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N mutated P199L + M234I

Function

Packages the positive strand viral genome RNA into a helical ribonucleocapsid (RNP) and plays a fundamental role during virion assembly through its interactions with the viral genome and membrane protein M (PubMed:33264373). Plays an important role in enhancing the efficiency of subgenomic viral RNA transcription as well as viral replication. Attenuates the stress granules formation by reducing host G3BP1 access to host mRNAs under stress conditions (PubMed:34901782, PubMed:36534661).

May block host chemokine function in vivo, facilitating viral replication and transmission (PubMed:35921414). Acts by being secreted into the extracellular space where it competes to host chemokines for binding to host glycosaminoglycans (GAG) (PubMed:35921414).

May induce inflammasome responses in cultured cells and mice. Acts by interacting with host NLRP3 to facilitate inflammasome assembly, which induces cytokine release that may play a role in COVID lung injury.

Post-translational modifications

ADP-ribosylated. The ADP-ribosylation is retained in the virion during infection.

Phosphorylated on serine residues by host GSK3A and GSK3B (PubMed:34593624, PubMed:35728038). This promotes the solubility of homodimers that would otherwise aggregate (PubMed:32974389). Host phosphatase would dephosphorylate the protein during assembly at M bound membranes (PubMed:32974389).

Proteolytically cleaved by host CASP6. The cleavage leads to two fragments and facilitates viral replication by inhibiting host IFN signaling. The two fragments may interact with IRF3 inhibiting its nuclear translocation after activation and reduce the expression of IFNB and IFN-stimulated genes.

Sequence similarities

Belongs to the betacoronavirus nucleocapsid protein family.

Cellular localization

  • Virion
  • Host cytoplasm
  • Secreted
  • Host extracellular space
  • Probably associates with ER-derived membranes where it participates in viral RNA synthesis and virus budding. When located inside the virion, complexed with the viral RNA. Can be secreted by unconventional protein secretion (UPS) (PubMed:35921414). When secreted, can bind to host glycosaminoglycans on infected and non infected cells (PubMed:35921414). Found in host cytoplasmic stress granules (PubMed:34901782).

Alternative names

Nucleoprotein, N, Nucleocapsid protein, NC, Protein N

Target type

Proteins

Primary research area

Immunology & Infectious Disease

Molecular weight

45626Da

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