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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)
Scope(s) Viruses
Template(s) P04512 (NSP4_ROTS1); [ Recover all ]
Triggered by HAMAP; MF_04091 (Get profile general information and statistics)

Propagated annotation [?]

Identifier, protein and gene names [?]

Identifier NSP4
Protein name RecName: Full=Non-structural glycoprotein 4;
AltName: Full=NCVP5;
AltName: Full=NS28;

Comments [?]

FUNCTIONPlays 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.
FUNCTIONThe 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.
SUBUNITHomotetramer. 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 LOCATIONHost 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>
DOMAINBinds 1 calcium ion per tetramer.
end case
PTMThe N-glycosyl content is primarily Man(9)GlcNAc, with a small amount of Man(8)GlcNAc.
SIMILARITYBelongs to the rotavirus NSP4 family.

Keywords [?]

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

Features [?]

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

Additional information [?]

Size range 150-219 amino acids
Related rules None
Fusion Nter: None Cter: None

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