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Protein

Non-structural glycoprotein 4

Gene
N/A
Organism
Rotavirus A (strain RVA/Cow/United States/NCDV-Lincoln/1969/G6P6[1]) (RV-A) (Rotavirus A (strain Nebraska calf diarrhea virus))
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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 cyctoplasmic calcium trigger membrane trafficking and transport of viral ER-associated proteins to viroplasms, sites of viral genome replication and immature particle assembly.UniRule annotation
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.UniRule annotation

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi120CalciumUniRule annotation1
Metal bindingi123CalciumUniRule annotation1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionEnterotoxin, Ion channel, Toxin, Viral ion channel
Biological processActivation of host autophagy by virus, Host-virus interaction, Ion transport, Transport, Virulence
LigandCalcium, Metal-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Non-structural glycoprotein 4UniRule annotation
Short name:
NSP4UniRule annotation
Alternative name(s):
NCVP5UniRule annotation
NS28UniRule annotation
OrganismiRotavirus A (strain RVA/Cow/United States/NCDV-Lincoln/1969/G6P6[1]) (RV-A) (Rotavirus A (strain Nebraska calf diarrhea virus))
Taxonomic identifieri36439 [NCBI]
Taxonomic lineageiVirusesdsRNA virusesReoviridaeSedoreovirinaeRotavirusRotavirus A
Virus hostiBos taurus (Bovine) [TaxID: 9913]

Subcellular locationi

  • Host rough endoplasmic reticulum membrane UniRule annotation1 Publication; Single-pass type III membrane protein UniRule annotation
  • host caveola UniRule annotation; Single-pass type III membrane protein UniRule annotation
  • Secreted UniRule annotation
  • 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.UniRule annotation

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 28LumenalUniRule annotation1 PublicationAdd BLAST28
Transmembranei29 – 51Helical; Signal-anchor for type III membrane proteinUniRule annotationAdd BLAST23
Topological domaini52 – 175CytoplasmicUniRule annotation1 PublicationAdd BLAST124

GO - Cellular componenti

Keywords - Cellular componenti

Host endoplasmic reticulum, Host membrane, Membrane, Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001496221 – 175Non-structural glycoprotein 4Add BLAST175

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi8N-linked (GlcNAc...) asparagine; by hostUniRule annotation1 Publication1
Glycosylationi18N-linked (GlcNAc...) asparagine; by hostUniRule annotation1 Publication1

Post-translational modificationi

Mannosylated.
The N-glycosyl content is primarily Man9GlcNAc, with a small amount of Man8GlcNAc.UniRule annotation

Keywords - PTMi

Glycoprotein

PTM databases

iPTMnetiP08434

Interactioni

Subunit structurei

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.UniRule annotation

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5Y2EX-ray2.70A/B/C/D95-140[»]
ProteinModelPortaliP08434
SMRiP08434
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni7 – 21HydrophobicAdd BLAST15
Regioni67 – 85HydrophobicAdd BLAST19

Domaini

A disordered 28 aa C-terminal domain is presented to the cytoplasm by each subunit of the tetrameric receptor.
Binds 1 calcium ion per tetramer.UniRule annotation

Sequence similaritiesi

Belongs to the rotavirus NSP4 family.UniRule annotation

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Family and domain databases

HAMAPiMF_04091 ROTA_NSP4, 1 hit
InterProiView protein in InterPro
IPR002107 Rotavirus_NSP4
PfamiView protein in Pfam
PF01452 Rota_NSP4, 1 hit
ProDomiView protein in ProDom or Entries sharing at least one domain
PD002202 NSP4_rotavirus, 1 hit

Sequencei

Sequence statusi: Complete.

P08434-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEKLTDLNYT SSVITLMNST LHTILEDPGM AYFPYIASVL TVLFTLHKAS
60 70 80 90 100
IPTMKIALKT SKCSYKVVKY CIVTIFNTLL KLAGYKEQIT TKDEIEKQMD
110 120 130 140 150
RVVKEMRRQL EMIDKLTTRE IEQVELLKRI HDKLMIRAVD EIDMTKEINQ
160 170
KNVRTLEEWE NGKNPYEPKE VTAAM
Length:175
Mass (Da):20,380
Last modified:August 1, 1988 - v1
Checksum:iFD7C0CCF75C4CE20
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X06806 Genomic RNA Translation: CAA29959.1
PIRiS01888 VGXRP5

Similar proteinsi

Entry informationi

Entry nameiNSP4_ROTBN
AccessioniPrimary (citable) accession number: P08434
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1988
Last sequence update: August 1, 1988
Last modified: April 25, 2018
This is version 88 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure
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Main funding by: National Institutes of Health