ID POLS_SAGV Reviewed; 1253 AA. AC Q9JGK8; Q80S33; DT 30-MAY-2006, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-2000, sequence version 1. DT 05-JUN-2019, entry version 98. DE RecName: Full=Structural polyprotein; DE AltName: Full=p130; DE Contains: DE RecName: Full=Capsid protein; DE EC=3.4.21.90 {ECO:0000250|UniProtKB:P03315}; DE AltName: Full=Coat protein; DE Short=C; DE Contains: DE RecName: Full=Precursor of protein E3/E2; DE AltName: Full=p62; DE AltName: Full=pE2; DE Contains: DE RecName: Full=Assembly protein E3; DE Contains: DE RecName: Full=Spike glycoprotein E2; DE AltName: Full=E2 envelope glycoprotein; DE Contains: DE RecName: Full=6K protein; DE Contains: DE RecName: Full=Spike glycoprotein E1; DE AltName: Full=E1 envelope glycoprotein; OS Sagiyama virus (SAGV). OC Viruses; Riboviria; Togaviridae; Alphavirus. OX NCBI_TaxID=59303; OH NCBI_TaxID=7158; Aedes. OH NCBI_TaxID=7178; Culex tritaeniorhynchus (Mosquito). OH NCBI_TaxID=9796; Equus caballus (Horse). OH NCBI_TaxID=9606; Homo sapiens (Human). OH NCBI_TaxID=9823; Sus scrofa (Pig). RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA]. RX PubMed=10769079; RA Shirako Y., Yamaguchi Y.; RT "Genome structure of Sagiyama virus and its relatedness to other RT alphaviruses."; RL J. Gen. Virol. 81:1353-1360(2000). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA]. RA Kinney R.M., Pfeffer M.; RT "Nucleotide sequence analyses of the 26S mRNAs of viruses of the genus RT Alphavirus."; RL Submitted (JAN-2001) to the EMBL/GenBank/DDBJ databases. CC -!- FUNCTION: Capsid protein: Forms an icosahedral capsid with a T=4 CC symmetry composed of 240 copies of the capsid protein surrounded CC by a lipid membrane through which penetrate 80 spikes composed of CC trimers of E1-E2 heterodimers (By similarity). The capsid protein CC binds to the viral RNA genome at a site adjacent to a ribosome CC binding site for viral genome translation following genome release CC (By similarity). Possesses a protease activity that results in its CC autocatalytic cleavage from the nascent structural protein (By CC similarity). Following its self-cleavage, the capsid protein CC transiently associates with ribosomes, and within several minutes CC the protein binds to viral RNA and rapidly assembles into CC icosahedric core particles (By similarity). The resulting CC nucleocapsid eventually associates with the cytoplasmic domain of CC the spike glycoprotein E2 at the cell membrane, leading to budding CC and formation of mature virions (By similarity). In case of CC infection, new virions attach to target cells and after clathrin- CC mediated endocytosis their membrane fuses with the host endosomal CC membrane (By similarity). This leads to the release of the CC nucleocapsid into the cytoplasm, followed by an uncoating event CC necessary for the genomic RNA to become accessible (By CC similarity). The uncoating might be triggered by the interaction CC of capsid proteins with ribosomes (By similarity). Binding of CC ribosomes would release the genomic RNA since the same region is CC genomic RNA-binding and ribosome-binding (By similarity). CC {ECO:0000250|UniProtKB:P03315, ECO:0000250|UniProtKB:P03316, CC ECO:0000250|UniProtKB:P27284}. CC -!- FUNCTION: Assembly protein E3: Provides the signal sequence for CC the translocation of the precursor of protein E3/E2 to the host CC endoplasmic reticulum. Furin-cleaved E3 remains associated with CC spike glycoprotein E1 and mediates pH protection of the latter CC during the transport via the secretory pathway. After virion CC release from the host cell, the assembly protein E3 is gradually CC released in the extracellular space. CC {ECO:0000250|UniProtKB:P03315}. CC -!- FUNCTION: Spike glycoprotein E2: Plays a role in viral attachment CC to target host cell, by binding to the cell receptor. Synthesized CC as a p62 precursor which is processed by furin at the cell CC membrane just before virion budding, giving rise to E2-E1 CC heterodimer. The p62-E1 heterodimer is stable, whereas E2-E1 is CC unstable and dissociate at low pH. p62 is processed at the last CC step, presumably to avoid E1 fusion activation before its final CC export to cell surface. E2 C-terminus contains a transitory CC transmembrane that would be disrupted by palmitoylation, resulting CC in reorientation of the C-terminal tail from lumenal to CC cytoplasmic side. This step is critical since E2 C-terminus is CC involved in budding by interacting with capsid proteins. This CC release of E2 C-terminus in cytoplasm occurs lately in protein CC export, and precludes premature assembly of particles at the CC endoplasmic reticulum membrane. {ECO:0000250|UniProtKB:P03315}. CC -!- FUNCTION: 6K protein: Constitutive membrane protein involved in CC virus glycoprotein processing, cell permeabilization, and the CC budding of viral particles. Disrupts the calcium homeostasis of CC the cell, probably at the endoplasmic reticulum level. This leads CC to cytoplasmic calcium elevation. Because of its lipophilic CC properties, the 6K protein is postulated to influence the CC selection of lipids that interact with the transmembrane domains CC of the glycoproteins, which, in turn, affects the deformability of CC the bilayer required for the extreme curvature that occurs as CC budding proceeds. Present in low amount in virions, about 3% CC compared to viral glycoproteins. {ECO:0000250|UniProtKB:P03315}. CC -!- FUNCTION: Spike glycoprotein E1: Class II viral fusion protein. CC Fusion activity is inactive as long as E1 is bound to E2 in mature CC virion. After virus attachment to target cell and endocytosis, CC acidification of the endosome would induce dissociation of E1/E2 CC heterodimer and concomitant trimerization of the E1 subunits. This CC E1 trimer is fusion active, and promotes release of viral CC nucleocapsid in cytoplasm after endosome and viral membrane CC fusion. Efficient fusion requires the presence of cholesterol and CC sphingolipid in the target membrane. Fusion is optimal at levels CC of about 1 molecule of cholesterol per 2 molecules of CC phospholipids, and is specific for sterols containing a 3-beta- CC hydroxyl group. {ECO:0000250|UniProtKB:P03315}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Autocatalytic release of the core protein from the N- CC terminus of the togavirus structural polyprotein by hydrolysis CC of a -Trp-|-Ser- bond.; EC=3.4.21.90; CC Evidence={ECO:0000250|UniProtKB:P03315}; CC -!- SUBUNIT: Capsid protein: Homodimer (By similarity). Homomultimer CC (Probable). Capsid protein: Interacts with host karyopherin KPNA4; CC this interaction allows the nuclear import of the viral capsid CC protein (By similarity). Precursor of protein E3/E2: The precursor CC of protein E3/E2 and E1 form a heterodimer shortly after synthesis CC (By similarity). Spike glycoprotein E1: The precursor of protein CC E3/E2 and E1 form a heterodimer shortly after synthesis (By CC similarity). Spike glycoprotein E1: Processing of the precursor of CC protein E3/E2 into E2 and E3 results in a heterodimer of the spike CC glycoproteins E2 and E1 (By similarity). Spike glycoprotein E2: CC Processing of the precursor of protein E3/E2 into E2 and E3 CC results in a heterodimer of the spike glycoproteins E2 and E1 (By CC similarity). Spike glycoprotein E1: Spike at virion surface are CC constituted of three E2-E1 heterodimers (By similarity). Spike CC glycoprotein E2: Spike at virion surface are constituted of three CC E2-E1 heterodimers (By similarity). Spike glycoprotein E1: After CC target cell attachment and endocytosis, E1 change conformation to CC form homotrimers (By similarity). 6K protein: Interacts with spike CC glycoprotein E1 (By similarity). Spike glycoprotein E1: Interacts CC with 6K protein (By similarity). 6K protein: Interacts with spike CC glycoprotein E2 (By similarity). Spike glycoprotein E2: Interacts CC with 6K protein (By similarity). Spike glycoprotein E2: Interacts CC with host MXRA8; this interaction mediates virus entry (By CC similarity). {ECO:0000250|UniProtKB:P03315, CC ECO:0000250|UniProtKB:P03316, ECO:0000250|UniProtKB:P0DOK1, CC ECO:0000250|UniProtKB:Q8JUX5, ECO:0000305}. CC -!- SUBCELLULAR LOCATION: Capsid protein: Virion CC {ECO:0000250|UniProtKB:P03316}. Host cytoplasm CC {ECO:0000250|UniProtKB:Q8JUX5}. Host cell membrane CC {ECO:0000250|UniProtKB:P03316}. Host nucleus CC {ECO:0000250|UniProtKB:Q8JUX5}. Note=Shuttles between the CC cytoplasm and the nucleus. {ECO:0000250|UniProtKB:Q8JUX5}. CC -!- SUBCELLULAR LOCATION: Spike glycoprotein E2: Virion membrane CC {ECO:0000250|UniProtKB:Q8JUX5}; Single-pass type I membrane CC protein {ECO:0000255}. Host cell membrane CC {ECO:0000250|UniProtKB:P03316}; Single-pass type I membrane CC protein {ECO:0000250|UniProtKB:Q8JUX5}. CC -!- SUBCELLULAR LOCATION: 6K protein: Host cell membrane CC {ECO:0000250|UniProtKB:P03316}; Multi-pass membrane protein CC {ECO:0000255}. Virion membrane {ECO:0000250|UniProtKB:P03316}; CC Multi-pass membrane protein {ECO:0000255}. CC -!- SUBCELLULAR LOCATION: Spike glycoprotein E1: Virion membrane CC {ECO:0000250|UniProtKB:Q8JUX5}; Single-pass type I membrane CC protein {ECO:0000255}. Host cell membrane CC {ECO:0000250|UniProtKB:P03316, ECO:0000250|UniProtKB:Q8JUX5}; CC Single-pass type I membrane protein {ECO:0000255}. CC -!- DOMAIN: Capsid protein: The very N-terminus also plays a role in CC the particle assembly process (By similarity). The N-terminus also CC contains a nuclear localization signal and a supra nuclear export CC signal (supraNES), which is an unusually strong NES that mediates CC host CRM1 binding in the absence of RanGTP and thus can bind CRM1, CC not only in the nucleus, but also in the cytoplasm (By CC similarity). The C-terminus functions as a protease during CC translation to cleave itself from the translating structural CC polyprotein (By similarity). {ECO:0000250|UniProtKB:P03316, CC ECO:0000250|UniProtKB:P09592}. CC -!- DOMAIN: Structural polyprotein: As soon as the capsid protein has CC been autocleaved, an internal uncleaved signal peptide directs the CC remaining polyprotein to the endoplasmic reticulum. CC {ECO:0000250|UniProtKB:P03315}. CC -!- PTM: Structural polyprotein: Specific enzymatic cleavages in vivo CC yield mature proteins. Capsid protein is auto-cleaved during CC polyprotein translation, unmasking a signal peptide at the N- CC terminus of the precursor of E3/E2 (By similarity). The remaining CC polyprotein is then targeted to the host endoplasmic reticulum, CC where host signal peptidase cleaves it into pE2, 6K and E1 CC proteins. pE2 is further processed to mature E3 and E2 by host CC furin in trans-Golgi vesicle (By similarity). CC {ECO:0000250|UniProtKB:P03315}. CC -!- PTM: Spike glycoprotein E2: Palmitoylated via thioester bonds. CC These palmitoylations may induce disruption of the C-terminus CC transmembrane. This would result in the reorientation of E2 C- CC terminus from lumenal to cytoplasmic side. CC {ECO:0000250|UniProtKB:P03315}. CC -!- PTM: Spike glycoprotein E1: N-glycosylated. CC {ECO:0000250|UniProtKB:P03315}. CC -!- PTM: Spike glycoprotein E2: N-glycosylated. CC {ECO:0000250|UniProtKB:P03315}. CC -!- PTM: Assembly protein E3: N-glycosylated. CC {ECO:0000250|UniProtKB:P03315}. CC -!- PTM: 6K protein: Palmitoylated via thioester bonds. CC {ECO:0000250|UniProtKB:P03315}. CC -!- MISCELLANEOUS: Structural polyprotein: Translated from a CC subgenomic RNA synthesized during togavirus replication. CC {ECO:0000250|UniProtKB:Q86925}. 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; AB032553; BAA92847.1; -; Genomic_RNA. DR EMBL; AF339483; AAO33337.1; -; Genomic_RNA. DR SMR; Q9JGK8; -. DR MEROPS; S03.001; -. DR Proteomes; UP000007138; 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:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell. DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW. DR GO; GO:0039619; C:T=4 icosahedral viral capsid; IEA:UniProtKB-KW. DR GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell. DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW. DR GO; GO:0004252; F:serine-type endopeptidase activity; IEA:InterPro. DR GO; GO:0005198; F:structural molecule activity; IEA:InterPro. DR GO; GO:0039654; P:fusion of virus membrane with host endosome membrane; IEA:UniProtKB-KW. DR GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-KW. DR Gene3D; 2.60.40.2400; -; 1. DR Gene3D; 2.60.40.3200; -; 1. DR Gene3D; 2.60.40.350; -; 1. DR Gene3D; 2.60.98.10; -; 3. DR Gene3D; 3.30.1490.280; -; 1. DR InterPro; IPR002548; Alpha_E1_glycop. DR InterPro; IPR000936; Alpha_E2_glycop. DR InterPro; IPR002533; Alpha_E3_glycop. DR InterPro; IPR042304; Alphavir_E2_A. DR InterPro; IPR042305; Alphavir_E2_B. DR InterPro; IPR042306; Alphavir_E2_C. DR InterPro; IPR000336; Flavivir/Alphavir_Ig-like_sf. DR InterPro; IPR036253; Glycoprot_cen/dimer_sf. DR InterPro; IPR038055; Glycoprot_E_dimer_dom. DR InterPro; IPR014756; Ig_E-set. DR InterPro; IPR009003; Peptidase_S1_PA. DR InterPro; IPR000930; Peptidase_S3. DR Pfam; PF01589; Alpha_E1_glycop; 1. DR Pfam; PF00943; Alpha_E2_glycop; 1. DR Pfam; PF01563; Alpha_E3_glycop; 1. DR Pfam; PF00944; Peptidase_S3; 1. DR PRINTS; PR00798; TOGAVIRIN. DR SUPFAM; SSF50494; SSF50494; 1. DR SUPFAM; SSF56983; SSF56983; 1. DR SUPFAM; SSF81296; SSF81296; 1. DR PROSITE; PS51690; ALPHAVIRUS_CP; 1. PE 3: Inferred from homology; KW Capsid protein; Cleavage on pair of basic residues; Complete proteome; KW Disulfide bond; Fusion of virus membrane with host endosomal membrane; KW Fusion of virus membrane with host membrane; Glycoprotein; KW Host cell membrane; Host cytoplasm; Host membrane; Host nucleus; KW Host-virus interaction; Hydrolase; Lipoprotein; Membrane; Palmitate; KW Protease; RNA-binding; Serine protease; KW T=4 icosahedral capsid protein; Transmembrane; Transmembrane helix; KW Viral attachment to host cell; Viral penetration into host cytoplasm; KW Virion; Virus entry into host cell. FT CHAIN 1 268 Capsid protein. {ECO:0000250}. FT /FTId=PRO_0000238766. FT CHAIN 269 754 Precursor of protein E3/E2. FT {ECO:0000250}. FT /FTId=PRO_0000238767. FT CHAIN 269 332 Assembly protein E3. {ECO:0000250}. FT /FTId=PRO_0000238768. FT CHAIN 333 754 Spike glycoprotein E2. {ECO:0000250}. FT /FTId=PRO_0000238769. FT CHAIN 755 815 6K protein. {ECO:0000250}. FT /FTId=PRO_0000238770. FT CHAIN 816 1253 Spike glycoprotein E1. {ECO:0000250}. FT /FTId=PRO_0000238771. FT TOPO_DOM 333 694 Extracellular. {ECO:0000255}. FT TRANSMEM 695 715 Helical. {ECO:0000255}. FT TOPO_DOM 716 754 Cytoplasmic. {ECO:0000255}. FT TOPO_DOM 755 769 Extracellular. {ECO:0000255}. FT TRANSMEM 770 790 Helical. {ECO:0000255}. FT TOPO_DOM 791 792 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 793 813 Helical. {ECO:0000255}. FT TOPO_DOM 814 1227 Extracellular. {ECO:0000255}. FT TRANSMEM 1228 1248 Helical. {ECO:0000255}. FT TOPO_DOM 1249 1253 Cytoplasmic. {ECO:0000255}. FT DOMAIN 120 268 Peptidase S3. {ECO:0000255|PROSITE- FT ProRule:PRU01027}. FT REGION 1 114 Intrinsically disordered, in contact with FT genomic RNA in nucleocapsid. FT {ECO:0000255}. FT REGION 43 77 Host transcription inhibition. FT {ECO:0000250|UniProtKB:P09592}. FT REGION 90 121 Binding to the viral RNA. FT {ECO:0000250|UniProtKB:P27284}. FT REGION 106 120 Ribosome-binding. FT {ECO:0000250|UniProtKB:P27284}. FT REGION 190 200 Dimerization of the capsid protein. FT {ECO:0000250|UniProtKB:P0DOK1}. FT REGION 226 230 Dimerization of the capsid protein. FT {ECO:0000250|UniProtKB:P0DOK1}. FT REGION 269 280 Functions as an uncleaved signal peptide FT for the precursor of protein E3/E2. FT {ECO:0000250|UniProtKB:P03315}. FT REGION 727 747 Transient transmembrane before p62-6K FT protein processing. {ECO:0000255}. FT REGION 899 916 E1 fusion peptide loop. FT {ECO:0000250|UniProtKB:Q8JUX5}. FT MOTIF 70 106 Nuclear localization signal. FT {ECO:0000250|UniProtKB:P09592}. FT MOTIF 151 161 Nuclear export signal. FT {ECO:0000250|UniProtKB:P09592}. FT ACT_SITE 146 146 Charge relay system. FT {ECO:0000255|PROSITE-ProRule:PRU01027}. FT ACT_SITE 168 168 Charge relay system. FT {ECO:0000255|PROSITE-ProRule:PRU01027}. FT ACT_SITE 220 220 Charge relay system. FT {ECO:0000255|PROSITE-ProRule:PRU01027}. FT SITE 194 194 Involved in dimerization of the capsid FT protein. {ECO:0000250|UniProtKB:Q86925}. FT SITE 227 227 Involved in dimerization of the capsid FT protein. {ECO:0000250|UniProtKB:Q86925}. FT SITE 268 269 Cleavage; by autolysis. FT {ECO:0000250|UniProtKB:P03315}. FT SITE 332 333 Cleavage; by host furin. {ECO:0000250}. FT SITE 754 755 Cleavage; by host signal peptidase. FT {ECO:0000250}. FT SITE 815 816 Cleavage; by host signal peptidase. FT {ECO:0000250}. FT LIPID 727 727 S-palmitoyl cysteine; by host. FT {ECO:0000250}. FT LIPID 747 747 S-palmitoyl cysteine; by host. FT {ECO:0000250}. FT LIPID 748 748 S-palmitoyl cysteine; by host. FT {ECO:0000250}. FT CARBOHYD 279 279 N-linked (GlcNAc...) asparagine; by host. FT {ECO:0000255}. FT CARBOHYD 594 594 N-linked (GlcNAc...) asparagine; by host. FT {ECO:0000255}. FT CARBOHYD 956 956 N-linked (GlcNAc...) asparagine; by host. FT {ECO:0000255}. FT DISULFID 864 929 {ECO:0000250}. FT DISULFID 877 909 {ECO:0000250}. FT DISULFID 878 911 {ECO:0000250}. FT DISULFID 883 893 {ECO:0000250}. FT DISULFID 1074 1086 {ECO:0000250}. FT DISULFID 1116 1191 {ECO:0000250}. FT DISULFID 1121 1195 {ECO:0000250}. FT DISULFID 1143 1185 {ECO:0000250}. FT VARIANT 403 403 V -> A. FT VARIANT 519 519 D -> N. FT VARIANT 872 872 P -> S. FT VARIANT 1242 1242 A -> V. SQ SEQUENCE 1253 AA; 138060 MW; D8F11776CF2152F2 CRC64; MNYIPTQTFY GRRWRPRPAF RPWRVPMQPA PPMVIPELQT PIVQAQQMQQ LISAVSALTT KQNGKAPKKP KKKPQKAKAK KNEQQKKNEN KKPPPKQKNL AKKKKPGKRE RMCMKIENDC IFEVKLDGKV TGYACLVGDK VMKPAHVKGV IDNPDLAKLT YKKSSKYDLE CAQIPVHMKS DASKYTHEKP EGHYNWHHGA VQYSGGRFTI PTGAGKPGDS GRPIFDNKGR VVAIVLGGAN EGARTALSVV TWTKDMVTRY TPEGTEEWSA ALMMCVLANV TFPCSEPACA PCCYEKQPEQ TLRMLEDNVD RPGYYDLLEA TMTCNNSARH RRSVTEHFNV YKATKPYLAY CADCGDGQFC YSPVAIEKIR DEASDGMIKI QVAAQIGINK RGTHEHNKIR YIVGHYMKEA NRDSLQVHTS GVCAIRGTMG HFIVAYCPPG DELKVQFQDA ESHTQACKVQ YKHDPAPVGR EKFTVRPHFG IEVPCTTYQL TTAPTEEEID MHTPPDIPDI TLLSQQSGDV KITAGGKTIR YNCTCGSGNV GTTSSDKTIN SCKIAQCHAA VTNHDKWQYT SSFVPRADQL PRKGKVHVPF PLTNSTCRVP LARAPGVTYG KRELTVKLHP DHPTLLTYRS LGADPRPYEE WIDRYVERTI PVTEDGIEYR WGNNPPVRLW AQLTTEGKPH GWPHEIILYY YGLYPAATIA AVSAAGLAVV LSLLASCYMF ATARRKCLTP YALTPGAVVP VTLGVLCCAP RAHAASFAES MAYLWDENQT LFWLELATPL AAIIILVCCL KNLLCCCQPL SFLVLVSLGT PVVKSYEHTA TIPNVVGFPY KAHIERNGFS PMTLQLEVLG TSLEPTLNLE YITCEYKTVV PPPYIKCCGA SECRSMERPD YQCQVYTGVY PFMWGGAYCF CDTENTQLSE AYVDRSDVCK HDHAAAYKAH TAAMKATIRI SYGNLNQTTT AFVNGEHTVT VGGSRFTFGP ISTAWTPFDN KIVVYKNDVY NQDFPPYGSG QPGRFGDVQS RTVESKDLYA NTALKLSRPS SGTVHVPYTQ TPSGFKYWIK ERGTSLNDKA PFGCVIKTNP VRAENCAVGN IPVSMDIPDS AFTRVIDAPA VTNLECQVAV CTHSSDFGGI ATLTFKTDKP GKCAVHSHSN VATIQEAAVD IKTDGKITLH FSTASASPAF MVSVCSAKTT CMAACEPPKD HIVPYGASHN NQVFPDMSGT AMTWVQRVAG GLGGLTLAAV AALILVTCVT MRR //