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Protein

Non-structural glycoprotein 4

Gene
N/A
Organism
Rotavirus A (strain RVA/SA11-Both/G3P5B[2]) (RV-A) (Simian Agent 11 (strain Both))
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 annotation3 Publications
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 annotation2 Publications

Caution

A candidate enterotoxigenic cleaved form of the protein has been suggested [PubMed:11090165], but it remains unclear whether this truncated form constitutes an active enterotoxin in vivo.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi120Calcium; shared with all tetrameric partners; partialUniRule annotation1
Metal bindingi123Calcium; shared with all tetrameric partnersUniRule 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

Protein family/group databases

TCDBi1.A.94.1.1 the rotavirus non-structural glycoprotein 4 viroporin (nsp4) family

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/SA11-Both/G3P5B[2]) (RV-A) (Simian Agent 11 (strain Both))
Taxonomic identifieri37137 [NCBI]
Taxonomic lineageiVirusesdsRNA virusesReoviridaeSedoreovirinaeRotavirusRotavirus A
Virus hostiMacaca mulatta (Rhesus macaque) [TaxID: 9544]
Proteomesi
  • UP000007180 Componenti: Genome

Subcellular locationi

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

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi63C → S: No effect on receptor activity nor on oligomer formation. No effect on receptor activity nor on oligomer formation; when associated with C-71. 1 Publication1
Mutagenesisi71C → S: No effect on receptor activity nor on oligomer formation. No effect on receptor activity nor on oligomer formation; when associated with C-63. 1 Publication1
Mutagenesisi120E → A: Complete loss of interaction with integrin ITGA2. 1 Publication1
Mutagenesisi166Y → I: Loss of ICP-binding activity. 1 Publication1
Mutagenesisi174 – 175Missing : Abolishes receptor activity. 1 Publication2
Mutagenesisi175M → G, K or I: Abolishes receptor activity. 1 Publication1
Mutagenesisi175Missing : Abolishes receptor activity. No effect on subcellular location. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001496281 – 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

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

Keywords - PTMi

Glycoprotein

Proteomic databases

PRIDEiP04512

PTM databases

iPTMnetiP04512

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 (PubMed:18587047). Interaction with microtubules blocks trafficking to the Golgi apparatus (PubMed:11101519).UniRule annotation7 Publications

Binary interactionsi

Show more details

Protein-protein interaction databases

DIPiDIP-46136N
IntActiP04512, 2 interactors

Structurei

Secondary structure

1175
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi96 – 136Combined sources41

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1G1IX-ray2.00A/B95-137[»]
1G1JX-ray1.86A/B95-137[»]
2O1KX-ray1.67A/B95-146[»]
ProteinModelPortaliP04512
SMRiP04512
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP04512

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni122 – 175Required for interaction with microtubulesAdd BLAST54
Regioni159 – 175ICP binding domainAdd BLAST17

Domaini

Binds 1 calcium ion per tetramer.UniRule annotation
The coiled coil region mediates oligomerization.

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.

P04512-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEKLTDLNYT LSVITLMNNT LHTILEDPGM AYFPYIASVL TGLFALNKAS
60 70 80 90 100
IPTMKIALKT SKCSYKVVKY CIVTIFNTLL KLAGYKEQIT TKDEIEKQMD
110 120 130 140 150
RVVKEMRRQL EMIDKLTTRE IEQVELLKRI YDKLTVQTTG EIDMTKEINQ
160 170
KNVRTLEEWE SGKNPYEPRE VTAAM
Length:175
Mass (Da):20,267
Last modified:August 13, 1987 - v1
Checksum:i1E72A3223C567309
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
K01138 Genomic RNA Translation: AAA47291.1
PIRiA04140 VGXRTS

Similar proteinsi

Entry informationi

Entry nameiNSP4_ROTS1
AccessioniPrimary (citable) accession number: P04512
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 13, 1987
Last sequence update: August 13, 1987
Last modified: April 25, 2018
This is version 106 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, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

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