Host Protein General Information (ID: PT0833)
  Protein Name
Protein arginine methyltransferase 5 (PRMT5)
  Gene Name
PRMT5
  Host Species
Homo sapiens
  Uniprot Entry Name
ANM5_HUMAN
  Protein Families
Class I-like SAM-binding methyltransferase superfamily
  EC Number
2.1.1.32.
  Subcellular Location
Cytoplasm Nucleus Chromosome Golgi apparatus
  External Link
NCBI Gene ID
10419
Uniprot ID
O14744
Ensembl ID
ENSG00000100462
HGNC ID
HGNC:10894
  Function in Host
Arginine methyltransferase that can both catalyze theformation of omega-N monomethylarginine (MMA) and symmetricaldimethylarginine (sDMA), with a preference for the formation of MMA (, , , , , , , ). Specifically mediates the symmetrical dimethylation of arginineresidues in the small nuclear ribonucleoproteins Sm D1 (SNRPD1) and SmD3 (SNRPD3); such methylation being required for the assembly andbiogenesis of snRNP core particles. Methylates SUPT5H and may regulate itstranscriptional elongation properties. Mono- anddimethylates arginine residues of myelin basic protein (MBP) in vitro. May play a role in cytokine-activated transduction pathways. Negativelyregulates cyclin E1 promoter activity and cellular proliferation. Methylates histone H2A and H4 'Arg-3' during germ cell development. Methylates histone H3 'Arg-8', which may represstranscription. Methylates the Piwi proteins (PIWIL1, PIWIL2 and PIWIL4), methylation of Piwi proteins being required for theinteraction with Tudor domain-containing proteins and subsequentlocalization to the meiotic nuage. Methylates RPS10. Attenuates EGF signaling through the MAPK1/MAPK3 pathway acting at 2levels. First, monomethylates EGFR; this enhances EGFR 'Tyr-1197'phosphorylation and PTPN6 recruitment, eventually leading to reducedSOS1 phosphorylation. Second, methylates RAF1 and probably BRAF, hence destabilizing these 2signaling proteins and reducing their catalytic activity. Required for induction of E-selectin and VCAM-1, onthe endothelial cells surface at sites of inflammation. MethylatesHOXA9. Methylates and regulates SRGAP2 which isinvolved in cell migration and differentiation. Actsas a transcriptional corepressor in CRY1-mediated repression of thecore circadian component PER1 by regulating the H4R3 dimethylation atthe PER1 promoter. Methylates GM130/GOLGA2, regulatingGolgi ribbon formation. Methylates H4R3 in genesinvolved in glioblastomagenesis in a CHTOP- and/or TET1-dependentmanner. Symmetrically methylates POLR2A, amodification that allows the recruitment to POLR2A of proteinsincluding SMN1/SMN2 and SETX. This is required for resolving RNA-DNAhybrids created by RNA polymerase II, that form R-loop in transcriptionterminal regions, an important step in proper transcription termination. Along with LYAR, binds the promoter of gamma-globinHBG1/HBG2 and represses its expression. Symmetricallymethylates NCL. Methylates p53/TP53; methylationmight possibly affect p53/TP53 target gene specificity. Involved in spliceosome maturation and mRNA splicingin prophase I spermatocytes through the catalysis of the symmetricalarginine dimethylation of SNRPB (small nuclear ribonucleoprotein-associated protein) and the interaction with tudor domain-containingprotein TDRD6. [1-13]
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  3D Structure

Function of This Protein During Virus Infection
Virus NameSARS-COV-2 Protein Function Anti-viral [14]
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 PRMT5 in viral infection, PRMT5 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 PRMT5 increases SARS-CoV-2 RNA levels compared with control group.

 Full List of Virus RNA Interacting with This Protien
            RNA Region: ORF10 (hCoV-19/Not Specified Virus Strain )
              RNA Region Details RNA Info Click to show the detail information of this RNA binding region [15]
              Strains Name
hCoV-19/Not Specified Virus Strain
              RNA Binding Region
ORF10
              Virus Name
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
              Infection Cells Calu-3 cells (Human Lung Cancer Cell)  (CVCL_0609 )
              Cell Originated Tissue Liver
              Interaction Score P-value < 0.05
              Method Description RNA pull-down assays; liquid chromatography with tandem mass spectrometry (LC-MS/MS); Wilcoxon test; MS2 affinity purification coupled with liquid chromatography-mass spectrometry (MAMS)

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
MAAMAVGGAGGSRVSSGRDLNCVPEIADTLGAVAKQGFDFLCMPVFHPRFKREFIQEPAKNRPGPQTRSDLLLSGRDWNTLIVGKLSPWIRPDSKVEKIRRNSEAAMLQELNFGAYLGLPAFLLPLNQEDNTNLARVLTNHIHTGHHSSMFWMRVPLVAPEDLRDDIIENAPTTHTEEYSGEEKTWMWWHNFRTLCDYSKRIAVALEIGADLPSNHVIDRWLGEPIKAAILPTSIFLTNKKGFPVLSKMHQRLIFRLLKLEVQFIITGTNHHSEKEFCSYLQYLEYLSQNRPPPNAYELFAKGYEDYLQSPLQPLMDNLESQTYEVFEKDPIKYSQYQQAIYKCLLDRVPEEEKDTNVQVLMVLGAGRGPLVNASLRAAKQADRRIKLYAVEKNPNAVVTLENWQFEEWGSQVTVVSSDMREWVAPEKADIIVSELLGSFADNELSPECLDGAQHFLKDDGVSIPGEYTSFLAPISSSKLYNEVRACREKDRDPEAQFEMPYVVRLHNFHQLSAPQPCFTFSHPNRDPMIDNNRYCTLEFPVEVNTVLHGFAGYFETVLYQDITLSIRPETHSPGMFSWFPILFPIKQPITVREGQTICVRFWRCSNSKKVWYEWAVTAPVCSAIHNPTGRSYTIGL
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References
1 HOXA9 methylation by PRMT5 is essential for endothelial cell expression of leukocyte adhesion molecules. Mol Cell Biol. 2012 Apr;32(7):1202-13.
2 Protein arginine methyltransferase 5 regulates ERK1/2 signal transduction amplitude and cell fate through CRAF. Sci Signal. 2011 Sep 13;4(190):ra58.
3 RioK1, a new interactor of protein arginine methyltransferase 5 (PRMT5), competes with pICln for binding and modulates PRMT5 complex composition and substrate specificity. J Biol Chem. 2011 Jan 21;286(3):1976-86.
4 Crosstalk between Arg 1175 methylation and Tyr 1173 phosphorylation negatively modulates EGFR-mediated ERK activation. Nat Cell Biol. 2011 Feb;13(2):174-81.
5 srGAP2 arginine methylation regulates cell migration and cell spreading through promoting dimerization. J Biol Chem. 2010 Nov 5;285(45):35133-41.
6 Methylation of ribosomal protein S10 by protein-arginine methyltransferase 5 regulates ribosome biogenesis. J Biol Chem. 2010 Apr 23;285(17):12695-705.
7 Two distinct arginine methyltransferases are required for biogenesis of Sm-class ribonucleoproteins. J Cell Biol. 2007 Aug 27;178(5):733-40.
8 The tumor suppressor DAL-1/4.1B modulates protein arginine N-methyltransferase 5 activity in a substrate-specific manner. Biochem Biophys Res Commun. 2005 Apr 8;329(2):522-30.
9 Methylation of SPT5 regulates its interaction with RNA polymerase II and transcriptional elongation properties. Mol Cell. 2003 Apr;11(4):1055-66.
10 Assisted RNP assembly: SMN and PRMT5 complexes cooperate in the formation of spliceosomal UsnRNPs. EMBO J. 2002 Nov 1;21(21):5853-63.
11 Methylation of Sm proteins by a complex containing PRMT5 and the putative U snRNP assembly factor pICln. Curr Biol. 2001 Dec 11;11(24):1990-4.
12 Prmt5, which forms distinct homo-oligomers, is a member of the protein-arginine methyltransferase family. J Biol Chem. 2001 Apr 6;276(14):11393-401.
13 The human homologue of the yeast proteins Skb1 and Hsl7p interacts with Jak kinases and contains protein methyltransferase activity. J Biol Chem. 1999 Oct 29;274(44):31531-42.
14 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.
15 Mapping the host protein interactome of non-coding regions in SARS-CoV-2 genome. bioRxiv. 2021 Jun; DOI:10.1101/2021.06.19.449092.