A0A0A7HIU6 · A0A0A7HIU6_9REOV
- ProteinNon-structural glycoprotein 4
- GeneNSP4
- StatusUniProtKB unreviewed (TrEMBL)
- Organism
- Amino acids175 (go to sequence)
- Protein existenceInferred from homology
- Annotation score4/5
Function
function
Plays an essential role in the virus replication cycle by acting as a viroporin. Creates a pore in the host reticulum endoplasmic and as a consequence releases Ca2+ in the cytoplasm of infected cell. In turn, high levels of cytoplasmic calcium trigger membrane trafficking and transport of viral ER-associated proteins to viroplasms, sites of viral genome replication and immature particle assembly.
The secreted form acts as an enterotoxin that causes phospholipase C-dependent elevation of the intracellular calcium concentration in host intestinal mucosa cells. Increased concentration of intracellular calcium disrupts the cytoskeleton and the tight junctions, raising the paracellular permeability. Potentiates chloride ion secretion through a calcium ion-dependent signaling pathway, inducing age-dependent diarrhea. To perform this enterotoxigenic role in vivo, NSP4 is released from infected enterocytes in a soluble form capable of diffusing within the intestinal lumen and interacting with host plasma membrane receptors on neighboring epithelial cells such as integrins ITGA1/ITGB1 and ITGA2/ITGB1.
Features
Showing features for binding site.
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Aspect | Term | |
---|---|---|
Cellular Component | extracellular region | |
Cellular Component | host caveola | |
Cellular Component | host cell rough endoplasmic reticulum membrane | |
Cellular Component | membrane | |
Molecular Function | channel activity | |
Molecular Function | metal ion binding | |
Molecular Function | toxin activity | |
Biological Process | induction by virus of host autophagy | |
Biological Process | monoatomic ion transmembrane transport |
Keywords
- Molecular function
- Biological process
- Ligand
Names & Taxonomy
Protein names
- Recommended nameNon-structural glycoprotein 4
- Short namesNSP4
- Alternative names
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageViruses > Riboviria > Orthornavirae > Duplornaviricota > Resentoviricetes > Reovirales > Sedoreoviridae > Rotavirus > Rotavirus A
Accessions
- Primary accessionA0A0A7HIU6
Subcellular Location
UniProt Annotation
GO Annotation
Host rough endoplasmic reticulum membrane ; Single-pass type III membrane protein
Host membrane, host caveola ; Single-pass type III membrane protein
Note: NSP4 localizes also in vesicular structures which contain autophagosomal markers and associate with viroplasms in virus-infected cells. Additionally, a soluble form of glycosylated NSP4 is secreted despite retention of its transmembrane domain.
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-28 | Lumenal | ||||
Sequence: MEKLTDLNYTLSVITLMNSTLHTILEDP | ||||||
Transmembrane | 29-46 | Helical | ||||
Sequence: GMAYFPYIASVLTVLFTL | ||||||
Topological domain | 52-175 | Cytoplasmic | ||||
Sequence: PTMKIALKTSKCSYKVVKYCIVTIINTLLNLAGYKEQITTKDEIEKQMDRVIKEMRRQLEMIDKLTTREIEQVELLKRIYDKLIVRSTDEIDMTKEINQKNVRTLEEWESGKNPYEPKEVTAAM |
Keywords
- Cellular component
PTM/Processing
Features
Showing features for glycosylation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Glycosylation | 8 | N-linked (GlcNAc...) asparagine; by host | ||||
Sequence: N | ||||||
Glycosylation | 18 | N-linked (GlcNAc...) asparagine; by host | ||||
Sequence: N |
Post-translational modification
The N-glycosyl content is primarily Man9GlcNAc, with a small amount of Man8GlcNAc.
Keywords
- PTM
PTM databases
Interaction
Subunit
Homotetramer. Interacts with the immature particle in the viroplasm. Interacts with host CAV1, early and late in infection. Interacts with host integrin ITGA1/ITGB1 heterodimer. Interacts with host integrin ITGA2/ITGB1 heterodimer. Interaction with microtubules blocks trafficking to the Golgi apparatus.
Structure
Family & Domains
Sequence
- Sequence statusComplete
- Length175
- Mass (Da)20,357
- Last updated2015-03-04 v1
- ChecksumA88482D5718794DF