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Protein

Non-structural glycoprotein 4

Gene
N/A
Organism
Rotavirus A (isolate RVA/Human/United States/WI61/1983/G9P1A[8]) (RV-A)
Status
Reviewed-Annotation score: -Protein inferred from homologyi

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 (isolate RVA/Human/United States/WI61/1983/G9P1A[8]) (RV-A)
Taxonomic identifieri578830 [NCBI]
Taxonomic lineageiVirusesdsRNA virusesReoviridaeSedoreovirinaeRotavirusRotavirus A
Virus hostiHomo sapiens (Human) [TaxID: 9606]
Proteomesi
  • UP000006580 Componenti: Genome

Subcellular locationi

  • Host rough endoplasmic reticulum membrane UniRule annotation; 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 annotationAdd BLAST28
Transmembranei29 – 51Helical; Signal-anchor for type III membrane proteinUniRule annotationAdd BLAST23
Topological domaini52 – 175CytoplasmicUniRule annotationAdd BLAST124

GO - Cellular componenti

Keywords - Cellular componenti

Host endoplasmic reticulum, Host membrane, Membrane, Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003694691 – 175Non-structural glycoprotein 4Add BLAST175

Amino acid modifications

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

Post-translational modificationi

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

Keywords - PTMi

Glycoprotein

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

SMRiB3SRY0
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domaini

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

Phylogenomic databases

OrthoDBiVOG090000V0

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.

B3SRY0-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDKFADLNYT LSVITLMNDT LHSIIQDPGM AYFPYIASVL TVLFTLHKAS
60 70 80 90 100
IPTMKIALKT SKCSYKVIKC CIVTIINTLL KLAGYKEQVT TKDEIEQQMD
110 120 130 140 150
RIVKEMRRQL EMIDKLTTRE IEQVELLKRI HDNLIIKPVD VIDMSKEFNQ
160 170
KNIKTLDEWE SGKNPYEPLE VTASM
Length:175
Mass (Da):20,231
Last modified:September 2, 2008 - v1
Checksum:i8B75D3118806B87F
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
EF672624 Genomic RNA Translation: ABV53305.1

Similar proteinsi

Entry informationi

Entry nameiNSP4_ROTWI
AccessioniPrimary (citable) accession number: B3SRY0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 14, 2009
Last sequence update: September 2, 2008
Last modified: April 25, 2018
This is version 31 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

Complete proteome
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Main funding by: National Institutes of Health