Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Structural polyprotein

Gene
N/A
Organism
Venezuelan equine encephalitis virus (strain Trinidad donkey) (VEEV)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Capsid protein possesses a protease activity that results in its autocatalytic cleavage from the nascent structural protein. 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 icosaedric core particles. The resulting nucleocapsid eventually associates with the cytoplasmic domain of E2 at the cell membrane, leading to budding and formation of mature virions. New virions attach to target cells, and after clathrin-mediated endocytosis their membrane fuses with the host endosomal membrane. This leads to the release of the nucleocapsid into the cytoplasm, followed by an uncoating event necessary for the genomic RNA to become accessible. The uncoating might be triggered by the interaction of capsid proteins with ribosomes. Binding of ribosomes would release the genomic RNA since the same region is genomic RNA-binding and ribosome-binding (By similarity).By similarity
E3 protein's function is unknown.By similarity
E2 is responsible for viral attachment to target host cell, by binding to the cell receptor. 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 similarity).By similarity
6K is a constitutive 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 similarity).By similarity
E1 is a class II viral fusion protein. Fusion activity is inactive as long as E1 is bound to E2 in mature virion. After virus attachment to target cell 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 (By similarity).By similarity

Catalytic activityi

Autocatalytic release of the core protein from the N-terminus of the togavirus structural polyprotein by hydrolysis of a -Trp-|-Ser- bond.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei152 – 1521Charge relay systemPROSITE-ProRule annotation
Active sitei158 – 1581Charge relay systemPROSITE-ProRule annotation
Active sitei226 – 2261Charge relay systemPROSITE-ProRule annotation

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Serine protease

Keywords - Biological processi

Clathrin-mediated endocytosis of virus by host, Fusion of virus membrane with host endosomal membrane, Fusion of virus membrane with host membrane, Host-virus interaction, Viral attachment to host cell, Viral penetration into host cytoplasm, Virus endocytosis by host, Virus entry into host cell

Protein family/group databases

MEROPSiS03.001.

Names & Taxonomyi

Protein namesi
Recommended name:
Structural polyprotein
Alternative name(s):
p130
Cleaved into the following 6 chains:
Alternative name(s):
Coat protein
Short name:
C
Alternative name(s):
E3/E2
Alternative name(s):
Spike glycoprotein E3
Alternative name(s):
Spike glycoprotein E2
Alternative name(s):
Spike glycoprotein E1
OrganismiVenezuelan equine encephalitis virus (strain Trinidad donkey) (VEEV)
Taxonomic identifieri11038 [NCBI]
Taxonomic lineageiVirusesssRNA virusesssRNA positive-strand viruses, no DNA stageTogaviridaeAlphavirusVEEV complex
Virus hostiBos 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
  • UP000008659 Componenti: Genome

Subcellular locationi

Capsid protein :

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini276 – 701426ExtracellularSequence analysisAdd
BLAST
Transmembranei702 – 72221HelicalSequence analysisAdd
BLAST
Topological domaini723 – 75735CytoplasmicSequence analysisAdd
BLAST
Topological domaini758 – 77215ExtracellularSequence analysisAdd
BLAST
Transmembranei773 – 79321HelicalSequence analysisAdd
BLAST
Topological domaini794 – 7952CytoplasmicSequence analysis
Transmembranei796 – 81621HelicalSequence analysisAdd
BLAST
Topological domaini817 – 1224408ExtracellularSequence analysisAdd
BLAST
Transmembranei1225 – 124521HelicalSequence analysisAdd
BLAST
Topological domaini1246 – 12549CytoplasmicSequence analysis

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Capsid protein, Host cell membrane, Host cytoplasm, Host membrane, Membrane, T=4 icosahedral capsid protein, Viral envelope protein, Virion

Pathology & Biotechi

Chemistry

DrugBankiDB03904. Urea.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 275275Capsid proteinPRO_0000041276Add
BLAST
Chaini276 – 757482p62PRO_0000234323Add
BLAST
Chaini276 – 33459E3 proteinPRO_0000041277Add
BLAST
Signal peptidei276 – 29015Not cleavedSequence analysisAdd
BLAST
Chaini335 – 757423E2 envelope glycoproteinPRO_0000041278Add
BLAST
Chaini758 – 812556K proteinPRO_0000041279Add
BLAST
Chaini813 – 1254442E1 envelope glycoproteinPRO_0000041280Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi286 – 2861N-linked (GlcNAc...); by hostSequence analysis
Glycosylationi546 – 5461N-linked (GlcNAc...); by hostSequence analysis
Glycosylationi652 – 6521N-linked (GlcNAc...); by hostSequence analysis
Lipidationi730 – 7301S-palmitoyl cysteine; by hostBy similarity
Lipidationi750 – 7501S-palmitoyl cysteine; by hostBy similarity
Lipidationi751 – 7511S-palmitoyl cysteine; by hostBy similarity
Disulfide bondi861 ↔ 926By similarity
Disulfide bondi874 ↔ 906By similarity
Disulfide bondi875 ↔ 908By similarity
Disulfide bondi880 ↔ 890By similarity
Glycosylationi946 – 9461N-linked (GlcNAc...); by hostSequence analysis
Disulfide bondi1071 ↔ 1083By similarity
Disulfide bondi1113 ↔ 1188By similarity
Disulfide bondi1118 ↔ 1192By similarity
Disulfide bondi1140 ↔ 1182By similarity

Post-translational modificationi

Specific enzymatic cleavages in vivo yield mature proteins. Capsid protein is auto-cleaved during polyprotein translation, unmasking p62 signal peptide. The remaining polyprotein is then targeted to the endoplasmic reticulum, where host signal peptidase cleaves it into p62, 6K and E1 proteins. p62 is further processed to mature E3 and E2 by host furin in trans-Golgi vesicle (By similarity).By similarity
E2 and 6K are palmitoylated via thioester bonds.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei275 – 2762Cleavage; by capsid proteinBy similarity
Sitei334 – 3352Cleavage; by host furinBy similarity
Sitei757 – 7582Cleavage; by host signal peptidaseBy similarity
Sitei812 – 8132Cleavage; by host signal peptidaseBy similarity

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein, Lipoprotein, Palmitate

Interactioni

Subunit structurei

p62 and E1 form a heterodimer shortly after synthesis. Processing of p62 into E2 and E3 results in a heterodimer of E2 and E1. Spike at virion surface are constituted of three E2-E1 heterodimers. After target cell attachment and endocytosis, E1 change conformation to form homotrimers (By similarity).By similarity

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3VE6X-ray2.83B59-70[»]
ProteinModelPortaliP09592.
SMRiP09592. Positions 119-275.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini126 – 275150Peptidase S3PROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni99 – 11315Ribosome-bindingBy similarityAdd
BLAST
Regioni730 – 75021Transient transmembrane before p62-6K protein processingSequence analysisAdd
BLAST
Regioni896 – 91318E1 fusion peptide loopBy similarityAdd
BLAST

Sequence similaritiesi

Contains 1 peptidase S3 domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Family and domain databases

Gene3Di2.60.40.350. 1 hit.
2.60.98.10. 3 hits.
InterProiIPR002548. Alpha_E1_glycop.
IPR000936. Alpha_E2_glycop.
IPR002533. Alpha_E3_glycop.
IPR000336. Flavivir/Alphavir_Ig-like.
IPR011998. Glycoprot_cen/dimer.
IPR013754. GlyE_dim.
IPR014756. Ig_E-set.
IPR009003. Peptidase_S1_PA.
IPR000930. Peptidase_S3.
[Graphical view]
PfamiPF01589. Alpha_E1_glycop. 1 hit.
PF00943. Alpha_E2_glycop. 1 hit.
PF01563. Alpha_E3_glycop. 1 hit.
PF00944. Peptidase_S3. 1 hit.
[Graphical view]
PRINTSiPR00798. TOGAVIRIN.
SUPFAMiSSF50494. SSF50494. 1 hit.
SSF56983. SSF56983. 1 hit.
SSF81296. SSF81296. 1 hit.
PROSITEiPS51690. ALPHAVIRUS_CP. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P09592-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MFPFQPMYPM QPMPYRNPFA APRRPWFPRT DPFLAMQVQE LTRSMANLTF
60 70 80 90 100
KQRRDAPPEG PSAKKPKKEA SQKQKGGGQG 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
RYDMHGTIKE IPLHQVSLHT SRPCHIVDGH GYFLLARCPA GDSITMEFKK
460 470 480 490 500
DSVTHSCSVP YEVKFNPVGR ELYTHPPEHG VEQACQVYAH DAQNRGAYVE
510 520 530 540 550
MHLPGSEVDS SLVSLSGSSV TVTPPVGTSA LVECECGGTK ISETINKTKQ
560 570 580 590 600
FSQCTKKEQC RAYRLQNDKW VYNSDKLPKA AGATLKGKLH VPFLLADGKC
610 620 630 640 650
TVPLAPEPMI TFGFRSVSLK LHPKNPTYLT TRQLADEPHY THELISEPAV
660 670 680 690 700
RNFTVTEKGW EFVWGNHPPK RFWAQETAPG NPHGLPHEVI THYYHRYPMS
710 720 730 740 750
TILGLSICAA IATVSVAAST WLFCRSRVAC LTPYRLTPNA RIPFCLAVLC
760 770 780 790 800
CARTARAETT WESLDHLWNN NQQMFWIQLL IPLAALIVVT RLLRCVCCVV
810 820 830 840 850
PFLVMAGAAA GAYEHATTMP SQAGISYNTI VNRAGYAPLP ISITPTKIKL
860 870 880 890 900
IPTVNLEYVT CHYKTGMDSP AIKCCGSQEC TPTYRPDEQC KVFTGVYPFM
910 920 930 940 950
WGGAYCFCDT ENTQVSKAYV MKSDDCLADH AEAYKAHTAS VQAFLNITVG
960 970 980 990 1000
EHSIVTTVYV NGETPVNFNG VKLTAGPLST AWTPFDRKIV QYAGEIYNYD
1010 1020 1030 1040 1050
FPEYGAGQPG AFGDIQSRTV SSSDLYANTN LVLQRPKAGA IHVPYTQAPS
1060 1070 1080 1090 1100
GFEQWKKDKA PSLKFTAPFG CEIYTNPIRA ENCAVGSIPL AFDIPDALFT
1110 1120 1130 1140 1150
RVSETPTLSA AECTLNECVY SSDFGGIATV KYSASKSGKC AVHVPSGTAT
1160 1170 1180 1190 1200
LKEAAVELTE QGSATIHFST ANIHPEFRLQ ICTSYVTCKG DCHPPKDHIV
1210 1220 1230 1240 1250
THPQYHAQTF TAAVSKTAWT WLTSLLGGSA VIIIIGLVLA TIVAMYVLTN

QKHN
Length:1,254
Mass (Da):138,351
Last modified:May 30, 2006 - v2
Checksum:i8B5398709A1B4020
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti341 – 3411K → N in strain: Isolate TC-83.
Natural varianti419 – 4191H → Y in strain: Isolate TC-83.
Natural varianti454 – 4541T → R in strain: Isolate TC-83.
Natural varianti526 – 5261V → D in strain: Isolate TC-83.
Natural varianti630 – 6301T → I in strain: Isolate TC-83.
Natural varianti810 – 8101A → GA in strain: Isolate CoAn5384 and Isolate TC-83.
Natural varianti811 – 8111G → P.
Natural varianti973 – 9731L → I in strain: Isolate TC-83.

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M14937 Genomic RNA. Translation: AAA42997.1.
J04332 Genomic RNA. Translation: AAB02519.1.
L01443 Genomic RNA. Translation: AAB02517.1.
L01442 Genomic RNA. Translation: AAC19322.1.
AF004466 Genomic RNA. Translation: AAC36382.1.
PIRiB31467. VHWVVT.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M14937 Genomic RNA. Translation: AAA42997.1.
J04332 Genomic RNA. Translation: AAB02519.1.
L01443 Genomic RNA. Translation: AAB02517.1.
L01442 Genomic RNA. Translation: AAC19322.1.
AF004466 Genomic RNA. Translation: AAC36382.1.
PIRiB31467. VHWVVT.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3VE6X-ray2.83B59-70[»]
ProteinModelPortaliP09592.
SMRiP09592. Positions 119-275.
ModBaseiSearch...
MobiDBiSearch...

Chemistry

DrugBankiDB03904. Urea.

Protein family/group databases

MEROPSiS03.001.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Family and domain databases

Gene3Di2.60.40.350. 1 hit.
2.60.98.10. 3 hits.
InterProiIPR002548. Alpha_E1_glycop.
IPR000936. Alpha_E2_glycop.
IPR002533. Alpha_E3_glycop.
IPR000336. Flavivir/Alphavir_Ig-like.
IPR011998. Glycoprot_cen/dimer.
IPR013754. GlyE_dim.
IPR014756. Ig_E-set.
IPR009003. Peptidase_S1_PA.
IPR000930. Peptidase_S3.
[Graphical view]
PfamiPF01589. Alpha_E1_glycop. 1 hit.
PF00943. Alpha_E2_glycop. 1 hit.
PF01563. Alpha_E3_glycop. 1 hit.
PF00944. Peptidase_S3. 1 hit.
[Graphical view]
PRINTSiPR00798. TOGAVIRIN.
SUPFAMiSSF50494. SSF50494. 1 hit.
SSF56983. SSF56983. 1 hit.
SSF81296. SSF81296. 1 hit.
PROSITEiPS51690. ALPHAVIRUS_CP. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPOLS_EEVVT
AccessioniPrimary (citable) accession number: P09592
Secondary accession number(s): Q66593
, Q66595, Q88691, Q88692, Q88693, Q88694, Q88695
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: May 30, 2006
Last modified: September 7, 2016
This is version 112 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

Miscellaneous

Structural polyprotein is translated from a subgenomic RNA synthesized during togaviruses replication.

Keywords - Technical termi

3D-structure, Complete proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. Peptidase families
    Classification of peptidase families and list of entries
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.