P08292 (POLG_CXB4J) 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 B4 (strain JVB / Benschoten / New York/51) [Complete proteome]
Taxonomic identifier	103906 [NCBI]
Taxonomic lineage	Viruses › ssRNA viruses › ssRNA positive-strand viruses, no DNA stage › Picornavirales › Picornaviridae › Enterovirus › Enterovirus B › Human coxsackievirus B4
Virus host	Homo sapiens (Human) [TaxID: 9606]

Protein attributes

Sequence length	2183 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	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_0000311050

Chain

2 – 69

68

Protein VP4 Potential

PRO_0000039615

Chain

70 – 330

261

Protein VP2 Potential

PRO_0000039616

Chain

331 – 568

238

Protein VP3 Potential

PRO_0000039617

Chain

569 – 849

281

Protein VP1 Potential

PRO_0000039618

Chain

850 – 999

150

Picornain 2A Potential

PRO_0000039619

Chain

1000 – 1098

99

Protein 2B Potential

PRO_0000039620

Chain

1099 – 1427

329

Protein 2C Potential

PRO_0000039621

Chain

1428 – 1516

89

Protein 3A Potential

PRO_0000039622

Chain

1517 – 1538

22

Protein 3B Potential

PRO_0000039623

Chain

1539 – 1721

183

Picornain 3C Potential

PRO_0000039624

Chain

1722 – 2183

462

RNA-directed RNA polymerase 3D-POL Potential

PRO_0000039625

Regions

Topological domain

2 – 1493

1492

Cytoplasmic Potential

Intramembrane

1494 – 1509

16

Potential

Topological domain

1510 – 2183

674

Cytoplasmic Potential

Domain

1203 – 1359

157

SF3 helicase

Domain

1948 – 2064

117

RdRp catalytic

Nucleotide binding

1227 – 1234

8

ATP Potential

Sites

Active site

870

1

For picornain 2A activity By similarity

Active site

888

1

For picornain 2A activity By similarity

Active site

959

1

For picornain 2A activity By similarity

Active site

1578

1

For picornain 3C activity Potential

Active site

1609

1

For picornain 3C activity Potential

Active site

1685

1

For picornain 3C activity By similarity

Site

69 – 70

2

Cleavage Potential

Site

330 – 331

2

Cleavage; by picornain 3C Potential

Site

849 – 850

2

Cleavage; by picornain 2A Potential

Site

999 – 1000

2

Cleavage; by picornain 3C Potential

Site

1098 – 1099

2

Cleavage; by picornain 3C Potential

Site

1427 – 1428

2

Cleavage; by picornain 3C Potential

Site

1516 – 1517

2

Cleavage; by picornain 3C Potential

Site

1538 – 1539

2

Cleavage; by picornain 3C Potential

Site

1721 – 1722

2

Cleavage; by picornain 3C Potential

Amino acid modifications

Modified residue

1519

1

O-(5'-phospho-RNA)-tyrosine By similarity

Lipidation

2

1

N-myristoyl glycine; by host By similarity

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

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.

.

.

.

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.

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2183

Helix Strand Turn

Details...

Beta strand

858 – 861

4

Beta strand

864 – 868

5

Helix

869 – 871

3

Helix

874 – 878

5

Beta strand

880 – 884

5

Turn

885 – 888

4

Beta strand

889 – 893

5

Beta strand

908 – 914

7

Turn

915 – 917

3

Beta strand

919 – 924

6

Beta strand

929 – 933

5

Beta strand

941 – 951

11

Beta strand

953 – 955

3

Beta strand

960 – 964

5

Beta strand

966 – 976

11

Beta strand

978 – 986

9

Sequences

	Sequence		Length	Mass (Da)
	P08292 [UniParc]. Last modified January 23, 2007. Version 4. Checksum: DEA069DE3AE91AF0	FASTA	2,183	244,014
	10 20 30 40 50 60 MGAQVSTQKT GAHETSLSAS GNSIIHYTNI NYYKDAASNS ANRQDFTQDP SKFTEPVKDV 70 80 90 100 110 120 MIKSLPALNS PTVEECGYSD RVRSITLGNS TITTQECANV VVGYGVWPDY LSDEEATAED 130 140 150 160 170 180 QPTQPDVATC RFYTLNSVKW EMQSAGWWWK FPDALSEMGL FGQNMQYHYL GRSGYTIHVQ 190 200 210 220 230 240 CNASKFHQGC LLVVCVPEAE MGCTNAENAP AYGDLCGGET AKSFEQNAAT GKTAVQTAVC 250 260 270 280 290 300 NAGMGVGVGN LTIYPHQWIN LRTNNSATIV MPYINSVPMD NMFRHNNFTL MIIPFAPLDY 310 320 330 340 350 360 VTGASSYIPI TVTVAPMSAE YNGLRLAGHQ GLPTMLTPGS TQFLTSDDFQ SPSAMPQFDV 370 380 390 400 410 420 TPEMNIPGQV RNLMEIAEVD SVVPINNLKA NLMTMEAYRV QVRSTDEMGG QIFGFPLQPG 430 440 450 460 470 480 ASSVLQRTLL GEILNYYTHW SGSLKLTFVF CGSAMATGKF LLAYSPPGAG APDSRKNAML 490 500 510 520 530 540 GTHVIWDVGL QSSCVLCVPW ISQTHYRYVV DDKYTASGFI SCWYQTNVIV PAEAQKSCYI 550 560 570 580 590 600 MCFVSACNDF SVRMLRDTQF IKQTNFYQGP TEESVERAMG RVADTIARGP SNSEQIPALT 610 620 630 640 650 660 AVETGHTSQV DPSDTMQTRH VHNYHSRSES SIENFLCRSA CVIYIKYSSA ESNNLKRYAE 670 680 690 700 710 720 WVINTRQVAQ LRRKMEMFTY IRCDMELTFV ITSHQEMSTA TNSDVPVQTH QIMYVPPGGP 730 740 750 760 770 780 VPTSVNDYVW QTSTNPSIFW TEGNAPPRMS IPFMSIGNAY TMFYDGWSNF SRDGIYGYNS 790 800 810 820 830 840 LNNMGTIYAR HVNDSSPGGL TSTIRIYFKP KHVKAYVPRP PRLCQYKKAK SVNFDVEAVT 850 860 870 880 890 900 AERASLITTG PYGHQSGAVY VGNYKVVNRH LATHVDWQNC VWEDYNRDLL VSTTTAHGCD 910 920 930 940 950 960 TIARCQCTTG VYFCASKSKH YPVSFEGPGL VEVQESEYYP KRYQSHVLLA TGFSEPGDCG 970 980 990 1000 1010 1020 GILRCEHGVI GLVTMGGEGV VGFADVRDLL WLEDDAMEQG VKDYVEQLGN AFGSGFTNQI 1030 1040 1050 1060 1070 1080 CEQVNLLKES LVGQDSILEK SLKALVKIIS ALVIVVRNHD DLITVTATLA LIGCTSSPWR 1090 1100 1110 1120 1130 1140 WLKHKVSQYY GIPMAERQNN GWLKKFTEMT NACKGMEWIA VKIQKFIEWL KVKILPEVKE 1150 1160 1170 1180 1190 1200 KHEFLSRLKQ LPLLESQIAT IEQSAPSQSD QEQLFSNVQY FAHYCRKYAP LYAAEAKRVF 1210 1220 1230 1240 1250 1260 SLEKKMSNYI QFKSKCRIEP VCLLLHGSPG AGKSVATNLI GRSLAEKLNS SVYSLPPDPD 1270 1280 1290 1300 1310 1320 HFDGYKQQAV VIMDDLCQNP DGKDVSLFCQ MVSSVDFVPP MAALEEKGIL FTSPFVLAST 1330 1340 1350 1360 1370 1380 NAGSINAPTV SDSRALARRF HFDMNIEVIS MYSQNGKINM PMSVKTCDEE CCPVNFKRCC 1390 1400 1410 1420 1430 1440 PLVCGKAIQF IDRKTQVRYS LDMLVTEMFR EYNHRHSVGA TLEALFQGPP VYREIKISVT 1450 1460 1470 1480 1490 1500 PETPPPPVIA DLLKSVDRQA IREYCKEKGW LVPEIDSILQ IEKHVSRAFI CLQALTTFVS 1510 1520 1530 1540 1550 1560 VAGIIYIIYK LFAGFQGAYT GMPNQKPKVP TLRQAKVQGP AFEFAVAMMK RNSSTVKTEY 1570 1580 1590 1600 1610 1620 GEFTMLGIYD RWAVLPRHAK PGPTILMNDQ EVGVLDAKEL IDRDGTNLEL TLLKLNRNEK 1630 1640 1650 1660 1670 1680 FRDIRGFLAK EEVEVNEAVL AINTSKFPNM YIPVGRVTDY GFLNLGGTPT KRMLMYNFPT 1690 1700 1710 1720 1730 1740 RAGQCGGVLM STGKVLGIHV GGNGHQGFSA GLLKHYFNDE QGEIEFIESS KDAGFPVINT 1750 1760 1770 1780 1790 1800 PSRTKLEPSV FHHVFEGNKE PAVLRNGDPR LKVNFEEAIF FKYIGNVNTH VDEYMLEAVD 1810 1820 1830 1840 1850 1860 HYAGQLATLD INTEPMKLED AVYGTEGLEA LDLTTSAGYP YVALGIKKRD ILSKKTKDLT 1870 1880 1890 1900 1910 1920 KLKECMDKYG LNLPMVTYVK DELRSAEKVA KGKSRLIEAS SLNDSVAMRQ TFGNLYKAFH 1930 1940 1950 1960 1970 1980 LNPGIVTGSA VGCDPDVFWS KIPVMLDGHL IAFDYSGYDA SLSPVWFACL KLLLEKLGYT 1990 2000 2010 2020 2030 2040 HKETNYIDYL CNSHHLYRDK HYFVRGGMPS GCSGTSIFNS MINNIIIRTL MLKVYKGIDL 2050 2060 2070 2080 2090 2100 DQFRMIAYGD DVIASYPWPI DASLLAEAGK DYGLIMTPAD KGECFNEVTW TNVTFLKRYF 2110 2120 2130 2140 2150 2160 RADEQYPFLV HPVMPMKDIH ESIRWTKDPK NTQDHVRSLC LLAWHNGEHE YEEFIQKIRS 2170 2180 VPVGRCLTLP AFSTLRRKWL DSF

References

[1]	"The complete nucleotide sequence of coxsackievirus B4 and its comparison to other members of the Picornaviridae." Jenkins O., Booth J.D., Minor P.D., Almond J.W. J. Gen. Virol. 68:1835-1848(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[2]	"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.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X05690 Genomic RNA. Translation: CAA29172.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1Z8R	NMR	-	A	842-999	[»]

ProteinModelPortal

P08292.

SMR

P08292. Positions 2-69, 77-568, 581-848, 850-999, 1539-2183.

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...

Other

EvolutionaryTrace

P08292.

Entry information

Entry name

POLG_CXB4J

Accession

Primary (citable) accession number: P08292

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1988
Last sequence update:	January 23, 2007
Last modified:	May 1, 2013
This is version 131 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program