ETHE1
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| ETHE1 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Identifiers | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Aliases | ETHE1, HSCO, YF13H12, persulfide dioxygenase, ETHE1 persulfide dioxygenase | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 608451; MGI: 1913321; HomoloGene: 8622; GeneCards: ETHE1; OMA:ETHE1 - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
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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.[5]
Structure
[edit]The human ETHE1 gene consists of 7 exons and encodes for a protein that is approximately 27 kDa in size.
Function
[edit]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.[5]
The ETHE1 protein is thought to localize primarily to the mitochondrial matrix[6][7] 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 + O2 + H2O sulfite + 2 H+ (overall reaction)
- (1a) glutathione + sulfur S-sulfanylglutathione (glutathione persulfide, spontaneous reaction)
- (1b) S-sulfanylglutathione + O2 + H2O glutathione + sulfite + 2 H+[6]
and requires iron[8] and possibly glutathione[8] as cofactors. The physiological substrate of ETHE1 is thought to be glutathione persulfide,[8] an intermediate metabolite involved in hydrogen sulfide degradation.
Clinical significance
[edit]Mutations in ETHE1 gene are thought to cause ethylmalonic encephalopathy,[7][9] 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.[8] Mouse models of Ethe1 genetic ablation likewise exhibited reduced sulfide dioxygenase catabolism and cranial features of ethylmalonic encephalopathy.[6] Decrease in sulfide dioxygenase activity results in abnormal catabolism of hydrogen sulfide, a gas-phase signaling molecule in the central nervous system,[8] whose accumulation is thought to inhibit cytochrome c oxidase activity in the respiratory chain of the mitochondrion.[6] However, other metabolic pathways may also be involved that could exert a modulatory effect on hydrogen sulfide toxicity.[10]
Interactions
[edit]ETHE1 has been shown to interact with RELA.[11]
References
[edit]- ^ a b c GRCh38: Ensembl release 89: ENSG00000105755 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000064254 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ a b "Entrez Gene: ETHE1 ethylmalonic encephalopathy 1".
- ^ a b c d Tiranti V, Viscomi C, Hildebrandt T, Di Meo I, Mineri R, Tiveron C, Levitt MD, Prelle A, Fagiolari G, Rimoldi M, Zeviani M (2009). "Loss of ETHE1, a mitochondrial dioxygenase, causes fatal sulfide toxicity in ethylmalonic encephalopathy". Nat. Med. 15 (2): 200–5. doi:10.1038/nm.1907. hdl:11577/3321438. PMID 19136963. S2CID 5970257.
- ^ a b 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 (2004). "Ethylmalonic encephalopathy is caused by mutations in ETHE1, a gene encoding a mitochondrial matrix protein". Am. J. Hum. Genet. 74 (2): 239–52. doi:10.1086/381653. PMC 1181922. PMID 14732903.
- ^ a b c d e Kabil O, Banerjee R (2012). "Characterization of patient mutations in human persulfide dioxygenase (ETHE1) involved in H2S catabolism". J. Biol. Chem. 287 (53): 44561–7. doi:10.1074/jbc.M112.407411. PMC 3531769. PMID 23144459.
- ^ "Encephalopathy, Ethylmalonic". Johns Hopkins University. Retrieved 2012-05-12.
- ^ 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 (2010). "Multiple sources of metabolic disturbance in ETHE1-related ethylmalonic encephalopathy". J. Inherit. Metab. Dis. 33 (Suppl 3): S443–53. doi:10.1007/s10545-010-9227-y. PMID 20978941. S2CID 29056515.
- ^ Higashitsuji H, Higashitsuji H, Nagao T, Nonoguchi K, Fujii S, Itoh K, Fujita J (Oct 2002). "A novel protein overexpressed in hepatoma accelerates export of NF-kappa B from the nucleus and inhibits p53-dependent apoptosis". Cancer Cell. 2 (4): 335–46. doi:10.1016/S1535-6108(02)00152-6. hdl:2433/148468. PMID 12398897.
Further reading
[edit]- McCoy JG, Bingman CA, Bitto E, Holdorf MM, Makaroff CA, Phillips GN (Sep 2006). "Structure of an ETHE1-like protein from Arabidopsis thaliana". Acta Crystallographica Section D. 62 (Pt 9): 964–70. Bibcode:2006AcCrD..62..964M. doi:10.1107/S0907444906020592. PMID 16929096.
- 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 (Jan 2006). "The LIFEdb database in 2006". Nucleic Acids Research. 34 (Database issue): D415-8. doi:10.1093/nar/gkj139. PMC 1347501. PMID 16381901.
- 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 (Oct 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID 16189514. S2CID 4427026.
- 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 (Apr 2006). "ETHE1 mutations are specific to ethylmalonic encephalopathy". Journal of Medical Genetics. 43 (4): 340–6. doi:10.1136/jmg.2005.036210. PMC 2563233. PMID 16183799.
- Wiemann S, Arlt D, Huber W, Wellenreuther R, Schleeger S, Mehrle A, Bechtel S, Sauermann M, Korf U, Pepperkok R, Sültmann H, Poustka A (Oct 2004). "From ORFeome to biology: a functional genomics pipeline". Genome Research. 14 (10B): 2136–44. doi:10.1101/gr.2576704. PMC 528930. PMID 15489336.
- 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 (Feb 2004). "Ethylmalonic encephalopathy is caused by mutations in ETHE1, a gene encoding a mitochondrial matrix protein". American Journal of Human Genetics. 74 (2): 239–52. doi:10.1086/381653. PMC 1181922. PMID 14732903.
- Higashitsuji H, Higashitsuji H, Nagao T, Nonoguchi K, Fujii S, Itoh K, Fujita J (Oct 2002). "A novel protein overexpressed in hepatoma accelerates export of NF-kappa B from the nucleus and inhibits p53-dependent apoptosis". Cancer Cell. 2 (4): 335–46. doi:10.1016/S1535-6108(02)00152-6. hdl:2433/148468. PMID 12398897.
- Simpson JC, Wellenreuther R, Poustka A, Pepperkok R, Wiemann S (Sep 2000). "Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing". EMBO Reports. 1 (3): 287–92. doi:10.1093/embo-reports/kvd058. PMC 1083732. PMID 11256614.
- Hartley JL, Temple GF, Brasch MA (Nov 2000). "DNA cloning using in vitro site-specific recombination". Genome Research. 10 (11): 1788–95. doi:10.1101/gr.143000. PMC 310948. PMID 11076863.
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