POLSF_SFV
ID POLSF_SFV Reviewed; 830 AA.
AC P0DJZ6;
DT 09-DEC-2015, integrated into UniProtKB/Swiss-Prot.
DT 09-DEC-2015, sequence version 1.
DT 03-AUG-2022, entry version 23.
DE RecName: Full=Frameshifted 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=p62;
DE AltName: Full=E3/E2;
DE Contains:
DE RecName: Full=Protein E3;
DE AltName: Full=Spike glycoprotein E3;
DE Contains:
DE RecName: Full=Envelope glycoprotein E2;
DE AltName: Full=Spike glycoprotein E2;
DE Contains:
DE RecName: Full=Protein TF;
OS Semliki forest virus (SFV).
OC Viruses; Riboviria; Orthornavirae; Kitrinoviricota; Alsuviricetes;
OC Martellivirales; Togaviridae; Alphavirus.
OX NCBI_TaxID=11033;
OH NCBI_TaxID=7158; Aedes.
OH NCBI_TaxID=9368; Atelerix albiventris (Middle-African hedgehog) (Four-toed hedgehog).
OH NCBI_TaxID=7178; Culex tritaeniorhynchus (Mosquito).
OH NCBI_TaxID=170865; Halcyon.
OH NCBI_TaxID=9606; Homo sapiens (Human).
OH NCBI_TaxID=158617; Quelea.
OH NCBI_TaxID=34630; Rhipicephalus.
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC STRAIN=A7;
RX PubMed=9225028; DOI=10.1099/0022-1317-78-7-1551;
RA Tarbatt C.J., Glasgow G.M., Mooney D.A., Sheahan B.J., Atkins G.J.;
RT "Sequence analysis of the avirulent, demyelinating A7 strain of Semliki
RT Forest virus.";
RL J. Gen. Virol. 78:1551-1557(1997).
RN [2]
RP FUNCTION (CAPSID PROTEIN), AUTOCATALYTIC CLEAVAGE BY CAPSID PROTEIN, AND
RP MUTAGENESIS OF 219-SER-GLY-220.
RX PubMed=3553612; DOI=10.1128/jvi.61.5.1301-1309.1987;
RA Melancon P., Garoff H.;
RT "Processing of the Semliki Forest virus structural polyprotein: role of the
RT capsid protease.";
RL J. Virol. 61:1301-1309(1987).
RN [3]
RP FUNCTION (ENVELOPE GLYCOPROTEIN E2).
RX PubMed=1714373; DOI=10.1002/j.1460-2075.1991.tb07773.x;
RA Kail M., Hollinshead M., Ansorge W., Pepperkok R., Frank R., Griffiths G.,
RA Vaux D.;
RT "The cytoplasmic domain of alphavirus E2 glycoprotein contains a short
RT linear recognition signal required for viral budding.";
RL EMBO J. 10:2343-2351(1991).
RN [4]
RP CLEAVAGE SITE OF P62, AND MUTAGENESIS OF ARG-330 AND ARG-333.
RX PubMed=2005112; DOI=10.1016/s0021-9258(19)67660-x;
RA Jain S.K., DeCandido S., Kielian M.;
RT "Processing of the p62 envelope precursor protein of Semliki Forest
RT virus.";
RL J. Biol. Chem. 266:5756-5761(1991).
RN [5]
RP FUNCTION (CAPSID PROTEIN), AND AUTOCATALYTIC CLEAVAGE BY CAPSID PROTEIN.
RX PubMed=9642067; DOI=10.1006/jmbi.1998.1817;
RA Skoging U., Liljestrom P.;
RT "Role of the C-terminal tryptophan residue for the structure-function of
RT the alphavirus capsid protein.";
RL J. Mol. Biol. 279:865-872(1998).
RN [6]
RP PROTEOLYTIC PROCESSING OF P62 BY HOST FURIN.
RX PubMed=12584323; DOI=10.1128/jvi.77.5.2981-2989.2003;
RA Zhang X., Fugere M., Day R., Kielian M.;
RT "Furin processing and proteolytic activation of Semliki Forest virus.";
RL J. Virol. 77:2981-2989(2003).
RN [7]
RP FUNCTION (PROTEIN TF), AND SUBCELLULAR LOCATION (PROTEIN TF).
RX PubMed=18822126; DOI=10.1186/1743-422x-5-108;
RA Firth A.E., Chung B.Y., Fleeton M.N., Atkins J.F.;
RT "Discovery of frameshifting in Alphavirus 6K resolves a 20-year enigma.";
RL Virol. J. 5:108-108(2008).
RN [8]
RP FUNCTION (PROTEIN E3).
RX PubMed=23864626; DOI=10.1128/jvi.01507-13;
RA Uchime O., Fields W., Kielian M.;
RT "The role of E3 in pH protection during alphavirus assembly and exit.";
RL J. Virol. 87:10255-10262(2013).
CC -!- FUNCTION: [Capsid protein]: Forms an icosahedral capsid with a T=4
CC symmetry composed of 240 copies of the capsid protein surrounded by a
CC lipid membrane through which penetrate 80 spikes composed of trimers of
CC E1-E2 heterodimers (By similarity). The capsid protein binds to the
CC viral RNA genome at a site adjacent to a ribosome binding site for
CC viral genome translation following genome release (By similarity).
CC Possesses a protease activity that results in its autocatalytic
CC cleavage from the nascent structural protein (By similarity). Following
CC its self-cleavage, the capsid protein transiently associates with
CC ribosomes, and within several minutes the protein binds to viral RNA
CC and rapidly assembles into icosahedric core particles (By similarity).
CC The resulting nucleocapsid eventually associates with the cytoplasmic
CC domain of the spike glycoprotein E2 at the cell membrane, leading to
CC budding 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 nucleocapsid
CC into the cytoplasm, followed by an uncoating event necessary for the
CC genomic RNA to become accessible (By similarity). The uncoating might
CC be triggered by the interaction of capsid proteins with ribosomes (By
CC similarity). Binding of ribosomes would release the genomic RNA since
CC the same region is genomic RNA-binding and ribosome-binding (By
CC similarity). Specifically inhibits interleukin-1 receptor-associated
CC kinase 1/IRAK1-dependent signaling during viral entry, representing a
CC means by which the alphaviruses may evade innate immune detection and
CC activation prior to viral gene expression (By similarity).
CC {ECO:0000250|UniProtKB:P03315, ECO:0000250|UniProtKB:P03316,
CC ECO:0000250|UniProtKB:P27284}.
CC -!- FUNCTION: [Protein E3]: Provides the signal sequence for p62 (E3/E2)
CC translocation to the host endoplasmic reticulum. Mediates pH protection
CC of E1 during secretory pathway trans- port.
CC {ECO:0000269|PubMed:23864626}.
CC -!- FUNCTION: [Envelope glycoprotein E2]: Plays a role in viral attachment
CC to target host cell, by binding to the cell receptor. Synthesized as a
CC p62 precursor which is processed by furin at the cell membrane just
CC before virion budding, giving rise to E2-E1 heterodimer. The p62-E1
CC heterodimer is stable, whereas E2-E1 is unstable and dissociate at low
CC pH. p62 is processed at the last step, presumably to avoid E1 fusion
CC activation before its final export to cell surface. E2 C-terminus
CC contains a transitory transmembrane that would be disrupted by
CC palmitoylation, resulting in reorientation of the C-terminal tail from
CC lumenal to cytoplasmic side. This step is critical since E2 C-terminus
CC is involved in budding by interacting with capsid proteins. This
CC release of E2 C-terminus in cytoplasm occurs lately in protein export,
CC and precludes premature assembly of particles at the endoplasmic
CC reticulum membrane. {ECO:0000269|PubMed:1714373}.
CC -!- FUNCTION: [Protein TF]: Virion component that may play a role during
CC viral assembly. {ECO:0000269|PubMed:18822126}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Autocatalytic release of the core protein from the N-terminus
CC of the togavirus structural polyprotein by hydrolysis of a -Trp-|-
CC Ser- bond.; EC=3.4.21.90; Evidence={ECO:0000250|UniProtKB:P03315};
CC -!- SUBUNIT: [Capsid protein]: Homodimer (By similarity). Homomultimer
CC (Probable). Interacts with host karyopherin KPNA4; this interaction
CC allows the nuclear import of the viral capsid protein (By similarity).
CC Precursor of protein E3/E2: The precursor of protein E3/E2 and E1 form
CC a heterodimer shortly after synthesis (By similarity). Interacts with
CC host IRAK1; the interaction leads to inhibition of IRAK1-dependent
CC signaling (By similarity). {ECO:0000250|UniProtKB:P03316,
CC ECO:0000250|UniProtKB:P0DOK1, ECO:0000250|UniProtKB:Q8JUX5,
CC ECO:0000305}.
CC -!- SUBUNIT: [Envelope glycoprotein E2]: 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 at virion surface are
CC constituted of three E2-E1 heterodimers (By similarity). Interacts with
CC 6K protein (By similarity). Interacts with host MXRA8; this interaction
CC mediates virus entry (By similarity). {ECO:0000250|UniProtKB:P03316,
CC ECO:0000250|UniProtKB:P0DOK1, ECO:0000250|UniProtKB:Q8JUX5,
CC 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 cytoplasm and
CC the nucleus. {ECO:0000250|UniProtKB:Q8JUX5}.
CC -!- SUBCELLULAR LOCATION: [p62]: Virion membrane {ECO:0000250}; Single-pass
CC type I membrane protein {ECO:0000250}. Host cell membrane
CC {ECO:0000250}; Single-pass type I membrane protein {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: [Envelope glycoprotein E2]: Virion membrane
CC {ECO:0000250}; Single-pass type I membrane protein {ECO:0000250}. Host
CC cell membrane {ECO:0000250}; Single-pass type I membrane protein
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: [Protein TF]: Virion
CC {ECO:0000269|PubMed:18822126}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Ribosomal frameshifting; Named isoforms=2;
CC Name=Frameshifted structural polyprotein;
CC IsoId=P0DJZ6-1; Sequence=Displayed;
CC Name=Structural polyprotein;
CC IsoId=P03315-1; Sequence=External;
CC -!- DOMAIN: [Capsid protein]: The N-terminus contains a nuclear
CC localization signal and a CRM1-mediated nuclear export signal (By
CC similarity). The C-terminus functions as a protease during translation
CC to cleave itself from the translating structural polyprotein (By
CC similarity). {ECO:0000250|UniProtKB:P03316,
CC ECO:0000250|UniProtKB:Q8JUX5}.
CC -!- PTM: [Isoform Frameshifted structural polyprotein]: Specific enzymatic
CC cleavages in vivo yield mature proteins. Capsid protein is auto-cleaved
CC during 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, where
CC host signal peptidase cleaves it into pE2 and TF. pE2 is further
CC processed to mature E3 and E2 by host furin in trans-Golgi vesicle (By
CC similarity). {ECO:0000250|UniProtKB:P03315}.
CC -!- MISCELLANEOUS: [Isoform Frameshifted structural polyprotein]: Produced
CC by -1 ribosomal frameshifting in Protein 6K ORF.
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; Z48163; -; NOT_ANNOTATED_CDS; Genomic_RNA.
DR SMR; P0DJZ6; -.
DR Proteomes; UP000108382; 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:0019031; C:viral envelope; IEA:UniProtKB-KW.
DR GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IEA:InterPro.
DR GO; GO:0005198; F:structural molecule activity; IEA:InterPro.
DR GO; GO:0075512; P:clathrin-dependent endocytosis of virus by host cell; IEA:UniProtKB-KW.
DR GO; GO:0039654; P:fusion of virus membrane with host endosome membrane; IEA:UniProtKB-KW.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR GO; GO:0039722; P:suppression by virus of host toll-like receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-KW.
DR Gene3D; 2.40.10.10; -; 2.
DR Gene3D; 2.60.40.2400; -; 1.
DR Gene3D; 2.60.40.3200; -; 1.
DR Gene3D; 2.60.40.4310; -; 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; IPR009003; Peptidase_S1_PA.
DR InterPro; IPR043504; Peptidase_S1_PA_chymotrypsin.
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 PROSITE; PS51690; ALPHAVIRUS_CP; 1.
PE 1: Evidence at protein level;
KW Autocatalytic cleavage; Capsid protein;
KW Clathrin-mediated endocytosis of virus by host;
KW Cleavage on pair of basic residues; Disulfide bond;
KW 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; Ribosomal frameshifting; Serine protease;
KW T=4 icosahedral capsid protein; Transmembrane; Transmembrane helix;
KW Viral attachment to host cell; Viral envelope protein;
KW Viral penetration into host cytoplasm; Virion; Virus endocytosis by host;
KW Virus entry into host cell.
FT CHAIN 1..267
FT /note="Capsid protein"
FT /evidence="ECO:0000250|UniProtKB:P03315"
FT /id="PRO_0000434879"
FT CHAIN 268..755
FT /note="p62"
FT /evidence="ECO:0000250|UniProtKB:P03315"
FT /id="PRO_0000434880"
FT CHAIN 268..333
FT /note="Protein E3"
FT /evidence="ECO:0000250|UniProtKB:P03315"
FT /id="PRO_0000434881"
FT CHAIN 334..755
FT /note="Envelope glycoprotein E2"
FT /evidence="ECO:0000250|UniProtKB:P03315"
FT /id="PRO_0000434882"
FT CHAIN 756..830
FT /note="Protein TF"
FT /evidence="ECO:0000250|UniProtKB:P03315"
FT /id="PRO_0000434883"
FT TRANSMEM 702..722
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 771..791
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 793..813
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 119..267
FT /note="Peptidase S3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01027"
FT REGION 58..109
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 94..106
FT /note="Ribosome-binding"
FT /evidence="ECO:0000250|UniProtKB:P03315"
FT REGION 728..748
FT /note="Transient transmembrane before p62-6K protein
FT processing"
FT /evidence="ECO:0000255"
FT COMPBIAS 64..81
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 145
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01027"
FT ACT_SITE 167
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:P0DOK0"
FT ACT_SITE 219
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01027"
FT SITE 267..268
FT /note="Cleavage; by capsid protein"
FT /evidence="ECO:0000250|UniProtKB:P03315"
FT SITE 333..334
FT /note="Cleavage; by host furin"
FT /evidence="ECO:0000250|UniProtKB:P03315"
FT SITE 755..756
FT /note="Cleavage; by host signal peptidase"
FT /evidence="ECO:0000250|UniProtKB:P03315"
FT LIPID 718
FT /note="S-palmitoyl cysteine; by host"
FT /evidence="ECO:0000255"
FT LIPID 728
FT /note="S-palmitoyl cysteine; by host"
FT /evidence="ECO:0000250"
FT LIPID 748
FT /note="S-palmitoyl cysteine; by host"
FT /evidence="ECO:0000250"
FT LIPID 749
FT /note="S-palmitoyl cysteine; by host"
FT /evidence="ECO:0000250"
FT CARBOHYD 280
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 327
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 533
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 595
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT DISULFID 119..134
FT /evidence="ECO:0000250|UniProtKB:P03315"
FT MUTAGEN 219..220
FT /note="SG->RST: Loss of autocatalytic cleavage by capsid
FT protein."
FT /evidence="ECO:0000269|PubMed:3553612"
FT MUTAGEN 330
FT /note="R->S: Complete loss of p62 precursor processing."
FT /evidence="ECO:0000269|PubMed:2005112"
FT MUTAGEN 333
FT /note="R->F: Complete loss of p62 precursor processing."
FT /evidence="ECO:0000269|PubMed:2005112"
SQ SEQUENCE 830 AA; 92349 MW; C095CB68C85C4985 CRC64;
MNYIPTQTFY GRRWRPRPAA RPWPLQATPV APVVPDFQAQ QMQQLISAVN ALTMRQNAIA
PARPPKPKKK KTTKPKPKTQ PKKINGKTQQ QKKKDKQADK KKKKPGKRER MCMKIENDCI
FEVKHEGKVT GYACLVGDKV MKPAHVKGVI DNADLAKLAF KKSSKYDLEC AQIPVHMRSD
ASKYTHEKPE GHYNWHHGAV QYSGGRFTIP TGAGKPGDSG RPIFDNKGRV VAIVLGGANE
GSRTALSVVT WNKDMVTRVT PEGSEEWSAP LITAMCVLAN ATFPCFQPPC VPCCYENNAE
ATLRMLEDNV DRPGYYDLLQ AALTCRNGTR HRRSVSQHFN VYKATRPYIA YCADCGAGHS
CHSPVAIEAV RSEATDGMLK IQFSAQIGID KSDNHDYTKI RYADGHAIEN AVRSSLKVAT
SGDCFVHGTM GHFILAKCPP GEFLQVSIQD TRNAVRACRI QYHHDPQPVG REKFTIRPHY
GKEIPCTTYQ QTTAETVEEI DMHMPPDTPD RTLLSQQSGN VKITVGGKKV KYNCTCGTGN
VGTTNSDMTI NTCLIEQCHV SVTDHKKWQF NSPFVPRADE PARKGKVHIP FPLDNITCRV
PMAREPTVIH GKREVTLHLH PDHPTLFSYR TLGEDPQYHE EWVTAAVERT IPVPVDGMEY
HWGNNDPVRL WSQLTTEGKP HGWPHQIVQY YYGLYPAATV SAVVGMSLLA LISIFASCYM
LVAARSKCLT PYALTPGAAV PWTLGILCCA PRAHAASVAE TMAYLWDQNQ ALFWLEFAAP
VACILIITYC LRNVLCCCKS LSFLSATEPR GHRQSLRTFD SNAERGGVPV
