A0A6F8PF22 · A0A6F8PF22_9REOV

  • Protein
    Non-structural glycoprotein 4
  • Gene
    NSP4
  • Status
    UniProtKB unreviewed (TrEMBL)
  • Amino acids
  • Protein existence
    Inferred from homology
  • Annotation score
    4/5

Function

function

Plays an essential role in the virus replication cycle by acting as a viroporin. Creates a pore in the host reticulum endoplasmic and as a consequence releases Ca2+ in the cytoplasm of infected cell. In turn, high levels of cytoplasmic calcium trigger membrane trafficking and transport of viral ER-associated proteins to viroplasms, sites of viral genome replication and immature particle assembly.
The secreted form acts as an enterotoxin that causes phospholipase C-dependent elevation of the intracellular calcium concentration in host intestinal mucosa cells. Increased concentration of intracellular calcium disrupts the cytoskeleton and the tight junctions, raising the paracellular permeability. Potentiates chloride ion secretion through a calcium ion-dependent signaling pathway, inducing age-dependent diarrhea. To perform this enterotoxigenic role in vivo, NSP4 is released from infected enterocytes in a soluble form capable of diffusing within the intestinal lumen and interacting with host plasma membrane receptors on neighboring epithelial cells such as integrins ITGA1/ITGB1 and ITGA2/ITGB1.

Features

Showing features for binding site.

117520406080100120140160
TypeIDPosition(s)Description
Binding site120Ca2+ (UniProtKB | ChEBI)
Binding site123Ca2+ (UniProtKB | ChEBI)

GO annotations

AspectTerm
Cellular Componentextracellular region
Cellular Componenthost caveola
Cellular Componenthost cell rough endoplasmic reticulum membrane
Cellular Componentmembrane
Molecular Functionchannel activity
Molecular Functionmetal ion binding
Molecular Functiontoxin activity
Biological Processinduction by virus of host autophagy
Biological Processmonoatomic ion transmembrane transport

Keywords

Names & Taxonomy

Protein names

  • Recommended name
    Non-structural glycoprotein 4
  • Short names
    NSP4
  • Alternative names
    • NCVP5
    • NS28

Gene names

    • Name
      NSP4

Organism names

  • Taxonomic identifier
  • Organism
  • Strain
    • RVA/Human-wt/VNM/RVN16.1024/2016/G9P[8]
  • Taxonomic lineage
    Viruses > Riboviria > Orthornavirae > Duplornaviricota > Resentoviricetes > Reovirales > Sedoreoviridae > Rotavirus > Rotavirus A

Accessions

  • Primary accession
    A0A6F8PF22

Subcellular Location

Host rough endoplasmic reticulum membrane
; Single-pass type III membrane protein
Host membrane, host caveola
; Single-pass type III membrane protein
Secreted
Note: NSP4 localizes also in vesicular structures which contain autophagosomal markers and associate with viroplasms in virus-infected cells. Additionally, a soluble form of glycosylated NSP4 is secreted despite retention of its transmembrane domain.

Features

Showing features for topological domain, transmembrane.

TypeIDPosition(s)Description
Topological domain1-28Lumenal
Transmembrane31-49Helical
Topological domain52-175Cytoplasmic

Keywords

PTM/Processing

Features

Showing features for glycosylation.

TypeIDPosition(s)Description
Glycosylation8N-linked (GlcNAc...) asparagine; by host
Glycosylation18N-linked (GlcNAc...) asparagine; by host

Post-translational modification

The N-glycosyl content is primarily Man9GlcNAc, with a small amount of Man8GlcNAc.

Keywords

PTM databases

Interaction

Subunit

Homotetramer. Interacts with the immature particle in the viroplasm. Interacts with host CAV1, early and late in infection. Interacts with host integrin ITGA1/ITGB1 heterodimer. Interacts with host integrin ITGA2/ITGB1 heterodimer. Interaction with microtubules blocks trafficking to the Golgi apparatus.

Family & Domains

Features

Showing features for coiled coil.

TypeIDPosition(s)Description
Coiled coil85-112

Domain

Binds 1 calcium ion per tetramer.

Sequence similarities

Belongs to the rotavirus NSP4 family.

Keywords

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    175
  • Mass (Da)
    20,277
  • Last updated
    2020-08-12 v1
  • Checksum
    47378C7E1DD33222
MEKLTDLNYTLSVITLMNSTLHTILEDPGMAYFPYIASVLTVLFTLHKASIPTMKIALKTSKCSYKVVKYCIVTIFNTLLKLAGYKEQITTKDEIEKQMDRVVKEMRRQLEMIDKLTTREIEQVELLKRIHDRLIVQSAGEIDMTKEINQKNVKTLEEWESGRNPYEPKEVTAAM

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
LC491449
EMBL· GenBank· DDBJ
BBM12422.1
EMBL· GenBank· DDBJ
Genomic RNA

Similar Proteins

Disclaimer

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