ETFA electron transfer flavoprotein subunit alpha [Homo sapiens (human)] - Gene

Summary

Official Symbol: ETFAprovided by HGNC
Official Full Name: electron transfer flavoprotein subunit alphaprovided by HGNC
Primary source: HGNC:HGNC:3481
See related: Ensembl:ENSG00000140374 MIM:608053; AllianceGenome:HGNC:3481
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: EMA; GA2; MADD
Summary: ETFA participates in catalyzing the initial step of the mitochondrial fatty acid beta-oxidation. It shuttles electrons between primary flavoprotein dehydrogenases and the membrane-bound electron transfer flavoprotein ubiquinone oxidoreductase. Defects in electron-transfer-flavoprotein have been implicated in type II glutaricaciduria in which multiple acyl-CoA dehydrogenase deficiencies result in large excretion of glutaric, lactic, ethylmalonic, butyric, isobutyric, 2-methyl-butyric, and isovaleric acids. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
Expression: Ubiquitous expression in liver (RPKM 95.3), heart (RPKM 73.2) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 15q24.2-q24.3

Exon count:: 13

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	15	NC_000015.10 (76215353..76311469, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	15	NC_060939.1 (74086268..74182563, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	15	NC_000015.9 (76507694..76603810, complement)

Chromosome 15 - NC_000015.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Platelet Microparticle-Derived MiR-320b Inhibits Hypertension with Atherosclerosis Development by Targeting ETFA.
Title: Platelet Microparticle-Derived MiR-320b Inhibits Hypertension with Atherosclerosis Development by Targeting ETFA.
NBPF4 mitigates progression in colorectal cancer through the regulation of EZH2-associated ETFA.
Title: NBPF4 mitigates progression in colorectal cancer through the regulation of EZH2-associated ETFA.
Screening of multiple acyl-CoA dehydrogenase deficiency in newborns and follow-up of patients.
Title: Screening of multiple acyl-CoA dehydrogenase deficiency in newborns and follow-up of patients.
A case report of a mild form of multiple acyl-CoA dehydrogenase deficiency due to compound heterozygous mutations in the ETFA gene.
Title: A case report of a mild form of multiple acyl-CoA dehydrogenase deficiency due to compound heterozygous mutations in the ETFA gene.
Molecular Oxygen Binding in the Mitochondrial Electron Transfer Flavoprotein.
Title: Molecular Oxygen Binding in the Mitochondrial Electron Transfer Flavoprotein.
Molecular and Clinical Investigations on Portuguese Patients with Multiple acyl-CoA Dehydrogenase Deficiency.
Title: Molecular and Clinical Investigations on Portuguese Patients with Multiple acyl-CoA Dehydrogenase Deficiency.
Data suggest that ETF (heterodimer of ETFA and ETFB) catalyzes irreversible and pH-dependent oxidation of 8alpha-methyl group of FAD to form to 8-formyl-FAD (8f-FAD).
Title: Oxidation of the FAD cofactor to the 8-formyl-derivative in human electron-transferring flavoprotein.
our results indicate that genetic variants in ETFA may modify individual susceptibility to non-GBM of glioma in the Han Chinese population and support the role of the ETFA genes in the occurrence of glioma.
Title: Additional evidence supports association of common genetic variants in VTI1A and ETFA with increased risk of glioma susceptibility.
the mechanism of tert-butyl hydroperoxide-induced an apoptosis cascade and endoplasmic reticulum stress in hepatocyte cells by up-regulation of ETFA, providing a new mechanism for liver injury.
Title: Exploring the effects of tert-butylhydroperoxide induced liver injury using proteomic approach.
These results are consistent with the electron transfer flavoprotein alpha II domain adopting orientations in solution that deviate from the crystal structure of free ETF towards the active, substrate-bound orientation.
Title: Electron transfer flavoprotein domain II orientation monitored using double electron-electron resonance between an enzymatically reduced, native FAD cofactor, and spin labels.

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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
Multiple acyl-CoA dehydrogenase deficiency MedGen: C0268596 OMIM: 231680 GeneReviews: Multiple Acyl-CoA Dehydrogenase Deficiency	Compare labs

EBI GWAS Catalog

Description
Genome-wide association analysis implicates the involvement of eight loci with response to tocilizumab for the treatment of rheumatoid arthritis. EBI GWAS Catalog EBI GWAS CatalogPubMed

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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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 electron-transfer-flavoprotein, alpha polypeptide (ETFA) expression by HIV-1 Vpr in Vpr transduced macrophages	PubMed

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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

STS-H78599 (e-PCR)
- UniSTS:82471

D15S922 (e-PCR)
- UniSTS:322

WI-20018 (e-PCR)
- UniSTS:46741

STS-J04058 (e-PCR)
- UniSTS:207

WI-18782 (e-PCR)
- UniSTS:23522

D15S925 (e-PCR)
- UniSTS:42745

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables electron transfer activity	IBA Inferred from Biological aspect of Ancestor more info
enables electron transfer activity	IDA Inferred from Direct Assay more info	PubMed
enables flavin adenine dinucleotide binding	IBA Inferred from Biological aspect of Ancestor more info
enables flavin adenine dinucleotide binding	IDA Inferred from Direct Assay more info	PubMed
enables oxidoreductase activity	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in amino acid catabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in fatty acid beta-oxidation using acyl-CoA dehydrogenase	IBA Inferred from Biological aspect of Ancestor more info
involved_in fatty acid beta-oxidation using acyl-CoA dehydrogenase	IDA Inferred from Direct Assay more info	PubMed
involved_in respiratory electron transport chain	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
part_of electron transfer flavoprotein complex	IPI Inferred from Physical Interaction more info	PubMed
located_in mitochondrial matrix	NAS Non-traceable Author Statement more info	PubMed
located_in mitochondrial matrix	TAS Traceable Author Statement more info
located_in mitochondrion	HDA 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

General protein information

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Preferred Names: electron transfer flavoprotein subunit alpha, mitochondrial

Names: alpha-ETF; electron transfer flavoprotein alpha subunit; electron transfer flavoprotein, alpha polypeptide; epididymis secretory sperm binding protein; glutaric aciduria II; multiple acyl-CoA dehydrogenase deficiency

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

NG_007077.2 RefSeqGene

Range

5001..101117

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000126.4 → NP_000117.1 electron transfer flavoprotein subunit alpha, mitochondrial isoform a

See identical proteins and their annotated locations for NP_000117.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (a).

Source sequence(s)

AA557337, AC091100, AK292979, BG261160

Consensus CDS

CCDS32299.1

UniProtKB/Swiss-Prot

B4DT43, P13804, Q53XN3

UniProtKB/TrEMBL

A0A0S2Z3L0, A0A8I5KYP7

Related

ENSP00000452762.1, ENST00000557943.6

Conserved Domains (1) summary

PLN00022
Location:3 → 333

PLN00022; electron transfer flavoprotein subunit alpha; Provisional
NM_001127716.2 → NP_001121188.1 electron transfer flavoprotein subunit alpha, mitochondrial isoform b

See identical proteins and their annotated locations for NP_001121188.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an alternate in-frame exon compared to variant 1. The resulting isoform (b) has the same N- and C-termini but is shorter compared to isoform a.

Source sequence(s)

AA557337, AC091100, AK292979, BG261160, BU176141

Consensus CDS

CCDS45311.1

UniProtKB/TrEMBL

A0A8I5KT03

Related

ENSP00000399273.2, ENST00000433983.6

Conserved Domains (2) summary

cd01715
Location:13 → 140

ETF_alpha; The electron transfer flavoprotein (ETF) serves as a specific electron acceptor for various mitochondrial dehydrogenases. ETF transfers electrons to the main respiratory chain via ETF-ubiquinone oxidoreductase. ETF is an heterodimer that consists of an ...

pfam00766
Location:162 → 244

ETF_alpha; Electron transfer flavoprotein FAD-binding domain