Q66474 (POLG_EC06C) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names	Recommended name: Genome polyprotein Cleaved into the following 12 chains: Protein VP0 Alternative name(s): VP4-VP2 Protein VP4 Alternative name(s): P1A Virion protein 4 Protein VP2 Alternative name(s): P1B Virion protein 2 Protein VP3 Alternative name(s): P1C Virion protein 3 Protein VP1 Alternative name(s): P1D Virion protein 1 Picornain 2A Short name=P2A Short name=Protein 2A EC=3.4.22.29 Protein 2B Short name=P2B Protein 2C Short name=P2C EC=3.6.1.15 Protein 3A Short name=P3A Protein 3B Short name=P3B Alternative name(s): VPg Picornain 3C EC=3.4.22.28 Alternative name(s): Protease 3C Short name=P3C RNA-directed RNA polymerase 3D-POL Short name=P3D-POL EC=2.7.7.48
Organism	Echovirus 6 (strain Charles) [Complete proteome]
Taxonomic identifier	103913 [NCBI]
Taxonomic lineage	Viruses › ssRNA viruses › ssRNA positive-strand viruses, no DNA stage › Picornavirales › Picornaviridae › Enterovirus › Enterovirus B › Echovirus E6
Virus host	Homo sapiens (Human) [TaxID: 9606]

Protein attributes

Sequence length	2191 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Inferred from homology

General annotation (Comments)

Function	Capsid proteins VP1, VP2, VP3 and VP4 form a closed capsid enclosing the viral positive strand RNA genome. VP4 lies on the inner surface of the protein shell formed by VP1, VP2 and VP3. All the three latter proteins contain a beta-sheet structure called beta-barrel jelly roll. Together they form an icosahedral capsid (T=3) composed of 60 copies of each VP1, VP2, and VP3, with a diameter of approximately 300 Angstroms. VP1 is situated at the 12 fivefold axes, whereas VP2 and VP3 are located at the quasi-sixfold axes By similarity. VP0 precursor is a component of immature procapsids By similarity. Protein 2A is a cysteine protease that is responsible for the cleavage between the P1 and P2 regions. It cleaves the host translation initiation factor EIF4G1, in order to shut down the capped cellular mRNA transcription By similarity. Protein 2B affects membrane integrity and cause an increase in membrane permeability By similarity. Protein 2C associates with and induces structural rearrangements of intracellular membranes. It displays RNA-binding, nucleotide binding and NTPase activities By similarity. Protein 3A, via its hydrophobic domain, serves as membrane anchor. It also inhibits endoplasmic reticulum-to-Golgi transport By similarity. Protein 3C is a cysteine protease that generates mature viral proteins from the precursor polyprotein. In addition to its proteolytic activity, it binds to viral RNA, and thus influences viral genome replication. RNA and substrate bind co-operatively to the protease By similarity. RNA-directed RNA polymerase 3D-POL replicates genomic and antigenomic RNA by recognizing replications specific signals By similarity.
Catalytic activity	Nucleoside triphosphate + RNA(n) = diphosphate + RNA(n+1). Selective cleavage of Tyr-|-Gly bond in the picornavirus polyprotein. Selective cleavage of Gln-|-Gly bond in the poliovirus polyprotein. In other picornavirus reactions Glu may be substituted for Gln, and Ser or Thr for Gly. NTP + H2O = NDP + phosphate.
Subcellular location	Protein VP2: Virion. Host cytoplasm Potential. Protein VP3: Virion. Host cytoplasm Potential. Protein VP1: Virion. Host cytoplasm Potential. Protein 2B: Host cytoplasmic vesicle membrane; Peripheral membrane protein; Cytoplasmic side Potential. Note: Probably localizes to the surface of intracellular membrane vesicles that are induced after virus infection as the site for viral RNA replication. These vesicles are derived from the endoplasmic reticulum By similarity. Protein 2C: Host cytoplasmic vesicle membrane; Peripheral membrane protein; Cytoplasmic side Potential. Note: Probably localizes to the surface of intracellular membrane vesicles that are induced after virus infection as the site for viral RNA replication. These vesicles are derived from the endoplasmic reticulum By similarity. Protein 3A: Host cytoplasmic vesicle membrane; Peripheral membrane protein; Cytoplasmic side Potential. Note: Probably localizes to the surface of intracellular membrane vesicles that are induced after virus infection as the site for viral RNA replication. These vesicles are derived from the endoplasmic reticulum By similarity. Protein 3B: Virion Potential. Picornain 3C: Host cytoplasm Potential. RNA-directed RNA polymerase 3D-POL: Host cytoplasmic vesicle membrane; Peripheral membrane protein; Cytoplasmic side Potential. Note: Probably localizes to the surface of intracellular membrane vesicles that are induced after virus infection as the site for viral RNA replication. These vesicles are derived from the endoplasmic reticulum By similarity.
Post-translational modification	Specific enzymatic cleavages in vivo by the viral proteases yield a variety of precursors and mature proteins. Polyprotein processing intermediates such as VP0 which is a VP4-VP2 precursor are produced. During virion maturation, non-infectious particles are rendered infectious following cleavage of VP0. This maturation cleavage is followed by a conformational change of the particle By similarity. VPg is uridylylated by the polymerase and is covalently linked to the 5'-end of genomic RNA. This uridylylated form acts as a nucleotide-peptide primer for the polymerase By similarity. Myristoylation of VP4 is required during RNA encapsidation and formation of the mature virus particle By similarity.
Sequence similarities	Belongs to the picornaviruses polyprotein family. Contains 2 peptidase C3 domains. Contains 1 RdRp catalytic domain. Contains 1 SF3 helicase domain.

Ontologies

Keywords
Biological process	Activation of host autophagy by virus Host-virus interaction Inhibition of host IFN-mediated response initiation by virus Inhibition of host RIG-I by virus Inhibition of host innate immune response by virus Ion transport Transport Viral RNA replication Viral attachment to host cell Viral immunoevasion Virus entry into host cell
Cellular component	Host cytoplasm Host cytoplasmic vesicle Host membrane Membrane Virion
Ligand	ATP-binding Nucleotide-binding RNA-binding
Molecular function	Capsid protein Helicase Hydrolase Ion channel Nucleotidyltransferase Protease RNA-directed RNA polymerase Thiol protease Transferase Viral ion channel
PTM	Covalent protein-RNA linkage Lipoprotein Myristate Phosphoprotein
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological_process	RNA-protein covalent cross-linking Inferred from electronic annotation. Source: UniProtKB-KW induction by virus of host autophagy Inferred from electronic annotation. Source: UniProtKB-KW ion transport Inferred from electronic annotation. Source: UniProtKB-KW proteolysis Inferred from electronic annotation. Source: UniProtKB-KW suppression by virus of host RIG-I activity Inferred from electronic annotation. Source: UniProtKB-KW suppression by virus of host type I interferon production Inferred from electronic annotation. Source: UniProtKB-KW transcription, DNA-dependent Inferred from electronic annotation. Source: InterPro viral attachment to host cell Inferred from electronic annotation. Source: UniProtKB-KW viral entry into host cell Inferred from electronic annotation. Source: UniProtKB-KW viral genome replication Inferred from electronic annotation. Source: InterPro
Cellular_component	host cell cytoplasmic vesicle membrane Inferred from electronic annotation. Source: UniProtKB-SubCell membrane Inferred from electronic annotation. Source: UniProtKB-KW viral capsid Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW RNA binding Inferred from electronic annotation. Source: UniProtKB-KW RNA helicase activity Inferred from electronic annotation. Source: InterPro RNA-directed RNA polymerase activity Inferred from electronic annotation. Source: UniProtKB-KW cysteine-type endopeptidase activity Inferred from electronic annotation. Source: InterPro structural molecule activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed; by host By similarity
	Chain	2 – 330	329	Protein VP0 Potential		PRO_0000311055
	Chain	2 – 69	68	Protein VP4 Potential		PRO_0000039670
	Chain	70 – 330	261	Protein VP2 Potential		PRO_0000039671
	Chain	331 – 568	238	Protein VP3 Potential		PRO_0000039672
	Chain	569 – 857	289	Protein VP1 Potential		PRO_0000039673
	Chain	858 – 1007	150	Picornain 2A Potential		PRO_0000039674
	Chain	1008 – 1106	99	Protein 2B Potential		PRO_0000039675
	Chain	1107 – 1435	329	Protein 2C Potential		PRO_0000039676
	Chain	1436 – 1524	89	Protein 3A Potential		PRO_0000039677
	Chain	1525 – 1546	22	Protein 3B Potential		PRO_0000039678
	Chain	1547 – 1729	183	Picornain 3C Potential		PRO_0000039679
	Chain	1730 – 2191	462	RNA-directed RNA polymerase 3D-POL Potential		PRO_0000039680
Regions
	Topological domain	2 – 1501	1500	Cytoplasmic Potential
	Intramembrane	1502 – 1517	16	Potential
	Topological domain	1518 – 2191	674	Cytoplasmic Potential
	Domain	1211 – 1367	157	SF3 helicase
	Domain	1956 – 2072	117	RdRp catalytic
	Nucleotide binding	1235 – 1242	8	ATP Potential
Sites
	Active site	878	1	For picornain 2A activity By similarity
	Active site	896	1	For picornain 2A activity By similarity
	Active site	967	1	For picornain 2A activity By similarity
	Active site	1586	1	For picornain 3C activity Potential
	Active site	1617	1	For picornain 3C activity Potential
	Active site	1693	1	For picornain 3C activity By similarity
	Site	69 – 70	2	Cleavage Potential
	Site	330 – 331	2	Cleavage; by picornain 3C Potential
	Site	857 – 858	2	Cleavage; by picornain 2A Potential
	Site	1007 – 1008	2	Cleavage; by picornain 3C Potential
	Site	1106 – 1107	2	Cleavage; by picornain 3C Potential
	Site	1435 – 1436	2	Cleavage; by picornain 3C Potential
	Site	1524 – 1525	2	Cleavage; by picornain 3C Potential
	Site	1546 – 1547	2	Cleavage; by picornain 3C Potential
	Site	1729 – 1730	2	Cleavage; by picornain 3C Potential
Amino acid modifications
	Modified residue	1527	1	O-(5'-phospho-RNA)-tyrosine By similarity
	Lipidation	2	1	N-myristoyl glycine; by host By similarity

Sequences

	Sequence		Length	Mass (Da)
	Q66474 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 47E70448B05716DB	FASTA	2,191	245,277
	10 20 30 40 50 60 MGAQVSTQKT GAHETGLSAS GNSIIHYTNI NYYKDAASNS ANRQDFTQDP GKFTEPVKDI 70 80 90 100 110 120 MAKTLPALNS PSAEECGYSD RVRSITLGNS TITTQESANV VVGYGVWPDY LKDDEATAED 130 140 150 160 170 180 QPTNPDVATC RFYTLDSVSW MKESQGWWWK FPDALRDMGL FGQNMQYHYL GRSGYTIHVQ 190 200 210 220 230 240 CNASKFHQGC LLVVCVPEAE MGAATVNEKI NREHLSNGEV ANTFTGTKSS NTNGVQQAVF 250 260 270 280 290 300 NAGMGVRVGN LTVFPHQWIN LRTNNCATIV MPYINSVPMD NMFRHYNFTL MIIPFAKLDY 310 320 330 340 350 360 AAGSSTYIPI TVTVAPMCAE YNGLRLAGHQ GLPVMSTPGS NQFLTSDDYQ SPTAMPQFDV 370 380 390 400 410 420 TPEMHIPGEV KNLMEIAEVD SVVPVNNVNE NVNSLEAYRI PVHSVTETGA QVFGFTLQPG 430 440 450 460 470 480 ADSVMERTLH GEILNYYANW SGSIKLTFMY CGSAMATGKF LLAYSPPGAG VPKNRKEAML 490 500 510 520 530 540 GTHMIWDIGL QSRCVLCVPW ISQTHYRFVS KDSYTDAGFI TCWYQTSIVV PAEVQNQSVI 550 560 570 580 590 600 LCFVSACNDF SVRLLRDSPF VTQTAFYQND VQNAVERSIV RVADTLPSGP SNSESIPALT 610 620 630 640 650 660 AAETGHTSQV VPSDTIQTRH VRNFHVRSES SVENFLSRSA CVYIVEYKTQ DTTPDKMYDS 670 680 690 700 710 720 WVINTRQVAQ LRRKLEFFTY VRFDVEVTFV ITSVQDDSTR QNTDTPVLTH QIMYVPPGGP 730 740 750 760 770 780 IPHAVDDYNW QTSTNPSVFW TEGNAPPRMS IPFMSVGNAY SNFYDGWSHF SQTGVYGFNT 790 800 810 820 830 840 LNNMGKLYFR HVNDRTISPI TSKVRIYFKP KHVKAWVPRP PRLCEYTHKD NVDYEPKGVT 850 860 870 880 890 900 TSRTSITITN SKHMETHGAF GQQSGAAYVG NYRVVNRHLA THTDWQNCVW EDYNRDLLVS 910 920 930 940 950 960 TTTAHGCDTI ARCHCTTGVY FCASRNKHHP VVFEGPGLVE VQESGYYPKR YQSHVLLAAG 970 980 990 1000 1010 1020 LSEPGDCGGI LRCEHGVIGI VTMGGEGVVG FADVRDLLWL EDDAMEQGVK DYVEQLGNAF 1030 1040 1050 1060 1070 1080 GSGFTNQICE QVNLLKESLI GQDSILEKSL KALVKIISAL VIVVRNHDDL ITVTATLALI 1090 1100 1110 1120 1130 1140 GCTSSPWRWL KQKVSQYYGI SMAERQNNGW LKKFTEMTNA CKGMEWIAIK IQKFIEWLKV 1150 1160 1170 1180 1190 1200 KILPEVREKH EFLNRLKQLP LLESQIATIE QSAPSQSDQE QLFSNVQYFA HYCRKYAPLY 1210 1220 1230 1240 1250 1260 AAEAKRVFSL EKKMSNYIQF KSKCRIEPVC LLLHGSPGVG KSVATNLIGR SLAEKLNSSI 1270 1280 1290 1300 1310 1320 YSLPPDPDHF DGYKQQAVVI MDDLCQNPDG KDVSLFCQMV SSVDFVPPMA ALEEKGILFT 1330 1340 1350 1360 1370 1380 SPFVLASTNA GSINAPTVSD SRALARRFHF DMNIEVISMY NQNGKINMPM SVKTCDEECC 1390 1400 1410 1420 1430 1440 PVNFKKCCPL VCGKAIQFID RRTQVRYSLD MLVTEMFREY NHRHSVGATL EALFQGPPVY 1450 1460 1470 1480 1490 1500 REIKISVAPE IPPPPAIADL LKSVDSEAVR DYCKEKGWLV PEVNSTLQIE KHVSRAFICL 1510 1520 1530 1540 1550 1560 QALTTFVSVA GIIYIIYKLF AGFQGAYTGM PNQKPKVPTL RQAKVQGPAF EFAVAMMKRN 1570 1580 1590 1600 1610 1620 SSTVKTEYGE FTMLGIYDRW AVLPRHAKPG PTILMNDQEV GVVDAKELVD KDGTNLELTL 1630 1640 1650 1660 1670 1680 LKLNRNEKFR DIRGFLAKEE VEVNEAVLAI NTSKFPNMYI PVGQVTDYGF LNLGGTPTKR 1690 1700 1710 1720 1730 1740 MLMYNFPTRA GQCGGVLMST GKVLGIHVGG NGHQGFSAAL LKHYFNDEQG EIEFIESSKD 1750 1760 1770 1780 1790 1800 AGYPVINTPS RTKLEPSVFH QVFEGSKEPA VLRNGDPRLK ANFEEAIFSK YIGNVNTHVD 1810 1820 1830 1840 1850 1860 EYMLEAIDHY AGQLATLDIS TEPMKLEDAV YGTEGLEALD LTTSAGYPYV ALGIKKRDIL 1870 1880 1890 1900 1910 1920 SKKTRDLTKL KECMDKYGLN LPMVTYVKDE LRSAEKVAKG KSRLIEASSL NDSVAMRQTF 1930 1940 1950 1960 1970 1980 GNLYKAFHQN PGIVTGSAVG CDPDLFWSKI PVMLDGHLIA FDYSGYDASL SPVWFACLKL 1990 2000 2010 2020 2030 2040 LLEKLGYTHK ETNYIDYLCN SHHLYRDKHY FVRGGMPSGC SGTSIFNSMI NNIIIRTLML 2050 2060 2070 2080 2090 2100 KVYKGIDLDQ FRMIAYGDDV IASYPWPIDA SLLAEAGKDY GLIMTPADKG ECFNEVTWTN 2110 2120 2130 2140 2150 2160 VTFLKRYFRA DEQYPFLVHP VMPMKDIHES IRWTKDPKNT QDHVRSLCLL AWHNGEQEYE 2170 2180 2190 EFIQKIRSVP VGRCLTLPAF STLRRKWLDS F

References

[1]	"The genome of echovirus 6." Righthand V.F., Gratsch T.E., Blackburn R.V. Submitted (OCT-1994) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[2]	"Construction of a recombinant cDNA of echovirus 6 that established a persistent in vitro infection." Gratsch T.E., Righthand V.F. Virology 201:341-348(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1526-2191.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U16283 Genomic RNA. Translation: AAA65044.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1Q1X	model	-	B	1483-1488	[»]

ProteinModelPortal

Q66474.

SMR

Q66474. Positions 2-69, 77-568, 570-849, 858-1007, 1547-2191.

ModBase

Search...

Protein family/group databases

MEROPS

C03.011.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Family and domain databases

Gene3D

4.10.80.10. 2 hits.

InterPro

IPR003593. AAA+_ATPase.
IPR000605. Helicase_SF3_ssDNA/RNA_vir.
IPR014759. Helicase_SF3_ssRNA_vir.
IPR014838. P3A.
IPR000081. Peptidase_C3.
IPR000199. Peptidase_C3A/C3B_picornavir.
IPR003138. Pico_P1A.
IPR002527. Pico_P2B.
IPR001676. Picornavirus_capsid.
IPR001205. RNA-dir_pol_C.
IPR007094. RNA-dir_pol_PSvirus.
IPR009003. Trypsin-like_Pept_dom.
[Graphical view]

Pfam

PF08727. P3A. 1 hit.
PF00548. Peptidase_C3. 1 hit.
PF02226. Pico_P1A. 1 hit.
PF00947. Pico_P2A. 1 hit.
PF01552. Pico_P2B. 1 hit.
PF00680. RdRP_1. 1 hit.
PF00073. Rhv. 3 hits.
PF00910. RNA_helicase. 1 hit.
[Graphical view]

ProDom

PD001306. Peptidase_C3. 1 hit.
PD649346. Pico_P2B. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SMART

SM00382. AAA. 1 hit.
[Graphical view]

SUPFAM

SSF89043. P3A. 1 hit.
SSF50494. Pept_Ser_Cys. 2 hits.

PROSITE

PS50507. RDRP_SSRNA_POS. 1 hit.
PS51218. SF3_HELICASE_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Entry information

Entry name

POLG_EC06C

Accession

Primary (citable) accession number: Q66474

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	January 23, 2007
Last modified:	May 1, 2013
This is version 119 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program