P22055 (POLG_CXA21) 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 A21 (strain Coe) [Complete proteome]
Taxonomic identifier	12070 [NCBI]
Taxonomic lineage	Viruses › ssRNA viruses › ssRNA positive-strand viruses, no DNA stage › Picornavirales › Picornaviridae › Enterovirus › Enterovirus C › Human coxsackievirus A21
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	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 capsid interacts with human ICAM1 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.
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 – 341

340

Protein VP0 Potential

PRO_0000311043

Chain

2 – 69

68

Protein VP4 Potential

PRO_0000039536

Chain

70 – 341

272

Protein VP2 Potential

PRO_0000039537

Chain

342 – 581

240

Protein VP3 Potential

PRO_0000039538

Chain

582 – 879

298

Protein VP1 Potential

PRO_0000039539

Chain

880 – 1028

149

Picornain 2A Potential

PRO_0000039540

Chain

1029 – 1125

97

Protein 2B Potential

PRO_0000039541

Chain

1126 – 1453

328

Protein 2C Potential

PRO_0000039542

Chain

1454 – 1540

87

Protein 3A Potential

PRO_0000039543

Chain

1541 – 1562

22

Protein 3B Potential

PRO_0000039544

Chain

1563 – 1745

183

Picornain 3C Potential

PRO_0000039545

Chain

1746 – 2206

461

RNA-directed RNA polymerase 3D-POL Potential

PRO_0000039546

Regions

Topological domain

2 – 1517

1516

Cytoplasmic Potential

Intramembrane

1518 – 1533

16

Potential

Topological domain

1534 – 2206

673

Cytoplasmic Potential

Domain

1230 – 1385

156

SF3 helicase

Domain

1972 – 2087

116

RdRp catalytic

Nucleotide binding

1254 – 1261

8

ATP Potential

Sites

Active site

899

1

For picornain 2A activity By similarity

Active site

917

1

For picornain 2A activity By similarity

Active site

988

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

341 – 342

2

Cleavage; by picornain 3C Potential

Site

879 – 880

2

Cleavage; by picornain 2A Potential

Site

1028 – 1029

2

Cleavage; by picornain 3C Potential

Site

1125 – 1126

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

Secondary structure

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2206

Helix Strand Turn

Details...

Beta strand

4 – 7

4

Beta strand

26 – 29

4

Beta strand

33 – 35

3

Helix

36 – 38

3

Helix

51 – 54

4

Beta strand

57 – 59

3

Beta strand

83 – 87

5

Beta strand

90 – 96

7

Helix

103 – 105

3

Turn

113 – 115

3

Helix

126 – 128

3

Beta strand

138 – 141

4

Beta strand

147 – 151

5

Helix

153 – 155

3

Helix

159 – 167

9

Beta strand

168 – 180

13

Beta strand

187 – 198

12

Beta strand

208 – 210

3

Helix

214 – 217

4

Helix

220 – 222

3

Helix

237 – 240

4

Beta strand

241 – 243

3

Helix

247 – 249

3

Turn

250 – 252

3

Helix

256 – 261

6

Beta strand

262 – 268

7

Turn

269 – 271

3

Beta strand

273 – 279

7

Beta strand

283 – 288

6

Turn

290 – 292

3

Beta strand

296 – 310

15

Beta strand

315 – 332

18

Turn

349 – 352

4

Beta strand

364 – 366

3

Beta strand

378 – 381

4

Helix

384 – 387

4

Turn

400 – 404

5

Helix

406 – 409

4

Beta strand

410 – 416

7

Beta strand

422 – 427

6

Turn

429 – 431

3

Turn

433 – 437

5

Helix

439 – 444

6

Beta strand

447 – 452

6

Beta strand

454 – 460

7

Beta strand

469 – 475

7

Beta strand

477 – 479

3

Helix

485 – 488

4

Beta strand

491 – 497

7

Beta strand

499 – 501

3

Beta strand

503 – 508

6

Beta strand

513 – 520

8

Beta strand

529 – 536

8

Beta strand

546 – 556

11

Beta strand

561 – 565

5

Sequences

	Sequence		Length	Mass (Da)
	P22055 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 537F6A13AD37723B	FASTA	2,206	246,051
	10 20 30 40 50 60 MGAQVSTQKT GAHENQNVAA NGSTINYTTI NYYKDSASNS ATRQDLSQDP SKFTEPVKDL 70 80 90 100 110 120 MLKTAPALNS PNVEACGYSD RVRQITLGNS TITTQEAANA IVAYGEWPTY INDSEANPVD 130 140 150 160 170 180 APTEPDVSSN RFYTLESVSW KTTSRGWWWK LPDCLKDMGM FGQNMYYHYL GRSGYTIHVQ 190 200 210 220 230 240 CNASKFHQGA LGVFLIPEFV MACNTESKTS YVSYINANPG ERGGEFTNTY NPSNTDVSEG 250 260 270 280 290 300 RQFAALDYLL GSGVLAGNAF VYPHQIINLR TNNSATIVVP YVNSLVIDCM AKHNNWGIVI 310 320 330 340 350 360 LPLAPLAFAA TSSPQVPITV TIAPMCTEFN GLRNITIPVH QGLPTMNTPG SNQFLTSDDF 370 380 390 400 410 420 QSPCALPNFD VTPPIHIPGE VKNMMELAEI DTLIPMNAVD GKVNTMEMYQ IPLNDNLSKA 430 440 450 460 470 480 PIFCLSLSPA SDKRLSHTML GEILNYYTHW TGSIRFTFLF CGSMMATGKL LLSYSPPGAK 490 500 510 520 530 540 PPTNRKDAML GTHIIWDLGL QSSCSMVAPW ISNTVYRRCA RDDFTEGGFI TCFYQTRIVV 550 560 570 580 590 600 PASTPTSMFM LGFVSACPDF SVRLLRDTSH ISQSKLIART QGIEDLIDTA IKNALRVSQP 610 620 630 640 650 660 LRPSQLKQPN GVNSQEVPAL TAVETGASGQ AIPSDVVETR HVINYKTRSE SCLESFFGRA 670 680 690 700 710 720 ACVTILSLTN SSKSGEEKKH FNIWNITYTD TVQLRRKLEF FTYSRFDLEM TFVFTENYPS 730 740 750 760 770 780 TASGEVRNQC DQIMYIPPGA PRPSSWDDYT WQSSSNPSIF YMYGNAPPRM SIPYVGIANA 790 800 810 820 830 840 YSHFYDGFAR VPLEGENTDA GDTFYGLVSI NDFGVLAVRA VNRSNPHTIH TSVRVYMKPK 850 860 870 880 890 900 HIRCWCPRPP RAVLYRGEGV DMISSAIQPL TKVDSITTFG FGHQNKAVYV AGYKICNYHL 910 920 930 940 950 960 ATPSDHLNAI SVLWDRDLMV VESRAQGTDT IARCSCRCGV YYCESRRKYY LVTFTGPTFR 970 980 990 1000 1010 1020 FMEANDYYPA RYQSHMLIGC GFAEPGDCGG ILRCTHGVIG IITAGGEGIV AFADIRDLWV 1030 1040 1050 1060 1070 1080 YEEEAMEQGI TSYIESLGTA FGAGFTHTIS EKVTELTTMV TSTITEKLLK NLVKIVSALV 1090 1100 1110 1120 1130 1140 IVVRNYEDTT TILATLALLG CDISPWQWLK KKACDLLEIP HVMRQGDGWM KKFTEACNAA 1150 1160 1170 1180 1190 1200 KGLRWVSNKI SKFVDWLKCK IIPEAKDKVE FLTKLKQLDM LENQIATIHQ SCPSQEQQEI 1210 1220 1230 1240 1250 1260 LFNNVRWLAV QSRRFAPLYA VEARRISKME STINNYIQFK SKHRIEPVCM LVHGSPGTGK 1270 1280 1290 1300 1310 1320 GIASSLIGRA IAERETTSVY SVPLAPSHFD GYKQQGYDMD DLNQNPDGMD MKLFCQMVST 1330 1340 1350 1360 1370 1380 VEFIPPMASL EEKGILFTSD YVLASTNSHS IAPPTVAHSD ALTRRFAFDV EVYTMSEHSV 1390 1400 1410 1420 1430 1440 KGKLNMATAT QLCKDCPTPA NFKKCCPLVC GKALQLMDRY TRQRFTVDEI TTLIMNEKNR 1450 1460 1470 1480 1490 1500 RANIGNCMEA LFQGPLRYKD LKIDVKTVPP PECISDLLQA VDSQEVRDYC EKKGWIVNVT 1510 1520 1530 1540 1550 1560 SQIQLERNIN RAMTILQAVT TFAAVAGVVY VMYKLFAGQQ GAYTGLPNKK PNVPTIRIAK 1570 1580 1590 1600 1610 1620 VQGPGFDYAV AMAKRNIVTA TTTKGEFTML GVHDNVAILP THAAPGETII VDGKEVEILD 1630 1640 1650 1660 1670 1680 ARALEDQAGT NLEITIITLK RNEKFRDIRP HIPTQITETN DGVLIVNTSK YPNMYVPVGA 1690 1700 1710 1720 1730 1740 VTEQGYLNLS GRQTARTLMY NFPTRAGQCG GIITCTGKVI GMHVGGNGSH GFAAALKRSY 1750 1760 1770 1780 1790 1800 FTQNQGEIQW MRSSKEVGYP IINAPSKTKL EPSAFHYVFE GVKEPAVLTK NDPRLKTDFE 1810 1820 1830 1840 1850 1860 EAIFSKYVGN KITEVDEYMK EAVDHYAGQL MSLDINTEQM CLEDAMYGTD GLEALDLSTS 1870 1880 1890 1900 1910 1920 AGYPYVAMGK KKRDILDKQT RDTKEMQRLL DTYGINLPLV TYVKDELRSK TKVEQGKSRL 1930 1940 1950 1960 1970 1980 IEASSLNDSV AMRMAFGNLY AAFHKNPGVV TGSAVGCDPD LFWSKIPVLM EEKLFAFDYT 1990 2000 2010 2020 2030 2040 GYDASLSPAW FEALKMVLEK IGFGNRVDYI DYLNHSHHLY KNKTYCVKGG MPSGCSGTSI 2050 2060 2070 2080 2090 2100 FNSMINNLII RTLLLRTYKG IDLDHLKMIA YGDDVIASYP HEVDASLLAQ SGKDYGLTMT 2110 2120 2130 2140 2150 2160 PADKSATFET VTWENVTFLK RFFRADEKYP FLVHPVMPMK EIHESIRWTK DPRNTQDHVR 2170 2180 2190 2200 SLCLLAWHNG EEEYNKFLAK IRSVPIGRAL LLPEYSTLYR RWLDSF

References

[1]	"The complete nucleotide sequence of coxsackievirus A21." Hughes P.J., North C., Minor P.D., Stanway G. J. Gen. Virol. 70:2943-2952(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
+	Additional computationally mapped references.

Web resources

Virus Particle ExploreR db

Icosahedral capsid structure

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

D00538 Genomic RNA. Translation: BAA00426.1.

PIR

GNNY21. A33373.

RefSeq

NP_040759.1. NC_001428.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1Z7S	X-ray	3.20	2/3	-	[»]
			4	2-69	[»]

ProteinModelPortal

P22055.

SMR

P22055. Positions 2-580, 597-1028, 1454-1512, 1563-2206.

ModBase

Search...

Protein family/group databases

MEROPS

C03.020.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Family and domain databases

Gene3D

4.10.80.10. 2 hits.

InterPro

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]

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

P22055.

Entry information

Entry name

POLG_CXA21

Accession

Primary (citable) accession number: P22055

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1991
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