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Details on Person UniProt:P03535 NSP4
Class:Id
ReferenceGeneProduct:9974703
_chainChangeLog
chain:1-175 for 9974703 added on Fri Feb 20 2026
_displayName
UniProt:P03535 NSP4
_timestamp
2026-02-20 21:32:41
chain
chain:1-175
checksum
D86A4B990D0EB733
comment
FUNCTION Plays an essential role in the virus replication cycle by acting as a viroporin. Creates a pore in the host endoplasmic reticulum 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.FUNCTION 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 NSP4 also localizes 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.DOMAIN Binds 1 calcium ion per tetramer.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.
Activation of host autophagy by virus Calcium Enterotoxin Glycoprotein Host endoplasmic reticulum Host membrane Host-virus interaction Ion channel Ion transport Membrane Metal-binding Secreted Signal-anchor Toxin Transmembrane Transmembrane helix Transport Viral ion channel Virulence
