Host Protein General Information (ID: PT0592)
  Protein Name
Sam68-like mammalian protein 2 (SLM-2)
  Gene Name
KHDRBS3
  Host Species
Homo sapiens
  Uniprot Entry Name
KHDR3_HUMAN
  Protein Families
KHDRBS family
  Subcellular Location
Nucleus
  External Link
NCBI Gene ID
10656
Uniprot ID
O75525
Ensembl ID
ENSG00000131773
HGNC ID
HGNC:18117
  Function in Host
RNA-binding protein that plays a role in the regulation ofalternative splicing and influences mRNA splice site selection and exoninclusion. Binds preferentially to the 5'-[AU]UAAA-3' motif in vitro. Binds optimally to RNA containing 5'-[AU]UAA-3' as a bipartite motifspaced by more than 15 nucleotides. Binds poly (A). RNA-bindingabilities are down-regulated by tyrosine kinase PTK6. Involved in splice site selection ofvascular endothelial growth factor. In vitroregulates CD44 alternative splicing by direct binding to purine-richexonic enhancer. Can regulate alternative splicing ofneurexins NRXN1-3 in the laminin G-like domain 6 containing theevolutionary conserved neurexin alternative spliced segment 4 (AS4) involved in neurexin selective targeting to postsynaptic partners suchas neuroligins and LRRTM family members. Targeted, cell-type specific splicing regulation of NRXN1 at AS4 is involved inneuronal glutamatergic synapse function and plasticity. May regulate expression of KHDRBS2/SLIM-1 in defined brain neuronpopulations by modifying its alternative splicing. Canbind FABP9 mRNA. May play a role as a negativeregulator of cell growth. Inhibits cell proliferation. [1-4]
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  3D Structure

Function of This Protein During Virus Infection
Virus NameSARS-COV-2 Protein Function Pro-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 KHDRBS3 in viral infection, KHDRBS3 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 KHDRBS3 leads to the decreased SARS-CoV-2 RNA levels compared with control group.

Host Protein - Virus RNA Network

 Full List of Virus RNA Interacting with This Protien
            RNA Region: 3'-UTR (hCoV-19/Wuhan-Hu-1/2019 )
              RNA Region Details RNA Info Click to show the detail information of this RNA binding region [6]
              Strains Name
hCoV-19/Wuhan-Hu-1/2019
              Strains Family
Beta (B.1.351)
              RNA Binding Region
3'-UTR
              Virus Name
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
              Interaction Type Potential binding protein
              Method Description ATtRACT Database; Position Weight Matrices (PWMs); TFBSTools R package
           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 [6]
              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)
              Interaction Type Potential binding protein
              Method Description ATtRACT Database; Position Weight Matrices (PWMs); TFBSTools R package
           RNA Region: ORF10 (hCoV-19/Wuhan-Hu-1/2019 )
              RNA Region Details RNA Info Click to show the detail information of this RNA binding region [6]
              Strains Name
hCoV-19/Wuhan-Hu-1/2019
              Strains Family
Beta (B.1.351)
              RNA Binding Region
ORF10
              Virus Name
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
              Interaction Type Potential binding protein
              Method Description ATtRACT Database; Position Weight Matrices (PWMs); TFBSTools R package
           RNA Region: ORF1ab (hCoV-19/Wuhan-Hu-1/2019 )
              RNA Region Details RNA Info Click to show the detail information of this RNA binding region [6]
              Strains Name
hCoV-19/Wuhan-Hu-1/2019
              Strains Family
Beta (B.1.351)
              RNA Binding Region
ORF1ab
              Virus Name
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
              Interaction Type Potential binding protein
              Method Description ATtRACT Database; Position Weight Matrices (PWMs); TFBSTools R package
           RNA Region: ORF3a (hCoV-19/Wuhan-Hu-1/2019 )
              RNA Region Details RNA Info Click to show the detail information of this RNA binding region [6]
              Strains Name
hCoV-19/Wuhan-Hu-1/2019
              Strains Family
Beta (B.1.351)
              RNA Binding Region
ORF3a
              Virus Name
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
              Interaction Type Potential binding protein
              Method Description ATtRACT Database; Position Weight Matrices (PWMs); TFBSTools R package
           RNA Region: ORF6 (hCoV-19/Wuhan-Hu-1/2019 )
              RNA Region Details RNA Info Click to show the detail information of this RNA binding region [6]
              Strains Name
hCoV-19/Wuhan-Hu-1/2019
              Strains Family
Beta (B.1.351)
              RNA Binding Region
ORF6
              Virus Name
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
              Interaction Type Potential binding protein
              Method Description ATtRACT Database; Position Weight Matrices (PWMs); TFBSTools R package
           RNA Region: ORF7a (hCoV-19/Wuhan-Hu-1/2019 )
              RNA Region Details RNA Info Click to show the detail information of this RNA binding region [6]
              Strains Name
hCoV-19/Wuhan-Hu-1/2019
              Strains Family
Beta (B.1.351)
              RNA Binding Region
ORF7a
              Virus Name
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
              Interaction Type Potential binding protein
              Method Description ATtRACT Database; Position Weight Matrices (PWMs); TFBSTools R package
           RNA Region: ORF8 (hCoV-19/Wuhan-Hu-1/2019 )
              RNA Region Details RNA Info Click to show the detail information of this RNA binding region [6]
              Strains Name
hCoV-19/Wuhan-Hu-1/2019
              Strains Family
Beta (B.1.351)
              RNA Binding Region
ORF8
              Virus Name
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
              Interaction Type Potential binding protein
              Method Description ATtRACT Database; Position Weight Matrices (PWMs); TFBSTools R package
           RNA Region: E region (hCoV-19/Wuhan-Hu-1/2019 )
              RNA Region Details RNA Info Click to show the detail information of this RNA binding region [6]
              Strains Name
hCoV-19/Wuhan-Hu-1/2019
              Strains Family
Beta (B.1.351)
              RNA Binding Region
E region
              Virus Name
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
              Interaction Type Potential binding protein
              Method Description ATtRACT Database; Position Weight Matrices (PWMs); TFBSTools R package
           RNA Region: M region (hCoV-19/Wuhan-Hu-1/2019 )
              RNA Region Details RNA Info Click to show the detail information of this RNA binding region [6]
              Strains Name
hCoV-19/Wuhan-Hu-1/2019
              Strains Family
Beta (B.1.351)
              RNA Binding Region
M region
              Virus Name
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
              Interaction Type Potential binding protein
              Method Description ATtRACT Database; Position Weight Matrices (PWMs); TFBSTools R package
           RNA Region: N region (hCoV-19/Wuhan-Hu-1/2019 )
              RNA Region Details RNA Info Click to show the detail information of this RNA binding region [6]
              Strains Name
hCoV-19/Wuhan-Hu-1/2019
              Strains Family
Beta (B.1.351)
              RNA Binding Region
N region
              Virus Name
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
              Interaction Type Potential binding protein
              Method Description ATtRACT Database; Position Weight Matrices (PWMs); TFBSTools R package
           RNA Region: S region (hCoV-19/Wuhan-Hu-1/2019 )
              RNA Region Details RNA Info Click to show the detail information of this RNA binding region [6]
              Strains Name
hCoV-19/Wuhan-Hu-1/2019
              Strains Family
Beta (B.1.351)
              RNA Binding Region
S region
              Virus Name
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
              Interaction Type Potential binding protein
              Method Description ATtRACT Database; Position Weight Matrices (PWMs); TFBSTools R package
           RNA Region: Not Specified Virus Region (hCoV-19/England/02/2020 )
              RNA Region Details RNA Info Click to show the detail information of this RNA binding region [7]
              Strains Name
hCoV-19/England/02/2020
              Strains Family
Beta (B.1.351)
              RNA Binding Region
Not Specified Virus Region
              Virus Name
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
              Infection Cells Calu-3 cells (Human lung cancer cell) Calu-3 cells (Human lung cancer cell)  (CVCL_0609 )
              Cell Originated Tissue Lung
              Infection Time 24 h
              Interaction Score P-adjust = 0.099
              Method Description UV protein-RNA crosslinking; RNA interactome capture (cRIC); RNA antisense purification coupled with mass spectrometry (RAP-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
MEEKYLPELMAEKDSLDPSFTHALRLVNQEIEKFQKGEGKDEEKYIDVVINKNMKLGQKVLIPVKQFPKFNFVGKLLGPRGNSLKRLQEETLTKMSILGKGSMRDKAKEEELRKSGEAKYFHLNDDLHVLIEVFAPPAEAYARMGHALEEIKKFLIPDYNDEIRQAQLQELTYLNGGSENADVPVVRGKPTLRTRGVPAPAITRGRGGVTARPVGVVVPRGTPTPRGVLSTRGPVSRGRGLLTPRARGVPPTGYRPPPPPPTQETYGEYDYDDGYGTAYDEQSYDSYDNSYSTPAQSGADYYDYGHGLSEETYDSYGQEEWTNSRHKAPSARTAKGVYRDQPYGRY
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References
1 Structural basis of RNA recognition and dimerization by the STAR proteins T-STAR and Sam68. Nat Commun. 2016 Jan 13;7:10355.
2 Rapid and systematic analysis of the RNA recognition specificities of RNA-binding proteins. Nat Biotechnol. 2009 Jul;27(7):667-70.
3 Sam68-like mammalian protein 2, identified by digital differential display as expressed by podocytes, is induced in proteinuria and involved in splice site selection of vascular endothelial growth factor. J Am Soc Nephrol. 2005 Jul;16(7):1958-65.
4 Salpalpha and Salpbeta, growth-arresting homologs of Sam68. Gene. 1999 Nov 15;240(1):133-47.
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 Genome-wide bioinformatic analyses predict key host and viral factors in SARS-CoV-2 pathogenesis. Commun Biol. 2021 May 17;4(1):590.
7 Global analysis of protein-RNA interactions in SARS-CoV-2-infected cells reveals key regulators of infection. Mol Cell. 2021 Jul 1;81(13):2851-2867.e7.