Q8JUX5 (POLS_CHIKS) Reviewed, UniProtKB/Swiss-Prot
Last modified October 16, 2013. Version 79. History...
Names and origin
|Protein names||Recommended name:|
Cleaved into the following 6 chains:
|Organism||Chikungunya virus (strain S27-African prototype) (CHIKV) [Reference proteome]|
|Taxonomic identifier||371094 [NCBI]|
|Taxonomic lineage||Viruses › ssRNA positive-strand viruses, no DNA stage › Togaviridae › Alphavirus › SFV complex ›|
|Virus host||Aedes aegypti (Yellowfever mosquito) (Culex aegypti) [TaxID: 7159]|
Aedes albopictus (Asian tiger mosquito) (Stegomyia albopicta) [TaxID: 7160]
Aedes furcifer (Mosquito) [TaxID: 299627]
Aedes polynesiensis (Polynesian tiger mosquito) [TaxID: 188700]
Cercopithecus [TaxID: 9533]
Homo sapiens (Human) [TaxID: 9606]
Macaca (macaques) [TaxID: 9539]
Pan troglodytes (Chimpanzee) [TaxID: 9598]
Papio (baboons) [TaxID: 9554]
Presbytis [TaxID: 9573]
|Sequence length||1248 AA.|
|Sequence processing||The displayed sequence is further processed into a mature form.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
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 endocytosis their membrane fuses with the target cell 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.
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.
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.
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.
Autocatalytic release of the core protein from the N-terminus of the togavirus structural polyprotein by hydrolysis of a -Trp-|-Ser- bond.
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.
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.
E2 is 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. 6K protein is also palmitoylated. E1 is stearoylated By similarity.
Structural polyprotein is translated from a subgenomic RNA synthesized during togavirus replication.
Contains 1 peptidase S3 domain.
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||1 – 261||261||Capsid protein By similarity||PRO_0000226219|
|Chain||262 – 748||487||p62 By similarity||PRO_0000226220|
|Chain||262 – 325||64||E3 protein By similarity||PRO_0000226221|
|Signal peptide||262 – 275||14||Not cleaved Potential|
|Chain||326 – 748||423||E2 envelope glycoprotein By similarity||PRO_0000226222|
|Chain||749 – 809||61||6K protein By similarity||PRO_0000226223|
|Chain||810 – 1248||439||E1 envelope glycoprotein By similarity||PRO_0000226224|
|Topological domain||262 – 692||431||Extracellular Potential|
|Transmembrane||693 – 713||21||Helical; Potential|
|Topological domain||714 – 748||35||Cytoplasmic Potential|
|Topological domain||749 – 763||15||Extracellular Potential|
|Transmembrane||764 – 784||21||Helical; Potential|
|Topological domain||785 – 795||11||Cytoplasmic Potential|
|Transmembrane||796 – 816||21||Helical; Potential|
|Topological domain||817 – 1224||408||Extracellular Potential|
|Transmembrane||1225 – 1245||21||Helical; Potential|
|Topological domain||1246 – 1248||3||Cytoplasmic Potential|
|Domain||106 – 261||156||Peptidase S3|
|Region||1 – 107||107||Intrinsically disordered, in contact with genomic RNA in nucleocapsid Potential|
|Region||91 – 100||10||Ribosome-binding By similarity|
|Region||721 – 741||21||Transient transmembrane before p62-6K protein processing Potential|
|Region||893 – 910||18||E1 fusion peptide loop By similarity|
|Compositional bias||60 – 98||39||Lys-rich|
|Active site||139||1||Charge relay system By similarity|
|Active site||145||1||Charge relay system By similarity|
|Active site||213||1||Charge relay system By similarity|
|Site||261 – 262||2||Cleavage; by capsid protein By similarity|
|Site||325 – 326||2||Cleavage; by host furin By similarity|
|Site||748 – 749||2||Cleavage; by host signal peptidase By similarity|
|Site||809 – 810||2||Cleavage; by host signal peptidase By similarity|
Amino acid modifications
|Lipidation||721||1||S-palmitoyl cysteine; by host By similarity|
|Lipidation||741||1||S-palmitoyl cysteine; by host By similarity|
|Lipidation||742||1||S-palmitoyl cysteine; by host By similarity|
|Lipidation||1242||1||S-stearoyl cysteine; by host By similarity|
|Glycosylation||273||1||N-linked (GlcNAc...); by host Potential|
|Glycosylation||588||1||N-linked (GlcNAc...); by host Potential|
|Glycosylation||670||1||N-linked (GlcNAc...); by host Potential|
|Glycosylation||950||1||N-linked (GlcNAc...); by host Potential|
|Disulfide bond||113 ↔ 128||By similarity|
|Disulfide bond||858 ↔ 923||By similarity|
|Disulfide bond||871 ↔ 903||By similarity|
|Disulfide bond||872 ↔ 905||By similarity|
|Disulfide bond||877 ↔ 887||By similarity|
|Disulfide bond||1068 ↔ 1080||By similarity|
|Disulfide bond||1110 ↔ 1185||By similarity|
|Disulfide bond||1115 ↔ 1189||By similarity|
|Disulfide bond||1137 ↔ 1179||By similarity|
|Sequence conflict||63||1||R → K in AAN05102. Ref.1|
|Sequence conflict||519 – 520||2||GR → SQ in AAN05102. Ref.1|
Helix Strand Turn
|Helix||895 – 899||5|
|Turn||904 – 907||4|
|||"Complete nucleotide sequence of chikungunya virus and evidence for an internal polyadenylation site."|
Khan A.H., Morita K., Parquet Md Mdel C., Hasebe F., Mathenge E.G., Igarashi A.
J. Gen. Virol. 83:3075-3084(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
|||"Nucleotide sequence analyses of the 26S mRNAs of viruses of the genus Alphavirus."|
Kinney R.M., Pfeffer M.
Submitted (JAN-2001) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
|||Logue C.H., Atkins G.J.|
Submitted (OCT-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
Strain: Isolate Ross.
|||Logue C.H., Chamberlain J.F., Atkins G.J.|
Submitted (FEB-2011) to the EMBL/GenBank/DDBJ databases
Cited for: SEQUENCE REVISION TO 91-97; 576 AND 592.
|+||Additional computationally mapped references.|
|AF369024 Genomic RNA. Translation: AAN05102.2.|
AF339485 Genomic RNA. Translation: AAO33341.1.
AF490259 Genomic RNA. Translation: AAM10747.2.
|RefSeq||NP_690589.2. NC_004162.2. |
3D structure databases
Protein family/group databases
Protocols and materials databases
Genome annotation databases
Family and domain databases
|Gene3D||184.108.40.2060. 1 hit. |
220.127.116.11. 3 hits.
|InterPro||IPR002548. Alpha_E1_glycop. |
|Pfam||PF01589. Alpha_E1_glycop. 1 hit. |
PF00943. Alpha_E2_glycop. 1 hit.
PF01563. Alpha_E3_glycop. 1 hit.
PF00944. Peptidase_S3. 1 hit.
|PRINTS||PR00798. TOGAVIRIN. |
|SUPFAM||SSF50494. SSF50494. 1 hit. |
SSF56983. SSF56983. 1 hit.
SSF81296. SSF81296. 1 hit.
|Accession||Primary (citable) accession number: Q8JUX5|
Secondary accession number(s): Q80S29, Q8QR21
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Viral Protein Annotation Program|