ID L0N427_9REOV Unreviewed; 175 AA.
AC L0N427;
DT 06-MAR-2013, integrated into UniProtKB/TrEMBL.
DT 06-MAR-2013, sequence version 1.
DT 27-MAR-2024, entry version 35.
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:BAM73318.1};
OS Human rotavirus A.
OC Viruses; Riboviria; Orthornavirae; Duplornaviricota; Resentoviricetes;
OC Reovirales; Sedoreoviridae; Rotavirus; Rotavirus A.
OX NCBI_TaxID=10941 {ECO:0000313|EMBL:BAM73318.1, ECO:0000313|Proteomes:UP000224712};
RN [1] {ECO:0000313|EMBL:BAM73318.1, ECO:0000313|Proteomes:UP000224712}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=RVA/Human-tc/JPN/AU605/1986/G2P[4]
RC {ECO:0000313|EMBL:BAM73318.1, ECO:0000313|Proteomes:UP000224712};
RX PubMed=22575821; DOI=10.1016/j.meegid.2012.04.023;
RA Doan Y.H., Nakagomi T., Nakagomi O.;
RT "Repeated circulation over 6 years of intergenogroup mono-reassortant
RT G2P[4] rotavirus strains with genotype N1 of the NSP2 gene.";
RL Infect. Genet. Evol. 12:1202-1212(2012).
RN [2] {ECO:0000313|EMBL:BAQ58987.1}
RP NUCLEOTIDE SEQUENCE.
RC STRAIN=RVA/Human-wt/JPN/87Y1438/1987/G2P[4]
RC {ECO:0000313|EMBL:BAQ58987.1}, RVA/Human-wt/JPN/88F007/1988/G2P[4]
RC {ECO:0000313|EMBL:BAQ58988.1}, and RVA/Human-wt/JPN/88Y259/1988/G2P[4]
RC {ECO:0000313|EMBL:BAQ58990.1};
RA Doan Y.H., Nakagomi T., Nakagomi O.;
RT "Replacement of genotype constellations of predominant G2P[4] rotaviruses
RT detected in Japan over 31 years (1980-2011).";
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}.
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DR EMBL; AB762778; BAM73318.1; -; Genomic_RNA.
DR EMBL; LC002038; BAQ58987.1; -; Genomic_RNA.
DR EMBL; LC002039; BAQ58988.1; -; Genomic_RNA.
DR EMBL; LC002041; BAQ58990.1; -; Genomic_RNA.
DR Proteomes; UP000221401; Genome.
DR Proteomes; UP000221755; Genome.
DR Proteomes; UP000224712; Genome.
DR Proteomes; UP000225929; 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:0051259; P:protein complex oligomerization; IEA:UniProtKB-KW.
DR GO; GO:0039707; P:virus-mediated pore formation in host cell membrane; 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|ARBA:ARBA00023050,
KW 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};
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};
KW Transmembrane helix {ECO:0000256|HAMAP-Rule:MF_04091};
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
FT /note="Lumenal"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_04091"
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; 20305 MW; 2379E95C1FAB45B3 CRC64;
MEKFTDLNYT LSVITLMNST LHTILEDPGM AYFPYIASAL TVLFTLHKAS IPTMKIALKT
SKCSYKVVKY CIVTILNTLL KLAGYKEQIT TKDEIEKQMD RVVKEMRRQL EMIDKLTTRE
IEQVELLKRI YDKLIVRSTG EIDMTKEINQ KNVRTLEEWE SGKNPYEPKE VTAAM
//
