ID A0A0C6DWB5_9REOV Unreviewed; 175 AA. AC A0A0C6DWB5; DT 29-APR-2015, integrated into UniProtKB/TrEMBL. DT 29-APR-2015, sequence version 1. DT 16-OCT-2019, entry version 10. 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; Reoviridae; Sedoreovirinae; Rotavirus; OC 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, RT the Philippines by one year survey with clinical and environmental RT samples."; RL Submitted (SEP-2014) to the EMBL/GenBank/DDBJ databases. CC -!- FUNCTION: Plays an essential role in the virus replication cycle CC by acting as a viroporin. Creates a pore in the host reticulum CC endoplasmic and as a consequence releases Ca(2+) in the cytoplasm CC of infected cell. In turn, high levels of cytoplasmic calcium CC trigger membrane trafficking and transport of viral ER-associated CC proteins to viroplasms, sites of viral genome replication and CC immature particle 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 CC concentration of intracellular calcium disrupts the cytoskeleton CC and the tight junctions, raising the paracellular permeability. CC Potentiates chloride ion secretion through a calcium ion-dependent CC signaling pathway, inducing age-dependent diarrhea. To perform CC this enterotoxigenic role in vivo, NSP4 is released from infected CC enterocytes in a soluble form capable of diffusing within the CC intestinal lumen and interacting with host plasma membrane CC receptors on neighboring epithelial cells such as integrins CC ITGA1/ITGB1 and ITGA2/ITGB1. {ECO:0000256|HAMAP-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 CC with host integrin ITGA2/ITGB1 heterodimer. Interaction with CC microtubules blocks trafficking to the Golgi apparatus. CC {ECO:0000256|HAMAP-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 CC caveola {ECO:0000256|HAMAP-Rule:MF_04091}; Single-pass type III CC membrane protein {ECO:0000256|HAMAP-Rule:MF_04091}. Secreted CC {ECO:0000256|HAMAP-Rule:MF_04091}. Note=NSP4 localizes also in CC 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 CC its transmembrane domain. {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 CC small amount of Man(8)GlcNAc. {ECO:0000256|HAMAP-Rule:MF_04091}. CC -!- SIMILARITY: Belongs to the rotavirus NSP4 family. CC {ECO:0000256|HAMAP-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 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:0016021; C:integral component of membrane; IEA:UniProtKB-UniRule. DR GO; GO:0044385; C:integral to membrane of host cell; IEA:UniProtKB-KW. DR GO; GO:0005216; F:ion channel activity; IEA:UniProtKB-KW. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-UniRule. 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 HAMAP; MF_04091; ROTA_NSP4; 1. DR InterPro; IPR002107; Rotavirus_NSP4. DR Pfam; PF01452; Rota_NSP4; 1. PE 3: Inferred from homology; KW Activation of host autophagy by virus {ECO:0000256|HAMAP- KW Rule:MF_04091}; Calcium {ECO:0000256|HAMAP-Rule:MF_04091}; KW Coiled coil {ECO:0000256|SAM:Coils}; KW Complete proteome {ECO:0000313|Proteomes:UP000223676}; KW Enterotoxin {ECO:0000256|HAMAP-Rule:MF_04091}; KW 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|HAMAP-Rule:MF_04091}; KW Secreted {ECO:0000256|HAMAP-Rule:MF_04091}; KW Signal-anchor {ECO:0000256|HAMAP-Rule:MF_04091}; KW Toxin {ECO:0000256|HAMAP-Rule:MF_04091}; KW Transmembrane {ECO:0000256|HAMAP-Rule:MF_04091, KW ECO:0000256|SAM:Phobius}; KW Transmembrane helix {ECO:0000256|HAMAP-Rule:MF_04091, KW ECO:0000256|SAM:Phobius}; KW 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 Lumenal. {ECO:0000256|HAMAP-Rule: FT MF_04091}. FT TRANSMEM 29 46 Helical. {ECO:0000256|SAM:Phobius}. FT TOPO_DOM 52 175 Cytoplasmic. {ECO:0000256|HAMAP-Rule: FT MF_04091}. FT COILED 85 112 {ECO:0000256|SAM:Coils}. FT METAL 120 120 Calcium. {ECO:0000256|HAMAP-Rule: FT MF_04091}. FT METAL 123 123 Calcium. {ECO:0000256|HAMAP-Rule: FT MF_04091}. FT CARBOHYD 8 8 N-linked (GlcNAc...) asparagine; by host. FT {ECO:0000256|HAMAP-Rule:MF_04091}. FT CARBOHYD 18 18 N-linked (GlcNAc...) asparagine; by host. FT {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 //