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P08434

- NSP4_ROTBN

UniProt

P08434 - NSP4_ROTBN

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Protein

Non-structural glycoprotein 4

Gene
N/A
Organism
Rotavirus 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))
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

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.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei111 – 1122Cleavage Reviewed prediction
Metal bindingi120 – 1201Calcium; shared with all tetrameric partners; partial By similarity
Metal bindingi123 – 1231Calcium; shared with all tetrameric partners By similarity

GO - Molecular functioni

  1. metal ion binding Source: UniProtKB-KW

GO - Biological processi

  1. pathogenesis Source: UniProtKB-KW
  2. viral process Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Enterotoxin, Toxin

Keywords - Biological processi

Host-virus interaction, Virulence

Keywords - Ligandi

Calcium, Metal-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Non-structural glycoprotein 4
Short name:
NSP4
Alternative name(s):
NCVP5
NS28
OrganismiRotavirus 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 identifieri36439 [NCBI]
Taxonomic lineageiVirusesdsRNA virusesReoviridaeSedoreovirinaeRotavirusRotavirus A
Virus hostiBos taurus (Bovine) [TaxID: 9913]

Subcellular locationi

Chain 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.1 Publication

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 2828Lumenal1 PublicationAdd
BLAST
Transmembranei29 – 4416Helical; Signal-anchor for type III membrane protein; InferredAdd
BLAST
Topological domaini45 – 175131Cytoplasmic1 PublicationAdd
BLAST

GO - Cellular componenti

  1. host caveola Source: UniProtKB-SubCell
  2. host cell rough endoplasmic reticulum membrane Source: UniProtKB-SubCell
  3. integral component of membrane Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Host endoplasmic reticulum, Host membrane, Membrane, Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 175175Non-structural glycoprotein 4PRO_0000149622Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi8 – 81N-linked (GlcNAc...); by host1 Publication
Glycosylationi18 – 181N-linked (GlcNAc...); by host1 Publication

Post-translational modificationi

Mannosylated.

Keywords - PTMi

Glycoprotein

Interactioni

Subunit structurei

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.

Structurei

3D structure databases

ProteinModelPortaliP08434.
SMRiP08434. Positions 95-137.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni7 – 2115HydrophobicAdd
BLAST
Regioni67 – 8519HydrophobicAdd
BLAST
Regioni85 – 12339Endoplasmic reticulum retention signal Reviewed predictionAdd
BLAST
Regioni114 – 13522Interaction with CAV1 By similarityAdd
BLAST
Regioni122 – 17554Required for interaction with microtubules By similarityAdd
BLAST
Regioni159 – 17517ICP binding domain By similarityAdd
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili85 – 11733 Reviewed predictionAdd
BLAST

Domaini

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.

Sequence similaritiesi

Belongs to the rotavirus NSP4 family.

Keywords - Domaini

Coiled coil, Signal-anchor, Transmembrane, Transmembrane helix

Family and domain databases

InterProiIPR002107. Rotavirus_NSP4.
[Graphical view]
PfamiPF01452. Rota_NSP4. 1 hit.
[Graphical view]
ProDomiPD002202. NSP4_rotavirus. 1 hit.
[Graphical view] [Entries sharing at least one domain]

Sequencei

Sequence statusi: Complete.

P08434-1 [UniParc]FASTAAdd to Basket

« Hide

MEKLTDLNYT SSVITLMNST LHTILEDPGM AYFPYIASVL TVLFTLHKAS    50
IPTMKIALKT SKCSYKVVKY CIVTIFNTLL KLAGYKEQIT TKDEIEKQMD 100
RVVKEMRRQL EMIDKLTTRE IEQVELLKRI HDKLMIRAVD EIDMTKEINQ 150
KNVRTLEEWE NGKNPYEPKE VTAAM 175
Length:175
Mass (Da):20,380
Last modified:August 1, 1988 - v1
Checksum:iFD7C0CCF75C4CE20
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
X06806 Genomic RNA. Translation: CAA29959.1.
PIRiS01888. VGXRP5.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
X06806 Genomic RNA. Translation: CAA29959.1 .
PIRi S01888. VGXRP5.

3D structure databases

ProteinModelPortali P08434.
SMRi P08434. Positions 95-137.
ModBasei Search...
MobiDBi Search...

Protocols and materials databases

Structural Biology Knowledgebase Search...

Family and domain databases

InterProi IPR002107. Rotavirus_NSP4.
[Graphical view ]
Pfami PF01452. Rota_NSP4. 1 hit.
[Graphical view ]
ProDomi PD002202. NSP4_rotavirus. 1 hit.
[Graphical view ] [Entries sharing at least one domain ]
ProtoNeti Search...

Publicationsi

  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.

Entry informationi

Entry nameiNSP4_ROTBN
AccessioniPrimary (citable) accession number: P08434
Entry historyi
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 statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

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.

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.

Documents

  1. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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