Details of Host Protein

 Host Protein General Information (ID: PT0379)
  Protein Name
Electron transfer flavoprotein subunit alpha (ETFA)
  Gene Name
ETFA
  Host Species
Homo sapiens
  Uniprot Entry Name
ETFA_HUMAN
  Protein Families
ETF alpha-subunit/FixB family
  Subcellular Location
Mitochondrion matrix
  External Link
NCBI Gene ID
2108
Uniprot ID
P13804
Ensembl ID
ENSG00000140374
HGNC ID
HGNC:3481
  Function in Host
Heterodimeric electron transfer flavoprotein that acceptselectrons from several mitochondrial dehydrogenases, including acyl-CoAdehydrogenases, glutaryl-CoA and sarcosine dehydrogenase. It transfers the electrons to the main mitochondrialrespiratory chain via ETF-ubiquinone oxidoreductase (ETF dehydrogenase). Required for normal mitochondrial fatty acidoxidation and normal amino acid metabolism. [1-9]
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  3D Structure
PDB ID: 1EFV 
FASTA   Download
  2D PNG Download  
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Function of This Protein During Virus Infection
Virus NameSARS-COV-2 Protein Function Pro-viral [10]
Infected TissueColon Infection Time48 h
Infected CellCaco-2 cells (Human colorectal adenocarcinoma cell) Cellosaurus IDCVCL_0025 
Method DescriptionTo detect the role of host protein ETFA in viral infection, ETFA protein knockout Caco-2 cells were infected with SARS-COV-2 for 48 h , and the effects on infection was detected through qPCR.
ResultsIt is reported that Knockdown of ETFA leads to the reduced the vRNA levels compared with control group.

 Full List of Virus RNA Interacting with This Protien
            RNA Region: 3'-UTR (hCoV-19/IPBCAMS-YL01/2020 )
              RNA Region Details RNA Info Click to show the detail information of this RNA binding region [10]
              Strains Name
hCoV-19/IPBCAMS-YL01/2020
              Strains Family
Beta (B.1.351)
              RNA Binding Region
3'-UTR
              Virus Name
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
              Interaction Type Unlikely to be direct binder
              Infection Cells Huh7.5.1 cells (Hepatocyte derived cellular carcinoma cell)  (CVCL_E049 )
              Cell Originated Tissue Liver
              Infection Time 30 h
              Interaction Score MIST = 0.986005038
              Method Description comprehensive identification of RNA-binding proteins by massspectrometry (ChIRP-MS)

Differential Gene Expression During SARS-COV-2 Infection
GEO Accession: GSE152641
Sample Type: Blood
Samples Details: Healthy Control: 24; COVID-19: 62
Platform: GPL24676 Illumina NovaSeq 6000
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GEO Accession: GSE162835
Sample Type: Nasopharyngeal Swabs
Samples Details: COVID-19 (Mild Symptoms): 37; COVID-19 (Moderate Symptoms): 10; COVID-19 (Severe Symptoms): 3
Platform: GPL24676 Illumina NovaSeq 6000
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GEO Accession: GSE175779
Sample Type: Human Bronchial Epithelial Cells
Samples Details: Healthy Control: 4 (0, 24, 48, 72 and 96 h); COVID-19: 4 (24, 48, 72 and 96 h)
Platform: GPL18573 Illumina NextSeq 500
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Protein Phosphorylation after Virus Infection
S133 [11]
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Potential Drug(s) that Targets This Protein
Drug Name DrunkBank ID Pubchem ID TTD ID REF
Carvedilol DB01136  2585  D0W9LX  [12]
L-Threonine DB00156  6288  D0N0GE  [13]

Protein Sequence Information
MFRAAAPGQLRRAASLLRFQSTLVIAEHANDSLAPITLNTITAATRLGGEVSCLVAGTKCDKVAQDLCKVAGIAKVLVAQHDVYKGLLPEELTPLILATQKQFNYTHICAGASAFGKNLLPRVAAKLEVAPISDIIAIKSPDTFVRTIYAGNALCTVKCDEKVKVFSVRGTSFDAAATSGGSASSEKASSTSPVEISEWLDQKLTKSDRPELTGAKVVVSGGRGLKSGENFKLLYDLADQLHAAVGASRAAVDAGFVPNDMQVGQTGKIVAPELYIAVGISGAIQHLAGMKDSKTIVAINKDPEAPIFQVADYGIVADLFKVVPEMTEILKKK
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References
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. J Clin Invest. 1992 Nov;90(5):1679-86.
2 Mitochondrial Protein Interaction Mapping Identifies Regulators of Respiratory Chain Function. Mol Cell. 2016 Aug 18;63(4):621-632.
3 Dynamics driving function: new insights from electron transferring flavoproteins and partner complexes. FEBS J. 2007 Nov;274(21):5481-504.
4 Stabilization of non-productive conformations underpins rapid electron transfer to electron-transferring flavoprotein. J Biol Chem. 2005 Aug 26;280(34):30361-6.
5 Extensive domain motion and electron transfer in the human electron transferring flavoprotein.medium chain Acyl-CoA dehydrogenase complex. J Biol Chem. 2004 Jul 30;279(31):32904-12.
6 Clear relationship between ETF/ETFDH genotype and phenotype in patients with multiple acyl-CoA dehydrogenation deficiency. Hum Mutat. 2003 Jul;22(1):12-23.
7 A polymorphic variant in the human electron transfer flavoprotein alpha-chain (alpha-T171) displays decreased thermal stability and is overrepresented in very-long-chain acyl-CoA dehydrogenase-deficient patients with mild childhood presentation. Mol Genet Metab. 1999 Jun;67(2):138-47.
8 Expression and characterization of two pathogenic mutations in human electron transfer flavoprotein. J Biol Chem. 1997 Oct 17;272(42):26425-33.
9 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. Am J Hum Genet. 1991 Sep;49(3):575-80.
10 Comparison of viral RNA-host protein interactomes across pathogenic RNA viruses informs rapid antiviral drug discovery for SARS-CoV-2. Cell Res. 2022 Jan;32(1):9-23.
11 Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV. Nature. 2021 Jun;594(7862):246-252.
12 Investigating the human protein-host protein interactome of SARS-CoV-2 infection in the small intestine. Gastroenterol Hepatol Bed Bench. Fall 2020;13(4):374-387.
13 Exploring the SARS-CoV-2 virus-host-drug interactome for drug repurposing. Nat Commun. 2020 Jul 14;11(1):3518.