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HAMAP rule MF_04091

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General rule information [?]

Accession MF_04091
Dates 27-FEB-2018 (Created)
19-NOV-2022 (Last updated, Version 8)
Viruses; Rotavirus
Template P04512 (NSP4_ROTS1)

Propagated annotation [?]

Identifier, protein and gene names [?]

Protein name
RecName: Full=Non-structural glycoprotein 4;
AltName: Full=NCVP5;
AltName: Full=NS28;

Comments [?]

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 Ca(2+) 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.
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.
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.
case <FTGroup:1>
Domain Binds 1 calcium ion per tetramer.
end case
Ptm The N-glycosyl content is primarily Man(9)GlcNAc, with a small amount of Man(8)GlcNAc.
Similarity Belongs to the rotavirus NSP4 family.

Keywords [?]

case <FTGroup:1>
end case

Gene Ontology [?]

GO:0005576; Cellular component: extracellular region.
GO:0044155; Cellular component: host caveola.
GO:0044169; Cellular component: host cell rough endoplasmic reticulum membrane.
GO:0016020; Cellular component: membrane.
case <FTGroup:1>
GO:0046872; Molecular function: metal ion binding.
end case
GO:0090729; Molecular function: toxin activity.
GO:0016032; Biological process: viral process.

Cross-references [?]

Pfam PF01452; Rota_NSP4; 1;

Computed features [?]

General Coiled_coil; -; 0-unlimited;
Transmembrane; -; 1;

Features [?]

From: NSP4_ROTS1 (P04512)
Key     From     To       Description   Tag   Condition   FTGroup
TOPO_DOM     Nter     28       Lumenal        
TRANSMEM     29     51       Helical; Signal-anchor for type III membrane protein        
TOPO_DOM     52     Cter       Cytoplasmic        
BINDING     120     120       /ligand="Ca(2+)" /ligand_id="ChEBI:CHEBI:29108     E   1
BINDING     123     123       /ligand="Ca(2+)" /ligand_id="ChEBI:CHEBI:29108     Q   1
CARBOHYD     8     8       N-linked (GlcNAc...) asparagine; by host     N  
CARBOHYD     18     18       N-linked (GlcNAc...) asparagine; by host     N  

Additional information [?]

Size range 150-219 amino acids
Related rules None
Fusion None