Details of Host Protein

 Host Protein General Information (ID: PT0276)
  Protein Name
Cleavage factor Im complex 59 kDa subunit (CFIm59)
  Gene Name
CPSF7
  Host Species
Homo sapiens
  Uniprot Entry Name
CPSF7_HUMAN
  Protein Families
RRM CPSF6/7 family
  Subcellular Location
Nucleus Cytoplasm
  External Link
NCBI Gene ID
79869
Uniprot ID
Q8N684
Ensembl ID
ENSG00000149532
HGNC ID
HGNC:30098
  Function in Host
Component of the cleavage factor Im (CFIm) complex thatfunctions as an activator of the pre-mRNA 3'-end cleavage andpolyadenylation processing required for the maturation of pre-mRNA intofunctional mRNAs. CFIm contributes to the recruitment of multiprotein complexes onspecific sequences on the pre-mRNA 3'-end, so called cleavage andpolyadenylation signals (pA signals). Most pre-mRNAs contain multiple pA signals, resulting in alternativecleavage and polyadenylation (APA) producing mRNAs with variable 3'-endformation. The CFIm complex acts asa key regulator of cleavage and polyadenylation site choice during APAthrough its binding to 5'-UGUA-3' elements localized in the 3'-untranslated region (UTR) for a huge number of pre-mRNAs. CPSF7 activates directly the mRNA3'-processing machinery. Binds to pA signals in RNAsubstrates. [1-5]
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  Related KEGG Pathway
Viral life cycle - HIV-1 hsa03250            Pathway Map 
mRNA surveillance pathway hsa03015            Pathway Map 
  3D Structure
PDB ID: 3N9U 
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  2D PNG Download  
PDB File Download

Function of This Protein During Virus Infection
Virus NameSARS-COV-2 Protein Function Anti-viral [6]
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 CPSF7 in viral infection, CPSF7 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 CPSF7 increases SARS-CoV-2 RNA levels compared with control group.

Host Protein - Virus RNA Network
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 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 [7]
              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)
              Infection Cells Huh7.5.1 cells (Hepatocyte derived cellular carcinoma cell)  (CVCL_E049 )
              Cell Originated Tissue Liver
              Infection Time 30 h
              Interaction Score Affinity = 0.971
              Method Description PrismNet; pull-down western (STAR methods); Mass spectrometry
           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 [8]
              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) 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)
           RNA Region: Not Specified Virus Region (hCoV-19/USA/WA1/2020 )
              RNA Region Details RNA Info Click to show the detail information of this RNA binding region [9]
              Strains Name
hCoV-19/USA/WA1/2020
              Strains Family
Alpha (B.1.1.7)
              RNA Binding Region
Not Specified Virus Region
              Virus Name
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
              Infection Cells Huh7.5 cells (Hepatocyte derived cellular carcinoma cell) Huh7.5 cells (Hepatocyte derived cellular carcinoma cell)  (CVCL_7927 )
              Cell Originated Tissue Liver
              Infection Time 48 h
              Interaction Score FDR ≤ 0.05
              Method Description comprehensive identification of RNA-binding proteins by massspectrometry (ChIRP-MS)
           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 [10]
              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 = 0.041
              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 Phosphorylation after Virus Infection
S205 [11]
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S46 [11]
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S48 [11]
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S60 [11]
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T203 [12]
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T203 [11]
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Protein Sequence Information
MSEGVDLIDIYADEEFNQDPEFNNTDQIDLYDDVLTATSQPSDDRSSSTEPPPPVRQEPSPKPNNKTPAILYTYSGLRNRRAAVYVGSFSWWTTDQQLIQVIRSIGVYDVVELKFAENRANGQSKGYAEVVVASENSVHKLLELLPGKVLNGEKVDVRPATRQNLSQFEAQARKRECVRVPRGGIPPRAHSRDSSDSADGRATPSENLVPSSARVDKPPSVLPYFNRPPSALPLMGLPPPPIPPPPPLSSSFGVPPPPPGIHYQHLMPPPPRLPPHLAVPPPGAIPPALHLNPAFFPPPNATVGPPPDTYMKASAPYNHHGSRDSGPPPSTVSEAEFEDIMKRNRAISSSAISKAVSGASAGDYSDAIETLLTAIAVIKQSRVANDERCRVLISSLKDCLHGIEAKSYSVGASGSSSRKRHRSRERSPSRSRESSRRHRDLLHNEDRHDDYFQERNREHERHRDRERDRHH
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References
1 Cleavage factor Im is a key regulator of 3 UTR length. RNA Biol. 2012 Dec;9(12):1405-12.
2 An interaction between U2AF 65 and CF I(m) links the splicing and 3 end processing machineries. EMBO J. 2006 Oct 18;25(20):4854-64.
3 Molecular Mechanisms for CFIm-Mediated Regulation of mRNA Alternative Polyadenylation. Mol Cell. 2018 Jan 4;69(1):62-74.e4.
4 Evidence that cleavage factor Im is a heterotetrameric protein complex controlling alternative polyadenylation. Genes Cells. 2010 Sep 1;15(9):1003-13.
5 Purification and characterization of human cleavage factor Im involved in the 3 end processing of messenger RNA precursors. J Biol Chem. 1996 Mar 15;271(11):6107-13.
6 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.
7 In vivo structural characterization of the SARS-CoV-2 RNA genome identifies host proteins vulnerable to repurposed drugs. Cell. 2021 Apr 1;184(7):1865-1883.e20.
8 Mapping the host protein interactome of non-coding regions in SARS-CoV-2 genome. bioRxiv. 2021 Jun; DOI:10.1101/2021.06.19.449092.
9 Discovery and functional interrogation of SARS-CoV-2 RNA-host protein interactions. Cell. 2021 Apr 29;184(9):2394-2411.e16.
10 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.
11 Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV. Nature. 2021 Jun;594(7862):246-252.
12 The Global Phosphorylation Landscape of SARS-CoV-2 Infection. Cell. 2020 Aug 6;182(3):685-712.e19.