref name="ReferenceA"/>

and requires [[iron]]<ref name="ReferenceC">{{cite journal |vauthors=Kabil O, Banerjee R |title=Characterization of patient mutations in human persulfide dioxygenase (ETHE1) involved in H2S catabolism |journal=J. Biol. Chem. |volume=287 |issue=53 |pages=44561–7 |year=2012 |pmid=23144459 |pmc=3531769 |doi=10.1074/jbc.M112.407411 |doi-access=free }}</ref> and possibly [[glutathione]]<ref name="ReferenceC"/> as [[Cofactor (biochemistry)|cofactors]]. The physiological [[substrate (biochemistry)|substrate]] of ETHE1 is thought to be [[glutathione persulfide]],<ref name="ReferenceC"/> an intermediate [[metabolite]] involved in [[hydrogen sulfide]] degradation.


== Clinical significance ==

Mutations in ETHE1 [[gene]]  are thought to cause [[ethylmalonic encephalopathy]],<ref name="ReferenceB"/><ref name=omim>{{cite web|title=Encephalopathy, Ethylmalonic|url=http://www.omim.org/entry/602473|publisher=[[Johns Hopkins University]]|access-date=2012-05-12}}</ref> a rare [[inborn error of metabolism]]. Patients carrying ETHE1 mutations have been found to exhibit lower activity of ETHE1 and affinity for the ETHE1 substrate.<ref name="ReferenceC"/> Mouse models of Ethe1 genetic ablation likewise exhibited reduced sulfide dioxygenase catabolism and cranial features of ethylmalonic encephalopathy.<ref name="ReferenceA"/> Decrease in sulfide dioxygenase activity results in abnormal [[catabolism]] of [[hydrogen sulfide]], a gas-phase signaling molecule in the central nervous system,<ref name="ReferenceC"/> whose accumulation is thought to inhibit [[cytochrome c oxidase]] activity in the [[respiratory chain]] of the [[mitochondrion]].<ref name="ReferenceA"/> However, other metabolic pathways may also be involved that could exert a modulatory effect on [[hydrogen sulfide]] toxicity.<ref>{{cite journal |vauthors=Barth M, Ottolenghi C, Hubert L, Chrétien D, Serre V, Gobin S, Romano S, Vassault A, Sefiani A, Ricquier D, Boddaert N, Brivet M, de Keyzer Y, Munnich A, Duran M, Rabier D, Valayannopoulos V, de Lonlay P |title=Multiple sources of metabolic disturbance in ETHE1-related ethylmalonic encephalopathy |journal=J. Inherit. Metab. Dis. |volume=33 |pages=S443–53 |year=2010 |issue=Suppl 3 |pmid=20978941 |doi=10.1007/s10545-010-9227-y |s2cid=29056515 }}</ref>

== Interactions ==

ETHE1 has been shown to [[Protein-protein interaction|interact]] with [[RELA]].<ref name=pmid12398897>{{cite journal | vauthors = Higashitsuji H, Higashitsuji H, Nagao T, Nonoguchi K, Fujii S, Itoh K, Fujita J | title = A novel protein overexpressed in hepatoma accelerates export of NF-kappa B from the nucleus and inhibits p53-dependent apoptosis | journal = Cancer Cell | volume = 2 | issue = 4 | pages = 335–46 | date = Oct 2002 | pmid = 12398897 | doi = 10.1016/S1535-6108(02)00152-6 | hdl = 2433/148468 | hdl-access = free }}</ref>

== References ==
{{reflist|33em}}

== Further reading ==
{{refbegin|33em}}
* {{cite journal | vauthors = McCoy JG, Bingman CA, Bitto E, Holdorf MM, Makaroff CA, Phillips GN | title = Structure of an ETHE1-like protein from Arabidopsis thaliana | journal = Acta Crystallographica Section D | volume = 62 | issue = Pt 9 | pages = 964–70 | date = Sep 2006 | pmid = 16929096 | doi = 10.1107/S0907444906020592 | bibcode = 2006AcCrD..62..964M }}
* {{cite journal | vauthors = Mehrle A, Rosenfelder H, Schupp I, del Val C, Arlt D, Hahne F, Bechtel S, Simpson J, Hofmann O, Hide W, Glatting KH, Huber W, Pepperkok R, Poustka A, Wiemann S | title = The LIFEdb database in 2006 | journal = Nucleic Acids Research | volume = 34 | issue = Database issue | pages = D415-8 | date = Jan 2006 | pmid = 16381901 | pmc = 1347501 | doi = 10.1093/nar/gkj139 }}
* {{cite journal | vauthors = Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M | title = Towards a proteome-scale map of the human protein-protein interaction network | journal = Nature | volume = 437 | issue = 7062 | pages = 1173–8 | date = Oct 2005 | pmid = 16189514 | doi = 10.1038/nature04209 | bibcode = 2005Natur.437.1173R | s2cid = 4427026 }}
* {{cite journal | vauthors = Tiranti V, Briem E, Lamantea E, Mineri R, Papaleo E, De Gioia L, Forlani F, Rinaldo P, Dickson P, Abu-Libdeh B, Cindro-Heberle L, Owaidha M, Jack RM, Christensen E, Burlina A, Zeviani M | title = ETHE1 mutations are specific to ethylmalonic encephalopathy | journal = Journal of Medical Genetics | volume = 43 | issue = 4 | pages = 340–6 | date = Apr 2006 | pmid = 16183799 | pmc = 2563233 | doi = 10.1136/jmg.2005.036210 }}
* {{cite journal | vauthors = Wiemann S, Arlt D, Huber W, Wellenreuther R, Schleeger S, Mehrle A, Bechtel S, Sauermann M, Korf U, Pepperkok R, Sültmann H, Poustka A | title = From ORFeome to biology: a functional genomics pipeline | journal = Genome Research | volume = 14 | issue = 10B | pages = 2136–44 | date = Oct 2004 | pmid = 15489336 | pmc = 528930 | doi = 10.1101/gr.2576704 }}
* {{cite journal | vauthors = Tiranti V, D'Adamo P, Briem E, Ferrari G, Mineri R, Lamantea E, Mandel H, Balestri P, Garcia-Silva MT, Vollmer B, Rinaldo P, Hahn SH, Leonard J, Rahman S, Dionisi-Vici C, Garavaglia B, Gasparini P, Zeviani M | title = Ethylmalonic encephalopathy is caused by mutations in ETHE1, a gene encoding a mitochondrial matrix protein | journal = American Journal of Human Genetics | volume = 74 | issue = 2 | pages = 239–52 | date = Feb 2004 | pmid = 14732903 | pmc = 1181922 | doi = 10.1086/381653 }}
* {{cite journal | vauthors = Higashitsuji H, Higashitsuji H, Nagao T, Nonoguchi K, Fujii S, Itoh K, Fujita J | title = A novel protein overexpressed in hepatoma accelerates export of NF-kappa B from the nucleus and inhibits p53-dependent apoptosis | journal = Cancer Cell | volume = 2 | issue = 4 | pages = 335–46 | date = Oct 2002 | pmid = 12398897 | doi = 10.1016/S1535-6108(02)00152-6 | hdl = 2433/148468 | hdl-access = free }}
* {{cite journal | vauthors = Simpson JC, Wellenreuther R, Poustka A, Pepperkok R, Wiemann S | title = Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing | journal = EMBO Reports | volume = 1 | issue = 3 | pages = 287–92 | date = Sep 2000 | pmid = 11256614 | pmc = 1083732 | doi = 10.1093/embo-reports/kvd058 }}
* {{cite journal | vauthors = Hartley JL, Temple GF, Brasch MA | title = DNA cloning using in vitro site-specific recombination | journal = Genome Research | volume = 10 | issue = 11 | pages = 1788–95 | date = Nov 2000 | pmid = 11076863 | pmc = 310948 | doi = 10.1101/gr.143000 }}
{{refend}}

[[Category:Genes]]
[[Category:Human proteins]]


{{gene-19-stub}}