UniProtKB - P36329 (POLS_EEVV3)
Structural polyprotein
Functioni
Forms an icosahedral capsid with a T=4 symmetry composed of 240 copies of the capsid protein surrounded by a lipid membrane through which penetrate 80 spikes composed of trimers of E1-E2 heterodimers (By similarity).
The capsid protein binds to the viral RNA genome at a site adjacent to a ribosome binding site for viral genome translation following genome release (By similarity).
Possesses a protease activity that results in its autocatalytic cleavage from the nascent structural protein (By similarity).
Following its self-cleavage, the capsid protein transiently associates with ribosomes, and within several minutes the protein binds to viral RNA and rapidly assembles into icosahedric core particles (By similarity).
The resulting nucleocapsid eventually associates with the cytoplasmic domain of the spike glycoprotein E2 at the cell membrane, leading to budding and formation of mature virions (By similarity).
In case of infection, new virions attach to target cells and after clathrin-mediated endocytosis their membrane fuses with the host endosomal membrane (PubMed:16427678).
This leads to the release of the nucleocapsid into the cytoplasm, followed by an uncoating event necessary for the genomic RNA to become accessible (By similarity).
The uncoating might be triggered by the interaction of capsid proteins with ribosomes (By similarity).
Binding of ribosomes would release the genomic RNA since the same region is genomic RNA-binding and ribosome-binding (By similarity).
Specifically inhibits interleukin-1 receptor-associated kinase 1/IRAK1-dependent signaling during viral entry, representing a means by which the alphaviruses may evade innate immune detection and activation prior to viral gene expression (By similarity).
Inhibits host transcription (By similarity).
Forms a tetrameric complex with XPO1/CRM1 and the nuclear import receptor importin (By similarity).
This complex blocks the central channel of host nuclear pores thereby inhibiting the receptor-mediated nuclear transport and thus the host mRNA and rRNA transcription (By similarity).
The inhibition of transcription is linked to a cytopathic effect on the host cell (By similarity).
By similarity1 PublicationProvides the signal sequence for the translocation of the precursor of protein E3/E2 to the host endoplasmic reticulum. Furin-cleaved E3 remains associated with spike glycoprotein E1 and mediates pH protection of the latter during the transport via the secretory pathway. After virion release from the host cell, the assembly protein E3 is gradually released in the extracellular space.
By similarityPlays a role in viral attachment to target host cell, by binding to the cell receptor LDLRAD3. Synthesized as a p62 precursor which is processed by furin at the cell membrane just before virion budding, giving rise to E2-E1 heterodimer. The p62-E1 heterodimer is stable, whereas E2-E1 is unstable and dissociate at low pH. p62 is processed at the last step, presumably to avoid E1 fusion activation before its final export to cell surface. E2 C-terminus contains a transitory transmembrane that would be disrupted by palmitoylation, resulting in reorientation of the C-terminal tail from lumenal to cytoplasmic side. This step is critical since E2 C-terminus is involved in budding by interacting with capsid proteins. This release of E2 C-terminus in cytoplasm occurs lately in protein export, and precludes premature assembly of particles at the endoplasmic reticulum membrane.
By similarityConstitutive membrane protein involved in virus glycoprotein processing, cell permeabilization, and the budding of viral particles. Disrupts the calcium homeostasis of the cell, probably at the endoplasmic reticulum level. This leads to cytoplasmic calcium elevation. Because of its lipophilic properties, the 6K protein is postulated to influence the selection of lipids that interact with the transmembrane domains of the glycoproteins, which, in turn, affects the deformability of the bilayer required for the extreme curvature that occurs as budding proceeds. Present in low amount in virions, about 3% compared to viral glycoproteins.
By similarityClass II viral fusion protein. Fusion activity is inactive as long as E1 is bound to E2 in mature virion. After virus attachment to cell receptor LDLRAD3 and endocytosis, acidification of the endosome would induce dissociation of E1/E2 heterodimer and concomitant trimerization of the E1 subunits. This E1 trimer is fusion active, and promotes release of viral nucleocapsid in cytoplasm after endosome and viral membrane fusion. Efficient fusion requires the presence of cholesterol and sphingolipid in the target membrane. Fusion is optimal at levels of about 1 molecule of cholesterol per 2 molecules of phospholipids, and is specific for sterols containing a 3-beta-hydroxyl group.
By similarityMiscellaneous
Catalytic activityi
- Autocatalytic release of the core protein from the N-terminus of the togavirus structural polyprotein by hydrolysis of a -Trp-|-Ser- bond.By similarity EC:3.4.21.90
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Active sitei | 152 | Charge relay systemPROSITE-ProRule annotation | 1 | |
Active sitei | 174 | Charge relay systemPROSITE-ProRule annotation | 1 | |
Sitei | 200 | Involved in dimerization of the capsid proteinBy similarity | 1 | |
Active sitei | 226 | Charge relay systemPROSITE-ProRule annotation | 1 | |
Sitei | 233 | Involved in dimerization of the capsid proteinBy similarity | 1 |
GO - Molecular functioni
- RNA binding Source: UniProtKB-KW
- serine-type endopeptidase activity Source: InterPro
- structural molecule activity Source: InterPro
GO - Biological processi
- clathrin-dependent endocytosis of virus by host cell Source: UniProtKB-KW
- fusion of virus membrane with host endosome membrane Source: UniProtKB-KW
- suppression by virus of host gene expression Source: UniProtKB-KW
- suppression by virus of host toll-like receptor signaling pathway Source: UniProtKB
- virion attachment to host cell Source: UniProtKB-KW
Keywordsi
Protein family/group databases
MEROPSi | S03.001 |
Names & Taxonomyi
Protein namesi | Recommended name: Structural polyproteinAlternative name(s): p130 Cleaved into the following 6 chains: Capsid protein (EC:3.4.21.90By similarity) Alternative name(s): Coat protein Short name: C Alternative name(s): p62 pE2 Alternative name(s): E2 envelope glycoprotein Alternative name(s): E1 envelope glycoprotein |
Organismi | Venezuelan equine encephalitis virus (strain 3880) (VEEV) |
Taxonomic identifieri | 36382 [NCBI] |
Taxonomic lineagei | Viruses › Riboviria › Orthornavirae › Kitrinoviricota › Alsuviricetes › Martellivirales › Togaviridae › Alphavirus › |
Virus hosti | Bos taurus (Bovine) [TaxID: 9913] Didelphis marsupialis (Southern opossum) [TaxID: 9268] Equus asinus (Donkey) (Equus africanus asinus) [TaxID: 9793] Equus caballus (Horse) [TaxID: 9796] Homo sapiens (Human) [TaxID: 9606] Melanoconion [TaxID: 53535] Philander opossum (Gray four-eyed opossum) [TaxID: 9272] Proechimys [TaxID: 10162] Sigmodon hispidus (Hispid cotton rat) [TaxID: 42415] |
Proteomesi |
|
Subcellular locationi
- Virion By similarity
- Host cytoplasm By similarity
- Host cell membrane By similarity
- Host nucleus By similarity
- Virion membrane By similarity; Single-pass type I membrane protein Sequence analysis
- Host cell membrane By similarity; Single-pass type I membrane protein By similarity
- Host cell membrane By similarity; Multi-pass membrane protein Sequence analysis
- Virion membrane By similarity; Multi-pass membrane protein Sequence analysis
- Virion membrane By similarity; Single-pass type I membrane protein Sequence analysis
- Host cell membrane By similarity; Single-pass type I membrane protein Sequence analysis
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 276 – 701 | ExtracellularSequence analysisAdd BLAST | 426 | |
Transmembranei | 702 – 722 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 723 – 757 | CytoplasmicSequence analysisAdd BLAST | 35 | |
Topological domaini | 758 – 772 | ExtracellularSequence analysisAdd BLAST | 15 | |
Transmembranei | 773 – 793 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 794 | CytoplasmicSequence analysis | 1 | |
Transmembranei | 795 – 815 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 816 – 1225 | ExtracellularSequence analysisAdd BLAST | 410 | |
Transmembranei | 1226 – 1246 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 1247 – 1255 | CytoplasmicSequence analysis | 9 |
Keywords - Cellular componenti
Capsid protein, Host cell membrane, Host cytoplasm, Host membrane, Host nucleus, Membrane, T=4 icosahedral capsid protein, Viral envelope protein, VirionPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000041251 | 1 – 275 | Capsid proteinAdd BLAST | 275 | |
ChainiPRO_0000234318 | 276 – 757 | Precursor of protein E3/E2Add BLAST | 482 | |
ChainiPRO_0000041252 | 276 – 334 | Assembly protein E3Add BLAST | 59 | |
ChainiPRO_0000041253 | 335 – 757 | Spike glycoprotein E2Add BLAST | 423 | |
ChainiPRO_0000041254 | 758 – 813 | 6K proteinAdd BLAST | 56 | |
ChainiPRO_0000041255 | 814 – 1255 | Spike glycoprotein E1Add BLAST | 442 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 47 | N-linked (GlcNAc...) asparagine; by hostSequence analysis | 1 | |
Modified residuei | 93 | PhosphothreonineBy similarity | 1 | |
Modified residuei | 108 | PhosphothreonineBy similarity | 1 | |
Modified residuei | 124 | PhosphoserineBy similarity | 1 | |
Modified residuei | 127 | PhosphothreonineBy similarity | 1 | |
Glycosylationi | 286 | N-linked (GlcNAc...) asparagine; by hostSequence analysis | 1 | |
Glycosylationi | 652 | N-linked (GlcNAc...) asparagine; by hostSequence analysis | 1 | |
Lipidationi | 730 | S-palmitoyl cysteine; by hostBy similarity | 1 | |
Lipidationi | 750 | S-palmitoyl cysteine; by hostBy similarity | 1 | |
Lipidationi | 751 | S-palmitoyl cysteine; by hostBy similarity | 1 | |
Disulfide bondi | 862 ↔ 927 | By similarity | ||
Disulfide bondi | 875 ↔ 907 | By similarity | ||
Disulfide bondi | 876 ↔ 909 | By similarity | ||
Disulfide bondi | 881 ↔ 891 | By similarity | ||
Glycosylationi | 947 | N-linked (GlcNAc...) asparagine; by hostSequence analysis | 1 | |
Disulfide bondi | 1072 ↔ 1084 | By similarity | ||
Disulfide bondi | 1114 ↔ 1189 | By similarity | ||
Disulfide bondi | 1119 ↔ 1193 | By similarity | ||
Disulfide bondi | 1141 ↔ 1183 | By similarity |
Post-translational modificationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 275 – 276 | Cleavage; by autolysisBy similarity | 2 | |
Sitei | 334 – 335 | Cleavage; by host furinBy similarity | 2 | |
Sitei | 757 – 758 | Cleavage; by host signal peptidaseBy similarity | 2 | |
Sitei | 813 – 814 | Cleavage; by host signal peptidaseBy similarity | 2 |
Keywords - PTMi
Cleavage on pair of basic residues, Disulfide bond, Glycoprotein, Lipoprotein, Palmitate, PhosphoproteinInteractioni
Subunit structurei
Part of a tetrameric complex composed of host CRM1, host importin alpha/beta dimer and the viral capsid; this complex blocks the receptor-mediated transport through the nuclear pore (By similarity).
Interacts with host phosphatase PPP1CA; this interaction dephosphorylates the capsid protein, which increases its ability to bind to the viral genome (By similarity).
Interacts with host karyopherin KPNA4; this interaction allows the nuclear import of the viral capsid protein (By similarity).
Interacts with spike glycoprotein E2 (By similarity).
Interacts with host IRAK1; the interaction leads to inhibition of IRAK1-dependent signaling (By similarity).
By similarityThe precursor of protein E3/E2 and E1 form a heterodimer shortly after synthesis (By similarity).
By similarityThe precursor of protein E3/E2 and E1 form a heterodimer shortly after synthesis (By similarity). Processing of the precursor of protein E3/E2 into E2 and E3 results in a heterodimer of the spike glycoproteins E2 and E1. Spike at virion surface are constituted of three E2-E1 heterodimers (By similarity). After target cell attachment and endocytosis, E1 change conformation to form homotrimers (By similarity).
Interacts with 6K protein (By similarity).
Interacts with host LDLRAD3; this interaction mediates viral entry to the host cell (By similarity).
By similarityProcessing of the precursor of protein E3/E2 into E2 and E3 results in a heterodimer of the spike glycoproteins E2 and E1 (By similarity). Spike at virion surface are constituted of three E2-E1 heterodimers (By similarity).
Interacts with 6K protein (By similarity).
Interacts with host LDLRAD3; this interaction mediates viral entry to the host cell (By similarity).
By similarityInteracts with spike glycoprotein E1 (By similarity).
Interacts with spike glycoprotein E2 (By similarity).
By similarityFamily & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 126 – 275 | Peptidase S3PROSITE-ProRule annotationAdd BLAST | 150 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 33 | Necessary for nucleocapsid assembly and virus assemblyBy similarityAdd BLAST | 33 | |
Regioni | 33 – 68 | Host transcription inhibitionBy similarityAdd BLAST | 36 | |
Regioni | 44 – 119 | DisorderedSequence analysisAdd BLAST | 76 | |
Regioni | 91 – 127 | Binding to the viral RNABy similarityAdd BLAST | 37 | |
Regioni | 112 – 126 | Ribosome-bindingBy similarityAdd BLAST | 15 | |
Regioni | 276 – 287 | Functions as an uncleaved signal peptide for the precursor of protein E3/E2By similarityAdd BLAST | 12 | |
Regioni | 730 – 750 | Transient transmembrane before p62-6K protein processingSequence analysisAdd BLAST | 21 | |
Regioni | 897 – 914 | E1 fusion peptide loopBy similarityAdd BLAST | 18 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 41 – 48 | Supraphysiological nuclear export signalBy similarity | 8 | |
Motifi | 64 – 68 | Nuclear localization signalBy similarity | 5 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 57 – 76 | Basic and acidic residuesSequence analysisAdd BLAST | 20 |
Domaini
Keywords - Domaini
Transmembrane, Transmembrane helixFamily and domain databases
Gene3Di | 2.40.10.10, 2 hits 2.60.40.2400, 1 hit 2.60.40.3200, 1 hit 2.60.40.350, 1 hit 2.60.40.4310, 1 hit 2.60.98.10, 3 hits |
InterProi | View protein in InterPro IPR002548, Alpha_E1_glycop IPR000936, Alpha_E2_glycop IPR002533, Alpha_E3_glycop IPR042304, Alphavir_E2_A IPR042305, Alphavir_E2_B IPR042306, Alphavir_E2_C IPR000336, Flavivir/Alphavir_Ig-like_sf IPR036253, Glycoprot_cen/dimer_sf IPR038055, Glycoprot_E_dimer_dom IPR014756, Ig_E-set IPR009003, Peptidase_S1_PA IPR043504, Peptidase_S1_PA_chymotrypsin IPR000930, Peptidase_S3 |
Pfami | View protein in Pfam PF01589, Alpha_E1_glycop, 1 hit PF00943, Alpha_E2_glycop, 1 hit PF01563, Alpha_E3_glycop, 1 hit PF00944, Peptidase_S3, 1 hit |
PRINTSi | PR00798, TOGAVIRIN |
SUPFAMi | SSF50494, SSF50494, 1 hit SSF56983, SSF56983, 1 hit SSF81296, SSF81296, 1 hit |
PROSITEi | View protein in PROSITE PS51690, ALPHAVIRUS_CP, 1 hit |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
10 20 30 40 50
MFPFQPMYPM QPMPYRNPFA APRRPWFPRT DPFLAMQVQE LTRSMANLTF
60 70 80 90 100
KQRREAPPEG PPAKKPKREA PQKQKGGGQG KKKKNQGKKK AKTGPPNPKA
110 120 130 140 150
QNGNKKKTNK KPGKRQRMVM KLESDKTFPI MLEGKINGYA CVVGGKLFRP
160 170 180 190 200
MHVEGKIDND VLAALKTKKA SKYDLEYADV PQNMRADTFK YTHEKPQGYY
210 220 230 240 250
SWHHGAVQYE NGRFTVPKGV GAKGDSGRPI LDNQGRVVAI VLGGVNEGSR
260 270 280 290 300
TALSVVMWNE KGVTVKYTPE NCEQWSLVTT MCLLANVTFP CAQPPICYDR
310 320 330 340 350
KPAETLAMLS VNVDNPGYDE LLEAAVKCPG RKRRSTEELF KEYKLTRPYM
360 370 380 390 400
ARCIRCAVGS CHSPIAIEAV KSDGHDGYVR LQTSSQYGLD SSGNLKGRTM
410 420 430 440 450
RYDMHGTIEE IPLHQVSLHT SRPCHIVDGH GYFLLARCPA GDSITMEFKK
460 470 480 490 500
DAVTHSCSVP YEVKFNPVGR ELYTHPPEHG AEQACQVYAH DAQNRGAYVE
510 520 530 540 550
MHLPGSEVDS SLVSLSGSSV TVTPPAGTSA LVECECGGTK ISETINTAKQ
560 570 580 590 600
FSQCTKKEQC RAYRLQNDKW VYNSDKLPKA AGATLKGKLH VPFLLADGKC
610 620 630 640 650
TVPLAPEPMI TFGFRSVSLK LHPKNPTYLT TRQLADEPHY THELISEPVV
660 670 680 690 700
RNFSVTEKGW EFVWGNHPPK RFWAQETAPG NPHGLPHEVI THYYHRYPMS
710 720 730 740 750
TILGLSICAA IVTVSIAAST WLLCKSRVSC LTPYRLTPNA RMPLCLAVLC
760 770 780 790 800
CARTARAETT WESLDHLWNN NQQMFWIQLL IPLAALIVVT RLLRCVCCVV
810 820 830 840 850
PFLVVAGAAG AGAYEHATTM PSQAGIPYNT IVNRAGYAPL PISITPTKIK
860 870 880 890 900
LIPTVNLEYV TCHYKTGMDS PAIKCCGSQE CTPTYRPDEQ CKVFTGVYPF
910 920 930 940 950
MWGGAYCFCD TENTQVSKAY VMKSDDCLAD HAEAYKAHTA SVQAFLNITV
960 970 980 990 1000
GEHSIVTTVY VNGETPVNFN GVKLTAGPLS TAWTPFDRKI VQYAGEIYNY
1010 1020 1030 1040 1050
DFPEYGAGQP GAFGDIQSRT VSSSDLYANT NLVLQRPKAG AIHVPYTQAP
1060 1070 1080 1090 1100
SGFEQWKKDK APSLKFTAPF GCEIYTNPIR AENCAVGSIP LAFDIPDALF
1110 1120 1130 1140 1150
TRVSETPTLS AAECTLNECV YSSDFGGIAT VKYSASKSGK CAVHVPSGTA
1160 1170 1180 1190 1200
TLKEAAIELA EQGSATIHFS TANIHPEFRL QICTSYVTCK GDCHPPKDHI
1210 1220 1230 1240 1250
VTHPQYHAQT FTAAVSKTAW TWLTSLLGGS AVIIIIGLVL ATIVAMYVLT
NQKHN
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | L00930 Genomic RNA Translation: AAC19325.1 |
PIRi | D44213 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | L00930 Genomic RNA Translation: AAC19325.1 |
PIRi | D44213 |
3D structure databases
SMRi | P36329 |
ModBasei | Search... |
Protein family/group databases
MEROPSi | S03.001 |
Family and domain databases
Gene3Di | 2.40.10.10, 2 hits 2.60.40.2400, 1 hit 2.60.40.3200, 1 hit 2.60.40.350, 1 hit 2.60.40.4310, 1 hit 2.60.98.10, 3 hits |
InterProi | View protein in InterPro IPR002548, Alpha_E1_glycop IPR000936, Alpha_E2_glycop IPR002533, Alpha_E3_glycop IPR042304, Alphavir_E2_A IPR042305, Alphavir_E2_B IPR042306, Alphavir_E2_C IPR000336, Flavivir/Alphavir_Ig-like_sf IPR036253, Glycoprot_cen/dimer_sf IPR038055, Glycoprot_E_dimer_dom IPR014756, Ig_E-set IPR009003, Peptidase_S1_PA IPR043504, Peptidase_S1_PA_chymotrypsin IPR000930, Peptidase_S3 |
Pfami | View protein in Pfam PF01589, Alpha_E1_glycop, 1 hit PF00943, Alpha_E2_glycop, 1 hit PF01563, Alpha_E3_glycop, 1 hit PF00944, Peptidase_S3, 1 hit |
PRINTSi | PR00798, TOGAVIRIN |
SUPFAMi | SSF50494, SSF50494, 1 hit SSF56983, SSF56983, 1 hit SSF81296, SSF81296, 1 hit |
PROSITEi | View protein in PROSITE PS51690, ALPHAVIRUS_CP, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | POLS_EEVV3 | |
Accessioni | P36329Primary (citable) accession number: P36329 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | June 1, 1994 |
Last sequence update: | June 1, 1994 | |
Last modified: | May 25, 2022 | |
This is version 127 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Viral Protein Annotation Program |