ETHE1 ETHE1 persulfide dioxygenase [Homo sapiens (human)] - Gene

Summary

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: mouse all
NEW: Try the new Gene table
Try the new Transcript table

Genomic context

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_000019.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

Go to the top of the page Help

Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Bibliography

Go to the top of the page Help

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
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.
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.
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.
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.
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.
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.
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

Go to the top of the page Help

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	Compare labs

Variation

Go to the top of the page Help

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

Go to the top of the page Help

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

Interactions

Go to the top of the page Help

Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

Go to the top of the page Help

Markers

ETHE1 (e-PCR)
- UniSTS:504429

D19S537 (e-PCR), detects polymorphism
- UniSTS:473247

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 more info	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

Go to the top of the page Help

Preferred Names: persulfide dioxygenase ETHE1, mitochondrial

Names: ethylmalonic encephalopathy 1; hepatoma subtracted clone one protein; protein ETHE1, mitochondrial; sulfur dioxygenase ETHE1

NP_001307796.1

EC 1.13.11.18

NP_001307797.1

EC 1.13.11.18

NP_001307798.1

EC 1.13.11.18

NP_055112.2

EC 1.13.11.18

XP_005258744.1

EC 1.13.11.18

XP_054176373.1

EC 1.13.11.18

NCBI Reference Sequences (RefSeq)

Go to the top of the page Help

NEW Try the new Transcript table

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

NG_008141.1 RefSeqGene

Range

5044..25526

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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
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
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
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