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O12674 (NSP4_ROTHV) Reviewed, UniProtKB/Swiss-Prot

Last modified February 19, 2014. Version 45. 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 (isolate Human/Italy/VA70/1975 G4-P1A[8]-Ix-Rx-Cx-Mx-Ax-Nx-Tx-E1-Hx) (RV-A)
Taxonomic identifier10961 [NCBI]
Taxonomic lineageVirusesdsRNA virusesReoviridaeSedoreovirinaeRotavirusRotavirus A
Virus hostHomo sapiens (Human) [TaxID: 9606]

Protein attributes

Sequence length175 AA.
Sequence statusComplete.
Protein existenceInferred from homology

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 By similarity.

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 By similarity. Host membranehost caveola; Single-pass type III membrane protein. 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.

Domain

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

The coiled coil region mediates oligomerization By similarity.

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_0000369467

Regions

Topological domain1 – 2828Lumenal By similarity
Transmembrane29 – 5123Helical; Potential
Topological domain52 – 175124Cytoplasmic By similarity
Region7 – 2115Hydrophobic By similarity
Region67 – 8519Hydrophobic By similarity
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 Potential
Glycosylation181N-linked (GlcNAc...); by host Potential

Sequences

Sequence LengthMass (Da)Tools
O12674 [UniParc].

Last modified July 1, 1997. Version 1.
Checksum: 6671B9F9471D5697

FASTA17520,319
        10         20         30         40         50         60 
MDKLADLNYT LSVITSMNDT LHSIIEDPGM AYFPYIASVL TVLFALHKAS IPTMKIALKT 

        70         80         90        100        110        120 
SKCSYKVIKY CIVTIINTLL KLVGYKEQVT TKDEIEQQMD RIVKEMRRQL EMIDKLTTRE 

       130        140        150        160        170 
IEQVELLKRI HDNLITRPVD VIDMSKEFNQ KNIKTLDEWE SRKNPYEPSE VTASM 

« Hide

References

[1]"Genetic characterization of the rotavirus nonstructural protein, NSP4."
Kirkwood C.D., Palombo E.A.
Virology 236:258-265(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U83798 Genomic RNA. Translation: AAB81297.1.

3D structure databases

ProteinModelPortalO12674.
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_ROTHV
AccessionPrimary (citable) accession number: O12674
Entry history
Integrated into UniProtKB/Swiss-Prot: April 14, 2009
Last sequence update: July 1, 1997
Last modified: February 19, 2014
This is version 45 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