Biology:ETHE1
 Generic protein structure example |
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.[1]
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.[1]
The ETHE1 protein is thought to localize primarily to the mitochondrial matrix[2][3] 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 [math]\displaystyle{ \rightleftharpoons }[/math] sulfite + 2 H+ (overall reaction)
- (1a) glutathione + sulfur [math]\displaystyle{ \rightleftharpoons }[/math] S-sulfanylglutathione (glutathione persulfide, spontaneous reaction)
- (1b) S-sulfanylglutathione + O2 + H2O [math]\displaystyle{ \rightleftharpoons }[/math] glutathione + sulfite + 2 H+[2]
and requires iron[4] and possibly glutathione[4] as cofactors. The physiological substrate of ETHE1 is thought to be glutathione persulfide,[4] an intermediate metabolite involved in hydrogen sulfide degradation.
Clinical significance
Mutations in ETHE1 gene are thought to cause ethylmalonic encephalopathy,[3][5] 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.[4] Mouse models of Ethe1 genetic ablation likewise exhibited reduced sulfide dioxygenase catabolism and cranial features of ethylmalonic encephalopathy.[2] Decrease in sulfide dioxygenase activity results in abnormal catabolism of hydrogen sulfide, a gas-phase signaling molecule in the central nervous system,[4] whose accumulation is thought to inhibit cytochrome c oxidase activity in the respiratory chain of the mitochondrion.[2] However, other metabolic pathways may also be involved that could exert a modulatory effect on hydrogen sulfide toxicity.[6]
Interactions
ETHE1 has been shown to interact with RELA.[7]
References
- ↑ 1.0 1.1 "Entrez Gene: ETHE1 ethylmalonic encephalopathy 1". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=23474.
- ↑ 2.0 2.1 2.2 2.3 "Loss of ETHE1, a mitochondrial dioxygenase, causes fatal sulfide toxicity in ethylmalonic encephalopathy". Nat. Med. 15 (2): 200–5. 2009. doi:10.1038/nm.1907. PMID 19136963.
- ↑ 3.0 3.1 "Ethylmalonic encephalopathy is caused by mutations in ETHE1, a gene encoding a mitochondrial matrix protein". Am. J. Hum. Genet. 74 (2): 239–52. 2004. doi:10.1086/381653. PMID 14732903.
- ↑ 4.0 4.1 4.2 4.3 4.4 "Characterization of patient mutations in human persulfide dioxygenase (ETHE1) involved in H2S catabolism". J. Biol. Chem. 287 (53): 44561–7. 2012. doi:10.1074/jbc.M112.407411. PMID 23144459.
- ↑ "Encephalopathy, Ethylmalonic". Johns Hopkins University. http://www.omim.org/entry/602473.
- ↑ "Multiple sources of metabolic disturbance in ETHE1-related ethylmalonic encephalopathy". J. Inherit. Metab. Dis. 33 (Suppl 3): S443–53. 2010. doi:10.1007/s10545-010-9227-y. PMID 20978941.
- ↑ "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. Oct 2002. doi:10.1016/S1535-6108(02)00152-6. PMID 12398897.
Further reading
- "Structure of an ETHE1-like protein from Arabidopsis thaliana". Acta Crystallographica Section D 62 (Pt 9): 964–70. Sep 2006. doi:10.1107/S0907444906020592. PMID 16929096. Bibcode: 2006AcCrD..62..964M.
- "The LIFEdb database in 2006". Nucleic Acids Research 34 (Database issue): D415-8. Jan 2006. doi:10.1093/nar/gkj139. PMID 16381901.
- "Towards a proteome-scale map of the human protein-protein interaction network". Nature 437 (7062): 1173–8. Oct 2005. doi:10.1038/nature04209. PMID 16189514. Bibcode: 2005Natur.437.1173R.
- "ETHE1 mutations are specific to ethylmalonic encephalopathy". Journal of Medical Genetics 43 (4): 340–6. Apr 2006. doi:10.1136/jmg.2005.036210. PMID 16183799.
- "From ORFeome to biology: a functional genomics pipeline". Genome Research 14 (10B): 2136–44. Oct 2004. doi:10.1101/gr.2576704. PMID 15489336.
- "Ethylmalonic encephalopathy is caused by mutations in ETHE1, a gene encoding a mitochondrial matrix protein". American Journal of Human Genetics 74 (2): 239–52. Feb 2004. doi:10.1086/381653. PMID 14732903.
- "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. Oct 2002. doi:10.1016/S1535-6108(02)00152-6. PMID 12398897.
- "Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing". EMBO Reports 1 (3): 287–92. Sep 2000. doi:10.1093/embo-reports/kvd058. PMID 11256614.
- "DNA cloning using in vitro site-specific recombination". Genome Research 10 (11): 1788–95. Nov 2000. doi:10.1101/gr.143000. PMID 11076863.
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