Q5XXP3 · POLS_CHIK3

Function

function

Capsid protein

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 (By similarity).
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).
Degrades host cyclic GMP-AMP synthase (CGAS) thereby inhibiting the cGAS-STING pathway (By similarity).

Assembly protein E3

Provides 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.

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.

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.

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.

Miscellaneous

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

Catalytic activity

  • Autocatalytic release of the core protein from the N-terminus of the togavirus structural polyprotein by hydrolysis of a -Trp-|-Ser- bond.
    EC:3.4.21.90 (UniProtKB | ENZYME | Rhea)

Features

Showing features for active site, site.

TypeIDPosition(s)Description
Active site139Charge relay system
Active site161Charge relay system
Site187Involved in dimerization of the capsid protein
Active site213Charge relay system
Site220Involved in dimerization of the capsid protein
Site261-262Cleavage; by autolysis
Site325-326Cleavage; by host furin
Site748-749Cleavage; by host signal peptidase
Site809-810Cleavage; by host signal peptidase

GO annotations

AspectTerm
Cellular Componenthost cell cytoplasm
Cellular Componenthost cell nucleus
Cellular Componenthost cell plasma membrane
Cellular Componentmembrane
Cellular ComponentT=4 icosahedral viral capsid
Cellular Componentvirion membrane
Molecular FunctionRNA binding
Molecular Functionserine-type endopeptidase activity
Molecular Functionstructural molecule activity
Biological Processfusion of virus membrane with host endosome membrane
Biological Processproteolysis
Biological Processsymbiont entry into host cell
Biological Processsymbiont-mediated suppression of host toll-like receptor signaling pathway
Biological Processvirion attachment to host cell

Keywords

Protein family/group databases

Names & Taxonomy

Protein names

Organism names

Accessions

  • Primary accession
    Q5XXP3

Proteomes

Subcellular Location

Capsid protein

Virion
Host cytoplasm
Host cell membrane
Host nucleus
Note: Shuttles between the cytoplasm and the nucleus.

Spike glycoprotein E2

Virion membrane
; Single-pass type I membrane protein
Host cell membrane
; Single-pass type I membrane protein

6K protein

Host cell membrane
; Multi-pass membrane protein
Virion membrane
; Multi-pass membrane protein

Spike glycoprotein E1

Virion membrane
; Single-pass type I membrane protein
Host cell membrane
; Single-pass type I membrane protein

Features

Showing features for topological domain, transmembrane.

TypeIDPosition(s)Description
Topological domain1-692Extracellular
Transmembrane693-713Helical
Topological domain714-748Cytoplasmic
Topological domain749-763Extracellular
Transmembrane764-784Helical
Topological domain785-795Cytoplasmic
Transmembrane796-816Helical
Topological domain817-1224Extracellular
Transmembrane1225-1245Helical
Topological domain1246-1248Cytoplasmic

Keywords

PTM/Processing

Features

Showing features for chain, disulfide bond, glycosylation, lipidation.

TypeIDPosition(s)Description
ChainPRO_00002262251-261Capsid protein
Disulfide bond113↔128
ChainPRO_0000226227262-325Assembly protein E3
ChainPRO_0000226226262-748Precursor of protein E3/E2
Glycosylation273N-linked (GlcNAc...) asparagine; by host
ChainPRO_0000226228326-748Spike glycoprotein E2
Glycosylation588N-linked (GlcNAc...) asparagine; by host
Glycosylation670N-linked (GlcNAc...) asparagine; by host
Lipidation721S-palmitoyl cysteine; by host
Lipidation741S-palmitoyl cysteine; by host
Lipidation742S-palmitoyl cysteine; by host
ChainPRO_0000226229749-8096K protein
ChainPRO_0000226230810-1248Spike glycoprotein E1
Disulfide bond858↔923
Disulfide bond871↔903
Disulfide bond872↔905
Disulfide bond877↔887
Glycosylation950N-linked (GlcNAc...) asparagine; by host
Disulfide bond1068↔1080
Disulfide bond1110↔1185
Disulfide bond1115↔1189
Disulfide bond1137↔1179
Lipidation1242S-stearoyl cysteine; by host

Post-translational modification

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 (By similarity).
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.

Spike glycoprotein E1

N-glycosylated.

Spike glycoprotein E2

N-glycosylated.

Assembly protein E3

N-glycosylated.

6K protein

Palmitoylated via thioester bonds.

Keywords

Interaction

Subunit

Capsid protein

Homodimer (By similarity).
Homomultimer (Probable). 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).

Precursor of protein E3/E2

The precursor of protein E3/E2 and E1 form a heterodimer shortly after synthesis (By similarity).

Spike glycoprotein E1

The 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 (By similarity).
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).

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 (By similarity).
Spike at virion surface are constituted of three E2-E1 heterodimers (By similarity).
Interacts with 6K protein (By similarity).
Interacts with host MXRA8; this interaction mediates virus entry (By similarity).

6K protein

Interacts with spike glycoprotein E1 (By similarity).
Interacts with spike glycoprotein E2 (By similarity).

Family & Domains

Features

Showing features for region, motif, compositional bias, domain.

TypeIDPosition(s)Description
Region14-104Disordered
Region36-68Host transcription inhibition
Motif61-99Nuclear localization signal
Compositional bias73-87Basic and acidic residues
Region84-114Binding to the viral RNA
Compositional bias88-102Basic residues
Region99-113Ribosome-binding
Domain113-261Peptidase S3
Motif144-154Nuclear export signal
Region183-193Dimerization of the capsid protein
Region219-223Dimerization of the capsid protein
Region262-274Functions as an uncleaved signal peptide for the precursor of protein E3/E2
Region721-741Transient transmembrane before p62-6K protein processing
Region893-910E1 fusion peptide loop

Domain

Capsid protein

The N-terminus contains a nuclear localization signal and a CRM1-mediated nuclear export signal (By similarity).
The C-terminus functions as a protease during translation to cleave itself from the translating structural polyprotein (By similarity).
Structural polyprotein: As soon as the capsid protein has been autocleaved, an internal uncleaved signal peptide directs the remaining polyprotein to the endoplasmic reticulum.

Keywords

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    1,248
  • Mass (Da)
    138,071
  • Last updated
    2004-11-23 v1
  • Checksum
    A19160F7E5ED521E
MEFIPTQTFYNRRYQPRPWAPRPTIQVIRPRPRPQRQAGQLAQLISAVNKLTMRAVPQQKPRRNRKNKKQRQKKQAPQNDPKQKKQPPQKKPAQKKKKPGRRERMCMKIENDCIFEVKHEGKVMGYACLVGDKVMKPAHVKGTIDNADLAKLAFKRSSKYDLECAQIPVHMKSDASKFTHEKPEGYYNWHHGAVQYSGGRFTIPTGAGKPGDSGRPIFDNKGRVVAIVLGGANEGARTALSVVTWNKDIVTKITPEGAEEWSLALPVLCLLANTTFPCSQPPCTPCCYEKEPESTLRMLEDNVMRPGYYQLLKASLTCSPHRQRRSTKDNFNVYKATRPYLAHCPDCGEGHSCHSPIALERIRNEATDGTLKIQVSLQIGIKTDDSHDWTKLRYMDSHTPADAERAGLLVRTSAPCTITGTMGHFILARCPKGETLTVGFTDSRKISHTCTHPFHHEPPVIGRERFHSRPQHGKELPCSTYVQSTAATAEEIEVHMPPDTPDRTLMTQQSGNVKITVNGQTVRYKCNCGGSNEGLTTTDKVINNCKIDQCHAAVTNHKNWQYNSPLVPRNAELGDRKGKIHIPFPLANVTCRVPKARNPTVTYGKNQVTMLLYPDHPTLLSYRNMGQEPNYHEEWVTHKKEVTLTVPTEGLEVTWGNNEPYKYWPQMSTNGTAHGHPHEIILYYYELYPTMTVVIVSVASFVLLSMVGTAVGMCVCARRRCITPYELTPGATVPFLLSLLCCVRTTKAATYYEAAAYLWNEQQPLFWLQALIPLAALIVLCNCLKLLPCCCKTLAFLAVMSIGAHTVSAYEHVTVIPNTVGVPYKTLVNRPGYSPMVLEMELQSVTLEPTLSLDYITCEYKTVIPSPYVKCCGTAECKDKSLPDYSCKVFTGVYPFMWGGAYCFCDAENTQLSEAHVEKSESCKTEFASAYRAHTASASAKLRVLYQGNNITVAAYANGDHAVTVKDAKFVVGPMSSAWTPFDNKIVVYKGDVYNMDYPPFGAGRPGQFGDIQSRTPESKDVYANTQLVLQRPAAGTVHVPYSQAPSGFKYWLKERGASLQHTAPFGCQIATNPVRAVNCAVGNIPISIDIPDAAFTRVVDAPSVTDMSCEVPACTHSSDFGGVAIIKYTASKKGKCAVHSMTNAVTIREADVEVEGNSQLQISFSTALASAEFRVQVCSTQVHCAAACHPPKDHIVNYPASHTTLGVQDISTTAMSWVQKITGGVGLIVAVAALILIVVLCVSFSRH

Features

Showing features for compositional bias.

TypeIDPosition(s)Description
Compositional bias73-87Basic and acidic residues
Compositional bias88-102Basic residues

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AY726732
EMBL· GenBank· DDBJ
AAU43881.1
EMBL· GenBank· DDBJ
Genomic RNA

Similar Proteins

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