HAMAP rule MF_04091

General rule information [?]

Accession	MF_04091
Dates	27-FEB-2018 (Created) 19-NOV-2022 (Last updated, Version 8)

Name

ROTA_NSP4

Scope

Viruses; Rotavirus

Template

P04512 (NSP4_ROTS1)

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;
		Short=NSP4;
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>

Calcium
Metal-binding

end case

Activation of host autophagy by virus
Enterotoxin
Glycoprotein
Host endoplasmic reticulum
Host membrane
Host-virus interaction
Ion channel
Ion transport
Membrane
Secreted
Signal-anchor
Toxin
Transmembrane
Transmembrane helix
Transport
Viral ion channel
Virulence

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

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