Q9YLG5 (POLG_CXB2O) 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	Coxsackievirus B2 (strain Ohio-1) [Complete proteome]
Taxonomic identifier	231473 [NCBI]
Taxonomic lineage	Viruses › ssRNA viruses › ssRNA positive-strand viruses, no DNA stage › Picornavirales › Picornaviridae › Enterovirus › Enterovirus B › Human coxsackievirus B2
Virus host	Homo sapiens (Human) [TaxID: 9606]

Protein attributes

Sequence length	2187 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 By similarity. Capsid proteins interact with host CAR/CXADR to provide virion attachment to target cell. 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	Capsid proteins interact with host CXADR.
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	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 – 333	332	Protein VP0 Potential		PRO_0000311046
	Chain	2 – 69	68	Protein VP4 Potential		PRO_0000039571
	Chain	70 – 333	264	Protein VP2 Potential		PRO_0000039572
	Chain	334 – 571	238	Protein VP3 Potential		PRO_0000039573
	Chain	572 – 853	282	Protein VP1 Potential		PRO_0000039574
	Chain	854 – 1003	150	Picornain 2A Potential		PRO_0000039575
	Chain	1004 – 1102	99	Protein 2B Potential		PRO_0000039576
	Chain	1103 – 1431	329	Protein 2C Potential		PRO_0000039577
	Chain	1432 – 1520	89	Protein 3A Potential		PRO_0000039578
	Chain	1521 – 1542	22	Protein 3B Potential		PRO_0000039579
	Chain	1543 – 1725	183	Picornain 3C Potential		PRO_0000039580
	Chain	1726 – 2187	462	RNA-directed RNA polymerase 3D-POL Potential		PRO_0000039581
Regions
	Topological domain	2 – 1497	1496	Cytoplasmic Potential
	Intramembrane	1498 – 1513	16	Potential
	Topological domain	1514 – 2187	674	Cytoplasmic Potential
	Domain	1207 – 1363	157	SF3 helicase
	Domain	1952 – 2068	117	RdRp catalytic
	Nucleotide binding	1231 – 1238	8	ATP Potential
Sites
	Active site	874	1	For picornain 2A activity By similarity
	Active site	892	1	For picornain 2A activity By similarity
	Active site	963	1	For picornain 2A activity By similarity
	Active site	1582	1	For picornain 3C activity Potential
	Active site	1613	1	For picornain 3C activity Potential
	Active site	1689	1	For picornain 3C activity By similarity
	Site	69 – 70	2	Cleavage Potential
	Site	333 – 334	2	Cleavage; by picornain 3C Potential
	Site	853 – 854	2	Cleavage; by picornain 2A Potential
	Site	1003 – 1004	2	Cleavage; by picornain 3C Potential
	Site	1102 – 1103	2	Cleavage; by picornain 3C Potential
	Site	1431 – 1432	2	Cleavage; by picornain 3C Potential
	Site	1520 – 1521	2	Cleavage; by picornain 3C Potential
	Site	1542 – 1543	2	Cleavage; by picornain 3C Potential
	Site	1725 – 1726	2	Cleavage; by picornain 3C Potential
Amino acid modifications
	Modified residue	1523	1	O-(5'-phospho-RNA)-tyrosine By similarity
	Lipidation	2	1	N-myristoyl glycine; by host By similarity
Experimental info
	Sequence conflict	214	1	K → N in AAD46138. Ref.2
	Sequence conflict	458	1	M → V in AAD46138. Ref.2
	Sequence conflict	800 – 805	6	NPGSIT → TQVASP in AAD46138. Ref.2
	Sequence conflict	848	1	D → N in AAD46138. Ref.2
	Sequence conflict	946	1	R → E in AAD46138. Ref.2
	Sequence conflict	954	1	A → T in AAD46138. Ref.2
	Sequence conflict	960 – 961	2	PG → TR in AAD46138. Ref.2
	Sequence conflict	1107	1	L → F in AAD46138. Ref.2
	Sequence conflict	1111	1	T → I in AAD46138. Ref.2
	Sequence conflict	1228	1	L → F in AAD46138. Ref.2
	Sequence conflict	1762	1	N → I in AAD46138. Ref.2
	Sequence conflict	1935	1	V → I in AAD46138. Ref.2
	Sequence conflict	2008	1	V → L in AAD46138. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q9YLG5 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 11628A42FF9B4C41	FASTA	2,187	244,392
	10 20 30 40 50 60 MGAQVSTQKT GAHETGLSAS GGSIIHYTNI NYYKDAASNS ANRQDFTQDP GKFTEPVKDI 70 80 90 100 110 120 MIKSMPALNS PSAEECGYSD RVRSITLGNS TITTQECANV VVGYGTWPRY LSDKEATAED 130 140 150 160 170 180 QPTQPDVATC RFYTLSSVQW QRESAGWWWK FPDALSDMGL FAQNMMYHYL GRTGYTIHVQ 190 200 210 220 230 240 CNASKFHQGC LLVVCVPEAE MGCTNKENTP LFEKLCGQDN AKEFTREGPT ISKGATDVQT 250 260 270 280 290 300 AVCNAGMGVG VGNLTIFPHQ WINLRTNNSA TIVMPYINSV PMDSMIRHNN FTLMIIPFVP 310 320 330 340 350 360 LDYVNGSSPY IPITVTVAPM SAEYNGLRLA STQGLPTMLT PGSNQFLTSD DFQSPSAMPQ 370 380 390 400 410 420 FDVTPEMNIP GRVHNLMEIA EVDSVVPLNN IQDNLRKMDI YRVQVSSQTS QGAQVFGFSL 430 440 450 460 470 480 QPGASSVLQR TLLGEILNYY THWSGSLKLT FVFCGSAMAT GKFLLAYSPP GAGVPPDRKK 490 500 510 520 530 540 AMLGTHVIWD VGLQSSCVLC VPWISQTHYR YTVKDEYTDS GYITCWYQTN VIAPADALST 550 560 570 580 590 600 CYIMCMVSAC NDFSVRMLRD TRFIKQTAFY QSPVEESIER SIGRVADTIG SGPSNSEAIP 610 620 630 640 650 660 VLTAVETGHT SQVTPSDTMQ TRHVHNYHSR SESSVENFLA RSACVFYTTY TNSKNAAKEK 670 680 690 700 710 720 KFATWKVSVR QAAQLRRKLE LFTYLRCDIE LTFVITSAQD PSTATNLDVP VLTHQIMYVP 730 740 750 760 770 780 PGGPVPETVD DYNWQTSTNP SLFWTEGNAP PRMSIPFMSI GNAYSMFYDG WSEFRHDGVY 790 800 810 820 830 840 GLNTLNNMGT IYARHVNADN PGSITSTVRI YFKPKHVKAW IPRPPRLAQY LKANNVNFKI 850 860 870 880 890 900 TDVTEKRDSL TTTGAFGQQS GAVYVGNYRV VNRHLATHID WQNCVWEDYN RDLLVSTTTA 910 920 930 940 950 960 HGCDTIARCQ CTSGVYYCAS KNKHYPVVFE GPGMVEVQES EYYPKRYQSH VLLAAGFSEP 970 980 990 1000 1010 1020 GDCGGILRCE HGVIGVVTMG GEGVVGFADV RDLLWLEDDA MEQGVKDYVE QLGNAFGSGF 1030 1040 1050 1060 1070 1080 TNQICEQVNL LKESLVGQDS ILEKSLKALV RIISALVIVV RNHDDIITVT ATLALIGCTS 1090 1100 1110 1120 1130 1140 SPWRWLKQKV SQYYGIPMAE RQNNGWLKKF TEMTNACKGM EWIAVKIQKF IEWLKVKILP 1150 1160 1170 1180 1190 1200 EVKEKHEFLN RLKQLPLLES QIATIEQSAP SQSDQEQLFS NVQYFAHYCR KYAPLYAAEA 1210 1220 1230 1240 1250 1260 KRVFSLEKKM SNYIQFKSKC RIEPVCLLLH GSPGAGKSVA TNLIGRSLAE KLNSSVYSLP 1270 1280 1290 1300 1310 1320 PDPDHFDGYK QQAVVIMDDL CQNPDGKDVS LFCQMVSSVD FVPPMAALEE KGILFTSPFV 1330 1340 1350 1360 1370 1380 LASTNAGSIN APTVSDSRAL ARRFHFDMNI EVISMYSQNG KINMPMSVKT CDDECCPVNF 1390 1400 1410 1420 1430 1440 KKCCPLVCGK AIQFIDRRTQ VRYSLDMLVT EMFREYNHRH SVGATLEALF QGPPIYREIK 1450 1460 1470 1480 1490 1500 ISVAPETPPP PAIADLLKSV DSEVVREYCK EKGWLVPEVN STLQIEKHVS RAFICLQALT 1510 1520 1530 1540 1550 1560 TFVSVAGIIY IIYKLFAGFQ GAYTGMPNQK PKVPTLRQAK VQGPAFEFAV AMMKRNSSTV 1570 1580 1590 1600 1610 1620 KTEYGEFTML GIYDRWAVLP RHAKPGPTIL MNDQEVSVLD AKELVDKDGT NLELVLLKLN 1630 1640 1650 1660 1670 1680 RNEKFRDIRG FLAKEEVEVN EAVLAINTSK FPNMYIPVGQ VTDYGFLNLG GTPTKRMLMY 1690 1700 1710 1720 1730 1740 NFPTRAGQCG GVLMSTGKVL GIHVGGNGHQ GFSAALLKHY FNDEQGEIEF IESSKDAGFP 1750 1760 1770 1780 1790 1800 VINAPSRTKL EPSVFHQVFE GNKEPAVLRN GDPRLKANFE EAIFSKYIGN VNTRVDEYML 1810 1820 1830 1840 1850 1860 EAVDHYAGQL ATLDISTEPM KLEDAVYGTE GLEALDLTTS AGYPYVALGI KKRDILSKKT 1870 1880 1890 1900 1910 1920 KDLTKLKECM DKYGLNLPMV TYVKDELRSA EKVAKGKSRL IEASSLNDSV AMRQTFGNLY 1930 1940 1950 1960 1970 1980 KAFHLNPGIV TGSAVGCDPD MFWSKIPVML DGHLIAFDYS GYDASLSPVW FACLKLLLEK 1990 2000 2010 2020 2030 2040 LGYTHKETNY IDYLCNSHHL YRDKHYFVRG GMPSGCSGTS IFNSMINNII IRTLMLKVYK 2050 2060 2070 2080 2090 2100 GIDLDQFRMI AYGDDVIASY PWPIDASLLA EAGKDYGLIM TPADKGECFN EVTWTNVTFL 2110 2120 2130 2140 2150 2160 KRYFRADEQY PFLVHPVMPM KDIHESIRWT KDPKNTQDHV RSLCLLAWHN GEHEYEEFIR 2170 2180 KIRSVPVGRC LSLPAFSTLR RKWLDSF

References

[1]	"Genomic and phylogenetic characterization of coxsackievirus B2 prototype strain Ohio-1." Polacek C., Lundgren A., Andersson A., Lindberg A.M. Virus Res. 59:229-238(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[2]	"Nucleotide sequence of coxsackievirus B2 Ohio." Zell R., Birch-Hirschfeld E., Fortmuller U., Henke A., Stelzner A. Submitted (JUL-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[3]	"The coxsackie-adenovirus receptor (CAR) is used by reference strains and clinical isolates representing all six serotypes of coxsackievirus group B and by swine vesicular disease virus." Martino T.A., Petric M., Weingartl H., Bergelson J.M., Opavsky M.A., Richardson C.D., Modlin J.F., Finberg R.W., Kain K.C., Willis N., Gauntt C.J., Liu P.P. Virology 271:99-108(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HOST CXADR.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF085363 Genomic RNA. Translation: AAD19874.1. AF081485 Genomic RNA. Translation: AAD46138.1.
3D structure databases
ProteinModelPortal	Q9YLG5.
SMR	Q9YLG5. Positions 2-69, 77-571, 584-852, 854-1003, 1543-2187.
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. IPR027417. P-loop_NTPase. 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. SSF52540. SSF52540. 1 hit.
PROSITE	PS50507. RDRP_SSRNA_POS. 1 hit. PS51218. SF3_HELICASE_2. 1 hit. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

POLG_CXB2O

Accession

Primary (citable) accession number: Q9YLG5
Secondary accession number(s): Q9QSN9

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 23, 2003
Last sequence update:	January 23, 2007
Last modified:	May 29, 2013
This is version 110 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program