NSP4_ROTPC
ID NSP4_ROTPC Reviewed; 150 AA.
AC Q9YS17; Q9YS18;
DT 14-APR-2009, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 23-FEB-2022, entry version 47.
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 C (strain RVC/Pig/United States/Cowden/1980) (RV-C).
OC Viruses; Riboviria; Orthornavirae; Duplornaviricota; Resentoviricetes;
OC Reovirales; Reoviridae; Sedoreovirinae; Rotavirus.
OX NCBI_TaxID=10916;
OH NCBI_TaxID=9823; Sus scrofa (Pig).
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Cowden-attenuated, and Cowden-virulent;
RX PubMed=10456791; DOI=10.1023/a:1008068218966;
RA Chang K.O., Kim Y.J., Saif L.J.;
RT "Comparisons of nucleotide and deduced amino acid sequences of NSP4 genes
RT of virulent and attenuated pairs of group A and C rotaviruses.";
RL Virus Genes 18:229-233(1999).
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 -!- 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; AF093202; AAC83711.1; -; mRNA.
DR EMBL; AF093203; AAC83712.1; -; mRNA.
DR SMR; Q9YS17; -.
DR Proteomes; UP000008175; 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: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.
PE 2: Evidence at transcript level;
KW Activation of host autophagy by virus; Enterotoxin; Glycoprotein;
KW Host endoplasmic reticulum; Host membrane; Host-virus interaction;
KW Ion channel; Ion transport; Membrane; Reference proteome; Secreted;
KW Signal-anchor; Toxin; Transmembrane; Transmembrane helix; Transport;
KW Viral ion channel; Virulence.
FT CHAIN 1..150
FT /note="Non-structural glycoprotein 4"
FT /id="PRO_0000369891"
FT TOPO_DOM 1..15
FT /note="Lumenal"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04091"
FT TRANSMEM 16..30
FT /note="Helical; Signal-anchor for type III membrane
FT protein"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04091"
FT TOPO_DOM 31..150
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04091"
FT CARBOHYD 5
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04091"
FT VARIANT 50
FT /note="F -> L (in strain: Cowden-virulent)"
FT VARIANT 97
FT /note="D -> N (in strain: Cowden-virulent)"
SQ SEQUENCE 150 AA; 17489 MW; 5093C34FEFBE8FC2 CRC64;
MEFINQTFFS DYSEGKIDTI PYALGIVLAL TNGSRILKFI NLLISLLRKF IITSKTVIGK
FKIENNTSHQ NDDIHKEYEE VMKQMREMRV HVTALFDSIH KDNMEWRMSE SIRREKKREM
KASTAENEVK IHTNDVNICD TSGLETEVCL
