Details of Host Protein

 Host Protein General Information (ID: PT0161)
  Protein Name
AFG3-like protein 2 (AFG3L2)
  Gene Name
AFG3L2
  Host Species
Homo sapiens
  Uniprot Entry Name
AFG32_HUMAN
  Protein Families
AAA ATPase family; Peptidase M41 family
  EC Number
3.4.24.-
  Subcellular Location
Multi-pass membrane protein
  External Link
NCBI Gene ID
10939
Uniprot ID
Q9Y4W6
Ensembl ID
ENSG00000141385
HGNC ID
HGNC:315
  Function in Host
ATP-dependent protease which is essential for axonal andneuron development. In neurons, mediates degradation of SMDT1/EMREbefore its assembly with the uniporter complex, limiting theavailability of SMDT1/EMRE for MCU assembly and promoting efficientassembly of gatekeeper subunits with MCU. Requiredfor paraplegin (SPG7) maturation. After its cleavageby mitochondrial-processing peptidase (MPP), it converts paraplegininto a proteolytically active mature form. Required forthe maturation of PINK1 into its 52kDa mature form after its cleavageby mitochondrial-processing peptidase (MPP). Involved in the regulation of OMA1-dependentprocessing of OPA1. [1-4]
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  Related KEGG Pathway
Spinocerebellar ataxia hsa05017            Pathway Map 
  3D Structure
PDB ID: 2LNA 
FASTA   Download
  2D PNG Download  
PDB File Download

Function of This Protein During Virus Infection
Virus NameSARS-COV-2 Protein Function Anti-viral [5]
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 AFG3L2 in viral infection, AFG3L2 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 AFG3L2 increases SARS-CoV-2 RNA levels compared with control group.

 Full List of Virus RNA Interacting with This Protien
            RNA Region: Not Specified Virus Region (hCoV-19/Not Specified Virus Strain )
              RNA Region Details RNA Info Click to show the detail information of this RNA binding region [6]
              Strains Name
hCoV-19/Not Specified Virus Strain
              RNA Binding Region
Not Specified Virus Region
              Virus Name
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
              Infection Cells Huh7 cells (liver carcinoma cell)  (CVCL_0336 )
              Cell Originated Tissue Liver
              Infection Time 24h
              Interaction Score log2FC = 9.10328E+14
              Method Description RNA antisense purification and quantitative mass spectrometry (RAP-MS); Tandem mass tag (TMT) labelling; liquid chromatography tandem mass spectrometry (LC-MS/MS); Westernblot

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
  PNG Download  
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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
  PNG Download  
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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
  PNG Download  
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Protein Sequence Information
MAHRCLRLWGRGGCWPRGLQQLLVPGGVGPGEQPCLRTLYRFVTTQARASRNSLLTDIIAAYQRFCSRPPKGFEKYFPNGKNGKKASEPKEVMGEKKESKPAATTRSSGGGGGGGGKRGGKKDDSHWWSRFQKGDIPWDDKDFRMFFLWTALFWGGVMFYLLLKRSGREITWKDFVNNYLSKGVVDRLEVVNKRFVRVTFTPGKTPVDGQYVWFNIGSVDTFERNLETLQQELGIEGENRVPVVYIAESDGSFLLSMLPTVLIIAFLLYTIRRGPAGIGRTGRGMGGLFSVGETTAKVLKDEIDVKFKDVAGCEEAKLEIMEFVNFLKNPKQYQDLGAKIPKGAILTGPPGTGKTLLAKATAGEANVPFITVSGSEFLEMFVGVGPARVRDLFALARKNAPCILFIDEIDAVGRKRGRGNFGGQSEQENTLNQLLVEMDGFNTTTNVVILAGTNRPDILDPALLRPGRFDRQIFIGPPDIKGRASIFKVHLRPLKLDSTLEKDKLARKLASLTPGFSGADVANVCNEAALIAARHLSDSINQKHFEQAIERVIGGLEKKTQVLQPEEKKTVAYHEAGHAVAGWYLEHADPLLKVSIIPRGKGLGYAQYLPKEQYLYTKEQLLDRMCMTLGGRVSEEIFFGRITTGAQDDLRKVTQSAYAQIVQFGMNEKVGQISFDLPRQGDMVLEKPYSEATARLIDDEVRILINDAYKRTVALLTEKKADVEKVALLLLEKEVLDKNDMVELLGPRPFAEKSTYEEFVEGTGSLDEDTSLPEGLKDWNKEREKEKEEPPGEKVAN
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References
1 A novel AFG3L2 mutation close to AAA domain leads to aberrant OMA1 and OPA1 processing in a family with optic atrophy. Acta Neuropathol Commun. 2020 Jun 29;8(1):93.
2 Concurrent AFG3L2 and SPG7 mutations associated with syndromic parkinsonism and optic atrophy with aberrant OPA1 processing and mitochondrial network fragmentation. Hum Mutat. 2018 Dec;39(12):2060-2071.
3 The m-AAA Protease Associated with Neurodegeneration Limits MCU Activity in Mitochondria. Mol Cell. 2016 Oct 6;64(1):148-162.
4 Mitochondrial processing peptidase regulates PINK1 processing, import and Parkin recruitment. EMBO Rep. 2012 Apr;13(4):378-85.
5 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.
6 The SARS-CoV-2 RNA-protein interactome in infected human cells. Nat Microbiol. 2021 Mar;6(3):339-353.