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P04512

- NSP4_ROTS1

UniProt

P04512 - NSP4_ROTS1

Protein

Non-structural glycoprotein 4

Gene
N/A
Organism
Rotavirus A (strain SA11-Both G3-P5B[2]-I2-R2-C5-M5-A5-N2-T5-E2-H5) (RV-A) (Simian Agent 11 (strain Both))
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 84 (01 Oct 2014)
      Sequence version 1 (13 Aug 1987)
      Previous versions | rss
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    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.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sitei111 – 1122CleavageSequence Analysis
    Metal bindingi120 – 1201Calcium; shared with all tetrameric partners; partial
    Metal bindingi123 – 1231Calcium; shared with all tetrameric partners

    GO - Molecular functioni

    1. metal ion binding Source: UniProtKB-KW

    GO - Biological processi

    1. pathogenesis Source: UniProtKB-KW
    2. viral process Source: UniProtKB-KW

    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 SA11-Both G3-P5B[2]-I2-R2-C5-M5-A5-N2-T5-E2-H5) (RV-A) (Simian Agent 11 (strain Both))
    Taxonomic identifieri37137 [NCBI]
    Taxonomic lineageiVirusesdsRNA virusesReoviridaeSedoreovirinaeRotavirusRotavirus A
    Virus hostiMacaca mulatta (Rhesus macaque) [TaxID: 9544]
    ProteomesiUP000007180: Genome

    Subcellular locationi

    Chain Non-structural glycoprotein 4 : Host rough endoplasmic reticulum membrane By similarity; Single-pass type III membrane protein By similarity. Host membranehost caveola; Single-pass type III membrane protein. 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.

    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

    Keywords - Cellular componenti

    Host endoplasmic reticulum, Host membrane, Membrane, Secreted

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi63 – 631C → 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 Publication
    Mutagenesisi71 – 711C → 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 Publication
    Mutagenesisi120 – 1201E → A: Complete loss of interaction with integrin ITGA2. 1 Publication
    Mutagenesisi166 – 1661Y → I: Loss of ICP-binding activity. 1 Publication
    Mutagenesisi174 – 1752Missing: Abolishes receptor activity.
    Mutagenesisi175 – 1751M → G, K or I: Abolishes receptor activity. 1 Publication
    Mutagenesisi175 – 1751Missing: Abolishes receptor activity. No effect on subcellular location. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 175175Non-structural glycoprotein 4PRO_0000149628Add
    BLAST

    Amino acid modifications

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

    Post-translational modificationi

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

    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.7 Publications

    Protein-protein interaction databases

    DIPiDIP-46136N.

    Structurei

    Secondary structure

    1
    175
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi96 – 13641

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1G1IX-ray2.00A/B95-137[»]
    1G1JX-ray1.86A/B95-137[»]
    2O1KX-ray1.67A/B95-146[»]
    ProteinModelPortaliP04512.
    SMRiP04512. Positions 95-137.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP04512.

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 2828LumenalAdd
    BLAST
    Topological domaini52 – 175124CytoplasmicAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei29 – 5123HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni7 – 2115HydrophobicBy similarityAdd
    BLAST
    Regioni67 – 8519HydrophobicBy similarityAdd
    BLAST
    Regioni85 – 12339Endoplasmic reticulum retention signalSequence AnalysisAdd
    BLAST
    Regioni114 – 13522Interaction with CAV1By similarityAdd
    BLAST
    Regioni122 – 17554Required for interaction with microtubulesAdd
    BLAST
    Regioni159 – 17517ICP binding domainAdd
    BLAST

    Coiled coil

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Coiled coili85 – 11733Sequence AnalysisAdd
    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.

    Sequence similaritiesi

    Belongs to the rotavirus NSP4 family.Curated

    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.

    P04512-1 [UniParc]FASTAAdd to Basket

    « Hide

    MEKLTDLNYT LSVITLMNNT LHTILEDPGM AYFPYIASVL TGLFALNKAS    50
    IPTMKIALKT SKCSYKVVKY CIVTIFNTLL KLAGYKEQIT TKDEIEKQMD 100
    RVVKEMRRQL EMIDKLTTRE IEQVELLKRI YDKLTVQTTG EIDMTKEINQ 150
    KNVRTLEEWE SGKNPYEPRE VTAAM 175
    Length:175
    Mass (Da):20,267
    Last modified:August 13, 1987 - v1
    Checksum:i1E72A3223C567309
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    K01138 Genomic RNA. Translation: AAA47291.1.
    PIRiA04140. VGXRTS.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    K01138 Genomic RNA. Translation: AAA47291.1 .
    PIRi A04140. VGXRTS.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1G1I X-ray 2.00 A/B 95-137 [» ]
    1G1J X-ray 1.86 A/B 95-137 [» ]
    2O1K X-ray 1.67 A/B 95-146 [» ]
    ProteinModelPortali P04512.
    SMRi P04512. Positions 95-137.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    DIPi DIP-46136N.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Miscellaneous databases

    EvolutionaryTracei P04512.

    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. "Coding assignment and nucleotide sequence of simian rotavirus SA11 gene segment 10: location of glycosylation sites suggests that the signal peptide is not cleaved."
      Both G.W., Siegman L.J., Bellamy A.R., Atkinson P.H.
      J. Virol. 48:335-339(1983) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA], SUBCELLULAR LOCATION, CARBOHYDRATE STRUCTURE, GLYCOSYLATION AT ASN-8 AND ASN-18.
    2. "A functional NSP4 enterotoxin peptide secreted from rotavirus-infected cells."
      Zhang M., Zeng C.Q.-Y., Morris A.P., Estes M.K.
      J. Virol. 74:11663-11670(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 112-120, PROTEOLYTIC CLEAVAGE, FUNCTION.
    3. "Transient expression and mutational analysis of the rotavirus intracellular receptor: the C-terminal methionine residue is essential for ligand binding."
      Taylor J.A., Meyer J.C., Legge M.A., O'Brien J.A., Street J.E., Lord V.J., Bergmann C.C., Bellamy A.R.
      J. Virol. 66:3566-3572(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, MUTAGENESIS OF CYS-63; CYS-71; MET-175 AND 174-ALA--MET-175.
    4. "The rotavirus nonstructural glycoprotein NSP4 mobilizes Ca2+ from the endoplasmic reticulum."
      Tian P., Estes M.K., Hu Y., Ball J.M., Zeng C.Q.-Y., Schilling W.P.
      J. Virol. 69:5763-5772(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    5. "The cytoplasmic tail of NSP4, the endoplasmic reticulum-localized non-structural glycoprotein of rotavirus, contains distinct virus binding and coiled coil domains."
      Taylor J.A., O'Brien J.A., Yeager M.
      EMBO J. 15:4469-4476(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: COILED-COIL DOMAIN.
    6. "The rotavirus enterotoxin NSP4 mobilizes intracellular calcium in human intestinal cells by stimulating phospholipase C-mediated inositol 1,4,5-trisphosphate production."
      Dong Y., Zeng C.Q.-Y., Ball J.M., Estes M.K., Morris A.P.
      Proc. Natl. Acad. Sci. U.S.A. 94:3960-3965(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    7. "Immobilization of the early secretory pathway by a virus glycoprotein that binds to microtubules."
      Xu A., Bellamy A.R., Taylor J.A.
      EMBO J. 19:6465-6474(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH MICROTUBULES, SUBCELLULAR LOCATION.
    8. "Probing the structure of rotavirus NSP4: a short sequence at the extreme C terminus mediates binding to the inner capsid particle."
      O'Brien J.A., Taylor J.A., Bellamy A.R.
      J. Virol. 74:5388-5394(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH ICP, MUTAGENESIS OF TYR-166.
    9. "A cytoplasmic region of the NSP4 enterotoxin of rotavirus is involved in retention in the endoplasmic reticulum."
      Mirazimi A., Magnusson K.-E., Svensson L.
      J. Gen. Virol. 84:875-883(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: ER RETENTION SIGNAL.
    10. "The rotavirus enterotoxin NSP4 directly interacts with the caveolar structural protein caveolin-1."
      Parr R.D., Storey S.M., Mitchell D.M., McIntosh A.L., Zhou M., Mir K.D., Ball J.M.
      J. Virol. 80:2842-2854(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HUMAN CAV1, SUBCELLULAR LOCATION.
    11. "Rotavirus NSP4 induces a novel vesicular compartment regulated by calcium and associated with viroplasms."
      Berkova Z., Crawford S.E., Trugnan G., Yoshimori T., Morris A.P., Estes M.K.
      J. Virol. 80:6061-6071(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION.
    12. "Full-length, glycosylated NSP4 is localized to plasma membrane caveolae by a novel raft isolation technique."
      Storey S.M., Gibbons T.F., Williams C.V., Parr R.D., Schroeder F., Ball J.M.
      J. Virol. 81:5472-5483(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HUMAN CAV1, SUBCELLULAR LOCATION, GLYCOSYLATION.
      Strain: SA11-4F.
    13. "Inaugural article: integrins alpha1beta1 and alpha2beta1 are receptors for the rotavirus enterotoxin."
      Seo N.-S., Zeng C.Q.-Y., Hyser J.M., Utama B., Crawford S.E., Kim K.J., Hoeoek M., Estes M.K.
      Proc. Natl. Acad. Sci. U.S.A. 105:8811-8818(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HUMAN INTEGRIN ITGA1/ITGB1 HETERODIMER, INTERACTION WITH HUMAN INTEGRIN ITGA2/ITGB1 HETERODIMER, MUTAGENESIS OF GLU-120.
    14. "Crystal structure of the oligomerization domain of NSP4 from rotavirus reveals a core metal-binding site."
      Bowman G.D., Nodelman I.M., Levy O., Lin S.L., Tian P., Zamb T.J., Udem S.A., Venkataraghavan B., Schutt C.E.
      J. Mol. Biol. 304:861-871(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.86 ANGSTROMS) OF 95-137 IN COMPLEX WITH CALCIUM OR STRONTIUM, METAL-BINDING AT GLN-123 AND GLU-120, SUBUNIT.

    Entry informationi

    Entry nameiNSP4_ROTS1
    AccessioniPrimary (citable) accession number: P04512
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 13, 1987
    Last sequence update: August 13, 1987
    Last modified: October 1, 2014
    This is version 84 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.By similarity

    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.Curated

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing

    Documents

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

    External Data

    Dasty 3