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Protein

Persulfide dioxygenase ETHE1, mitochondrial

Gene

ETHE1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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

Fe2+2 PublicationsNote: 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. iron ion binding Source: UniProtKB
  2. 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
Complete GO annotation...

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 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:23287. ETHE1.

Subcellular locationi

  1. Cytoplasm
  2. Nucleus
  3. Mitochondrion matrix

  4. 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. nucleoplasm Source: HPA
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Mitochondrion, Nucleus

Pathology & Biotechi

Involvement in diseasei

Ethylmalonic encephalopathy (EE)2 Publications

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionAutosomal 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.

See also OMIM:602473
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. 2 Publications
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. 2 Publications
VAR_069511

Keywords - Diseasei

Disease mutation

Organism-specific databases

MIMi602473. phenotype.
Orphaneti51188. Ethylmalonic encephalopathy.
PharmGKBiPA134879650.

Polymorphism and mutation databases

BioMutaiETHE1.

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 residuei19 – 191Phosphoserine1 Publication
Modified residuei66 – 661N6-acetyllysine1 Publication
Modified residuei172 – 1721N6-acetyllysine; alternateBy similarity
Modified residuei172 – 1721N6-succinyllysine; alternateBy similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

MaxQBiO95571.
PaxDbiO95571.
PeptideAtlasiO95571.
PRIDEiO95571.

2D gel databases

UCD-2DPAGEO95571.

PTM databases

PhosphoSiteiO95571.

Expressioni

Tissue specificityi

Ubiquitously expressed.1 Publication

Gene expression databases

BgeeiO95571.
CleanExiHS_ETHE1.
ExpressionAtlasiO95571. baseline and differential.
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. 10 interactions.
IntActiO95571. 4 interactions.
MINTiMINT-1368289.
STRINGi9606.ENSP00000292147.

Structurei

Secondary structure

1
254
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi24 – 307Combined sources
Turni31 – 344Combined sources
Beta strandi35 – 417Combined sources
Turni43 – 453Combined sources
Beta strandi47 – 526Combined sources
Helixi55 – 573Combined sources
Helixi58 – 6811Combined sources
Beta strandi71 – 766Combined sources
Beta strandi82 – 843Combined sources
Helixi88 – 947Combined sources
Beta strandi99 – 1035Combined sources
Helixi104 – 1063Combined sources
Beta strandi111 – 1144Combined sources
Beta strandi119 – 1224Combined sources
Beta strandi125 – 1317Combined sources
Beta strandi134 – 1363Combined sources
Beta strandi140 – 1445Combined sources
Beta strandi147 – 1537Combined sources
Helixi171 – 18111Combined sources
Turni182 – 1843Combined sources
Beta strandi190 – 1956Combined sources
Beta strandi197 – 1993Combined sources
Helixi205 – 2117Combined sources
Turni213 – 2164Combined sources
Helixi219 – 22810Combined sources
Helixi237 – 2459Combined sources
Turni246 – 2483Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4CHLX-ray2.61A/B21-254[»]
ProteinModelPortaliO95571.
SMRiO95571. Positions 23-245.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiCOG0491.
GeneTreeiENSGT00530000063033.
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

        10         20         30         40         50
MAEAVLRVAR RQLSQRGGSG APILLRQMFE PVSCTFTYLL GDRESREAVL
60 70 80 90 100
IDPVLETAPR DAQLIKELGL RLLYAVNTHC HADHITGSGL LRSLLPGCQS
110 120 130 140 150
VISRLSGAQA DLHIEDGDSI RFGRFALETR ASPGHTPGCV TFVLNDHSMA
160 170 180 190 200
FTGDALLIRG CGRTDFQQGC AKTLYHSVHE KIFTLPGDCL IYPAHDYHGF
210 220 230 240 250
TVSTVEEERT LNPRLTLSCE EFVKIMGNLN LPKPQQIDFA VPANMRCGVQ

TPTA
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. Curated

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. 2 Publications
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. 2 Publications
VAR_069511

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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_005258687.2.
UniGeneiHs.7486.

Genome annotation databases

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

Polymorphism and mutation databases

BioMutaiETHE1.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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_005258687.2.
UniGeneiHs.7486.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4CHLX-ray2.61A/B21-254[»]
ProteinModelPortaliO95571.
SMRiO95571. Positions 23-245.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi117034. 10 interactions.
IntActiO95571. 4 interactions.
MINTiMINT-1368289.
STRINGi9606.ENSP00000292147.

PTM databases

PhosphoSiteiO95571.

Polymorphism and mutation databases

BioMutaiETHE1.

2D gel databases

UCD-2DPAGEO95571.

Proteomic databases

MaxQBiO95571.
PaxDbiO95571.
PeptideAtlasiO95571.
PRIDEiO95571.

Protocols and materials databases

DNASUi23474.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi23474.
GeneCardsiGC19M044010.
HGNCiHGNC:23287. ETHE1.
HPAiHPA028360.
HPA029028.
HPA029029.
MIMi602473. phenotype.
608451. gene.
neXtProtiNX_O95571.
Orphaneti51188. Ethylmalonic encephalopathy.
PharmGKBiPA134879650.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG0491.
GeneTreeiENSGT00530000063033.
HOGENOMiHOG000058040.
HOVERGENiHBG053310.
InParanoidiO95571.
KOiK17725.
OrthoDBiEOG7MH107.
PhylomeDBiO95571.
TreeFamiTF312952.

Enzyme and pathway databases

ReactomeiREACT_116010. Sulfide oxidation to sulfate.

Miscellaneous databases

ChiTaRSiETHE1. human.
GeneWikiiETHE1.
GenomeRNAii23474.
NextBioi45809.
PROiO95571.
SOURCEiSearch...

Gene expression databases

BgeeiO95571.
CleanExiHS_ETHE1.
ExpressionAtlasiO95571. baseline and differential.
GenevestigatoriO95571.

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.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
    Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
    J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-19, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  10. "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: April 29, 2015
This is version 118 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

3D-structure, 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.