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   24-JAN-2024, entry version 148.
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,
RC   Pancreas, 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; 10090-ENSMUSP00000076433; -.
DR   PeptideAtlas; Q9DCM0; -.
DR   ProteomicsDB; 271503; -.
DR   Pumba; Q9DCM0; -.
DR   Antibodypedia; 31059; 292 antibodies from 26 providers.
DR   DNASU; 66071; -.
DR   Ensembl; ENSMUST00000077191.7; ENSMUSP00000076433.7; ENSMUSG00000064254.7.
DR   GeneID; 66071; -.
DR   KEGG; mmu:66071; -.
DR   UCSC; uc009fqb.2; mouse.
DR   AGR; MGI:1913321; -.
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; 5471651at2759; -.
DR   PhylomeDB; Q9DCM0; -.
DR   TreeFam; TF312952; -.
DR   Reactome; R-MMU-1614517; Sulfide oxidation to sulfate.
DR   BioGRID-ORCS; 66071; 3 hits in 78 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 240 other cell types or tissues.
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: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; Ribonuclease Z/Hydroxyacylglutathione hydrolase-like; 1.
DR   InterPro; IPR001279; Metallo-B-lactamas.
DR   InterPro; IPR044528; POD-like_MBL-fold.
DR   InterPro; IPR036866; RibonucZ/Hydroxyglut_hydro.
DR   PANTHER; PTHR43084; PERSULFIDE DIOXYGENASE ETHE1; 1.
DR   PANTHER; PTHR43084:SF1; PERSULFIDE DIOXYGENASE ETHE1, MITOCHONDRIAL; 1.
DR   Pfam; PF00753; Lactamase_B; 1.
DR   SMART; SM00849; Lactamase_B; 1.
DR   SUPFAM; SSF56281; Metallo-hydrolase/oxidoreductase; 1.
DR   Genevisible; Q9DCM0; MM.
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
//