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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

S-sulfanylglutathione + O2 + H2O = glutathione + 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
  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; catalyticCurated1
Metal bindingi135Iron; catalyticCurated1
Metal bindingi154Iron; catalyticCurated1

GO - Molecular functioni

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

GO - Biological processi

  • glutathione metabolic process Source: UniProtKB
  • hydrogen sulfide metabolic process Source: UniProtKB
  • sulfide oxidation, using sulfide:quinone oxidoreductase Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Dioxygenase, Oxidoreductase

Keywords - Ligandi

Metal-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000105755-MONOMER.
ReactomeiR-HSA-1614517. Sulfide oxidation to sulfate.

Names & Taxonomyi

Protein namesi
Recommended name:
Persulfide dioxygenase ETHE1, mitochondrial (EC:1.13.11.182 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

HGNCiHGNC:23287. ETHE1.

Subcellular locationi

GO - Cellular componenti

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)DescriptionActionsGraphical viewLength
Natural variantiVAR_02339538Y → C in EE. 1 Publication1
Natural variantiVAR_06950755L → P in EE; reduces protein stability. 1 PublicationCorresponds to variant rs182983506dbSNPEnsembl.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 rs745656120dbSNPEnsembl.1
Natural variantiVAR_023397163R → W in EE. 2 PublicationsCorresponds to variant rs28940289dbSNPEnsembl.1
Natural variantiVAR_069510164T → K in EE; reduces protein stability. 1 Publication1
Natural variantiVAR_023398185L → R in EE. 2 PublicationsCorresponds to variant rs387906987dbSNPEnsembl.1
Natural variantiVAR_069511196D → N in EE; reduces protein stability and affinity for substrate. 2 PublicationsCorresponds to variant rs763799125dbSNPEnsembl.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.

2D gel databases

UCD-2DPAGEO95571.

PTM databases

iPTMnetiO95571.
PhosphoSitePlusiO95571.
SwissPalmiO95571.

Expressioni

Tissue specificityi

Ubiquitously expressed.1 Publication

Gene expression databases

BgeeiENSG00000105755.
CleanExiHS_ETHE1.
ExpressionAtlasiO95571. baseline and differential.
GenevisibleiO95571. HS.

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 interactors.
IntActiO95571. 6 interactors.
MINTiMINT-1368289.
STRINGi9606.ENSP00000292147.

Structurei

Secondary structure

1254
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi24 – 30Combined sources7
Turni31 – 34Combined sources4
Beta strandi35 – 41Combined sources7
Turni43 – 45Combined sources3
Beta strandi47 – 52Combined sources6
Helixi55 – 57Combined sources3
Helixi58 – 68Combined sources11
Beta strandi71 – 76Combined sources6
Beta strandi82 – 84Combined sources3
Helixi88 – 94Combined sources7
Beta strandi99 – 103Combined sources5
Helixi104 – 106Combined sources3
Beta strandi111 – 114Combined sources4
Beta strandi119 – 122Combined sources4
Beta strandi125 – 131Combined sources7
Beta strandi134 – 136Combined sources3
Beta strandi140 – 144Combined sources5
Beta strandi147 – 153Combined sources7
Helixi171 – 181Combined sources11
Turni182 – 184Combined sources3
Beta strandi190 – 195Combined sources6
Beta strandi197 – 199Combined sources3
Helixi205 – 211Combined sources7
Turni213 – 216Combined sources4
Helixi219 – 228Combined sources10
Helixi237 – 245Combined sources9
Turni246 – 248Combined sources3

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...

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.
InterProiIPR001279. Metallo-B-lactamas.
[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 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 rs182983506dbSNPEnsembl.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 rs745656120dbSNPEnsembl.1
Natural variantiVAR_023397163R → W in EE. 2 PublicationsCorresponds to variant rs28940289dbSNPEnsembl.1
Natural variantiVAR_069510164T → K in EE; reduces protein stability. 1 Publication1
Natural variantiVAR_023398185L → R in EE. 2 PublicationsCorresponds to variant rs387906987dbSNPEnsembl.1
Natural variantiVAR_069511196D → N in EE; reduces protein stability and affinity for substrate. 2 PublicationsCorresponds to variant rs763799125dbSNPEnsembl.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.

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. 6 interactors.
MINTiMINT-1368289.
STRINGi9606.ENSP00000292147.

PTM databases

iPTMnetiO95571.
PhosphoSitePlusiO95571.
SwissPalmiO95571.

Polymorphism and mutation databases

BioMutaiETHE1.

2D gel databases

UCD-2DPAGEO95571.

Proteomic databases

EPDiO95571.
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.
DisGeNETi23474.
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

BioCyciZFISH:ENSG00000105755-MONOMER.
ReactomeiR-HSA-1614517. Sulfide oxidation to sulfate.

Miscellaneous databases

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

Gene expression databases

BgeeiENSG00000105755.
CleanExiHS_ETHE1.
ExpressionAtlasiO95571. baseline and differential.
GenevisibleiO95571. HS.

Family and domain databases

Gene3Di3.60.15.10. 1 hit.
InterProiIPR001279. Metallo-B-lactamas.
[Graphical view]
PfamiPF00753. Lactamase_B. 1 hit.
[Graphical view]
SMARTiSM00849. Lactamase_B. 1 hit.
[Graphical view]
SUPFAMiSSF56281. SSF56281. 1 hit.
ProtoNetiSearch...

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: November 2, 2016
This is version 134 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

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 one 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.