AC MF_04091; DC Protein; auto TR HAMAP; MF_04091; -; 1; level=0 XX Names: ROTA_NSP4 XX ID NSP4 DE RecName: Full=Non-structural glycoprotein 4; DE Short=NSP4; DE AltName: Full=NCVP5; DE AltName: Full=NS28; XX CC -!- FUNCTION: Plays an essential role in the virus replication cycle by CC acting as a viroporin. Creates a pore in the host reticulum endoplasmic CC and as a consequence releases Ca(2+) in the cytoplasm of infected cell. CC In turn, high levels of cytoplasmic calcium trigger membrane CC trafficking and transport of viral ER-associated proteins to CC viroplasms, sites of viral genome replication and immature particle CC assembly. CC -!- FUNCTION: The secreted form acts as an enterotoxin that causes CC phospholipase C-dependent elevation of the intracellular calcium CC concentration in host intestinal mucosa cells. Increased concentration CC of intracellular calcium disrupts the cytoskeleton and the tight CC junctions, raising the paracellular permeability. Potentiates chloride CC ion secretion through a calcium ion-dependent signaling pathway, CC inducing age-dependent diarrhea. To perform this enterotoxigenic role CC in vivo, NSP4 is released from infected enterocytes in a soluble form CC capable of diffusing within the intestinal lumen and interacting with CC host plasma membrane receptors on neighboring epithelial cells such as CC integrins ITGA1/ITGB1 and ITGA2/ITGB1. CC -!- SUBUNIT: Homotetramer. Interacts with the immature particle in the CC viroplasm. Interacts with host CAV1, early and late in infection. CC Interacts with host integrin ITGA1/ITGB1 heterodimer. Interacts with CC host integrin ITGA2/ITGB1 heterodimer. Interaction with microtubules CC blocks trafficking to the Golgi apparatus. CC -!- SUBCELLULAR LOCATION: Host rough endoplasmic reticulum membrane; CC Single-pass type III membrane protein. Host membrane, host caveola; CC Single-pass type III membrane protein. Secreted. Note=NSP4 localizes CC also in vesicular structures which contain autophagosomal markers and CC associate with viroplasms in virus-infected cells. Additionally, a CC soluble form of glycosylated NSP4 is secreted despite retention of its CC transmembrane domain. case CC -!- DOMAIN: Binds 1 calcium ion per tetramer. end case CC -!- PTM: The N-glycosyl content is primarily Man(9)GlcNAc, with a small CC amount of Man(8)GlcNAc. CC -!- SIMILARITY: Belongs to the rotavirus NSP4 family. XX DR Pfam; PF01452; Rota_NSP4; 1; trigger=no DR General; Coiled_coil; -; 0-unlimited; trigger=no DR General; Transmembrane; -; 1; trigger=no XX case KW Calcium KW Metal-binding end case KW Activation of host autophagy by virus KW Enterotoxin KW Glycoprotein KW Host endoplasmic reticulum KW Host membrane KW Host-virus interaction KW Ion channel KW Ion transport KW Membrane KW Secreted KW Signal-anchor KW Toxin KW Transmembrane KW Transmembrane helix KW Transport KW Viral ion channel KW Virulence XX GO GO:0005576; C:extracellular region GO GO:0044155; C:host caveola GO GO:0044169; C:host cell rough endoplasmic reticulum membrane GO GO:0016020; C:membrane case GO GO:0046872; F:metal ion binding end case GO GO:0090729; F:toxin activity GO GO:0016032; P:viral process XX FT From: NSP4_ROTS1 (P04512) FT TOPO_DOM Nter..28 FT /note="Lumenal" FT TRANSMEM 29..51 FT /note="Helical; Signal-anchor for type III membrane FT protein" FT TOPO_DOM 52..Cter FT /note="Cytoplasmic" FT BINDING 120 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT Group: 1; Condition: E FT BINDING 123 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT Group: 1; Condition: Q FT CARBOHYD 8 FT /note="N-linked (GlcNAc...) asparagine; by host" FT Condition: N FT CARBOHYD 18 FT /note="N-linked (GlcNAc...) asparagine; by host" FT Condition: N XX Size: 150-219; Related: None; Template: P04512; Scope: Viruses; Rotavirus Fusion: Nter: None Cter: None Duplicate: None Plasmid: None Comments: None XX # Revision 1.8 2022/11/19 //