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Protein

Persulfide dioxygenase ETHE1, mitochondrial

Gene

ETHE1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

S-sulfanylglutathione + O2 + H2O = glutathione + sulfite + 2 H+.3 Publications

Cofactori

Fe2+3 PublicationsNote: Binds 1 Fe2+ ion per subunit.3 Publications

Activity regulationi

Glutathione increases enzyme activity.1 Publication

Kineticsi

  1. KM=0.34 mM for glutathione persulfide (GSSH)1 Publication
  1. 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)DescriptionActionsGraphical viewLength
Metal bindingi79Iron; catalyticCombined sources1 Publication1
Metal bindingi135Iron; catalyticCombined sources1 Publication1
Metal bindingi154Iron; catalyticCombined sources1 Publication1

GO - Molecular functioni

  • iron ion binding Source: UniProtKB
  • sulfur dioxygenase activity Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionDioxygenase, Oxidoreductase
LigandMetal-binding

Enzyme and pathway databases

BioCyciMetaCyc:ENSG00000105755-MONOMER
ReactomeiR-HSA-1614517 Sulfide oxidation to sulfate

Names & Taxonomyi

Protein namesi
Recommended name:
Persulfide dioxygenase ETHE1, mitochondrial (EC:1.13.11.183 Publications)
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
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

EuPathDBiHostDB:ENSG00000105755.7
HGNCiHGNC:23287 ETHE1
MIMi608451 gene
neXtProtiNX_O95571

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Mitochondrion, Nucleus

Pathology & Biotechi

Involvement in diseasei

Ethylmalonic encephalopathy (EE)3 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)DescriptionActionsGraphical viewLength
Natural variantiVAR_02339538Y → C in EE. 1 Publication1
Natural variantiVAR_06950755L → P in EE; reduces protein stability. 1 PublicationCorresponds to variant dbSNP:rs182983506EnsemblClinVar.1
Natural variantiVAR_023396136T → A in EE. 2 Publications1
Natural variantiVAR_069508152T → I in EE; reduces protein stability, iron content and enzyme activity. 2 Publications1
Natural variantiVAR_069509163R → Q in EE. 1 PublicationCorresponds to variant dbSNP:rs745656120EnsemblClinVar.1
Natural variantiVAR_023397163R → W in EE. 2 PublicationsCorresponds to variant dbSNP:rs28940289EnsemblClinVar.1
Natural variantiVAR_069510164T → K in EE; reduces protein stability. 1 Publication1
Natural variantiVAR_023398185L → R in EE. 2 PublicationsCorresponds to variant dbSNP:rs387906987EnsemblClinVar.1
Natural variantiVAR_069511196D → N in EE; reduces protein stability and affinity for substrate. 2 PublicationsCorresponds to variant dbSNP:rs763799125EnsemblClinVar.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi23474
MalaCardsiETHE1
MIMi602473 phenotype
OpenTargetsiENSG00000105755
Orphaneti51188 Ethylmalonic encephalopathy
PharmGKBiPA134879650

Polymorphism and mutation databases

BioMutaiETHE1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 7Mitochondrion1 Publication7
ChainiPRO_00000122898 – 254Persulfide dioxygenase ETHE1, mitochondrialAdd BLAST247

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei14PhosphoserineBy similarity1
Modified residuei19PhosphoserineCombined sources1
Modified residuei66N6-acetyllysineCombined sources1
Modified residuei172N6-acetyllysine; alternateBy similarity1
Modified residuei172N6-succinyllysine; alternateBy similarity1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiO95571
MaxQBiO95571
PaxDbiO95571
PeptideAtlasiO95571
PRIDEiO95571
ProteomicsDBi50945

2D gel databases

UCD-2DPAGEiO95571

PTM databases

iPTMnetiO95571
PhosphoSitePlusiO95571
SwissPalmiO95571

Expressioni

Tissue specificityi

Ubiquitously expressed.1 Publication

Gene expression databases

BgeeiENSG00000105755 Expressed in 219 organ(s), highest expression level in mucosa of transverse colon
CleanExiHS_ETHE1
ExpressionAtlasiO95571 baseline and differential
GenevisibleiO95571 HS

Organism-specific databases

HPAiHPA028360
HPA029028
HPA029029

Interactioni

Subunit structurei

Homodimer (PubMed:25596185). Monomer (PubMed:23144459). Interacts with TST (PubMed:19136963). May interact with RELA (PubMed:12398897).4 Publications

Protein-protein interaction databases

BioGridi117034, 9 interactors
IntActiO95571, 11 interactors
MINTiO95571
STRINGi9606.ENSP00000292147

Structurei

Secondary structure

1254
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliO95571
SMRiO95571
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiKOG0814 Eukaryota
COG0491 LUCA
GeneTreeiENSGT00530000063033
HOGENOMiHOG000058040
HOVERGENiHBG053310
InParanoidiO95571
KOiK17725
PhylomeDBiO95571
TreeFamiTF312952

Family and domain databases

Gene3Di3.60.15.10, 1 hit
InterProiView protein in InterPro
IPR001279 Metallo-B-lactamas
IPR036866 RibonucZ/Hydroxyglut_hydro
PfamiView protein in Pfam
PF00753 Lactamase_B, 1 hit
SMARTiView protein in SMART
SM00849 Lactamase_B, 1 hit
SUPFAMiSSF56281 SSF56281, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

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

This entry has 1 described isoform and 3 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
M0QXB5M0QXB5_HUMAN
Persulfide dioxygenase ETHE1, mitoc...
ETHE1
260Annotation score:
M0QY80M0QY80_HUMAN
Persulfide dioxygenase ETHE1, mitoc...
ETHE1
95Annotation score:
M0QX80M0QX80_HUMAN
Persulfide dioxygenase ETHE1, mitoc...
ETHE1
51Annotation score:

Sequence cautioni

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

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02339538Y → C in EE. 1 Publication1
Natural variantiVAR_06950755L → P in EE; reduces protein stability. 1 PublicationCorresponds to variant dbSNP:rs182983506EnsemblClinVar.1
Natural variantiVAR_023396136T → A in EE. 2 Publications1
Natural variantiVAR_069508152T → I in EE; reduces protein stability, iron content and enzyme activity. 2 Publications1
Natural variantiVAR_069509163R → Q in EE. 1 PublicationCorresponds to variant dbSNP:rs745656120EnsemblClinVar.1
Natural variantiVAR_023397163R → W in EE. 2 PublicationsCorresponds to variant dbSNP:rs28940289EnsemblClinVar.1
Natural variantiVAR_069510164T → K in EE; reduces protein stability. 1 Publication1
Natural variantiVAR_023398185L → R in EE. 2 PublicationsCorresponds to variant dbSNP:rs387906987EnsemblClinVar.1
Natural variantiVAR_069511196D → N in EE; reduces protein stability and affinity for substrate. 2 PublicationsCorresponds to variant dbSNP:rs763799125EnsemblClinVar.1

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_001307796.1, NM_001320867.1
NP_001307797.1, NM_001320868.1
NP_001307798.1, NM_001320869.1
NP_055112.2, NM_014297.4
XP_005258744.1, XM_005258687.3
UniGeneiHs.7486

Genome annotation databases

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

Similar proteinsi

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_001307796.1, NM_001320867.1
NP_001307797.1, NM_001320868.1
NP_001307798.1, NM_001320869.1
NP_055112.2, NM_014297.4
XP_005258744.1, XM_005258687.3
UniGeneiHs.7486

3D structure databases

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

Protein-protein interaction databases

BioGridi117034, 9 interactors
IntActiO95571, 11 interactors
MINTiO95571
STRINGi9606.ENSP00000292147

PTM databases

iPTMnetiO95571
PhosphoSitePlusiO95571
SwissPalmiO95571

Polymorphism and mutation databases

BioMutaiETHE1

2D gel databases

UCD-2DPAGEiO95571

Proteomic databases

EPDiO95571
MaxQBiO95571
PaxDbiO95571
PeptideAtlasiO95571
PRIDEiO95571
ProteomicsDBi50945

Protocols and materials databases

DNASUi23474
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi23474
DisGeNETi23474
EuPathDBiHostDB:ENSG00000105755.7
GeneCardsiETHE1
HGNCiHGNC:23287 ETHE1
HPAiHPA028360
HPA029028
HPA029029
MalaCardsiETHE1
MIMi602473 phenotype
608451 gene
neXtProtiNX_O95571
OpenTargetsiENSG00000105755
Orphaneti51188 Ethylmalonic encephalopathy
PharmGKBiPA134879650
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0814 Eukaryota
COG0491 LUCA
GeneTreeiENSGT00530000063033
HOGENOMiHOG000058040
HOVERGENiHBG053310
InParanoidiO95571
KOiK17725
PhylomeDBiO95571
TreeFamiTF312952

Enzyme and pathway databases

BioCyciMetaCyc:ENSG00000105755-MONOMER
ReactomeiR-HSA-1614517 Sulfide oxidation to sulfate

Miscellaneous databases

ChiTaRSiETHE1 human
GeneWikiiETHE1
GenomeRNAii23474
PROiPR:O95571
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000105755 Expressed in 219 organ(s), highest expression level in mucosa of transverse colon
CleanExiHS_ETHE1
ExpressionAtlasiO95571 baseline and differential
GenevisibleiO95571 HS

Family and domain databases

Gene3Di3.60.15.10, 1 hit
InterProiView protein in InterPro
IPR001279 Metallo-B-lactamas
IPR036866 RibonucZ/Hydroxyglut_hydro
PfamiView protein in Pfam
PF00753 Lactamase_B, 1 hit
SMARTiView protein in SMART
SM00849 Lactamase_B, 1 hit
SUPFAMiSSF56281 SSF56281, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiETHE1_HUMAN
AccessioniPrimary (citable) accession number: O95571
Secondary accession number(s): Q96HR0, Q9H001
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 30, 2005
Last sequence update: March 1, 2003
Last modified: September 12, 2018
This is version 143 of the entry and version 2 of the sequence. See 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families
  3. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
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