Host Protein General Information (ID: PT0679)
  Protein Name
Nuclear cap-binding protein subunit 1 (NCBP1)
  Gene Name
NCBP1
  Host Species
Homo sapiens
  Uniprot Entry Name
NCBP1_HUMAN
  Protein Families
NCBP1 family
  Subcellular Location
Nucleus Cytoplasm
  External Link
NCBI Gene ID
4686
Uniprot ID
Q09161
Ensembl ID
ENSG00000136937
HGNC ID
HGNC:7658
  Function in Host
Component of the cap-binding complex (CBC), which bindscotranscriptionally to the 5'-cap of pre-mRNAs and is involved invarious processes such as pre-mRNA splicing, translation regulation, nonsense-mediated mRNA decay, RNA-mediated gene silencing (RNAi) bymicroRNAs (miRNAs) and mRNA export. The CBC complex is involved in mRNAexport from the nucleus via its interaction with ALYREF/THOC4/ALY, leading to the recruitment of the mRNA export machinery to the 5'-endof mRNA and to mRNA export in a 5' to 3' direction through the nuclearpore. The CBC complex is also involved in mediating U snRNA andintronless mRNAs export from the nucleus. The CBC complex is essentialfor a pioneer round of mRNA translation, before steady statetranslation when the CBC complex is replaced by cytoplasmic cap-bindingprotein eIF4E. The pioneer round of mRNA translation mediated by theCBC complex plays a central role in nonsense-mediated mRNA decay (NMD), NMD only taking place in mRNAs bound to the CBC complex, but not oneIF4E-bound mRNAs. The CBC complex enhances NMD in mRNAs containing atleast one exon-junction complex (EJC) via its interaction with UPF1, promoting the interaction between UPF1 and UPF2. The CBC complex isalso involved in 'failsafe' NMD, which is independent of the EJCcomplex, while it does not participate in Staufen-mediated mRNA decay (SMD). During cell proliferation, the CBC complex is also involved inmicroRNAs (miRNAs) biogenesis via its interaction with SRRT/ARS2 and isrequired for miRNA-mediated RNA interference. The CBC complex also actsas a negative regulator of PARN, thereby acting as an inhibitor of mRNAdeadenylation. In the CBC complex, NCBP1/CBP80 does not bind directlycapped RNAs (m7GpppG-capped RNA) but is required to stabilize themovement of the N-terminal loop of NCBP2/CBP20 and lock the CBC into ahigh affinity cap-binding state with the cap structure. Associates withNCBP3 to form an alternative cap-binding complex (CBC) which plays akey role in mRNA export and is particularly important in cellularstress situations such as virus infections. The conventional CBC withNCBP2 binds both small nuclear RNA (snRNA) and messenger (mRNA) and isinvolved in their export from the nucleus whereas the alternative CBCwith NCBP3 does not bind snRNA and associates only with mRNA therebyplaying a role only in mRNA export. NCBP1/CBP80 is required for cellgrowth and viability. [1-14]
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  Related KEGG Pathway
Nucleocytoplasmic transport hsa03013            Pathway Map 
mRNA surveillance pathway hsa03015            Pathway Map 
Spliceosome hsa03040            Pathway Map 
Amyotrophic lateral sclerosis hsa05014            Pathway Map 
  3D Structure

Function of This Protein During Virus Infection
Virus NameSARS-COV-2 Protein Function Anti-viral [15]
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 NCBP1 in viral infection, NCBP1 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 NCBP1 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 [16]
              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 Huh7 cells (human liver cell line)  (CVCL_0336 )
              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 Phosphorylation after Virus Infection
S22 [17]
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S22 [18]
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T21 [17]
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Protein Sequence Information
MSRRRHSDENDGGQPHKRRKTSDANETEDHLESLICKVGEKSACSLESNLEGLAGVLEADLPNYKSKILRLLCTVARLLPEKLTIYTTLVGLLNARNYNFGGEFVEAMIRQLKESLKANNYNEAVYLVRFLSDLVNCHVIAAPSMVAMFENFVSVTQEEDVPQVRRDWYVYAFLSSLPWVGKELYEKKDAEMDRIFANTESYLKRRQKTHVPMLQVWTADKPHPQEEYLDCLWAQIQKLKKDRWQERHILRPYLAFDSILCEALQHNLPPFTPPPHTEDSVYPMPRVIFRMFDYTDDPEGPVMPGSHSVERFVIEENLHCIIKSHWKERKTCAAQLVSYPGKNKIPLNYHIVEVIFAELFQLPAPPHIDVMYTTLLIELCKLQPGSLPQVLAQATEMLYMRLDTMNTTCVDRFINWFSHHLSNFQFRWSWEDWSDCLSQDPESPKPKFVREVLEKCMRLSYHQRILDIVPPTFSALCPANPTCIYKYGDESSNSLPGHSVALCLAVAFKSKATNDEIFSILKDVPNPNQDDDDDEGFSFNPLKIEVFVQTLLHLAAKSFSHSFSALAKFHEVFKTLAESDEGKLHVLRVMFEVWRNHPQMIAVLVDKMIRTQIVDCAAVANWIFSSELSRDFTRLFVWEILHSTIRKMNKHVLKIQKELEEAKEKLARQHKRRSDDDDRSSDRKDGVLEEQIERLQEKVESAQSEQKNLFLVIFQRFIMILTEHLVRCETDGTSVLTPWYKNCIERLQQIFLQHHQIIQQYMVTLENLLFTAELDPHILAVFQQFCALQA
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References
1 Human mRNA export machinery recruited to the 5 end of mRNA. Cell. 2006 Dec 29;127(7):1389-400.
2 mRNA export through an additional cap-binding complex consisting of NCBP1 and NCBP3. Nat Commun. 2015 Sep 18;6:8192.
3 A new MIF4G domain-containing protein, CTIF, directs nuclear cap-binding protein CBP80/20-dependent translation. Genes Dev. 2009 Sep 1;23(17):2033-45.
4 Ars2 links the nuclear cap-binding complex to RNA interference and cell proliferation. Cell. 2009 Jul 23;138(2):328-39.
5 NMD resulting from encephalomyocarditis virus IRES-directed translation initiation seems to be restricted to CBP80/20-bound mRNA. EMBO Rep. 2008 May;9(5):446-51.
6 Failsafe nonsense-mediated mRNA decay does not detectably target eIF4E-bound mRNA. Nat Struct Mol Biol. 2007 Oct;14(10):974-9.
7 Inhibition of mRNA deadenylation by the nuclear cap binding complex (CBC). J Biol Chem. 2006 Feb 17;281(7):4517-22.
8 CBP80 promotes interaction of Upf1 with Upf2 during nonsense-mediated mRNA decay in mammalian cells. Nat Struct Mol Biol. 2005 Oct;12(10):893-901.
9 eIF4G is required for the pioneer round of translation in mammalian cells. Nat Struct Mol Biol. 2004 Oct;11(10):992-1000.
10 The pioneer translation initiation complex is functionally distinct from but structurally overlaps with the steady-state translation initiation complex. Genes Dev. 2004 Apr 1;18(7):745-54.
11 The exon junction complex is detected on CBP80-bound but not eIF4E-bound mRNA in mammalian cells: dynamics of mRNP remodeling. EMBO J. 2002 Jul 1;21(13):3536-45.
12 Evidence for a pioneer round of mRNA translation: mRNAs subject to nonsense-mediated decay in mammalian cells are bound by CBP80 and CBP20. Cell. 2001 Sep 7;106(5):607-17.
13 A cap-binding protein complex mediating U snRNA export. Nature. 1995 Aug 24;376(6542):709-12.
14 A nuclear cap binding protein complex involved in pre-mRNA splicing. Cell. 1994 Aug 26;78(4):657-68.
15 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.
16 Mapping the host protein interactome of non-coding regions in SARS-CoV-2 genome. bioRxiv. 2021 Jun; DOI:10.1101/2021.06.19.449092.
17 The Global Phosphorylation Landscape of SARS-CoV-2 Infection. Cell. 2020 Aug 6;182(3):685-712.e19.
18 Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV. Nature. 2021 Jun;594(7862):246-252.