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MGP004684

UniProt Annotations

Entry Information
Gene Nameethylmalonic encephalopathy 1
Protein EntryETHE1_HUMAN
UniProt IDO95571
SpeciesHuman
Comments
Comment typeDescription
Biophysicochemical PropertiesKinetic parameters: KM=0.34 mM for glutathione persulfide (GSSH) {ECO:0000269|PubMed:23144459}; Vmax=113 umol/min/mg enzyme (in the presence of equimolar amounts of GSSH and GSH and at 22 degrees Celsius) {ECO:0000269|PubMed:23144459};
Catalytic ActivitySulfur + O(2) + H(2)O = sulfite + 2 H(+). {ECO:0000269|PubMed:19136963, ECO:0000269|PubMed:23144459}.
CofactorName=Fe(2+); Xref=ChEBI:CHEBI:29033; Evidence={ECO:0000269|PubMed:19136963, ECO:0000269|PubMed:23144459}; Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000269|PubMed:19136963, ECO:0000269|PubMed:23144459};
DiseaseEthylmalonic encephalopathy (EE) [MIM:602473]: Autosomal recessive disorder characterized by neurodevelopmental delay and regression, recurrent petechiae, acrocyanosis, diarrhea, leading to death in the first decade of life. It is also associated with persistent lactic acidemia and ethylmalonic and methylsuccinic aciduria. {ECO:0000269|PubMed:14732903, ECO:0000269|PubMed:18593870}. Note=The disease is caused by mutations affecting the gene represented in this entry.
Enzyme RegulationGlutathione increases enzyme activity. {ECO:0000269|PubMed:23144459}.
FunctionSulfur dioxygenase that plays an essential role in hydrogen sulfide catabolism in the mitochondrial matrix. Hydrogen sulfide (H(2)S) is first oxidized by SQRDL, giving rise to cysteine persulfide residues. ETHE1 consumes molecular oxygen to catalyze the oxidation of the persulfide, once it has been transferred to a thiophilic acceptor, such as glutathione (R-SSH). Plays an important role in metabolic homeostasis in mitochondria by metabolizing hydrogen sulfide and preventing the accumulation of supraphysiological H(2)S levels that have toxic effects, due to the inhibition of cytochrome c oxidase. First described as a protein that can shuttle between the nucleus and the cytoplasm and suppress p53-induced apoptosis by sequestering the transcription factor RELA/NFKB3 in the cytoplasm and preventing its accumulation in the nucleus (PubMed:12398897). {ECO:0000269|PubMed:12398897, ECO:0000269|PubMed:14732903, ECO:0000269|PubMed:19136963, ECO:0000269|PubMed:23144459}.
Sequence CautionSequence=AAG09063.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
SimilarityBelongs to the metallo-beta-lactamase superfamily. Glyoxalase II family. {ECO:0000305}.
Subcellular LocationCytoplasm. Nucleus. Mitochondrion matrix. Note=According to PubMed:12398897, it is cytoplasmic and nuclear. According to PubMed:14732903, it is found in the mitochondrial matrix.
SubunitMonomer. Interacts with TST. May interact with RELA. {ECO:0000269|PubMed:12398897, ECO:0000269|PubMed:19136963, ECO:0000269|PubMed:23144459}.
Tissue SpecificityUbiquitously expressed. {ECO:0000269|PubMed:14732903}.
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