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Protein

Structural polyprotein

Gene
N/A
Organism
Venezuelan equine encephalitis virus (strain Trinidad donkey) (VEEV)
Status
Reviewed-Annotation score: -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 icosahedric core particles. 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. In case of infection, 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
Assembly protein E3: Provides the signal sequence for the translocation of the precursor of protein E3/E2 to the host endoplasmic reticulum. Mediates pH protection of spike glycoprotein E1 during the transport via the secretory pathway.By similarity
Spike glycoprotein E2: Plays a role in 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
6K protein: 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
Spike glycoprotein E1: 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. 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 similarity

Miscellaneous

Structural polyprotein: Translated from a subgenomic RNA synthesized during togavirus replication.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.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei152Charge relay systemPROSITE-ProRule annotation1
Active sitei174Charge relay systemPROSITE-ProRule annotation1
Active sitei226Charge relay systemPROSITE-ProRule annotation1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Protease, Serine protease
Biological processClathrin-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

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):
p62
pE2
Alternative name(s):
E2 envelope glycoprotein
Alternative name(s):
E1 envelope glycoprotein
OrganismiVenezuelan equine encephalitis virus (strain Trinidad donkey) (VEEV)
Taxonomic identifieri11038 [NCBI]
Taxonomic lineageiVirusesssRNA virusesssRNA positive-strand viruses, no DNA stageTogaviridaeAlphavirus
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
  • UP000127220 Componenti: Genome
  • UP000146452 Componenti: Genome
  • UP000008659 Componenti: Genome

Subcellular locationi

Capsid protein :
  • Virion By similarity
  • Host cytoplasm By similarity
  • Host cell membrane By similarity
Spike glycoprotein E2 :
6K protein :
Spike glycoprotein E1 :

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini276 – 701ExtracellularSequence analysisAdd BLAST426
Transmembranei702 – 722HelicalSequence analysisAdd BLAST21
Topological domaini723 – 757CytoplasmicSequence analysisAdd BLAST35
Topological domaini758 – 772ExtracellularSequence analysisAdd BLAST15
Transmembranei773 – 793HelicalSequence analysisAdd BLAST21
Topological domaini794 – 795CytoplasmicSequence analysis2
Transmembranei796 – 816HelicalSequence analysisAdd BLAST21
Topological domaini817 – 1224ExtracellularSequence analysisAdd BLAST408
Transmembranei1225 – 1245HelicalSequence analysisAdd BLAST21
Topological domaini1246 – 1254CytoplasmicSequence analysis9

GO - Cellular componenti

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 databases

DrugBankiDB03904 Urea

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000412761 – 275Capsid proteinAdd BLAST275
ChainiPRO_0000234323276 – 757Precursor of protein E3/E2Add BLAST482
ChainiPRO_0000041277276 – 334Assembly protein E3Add BLAST59
ChainiPRO_0000041278335 – 757Spike glycoprotein E2Add BLAST423
ChainiPRO_0000041279758 – 8126K proteinAdd BLAST55
ChainiPRO_0000041280813 – 1254Spike glycoprotein E1Add BLAST442

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi286N-linked (GlcNAc...) asparagine; by hostSequence analysis1
Glycosylationi546N-linked (GlcNAc...) asparagine; by hostSequence analysis1
Glycosylationi652N-linked (GlcNAc...) asparagine; by hostSequence analysis1
Lipidationi730S-palmitoyl cysteine; by hostBy similarity1
Lipidationi750S-palmitoyl cysteine; by hostBy similarity1
Lipidationi751S-palmitoyl cysteine; by hostBy similarity1
Disulfide bondi861 ↔ 926By similarity
Disulfide bondi874 ↔ 906By similarity
Disulfide bondi875 ↔ 908By similarity
Disulfide bondi880 ↔ 890By similarity
Glycosylationi946N-linked (GlcNAc...) asparagine; by hostSequence analysis1
Disulfide bondi1071 ↔ 1083By similarity
Disulfide bondi1113 ↔ 1188By similarity
Disulfide bondi1118 ↔ 1192By similarity
Disulfide bondi1140 ↔ 1182By similarity

Post-translational modificationi

Structural polyprotein: Specific enzymatic cleavages in vivo yield mature proteins. Capsid protein is auto-cleaved during polyprotein translation, unmasking a signal peptide at the N-terminus of the precursor of E3/E2. The remaining polyprotein is then targeted to the host endoplasmic reticulum, where host signal peptidase cleaves it into pE2, 6K and E1 proteins. pE2 is further processed to mature E3 and E2 by host furin in trans-Golgi vesicle.By similarity
Spike glycoprotein E2: Palmitoylated via thioester bonds. These palmitoylations may induce disruption of the C-terminus transmembrane. This would result in the reorientation of E2 C-terminus from lumenal to cytoplasmic side.By similarity
Spike glycoprotein E1: N-glycosylated.By similarity
Spike glycoprotein E2: N-glycosylated.By similarity
Assembly protein E3: N-glycosylated.By similarity
6K protein: Palmitoylated via thioester bonds.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei275 – 276Cleavage; by autolysisBy similarity2
Sitei334 – 335Cleavage; by host furinBy similarity2
Sitei757 – 758Cleavage; by host signal peptidaseBy similarity2
Sitei812 – 813Cleavage; by host signal peptidaseBy similarity2

Keywords - PTMi

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

Interactioni

Subunit structurei

Precursor of protein E3/E2: The precursor of protein E3/E2 and E1 form a heterodimer shortly after synthesis. Spike glycoprotein E1: The precursor of protein E3/E2 and E1 form a heterodimer shortly after synthesis. Spike glycoprotein E1: Processing of the precursor of protein E3/E2 into E2 and E3 results in a heterodimer of the spike glycoproteins E2 and E1. Spike glycoprotein E2: Processing of the precursor of protein E3/E2 into E2 and E3 results in a heterodimer of the spike glycoproteins E2 and E1. Spike glycoprotein E1: Spike at virion surface are constituted of three E2-E1 heterodimers. Spike glycoprotein E2: Spike at virion surface are constituted of three E2-E1 heterodimers. Spike glycoprotein E1: After target cell attachment and endocytosis, E1 change conformation to form homotrimers. 6K protein: Interacts with spike glycoprotein E1. 6K protein: Interacts with spike glycoprotein E2. Spike glycoprotein E1: Interacts with 6K protein. Spike glycoprotein E2: Interacts with 6K protein.By similarity

Structurei

3D structure databases

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

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini126 – 275Peptidase S3PROSITE-ProRule annotationAdd BLAST150

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni99 – 113Ribosome-bindingBy similarityAdd BLAST15
Regioni276 – 287Functions as an uncleaved signal peptide for the precursor of protein E3/E2By similarityAdd BLAST12
Regioni730 – 750Transient transmembrane before p62-6K protein processingSequence analysisAdd BLAST21
Regioni896 – 913E1 fusion peptide loopBy similarityAdd BLAST18

Domaini

Structural polyprotein: As soon as the capsid protein has been autocleaved, an internal uncleaved signal peptide directs the remaining polyprotein to the endoplasmic reticulum.By similarity

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

OrthoDBiVOG0900007W

Family and domain databases

Gene3Di2.60.40.350, 1 hit
2.60.98.10, 3 hits
InterProiView protein in InterPro
IPR002548 Alpha_E1_glycop
IPR000936 Alpha_E2_glycop
IPR002533 Alpha_E3_glycop
IPR000336 Flavivir/Alphavir_Ig-like_sf
IPR036253 Glycoprot_cen/dimer_sf
IPR038055 Glycoprot_E_dimer_dom
IPR014756 Ig_E-set
IPR009003 Peptidase_S1_PA
IPR000930 Peptidase_S3
PfamiView 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
PRINTSiPR00798 TOGAVIRIN
SUPFAMiSSF50494 SSF50494, 1 hit
SSF56983 SSF56983, 1 hit
SSF81296 SSF81296, 1 hit
PROSITEiView protein in PROSITE
PS51690 ALPHAVIRUS_CP, 1 hit

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)DescriptionActionsGraphical viewLength
Natural varianti341K → N in strain: Isolate TC-83. 1
Natural varianti419H → Y in strain: Isolate TC-83. 1
Natural varianti454T → R in strain: Isolate TC-83. 1
Natural varianti526V → D in strain: Isolate TC-83. 1
Natural varianti630T → I in strain: Isolate TC-83. 1
Natural varianti810A → GA in strain: Isolate CoAn5384 and Isolate TC-83. 1
Natural varianti811G → P. 1
Natural varianti973L → I in strain: Isolate TC-83. 1

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

Similar proteinsi

Entry informationi

Entry nameiPOLS_EEVVT
AccessioniPrimary (citable) accession number: P09592
Secondary accession number(s): Q66593
, Q66595, Q88691, Q88692, Q88693, Q88694, Q88695
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: May 30, 2006
Last modified: April 25, 2018
This is version 122 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome
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Main funding by: National Institutes of Health