Host Protein General Information (ID: PT0274)
  Protein Name
Cleavage factor Im complex 25 kDa subunit (CFIm25)
  Gene Name
NUDT21
  Host Species
Homo sapiens
  Uniprot Entry Name
CPSF5_HUMAN
  Protein Families
Nudix hydrolase family
  Subcellular Location
Nucleus Cytoplasm
  External Link
NCBI Gene ID
11051
Uniprot ID
O43809
Ensembl ID
ENSG00000167005
HGNC ID
HGNC:13870
  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 pAsignals, resulting in alternative cleavage and polyadenylation (APA) producing mRNAs with variable 3'-end formation. The CFIm complex acts as a keyregulator 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. NUDT21/CPSF5activates indirectly the mRNA 3'-processing machinery by recruitingCPSF6 and/or CPSF7. Binds to 5'-UGUA-3' elementslocalized upstream of pA signals that act as enhancers of pre-mRNA 3'-end processing. The homodimermediates simultaneous sequence-specific recognition of two 5'-UGUA-3'elements within the pre-mRNA. Playsa role in somatic cell fate transitions and pluripotency by regulatingwidespread changes in gene expression through an APA-dependent function. Binds to chromatin. Binds to, but doesnot hydrolyze mono- and di-adenosine nucleotides. [1-8]
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  Related KEGG Pathway
mRNA surveillance pathway hsa03015            Pathway Map 
  3D Structure

Function of This Protein During Virus Infection
Virus NameSARS-COV-2 Protein Function Anti-viral [9]
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 NUDT21 in viral infection, NUDT21 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 NUDT21 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/France/IDF-220-95/2020 )
              RNA Region Details RNA Info Click to show the detail information of this RNA binding region [10]
              Strains Name
hCoV-19/France/IDF-220-95/2020
              RNA Binding Region
Not Specified Virus Region
              Virus Name
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
              Interaction Type Direct interaction
              Infection Cells HEK293 Cells (Human embryonic kidney cell)  (CVCL_0045 )
              Cell Originated Tissue Kidney
              Infection Time 48 h
              Interaction Score SAINT score ≥ 0.79
              Method Description comprehensive identification of RNA-binding proteins by massspectrometry (ChIRP-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
MSVVPPNRSQTGWPRGVTQFGNKYIQQTKPLTLERTINLYPLTNYTFGTKEPLYEKDSSVAARFQRMREEFDKIGMRRTVEGVLIVHEHRLPHVLLLQLGTTFFKLPGGELNPGEDEVEGLKRLMTEILGRQDGVLQDWVIDDCIGNWWRPNFEPPQYPYIPAHITKPKEHKKLFLVQLQEKALFAVPKNYKLVAAPLFELYDNAPGYGPIISSLPQLLSRFNFIYN
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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 A mechanism for the regulation of pre-mRNA 3 processing by human cleavage factor Im. Mol Cell. 2003 Dec;12(6):1467-76.
4 Molecular Mechanisms for CFIm-Mediated Regulation of mRNA Alternative Polyadenylation. Mol Cell. 2018 Jan 4;69(1):62-74.e4.
5 Evidence that cleavage factor Im is a heterotetrameric protein complex controlling alternative polyadenylation. Genes Cells. 2010 Sep 1;15(9):1003-13.
6 Knock-down of 25 kDa subunit of cleavage factor Im in Hela cells alters alternative polyadenylation within 3 -UTRs. Nucleic Acids Res. 2006;34(21):6264-71.
7 Human pre-mRNA cleavage factor Im is related to spliceosomal SR proteins and can be reconstituted in vitro from recombinant subunits. Mol Cell. 1998 Jan;1(2):243-53.
8 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.
9 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.
10 Characterization and functional interrogation of the SARS-CoV-2 RNA interactome. Cell Rep. 2022 Apr 26;39(4):110744.