Reviewed, UniProtKB/Swiss-Prot Q8JUX5 (POLS_CHIKS)

Names and origin

Protein names	Structural polyprotein Also known as:      p130 Cleaved into:      Capsid protein           EC 3.4.21.-           Coat protein           C      p62           E3/E2      E3 protein           Spike glycoprotein E3      E2 envelope glycoprotein           Spike glycoprotein E2      6K protein      E1 envelope glycoprotein           Spike glycoprotein E1
Organism	Chikungunya virus (strain S27-African prototype) (CHIKV)
Taxonomic identifier	371094 [NCBI]
Taxonomic lineage	Viruses › ssRNA positive-strand viruses, no DNA stage › Togaviridae › Alphavirus › SFV complex
Virus host	Aedes aegypti (Yellowfever mosquito) [TaxID: 7159] Aedes albopictus (Forest day mosquito) [TaxID: 7160] Cercopithecus [TaxID: 9533] Macaca (macaques) [TaxID: 9539] Papio (baboons) [TaxID: 9554] Presbytis [TaxID: 9573] Pan troglodytes (Chimpanzee) [TaxID: 9598] Homo sapiens (Human) [TaxID: 9606] Aedes polynesiensis [TaxID: 188700] Aedes furcifer [TaxID: 299627]
Protein existence	Inferred from homology.

General annotation (Comments)

Function	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. Synthetized 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, membrane permeabilization, and the budding of viral particles. 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 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 cell and viral membrane fusion. Efficient fusion requires the presence of cholesterol and sphingolipid in the target membrane By similarity.
Subunit structure	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.
Subcellular location	Capsid protein: Virion By similarity. Cytoplasm By similarity. p62: Virion membrane; Single-pass type I membrane protein By similarity. Cell membrane; Single-pass type I membrane protein By similarity. E2 envelope glycoprotein: Virion membrane; Single-pass type I membrane protein By similarity. Cell membrane; Single-pass type I membrane protein By similarity. E1 envelope glycoprotein: Virion membrane; Single-pass type I membrane protein By similarity. Cell membrane; Single-pass type I membrane protein By similarity. 6K protein: Cell membrane; Multi-pass membrane protein By similarity. Virion membrane; Multi-pass membrane protein By similarity.
Post-translational modification	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.
Miscellaneous	Structural polyprotein is translated from a subgenomic RNA synthesized during togavirus replication.
Sequence similarities	Contains 1 peptidase S3 domain.

Ontologies

Keywords
Cellular component	Capsid protein Cytoplasm Membrane Virion
Domain	Signal Transmembrane
Molecular function	Hydrolase Protease Serine protease
PTM	Cleavage on pair of basic residues Glycoprotein Lipoprotein Palmitate
Gene Ontology (GO)
Cellular component	plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell virion membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view
Molecule processing
	Chain	1 – 261	261	Capsid protein By similarity
	Chain	262 – 748	487	p62 By similarity
	Chain	262 – 325	64	E3 protein By similarity
	Signal peptide	262 – 275	14	Not cleaved Potential
	Chain	326 – 748	423	E2 envelope glycoprotein By similarity
	Chain	749 – 809	61	6K protein By similarity
	Chain	810 – 1248	439	E1 envelope glycoprotein By similarity
Regions
	Topological domain	262 – 692	431	Extracellular Potential
	Transmembrane	693 – 713	21	Potential
	Topological domain	714 – 748	35	Cytoplasmic Potential
	Topological domain	749 – 763	15	Extracellular Potential
	Transmembrane	764 – 784	21	Potential
	Topological domain	785 – 795	11	Cytoplasmic Potential
	Transmembrane	796 – 816	21	Potential
	Topological domain	817 – 1224	408	Extracellular Potential
	Transmembrane	1225 – 1245	21	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
Sites
	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...) Potential
	Glycosylation	588	1	N-linked (GlcNAc...) Potential
	Glycosylation	670	1	N-linked (GlcNAc...) Potential
	Glycosylation	950	1	N-linked (GlcNAc...) 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
Experimental info
	Sequence conflict	63	1	K → R Ref.2 Ref.3
	Sequence conflict	91 – 97	7	Missing Ref.3
	Sequence conflict	519 – 520	2	SQ → GR Ref.2 Ref.3
	Sequence conflict	576	1	R → P in AAM10747. Ref.3
	Sequence conflict	592	1	M → R in AAM10747. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Q8JUX5-1 [UniParc]. Last modified June 1, 2003. Version 2. Checksum: A56982D67B774153	FASTA	1,248	138,088
	10 20 30 40 50 60 MEFIPTQTFY NRRYQPRPWT PRPTIQVIRP RPRPQRQAGQ LAQLISAVNK LTMRAVPQQK 70 80 90 100 110 120 PRKNRKNKKQ KQKQQAPQNN TNQKKQPPKK KPAQKKKKPG RRERMCMKIE NDCIFEVKHE 130 140 150 160 170 180 GKVTGYACLV GDKVMKPAHV KGTIDNADLA KLAFKRSSKY DLECAQIPVH MKSDASKFTH 190 200 210 220 230 240 EKPEGYYNWH HGAVQYSGGR FTIPTGAGKP GDSGRPIFDN KGRVVAIVLG GANEGARTAL 250 260 270 280 290 300 SVVTWNKDIV TKITPEGAEE WSLAIPVMCL LANTTFPCSQ PPCIPCCYEK EPEETLRMLE 310 320 330 340 350 360 DNVMRPGYYQ LLQASLTCSP HRQRRSTKDN FNVYKATRPY LAHCPDCGEG HSCHSPVALE 370 380 390 400 410 420 RIRNEATDGT LKIQVSLQIG IGTDDSHDWT KLRYMDNHIP ADAGRAGLFV RTSAPCTITG 430 440 450 460 470 480 TMGHFILARC PKGETLTVGF TDSRKISHSC THPFHHDPPV IGREKFHSRP QHGKELPCST 490 500 510 520 530 540 YVQSNAATAE EIEVHMPPDT PDRTLLSQQS GNVKITVNSQ TVRYKCNCGG SNEGLITTDK 550 560 570 580 590 600 VINNCKVDQC HAAVTNHKKW QYNSPLVPRN AELGDRKGKI HIPFPLANVT CMVPKARNPT 610 620 630 640 650 660 VTYGKNQVIM LLYPDHPTLL SYRSMGEEPN YQEEWVTHKK EVVLTVPTEG LEVTWGNNEP 670 680 690 700 710 720 YKYWPQLSAN GTAHGHPHEI ILYYYELYPT MTVVVVSVAS FILLSMVGMA VGMCMCARRR 730 740 750 760 770 780 CITPYELTPG ATVPFLLSLI CCIRTAKAAT YQEAAVYLWN EQQPLFWLQA LIPLAALIVL 790 800 810 820 830 840 CNCLRLLPCC CKTLAFLAVM SIGAHTVSAY EHVTVIPNTV GVPYKTLVNR PGYSPMVLEM 850 860 870 880 890 900 ELLSVTLEPT LSLDYITCEY KTVIPSPYVK CCGTAECKDK NLPDYSCKVF TGVYPFMWGG 910 920 930 940 950 960 AYCFCDAENT QLSEAHVEKS ESCKTEFASA YRAHTASASA KLRVLYQGNN ITVTAYANGD 970 980 990 1000 1010 1020 HAVTVKDAKF IVGPMSSAWT PFDNKIVVYK GDVYNMDYPP FGAGRPGQFG DIQSRTPESK 1030 1040 1050 1060 1070 1080 DVYANTQLVL QRPAAGTVHV PYSQAPSGFK YWLKERGASL QHTAPFGCQI ATNPVRAMNC 1090 1100 1110 1120 1130 1140 AVGNMPISID IPDAAFTRVV DAPSLTDMSC EVPACTHSSD FGGVAIIKYA VSKKGKCAVH 1150 1160 1170 1180 1190 1200 SMTNAVTIRE AEIEVEGNSQ LQISFSTALA SAEFRVQVCS TQVHCAAECH PPKDHIVNYP 1210 1220 1230 1240 ASHTTLGVQD ISATAMSWVQ KITGGVGLVV AVAALILIVV LCVSFSRH

References

[1]	"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: 12466484] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[2]	"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].
[3]	Logue C.H., Atkins G.J. Submitted (OCT-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA]. Strain: Isolate Ross.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF369024 Genomic RNA. Translation: AAN05102.2. AF339485 Genomic RNA. Translation: AAO33341.1. AF490259 Genomic RNA. Translation: AAM10747.1.
RefSeq	NP_690589.2.
3D structure databases
HSSP	HSSP built from PDB template 1VCP based on UniProtKB P03315.
SMR	Q8JUX5. Positions 113-261.
ModBase	Search...
Protein family/group databases
MEROPS	S03.001.
Genome annotation databases
GeneID	956308.
Family and domain databases
InterPro	IPR002548. Alpha_E1_glycop. IPR000936. Alpha_E2_glycop. IPR002533. Alpha_E3_glycop. IPR000930. Peptidase_S3. [Graphical view]
Pfam	PF01589. Alpha_E1_glycop. 1 hit. PF00943. Alpha_E2_glycop. 1 hit. PF01563. Alpha_E3_glycop. 1 hit. PF00944. Peptidase_S3. 1 hit. [Graphical view]
PRINTS	PR00798. TOGAVIRIN.
ProDom	Q8JUX5. [Graphical view] [Entries sharing at least one domain]
BLOCKS	Search...
Other Resources
ProtoNet	Search...

Entry information

Entry name

POLS_CHIKS

Accession

Primary (citable) accession number: Q8JUX5
Secondary accession number(s): Q80S29, Q8QR21

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 7, 2006
Last sequence update:	June 1, 2003
Last modified:	June 10, 2008
This is version 45 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

Virus annotation project