NSP4_ROTBN
ID NSP4_ROTBN Reviewed; 175 AA.
AC P08434;
DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1988, sequence version 1.
DT 03-AUG-2022, entry version 100.
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 States/NCDV-Lincoln/1969/G6P6[1]) (RV-A)
OS (Rotavirus A (strain Nebraska calf diarrhea virus)).
OC Viruses; Riboviria; Orthornavirae; Duplornaviricota; Resentoviricetes;
OC Reovirales; Reoviridae; Sedoreovirinae; Rotavirus; Rotavirus A.
OX NCBI_TaxID=36439;
OH NCBI_TaxID=9913; Bos taurus (Bovine).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=2829135; DOI=10.1093/nar/16.2.763;
RA Powell K.F.H., Gunn P.R., Bellamy A.R.;
RT "Nucleotide sequence of bovine rotavirus genomic segment 10: an RNA
RT encoding the viral nonstructural glycoprotein.";
RL Nucleic Acids Res. 16:763-763(1988).
RN [2]
RP TOPOLOGY, SUBCELLULAR LOCATION, GLYCOSYLATION AT ASN-8 AND ASN-18, AND
RP STRUCTURE OF CARBOHYDRATE.
RX PubMed=2548854; DOI=10.1002/j.1460-2075.1989.tb03561.x;
RA Bergmann C.C., Maass D., Poruchynsky M.S., Atkinson P.H., Bellamy A.R.;
RT "Topology of the non-structural rotavirus receptor glycoprotein NS28 in the
RT rough endoplasmic reticulum.";
RL EMBO J. 8:1695-1703(1989).
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, ECO:0000269|PubMed:2548854}; Single-
CC pass type III membrane protein {ECO:0000255|HAMAP-Rule:MF_04091}. Host
CC membrane, host caveola {ECO:0000255|HAMAP-Rule:MF_04091}; Single-pass
CC type III membrane protein {ECO:0000255|HAMAP-Rule:MF_04091}. Secreted
CC {ECO:0000255|HAMAP-Rule:MF_04091}. Note=NSP4 localizes also in
CC vesicular structures which contain autophagosomal markers and associate
CC with viroplasms in virus-infected cells. Additionally, a soluble form
CC of glycosylated NSP4 is secreted despite retention of its transmembrane
CC domain. {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}.
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; X06806; CAA29959.1; -; Genomic_RNA.
DR PIR; S01888; VGXRP5.
DR PDB; 5Y2E; X-ray; 2.70 A; A/B/C/D=95-140.
DR PDBsum; 5Y2E; -.
DR SMR; P08434; -.
DR iPTMnet; P08434; -.
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 3D-structure; Activation of host autophagy by virus; Calcium; Enterotoxin;
KW Glycoprotein; Host endoplasmic reticulum; Host membrane;
KW Host-virus interaction; Ion channel; Ion transport; Membrane;
KW Metal-binding; Secreted; Signal-anchor; Toxin; Transmembrane;
KW Transmembrane helix; Transport; Viral ion channel; Virulence.
FT CHAIN 1..175
FT /note="Non-structural glycoprotein 4"
FT /id="PRO_0000149622"
FT TOPO_DOM 1..28
FT /note="Lumenal"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04091,
FT ECO:0000269|PubMed:2548854"
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 ECO:0000269|PubMed:2548854"
FT REGION 7..21
FT /note="Hydrophobic"
FT REGION 67..85
FT /note="Hydrophobic"
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:2548854"
FT CARBOHYD 18
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04091,
FT ECO:0000269|PubMed:2548854"
FT HELIX 95..138
FT /evidence="ECO:0007829|PDB:5Y2E"
SQ SEQUENCE 175 AA; 20380 MW; FD7C0CCF75C4CE20 CRC64;
MEKLTDLNYT SSVITLMNST LHTILEDPGM AYFPYIASVL TVLFTLHKAS IPTMKIALKT
SKCSYKVVKY CIVTIFNTLL KLAGYKEQIT TKDEIEKQMD RVVKEMRRQL EMIDKLTTRE
IEQVELLKRI HDKLMIRAVD EIDMTKEINQ KNVRTLEEWE NGKNPYEPKE VTAAM
