ID SIGM3_REOVD Reviewed; 365 AA. AC P03527; A4ZY29; Q99AV2; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 22-JUL-2008, sequence version 2. DT 27-MAR-2024, entry version 111. DE RecName: Full=Outer capsid protein sigma-3; DE Short=Sigma3; GN Name=S4; OS Reovirus type 3 (strain Dearing) (T3D) (Mammalian orthoreovirus 3). OC Viruses; Riboviria; Orthornavirae; Duplornaviricota; Resentoviricetes; OC Reovirales; Spinareoviridae; Orthoreovirus; Mammalian orthoreovirus. OX NCBI_TaxID=10886; OH NCBI_TaxID=40674; Mammalia. RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA]. RX PubMed=6492267; DOI=10.1128/jvi.52.3.984-987.1984; RA Giantini M., Seliger L.S., Furuichi Y., Shatkin A.J.; RT "Reovirus type 3 genome segment S4: nucleotide sequence of the gene RT encoding a major virion surface protein."; RL J. Virol. 52:984-987(1984). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA]. RC STRAIN=Isolate D-EA1, and Isolate D-EA3; RX PubMed=11238846; DOI=10.1128/jvi.75.7.3197-3206.2001; RA Ebert D.H., Wetzel J.D., Brumbaugh D.E., Chance S.R., Stobie L.E., RA Baer G.S., Dermody T.S.; RT "Adaptation of reovirus to growth in the presence of protease inhibitor E64 RT segregates with a mutation in the carboxy terminus of viral outer-capsid RT protein sigma3."; RL J. Virol. 75:3197-3206(2001). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA]. RC STRAIN=Infectious clone; RX PubMed=18005692; DOI=10.1016/j.chom.2007.03.003; RA Kobayashi T., Antar A.A., Boehme K.W., Danthi P., Eby E.A., Guglielmi K.M., RA Holm G.H., Johnson E.M., Maginnis M.S., Naik S., Skelton W.B., Wetzel J.D., RA Wilson G.J., Chappell J.D., Dermody T.S.; RT "A plasmid-based reverse genetics system for animal double-stranded RNA RT viruses."; RL Cell Host Microbe 1:147-157(2007). RN [4] RP FUNCTION. RX PubMed=9268168; DOI=10.1006/viro.1997.8664; RA Yue Z., Shatkin A.J.; RT "Double-stranded RNA-dependent protein kinase (PKR) is regulated by RT reovirus structural proteins."; RL Virology 234:364-371(1997). RN [5] RP PROTEOLYTIC CLEAVAGE, AND MUTAGENESIS OF TYR-354. RX PubMed=12208961; DOI=10.1128/jvi.76.19.9832-9843.2002; RA Wilson G.J., Nason E.L., Hardy C.S., Ebert D.H., Wetzel J.D., RA Venkataram Prasad B.V., Dermody T.S.; RT "A single mutation in the carboxy terminus of reovirus outer-capsid protein RT sigma 3 confers enhanced kinetics of sigma 3 proteolysis, resistance to RT inhibitors of viral disassembly, and alterations in sigma 3 structure."; RL J. Virol. 76:9832-9843(2002). RN [6] RP SUBCELLULAR LOCATION. RX PubMed=12719587; DOI=10.1128/jvi.77.10.5948-5963.2003; RA Becker M.M., Peters T.R., Dermody T.S.; RT "Reovirus sigma NS and mu NS proteins form cytoplasmic inclusion structures RT in the absence of viral infection."; RL J. Virol. 77:5948-5963(2003). RN [7] RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS), AND ZINC-FINGER. RX PubMed=11230122; DOI=10.1093/emboj/20.5.979; RA Olland A.M., Jane-Valbuena J., Schiff L.A., Nibert M.L., Harrison S.C.; RT "Structure of the reovirus outer capsid and dsRNA-binding protein sigma3 at RT 1.8 A resolution."; RL EMBO J. 20:979-989(2001). CC -!- FUNCTION: Stimulates translation by blocking the activation of the CC dsRNA-dependent protein kinase EIF2AK2/PKR, thereby inhibiting the host CC interferon response. Sigma3 prevents the activation of EIF2AK2 by CC competing with the kinase for dsRNA-binding. CC {ECO:0000269|PubMed:9268168}. CC -!- FUNCTION: The viral outer shell polypeptides, of which sigma-3 is one, CC impose structural constraints that prevent elongation of nascent CC transcripts by the RNA-dependent RNA polymerase lambda-3. CC {ECO:0000250}. CC -!- SUBUNIT: Heterohexamer of three sigma-3 and three Mu-1 proteins (By CC similarity). The RNA-binding form is probably a homodimer. CC {ECO:0000250}. CC -!- SUBCELLULAR LOCATION: Virion. Host cytoplasm CC {ECO:0000269|PubMed:12719587}. Host nucleus CC {ECO:0000269|PubMed:12719587}. Note=Found in the outer capsid. Each CC subunit is positioned with the small lobe anchoring it to the protein CC mu1 on the surface of the virion, and the large lobe, the site of CC initial cleavages during entry-related proteolytic disassembly, CC protruding outwards. CC -!- PTM: Cleaved during virus the endosomal proteolytic disassembly of the CC outer capsid. {ECO:0000269|PubMed:12208961}. CC -!- SIMILARITY: Belongs to the orthoreovirus sigma-3 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; K02739; AAA47283.1; -; Genomic_RNA. DR EMBL; AF332137; AAK07648.1; -; Genomic_RNA. DR EMBL; EF494444; ABP48922.1; -; Genomic_RNA. DR PIR; A04127; MNXRS3. DR PDB; 1FN9; X-ray; 1.80 A; A/B=1-365. DR PDB; 7LUP; EM; 6.20 A; Q=1-365. DR PDBsum; 1FN9; -. DR PDBsum; 7LUP; -. DR EMDB; EMD-13149; -. DR EMDB; EMD-13150; -. DR EMDB; EMD-23526; -. DR SMR; P03527; -. DR EvolutionaryTrace; P03527; -. DR Proteomes; UP000006373; 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:0039624; C:viral outer capsid; IEA:UniProtKB-KW. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0030291; F:protein serine/threonine kinase inhibitor activity; IEA:UniProtKB-KW. DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW. DR GO; GO:0005198; F:structural molecule activity; IEA:InterPro. DR GO; GO:0039580; P:suppression by virus of host PKR signaling; IEA:UniProtKB-KW. DR GO; GO:0039502; P:suppression by virus of host type I interferon-mediated signaling pathway; IEA:UniProtKB-KW. DR GO; GO:0019058; P:viral life cycle; IEA:InterPro. DR Gene3D; 3.90.1320.10; Outer-capsid protein sigma 3, large lobe; 1. DR Gene3D; 3.90.1630.10; Outer-capsid protein sigma 3, small lobe; 1. DR InterPro; IPR000153; Reo_capsid_sigma3. DR InterPro; IPR023634; Reovirus_capsid_sigma-3_dom_sf. DR Pfam; PF00979; Reovirus_cap; 1. DR SUPFAM; SSF64465; Outer capsid protein sigma 3; 1. PE 1: Evidence at protein level; KW 3D-structure; Capsid protein; Host cytoplasm; Host nucleus; KW Host-virus interaction; 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 Metal-binding; Outer capsid protein; RNA-binding; Transcription; KW Transcription regulation; Translation regulation; Viral immunoevasion; KW Virion; Zinc; Zinc-finger. FT CHAIN 1..365 FT /note="Outer capsid protein sigma-3" FT /id="PRO_0000222752" FT ZN_FING 51..73 FT /note="CCHC-type" FT /evidence="ECO:0000269|PubMed:11230122" FT VARIANT 354 FT /note="Y -> H (in strain: Isolate D-EA1 and Isolate D-EA3; FT altered susceptibility to proteolysis during virus FT disassembly)" FT /evidence="ECO:0000269|PubMed:12208961" FT CONFLICT 133 FT /note="W -> R (in Ref. 1; AAA47283)" FT /evidence="ECO:0000305" FT CONFLICT 198 FT /note="G -> E (in Ref. 1; AAA47283)" FT /evidence="ECO:0000305" FT HELIX 8..18 FT /evidence="ECO:0007829|PDB:1FN9" FT TURN 19..21 FT /evidence="ECO:0007829|PDB:1FN9" FT STRAND 25..27 FT /evidence="ECO:0007829|PDB:1FN9" FT TURN 28..30 FT /evidence="ECO:0007829|PDB:1FN9" FT STRAND 41..45 FT /evidence="ECO:0007829|PDB:1FN9" FT STRAND 48..51 FT /evidence="ECO:0007829|PDB:1FN9" FT TURN 52..54 FT /evidence="ECO:0007829|PDB:1FN9" FT STRAND 57..60 FT /evidence="ECO:0007829|PDB:1FN9" FT HELIX 61..63 FT /evidence="ECO:0007829|PDB:1FN9" FT HELIX 79..111 FT /evidence="ECO:0007829|PDB:1FN9" FT HELIX 115..124 FT /evidence="ECO:0007829|PDB:1FN9" FT STRAND 126..130 FT /evidence="ECO:0007829|PDB:1FN9" FT HELIX 133..135 FT /evidence="ECO:0007829|PDB:1FN9" FT TURN 141..143 FT /evidence="ECO:0007829|PDB:1FN9" FT HELIX 159..176 FT /evidence="ECO:0007829|PDB:1FN9" FT STRAND 180..186 FT /evidence="ECO:0007829|PDB:1FN9" FT HELIX 189..192 FT /evidence="ECO:0007829|PDB:1FN9" FT HELIX 199..203 FT /evidence="ECO:0007829|PDB:1FN9" FT STRAND 221..223 FT /evidence="ECO:0007829|PDB:1FN9" FT HELIX 226..230 FT /evidence="ECO:0007829|PDB:1FN9" FT HELIX 232..234 FT /evidence="ECO:0007829|PDB:1FN9" FT HELIX 236..242 FT /evidence="ECO:0007829|PDB:1FN9" FT HELIX 246..249 FT /evidence="ECO:0007829|PDB:1FN9" FT HELIX 252..254 FT /evidence="ECO:0007829|PDB:1FN9" FT STRAND 259..261 FT /evidence="ECO:0007829|PDB:1FN9" FT STRAND 270..272 FT /evidence="ECO:0007829|PDB:1FN9" FT HELIX 275..277 FT /evidence="ECO:0007829|PDB:1FN9" FT STRAND 282..284 FT /evidence="ECO:0007829|PDB:1FN9" FT HELIX 288..292 FT /evidence="ECO:0007829|PDB:1FN9" FT HELIX 293..295 FT /evidence="ECO:0007829|PDB:1FN9" FT HELIX 296..305 FT /evidence="ECO:0007829|PDB:1FN9" FT HELIX 308..315 FT /evidence="ECO:0007829|PDB:1FN9" FT HELIX 319..334 FT /evidence="ECO:0007829|PDB:1FN9" FT HELIX 338..341 FT /evidence="ECO:0007829|PDB:1FN9" FT STRAND 351..354 FT /evidence="ECO:0007829|PDB:1FN9" FT STRAND 356..358 FT /evidence="ECO:0007829|PDB:1FN9" FT STRAND 362..365 FT /evidence="ECO:0007829|PDB:1FN9" SQ SEQUENCE 365 AA; 41118 MW; CF50174AA43244EB CRC64; MEVCLPNGHQ VVDLINNAFE GRVSIYSAQE GWDKTISAQP DMMVCGGAVV CMHCLGVVGS LQRKLKHLPH HRCNQQIRHQ DYVDVQFADR VTAHWKRGML SFVAQMHEMM NDVSPDDLDR VRTEGGSLVE LNWLQVDPNS MFRSIHSSWT DPLQVVDDLD TKLDQYWTAL NLMIDSSDLI PNFMMRDPSH AFNGVKLGGD ARQTQFSRTF DSRSSLEWGV MVYDYSELEH DPSKGRAYRK ELVTPARDFG HFGLSHYSRA TTPILGKMPA VFSGMLTGNC KMYPFIKGTA KLKTVRKLVE AVNHAWGVEK IRYALGPGGM TGWYNRTMQQ APIVLTPAAL TMFPDTIKFG DLNYPVMIGD PMILG //