NSP4_ROTBU
ID NSP4_ROTBU Reviewed; 175 AA.
AC P04513; P12477;
DT 13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1990, sequence version 2.
DT 03-AUG-2022, entry version 109.
DE RecName: Full=Non-structural glycoprotein 4 {ECO:0000255|HAMAP-Rule:MF_04091};
DE Short=NSP4 {ECO:0000255|HAMAP-Rule:MF_04091};
DE AltName: Full=NCVP5 {ECO:0000255|HAMAP-Rule:MF_04091};
DE AltName: Full=NS28 {ECO:0000255|HAMAP-Rule:MF_04091};
OS Rotavirus A (strain RVA/Cow/United Kingdom/UK/1975/G6P7[5]) (RV-A).
OC Viruses; Riboviria; Orthornavirae; Duplornaviricota; Resentoviricetes;
OC Reovirales; Reoviridae; Sedoreovirinae; Rotavirus; Rotavirus A.
OX NCBI_TaxID=10934;
OH NCBI_TaxID=9913; Bos taurus (Bovine).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=6099939; DOI=10.1016/0168-1702(84)90011-x;
RA Baybutt H.N., McCrae M.A.;
RT "The molecular biology of rotaviruses. VII. Detailed structural analysis of
RT gene 10 of bovine rotavirus.";
RL Virus Res. 1:533-541(1984).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=2998051; DOI=10.1016/0042-6822(85)90275-2;
RA Ward C.W., Azad A.A., Dyall-Smith M.L.;
RT "Structural homologies between RNA gene segments 10 and 11 from UK bovine,
RT simian SA11, and human Wa rotaviruses.";
RL Virology 144:328-336(1985).
RN [3]
RP SUBCELLULAR LOCATION, AND GLYCOSYLATION.
RX PubMed=17035333; DOI=10.1128/jvi.01378-06;
RA Bugarcic A., Taylor J.A.;
RT "Rotavirus nonstructural glycoprotein NSP4 is secreted from the apical
RT surfaces of polarized epithelial cells.";
RL J. Virol. 80:12343-12349(2006).
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:0000255|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:0000255|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:0000255|HAMAP-
CC Rule:MF_04091}.
CC -!- SUBCELLULAR LOCATION: Host rough endoplasmic reticulum membrane
CC {ECO:0000255|HAMAP-Rule:MF_04091}; Single-pass type III membrane
CC protein {ECO:0000255|HAMAP-Rule:MF_04091}. Host membrane, host caveola
CC {ECO:0000255|HAMAP-Rule:MF_04091}; Single-pass type III membrane
CC protein {ECO:0000255|HAMAP-Rule:MF_04091}. Secreted {ECO:0000255|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:0000255|HAMAP-Rule:MF_04091}.
CC -!- DOMAIN: A disordered 28 aa C-terminal domain is presented to the
CC cytoplasm by each subunit of the tetrameric receptor.
CC -!- DOMAIN: Binds 1 calcium ion per tetramer. {ECO:0000255|HAMAP-
CC Rule:MF_04091}.
CC -!- PTM: Mannosylated.
CC -!- PTM: The N-glycosyl content is primarily Man(9)GlcNAc, with a small
CC amount of Man(8)GlcNAc. {ECO:0000255|HAMAP-Rule:MF_04091}.
CC -!- SIMILARITY: Belongs to the rotavirus NSP4 family. {ECO:0000255|HAMAP-
CC Rule:MF_04091}.
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DR EMBL; M21885; AAA47313.1; -; Genomic_RNA.
DR EMBL; K03384; AAA47288.1; -; Genomic_RNA.
DR PIR; A04141; VGXRBR.
DR iPTMnet; P04513; -.
DR Proteomes; UP000008657; 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 1: Evidence at protein level;
KW Activation of host autophagy by virus; Calcium; Enterotoxin; Glycoprotein;
KW Host endoplasmic reticulum; Host membrane; Host-virus interaction;
KW Ion channel; Ion transport; Membrane; Metal-binding; Secreted;
KW Signal-anchor; Toxin; Transmembrane; Transmembrane helix; Transport;
KW Viral ion channel; Virulence.
FT CHAIN 1..175
FT /note="Non-structural glycoprotein 4"
FT /id="PRO_0000149623"
FT TOPO_DOM 1..28
FT /note="Lumenal"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04091"
FT TRANSMEM 29..51
FT /note="Helical; Signal-anchor for type III membrane
FT protein"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04091"
FT TOPO_DOM 52..175
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04091"
FT BINDING 120
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04091"
FT BINDING 123
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04091"
FT CARBOHYD 8
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04091,
FT ECO:0000269|PubMed:17035333"
FT CARBOHYD 18
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04091,
FT ECO:0000269|PubMed:17035333"
FT CONFLICT 19
FT /note="S -> N (in Ref. 2; AAA47288)"
FT CONFLICT 37
FT /note="V -> A (in Ref. 2; AAA47288)"
FT CONFLICT 131
FT /note="H -> Y (in Ref. 2; AAA47288)"
FT CONFLICT 136..140
FT /note="IRTVD -> VRSTG (in Ref. 2; AAA47288)"
FT CONFLICT 161..163
FT /note="NGR -> SGK (in Ref. 2; AAA47288)"
SQ SEQUENCE 175 AA; 20492 MW; 86584FDB806CF240 CRC64;
MEKLTDLNYT LSVITLMNST LHTILEDPGM AYFPYIVSVL TVLFTLHKAS IPTMKIALKT
SKCSYKVVKY CIVTIFNTLL KLAGYKEQIT TKDEIEKQMD RVVKEMRRQL EMIDKLTTRE
IEQVELLKRI HDKLMIRTVD EIDMTKEINQ KNVRTLEEWE NGRNPYEPKE VTAAM
