ID A0A0C6DWB5_9REOV Unreviewed; 175 AA. AC A0A0C6DWB5; DT 29-APR-2015, integrated into UniProtKB/TrEMBL. DT 29-APR-2015, sequence version 1. DT 03-MAY-2023, entry version 22. DE RecName: Full=Non-structural glycoprotein 4 {ECO:0000256|HAMAP-Rule:MF_04091}; DE Short=NSP4 {ECO:0000256|HAMAP-Rule:MF_04091}; DE AltName: Full=NCVP5 {ECO:0000256|HAMAP-Rule:MF_04091}; DE AltName: Full=NS28 {ECO:0000256|HAMAP-Rule:MF_04091}; GN Name=NSP4 {ECO:0000313|EMBL:BAQ19308.1}; OS Human rotavirus A. OC Viruses; Riboviria; Orthornavirae; Duplornaviricota; Resentoviricetes; OC Reovirales; Sedoreoviridae; Rotavirus; Rotavirus A. OX NCBI_TaxID=10941 {ECO:0000313|EMBL:BAQ19308.1, ECO:0000313|Proteomes:UP000223676}; RN [1] {ECO:0000313|EMBL:BAQ19308.1, ECO:0000313|Proteomes:UP000223676} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=TGE13-77 {ECO:0000313|EMBL:BAQ19308.1, RC ECO:0000313|Proteomes:UP000223676}; RA Imagawa T., Yamamoto D., Saito M., Gaylon R., Saito M., Masago Y., RA Angulo R., Hijada J.R., Mercado E.S., Lupisan S.P., Oshitani H.; RT "Various genotypes of group A rotavirus circulating in Tacloban city, the RT Philippines by one year survey with clinical and environmental samples."; RL Submitted (SEP-2014) to the EMBL/GenBank/DDBJ databases. 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. {ECO:0000256|HAMAP-Rule:MF_04091}. 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. {ECO:0000256|HAMAP- CC Rule:MF_04091}. 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. {ECO:0000256|HAMAP- CC Rule:MF_04091}. CC -!- SUBCELLULAR LOCATION: Host rough endoplasmic reticulum membrane CC {ECO:0000256|HAMAP-Rule:MF_04091}; Single-pass type III membrane CC protein {ECO:0000256|HAMAP-Rule:MF_04091}. Host membrane, host caveola CC {ECO:0000256|HAMAP-Rule:MF_04091}; Single-pass type III membrane CC protein {ECO:0000256|HAMAP-Rule:MF_04091}. Secreted {ECO:0000256|HAMAP- CC Rule:MF_04091}. Note=NSP4 localizes also in vesicular structures which CC contain autophagosomal markers and associate with viroplasms in virus- CC infected cells. Additionally, a soluble form of glycosylated NSP4 is CC secreted despite retention of its transmembrane domain. CC {ECO:0000256|HAMAP-Rule:MF_04091}. CC -!- DOMAIN: Binds 1 calcium ion per tetramer. {ECO:0000256|HAMAP- CC Rule:MF_04091}. CC -!- PTM: The N-glycosyl content is primarily Man(9)GlcNAc, with a small CC amount of Man(8)GlcNAc. {ECO:0000256|HAMAP-Rule:MF_04091}. CC -!- SIMILARITY: Belongs to the rotavirus NSP4 family. {ECO:0000256|HAMAP- CC Rule:MF_04091}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; LC000542; BAQ19308.1; -; Genomic_RNA. DR GlyCosmos; A0A0C6DWB5; 2 sites, No reported glycans. DR Proteomes; UP000223676; Genome. DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell. DR GO; GO:0044155; C:host caveola; IEA:UniProtKB-SubCell. DR GO; GO:0044169; C:host cell rough endoplasmic reticulum membrane; IEA:UniProtKB-SubCell. DR GO; GO:0016020; C:membrane; IEA:UniProtKB-UniRule. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-UniRule. DR GO; GO:0005216; F:monoatomic ion channel activity; IEA:UniProtKB-KW. DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-UniRule. DR GO; GO:0039520; P:induction by virus of host autophagy; IEA:UniProtKB-KW. DR GO; GO:0039707; P:pore formation by virus in membrane of host cell; IEA:UniProtKB-KW. DR GO; GO:0051259; P:protein complex oligomerization; IEA:UniProtKB-KW. DR Gene3D; 1.20.5.430; -; 1. DR HAMAP; MF_04091; ROTA_NSP4; 1. DR InterPro; IPR002107; Rotavirus_NSP4. DR Pfam; PF01452; Rota_NSP4; 1. DR SUPFAM; SSF58030; Rotavirus nonstructural proteins; 1. PE 3: Inferred from homology; KW Activation of host autophagy by virus {ECO:0000256|HAMAP-Rule:MF_04091}; KW Calcium {ECO:0000256|ARBA:ARBA00022837, ECO:0000256|HAMAP-Rule:MF_04091}; KW Coiled coil {ECO:0000256|SAM:Coils}; KW Enterotoxin {ECO:0000256|ARBA:ARBA00022861, ECO:0000256|HAMAP- KW Rule:MF_04091}; Glycoprotein {ECO:0000256|HAMAP-Rule:MF_04091}; KW Host endoplasmic reticulum {ECO:0000256|HAMAP-Rule:MF_04091}; KW Host membrane {ECO:0000256|HAMAP-Rule:MF_04091}; KW Host-virus interaction {ECO:0000256|HAMAP-Rule:MF_04091}; KW Ion channel {ECO:0000256|HAMAP-Rule:MF_04091}; KW Ion transport {ECO:0000256|HAMAP-Rule:MF_04091}; KW Membrane {ECO:0000256|HAMAP-Rule:MF_04091, ECO:0000256|SAM:Phobius}; KW Metal-binding {ECO:0000256|ARBA:ARBA00022723, ECO:0000256|HAMAP- KW Rule:MF_04091}; Secreted {ECO:0000256|HAMAP-Rule:MF_04091}; KW Signal-anchor {ECO:0000256|HAMAP-Rule:MF_04091}; KW Toxin {ECO:0000256|ARBA:ARBA00022656, ECO:0000256|HAMAP-Rule:MF_04091}; KW Transmembrane {ECO:0000256|HAMAP-Rule:MF_04091, ECO:0000256|SAM:Phobius}; KW Transmembrane helix {ECO:0000256|HAMAP-Rule:MF_04091, KW ECO:0000256|SAM:Phobius}; Transport {ECO:0000256|HAMAP-Rule:MF_04091}; KW Viral ion channel {ECO:0000256|HAMAP-Rule:MF_04091}; KW Virulence {ECO:0000256|HAMAP-Rule:MF_04091}. FT TOPO_DOM 1..28 FT /note="Lumenal" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04091" FT TRANSMEM 29..46 FT /note="Helical" FT /evidence="ECO:0000256|SAM:Phobius" FT TOPO_DOM 52..175 FT /note="Cytoplasmic" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04091" FT COILED 85..112 FT /evidence="ECO:0000256|SAM:Coils" FT BINDING 120 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04091" FT BINDING 123 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04091" FT CARBOHYD 8 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04091" FT CARBOHYD 18 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04091" SQ SEQUENCE 175 AA; 20325 MW; C21EDFBEB657429A CRC64; MDKLADLNYT LSVITLMNDT LHSILQDPGM AYFPYIASVL TVLFTLHKAS IPTMKIALKT SKCSYKVIKY CMVTVINTLL KLAGYKEQVT TKDEIEQQMD RIVKEMRRQL EMIDKLTTRE IEQVELLKRI HDRLMTRPVD VIDMSKEFNQ KNVRTLDEWE SGKNPYEPSE VTASM //