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ETHE1 ETHE1 persulfide dioxygenase [ Homo sapiens (human) ]

Gene ID: 23474, updated on 27-Nov-2024

Summary

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Official Symbol
ETHE1provided by HGNC
Official Full Name
ETHE1 persulfide dioxygenaseprovided by HGNC
Primary source
HGNC:HGNC:23287
See related
Ensembl:ENSG00000105755 MIM:608451; AllianceGenome:HGNC:23287
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
HSCO; YF13H12
Summary
This gene encodes a member of the metallo beta-lactamase family of iron-containing proteins involved in the mitochondrial sulfide oxidation pathway. The encoded protein catalyzes the oxidation of a persulfide substrate to sulfite. Certain mutations in this gene cause ethylmalonic encephalopathy, an infantile metabolic disorder affecting the brain, gastrointestinal tract and peripheral vessels. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2016]
Expression
Broad expression in colon (RPKM 85.9), duodenum (RPKM 30.9) and 20 other tissues See more
Orthologs
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Genomic context

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See ETHE1 in Genome Data Viewer
Location:
19q13.31
Exon count:
7
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 19 NC_000019.10 (43506719..43527201, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 19 NC_060943.1 (46327106..46348785, complement)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 19 NC_000019.9 (44010871..44031353, complement)

Chromosome 19 - NC_000019.10Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14723 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14724 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10717 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:43967981-43968512 Neighboring gene LY6/PLAUR domain containing 3 Neighboring gene pleckstrin homology like domain family B member 3 Neighboring gene Sharpr-MPRA regulatory region 2471 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:44008034-44008556 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10719 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:44017305-44017805 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10720 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:44029999-44030504 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:44030505-44031009 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10721 Neighboring gene ReSE screen-validated silencer GRCh37_chr19:44035307-44035478 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10722 Neighboring gene zinc finger protein 575 Neighboring gene X-ray repair cross complementing 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:44067237-44067737 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10723 Neighboring gene phospholipase A2 inhibitor and LY6/PLAUR domain containing

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Multiple sources of metabolic disturbance in ETHE1-related ethylmalonic encephalopathy. Barth M, et al. J Inherit Metab Dis, 2010 Dec. PMID 20978941
  2. Ethylmalonic encephalopathy ETHE1 R163W/R163Q mutations alter protein stability and redox properties of the iron centre. Henriques BJ, et al. PLoS One, 2014. PMID 25198162, Free PMC Article
  3. Untargeted Metabolomics Analysis Reveals a Link between ETHE1-Mediated Disruptive Redox State and Altered Metabolic Regulation. Sahebekhtiari N, et al. J Proteome Res, 2016 May 6. PMID 27074420
  4. Protein polysulfidation-dependent persulfide dioxygenase activity of ethylmalonic encephalopathy protein 1. Jung M, et al. Biochem Biophys Res Commun, 2016 Nov 11. PMID 27742479
  5. Ethylmalonic Encephalopathy. Adam MP, et al. , 1993. PMID 28933811

See all (51) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Ethylmalonic encephalopathy ETHE1 p. D165H mutation alters the mitochondrial function in human skeletal muscle proteome.
    Title: Ethylmalonic encephalopathy ETHE1 p. D165H mutation alters the mitochondrial function in human skeletal muscle proteome.
  2. Ethylmalonic encephalopathy 1 initiates overactive autophagy in depleted uranium-induced cytotoxicity in the human embryonic kidney 293 cells.
    Title: Ethylmalonic encephalopathy 1 initiates overactive autophagy in depleted uranium-induced cytotoxicity in the human embryonic kidney 293 cells.
  3. ETHE1 and MOCS1 deficiencies: Disruption of mitochondrial bioenergetics, dynamics, redox homeostasis and endoplasmic reticulum-mitochondria crosstalk in patient fibroblasts.
    Title: ETHE1 and MOCS1 deficiencies: Disruption of mitochondrial bioenergetics, dynamics, redox homeostasis and endoplasmic reticulum-mitochondria crosstalk in patient fibroblasts.
  4. The mitochondrial enzyme ETHE1 is a persulfide dioxygenase essential for cellular sulfide detoxification, and its deficiency causes the severe and complex inherited metabolic disorder ethylmalonic encephalopathy (EE).
    Title: Deficiency of the mitochondrial sulfide regulator ETHE1 disturbs cell growth, glutathione level and causes proteome alterations outside mitochondria.
  5. observations indicate the severe impact of ETHE1 deficiency on cellular physiology and redox state
    Title: Untargeted Metabolomics Analysis Reveals a Link between ETHE1-Mediated Disruptive Redox State and Altered Metabolic Regulation.
  6. ETHE1 is a major enzyme regulating endogenous glutathione persulfide /GS-(S)n-H and that its activity is controlled by polysulfidation of the Cys247 residue.
    Title: Protein polysulfidation-dependent persulfide dioxygenase activity of ethylmalonic encephalopathy protein 1.
  7. ETHE1 R163W/R163Q mutations are associated with Ethylmalonic encephalopathy.
    Title: Ethylmalonic encephalopathy ETHE1 R163W/R163Q mutations alter protein stability and redox properties of the iron centre.
  8. Case Report: metabolic disturbances in 15-month-old male presenting with typical ethylmalonic encephalopathy associated with a homozygous ETHE1 mutation.
    Title: Multiple sources of metabolic disturbance in ETHE1-related ethylmalonic encephalopathy.
  9. T152I mutation of ETHE1 results in a 3-fold lower activity.
    Title: Characterization of patient mutations in human persulfide dioxygenase (ETHE1) involved in H2S catabolism.
  10. Observational study of gene-disease association. (HuGE Navigator)
    Title: Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression.
Submit: New GeneRIF Correction See all GeneRIFs (15)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
Ethylmalonic encephalopathy
MedGen: C1865349 OMIM: 602473 GeneReviews: Ethylmalonic Encephalopathy
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Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Replication interactions

Interaction Pubs
Knockdown of ethylmalonic encephalopathy 1 (ETHE1) by siRNA inhibits HIV-1 replication in HeLa-derived TZM-bl cells PubMed

Protein interactions

Protein Gene Interaction Pubs
Vpr vpr A stable-isotope labeling by amino acids in cell culture coupled with mass spectrometry-based proteomics identifies downregulation of ethylmalonic encephalopathy 1 (ETHE1) expression by HIV-1 Vpr in Vpr transduced macrophages PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables identical protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables iron ion binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables sulfur dioxygenase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables sulfur dioxygenase activity IDA
Inferred from Direct Assay
more info
 PubMed 
Process Evidence Code Pubs
involved_in glutathione metabolic process IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in glutathione metabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in hydrogen sulfide metabolic process IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in hydrogen sulfide metabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
Component Evidence Code Pubs
located_in cytoplasm IDA
Inferred from Direct Assay
more info
  
located_in mitochondrial matrix TAS
Traceable Author Statement
more info
  
located_in mitochondrion HTP PubMed 
is_active_in mitochondrion IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in mitochondrion IDA
Inferred from Direct Assay
more info
  
located_in nucleoplasm IDA
Inferred from Direct Assay
more info
  

General protein information

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Preferred Names
persulfide dioxygenase ETHE1, mitochondrial
Names
ethylmalonic encephalopathy 1
hepatoma subtracted clone one protein
protein ETHE1, mitochondrial
sulfur dioxygenase ETHE1
NP_001307796.1
NP_001307797.1
NP_001307798.1
NP_055112.2
XP_005258744.1
XP_054176373.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_008141.1 RefSeqGene

    Range
    5044..25526
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001320867.2 → NP_001307796.1  persulfide dioxygenase ETHE1, mitochondrial isoform 2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) uses an alternate in-frame splice site in the 5' coding region, compared to variant 1. It encodes isoform 2, which is shorter than isoform 1.
    Source sequence(s)
    BC008250, BP252912, KU178566
    UniProtKB/TrEMBL
    A0A0S2Z580, M0QXB5
    Conserved Domains (2) summary
    PLN02962
    Location:13 → 243
    PLN02962; hydroxyacylglutathione hydrolase
    cd07724
    Location:24 → 186
    POD-like_MBL-fold; ETHE1 (PDO type I), persulfide dioxygenase A (PDOA, PDO type II) and related proteins; MBL-fold metallo-hydrolase domain

  2. NM_001320868.2 → NP_001307797.1  persulfide dioxygenase ETHE1, mitochondrial isoform 3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) differs in the 5' UTR, lacks a portion of the 5' coding region and initiates translation at an alternate start site, compared to variant 1. It encodes isoform 3, which is shorter and has a distinct N-terminus compared to isoform 1.
    Source sequence(s)
    BC008250, BG706505
    UniProtKB/Swiss-Prot
    O95571
    Conserved Domains (1) summary
    cl23716
    Location:2 → 74
    metallo-hydrolase-like_MBL-fold; mainly hydrolytic enzymes and related proteins which carry out various biological functions; MBL-fold metallohydrolase domain

  3. NM_001320869.2 → NP_001307798.1  persulfide dioxygenase ETHE1, mitochondrial isoform 4

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) lacks two alternate exons in the 5' coding region, compared to variant 1. It encodes isoform 4, which is shorter than isoform 1.
    Source sequence(s)
    BC008250, BP252912, KU178567
    UniProtKB/TrEMBL
    A0A0S2Z5N8
    Conserved Domains (1) summary
    cl23716
    Location:29 → 99
    metallo-hydrolase-like_MBL-fold; mainly hydrolytic enzymes and related proteins which carry out various biological functions; MBL-fold metallohydrolase domain

  4. NM_014297.5 → NP_055112.2  persulfide dioxygenase ETHE1, mitochondrial isoform 1

    See identical proteins and their annotated locations for NP_055112.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
    Source sequence(s)
    BC008250, BP252912, D83198
    Consensus CDS
    CCDS12622.1
    UniProtKB/Swiss-Prot
    O95571, Q96HR0, Q9H001
    UniProtKB/TrEMBL
    A0A0S2Z5B3, M0QXB5
    Related
    ENSP00000292147.1, ENST00000292147.7
    Conserved Domains (1) summary
    cl25711
    Location:13 → 254
    HAGH_C; Hydroxyacylglutathione hydrolase C-terminus

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000019.10 Reference GRCh38.p14 Primary Assembly

    Range
    43506719..43527201 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_005258687.5 → XP_005258744.1  persulfide dioxygenase ETHE1, mitochondrial isoform X1

    See identical proteins and their annotated locations for XP_005258744.1

    UniProtKB/TrEMBL
    B2RCZ7, M0QXB5
    Conserved Domains (1) summary
    PLN02962
    Location:1 → 227
    PLN02962; hydroxyacylglutathione hydrolase

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060943.1 Alternate T2T-CHM13v2.0

    Range
    46327106..46348785 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054320398.1 → XP_054176373.1  persulfide dioxygenase ETHE1, mitochondrial isoform X1

    UniProtKB/TrEMBL
    B2RCZ7
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
O95571.2 GenPept UniProtKB/Swiss-Prot:O95571

Gene LinkOut

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