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O95571

- ETHE1_HUMAN

UniProt

O95571 - ETHE1_HUMAN

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Protein

Persulfide dioxygenase ETHE1, mitochondrial

Gene

ETHE1

Organism
Homo sapiens (Human)
Status
Reviewed - 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

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: 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
Complete GO annotation...

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

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

3D structure databases

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.

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. 10 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.
GeneTreei ENSGT00530000063033.
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

Bgeei O95571.
CleanExi HS_ETHE1.
ExpressionAtlasi O95571. baseline and differential.
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

« 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. "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 29, 2014
This is version 112 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