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

    Gene ID: 2108, updated on 3-Nov-2024

    Summary

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    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

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    See ETFA in Genome Data Viewer
    Location:
    15q24.2-q24.3
    Exon count:
    13
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 15 NC_000015.10 (76215353..76311469, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 15 NC_060939.1 (74086268..74182563, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 15 NC_000015.9 (76507694..76603810, complement)

    Chromosome 15 - NC_000015.10Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC124903531 Neighboring gene transmembrane protein 266 Neighboring gene Sharpr-MPRA regulatory region 3592 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr15:76432149-76432982 Neighboring gene ReSE screen-validated silencer GRCh37_chr15:76442422-76442685 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr15:76442959-76443537 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9873 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr15:76444006-76444636 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:76453363-76454200 Neighboring gene uncharacterized LOC101929439 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9875 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9874 Neighboring gene ReSE screen-validated silencer GRCh37_chr15:76482438-76482591 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9876 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:76488419-76488980 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:76488981-76489540 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:76489541-76490100 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:76491300-76491944 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:76491945-76492588 Neighboring gene NANOG hESC enhancer GRCh37_chr15:76526655-76527344 Neighboring gene H3K27ac hESC enhancer GRCh37_chr15:76603062-76603562 Neighboring gene H3K27ac hESC enhancer GRCh37_chr15:76603563-76604063 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9877 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9878 Neighboring gene CRISPRi-validated cis-regulatory element chr15.2471 Neighboring gene TYRO3P protein tyrosine kinase pseudogene Neighboring gene Sharpr-MPRA regulatory region 228 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr15:76629623-76630434 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9880 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr15:76632479-76633234 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9881 Neighboring gene uncharacterized LOC124903532 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:76638487-76638988 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6688 Neighboring gene ReSE screen-validated silencer GRCh37_chr15:76663676-76663893 Neighboring gene tRNA-Lys (anticodon CTT) 16-1 Neighboring gene S-phase cyclin A associated protein in the ER Neighboring gene ISL LIM homeobox 2

    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 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. Glutaric acidemia type II. Heterogeneity in beta-oxidation flux, polypeptide synthesis, and complementary DNA mutations in the alpha subunit of electron transfer flavoprotein in eight patients. Freneaux E, et al. J Clin Invest, 1992 Nov. PMID 1430199, Free PMC Article
    2. Molecular characterization of variant alpha-subunit of electron transfer flavoprotein in three patients with glutaric acidemia type II--and identification of glycine substitution for valine-157 in the sequence of the precursor, producing an unstable mature protein in a patient. Indo Y, et al. Am J Hum Genet, 1991 Sep. PMID 1882842, Free PMC Article
    3. Acyl-CoA dehydrogenases, electron transfer flavoprotein and electron transfer flavoprotein dehydrogenase. Frerman FE. Biochem Soc Trans, 1988 Jun. PMID 3053288
    4. Molecular cloning and nucleotide sequence of cDNAs encoding the alpha-subunit of human electron transfer flavoprotein. Finocchiaro G, et al. J Biol Chem, 1988 Oct 25. PMID 3170610
    5. A case report of a mild form of multiple acyl-CoA dehydrogenase deficiency due to compound heterozygous mutations in the ETFA gene. Chautard R, et al. BMC Med Genomics, 2020 Jan 29. PMID 31996215, Free PMC Article

    See all (143) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. 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.
    2. 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.
    3. 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.
    4. 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.
    5. Molecular Oxygen Binding in the Mitochondrial Electron Transfer Flavoprotein.
      Title: Molecular Oxygen Binding in the Mitochondrial Electron Transfer Flavoprotein.
    6. 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.
    7. 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.
    8. 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.
    9. 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.
    10. 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.
    Submit: New GeneRIF Correction See all GeneRIFs (16)

    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

    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

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    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

    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 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 PubMed 
    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
    		  

    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

    1. NG_007077.2 RefSeqGene

      Range
      5001..101117
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. 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

    2. 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

    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_000015.10 Reference GRCh38.p14 Primary Assembly

      Range
      76215353..76311469 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    RNA

    1. XR_007064434.1 RNA Sequence

      Related
      ENST00000688637.1

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060939.1 Alternate T2T-CHM13v2.0

      Range
      74086268..74182563 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    RNA

    1. XR_008488929.1 RNA Sequence

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P13804.1 GenPept UniProtKB/Swiss-Prot:P13804

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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