Reviewed, UniProtKB/Swiss-Prot P22056 (POLS_ONNVG)

Names and origin

Protein names	Recommended name:     Structural polyprotein Alternative name(s):     p130 Cleaved into the following 6 chains:     1- Recommended name:             Capsid protein               EC=3.4.21.-         Alternative name(s):             Coat protein               Short name=C     2- Recommended name:             p62         Alternative name(s):             E3/E2     3- Recommended name:             E3 protein         Alternative name(s):             Spike glycoprotein E3     4- Recommended name:             E2 envelope glycoprotein         Alternative name(s):             Spike glycoprotein E2     5- Recommended name:             6K protein     6- Recommended name:             E1 envelope glycoprotein         Alternative name(s):             Spike glycoprotein E1
Organism	O'nyong-nyong virus (strain Gulu) (ONNV)
Taxonomic identifier	11028 [NCBI]
Taxonomic lineage	Viruses › ssRNA positive-strand viruses, no DNA stage › Togaviridae › Alphavirus › SFV complex
Virus host	Homo sapiens (Human) [TaxID: 9606] Anopheles [TaxID: 44482]

Protein attributes

Sequence length	1247 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
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 E3/E2 precursor which is processed by furin at the cell membrane just before virion budding, giving rise to E2-E1 heterodimer. P62-E1 heterodimer is stable, whereas E2-E1 is unstable and dissociate at low pH. P62 E3/E2 precursor 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: VirionBy similarity. CytoplasmBy similarity. p62: Virion membrane; Single-pass type I membrane proteinBy similarity. Cell membrane; Single-pass type I membrane proteinBy similarity. E2 envelope glycoprotein: Virion membrane; Single-pass type I membrane proteinBy similarity. Cell membrane; Single-pass type I membrane proteinBy similarity. E1 envelope glycoprotein: Virion membrane; Single-pass type I membrane proteinBy similarity. Cell membrane; Single-pass type I membrane proteinBy similarity. 6K protein: Cell membrane; Multi-pass membrane proteinBy similarity. Virion membrane; Multi-pass membrane proteinBy 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 Cell membrane 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	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 – 260	260	Capsid protein By similarity
	Chain	261 – 747	487	p62 By similarity
	Chain	261 – 324	64	E3 protein By similarity
	Signal peptide	261 – 274	14	Not cleaved Potential
	Chain	325 – 747	423	E2 envelope glycoprotein By similarity
	Chain	748 – 808	61	6K protein By similarity
	Chain	809 – 1247	439	E1 envelope glycoprotein By similarity
Regions
	Transmembrane	692 – 712	21	Potential
	Transmembrane	720 – 740	21	Potential
	Transmembrane	763 – 783	21	Potential
	Transmembrane	1224 – 1244	21	Potential
	Domain	105 – 260	156	Peptidase S3
	Region	1 – 106	106	Intrinsically disordered, in contact with genomic RNA in nucleocapsid Potential
	Region	86 – 99	14	Ribosome-binding By similarity
	Region	720 – 740	21	Transient transmembrane before p62-6K protein processing Potential
	Region	892 – 909	18	E1 fusion peptide loop By similarity
Sites
	Active site	138	1	Charge relay system By similarity
	Active site	144	1	Charge relay system By similarity
	Active site	212	1	Charge relay system By similarity
	Site	260 – 261	2	Cleavage; by capsid protein By similarity
	Site	324 – 325	2	Cleavage; by host furin By similarity
	Site	747 – 748	2	Cleavage; by host signal peptidase By similarity
	Site	808 – 809	2	Cleavage; by host signal peptidase By similarity
Amino acid modifications
	Lipidation	720	1	S-palmitoyl cysteine; by host By similarity
	Lipidation	740	1	S-palmitoyl cysteine; by host By similarity
	Lipidation	741	1	S-palmitoyl cysteine; by host By similarity
	Lipidation	1241	1	S-stearoyl cysteine; by host By similarity
	Glycosylation	272	1	N-linked (GlcNAc...) Potential
	Glycosylation	587	1	N-linked (GlcNAc...) Potential
	Glycosylation	669	1	N-linked (GlcNAc...) Potential
	Glycosylation	949	1	N-linked (GlcNAc...) Potential
	Disulfide bond	112 ↔ 127		By similarity
	Disulfide bond	857 ↔ 922		By similarity
	Disulfide bond	870 ↔ 902		By similarity
	Disulfide bond	871 ↔ 904		By similarity
	Disulfide bond	876 ↔ 886		By similarity
	Disulfide bond	1067 ↔ 1079		By similarity
	Disulfide bond	1109 ↔ 1184		By similarity
	Disulfide bond	1114 ↔ 1188		By similarity
	Disulfide bond	1136 ↔ 1178		By similarity

Sequences

	Sequence		Length	Mass (Da)
	P22056-1 [UniParc]. Last modified August 1, 1991. Version 1. Checksum: B7DCBDD17D9563CB	FASTA	1,247	137,970
	10 20 30 40 50 60 MEFIPAQTYY NRRYQPRPWT QRPTIQVIRP KPRRRRPAGQ LAQLISAVSR LALRTVPQKP 70 80 90 100 110 120 RRTRKIKKQK QVKQEQQSTT NQKKKAPKQK QTQKKKRPGR RERMCMKIEN DCIFEVRHEG 130 140 150 160 170 180 KVTGYACLVG DKVMKPAHVK GTIDNADLAK LAFKRSSKYD LECAQIPVHM KSDASKFTHE 190 200 210 220 230 240 KPEGYYNWHH GAVQYSGGRF TIPTGAGKPG DSGRPIFDNK GRVVAIVLGG ANEGTRTALS 250 260 270 280 290 300 VVTWNKDIVT KITPEGSVEW SLALPVMCLL ANTTFPCSQP PCAPCCYEKK PEETLRMLED 310 320 330 340 350 360 NVMQPGYYQL LDSALACSQR RQKRNARENF NVYKVTRPYL AHCPDCGEGH SCHSPIALER 370 380 390 400 410 420 IRSEATDGTL KIQVSLQIGI KTDDSHDWTK LRYMDSHTPV DADRSGLFVR TSAPCTITGT 430 440 450 460 470 480 MGHFILARCP KGETLTVGFV DSRRISHTCM HPFRHEPPLI GREKFHSRPQ HGKELPCSTY 490 500 510 520 530 540 VHTTAATAEE IEVHMPPDTP DYTLMTQQAG NVKITVDGQT VRYKCKCDGS NEGLITADKV 550 560 570 580 590 600 INNCKVDQCH TAVTNHKKWQ YNSPLTPRNS EQGDRKGKIH IPFPLVNTTC RVPKARNPTV 610 620 630 640 650 660 TYGKNRVTLL LHPDHPTLLS YRAMGRIPDY HEEWITNKKE ISITVPAEGL EVTWGNNDPY 670 680 690 700 710 720 KYWPQLSTNG TAHGHPHEII LYYYELYPTT TIAVLAAASI VITSLVGLSL GMCICARRRC 730 740 750 760 770 780 ITPYELTPGA TIPFLLGVLC CARTAKAASY YEAATYLWNE QQPLFWLQLL IPLSAAIVVC 790 800 810 820 830 840 NCLKLLPCCC KTLTFLAVMS IGARTVTAYE HATVIPNTVG VPCKTLVSRP GYSPMVLEME 850 860 870 880 890 900 LQSVTLEPAL SLDYITCEYK TITPSPYVKC CGTAECKAKN LPDYNCKVFT GVYPFMWGGA 910 920 930 940 950 960 YCFCDAENTQ LSEAHVEKSE SCKTEFASAY RAHTASVSAK LRVFYQGNNI TVSAYANGDH 970 980 990 1000 1010 1020 AVTVEDAKFV IGPLSSAWSP FDNKIVVYKG EVYNMDYPPF GAGRPGQFGD IQSRTPDSKD 1030 1040 1050 1060 1070 1080 VYANTQLILQ RPAAGAIHVP YSQAPSGFKY WLKEKGASLQ HTAPFGCQIA TNPVRAVNCA 1090 1100 1110 1120 1130 1140 VGNIPVSIDI PDAAFTRVTD APSITDMSCE VASCTHSSDF GGAAVIKYTA SKKGKCAVHS 1150 1160 1170 1180 1190 1200 VTNAVTIREP NVDVKGTAQL QIAFSTALAS AEFKVQICST LVHCSATCHP PKDHIVNYPS 1210 1220 1230 1240 PHTTLGVQDI STTAMSWVQK ITGGVGLVVA IAALILIIVL CVSFSRH

References

[1]	"Complete sequence of the genomic RNA of O'nyong-nyong virus and its use in the construction of alphavirus phylogenetic trees." Levinson R.S., Strauss J.H., Strauss E.G. Virology 175:110-123(1990) [PubMed: 2155505] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].

Cross-references

Sequence databases
EMBLGenBankDDBJ	M20303 Genomic RNA. Translation: AAA46785.1.
PIR	VHWVN2. B34680.
RefSeq	NP_041255.1.
3D structure databases
HSSP	HSSP built from PDB template 1VCP based on UniProtKB P03315.
SMR	P22056. Positions 112-260.
ModBase	Search...
Genome annotation databases
GeneID	1502147.
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	P22056. [Graphical view] [Entries sharing at least one domain]
BLOCKS	Search...
Other Resources
ProtoNet	Search...

Entry information

Entry name

POLS_ONNVG

Accession

Primary (citable) accession number: P22056

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1991
Last sequence update:	August 1, 1991
Last modified:	September 2, 2008
This is version 72 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

Virus (Virus annotation project)