POLSF_CHIKS
ID POLSF_CHIKS Reviewed; 824 AA.
AC P0DOK1;
DT 31-JAN-2018, integrated into UniProtKB/Swiss-Prot.
DT 31-JAN-2018, sequence version 1.
DT 03-AUG-2022, entry version 20.
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=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=Protein TF;
OS Chikungunya virus (strain S27-African prototype) (CHIKV).
OC Viruses; Riboviria; Orthornavirae; Kitrinoviricota; Alsuviricetes;
OC Martellivirales; Togaviridae; Alphavirus.
OX NCBI_TaxID=371094;
OH NCBI_TaxID=7159; Aedes aegypti (Yellowfever mosquito) (Culex aegypti).
OH NCBI_TaxID=7160; Aedes albopictus (Asian tiger mosquito) (Stegomyia albopicta).
OH NCBI_TaxID=299627; Aedes furcifer (Mosquito).
OH NCBI_TaxID=188700; Aedes polynesiensis (Polynesian tiger mosquito).
OH NCBI_TaxID=9533; Cercopithecus.
OH NCBI_TaxID=9606; Homo sapiens (Human).
OH NCBI_TaxID=9539; Macaca (macaques).
OH NCBI_TaxID=9598; Pan troglodytes (Chimpanzee).
OH NCBI_TaxID=9554; Papio (baboons).
OH NCBI_TaxID=9573; Presbytis.
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=12466484; DOI=10.1099/0022-1317-83-12-3075;
RA Khan A.H., Morita K., Parquet Md Mdel C., Hasebe F., Mathenge E.G.,
RA Igarashi A.;
RT "Complete nucleotide sequence of chikungunya virus and evidence for an
RT internal polyadenylation site.";
RL J. Gen. Virol. 83:3075-3084(2002).
RN [2]
RP SUBCELLULAR LOCATION (SPIKE GLYCOPROTEIN E2).
RX PubMed=6726893; DOI=10.1128/jvi.51.1.254-258.1984;
RA Simizu B., Yamamoto K., Hashimoto K., Ogata T.;
RT "Structural proteins of Chikungunya virus.";
RL J. Virol. 51:254-258(1984).
RN [3]
RP SUBCELLULAR LOCATION (SPIKE GLYCOPROTEIN E2).
RX PubMed=21762510; DOI=10.1186/1743-422x-8-353;
RA Metz S.W., Geertsema C., Martina B.E., Andrade P., Heldens J.G.,
RA van Oers M.M., Goldbach R.W., Vlak J.M., Pijlman G.P.;
RT "Functional processing and secretion of Chikungunya virus E1 and E2
RT glycoproteins in insect cells.";
RL Virol. J. 8:353-353(2011).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 106-261, AND SUBUNIT.
RX PubMed=29306785; DOI=10.1016/j.virol.2017.12.020;
RA Sharma R., Kesari P., Kumar P., Tomar S.;
RT "Structure-function insights into chikungunya virus capsid protein: Small
RT molecules targeting capsid hydrophobic pocket.";
RL Virology 515:223-234(2018).
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: [Assembly protein E3]: Provides the signal sequence for the
CC translocation of the precursor of protein E3/E2 to the host endoplasmic
CC reticulum. Furin-cleaved E3 remains associated with spike glycoprotein
CC E1 and mediates pH protection of the latter during the transport via
CC the secretory pathway. After virion release from the host cell, the
CC assembly protein E3 is gradually released in the extracellular space.
CC {ECO:0000250|UniProtKB:P03315}.
CC -!- FUNCTION: [Spike glycoprotein E2]: Plays a role in viral attachment to
CC target host cell, by binding to the cell receptor. Synthesized as a p62
CC precursor which is processed by furin at the cell membrane just before
CC 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:0000250|UniProtKB:P03315}.
CC -!- FUNCTION: [Protein TF]: Plays a role in viral assembly and release.
CC {ECO:0000250|UniProtKB:P0DOK0}.
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:P03316};
CC -!- SUBUNIT: [Capsid protein]: Homodimer (PubMed:29306785). Homomultimer
CC (Probable). Interacts with host karyopherin KPNA4; this interaction
CC allows the nuclear import of the viral capsid protein (By
CC similarity).Interacts with spike glycoprotein E2 (By similarity).
CC Interacts with host IRAK1; the interaction leads to inhibition of
CC IRAK1-dependent signaling (By similarity).
CC {ECO:0000250|UniProtKB:P03316, ECO:0000250|UniProtKB:Q8JUX5,
CC ECO:0000269|PubMed:29306785, ECO:0000305}.
CC -!- SUBUNIT: [Precursor of protein E3/E2]: The precursor of protein E3/E2
CC and E1 form a heterodimer shortly after synthesis (By similarity).
CC {ECO:0000250|UniProtKB:P03316, ECO:0000250|UniProtKB:Q8JUX5}.
CC -!- SUBUNIT: [Spike 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:Q8JUX5}.
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: [Spike glycoprotein E2]: Virion membrane
CC {ECO:0000250|UniProtKB:Q8JUX5}; Single-pass type I membrane protein
CC {ECO:0000255}. Host cell membrane {ECO:0000269|PubMed:21762510};
CC Single-pass type I membrane protein {ECO:0000250|UniProtKB:Q8JUX5}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Ribosomal frameshifting; Named isoforms=2;
CC Name=Frameshifted structural polyprotein;
CC IsoId=P0DOK1-1; Sequence=Displayed;
CC Name=Structural polyprotein;
CC IsoId=Q8JUX5-1; 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 -!- DOMAIN: Structural polyprotein: As soon as the capsid protein has been
CC autocleaved, an internal uncleaved signal peptide directs the remaining
CC polyprotein to the endoplasmic reticulum.
CC {ECO:0000250|UniProtKB:P03315}.
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 -!- PTM: [Spike glycoprotein E2]: Palmitoylated via thioester bonds. These
CC palmitoylations may induce disruption of the C-terminus transmembrane.
CC This would result in the reorientation of E2 C-terminus from lumenal to
CC cytoplasmic side. {ECO:0000250|UniProtKB:P0DOK0}.
CC -!- PTM: [Protein TF]: Palmitoylated via thioester bonds.
CC {ECO:0000250|UniProtKB:P0DOK0}.
CC -!- MISCELLANEOUS: [Isoform Frameshifted structural polyprotein]:
CC Translated from a subgenomic RNA synthesized during togavirus
CC replication. {ECO:0000305}.
CC -!- MISCELLANEOUS: Structural polyprotein is translated from a subgenomic
CC RNA synthesized during togavirus replication.
CC {ECO:0000250|UniProtKB:P0DOK0}.
CC -!- MISCELLANEOUS: [Isoform Frameshifted structural polyprotein]: Produced
CC by ribosomal frameshifting.
CC -!- SIMILARITY: Belongs to the alphavirus frameshifted structural
CC polyprotein family. {ECO:0000305}.
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DR EMBL; AF369024; -; NOT_ANNOTATED_CDS; Genomic_RNA.
DR PDB; 5H23; X-ray; 2.20 A; A/B=106-261.
DR PDBsum; 5H23; -.
DR SMR; P0DOK1; -.
DR SwissPalm; P0DOK1; -.
DR Proteomes; UP000000569; 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: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: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:0046718; P:viral entry into host cell; IEA:UniProtKB-KW.
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 3D-structure; Capsid protein; Cleavage on pair of basic residues;
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; Reference proteome; Ribosomal frameshifting; 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..261
FT /note="Capsid protein"
FT /id="PRO_0000442839"
FT CHAIN 262..748
FT /note="Precursor of protein E3/E2"
FT /id="PRO_0000442840"
FT CHAIN 262..325
FT /note="Assembly protein E3"
FT /id="PRO_0000442841"
FT CHAIN 326..748
FT /note="Spike glycoprotein E2"
FT /id="PRO_0000442842"
FT CHAIN 749..824
FT /note="Protein TF"
FT /id="PRO_0000442843"
FT TOPO_DOM 262..692
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 693..713
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 714..748
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TOPO_DOM 749..763
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 764..784
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 785..795
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 113..261
FT /note="Peptidase S3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01027"
FT REGION 1..104
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 36..68
FT /note="Host transcription inhibition"
FT /evidence="ECO:0000250|UniProtKB:P09592"
FT REGION 84..114
FT /note="Binding to the viral RNA"
FT /evidence="ECO:0000250|UniProtKB:P27284"
FT REGION 91..100
FT /note="Ribosome-binding"
FT /evidence="ECO:0000250"
FT REGION 99..113
FT /note="Ribosome-binding"
FT /evidence="ECO:0000250|UniProtKB:P27284"
FT REGION 183..193
FT /note="Dimerization of the capsid protein"
FT /evidence="ECO:0000269|PubMed:29306785"
FT REGION 219..223
FT /note="Dimerization of the capsid protein"
FT /evidence="ECO:0000269|PubMed:29306785"
FT REGION 262..274
FT /note="Functions as an uncleaved signal peptide for the
FT precursor of protein E3/E2"
FT /evidence="ECO:0000250|UniProtKB:P03315"
FT REGION 721..741
FT /note="Transient transmembrane before p62-6K protein
FT processing"
FT /evidence="ECO:0000255"
FT MOTIF 61..99
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250|UniProtKB:P09592"
FT MOTIF 144..154
FT /note="Nuclear export signal"
FT /evidence="ECO:0000250|UniProtKB:P09592"
FT COMPBIAS 73..87
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 88..102
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 139
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01027"
FT ACT_SITE 161
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01027"
FT ACT_SITE 213
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01027"
FT SITE 261..262
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000250|UniProtKB:P03315"
FT SITE 325..326
FT /note="Cleavage; by host furin"
FT /evidence="ECO:0000250"
FT SITE 748..749
FT /note="Cleavage; by host signal peptidase"
FT /evidence="ECO:0000250"
FT SITE 809..810
FT /note="Cleavage; by host signal peptidase"
FT /evidence="ECO:0000250"
FT LIPID 721
FT /note="S-palmitoyl cysteine; by host"
FT /evidence="ECO:0000250"
FT LIPID 741
FT /note="S-palmitoyl cysteine; by host"
FT /evidence="ECO:0000250"
FT LIPID 742
FT /note="S-palmitoyl cysteine; by host"
FT /evidence="ECO:0000250"
FT CARBOHYD 273
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 588
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 670
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT DISULFID 113..128
FT /evidence="ECO:0000250"
FT STRAND 113..119
FT /evidence="ECO:0007829|PDB:5H23"
FT STRAND 122..130
FT /evidence="ECO:0007829|PDB:5H23"
FT STRAND 133..137
FT /evidence="ECO:0007829|PDB:5H23"
FT STRAND 142..145
FT /evidence="ECO:0007829|PDB:5H23"
FT HELIX 147..150
FT /evidence="ECO:0007829|PDB:5H23"
FT STRAND 155..157
FT /evidence="ECO:0007829|PDB:5H23"
FT TURN 158..161
FT /evidence="ECO:0007829|PDB:5H23"
FT STRAND 162..166
FT /evidence="ECO:0007829|PDB:5H23"
FT HELIX 169..174
FT /evidence="ECO:0007829|PDB:5H23"
FT STRAND 184..189
FT /evidence="ECO:0007829|PDB:5H23"
FT STRAND 192..197
FT /evidence="ECO:0007829|PDB:5H23"
FT STRAND 200..204
FT /evidence="ECO:0007829|PDB:5H23"
FT STRAND 216..218
FT /evidence="ECO:0007829|PDB:5H23"
FT STRAND 224..233
FT /evidence="ECO:0007829|PDB:5H23"
FT STRAND 235..246
FT /evidence="ECO:0007829|PDB:5H23"
FT STRAND 249..253
FT /evidence="ECO:0007829|PDB:5H23"
SQ SEQUENCE 824 AA; 92620 MW; 73030BAB8BAD599D CRC64;
MEFIPTQTFY NRRYQPRPWT PRPTIQVIRP RPRPQRQAGQ LAQLISAVNK LTMRAVPQQK
PRKNRKNKKQ KQKQQAPQNN TNQKKQPPKK KPAQKKKKPG RRERMCMKIE NDCIFEVKHE
GKVTGYACLV GDKVMKPAHV KGTIDNADLA KLAFKRSSKY DLECAQIPVH MKSDASKFTH
EKPEGYYNWH HGAVQYSGGR FTIPTGAGKP GDSGRPIFDN KGRVVAIVLG GANEGARTAL
SVVTWNKDIV TKITPEGAEE WSLAIPVMCL LANTTFPCSQ PPCIPCCYEK EPEETLRMLE
DNVMRPGYYQ LLQASLTCSP HRQRRSTKDN FNVYKATRPY LAHCPDCGEG HSCHSPVALE
RIRNEATDGT LKIQVSLQIG IGTDDSHDWT KLRYMDNHIP ADAGRAGLFV RTSAPCTITG
TMGHFILARC PKGETLTVGF TDSRKISHSC THPFHHDPPV IGREKFHSRP QHGKELPCST
YVQSNAATAE EIEVHMPPDT PDRTLLSQQS GNVKITVNSQ TVRYKCNCGG SNEGLITTDK
VINNCKVDQC HAAVTNHKKW QYNSPLVPRN AELGDRKGKI HIPFPLANVT CMVPKARNPT
VTYGKNQVIM LLYPDHPTLL SYRSMGEEPN YQEEWVTHKK EVVLTVPTEG LEVTWGNNEP
YKYWPQLSAN GTAHGHPHEI ILYYYELYPT MTVVVVSVAS FILLSMVGMA VGMCMCARRR
CITPYELTPG ATVPFLLSLI CCIRTAKAAT YQEAAVYLWN EQQPLFWLQA LIPLAALIVL
CNCLRLLPCC CKTLAFLSRN EHRCPHCERV RTRNSDPEHG GSTV
