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P08434 (NSP4_ROTBN) Reviewed, UniProtKB/Swiss-Prot

Last modified February 19, 2014. Version 74. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
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Names and origin

Protein namesRecommended name:
Non-structural glycoprotein 4

Short name=NSP4
Alternative name(s):
NCVP5
NS28
OrganismRotavirus A (strain Cow/United States/NCDV-Lincoln/1969 G6-P6[1]-I2-R2-C2-M2-Ax-N2-T6-E2-Hx) (RV-A) (Rotavirus A (strain Nebraska calf diarrhea virus))
Taxonomic identifier36439 [NCBI]
Taxonomic lineageVirusesdsRNA virusesReoviridaeSedoreovirinaeRotavirusRotavirus A
Virus hostBos taurus (Bovine) [TaxID: 9913]

Protein attributes

Sequence length175 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Involved in virus morphogenesis. Functions as a receptor for the immature double-layered inner capsid particle (ICP) which transiently buds into the lumen of the rough endoplasmic reticulum during viral maturation.

Enterotoxin that causes a 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 probably released from infected enterocytes in a soluble form capable of diffusing within the intestinal lumen and interacting with the plasma membrane receptors on neighboring epithelial cells. Possible receptors for NSP4 are alpha-1/beta-1 and alpha-2/beta-1 integrin heterodimers By similarity.

Subunit structure

Homotetramer. Forms a complex with the ICP. Interacts, via the active enterotoxic peptide region, 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 By similarity.

Subcellular location

Non-structural glycoprotein 4: Host rough endoplasmic reticulum membrane; Single-pass type III membrane protein. Host membranehost caveola; Single-pass type III membrane protein By similarity. Secreted By similarity. Note: Immature double-layered particles assembled in the cytoplasm bud across the membrane of the endoplasmic reticulum, acquiring during this process a transient lipid membrane that is modified with the ER resident viral glycoproteins NSP4 and VP7; these enveloped particles also contain VP4. As the particles move towards the interior of the ER cisternae, the transient lipid membrane and the non-structural protein NSP4 are lost, while the virus surface proteins VP4 and VP7 rearrange to form the outermost virus protein layer, yielding mature infectious triple-layered particles. NSP4 also localizes in vesicular structures, which contain an autophagosomal marker and associate with viroplasms in virus-infected cells By similarity. Ref.2

Domain

A disordered 28 aa C-terminal domain is presented to the cytoplasm by each subunit of the tetrameric receptor.

The coiled coil region mediates oligomerization By similarity.

Post-translational modification

Mannosylated.

Miscellaneous

Binds 1 calcium ion per tetramer. The calcium ion is bound by a glutamine from each tetrameric partner and by a glutamic acid from two of the tetrameric partners, while the glutamic acid from the other two partners do not participate in binding the ion By similarity.

Sequence similarities

Belongs to the rotavirus NSP4 family.

Caution

A candidate enterotoxigenic cleaved form of the protein has been suggested, but it remains unclear whether this truncated form constitutes an active enterotoxin in vivo.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 175175Non-structural glycoprotein 4
PRO_0000149622

Regions

Topological domain1 – 2828Lumenal Ref.2
Transmembrane29 – 4416Helical; Signal-anchor for type III membrane protein; Probable
Topological domain45 – 175131Cytoplasmic Ref.2
Region7 – 2115Hydrophobic
Region67 – 8519Hydrophobic
Region85 – 12339Endoplasmic reticulum retention signal Potential
Region114 – 13522Interaction with CAV1 By similarity
Region122 – 17554Required for interaction with microtubules By similarity
Region159 – 17517ICP binding domain By similarity
Coiled coil85 – 11733 Potential

Sites

Metal binding1201Calcium; shared with all tetrameric partners; partial By similarity
Metal binding1231Calcium; shared with all tetrameric partners By similarity
Site111 – 1122Cleavage Potential

Amino acid modifications

Glycosylation81N-linked (GlcNAc...); by host Ref.2
Glycosylation181N-linked (GlcNAc...); by host Ref.2

Sequences

Sequence LengthMass (Da)Tools
P08434 [UniParc].

Last modified August 1, 1988. Version 1.
Checksum: FD7C0CCF75C4CE20

FASTA17520,380
        10         20         30         40         50         60 
MEKLTDLNYT SSVITLMNST LHTILEDPGM AYFPYIASVL TVLFTLHKAS IPTMKIALKT 

        70         80         90        100        110        120 
SKCSYKVVKY CIVTIFNTLL KLAGYKEQIT TKDEIEKQMD RVVKEMRRQL EMIDKLTTRE 

       130        140        150        160        170 
IEQVELLKRI HDKLMIRAVD EIDMTKEINQ KNVRTLEEWE NGKNPYEPKE VTAAM 

« Hide

References

[1]"Nucleotide sequence of bovine rotavirus genomic segment 10: an RNA encoding the viral nonstructural glycoprotein."
Powell K.F.H., Gunn P.R., Bellamy A.R.
Nucleic Acids Res. 16:763-763(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[2]"Topology of the non-structural rotavirus receptor glycoprotein NS28 in the rough endoplasmic reticulum."
Bergmann C.C., Maass D., Poruchynsky M.S., Atkinson P.H., Bellamy A.R.
EMBO J. 8:1695-1703(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: TOPOLOGY, SUBCELLULAR LOCATION, GLYCOSYLATION AT ASN-8 AND ASN-18, CARBOHYDRATE STRUCTURE.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X06806 Genomic RNA. Translation: CAA29959.1.
PIRVGXRP5. S01888.

3D structure databases

ProteinModelPortalP08434.
SMRP08434. Positions 95-137.
ModBaseSearch...
MobiDBSearch...

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Family and domain databases

InterProIPR002107. Rotavirus_NSP4.
[Graphical view]
PfamPF01452. Rota_NSP4. 1 hit.
[Graphical view]
ProDomPD002202. NSP4_rotavirus. 1 hit.
[Graphical view] [Entries sharing at least one domain]
ProtoNetSearch...

Entry information

Entry nameNSP4_ROTBN
AccessionPrimary (citable) accession number: P08434
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1988
Last sequence update: August 1, 1988
Last modified: February 19, 2014
This is version 74 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families