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O95571 (ETHE1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 106. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:ETHE1
Synonyms:HSCO
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length254 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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 (Ref.1). Ref.1 Ref.2 Ref.5 Ref.8

Catalytic activity

Sulfur + O2 + H2O = sulfite + 2 H+. Ref.5 Ref.8

Cofactor

Binds 1 Fe2+ ion per subunit. Ref.5 Ref.8

Enzyme regulation

Glutathione increases enzyme activity. Ref.8

Subunit structure

Monomer. Interacts with TST. May interact with RELA. Ref.1 Ref.5 Ref.8

Subcellular location

Cytoplasm. Nucleus. Mitochondrion matrix. Note: According to Ref.1, it is cytoplasmic and nuclear. According to Ref.2, it is found in the mitochondrial matrix. Ref.1 Ref.2 Ref.5

Tissue specificity

Ubiquitously expressed. Ref.2

Involvement in disease

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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.2 Ref.5 Ref.8 Ref.9

Sequence similarities

Belongs to the metallo-beta-lactamase superfamily. Glyoxalase II family.

Biophysicochemical properties

Kinetic parameters:

KM=0.34 mM for glutathione persulfide (GSSH) Ref.8

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

Sequence caution

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 77Mitochondrion
Chain8 – 254247Persulfide dioxygenase ETHE1, mitochondrial
PRO_0000012289

Sites

Metal binding791Iron; catalytic Probable
Metal binding1351Iron; catalytic Probable
Metal binding1541Iron; catalytic Probable

Amino acid modifications

Modified residue661N6-acetyllysine Ref.6
Modified residue1721N6-acetyllysine; alternate By similarity
Modified residue1721N6-succinyllysine; alternate By similarity

Natural variations

Natural variant381Y → C in EE. Ref.2
VAR_023395
Natural variant551L → P in EE; reduces protein stability. Ref.9
VAR_069507
Natural variant1361T → A in EE. Ref.2 Ref.9
VAR_023396
Natural variant1521T → I in EE; reduces protein stability, iron content and enzyme activity. Ref.8 Ref.9
VAR_069508
Natural variant1631R → Q in EE. Ref.9
VAR_069509
Natural variant1631R → W in EE. Ref.2 Ref.9
Corresponds to variant rs28940289 [ dbSNP | Ensembl ].
VAR_023397
Natural variant1641T → K in EE; reduces protein stability. Ref.9
VAR_069510
Natural variant1851L → R in EE. Ref.2 Ref.9
VAR_023398
Natural variant1961D → N in EE; reduces protein stability and affinity for substrate. Ref.8 Ref.9
VAR_069511

Sequences

Sequence LengthMass (Da)Tools
O95571 [UniParc].

Last modified March 1, 2003. Version 2.
Checksum: 52073D52A487ACD4

FASTA25427,873
        10         20         30         40         50         60 
MAEAVLRVAR RQLSQRGGSG APILLRQMFE PVSCTFTYLL GDRESREAVL IDPVLETAPR 

        70         80         90        100        110        120 
DAQLIKELGL RLLYAVNTHC HADHITGSGL LRSLLPGCQS VISRLSGAQA DLHIEDGDSI 

       130        140        150        160        170        180 
RFGRFALETR ASPGHTPGCV TFVLNDHSMA FTGDALLIRG CGRTDFQQGC AKTLYHSVHE 

       190        200        210        220        230        240 
KIFTLPGDCL IYPAHDYHGF TVSTVEEERT LNPRLTLSCE EFVKIMGNLN LPKPQQIDFA 

       250 
VPANMRCGVQ TPTA 

« Hide

References

« Hide 'large scale' references
[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]"Ethylmalonic encephalopathy is caused by mutations in ETHE1, a gene encoding a mitochondrial matrix protein."
Tiranti V., D'Adamo P., Briem E., Ferrari G., Mineri R., Lamantea E., Mandel H., Balestri P., Garcia-Silva M.-T., Vollmer B., Rinaldo P., Hahn S.H., Leonard J., Rahman S., Dionisi-Vici C., Garavaglia B., Gasparini P., Zeviani M.
Am. J. Hum. Genet. 74:239-252(2004) [PubMed] [Europe PMC] [Abstract]
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. expand/collapse author list , 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]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
D83198 mRNA. Translation: BAA34595.2.
AC018758 Genomic DNA. Translation: AAG09063.1. Sequence problems.
BC008250 mRNA. Translation: AAH08250.1.
RefSeqNP_055112.2. NM_014297.3.
XP_005258744.1. XM_005258687.1.
UniGeneHs.7486.

3D structure databases

ProteinModelPortalO95571.
SMRO95571. Positions 23-245.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid117034. 7 interactions.
IntActO95571. 4 interactions.
MINTMINT-1368289.
STRING9606.ENSP00000292147.

PTM databases

PhosphoSiteO95571.

2D gel databases

UCD-2DPAGEO95571.

Proteomic databases

PaxDbO95571.
PeptideAtlasO95571.
PRIDEO95571.

Protocols and materials databases

DNASU23474.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000292147; ENSP00000292147; ENSG00000105755.
GeneID23474.
KEGGhsa:23474.
UCSCuc002owp.3. human.

Organism-specific databases

CTD23474.
GeneCardsGC19M044010.
HGNCHGNC:23287. ETHE1.
HPAHPA028360.
HPA029028.
HPA029029.
MIM602473. phenotype.
608451. gene.
neXtProtNX_O95571.
Orphanet51188. Ethylmalonic encephalopathy.
PharmGKBPA134879650.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0491.
HOGENOMHOG000058040.
HOVERGENHBG053310.
InParanoidO95571.
KOK17725.
OrthoDBEOG7MH107.
PhylomeDBO95571.
TreeFamTF312952.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.

Gene expression databases

ArrayExpressO95571.
BgeeO95571.
CleanExHS_ETHE1.
GenevestigatorO95571.

Family and domain databases

Gene3D3.60.15.10. 1 hit.
InterProIPR001279. Beta-lactamas-like.
[Graphical view]
PfamPF00753. Lactamase_B. 1 hit.
[Graphical view]
SMARTSM00849. Lactamase_B. 1 hit.
[Graphical view]
SUPFAMSSF56281. SSF56281. 1 hit.
ProtoNetSearch...

Other

GeneWikiETHE1.
GenomeRNAi23474.
NextBio45809.
PROO95571.
SOURCESearch...

Entry information

Entry nameETHE1_HUMAN
AccessionPrimary (citable) accession number: O95571
Secondary accession number(s): Q96HR0, Q9H001
Entry history
Integrated into UniProtKB/Swiss-Prot: August 30, 2005
Last sequence update: March 1, 2003
Last modified: April 16, 2014
This is version 106 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM