Q66282 (POLG_CXB3W) 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 B3 (strain Woodruff) [Complete proteome]
Taxonomic identifier	103904 [NCBI]
Taxonomic lineage	Viruses › ssRNA viruses › ssRNA positive-strand viruses, no DNA stage › Picornavirales › Picornaviridae › Enterovirus › Enterovirus B › Human coxsackievirus B3
Virus host	Homo sapiens (Human) [TaxID: 9606]

Protein attributes

Sequence length	2185 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. 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

Chain

2 – 332

331

Protein VP0 Potential

PRO_0000311048

Chain

2 – 69

68

Protein VP4 Potential

PRO_0000039593

Chain

70 – 332

263

Protein VP2 Potential

PRO_0000039594

Chain

333 – 570

238

Protein VP3 Potential

PRO_0000039595

Chain

571 – 851

281

Protein VP1 Potential

PRO_0000039596

Chain

852 – 1001

150

Picornain 2A Potential

PRO_0000039597

Chain

1002 – 1100

99

Protein 2B Potential

PRO_0000039598

Chain

1101 – 1429

329

Protein 2C Potential

PRO_0000039599

Chain

1430 – 1518

89

Protein 3A Potential

PRO_0000039600

Chain

1519 – 1540

22

Protein 3B Potential

PRO_0000039601

Chain

1541 – 1723

183

Picornain 3C Potential

PRO_0000039602

Chain

1724 – 2185

462

RNA-directed RNA polymerase 3D-POL Potential

PRO_0000039603

Regions

Topological domain

2 – 1495

1494

Cytoplasmic Potential

Intramembrane

1496 – 1511

16

Potential

Topological domain

1512 – 2185

674

Cytoplasmic Potential

Domain

1205 – 1361

157

SF3 helicase

Domain

1950 – 2066

117

RdRp catalytic

Nucleotide binding

1229 – 1236

8

ATP Potential

Sites

Active site

872

1

For picornain 2A activity By similarity

Active site

890

1

For picornain 2A activity By similarity

Active site

961

1

For picornain 2A activity By similarity

Active site

1580

1

For picornain 3C activity Potential

Active site

1611

1

For picornain 3C activity Potential

Active site

1687

1

For picornain 3C activity By similarity

Site

69 – 70

2

Cleavage Potential

Site

332 – 333

2

Cleavage; by picornain 3C Potential

Site

851 – 852

2

Cleavage; by picornain 2A Potential

Site

1001 – 1002

2

Cleavage; by picornain 3C Potential

Site

1100 – 1101

2

Cleavage; by picornain 3C Potential

Site

1429 – 1430

2

Cleavage; by picornain 3C Potential

Site

1518 – 1519

2

Cleavage; by picornain 3C Potential

Site

1540 – 1541

2

Cleavage; by picornain 3C Potential

Site

1723 – 1724

2

Cleavage; by picornain 3C Potential

Amino acid modifications

Modified residue

1521

1

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

Lipidation

2

1

N-myristoyl glycine; by host Ref.2

Secondary structure

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2185

Helix Strand Turn

Details...

Beta strand

83 – 87

5

Beta strand

90 – 96

7

Turn

113 – 115

3

Helix

126 – 128

3

Beta strand

133 – 140

8

Beta strand

147 – 151

5

Turn

152 – 154

3

Helix

159 – 167

9

Beta strand

168 – 180

13

Beta strand

188 – 197

10

Beta strand

203 – 205

3

Helix

212 – 215

4

Beta strand

218 – 220

3

Beta strand

225 – 227

3

Helix

241 – 243

3

Turn

244 – 247

4

Helix

250 – 255

6

Beta strand

256 – 262

7

Turn

263 – 265

3

Beta strand

267 – 273

7

Beta strand

278 – 280

3

Turn

284 – 286

3

Beta strand

290 – 301

12

Beta strand

310 – 326

17

Turn

340 – 343

4

Beta strand

355 – 357

3

Beta strand

369 – 374

6

Helix

376 – 379

4

Helix

391 – 395

5

Helix

397 – 400

4

Beta strand

402 – 405

4

Beta strand

408 – 410

3

Beta strand

413 – 419

7

Turn

421 – 423

3

Turn

425 – 429

5

Helix

431 – 436

6

Beta strand

439 – 443

5

Beta strand

446 – 452

7

Beta strand

461 – 467

7

Beta strand

469 – 471

3

Helix

477 – 480

4

Beta strand

483 – 489

7

Beta strand

491 – 493

3

Beta strand

495 – 500

6

Beta strand

505 – 512

8

Beta strand

521 – 528

8

Beta strand

538 – 548

11

Beta strand

553 – 557

5

Beta strand

599 – 602

4

Helix

604 – 606

3

Helix

614 – 617

4

Helix

634 – 638

5

Beta strand

642 – 654

13

Beta strand

656 – 661

6

Helix

668 – 674

7

Beta strand

677 – 694

18

Beta strand

708 – 714

7

Helix

727 – 730

4

Beta strand

732 – 734

3

Beta strand

736 – 740

5

Beta strand

747 – 750

4

Beta strand

755 – 761

7

Beta strand

765 – 768

4

Turn

769 – 771

3

Beta strand

772 – 776

5

Helix

777 – 779

3

Beta strand

785 – 791

7

Beta strand

795 – 797

3

Beta strand

799 – 817

19

Beta strand

828 – 830

3

Sequences

	Sequence		Length	Mass (Da)
	Q66282 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: FD93A677904252FA	FASTA	2,185	243,682
	10 20 30 40 50 60 MGAQVSTQKT GAHETGLNAS GNSIIHYTNI NYYKDAASNS ANRQDFTQDP SKFTEPVKDI 70 80 90 100 110 120 MIKSLPALNS PTVEECGYSD RVRSITLGNS TITTQECANV VVGYGVWPDY LKDSEATAED 130 140 150 160 170 180 QPTQPDVATC RFYTLDSVQW QKTSPGWWWK LPDALSNLGL FGQNMQYHYL GRTGYTIHVQ 190 200 210 220 230 240 CNASKFHQGC LLVVCVPEAE MGCATLNNTP SSAELLGGDS AKEFADKPVA SGSNKLVQRV 250 260 270 280 290 300 VYNAGMGVGV GNLTIFPHQW INLRTNNSAT IVMPYTNSVP MDNMFRHNNV TLMVIPFVPL 310 320 330 340 350 360 DYCPGSTTYV PITITIAPMC AEYNGLRLAG HQGLPTMNTP GSCQFLTSDD FQSPSAMPQY 370 380 390 400 410 420 DVTPEMRIPG EVKNLMEIAE VDSVVPVQNV GEKVNSMEAY QIPVRSNEGS GTQVFGFPLQ 430 440 450 460 470 480 PGYSSVFSRT LLGEILNYYT HWSGSIKLTF MFCGSAMATG KFLLAYSPPG AGAPTKRVDA 490 500 510 520 530 540 MLGTHVVWDV GLQSSCVLCI PWISQTHYRY VASDEYTAGG FITCWYQTNI VVPADAQSSC 550 560 570 580 590 600 YIMCFVSACN DFSVRLLKDT PFISQQNFFQ GPVEDAITAA IGRVADTVGT GPTNSEAIPA 610 620 630 640 650 660 LTAAETGHTS QVVPSDTMQT RHVKNYHSRS ESTIENFLCR SACVYFTEYE NSGAKRYAEW 670 680 690 700 710 720 VITPRQAAQL RRKLEFFTYV RFDLELTFVI TSTQQPSTTQ NQDAQILTHQ IMYVPPGGPV 730 740 750 760 770 780 PDKVDSYVWQ TSTNPSVFWT EGNAPPRMSV PFLSIGNAYS NFYDGWSEFS RNGVYGINTL 790 800 810 820 830 840 NNMGTLYARH VNAGSTGPIK STIRIYFKPK HVKAWIPRPP RLCQYEKAKN VNFQPSGVTT 850 860 870 880 890 900 TRQSITTMTN TGAFGQQSGA VYVGNYRVVN RHLATSADWQ NCVWENYNRD LLVSTTTAHG 910 920 930 940 950 960 CDIIARCRCT TGVYFCASKN KHYPISFEGP GIVEVQESEY YPRRYQSHVL LAAGFSEPGD 970 980 990 1000 1010 1020 CGGILRCEHG VIGIVTMGGE GVVGFADIRD LLWLEDDAME QGVKDYVEQL GNAFGSGFTN 1030 1040 1050 1060 1070 1080 QICEQVNLLK ESLVGQDSIL EKSLKALVKI ISALVIVVRN HDDLITVTAT LALIGCTSSP 1090 1100 1110 1120 1130 1140 WRWLKQKVSQ YYGIPMAERQ NNGWLKKFTE MTNACKGMEW IAIKIQKFIE WLKVKILPEV 1150 1160 1170 1180 1190 1200 REKHEFLNRL KQLPLLESQI ATIEQSAPSQ SDQEQLFSNV QYFAHYCRKY APLYASEAKR 1210 1220 1230 1240 1250 1260 VFSLEKKMSN YIQFKSKCRI EPVCLLLHGS PGAGKSVATN LIGRSLAEKL NSSVYSLPPD 1270 1280 1290 1300 1310 1320 PDHFDGYKQQ AVVIMDDLCQ KPDGKDVSLF CQMVSSVDFV PPMAALEEKG ILFTSPFVLA 1330 1340 1350 1360 1370 1380 STNAGSINAP TVSDSRALAR RFHFDMNIEV ISMYSQNGKI NMPMSVKTCD EECCPVNFKK 1390 1400 1410 1420 1430 1440 CCPLVCGKAI QFIDRRTQVR YSLDMLVTEM FREYNHRHSV GATLEALFQG PPVYREIKIS 1450 1460 1470 1480 1490 1500 VAPETPPPPR IADLLKSVDS EAVREYCKEK GWLVPEVNST LQIEKHVSRA FICLQAITTF 1510 1520 1530 1540 1550 1560 VSVAGIIYII YKLFAGFQGA YTGIPNQKPK VPTLRQAKVQ GPAFEFAVAM MKRNSSTVKT 1570 1580 1590 1600 1610 1620 EYGEFTMLGI YDRWAVLPRH AKPGPTILMN DQEVGVLDAK ELVDKDGTNL ELTLLKLNRN 1630 1640 1650 1660 1670 1680 EKFRDIRGFL AKEEVEVNEA VLAINTSKFP NMYIPVGQVT DYGFLNLGGT PTKRMLMYNF 1690 1700 1710 1720 1730 1740 PTRAGQCGGV LMSTGKVLGI HVGGNGHQGF SAALLKHYFN DEQGEIEFIE SSKEAGFPII 1750 1760 1770 1780 1790 1800 NTPSKTKLEP SVFHQVFEGD KEPAVLRNGD PRLKVNFEEA IFSKYIGNVN THVDEYMMEA 1810 1820 1830 1840 1850 1860 VDHYAGQLAT LDISTEPMKL EDAVYGTEGL EALDLTTSAG YPYVALGIKK RDILSKKTRD 1870 1880 1890 1900 1910 1920 LTKLKECMDK YGLNLPMVTY VKDELRSAEK VAKGKSRLIE ASSLNDSVAM RQTFGNLYKT 1930 1940 1950 1960 1970 1980 FHLNPGVVTG SAVGCDPDLF WSKIPVMLDG HLIAFDYSGY DASLSPVWFA CLKLLLEKLG 1990 2000 2010 2020 2030 2040 YSHKETNYID YLCNSHHLYR DKHYFVRGGM PSGCSGTSIF NSMINNIIIR TLMLKVYKGI 2050 2060 2070 2080 2090 2100 DLDQFRMIAY GDDVIASYPW PIDASLLAEA GKDYGLIMTP ADKGECFNEV TWTNVTFLKR 2110 2120 2130 2140 2150 2160 YFRADEQYPF LVHPVMPMKD IHESIRWTKD PKNTQDHVRS LCLLAWHNGE HEYEEFIRKI 2170 2180 RSVPVGRCLT LPAFSTIRRK WLDSF

References

[1]	"A mutation in the puff region of VP2 attenuates the myocarditic phenotype of an infectious cDNA of the Woodruff virus." Knowlton K.U., Jeon E.S., Berkley R.W., Wessely R., Huber S. Submitted (APR-1996) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[2]	"The structure of coxsackievirus B3 at 3.5 A resolution." Muckelbauer J.K., Kremer M., Minor I., Diana G., Dutko F.J., Groarke J., Pevear D.C., Rossmann M.G. Structure 3:653-667(1995) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY ELECTRON MICROSCOPY (3.5 ANGSTROMS) OF 70-851, MYRISTOYLATION AT GLY-2.
+	Additional computationally mapped references.

Web resources

Virus Particle ExploreR db

Icosahedral capsid structure

Virus Particle ExploreR db

Icosahedral capsid structure

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U57056 Genomic RNA. Translation: AAB02228.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1COV	X-ray	3.50	1	571-851	[»]
			2	70-332	[»]
			3	333-570	[»]
			4	2-69	[»]
1JEW	electron microscopy	22.00	1	571-851	[»]
			2	70-332	[»]
			3	333-570	[»]
			4	2-69	[»]

ProteinModelPortal

Q66282.

SMR

Q66282. Positions 2-69, 77-570, 583-1001, 1541-2185.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q66282. 1 interaction.

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

Q66282.

Entry information

Entry name

POLG_CXB3W

Accession

Primary (citable) accession number: Q66282

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	January 23, 2007
Last modified:	May 1, 2013
This is version 123 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program