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 27-MAR-2024, entry version 73. 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; OC Phlebovirus riftense. 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; Interferon antiviral system evasion; KW Phosphoprotein; Reference proteome; 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 //