P06209 (POLG_POL32) 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	Poliovirus type 3 (strain 23127) [Complete proteome]
Taxonomic identifier	12087 [NCBI]
Taxonomic lineage	Viruses › ssRNA viruses › ssRNA positive-strand viruses, no DNA stage › Picornavirales › Picornaviridae › Enterovirus › Enterovirus C › Human poliovirus 3
Virus host	Homo sapiens (Human) [TaxID: 9606]

Protein attributes

Sequence length	2206 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. The interaction of five VP1 proteins in the fivefold axes results in a prominent protusion extending to about 25 Angstroms from the capsid shell. The resulting structure appears as a steep plateau encircled by a valley or cleft. This depression also termed canyon is the receptor binding site. The capsid interacts with human PVR at this site to provide virion attachment to target cell. This attachment induces virion internalization predominantly through clathrin- and caveolin-independent endocytosis in Hela cells and through caveolin-mediated endocytosis in brain microvascular endothelial cells. VP4 and VP1 subsequently undergo conformational changes leading to the formation of a pore in the endosomal membrane, thereby delivering the viral genome into the cytoplasm 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 Clathrin- and caveolin-independent endocytosis of virus by host Host gene expression shutoff by virus Host transcription shutoff 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 Inhibition of host transcription initiation by virus Ion transport Pore-mediated penetration of viral genome into host cell Transport Viral RNA replication Viral attachment to host cell Viral immunoevasion Viral penetration into host cytoplasm Virus endocytosis by host 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	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 pore-mediated entry of viral genome into host cell Inferred from electronic annotation. Source: UniProtKB-KW proteolysis Inferred from electronic annotation. Source: UniProtKB-KW suppression by virus of host DNA-dependent transcription, initiation 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 via endocytosis 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 – 340	339	Protein VP0 Potential		PRO_0000311082
	Chain	2 – 69	68	Protein VP4 Potential		PRO_0000040124
	Chain	70 – 340	271	Protein VP2 Potential		PRO_0000040125
	Chain	341 – 578	238	Protein VP3 Potential		PRO_0000040126
	Chain	579 – 878	300	Protein VP1 Potential		PRO_0000040127
	Chain	879 – 1027	149	Picornain 2A Potential		PRO_0000040128
	Chain	1028 – 1124	97	Protein 2B Potential		PRO_0000040129
	Chain	1125 – 1453	329	Protein 2C Potential		PRO_0000040130
	Chain	1454 – 1540	87	Protein 3A Potential		PRO_0000040131
	Chain	1541 – 1562	22	Protein 3B Potential		PRO_0000040132
	Chain	1563 – 1745	183	Picornain 3C Potential		PRO_0000040133
	Chain	1746 – 2206	461	RNA-directed RNA polymerase 3D-POL Potential		PRO_0000040134
Regions
	Topological domain	2 – 1517	1516	Cytoplasmic Potential
	Intramembrane	1518 – 1533	16	Potential
	Topological domain	1534 – 2206	673	Cytoplasmic Potential
	Domain	1229 – 1385	157	SF3 helicase
	Domain	1972 – 2087	116	RdRp catalytic
	Nucleotide binding	1253 – 1260	8	ATP Potential
Sites
	Active site	898	1	For picornain 2A activity By similarity
	Active site	916	1	For picornain 2A activity By similarity
	Active site	987	1	For picornain 2A activity By similarity
	Active site	1602	1	For picornain 3C activity Potential
	Active site	1633	1	For picornain 3C activity Potential
	Active site	1709	1	For picornain 3C activity By similarity
	Site	69 – 70	2	Cleavage Potential
	Site	340 – 341	2	Cleavage; by picornain 3C Potential
	Site	878 – 879	2	Cleavage; by picornain 2A Potential
	Site	1027 – 1028	2	Cleavage; by picornain 3C Potential
	Site	1124 – 1125	2	Cleavage; by picornain 3C Potential
	Site	1453 – 1454	2	Cleavage; by picornain 3C Potential
	Site	1540 – 1541	2	Cleavage; by picornain 3C Potential
	Site	1562 – 1563	2	Cleavage; by picornain 3C Potential
	Site	1745 – 1746	2	Cleavage; by picornain 3C Potential
Amino acid modifications
	Modified residue	1543	1	O-(5'-phospho-RNA)-tyrosine By similarity
	Lipidation	2	1	N-myristoyl glycine; by host By similarity

Sequences

	Sequence		Length	Mass (Da)
	P06209 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: F226AD85403C37BA	FASTA	2,206	245,733
	10 20 30 40 50 60 MGAQVSSQKV GAHENSNRAY GGSTINYTTI NYYKDSASNA ASKQDYSQDP SKFTEPLKDV 70 80 90 100 110 120 LIKTAPALNS PNVEACGYSD RVLQLTLGNS TITTQEAANS VVAYGRWPEF IRDDEANPVD 130 140 150 160 170 180 QPTEPDVATS RFYTLDTVMW GKESRGWWWK LPDALRDMGL FGQNMYYHYL GRSGYTVHVQ 190 200 210 220 230 240 CNASKFHQGS LGVFAIPEFC LAGDSDTQRY TSYANANPGE KGGKFYAQFN KDTAVTSPKR 250 260 270 280 290 300 EFCPVDYLLG CGVLIGNAFV FPHQIINLRT NNSATLVLPY VNALSIDSMV KHNNWGIAIL 310 320 330 340 350 360 PLSPLDFAQD SSVEIPITVT IAPMCSEFNG LRNVTAPKLQ GLPVLNTPGS NQYLTSDNHQ 370 380 390 400 410 420 SPCAIPEFDV TPPIDIPGEV KNVMELAEID TMIPLNLENT KRNTMDMYRV RLSDSANLSG 430 440 450 460 470 480 PILCLSLSPA ADPRLSHTML GEVLNYYTHW AGSLKFTFLF CGSMMATGKL LVAYAPPGAQ 490 500 510 520 530 540 PPTSRKEAML GTHVIWDLGL QSSCTMVVPW ISNVTYRQTT QDSFTEGGYI SMFYQTRIVV 550 560 570 580 590 600 PLSTPKAMDM LGFVSACNDF SVRLLRDTTH ISQAAMPQGV DDLITEVAQN ALALSLPKPQ 610 620 630 640 650 660 SNLPDTKASG PAHSKEVPTL TAVETGATNP LVPSDTVQTR HVIQQRSRSE STIESFFARG 670 680 690 700 710 720 ACVAIIEVDN EQPATNVQKL FATWRITYKD TVQLRRKLEF FTYSRFDMEF TFVVTANFTN 730 740 750 760 770 780 SNNGHALNQV YQIMYIPPGA PTPKSWDDYT WQTSSNPSIF YTYGAAPARI SVPYVGLANA 790 800 810 820 830 840 YSHFYDGFAK VPLKSDANDQ VGDSLYSAMA VDDFGVLAIR VVNDHNPTKV TSKVRVYMKP 850 860 870 880 890 900 KHVRVWCPRP PRAVPYYGPG VDYKDGLAPL SEKGLTTYGF GHQNKAVYTA GYKICNYHLA 910 920 930 940 950 960 TQEDLQNAVS VMWNRDLLVT ESKAQGIDSI ARCNCSTGVY YCESRSRYYP VSFVGPTFQY 970 980 990 1000 1010 1020 MEANDYYPAR YQSHMLIGHG FASPGDCGGI LRCQHGVIGI ITAGGEGLVA FSDIRDLYAY 1030 1040 1050 1060 1070 1080 EEEAMEQGIS SYVESLGAAF GSGFTQQIGD KIIELTGMVT STITEKLLKN LIKIVSSLVI 1090 1100 1110 1120 1130 1140 ITRNYDDTTT VLATLALLGC DVSPWQWLKK KACDILEIPY VMRQGDSWLK KFTEACNAAK 1150 1160 1170 1180 1190 1200 GLEWVSNKIS KFIDWLREKI IPQARDKLEF VTKLKQLEML ENQIATIHQS CPSQEHQEIL 1210 1220 1230 1240 1250 1260 FNNVRWLSIQ SKRFAPLYAL EAKRIQKLEH TINNYIQFKS KHRIEPVCLL VHGSPGTGKS 1270 1280 1290 1300 1310 1320 VATNLIARAI AEKENTSTYS LPPDPSHFDG YKQQGVVIMD DLNQNPDGAD MKLFCQMVST 1330 1340 1350 1360 1370 1380 VEFIPPMASL EEKGILFTSN YVLASTNSSR ITPPTVAHSD ALARRFAFDM DIQVMSEYSR 1390 1400 1410 1420 1430 1440 DGKLNMTMAT EMCKNCHQPA NFKRCCPLVC GKAIQLMDKS SRVRYSIDQI TTMIVNEKNR 1450 1460 1470 1480 1490 1500 RSNIGNCMEA LFQGPLQYKD LKIDIKTTPP PECINDLLQA VDSQEVRDYC EKKGWIVNIT 1510 1520 1530 1540 1550 1560 SQVQTERNIN RAMTILQAVT TFAAVAGVVY VMYKLFAGHQ GAYTGLPNKR PNVPTIRTAK 1570 1580 1590 1600 1610 1620 VQGPGFDYAV AMAKRNILTA TTSKGEFTML GVHDNVAILP THASPGETIV IDGKEIEVLD 1630 1640 1650 1660 1670 1680 AKALEDQAGT NLEITIVTLK RNEKFRDIRP HIPAQITETN DGVLIVNTSK YPNMYVPVGA 1690 1700 1710 1720 1730 1740 VTEQGYLNLG GRQTARTLMY NFPTRAGQCG GVITCTGKVI GMHVGGNGSH GFAAALKRSY 1750 1760 1770 1780 1790 1800 FTQSQGEIQW MRPSKEVGYP IINAPSKTKL EPSAFHYVFE GVKEPAVLTK NDPRFKTGFE 1810 1820 1830 1840 1850 1860 EAIFSKYVGN KITEVDEYMK EAVDHYAGQL MSLDINTEQM CLEDAMYGTD GLEALDLSTS 1870 1880 1890 1900 1910 1920 AGYPYVTMGK KKRDILNKQT RDTKEMQRLL DTYGINLPLV TYVKDELRSK TKVEQGKSRL 1930 1940 1950 1960 1970 1980 IEASSLNDSV AMRMAFGNLY AAFHKNPGVV TGSAVGCDPD LFWSKIPVLM EEKLFAFDYT 1990 2000 2010 2020 2030 2040 GYDASLSPAW FEALKMVLEK IGFGDRVDYI DYLNHSHHLY KNKTYCVKGG MPSGCSGTSI 2050 2060 2070 2080 2090 2100 FNSMINNLII RTLLLKTYKG IDLDHLKMIA YGDDVIASYP HEVDASLLAQ SGKDYGLTMT 2110 2120 2130 2140 2150 2160 PADKSATFET VTWENVTFLK RFFRADERYP FLIHPVMPMK EIHESIRWTK DPRNTQDHVR 2170 2180 2190 2200 SLCLLAWHNG EDEYNKFLAM IRSVPIGRAL LLPEYSTLYR RWLDSF

References

[1]

"The nucleotide sequence of a type 3 poliovirus isolated during a recent outbreak of poliomyelitis in Finland." Hughes P.J., Evans D.M.A., Minor P.D., Schild G.C., Almond J.W., Stanway G. J. Gen. Virol. 67:2093-2102(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].

Cross-references

Sequence databases
EMBL GenBank DDBJ	X04468 Genomic RNA. Translation: CAA28155.1.
PIR	GNNY27. A27245.
3D structure databases
ProteinModelPortal	P06209.
SMR	P06209. Positions 2-575, 600-1027, 1454-1512, 1563-2206.
ModBase	Search...
Protein family/group databases
MEROPS	C03.001.
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_POL32

Accession

Primary (citable) accession number: P06209

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 1, 1988
Last sequence update:	January 23, 2007
Last modified:	May 1, 2013
This is version 125 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program