Host Protein General Information (ID: PT0157)
  Protein Name
Adenine nucleotide translocator 4 (ANT 4)
  Gene Name
SLC25A31
  Host Species
Homo sapiens
  Uniprot Entry Name
ADT4_HUMAN
  Protein Families
Mitochondrial carrier(TC 2.A.29) family
  Subcellular Location
Plasma membrane; mitochondrion
  External Link
NCBI Gene ID
83447
Uniprot ID
Q9H0C2
Ensembl ID
ENSG00000101745
HGNC ID
HGNC:25319
  Function in Host
ADP:ATP antiporter that mediates import of ADP into themitochondrial matrix for ATP synthesis, and export of ATP out to fuelthe cell. Cycles between the cytoplasmic-open state (c-state) and the matrix-open state (m-state) : operates by the alternatingaccess mechanism with a single substrate-binding site intermittentlyexposed to either the cytosolic (c-state) or matrix (m-state) side ofthe inner mitochondrial membrane. Specifically requiredduring spermatogenesis, probably to mediate ADP:ATP exchange inspermatocytes. Large ATP supplies from mitochondriamay be critical for normal progression of spermatogenesis during earlystages of meiotic prophase I, including DNA double-strand break repairand chromosomal synapsis. In addition to its ADP:ATPantiporter activity, also involved in mitochondrial uncoupling andmitochondrial permeability transition pore (mPTP) activity. Plays a role in mitochondrial uncoupling by acting as aproton transporter: proton transport uncouples the proton flows via theelectron transport chain and ATP synthase to reduce the efficiency ofATP production and cause mitochondrial thermogenesis. Proton transporter activity is inhibited by ADP:ATP antiporteractivity, suggesting that SLC25A31/ANT4 acts as a master regulator ofmitochondrial energy output by maintaining a delicate balance betweenATP production (ADP:ATP antiporter activity) and thermogenesis (protontransporter activity). Proton transporter activityrequires free fatty acids as cofactor, but does not transport it. Also plays a key role in mPTP opening, a non-specific porethat enables free passage of the mitochondrial membranes to solutes ofup to 1. 5 kDa, and which contributes to cell death. Itis however unclear if SLC25A31/ANT4 constitutes a pore-formingcomponent of mPTP or regulates it.
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  Related KEGG Pathway
Neutrophil extracellular trap formation hsa04613            Pathway Map 
Influenza A hsa05164            Pathway Map 
Human T-cell leukemia virus 1 infection hsa05166            Pathway Map 
Calcium signaling pathway hsa04020            Pathway Map 
cGMP-PKG signaling pathway hsa04022            Pathway Map 
Necroptosis hsa04217            Pathway Map 
Cellular senescence hsa04218            Pathway Map 
Chemical carcinogenesis - reactive oxygen species hsa05208            Pathway Map 
  3D Structure

Function of This Protein During Virus Infection
Virus NameSARS-COV-2 Protein Function Anti-viral [1]
Infected TissueLung Infection Time7-9 Days
Infected CellCalu-3 Cells (Human epithelial cell line) Cellosaurus IDCVCL_0609 
Method DescriptionTo detect the role of host protein SLC25A31 in viral infection, SLC25A31 protein knockout Calu-3 Cells were infected with SARS-COV-2 for 7 - 9 Days , and the effects on infection was detected through CRISPR-based genome-wide gene-knockout screen.
ResultsIt is reported that knockout of SLC25A31 increases SARS-CoV-2 RNA levels compared with control group.

 Full List of Virus RNA Interacting with This Protien
            RNA Region: 5'-UTR (hCoV-19/Wuhan-Hu-1/2019 )
              RNA Region Details RNA Info Click to show the detail information of this RNA binding region [2]
              Strains Name
hCoV-19/Wuhan-Hu-1/2019
              Strains Family
Beta (B.1.351)
              RNA Binding Region
5'-UTR
              Virus Name
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
              Infection Cells HEK293 Cells (Human embryonic kidney cell)  (CVCL_0045 )
              Cell Originated Tissue Liver
              Infection Time 48 h
              Interaction Score Prot score = 60
              Method Description RNA-protein interaction detection (RaPID) assay; liquid chromatography with tandem mass spectrometry (LC-MS/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 Sequence Information
MHREPAKKKAEKRLFDASSFGKDLLAGGVAAAVSKTAVAPIERVKLLLQVQASSKQISPEARYKGMVDCLVRIPREQGFFSFWRGNLANVIRYFPTQALNFAFKDKYKQLFMSGVNKEKQFWRWFLANLASGGAAGATSLCVVYPLDFARTRLGVDIGKGPEERQFKGLGDCIMKIAKSDGIAGLYQGFGVSVQGIIVYRASYFGAYDTVKGLLPKPKKTPFLVSFFIAQVVTTCSGILSYPFDTVRRRMMMQSGEAKRQYKGTLDCFVKIYQHEGISSFFRGAFSNVLRGTGGALVLVLYDKIKEFFHIDIGGR
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References
1 Genome-wide CRISPR screens identify GATA6 as a proviral host factor for SARS-CoV-2 via modulation of ACE2. Nat Commun. 2022 Apr 25;13(1):2237.
2 RNA-Protein Interaction Analysis of SARS-CoV-2 5 and 3 Untranslated Regions Reveals a Role of Lysosome-Associated Membrane Protein-2a during Viral Infection. mSystems. 2021 Aug 31;6(4):e0064321.