Reviewed, UniProtKB/Swiss-Prot P03301 (POLG_POL1S)

Names and origin

Protein names	Recommended name:     Genome polyprotein Cleaved into the following 12 chains:     1- Recommended name:             Protein VP0         Alternative name(s):             VP4-VP2     2- Recommended name:             Protein VP4         Alternative name(s):             Virion protein 4             P1A     3- Recommended name:             Protein VP2         Alternative name(s):             Virion protein 2             P1B     4- Recommended name:             Protein VP3         Alternative name(s):             Virion protein 3             P1C     5- Recommended name:             Protein VP1         Alternative name(s):             Virion protein 1             P1D     6- Recommended name:             Picornain 2A                 Short name=Protein 2A                 Short name=P2A               EC=3.4.22.29     7- Recommended name:             Protein 2B                 Short name=P2B     8- Recommended name:             Protein 2C                 Short name=P2C               EC=3.6.1.15     9- Recommended name:             Protein 3A                 Short name=P3A     10- Recommended name:             Protein 3B                 Short name=P3B         Alternative name(s):             VPg     11- Recommended name:             Picornain 3C               EC=3.4.22.28         Alternative name(s):             Protease 3C               Short name=P3C     12- Recommended name:             RNA-directed RNA polymerase 3D-POL                 Short name=P3D-POL               EC=2.7.7.48
Organism	Poliovirus type 1 (strain Sabin) [Complete proteome]
Taxonomic identifier	12082 [NCBI]
Taxonomic lineage	Viruses › ssRNA positive-strand viruses, no DNA stage › Picornavirales › Picornaviridae › Enterovirus
Virus host	Homo sapiens (Human) [TaxID: 9606]

Protein attributes

Sequence length	2209 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

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 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.
Subunit structure	P2C N-terminus interacts with human RTN3. This interaction is important for viral replication. Interacts with human PVR By similarity.
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.
Miscellaneous	This virus is a live vaccine strain derived from the mahoney strain by spontaneous mutations during the attenuation process.
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	Host-virus interaction RNA replication
Cellular component	Capsid protein Cytoplasm Cytoplasmic vesicle Membrane Virion
Ligand	ATP-binding Nucleotide-binding RNA-binding
Molecular function	Helicase Hydrolase Nucleotidyltransferase Protease RNA-directed RNA polymerase Thiol protease Transferase
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 interspecies interaction between organisms Inferred from electronic annotation. Source: UniProtKB-KW proteolysis Inferred from electronic annotation. Source: InterPro transcription, RNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW viral genome replication Inferred from electronic annotation. Source: InterPro
Cellular component	cytoplasmic vesicle Inferred from electronic annotation. Source: UniProtKB-KW host cell cytoplasm 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: UniProtKB-KW
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 – 341	340	Protein VP0 Potential		PRO_0000311079
	Chain	2 – 69	68	Protein VP4 Potential		PRO_0000040091
	Chain	70 – 341	272	Protein VP2 Potential		PRO_0000040092
	Chain	342 – 579	238	Protein VP3 Potential		PRO_0000040093
	Chain	580 – 881	302	Protein VP1 Potential		PRO_0000040094
	Chain	882 – 1030	149	Picornain 2A Potential		PRO_0000040095
	Chain	1031 – 1127	97	Protein 2B Potential		PRO_0000040096
	Chain	1128 – 1456	329	Protein 2C Potential		PRO_0000040097
	Chain	1457 – 1543	87	Protein 3A Potential		PRO_0000040098
	Chain	1544 – 1565	22	Protein 3B Potential		PRO_0000040099
	Chain	1566 – 1747	182	Picornain 3C Potential		PRO_0000040100
	Chain	1748 – 2209	462	RNA-directed RNA polymerase 3D-POL Potential		PRO_0000040101
Regions
	Topological domain	2 – 1520	1519	Cytoplasmic Potential
	Topological domain	1521 – 1536	16	In membrane Potential
	Topological domain	1537 – 2209	673	Cytoplasmic Potential
	Domain	1232 – 1388	157	SF3 helicase
	Domain	1975 – 2090	116	RdRp catalytic
	Nucleotide binding	1256 – 1263	8	ATP Potential
Sites
	Active site	901	1	For picornain 2A activity By similarity
	Active site	919	1	For picornain 2A activity By similarity
	Active site	990	1	For picornain 2A activity By similarity
	Active site	1605	1	For picornain 3C activity Potential
	Active site	1636	1	For picornain 3C activity Potential
	Active site	1712	1	For picornain 3C activity By similarity
	Site	25	1	Involved in the interaction with human RTN3 By similarity
	Site	69 – 70	2	Cleavage Potential
	Site	341 – 342	2	Cleavage; by picornain 3C Potential
	Site	881 – 882	2	Cleavage; by picornain 2A Potential
	Site	1030 – 1031	2	Cleavage; by picornain 3C Potential
	Site	1127 – 1128	2	Cleavage; by picornain 3C Potential
	Site	1456 – 1457	2	Cleavage; by picornain 3C Potential
	Site	1543 – 1544	2	Cleavage; by picornain 3C Potential
	Site	1565 – 1566	2	Cleavage; by picornain 3C Potential
	Site	1748 – 1749	2	Cleavage; by picornain 3C Potential
Amino acid modifications
	Modified residue	1546	1	O-(5'-phospho-RNA)-tyrosine By similarity
	Lipidation	2	1	N-myristoyl glycine; by host By similarity
Experimental info
	Mutagenesis	1605	1	H → Y: Complete loss of protease activity. Ref.2
	Mutagenesis	1636	1	E → Q: Complete loss of protease activity. Ref.2
	Mutagenesis	1650	1	D → N: No effect on protease activity; complete loss of autoprocessing ability. Ref.2
	Mutagenesis	1712	1	C → S: Complete loss of protease activity. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P03301-1 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 9EC1EF4D174A28A4	FASTA	2,209	246,578
	10 20 30 40 50 60 MGAQVSSQKV GAHENSNRAY GGSTINYTTI NYYRDSASNA ASKQDFSQDP SKFTEPIKDV 70 80 90 100 110 120 LIKTSPMLNS PNIEACGYSD RVLQLTLGNS TITTQEAANS VVAYGRWPEY LRDSEANPVD 130 140 150 160 170 180 QPTEPDVAAC RFYTLDTVSW TKESRGWWWK LPDALRDMGL FGQNMYYHYL GRSGYTVHVQ 190 200 210 220 230 240 CNASKFHQGA LGVFAVPEMC LAGDSNTTTM HTSYQNANPG EKGGTFTGTF TPDDNQTSPA 250 260 270 280 290 300 RRFCPVDYLF GNGTLLGNAF VFPHQIINLR TNNCATLVLP YVNSLSIDSM VKHNNWGIAI 310 320 330 340 350 360 LPLAPLNFAS ESSPEIPITL TIAPMCCEFN GLRNITLPRL QGLPVMNTPG SNQYLTADNF 370 380 390 400 410 420 QSPCALPEFD VTPPIDIPGE VKNMMELAEI DTMIPFDLSA KKKNTMEMYR VRLSDKPHTD 430 440 450 460 470 480 DPILCLSLSP ASDPRLSHTM LGEILNYYTH WAGSLKFTFL FCGSMMATGK LLVSYAPPGA 490 500 510 520 530 540 DPPKKRKEAM LGTHVIWDIG LQSSCTMVVP WISNTTYRQT IDDSFTEGGY ISVFYQTRIV 550 560 570 580 590 600 VPLSTPREMD ILGFVSACND FSVRLMRDTT HIEQKALAQG LGQMLESMID NTVRETVGAA 610 620 630 640 650 660 TSRDALPNTE ASGPAHSKEI PALTAVETGA TNPLVPSDTV QTRHVVQHRS RSESSIESFF 670 680 690 700 710 720 ARGACVAIIT VDNSASTKNK DKLFTVWKIT YKDTVQLRRK LEFFTYSRFD MEFTFVVTAN 730 740 750 760 770 780 FTETNNGHAL NQVYQIMYVP PGAPVPEKWD DYTWQTSSNP SIFYTYGTAP ARISVPYVGI 790 800 810 820 830 840 SNAYSHFYDG FSKVPLKDQS AALGDSLYGA ASLNDFGILA VRVVNDHNPT KVTSKIRVYL 850 860 870 880 890 900 KPKHIRVWCP RPPRAVAYYG PGVDYKDGTL TPLSTKDLTT YGFGHQNKAV YTAGYKICNY 910 920 930 940 950 960 HLATQEDLQN AVNVMWNRDL LVTESRAQGT DSIARCNCNA GVYYCESRRK YYPVSFVGPT 970 980 990 1000 1010 1020 FQYMEANNYY PARYQSHMLI GHGFASPGDC GGILRCHHGV IGIITAGGEG LVAFTDIRDL 1030 1040 1050 1060 1070 1080 YAYEEEAMEQ GITNYIESLG AAFGSGFTQQ IGDKITELTN MVTSTITEKL LKNLIKIISS 1090 1100 1110 1120 1130 1140 LVIITRNYED TTTVLATLAL LGCDASPWQW LRKKACDVLE IPYVTKQGDS WLKKFTEACN 1150 1160 1170 1180 1190 1200 AAKGLEWVSN KISKFIDWLK EKIIPQARDK LEFVTKLRQL EMLENQISTI HQSCPSQEHQ 1210 1220 1230 1240 1250 1260 EILFNNVRWL SIQSKRFAPL YAVEAKRIQK LEHTINNYIQ FKSKHRIEPV CLLVHGSPGT 1270 1280 1290 1300 1310 1320 GKSVATNLIA RAIAERENTS TYSLPPDPSH FDGYKQQGVV IMDDLNQNPD GADMKLFCQM 1330 1340 1350 1360 1370 1380 VSTVEFIPPM ASLEEKGILF TSNYVLASTN SSRISPPTVA HSDALARRFA FDMDIQVMNE 1390 1400 1410 1420 1430 1440 YSRDGKLNMA MATEMCKNCH QPANFKRCCP LVCGKAIQLM DKSSRVRYSI DQITTMIINE 1450 1460 1470 1480 1490 1500 RNRRSNIGNC MEALFQGPLQ YKDLKIDIKT SPPPECINDL LQAVDSQEVR DYCEKKGWIV 1510 1520 1530 1540 1550 1560 NITSQVQTER NINRAMTILQ AVTTFAAVAG VVYVMYKLFA GHQGAYTGLP NKKPNVPTIR 1570 1580 1590 1600 1610 1620 TAKVQGPGFD YAVAMAKRNI VTATTSKGEF TMLGVHDNVA ILPTHASPGE SIVIDGKEVE 1630 1640 1650 1660 1670 1680 ILDAKALEDQ AGTNLEITII TLKRNEKFRD IRPHIPTQIT ETNDGVLIVN TSKYPNMYVP 1690 1700 1710 1720 1730 1740 VGAVTEQGYL NLGGRQTART LMYNFPTRAG QCGGVITCTG KVIGMHVGGN GSHGFAAALK 1750 1760 1770 1780 1790 1800 RSYFTQSQGE IQWMRPSKEV GYPIINAPSK TKLEPSAFHY VFEGVKEPAV LTKNDPRLKT 1810 1820 1830 1840 1850 1860 NFEEAIFSKY VGNKITEVDE HMKEAVDHYA GQLMSLDINT EQMCLEDAMY GTDGLEALDL 1870 1880 1890 1900 1910 1920 STSAGYPYVA MGKKKRDILN KQTRDTKEMQ KLLDTYGINL PLVTYVKDEL RSKTKVEQGK 1930 1940 1950 1960 1970 1980 SRLIEASSLN DSVAMRMAFG NLYAAFHKNP GVITGSAVGC DPDLFWSKIP VLMEEKLFAF 1990 2000 2010 2020 2030 2040 DYTGYDASLS PAWFEALEMV LEKIGFGDRV DYIDYLNHSH HLYKNKTYCV KGGMPSGCSG 2050 2060 2070 2080 2090 2100 TSIFNSMINN LIIRTLLLKT YKGIDLDHLK MIAYGDDVIA SYPHEVDASL LAQSGKDYGL 2110 2120 2130 2140 2150 2160 TMTPADKSAI FETVTWENVT FLKRFFRADE KYPFLIHPVM PMKEIHESIR WTKDPRNTQD 2170 2180 2190 2200 HVRSLCLLAW HNGEEEYNKF LAKIRSVPIG RALLLPEYST LYRRWLDSF

References

[1]	"Complete nucleotide sequence of the attenuated poliovirus Sabin 1 strain genome." Nomoto A., Omata T., Toyoda H., Kuge S., Horie H., Kataoka Y., Genba Y., Nakano Y., Imura N. Proc. Natl. Acad. Sci. U.S.A. 79:5793-5797(1982) [PubMed: 6310545] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[2]	"Site-directed mutagenesis of the putative catalytic triad of poliovirus 3C proteinase." Haemmerle T., Hellen C.U.T., Wimmer E. J. Biol. Chem. 266:5412-5416(1991) [PubMed: 1848550] [Abstract] Cited for: ACTIVE SITE OF P3C, MUTAGENESIS OF HIS-1605; GLU-1636; ASP-1650 AND CYS-1712.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	V01150 Genomic RNA. Translation: CAA24465.1.
PIR	GNNY3P. A03899.
3D structure databases
ModBase	Search...
Protein family/group databases
MEROPS	C03.020.
Family and domain databases
InterPro	IPR003593. ATPase_AAA+_core. IPR004004. Helicase/Pol/Pept_Calicivir. IPR000605. Helicase_SF3_ssDNA/RNA_vir. IPR014759. Helicase_SF3_ssRNA_vir. IPR014838. P3A. IPR000199. Pept_C3_picorn. IPR000081. Peptidase_C3. IPR003138. Pico_P1A. IPR002527. Pico_P2B. IPR001676. Picornavirus_capsid. IPR001205. RNA_pol_P3D. IPR007094. RNA_pol_PSvir. [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]
PRINTS	PR00918. CALICVIRUSNS.
ProDom	PD001125. Pept_C3_picorn. 1 hit. PD001306. Peptidase_C3_2. 1 hit. PD001274. Pico_P2B. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00382. AAA. 1 hit. [Graphical view]
PROSITE	PS50507. RDRP_SSRNA_POS. 1 hit. PS51218. SF3_HELICASE_2. 1 hit. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

POLG_POL1S

Accession

Primary (citable) accession number: P03301
Secondary accession number(s): Q84881 , Q84882, Q84883, Q84884, Q84885, Q84886, Q84887, Q84888, Q84889, Q84890

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	January 23, 2007
Last modified:	June 16, 2009
This is version 99 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

Virus (Virus annotation project)