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Protein

Non-structural glycoprotein 4

Gene
N/A
Organism
Rotavirus C (strain RVC/Pig/United States/Cowden/1980) (RV-C)
Status
Reviewed-Annotation score: -Experimental evidence at transcript 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 cytoplasmic 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

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

Names & Taxonomyi

Protein namesi
Recommended name:
Non-structural glycoprotein 4UniRule annotation
Short name:
NSP4UniRule annotation
Alternative name(s):
NCVP5UniRule annotation
NS28UniRule annotation
OrganismiRotavirus C (strain RVC/Pig/United States/Cowden/1980) (RV-C)
Taxonomic identifieri10916 [NCBI]
Taxonomic lineageiVirusesdsRNA virusesReoviridaeSedoreovirinaeRotavirus
Virus hostiSus scrofa (Pig) [TaxID: 9823]
Proteomesi
  • UP000008175 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 – 15LumenalUniRule annotationAdd BLAST15
Transmembranei16 – 30Helical; Signal-anchor for type III membrane proteinUniRule annotationAdd BLAST15
Topological domaini31 – 150CytoplasmicUniRule annotationAdd BLAST120

GO - Cellular componenti

Keywords - Cellular componenti

Host endoplasmic reticulum, Host membrane, Membrane, Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003698911 – 150Non-structural glycoprotein 4Add BLAST150

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi5N-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

Family & Domainsi

Sequence similaritiesi

Belongs to the rotavirus NSP4 family.UniRule annotation

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

OrthoDBiVOG090002KK

Family and domain databases

HAMAPiMF_04091 ROTA_NSP4, 1 hit

Sequencei

Sequence statusi: Complete.

Q9YS17-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEFINQTFFS DYSEGKIDTI PYALGIVLAL TNGSRILKFI NLLISLLRKF
60 70 80 90 100
IITSKTVIGK FKIENNTSHQ NDDIHKEYEE VMKQMREMRV HVTALFDSIH
110 120 130 140 150
KDNMEWRMSE SIRREKKREM KASTAENEVK IHTNDVNICD TSGLETEVCL
Length:150
Mass (Da):17,489
Last modified:May 1, 1999 - v1
Checksum:i5093C34FEFBE8FC2
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti50F → L in strain: Cowden-virulent. 1
Natural varianti97D → N in strain: Cowden-virulent. 1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF093202 mRNA Translation: AAC83711.1
AF093203 mRNA Translation: AAC83712.1

Similar proteinsi

Entry informationi

Entry nameiNSP4_ROTPC
AccessioniPrimary (citable) accession number: Q9YS17
Secondary accession number(s): Q9YS18
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 14, 2009
Last sequence update: May 1, 1999
Last modified: June 20, 2018
This is version 35 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

Documents

  1. SIMILARITY comments
    Index of protein domains and families

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