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O95571

- ETHE1_HUMAN

UniProt

O95571 - ETHE1_HUMAN

Protein

Persulfide dioxygenase ETHE1, mitochondrial

Gene

ETHE1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 111 (01 Oct 2014)
      Sequence version 2 (01 Mar 2003)
      Previous versions | rss
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    Functioni

    Sulfur dioxygenase that plays an essential role in hydrogen sulfide catabolism in the mitochondrial matrix. Hydrogen sulfide (H2S) 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 H2S 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).4 Publications

    Catalytic activityi

    Sulfur + O2 + H2O = sulfite + 2 H+.2 Publications

    Cofactori

    Binds 1 Fe2+ ion per subunit.2 Publications

    Enzyme regulationi

    Glutathione increases enzyme activity.1 Publication

    Kineticsi

    1. KM=0.34 mM for glutathione persulfide (GSSH)1 Publication

    Vmax=113 µmol/min/mg enzyme (in the presence of equimolar amounts of GSSH and GSH and at 22 degrees Celsius)1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi79 – 791Iron; catalyticCurated
    Metal bindingi135 – 1351Iron; catalyticCurated
    Metal bindingi154 – 1541Iron; catalyticCurated

    GO - Molecular functioni

    1. hydrolase activity Source: InterPro
    2. iron ion binding Source: UniProtKB
    3. sulfur dioxygenase activity Source: UniProtKB

    GO - Biological processi

    1. cellular nitrogen compound metabolic process Source: Reactome
    2. glutathione metabolic process Source: UniProtKB
    3. hydrogen sulfide metabolic process Source: UniProtKB
    4. small molecule metabolic process Source: Reactome
    5. sulfide oxidation, using sulfide:quinone oxidoreductase Source: Reactome
    6. sulfur amino acid catabolic process Source: Reactome
    7. sulfur amino acid metabolic process Source: Reactome

    Keywords - Molecular functioni

    Dioxygenase, Oxidoreductase

    Keywords - Ligandi

    Metal-binding

    Enzyme and pathway databases

    ReactomeiREACT_116010. Sulfide oxidation to sulfate.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Persulfide dioxygenase ETHE1, mitochondrial (EC:1.13.11.18)
    Alternative name(s):
    Ethylmalonic encephalopathy protein 1
    Hepatoma subtracted clone one protein
    Sulfur dioxygenase ETHE1
    Gene namesi
    Name:ETHE1
    Synonyms:HSCO
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 19

    Organism-specific databases

    HGNCiHGNC:23287. ETHE1.

    Subcellular locationi

    Cytoplasm. Nucleus. Mitochondrion matrix
    Note: According to PubMed:12398897, it is cytoplasmic and nuclear. According to PubMed:14732903, it is found in the mitochondrial matrix.

    GO - Cellular componenti

    1. cytoplasm Source: LIFEdb
    2. mitochondrial matrix Source: Reactome
    3. mitochondrion Source: HPA
    4. nucleus Source: HPA

    Keywords - Cellular componenti

    Cytoplasm, Mitochondrion, Nucleus

    Pathology & Biotechi

    Involvement in diseasei

    Ethylmalonic 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.2 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti38 – 381Y → C in EE. 1 Publication
    VAR_023395
    Natural varianti55 – 551L → P in EE; reduces protein stability. 1 Publication
    VAR_069507
    Natural varianti136 – 1361T → A in EE. 2 Publications
    VAR_023396
    Natural varianti152 – 1521T → I in EE; reduces protein stability, iron content and enzyme activity. 1 Publication
    VAR_069508
    Natural varianti163 – 1631R → Q in EE. 1 Publication
    VAR_069509
    Natural varianti163 – 1631R → W in EE. 2 Publications
    Corresponds to variant rs28940289 [ dbSNP | Ensembl ].
    VAR_023397
    Natural varianti164 – 1641T → K in EE; reduces protein stability. 1 Publication
    VAR_069510
    Natural varianti185 – 1851L → R in EE. 2 Publications
    VAR_023398
    Natural varianti196 – 1961D → N in EE; reduces protein stability and affinity for substrate. 1 Publication
    VAR_069511

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

    MIMi602473. phenotype.
    Orphaneti51188. Ethylmalonic encephalopathy.
    PharmGKBiPA134879650.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transit peptidei1 – 77Mitochondrion1 Publication
    Chaini8 – 254247Persulfide dioxygenase ETHE1, mitochondrialPRO_0000012289Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei66 – 661N6-acetyllysine1 Publication
    Modified residuei172 – 1721N6-acetyllysine; alternateBy similarity
    Modified residuei172 – 1721N6-succinyllysine; alternateBy similarity

    Keywords - PTMi

    Acetylation

    Proteomic databases

    MaxQBiO95571.
    PaxDbiO95571.
    PeptideAtlasiO95571.
    PRIDEiO95571.

    2D gel databases

    UCD-2DPAGEO95571.

    PTM databases

    PhosphoSiteiO95571.

    Expressioni

    Tissue specificityi

    Ubiquitously expressed.1 Publication

    Gene expression databases

    ArrayExpressiO95571.
    BgeeiO95571.
    CleanExiHS_ETHE1.
    GenevestigatoriO95571.

    Organism-specific databases

    HPAiHPA028360.
    HPA029028.
    HPA029029.

    Interactioni

    Subunit structurei

    Monomer. Interacts with TST. May interact with RELA.3 Publications

    Protein-protein interaction databases

    BioGridi117034. 9 interactions.
    IntActiO95571. 4 interactions.
    MINTiMINT-1368289.
    STRINGi9606.ENSP00000292147.

    Structurei

    3D structure databases

    ProteinModelPortaliO95571.
    SMRiO95571. Positions 23-245.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Keywords - Domaini

    Transit peptide

    Phylogenomic databases

    eggNOGiCOG0491.
    HOGENOMiHOG000058040.
    HOVERGENiHBG053310.
    InParanoidiO95571.
    KOiK17725.
    OrthoDBiEOG7MH107.
    PhylomeDBiO95571.
    TreeFamiTF312952.

    Family and domain databases

    Gene3Di3.60.15.10. 1 hit.
    InterProiIPR001279. Beta-lactamas-like.
    [Graphical view]
    PfamiPF00753. Lactamase_B. 1 hit.
    [Graphical view]
    SMARTiSM00849. Lactamase_B. 1 hit.
    [Graphical view]
    SUPFAMiSSF56281. SSF56281. 1 hit.

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    O95571-1 [UniParc]FASTAAdd to Basket

    « Hide

    MAEAVLRVAR RQLSQRGGSG APILLRQMFE PVSCTFTYLL GDRESREAVL    50
    IDPVLETAPR DAQLIKELGL RLLYAVNTHC HADHITGSGL LRSLLPGCQS 100
    VISRLSGAQA DLHIEDGDSI RFGRFALETR ASPGHTPGCV TFVLNDHSMA 150
    FTGDALLIRG CGRTDFQQGC AKTLYHSVHE KIFTLPGDCL IYPAHDYHGF 200
    TVSTVEEERT LNPRLTLSCE EFVKIMGNLN LPKPQQIDFA VPANMRCGVQ 250
    TPTA 254
    Length:254
    Mass (Da):27,873
    Last modified:March 1, 2003 - v2
    Checksum:i52073D52A487ACD4
    GO

    Sequence cautioni

    The sequence AAG09063.1 differs from that shown. Reason: Erroneous gene model prediction.

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti38 – 381Y → C in EE. 1 Publication
    VAR_023395
    Natural varianti55 – 551L → P in EE; reduces protein stability. 1 Publication
    VAR_069507
    Natural varianti136 – 1361T → A in EE. 2 Publications
    VAR_023396
    Natural varianti152 – 1521T → I in EE; reduces protein stability, iron content and enzyme activity. 1 Publication
    VAR_069508
    Natural varianti163 – 1631R → Q in EE. 1 Publication
    VAR_069509
    Natural varianti163 – 1631R → W in EE. 2 Publications
    Corresponds to variant rs28940289 [ dbSNP | Ensembl ].
    VAR_023397
    Natural varianti164 – 1641T → K in EE; reduces protein stability. 1 Publication
    VAR_069510
    Natural varianti185 – 1851L → R in EE. 2 Publications
    VAR_023398
    Natural varianti196 – 1961D → N in EE; reduces protein stability and affinity for substrate. 1 Publication
    VAR_069511

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    D83198 mRNA. Translation: BAA34595.2.
    AC018758 Genomic DNA. Translation: AAG09063.1. Sequence problems.
    BC008250 mRNA. Translation: AAH08250.1.
    CCDSiCCDS12622.1.
    RefSeqiNP_055112.2. NM_014297.3.
    XP_005258744.1. XM_005258687.1.
    UniGeneiHs.7486.

    Genome annotation databases

    EnsembliENST00000292147; ENSP00000292147; ENSG00000105755.
    GeneIDi23474.
    KEGGihsa:23474.
    UCSCiuc002owp.3. human.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    D83198 mRNA. Translation: BAA34595.2 .
    AC018758 Genomic DNA. Translation: AAG09063.1 . Sequence problems.
    BC008250 mRNA. Translation: AAH08250.1 .
    CCDSi CCDS12622.1.
    RefSeqi NP_055112.2. NM_014297.3.
    XP_005258744.1. XM_005258687.1.
    UniGenei Hs.7486.

    3D structure databases

    ProteinModelPortali O95571.
    SMRi O95571. Positions 23-245.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 117034. 9 interactions.
    IntActi O95571. 4 interactions.
    MINTi MINT-1368289.
    STRINGi 9606.ENSP00000292147.

    PTM databases

    PhosphoSitei O95571.

    2D gel databases

    UCD-2DPAGE O95571.

    Proteomic databases

    MaxQBi O95571.
    PaxDbi O95571.
    PeptideAtlasi O95571.
    PRIDEi O95571.

    Protocols and materials databases

    DNASUi 23474.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000292147 ; ENSP00000292147 ; ENSG00000105755 .
    GeneIDi 23474.
    KEGGi hsa:23474.
    UCSCi uc002owp.3. human.

    Organism-specific databases

    CTDi 23474.
    GeneCardsi GC19M044010.
    HGNCi HGNC:23287. ETHE1.
    HPAi HPA028360.
    HPA029028.
    HPA029029.
    MIMi 602473. phenotype.
    608451. gene.
    neXtProti NX_O95571.
    Orphaneti 51188. Ethylmalonic encephalopathy.
    PharmGKBi PA134879650.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0491.
    HOGENOMi HOG000058040.
    HOVERGENi HBG053310.
    InParanoidi O95571.
    KOi K17725.
    OrthoDBi EOG7MH107.
    PhylomeDBi O95571.
    TreeFami TF312952.

    Enzyme and pathway databases

    Reactomei REACT_116010. Sulfide oxidation to sulfate.

    Miscellaneous databases

    GeneWikii ETHE1.
    GenomeRNAii 23474.
    NextBioi 45809.
    PROi O95571.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi O95571.
    Bgeei O95571.
    CleanExi HS_ETHE1.
    Genevestigatori O95571.

    Family and domain databases

    Gene3Di 3.60.15.10. 1 hit.
    InterProi IPR001279. Beta-lactamas-like.
    [Graphical view ]
    Pfami PF00753. Lactamase_B. 1 hit.
    [Graphical view ]
    SMARTi SM00849. Lactamase_B. 1 hit.
    [Graphical view ]
    SUPFAMi SSF56281. SSF56281. 1 hit.
    ProtoNeti Search...

    Publicationsi

    1. "A novel protein overexpressed in hepatoma accelerates export of NF-kappa B from the nucleus and inhibits p53-dependent apoptosis."
      Higashitsuji H., Higashitsuji H., Nagao T., Nonoguchi K., Fujii S., Itoh K., Fujita J.
      Cancer Cell 2:335-346(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, INTERACTION WITH RELA, FUNCTION, ABSENCE OF GLYOXALASE II ACTIVITY.
      Tissue: Liver.
    2. Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, TISSUE SPECIFICITY, FUNCTION, ABSENCE OF GLYOXALASE II ACTIVITY, VARIANTS EE CYS-38; ALA-136; TRP-163 AND ARG-185.
    3. "The DNA sequence and biology of human chromosome 19."
      Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V.
      , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M.
      Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Eye.
    5. "Loss of ETHE1, a mitochondrial dioxygenase, causes fatal sulfide toxicity in ethylmalonic encephalopathy."
      Tiranti V., Viscomi C., Hildebrandt T., Di Meo I., Mineri R., Tiveron C., Levitt M.D., Prelle A., Fagiolari G., Rimoldi M., Zeviani M.
      Nat. Med. 15:200-205(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ROLE IN DISEASE, SUBCELLULAR LOCATION, TRANSIT PEPTIDE CLEAVAGE SITE, IDENTIFICATION BY MASS SPECTROMETRY, INTERACTION WITH TST.
    6. "Lysine acetylation targets protein complexes and co-regulates major cellular functions."
      Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
      Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-66, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    7. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    8. "Characterization of patient mutations in human persulfide dioxygenase (ETHE1) involved in H2S catabolism."
      Kabil O., Banerjee R.
      J. Biol. Chem. 287:44561-44567(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, CATALYTIC ACTIVITY, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, ENZYME REGULATION, CHARACTERIZATION OF VARIANTS EE ILE-152 AND ASN-196.
    9. "Identification of new mutations in the ETHE1 gene in a cohort of 14 patients presenting with ethylmalonic encephalopathy."
      Mineri R., Rimoldi M., Burlina A.B., Koskull S., Perletti C., Heese B., von Dobeln U., Mereghetti P., Di Meo I., Invernizzi F., Zeviani M., Uziel G., Tiranti V.
      J. Med. Genet. 45:473-478(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS EE PRO-55; ALA-136; ILE-152; GLN-163; TRP-163; LYS-164; ARG-185 AND ASN-196, CHARACTERIZATION OF VARIANTS EE PRO-55 AND LYS-164.

    Entry informationi

    Entry nameiETHE1_HUMAN
    AccessioniPrimary (citable) accession number: O95571
    Secondary accession number(s): Q96HR0, Q9H001
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 30, 2005
    Last sequence update: March 1, 2003
    Last modified: October 1, 2014
    This is version 111 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 19
      Human chromosome 19: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3