ETHE1_MOUSE
ID ETHE1_MOUSE Reviewed; 254 AA.
AC Q9DCM0; Q9ESL5;
DT 30-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 2.
DT 03-AUG-2022, entry version 141.
DE RecName: Full=Persulfide dioxygenase ETHE1, mitochondrial;
DE EC=1.13.11.18 {ECO:0000250|UniProtKB:O95571};
DE AltName: Full=Ethylmalonic encephalopathy protein 1 homolog;
DE AltName: Full=Hepatoma subtracted clone one protein;
DE AltName: Full=Sulfur dioxygenase ETHE1;
DE Flags: Precursor;
GN Name=Ethe1; Synonyms=Hsco;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RA Fujita J., Higashitsuji H., Higashitsuji H.;
RT "Expression of HSCO in hepatomas.";
RL Submitted (OCT-2000) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Kidney;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Colon, Kidney, and Mammary tumor;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=19136963; DOI=10.1038/nm.1907;
RA Tiranti V., Viscomi C., Hildebrandt T., Di Meo I., Mineri R., Tiveron C.,
RA Levitt M.D., Prelle A., Fagiolari G., Rimoldi M., Zeviani M.;
RT "Loss of ETHE1, a mitochondrial dioxygenase, causes fatal sulfide toxicity
RT in ethylmalonic encephalopathy.";
RL Nat. Med. 15:200-205(2009).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-14 AND SER-17, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-32 AND LYS-172, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
RN [7]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-32; LYS-66 AND LYS-172, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23576753; DOI=10.1073/pnas.1302961110;
RA Rardin M.J., Newman J.C., Held J.M., Cusack M.P., Sorensen D.J., Li B.,
RA Schilling B., Mooney S.D., Kahn C.R., Verdin E., Gibson B.W.;
RT "Label-free quantitative proteomics of the lysine acetylome in mitochondria
RT identifies substrates of SIRT3 in metabolic pathways.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:6601-6606(2013).
CC -!- FUNCTION: First described as a protein that can shuttle between the
CC nucleus and the cytoplasm and suppress p53-induced apoptosis by
CC sequestering the transcription factor RELA/NFKB3 in the cytoplasm and
CC preventing its accumulation in the nucleus (By similarity). Sulfur
CC dioxygenase that plays an essential role in hydrogen sulfide catabolism
CC in the mitochondrial matrix. Hydrogen sulfide (H(2)S) is first oxidized
CC by SQRDL, giving rise to cysteine persulfide residues. ETHE1 consumes
CC molecular oxygen to catalyze the oxidation of the persulfide, once it
CC has been transferred to a thiophilic acceptor, such as glutathione (R-
CC SSH). Plays an important role in metabolic homeostasis in mitochondria
CC by metabolizing hydrogen sulfide and preventing the accumulation of
CC supraphysiological H(2)S levels that have toxic effects, due to the
CC inhibition of cytochrome c oxidase. {ECO:0000250|UniProtKB:O95571,
CC ECO:0000269|PubMed:19136963}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + O2 + S-sulfanylglutathione = glutathione + 2 H(+) +
CC sulfite; Xref=Rhea:RHEA:12981, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:17359, ChEBI:CHEBI:57925,
CC ChEBI:CHEBI:58905; EC=1.13.11.18;
CC Evidence={ECO:0000250|UniProtKB:O95571};
CC -!- COFACTOR:
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC Evidence={ECO:0000250|UniProtKB:O95571};
CC Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000250|UniProtKB:O95571};
CC -!- SUBUNIT: Homodimer. Monomer. Interacts with TST. May interact with
CC RELA. {ECO:0000250|UniProtKB:O95571}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:O95571}. Nucleus
CC {ECO:0000250|UniProtKB:O95571}. Mitochondrion matrix
CC {ECO:0000250|UniProtKB:O95571}.
CC -!- DISRUPTION PHENOTYPE: Mice are born at slightly less than the expected
CC Mendelian rate. Pups display growth arrest at about 15 days after birth
CC and die five to six weeks after birth. Mice exhibit elevated levels of
CC hydrogen sulfide (H(2)S) in liver, muscle and brain, together with
CC increased urinary levels of ethylmalonic acid and thiosulfate. Their
CC mitochondria show decreased cytochrome c oxidase activity, probably due
CC to the toxic effects of supraphysiological levels of hydrogen sulfide.
CC {ECO:0000269|PubMed:19136963}.
CC -!- SIMILARITY: Belongs to the metallo-beta-lactamase superfamily.
CC Glyoxalase II family. {ECO:0000305}.
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DR EMBL; AB049623; BAB16409.1; -; mRNA.
DR EMBL; AK002666; BAB22271.2; -; mRNA.
DR EMBL; BC010592; AAH10592.1; -; mRNA.
DR EMBL; BC083162; AAH83162.1; -; mRNA.
DR EMBL; BC094044; AAH94044.1; -; mRNA.
DR CCDS; CCDS20957.1; -.
DR RefSeq; NP_075643.1; NM_023154.3.
DR RefSeq; XP_017167710.1; XM_017312221.1.
DR AlphaFoldDB; Q9DCM0; -.
DR SMR; Q9DCM0; -.
DR BioGRID; 211193; 4.
DR STRING; 10090.ENSMUSP00000076433; -.
DR iPTMnet; Q9DCM0; -.
DR PhosphoSitePlus; Q9DCM0; -.
DR SwissPalm; Q9DCM0; -.
DR REPRODUCTION-2DPAGE; Q9DCM0; -.
DR EPD; Q9DCM0; -.
DR jPOST; Q9DCM0; -.
DR MaxQB; Q9DCM0; -.
DR PaxDb; Q9DCM0; -.
DR PeptideAtlas; Q9DCM0; -.
DR PRIDE; Q9DCM0; -.
DR ProteomicsDB; 271503; -.
DR Antibodypedia; 31059; 267 antibodies from 26 providers.
DR DNASU; 66071; -.
DR Ensembl; ENSMUST00000077191; ENSMUSP00000076433; ENSMUSG00000064254.
DR GeneID; 66071; -.
DR KEGG; mmu:66071; -.
DR UCSC; uc009fqb.2; mouse.
DR CTD; 23474; -.
DR MGI; MGI:1913321; Ethe1.
DR VEuPathDB; HostDB:ENSMUSG00000064254; -.
DR eggNOG; KOG0814; Eukaryota.
DR GeneTree; ENSGT00940000159046; -.
DR HOGENOM; CLU_030571_7_0_1; -.
DR InParanoid; Q9DCM0; -.
DR OMA; DYKGDTV; -.
DR OrthoDB; 1203911at2759; -.
DR PhylomeDB; Q9DCM0; -.
DR TreeFam; TF312952; -.
DR Reactome; R-MMU-1614517; Sulfide oxidation to sulfate.
DR BioGRID-ORCS; 66071; 3 hits in 73 CRISPR screens.
DR ChiTaRS; Ethe1; mouse.
DR PRO; PR:Q9DCM0; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q9DCM0; protein.
DR Bgee; ENSMUSG00000064254; Expressed in right colon and 237 other tissues.
DR Genevisible; Q9DCM0; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0016788; F:hydrolase activity, acting on ester bonds; IEA:InterPro.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0005506; F:iron ion binding; ISS:UniProtKB.
DR GO; GO:0050313; F:sulfur dioxygenase activity; ISS:UniProtKB.
DR GO; GO:0006749; P:glutathione metabolic process; ISS:UniProtKB.
DR GO; GO:0070813; P:hydrogen sulfide metabolic process; ISS:UniProtKB.
DR CDD; cd07724; POD-like_MBL-fold; 1.
DR Gene3D; 3.60.15.10; -; 1.
DR InterPro; IPR001279; Metallo-B-lactamas.
DR InterPro; IPR044528; POD-like_MBL-fold.
DR InterPro; IPR036866; RibonucZ/Hydroxyglut_hydro.
DR Pfam; PF00753; Lactamase_B; 1.
DR SMART; SM00849; Lactamase_B; 1.
DR SUPFAM; SSF56281; SSF56281; 1.
PE 1: Evidence at protein level;
KW Acetylation; Cytoplasm; Dioxygenase; Iron; Metal-binding; Mitochondrion;
KW Nucleus; Oxidoreductase; Phosphoprotein; Reference proteome;
KW Transit peptide.
FT TRANSIT 1..7
FT /note="Mitochondrion"
FT /evidence="ECO:0000250|UniProtKB:O95571"
FT CHAIN 8..254
FT /note="Persulfide dioxygenase ETHE1, mitochondrial"
FT /id="PRO_0000012290"
FT BINDING 79
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:O95571"
FT BINDING 135
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:O95571"
FT BINDING 154
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:O95571"
FT MOD_RES 14
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 17
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 19
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O95571"
FT MOD_RES 32
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 32
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 66
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 172
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 172
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
SQ SEQUENCE 254 AA; 27739 MW; 3F28C0ED465A3062 CRC64;
MASAVVRVAG RRLSQQSASG APVLLRQMFE PKSCTYTYLL GDRESREAVL IDPVLETAHR
DAQLIKELGL KLLYAVNTHC HADHITGTGV LRSLLPGCQS VISRLSGAQA DLHIGEGDSI
RFGRFALETR ASPGHTPGCV TFVLNDQSMA FTGDALLIRG CGRTDFQQGC AKTLYHSVHE
KIFTLPGNCL IYPAHDYHGL TVSTVEEERT LNPRLTLSCE EFIKVMDNLN LPKPQQIDIA
VPANMRCGVQ TPPS
