NSS_RVFVZ
ID NSS_RVFVZ Reviewed; 265 AA.
AC P21698; A2SZX2;
DT 01-MAY-1991, integrated into UniProtKB/Swiss-Prot.
DT 05-JUN-2019, sequence version 2.
DT 03-AUG-2022, entry version 70.
DE RecName: Full=Non-structural protein S;
DE Short=NSs;
GN Name=NSS;
OS Rift valley fever virus (strain ZH-548 M12) (RVFV).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC Ellioviricetes; Bunyavirales; Phenuiviridae; Phlebovirus.
OX NCBI_TaxID=11589;
OH NCBI_TaxID=7158; Aedes.
OH NCBI_TaxID=9913; Bos taurus (Bovine).
OH NCBI_TaxID=297284; Bos taurus x Bison bison (beefalo).
OH NCBI_TaxID=9837; Camelus bactrianus (Bactrian camel).
OH NCBI_TaxID=9925; Capra hircus (Goat).
OH NCBI_TaxID=9606; Homo sapiens (Human).
OH NCBI_TaxID=9940; Ovis aries (Sheep).
OH NCBI_TaxID=29031; Phlebotomus papatasi (Sandfly).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=1846496; DOI=10.1016/0042-6822(91)90087-r;
RA Giorgi C., Accardi L., Nicoletti L., Gro M.C., Takehara K., Hilditch C.,
RA Morikawa S., Bishop D.H.L.;
RT "Sequences and coding strategies of the S RNAs of Toscana and Rift Valley
RT fever viruses compared to those of Punta Toro, Sicilian Sandfly fever, and
RT Uukuniemi viruses.";
RL Virology 180:738-753(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC STRAIN=2250/74, MgH824, ZH-501, and ZH-548;
RX PubMed=17192303; DOI=10.1128/JVI.02095-06;
RA Bird B.H., Khristova M.L., Rollin P.E., Ksiazek T.G., Nichol S.T.;
RT "Complete genome analysis of 33 ecologically and biologically diverse Rift
RT Valley fever virus strains reveals widespread virus movement and low
RT genetic diversity due to recent common ancestry.";
RL J. Virol. 81:2805-2816(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC STRAIN=272660;
RX PubMed=28638845; DOI=10.1093/ofid/ofx087;
RA Bob N.S., Ba H., Fall G., Ishagh E., Diallo M.Y., Sow A., Sembene P.M.,
RA Faye O., El Kouri B., Sidi M.L., Sall A.A.;
RT "Detection of the Northeastern African Rift Valley Fever Virus Lineage
RT During the 2015 Outbreak in Mauritania.";
RL Open Forum Infect. Dis. 4:OFX087-OFX087(2017).
RN [4]
RP SUBCELLULAR LOCATION.
RX PubMed=7108491; DOI=10.1099/0022-1317-60-2-381;
RA Struthers J.K., Swanepoel R.;
RT "Identification of a major non-structural protein in the nuclei of Rift
RT Valley fever virus-infected cells.";
RL J. Gen. Virol. 60:381-384(1982).
RN [5]
RP SUBCELLULAR LOCATION, FUNCTION, SUBUNIT, PHOSPHORYLATION AT SER-252 AND
RP SER-256, AND DOMAIN.
RX PubMed=10233964; DOI=10.1128/jvi.73.6.5018-5025.1999;
RA Yadani F.Z., Kohl A., Prehaud C., Billecocq A., Bouloy M.;
RT "The carboxy-terminal acidic domain of Rift Valley Fever virus NSs protein
RT is essential for the formation of filamentous structures but not for the
RT nuclear localization of the protein.";
RL J. Virol. 73:5018-5025(1999).
RN [6]
RP FUNCTION.
RX PubMed=19751406; DOI=10.1111/j.1749-6632.2009.05054.x;
RA Ikegami T., Narayanan K., Won S., Kamitani W., Peters C.J., Makino S.;
RT "Dual functions of Rift Valley fever virus NSs protein: inhibition of host
RT mRNA transcription and post-transcriptional downregulation of protein
RT kinase PKR.";
RL Ann. N. Y. Acad. Sci. 1171:E75-E85(2009).
RN [7]
RP FUNCTION.
RX PubMed=19211744; DOI=10.1128/jvi.02148-08;
RA Habjan M., Pichlmair A., Elliott R.M., Overby A.K., Glatter T.,
RA Gstaiger M., Superti-Furga G., Unger H., Weber F.;
RT "NSs protein of rift valley fever virus induces the specific degradation of
RT the double-stranded RNA-dependent protein kinase.";
RL J. Virol. 83:4365-4375(2009).
RN [8]
RP FUNCTION.
RX PubMed=19197350; DOI=10.1371/journal.ppat.1000287;
RA Ikegami T., Narayanan K., Won S., Kamitani W., Peters C.J., Makino S.;
RT "Rift Valley fever virus NSs protein promotes post-transcriptional
RT downregulation of protein kinase PKR and inhibits eIF2alpha
RT phosphorylation.";
RL PLoS Pathog. 5:E1000287-E1000287(2009).
RN [9]
RP FUNCTION.
RX PubMed=21543505; DOI=10.1128/jvi.02255-10;
RA Kalveram B., Lihoradova O., Ikegami T.;
RT "NSs protein of rift valley fever virus promotes posttranslational
RT downregulation of the TFIIH subunit p62.";
RL J. Virol. 85:6234-6243(2011).
RN [10]
RP FUNCTION, AND MUTAGENESIS OF ARG-173.
RX PubMed=23063407; DOI=10.1016/j.virol.2012.09.031;
RA Kalveram B., Lihoradova O., Indran S.V., Lokugamage N., Head J.A.,
RA Ikegami T.;
RT "Rift Valley fever virus NSs inhibits host transcription independently of
RT the degradation of dsRNA-dependent protein kinase PKR.";
RL Virology 435:415-424(2013).
RN [11]
RP INTERACTION WITH HOST FBXO3 ISOFORMS 1 AND 2, AND FUNCTION.
RX PubMed=24403578; DOI=10.1128/jvi.02914-13;
RA Kainulainen M., Habjan M., Hubel P., Busch L., Lau S., Colinge J.,
RA Superti-Furga G., Pichlmair A., Weber F.;
RT "Virulence factor NSs of rift valley fever virus recruits the F-box protein
RT FBXO3 to degrade subunit p62 of general transcription factor TFIIH.";
RL J. Virol. 88:3464-3473(2014).
RN [12]
RP FUNCTION, INTERACTION WITH HOST FBXW11, AND DOMAIN.
RX PubMed=26837067; DOI=10.1371/journal.ppat.1005437;
RA Mudhasani R., Tran J.P., Retterer C., Kota K.P., Whitehouse C.A.,
RA Bavari S.;
RT "Protein Kinase R degradation is essential for Rift valley fever Virus
RT infection and is regulated by SKP1-CUL1-F-box (SCF)FBXW11-NSs E3 ligase.";
RL PLoS Pathog. 12:E1005437-E1005437(2016).
RN [13]
RP FUNCTION.
RC STRAIN=MP12, and ZH548;
RX PubMed=33087469; DOI=10.1128/jvi.01768-20;
RA Bamia A., Marcato V., Boissiere M., Mansuroglu Z., Tamietti C., Romani M.,
RA Simon D., Tian G., Niedergang F., Panthier J.J., Flamand M., Soues S.,
RA Bonnefoy E.;
RT "The NSs Protein Encoded by the Virulent Strain of Rift Valley Fever Virus
RT Targets the Expression of Abl2 and the Actin Cytoskeleton of the Host,
RT Affecting Cell Mobility, Cell Shape, and Cell-Cell Adhesion.";
RL J. Virol. 95:0-0(2020).
RN [14]
RP FUNCTION.
RX PubMed=32612175; DOI=10.1038/s41467-020-17101-y;
RA Leger P., Nachman E., Richter K., Tamietti C., Koch J., Burk R., Kummer S.,
RA Xin Q., Stanifer M., Bouloy M., Boulant S., Kraeusslich H.G.,
RA Montagutelli X., Flamand M., Nussbaum-Krammer C., Lozach P.Y.;
RT "NSs amyloid formation is associated with the virulence of Rift Valley
RT fever virus in mice.";
RL Nat. Commun. 11:3281-3281(2020).
RN [15]
RP STRUCTURE BY NMR OF 247-265, INTERACTION WITH HOST GTF2H1, DOMAIN,
RP MUTAGENESIS OF PHE-261, AND SUBCELLULAR LOCATION.
RX PubMed=25918396; DOI=10.1073/pnas.1503688112;
RA Cyr N., de la Fuente C., Lecoq L., Guendel I., Chabot P.R., Kehn-Hall K.,
RA Omichinski J.G.;
RT "A OmegaXaV motif in the Rift Valley fever virus NSs protein is essential
RT for degrading p62, forming nuclear filaments and virulence.";
RL Proc. Natl. Acad. Sci. U.S.A. 112:6021-6026(2015).
RN [16] {ECO:0007744|PDB:5OOO}
RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 83-248, SUBUNIT, AND FUNCTION.
RX PubMed=28915104; DOI=10.7554/elife.29236;
RA Barski M., Brennan B., Miller O.K., Potter J.A., Vijayakrishnan S.,
RA Bhella D., Naismith J.H., Elliott R.M., Schwarz-Linek U.;
RT "Rift Valley fever phlebovirus NSs protein core domain structure suggests
RT molecular basis for nuclear filaments.";
RL Elife 6:0-0(2017).
CC -!- FUNCTION: Plays a role in the escape of host innate immune response by
CC promoting the degradation of host EIF2AK2/PKR and inhibiting host
CC transcription (PubMed:19751406, PubMed:19211744, PubMed:19197350).
CC Cytoplasmic NSs interacts with host FBXW11 to degrade PKR whereas
CC nuclear pool binds to host FBXO3 to target TFIIH subunit GTF2H1 for
CC proteasomal degradation with the help of the linker protein SKP1
CC (PubMed:19211744, PubMed:21543505, PubMed:23063407, PubMed:26837067).
CC Removes FBXO3 isoform 1 from the nucleus (PubMed:24403578). Forms
CC nuclear amyloid-like filaments of about 12 nm in width that may
CC sequester NSs binding partners, causing cell cycle arrest
CC (PubMed:10233964, PubMed:28915104, PubMed:32612175). Also aggragates in
CC the cytosol as short fibrils late after host cell infection
CC (PubMed:32612175). Plays a role in cell morphology and/or motility,
CC reduction of lamellipodia, cell spreading, and dissolution of adherens
CC junctions (PubMed:33087469). {ECO:0000269|PubMed:10233964,
CC ECO:0000269|PubMed:19197350, ECO:0000269|PubMed:19211744,
CC ECO:0000269|PubMed:19751406, ECO:0000269|PubMed:21543505,
CC ECO:0000269|PubMed:23063407, ECO:0000269|PubMed:24403578,
CC ECO:0000269|PubMed:26837067, ECO:0000269|PubMed:28915104,
CC ECO:0000269|PubMed:32612175, ECO:0000269|PubMed:33087469}.
CC -!- SUBUNIT: Multimerizes; forms 0.5-1 mm thick proteinaceous filaments in
CC the nucleus (PubMed:28915104, PubMed:10233964). Interacts (via omegaXaV
CC motif) with host FBXW11; this interaction is important for EIF2AK2/PKR
CC degradation (PubMed:21543505, PubMed:26837067). Interacts (via omegaXaV
CC motif) with host GTF2H1 (PubMed:25918396). Interacts with the host E3
CC ubiquitin ligase component FBXO3; this interaction is important for
CC GTF2H1 degradation (PubMed:24403578). {ECO:0000269|PubMed:10233964,
CC ECO:0000269|PubMed:21543505, ECO:0000269|PubMed:24403578,
CC ECO:0000269|PubMed:25918396, ECO:0000269|PubMed:26837067,
CC ECO:0000269|PubMed:28915104}.
CC -!- SUBCELLULAR LOCATION: Host nucleus {ECO:0000269|PubMed:10233964,
CC ECO:0000269|PubMed:25918396, ECO:0000269|PubMed:7108491}. Host
CC cytoplasm {ECO:0000269|PubMed:25918396}.
CC -!- DOMAIN: The C-terminus disordered region is involved in
CC multimerization, filament formation, but not nuclear localization
CC (PubMed:10233964). OmegaXaV motif is required for both nuclear filament
CC formation and degradation of host GTF2H1 (PubMed:25918396). This motif
CC also mediates FBXW11 binding (PubMed:26837067).
CC {ECO:0000269|PubMed:10233964, ECO:0000269|PubMed:25918396,
CC ECO:0000269|PubMed:26837067}.
CC -!- PTM: Phosphorylated. {ECO:0000269|PubMed:10233964}.
CC -!- SIMILARITY: Belongs to the phlebovirus NS-S protein family.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; X53771; CAA37788.1; -; Genomic_RNA.
DR EMBL; DQ380143; ABD38716.1; -; Genomic_RNA.
DR EMBL; KY366328; ASF20659.1; -; Genomic_RNA.
DR EMBL; EU312138; ACA14424.1; -; Genomic_RNA.
DR EMBL; EU312137; ACA14422.1; -; Genomic_RNA.
DR EMBL; EU312134; ACA14416.1; -; Genomic_RNA.
DR EMBL; EU312112; ACA14372.1; -; Genomic_RNA.
DR EMBL; EU312110; ACA14368.1; -; Genomic_RNA.
DR EMBL; DQ380149; ABD38728.1; -; Genomic_RNA.
DR EMBL; DQ380148; ABD38726.1; -; Genomic_RNA.
DR EMBL; DQ380147; ABD38724.1; -; Genomic_RNA.
DR EMBL; DQ380144; ABD38718.1; -; Genomic_RNA.
DR PIR; C38552; MNVURV.
DR RefSeq; YP_003848706.1; NC_014395.1.
DR PDB; 2N0Y; NMR; -; B=247-265.
DR PDB; 5OOO; X-ray; 2.20 A; A/B=83-248.
DR PDBsum; 2N0Y; -.
DR PDBsum; 5OOO; -.
DR SMR; P21698; -.
DR IntAct; P21698; 26.
DR GeneID; 9538292; -.
DR KEGG; vg:9538292; -.
DR Proteomes; UP000002477; Genome.
DR GO; GO:0030430; C:host cell cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0030291; F:protein serine/threonine kinase inhibitor activity; IEA:UniProtKB-KW.
DR GO; GO:0039689; P:negative stranded viral RNA replication; IMP:CACAO.
DR GO; GO:0039657; P:suppression by virus of host gene expression; IMP:CACAO.
DR GO; GO:0039580; P:suppression by virus of host PKR signaling; IEA:UniProtKB-KW.
DR GO; GO:0039653; P:suppression by virus of host transcription; IMP:CACAO.
DR GO; GO:0039602; P:suppression by virus of host transcription initiation from RNA polymerase II promoter; IDA:CACAO.
DR GO; GO:0039501; P:suppression by virus of host type I interferon production; IMP:CACAO.
DR GO; GO:0039502; P:suppression by virus of host type I interferon-mediated signaling pathway; IEA:UniProtKB-KW.
DR InterPro; IPR039434; NSs-like.
DR InterPro; IPR024376; RVFV_non-structural.
DR Pfam; PF11073; NSs; 1.
DR PIRSF; PIRSF003956; NS-S_PhleboV; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Eukaryotic host gene expression shutoff by virus;
KW Eukaryotic host transcription shutoff by virus; Host cytoplasm;
KW Host gene expression shutoff by virus; Host nucleus;
KW Host-virus interaction;
KW Inhibition of eukaryotic host transcription initiation by virus;
KW Inhibition of host innate immune response by virus;
KW Inhibition of host interferon signaling pathway by virus;
KW Inhibition of host PKR by virus; Phosphoprotein; Reference proteome;
KW Viral immunoevasion.
FT CHAIN 1..265
FT /note="Non-structural protein S"
FT /id="PRO_0000221979"
FT REGION 249..265
FT /note="Disordered"
FT /evidence="ECO:0000269|PubMed:28915104"
FT MOTIF 261..265
FT /note="OmegaXaV"
FT /evidence="ECO:0000269|PubMed:25918396"
FT MOD_RES 252
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:10233964"
FT MOD_RES 256
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:10233964"
FT MUTAGEN 173
FT /note="R->A: Complete loss of binding to host EIF2AK2/PKR."
FT /evidence="ECO:0000269|PubMed:23063407"
FT MUTAGEN 261
FT /note="F->P,S: Loss of formation of nuclear filaments and
FT GTF2H1 degradation. Decreased virulence."
FT CONFLICT 160
FT /note="V -> A (in Ref. 1; CAA37788)"
FT /evidence="ECO:0000305|PubMed:1846496"
FT HELIX 87..93
FT /evidence="ECO:0007829|PDB:5OOO"
FT HELIX 98..102
FT /evidence="ECO:0007829|PDB:5OOO"
FT HELIX 105..110
FT /evidence="ECO:0007829|PDB:5OOO"
FT TURN 111..116
FT /evidence="ECO:0007829|PDB:5OOO"
FT HELIX 121..126
FT /evidence="ECO:0007829|PDB:5OOO"
FT HELIX 134..149
FT /evidence="ECO:0007829|PDB:5OOO"
FT HELIX 155..173
FT /evidence="ECO:0007829|PDB:5OOO"
FT HELIX 177..179
FT /evidence="ECO:0007829|PDB:5OOO"
FT HELIX 185..206
FT /evidence="ECO:0007829|PDB:5OOO"
FT HELIX 213..228
FT /evidence="ECO:0007829|PDB:5OOO"
FT HELIX 230..233
FT /evidence="ECO:0007829|PDB:5OOO"
FT HELIX 253..256
FT /evidence="ECO:0007829|PDB:2N0Y"
SQ SEQUENCE 265 AA; 29931 MW; CD65B9FA3E614435 CRC64;
MDYFPVISVD LQSGRRVVSV EYFRGDGPPR IPYSMVGPCC VFLMHHRPSH EVRLRFSDFY
NVGEFPYRVG LGDFASNVAP PPAKPFQRLI DLIGHMTLSD FTRFPNLKEA ISWPLGEPSL
AFFDLSSTRV HRNDDIRRDQ IATLAMRSCK ITNDLEDSFV GLHRMIATEA ILRGIDLCLL
PGFDLMYEVA HVQCVRLLQA AKEDISNAVV PNSALIVLME ESLMLRSSLP SMMGRNNWIP
VIPPIPDVEM ESEEESDDDG FVEVD
