P27285 (POLS_SINDO) Reviewed, UniProtKB/Swiss-Prot
Last modified May 14, 2014. Version 110. History...
Names and origin
|Protein names||Recommended name:|
Cleaved into the following 6 chains:
|Organism||Sindbis virus subtype Ockelbo (strain Edsbyn 82-5) (OCKV) (Ockelbo virus) [Complete proteome]|
|Taxonomic identifier||31699 [NCBI]|
|Taxonomic lineage||Viruses › ssRNA positive-strand viruses, no DNA stage › Togaviridae › Alphavirus › WEEV complex ›|
|Virus host||Acrocephalus scirpaceus (Eurasian reed-warbler) [TaxID: 48156]|
Aedes [TaxID: 7158]
Culex [TaxID: 53527]
Homo sapiens (Human) [TaxID: 9606]
Motacilla alba (White wagtail) (Pied wagtail) [TaxID: 45807]
Streptopelia turtur [TaxID: 177155]
|Sequence length||1245 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 and 6K are palmitoylated via thioester bonds.
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 – 264||264||Capsid protein||PRO_0000041316|
|Chain||265 – 751||487||p62 By similarity||PRO_0000226240|
|Chain||265 – 328||64||E3 protein||PRO_0000041317|
|Signal peptide||265 – 280||16||Not cleaved Potential|
|Chain||329 – 751||423||E2 envelope glycoprotein||PRO_0000041318|
|Chain||752 – 806||55||6K protein||PRO_0000041319|
|Chain||807 – 1245||439||E1 envelope glycoprotein||PRO_0000041320|
|Transmembrane||696 – 712||17||Helical; Potential|
|Transmembrane||728 – 746||19||Helical; Potential|
|Transmembrane||768 – 784||17||Helical; Potential|
|Transmembrane||786 – 802||17||Helical; Potential|
|Transmembrane||1216 – 1234||19||Helical; Potential|
|Domain||114 – 264||151||Peptidase S3|
|Region||93 – 101||9||Ribosome-binding By similarity|
|Active site||141||1||Charge relay system By similarity|
|Active site||147||1||Charge relay system By similarity|
|Active site||215||1||Charge relay system By similarity|
|Site||264 – 265||2||Cleavage; by capsid protein By similarity|
|Site||328 – 329||2||Cleavage; by host furin By similarity|
|Site||751 – 752||2||Cleavage; by host signal peptidase By similarity|
|Site||806 – 807||2||Cleavage; by host signal peptidase By similarity|
Amino acid modifications
|Lipidation||724||1||S-palmitoyl cysteine; by host By similarity|
|Lipidation||744||1||S-palmitoyl cysteine; by host By similarity|
|Lipidation||745||1||S-palmitoyl cysteine; by host By similarity|
|Glycosylation||278||1||N-linked (GlcNAc...); by host Potential|
|Glycosylation||524||1||N-linked (GlcNAc...); by host Potential|
|Glycosylation||646||1||N-linked (GlcNAc...); by host Potential|
|Glycosylation||945||1||N-linked (GlcNAc...); by host Potential|
|Glycosylation||1051||1||N-linked (GlcNAc...); by host Potential|
|Disulfide bond||855 ↔ 920||By similarity|
|Disulfide bond||868 ↔ 900||By similarity|
|Disulfide bond||869 ↔ 902||By similarity|
|Disulfide bond||874 ↔ 884||By similarity|
|Disulfide bond||1065 ↔ 1077||By similarity|
|Disulfide bond||1107 ↔ 1182||By similarity|
|Disulfide bond||1112 ↔ 1186||By similarity|
|Disulfide bond||1134 ↔ 1176||By similarity|
Helix Strand Turn
|Beta strand||115 – 119||5|
|Beta strand||125 – 132||8|
|Beta strand||135 – 139||5|
|Beta strand||144 – 148||5|
|Helix||151 – 153||3|
|Beta strand||157 – 159||3|
|Helix||160 – 162||3|
|Beta strand||164 – 168||5|
|Turn||171 – 176||6|
|Beta strand||186 – 191||6|
|Beta strand||194 – 199||6|
|Beta strand||202 – 206||5|
|Beta strand||218 – 220||3|
|Beta strand||226 – 236||11|
|Beta strand||239 – 247||9|
|Beta strand||253 – 256||4|
|||"Structure of the Ockelbo virus genome and its relationship to other Sindbis viruses."|
Shirako Y., Niklasson B., Dalrymple J.M., Strauss E.G., Strauss J.H.
Virology 182:753-764(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
|+||Additional computationally mapped references.|
|M69205 Genomic RNA. Translation: AAA96973.1.|
M69207 Genomic RNA. Translation: AAA73066.1.
|PIR||VHWV82. B39991. |
3D structure databases
|SMR||P27285. Positions 106-264, 691-726, 807-1096, 1101-1189, 1215-1245. |
Protocols and materials databases
Family and domain databases
|Gene3D||188.8.131.520. 1 hit. |
184.108.40.206. 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.
|PROSITE||PS51690. ALPHAVIRUS_CP. 1 hit. |
|Accession||Primary (citable) accession number: P27285|
Secondary accession number(s): Q00349
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Viral Protein Annotation Program|