A5X363 · A5X363_9REOV
- ProteinNon-structural glycoprotein 4
- GeneNSP4
- StatusUniProtKB unreviewed (TrEMBL)
- Organism
- Amino acids175 (go to sequence)
- Protein existenceInferred from homology
- Annotation score4/5
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.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | extracellular region | |
Cellular Component | host caveola | |
Cellular Component | host cell rough endoplasmic reticulum membrane | |
Cellular Component | membrane | |
Molecular Function | channel activity | |
Molecular Function | metal ion binding | |
Molecular Function | toxin activity | |
Biological Process | induction by virus of host autophagy | |
Biological Process | monoatomic ion transmembrane transport |
Keywords
- Molecular function
- Biological process
- Ligand
Names & Taxonomy
Protein names
- Recommended nameNon-structural glycoprotein 4
- Short namesNSP4
- Alternative names
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageViruses > Riboviria > Orthornavirae > Duplornaviricota > Resentoviricetes > Reovirales > Sedoreoviridae > Rotavirus > Rotavirus A
Accessions
- Primary accessionA5X363
Subcellular Location
UniProt Annotation
GO Annotation
Host rough endoplasmic reticulum membrane ; Single-pass type III membrane protein
Host membrane, host caveola ; Single-pass type III membrane protein
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.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-28 | Lumenal | ||||
Sequence: MDKLADLNYTLSVITLMNDTLHSIIRDP | ||||||
Transmembrane | 29-46 | Helical | ||||
Sequence: GMAYFPYIASVLTVLFTL | ||||||
Topological domain | 52-175 | Cytoplasmic | ||||
Sequence: PTMKIALRTSKCSYKVIKYCMVTIINTLLKLAGYKEQVTTKDEIEQQMDRIVKEMRRQLEMIDKLTTREIEQVELLKRIHDKLVARPVDAIDMSKEFNQKNIRTLDEWESGKNPYEPLEVTASM |
Keywords
- Cellular component
PTM/Processing
Features
Showing features for glycosylation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Glycosylation | 8 | N-linked (GlcNAc...) asparagine; by host | ||||
Sequence: N | ||||||
Glycosylation | 18 | N-linked (GlcNAc...) asparagine; by host | ||||
Sequence: N |
Post-translational modification
The N-glycosyl content is primarily Man9GlcNAc, with a small amount of Man8GlcNAc.
Keywords
- PTM
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.
Structure
Family & Domains
Sequence
- Sequence statusComplete
- Length175
- Mass (Da)20,317
- Last updated2007-07-10 v1
- Checksum83EA05C648EDE5E9