P03304 (POLG_EMCV) 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 Rho Virion protein 4 Protein VP2 Alternative name(s): Beta P1B Virion protein 2 Protein VP3 Alternative name(s): Gamma P1C Virion protein 3 Protein VP1 Alternative name(s): Alpha P1D Virion protein 1 Protein 2A Short name=P2A Alternative name(s): G Protein 2B Short name=I Short name=P2B Protein 2C Short name=C Short name=P2C EC=3.6.1.15 Protein 3A Short name=P3A Protein 3B Short name=P3B Alternative name(s): H VPg Picornain 3C EC=3.4.22.28 Alternative name(s): Protease 3C Short name=P3C p22 RNA-directed RNA polymerase 3D-POL Short name=E Short name=P3D-POL EC=2.7.7.48
Organism	Encephalomyocarditis virus [Complete proteome]
Taxonomic identifier	12104 [NCBI]
Taxonomic lineage	Viruses › ssRNA viruses › ssRNA positive-strand viruses, no DNA stage › Picornavirales › Picornaviridae › Cardiovirus
Virus host	Homo sapiens (Human) [TaxID: 9606] Mus musculus (Mouse) [TaxID: 10090] Sigmodon hispidus (Hispid cotton rat) [TaxID: 42415] Sus scrofa (Pig) [TaxID: 9823]

Protein attributes

Sequence length	2290 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 host VCAM1 to provide virion attachment on murine vascular endothelial cells By similarity. VP0 precursor is a component of immature procapsids 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 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 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	Protease 3C interacts with host TRIM22; this interaction leads to the ubiquitination of protease 3C and may restrict the virus replication. Ref.3
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 by the viral protease in vivo 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. The polyprotein seems to be cotranslationally cleaved at the 2A/2B junction by a ribosomal skip from one codon to the next without formation of a peptide bond. This process would release the L-P1-2A peptide from the translational complex 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	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 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 icosahedral viral capsid Inferred from electronic annotation. Source: InterPro membrane 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
	Propeptide	1 – 67	67	Leader peptide		PRO_0000039780
	Chain	68 – 391	324	Protein VP0 Potential		PRO_0000310967
	Chain	68 – 136	69	Protein VP4 Potential		PRO_0000039781
	Chain	137 – 391	255	Protein VP2 Potential		PRO_0000039782
	Chain	392 – 622	231	Protein VP3 Potential		PRO_0000039783
	Chain	623 – 899	277	Protein VP1 Potential		PRO_0000039784
	Chain	900 – 1042	143	Protein 2A Potential		PRO_0000039785
	Chain	1043 – 1192	150	Protein 2B Potential		PRO_0000039786
	Chain	1193 – 1517	325	Protein 2C Potential		PRO_0000039787
	Chain	1518 – 1605	88	Protein 3A Potential		PRO_0000039788
	Chain	1606 – 1625	20	Protein 3B Potential		PRO_0000039789
	Chain	1626 – 1830	205	Picornain 3C Potential		PRO_0000039790
	Chain	1831 – 2290	460	RNA-directed RNA polymerase 3D-POL Potential		PRO_0000039791
Regions
	Topological domain	1 – 1562	1562	Cytoplasmic Potential
	Intramembrane	1563 – 1581	19	Potential
	Topological domain	1582 – 2290	709	Cytoplasmic Potential
	Domain	1279 – 1445	167	SF3 helicase
	Domain	2059 – 2177	119	RdRp catalytic
	Nucleotide binding	1311 – 1318	8	ATP Potential
Sites
	Active site	1671	1	For picornain 3C activity Potential
	Active site	1703	1	For picornain 3C activity Potential
	Active site	1784	1	For picornain 3C activity Potential
	Site	136 – 137	2	Cleavage Potential
	Site	391 – 392	2	Cleavage; by picornain 3C Potential
	Site	622 – 623	2	Cleavage; by picornain 3C Potential
	Site	899 – 900	2	Cleavage; by picornain 3C Potential
	Site	1042 – 1043	2	Cleavage; by ribosomal skip Potential
	Site	1192 – 1193	2	Cleavage; by picornain 3C Potential
	Site	1517 – 1518	2	Cleavage; by picornain 3C Potential
	Site	1605 – 1606	2	Cleavage; by picornain 3C Potential
	Site	1625 – 1626	2	Cleavage; by picornain 3C Potential
	Site	1830 – 1831	2	Cleavage; by picornain 3C Potential
Amino acid modifications
	Modified residue	1608	1	O-(5'-phospho-RNA)-tyrosine By similarity
	Lipidation	68	1	N-myristoyl glycine; by host By similarity
Experimental info
	Sequence conflict	1337	1	S → P in AAA43036. Ref.2
	Sequence conflict	1397	1	F → L in AAA43036. Ref.2
	Sequence conflict	1518	1	G → A in AAA43036. Ref.2
	Sequence conflict	1537	1	Q → E in AAA43036. Ref.2
	Sequence conflict	1557	1	N → S in AAA43036. Ref.2
	Sequence conflict	1612	1	A → T in AAA43036. Ref.2
	Sequence conflict	1755	1	L → V in AAA43036. Ref.2
	Sequence conflict	1916	1	D → N in AAA43036. Ref.2
	Sequence conflict	1987 – 1988	2	FL → IH in AAA43036. Ref.2
	Sequence conflict	2008	1	V → I in AAA43036. Ref.2
	Sequence conflict	2049	1	T → H in AAA43036. Ref.2
	Sequence conflict	2194	1	T → K in AAA43036. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P03304 [UniParc]. Last modified July 21, 1986. Version 1. Checksum: 26BC81BB7CF68CB5	FASTA	2,290	255,758
	10 20 30 40 50 60 MATTMEQETC AHSLTFEECP KCSALQYRNG FYLLKYDEEW YPEELLTDGE DDVFDPELDM 70 80 90 100 110 120 EVVFELQGNS TSSDKNNSSS EGNEGVIINN FYSNQYQNSI DLSANAAGSD PPRLRSIFES 130 140 150 160 170 180 LSGAVNAFSN MLPLLADQNT EEMENLSDRG LKTLPAIRSQ TPSQQWAVLS VMVPFMMESI 190 200 210 220 230 240 RHHVLTLLQK RFWRWKGTTP SRLMIGHQHK SPLSTSAFPF LTSCPVKMVV SLVALRRHYL 250 260 270 280 290 300 VKTGWRVQVQ CNASQFHAGG LLVFMAPEYP TLDAFAMDNR WSKDNLPNGT RTQTNKKGPF 310 320 330 340 350 360 AMDHQNFWQW TLYPHQFLNL RTNTTVDLEV PYVNIAPTSS WTQHASWTLV IAVVAPLTYS 370 380 390 400 410 420 TGASTSLDIT ASIQPVRPVF NGLRHETLSR QSPIPVTIRE HAGTWYSTLP DSTVPIYGKT 430 440 450 460 470 480 PVAPSNYMVG EYKDFLEIAQ IPTFIGNKIP NAVPYIEASN TAVKTQPLAT YQVTLSCSCL 490 500 510 520 530 540 ANTFLAALSR NFAQYRGSLV YTFVFTGTAM MKGKFLIAYT PPGAGKPTSR DQAMQATYAI 550 560 570 580 590 600 WDLGLNSSYS FTVPFISPTH FRMVGTDQVN ITNADGWVTV WQLTPLTYPP GCPTSAKILT 610 620 630 640 650 660 MVSAGKDFSL KMPISPAPWS PQGVENAEKG VTENTNATAD FVAQPVYLPE NQTKVAFFYN 670 680 690 700 710 720 RSSPIGAFTV KSGSLESGFA PFSNGTCPNS VILTPGPQFD PAYDQLRPQR LTEIWGNGNE 730 740 750 760 770 780 ETSKVFPLKS KQDYSFCLFS PFVYYKCDLE VTLSPHTSGN HGLLVRWCPT GTPTKPTTQV 790 800 810 820 830 840 LHEVSSLSEG RTPQVYSAGP GISNQISFVV PYNSPLSVLS AVWYNGHKRF DNTGSLGIAP 850 860 870 880 890 900 NSDFGTLFFA GTKPDIKFTV YLRYKNKRVF CPRPTVFFPW PTSGDKIDMT PRAGVLMLES 910 920 930 940 950 960 PNALDISRTY PTLHVLIQFN HRGLEVRLFR HGHFWAETRA DVILRSKTKQ VSFLSNGNYP 970 980 990 1000 1010 1020 SMDSRAPWNP WKNTYQAVLR AEPCRVTMDI YYKRVRPFRL PLVQKEWPVR EENVFGLYRI 1030 1040 1050 1060 1070 1080 FNAHYAGYFA DLLIHDIETN PGPFMFRPRK QVFQTQGAAV SSMAQTLLPN DLASKAMGSA 1090 1100 1110 1120 1130 1140 FTALLDANED AQKAMKIIKT LSSLSDAWEN VKETLNNPEF WKQLLSRCVQ LIAGMTIAVM 1150 1160 1170 1180 1190 1200 HPDPLTLLCL GTLTAAEITS QTSLCEEIAA KFKTIFITPP PRFPTISLFQ QQSPLKQVND 1210 1220 1230 1240 1250 1260 IFSLAKNLDW AVKTVEKVVD WFGTWIVQEE KEQTLDQLLQ RFPEHAKRIS DLRNGMAAYV 1270 1280 1290 1300 1310 1320 ECKESFDFFE KLYNQAVKEK RTGIAAVCEK FRQKHDHATA RCEPVVIVLR GDAGQGKSLS 1330 1340 1350 1360 1370 1380 SQVIAQAVSK TIFGRQSVYS LPPDSDFFDG YENQFAAIMD DLGQNPDGSD FTTFCQMVST 1390 1400 1410 1420 1430 1440 TNFLPNMASL ERKGTPFTSQ LVVATTNLPE FRPVTIAHYP AVERRITFDY SVSAGPVCSK 1450 1460 1470 1480 1490 1500 TEAGYKVLDV ERAFRPTGEA PLPCFQNNCL FLEKAGLQFR DNRTKEIISL VDVIERAVAR 1510 1520 1530 1540 1550 1560 IERKKKVLTT VQTLVAQGPV DEVSFHSVVQ QLKARQQATD EQLEELQEAF AKVQERNSVF 1570 1580 1590 1600 1610 1620 SDWLKISAML CAATLALSQV VKMAKAVKQM VKPDLVRVQL DEQEQGPYNE TARVKPKTLQ 1630 1640 1650 1660 1670 1680 LLDIQGPNPV MDFEKYVAKH VTAPIGFVYP TGVSTQTCLL VRGRTLVVNR HMAESDWTSI 1690 1700 1710 1720 1730 1740 VVRGVTHARS TVKILAIAKA GKETDVSFIR LSSGPLFRDN TSKFVKAGDV LPTGAAPVTG 1750 1760 1770 1780 1790 1800 IMNTDIPMMY TGTFLKAGVS VPVETGQTFN HCIHYKANTR KGWCGSALLA DLGGSKKILG 1810 1820 1830 1840 1850 1860 IHSAGSMGIA AASIVSQEMI RAVVNAFEPQ GALERLPDGP RIHVPRKTAL RPTVARQVFQ 1870 1880 1890 1900 1910 1920 PAYAPAVLSK FDPRTEADVD EVAFSKHTSN QESLPPVFRM VAKEYANRVF TLLGKDNGRL 1930 1940 1950 1960 1970 1980 TVKQALEGLE GMDPMDRNTS PGLPYTALGM RRTDVVDWES ATLIPFAAER LRKMNEGDFS 1990 2000 2010 2020 2030 2040 EVVYQTFLKD ELRPIEKVQA AKTRIVDVPP FEHCILGRQL LGKFASKFQT QPGLELGSAI 2050 2060 2070 2080 2090 2100 GCDPDVHWTA FGVAMQGFER VYDVDYSNFD STHSVAMFRL LAEEFFTPEN GFDPLTREYL 2110 2120 2130 2140 2150 2160 ESLAISTHAF EEKRFLITGG LPSGCAATSM LNTIMNNIII RAGLYLTYKN FEFDDVKVLS 2170 2180 2190 2200 2210 2220 YGDDLLVATN YQLDFDKVRA SLAKTGYKIT PANTTSTFPL NSTLEDVVFL KRKFKKEGPL 2230 2240 2250 2260 2270 2280 YRPVMNREAL EAMLSYYRPG TLSEKLTSIT MLAVHSGKQE YDRLFAPFRE VGVVVPSFES 2290 VEYRWRSLFW

References

[1]	"The nucleotide and deduced amino acid sequences of the encephalomyocarditis viral polyprotein coding region." Palmenberg A.C., Kirby E.M., Janda M.R., Drake N.L., Duke G.M., Potratz K.F., Collett M.S. Nucleic Acids Res. 12:2969-2985(1984) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[2]	"Nucleotide sequence of the 3'-terminus of encephalomyocarditis virus RNA." Petrov N.A., Chizhikov V.E., Blinov V.M., Karginov V.A., Mikryukov N.N., Gutorov V.V., Grishaev M.P., Beklemishev A.B., Vassilenko S.K. Bioorg. Khim. 10:274-279(1984) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1337-2290.
[3]	"TRIM22 E3 ubiquitin ligase activity is required to mediate antiviral activity against encephalomyocarditis virus." Eldin P., Papon L., Oteiza A., Brocchi E., Lawson T.G., Mechti N. J. Gen. Virol. 90:536-545(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HUMAN TRIM22.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X00463 Genomic RNA. Translation: CAA25152.1. M54935 Genomic RNA. Translation: AAA43036.1.
PIR	GNNYE. A03906.
3D structure databases
ProteinModelPortal	P03304.
SMR	P03304. Positions 1-32, 76-896.
ModBase	Search...
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Family and domain databases
Gene3D	4.10.90.10. 1 hit.
InterPro	IPR015031. Capsid_VP4_Picornavir. IPR004004. Helic/Pol/Pept_Calicivir-typ. IPR000605. Helicase_SF3_ssDNA/RNA_vir. IPR014759. Helicase_SF3_ssRNA_vir. IPR021573. Leader_pept_picornaV. IPR000199. Peptidase_C3A/C3B_picornavir. IPR001676. Picornavirus_capsid. IPR001205. RNA-dir_pol_C. IPR007094. RNA-dir_pol_PSvirus. IPR009003. Trypsin-like_Pept_dom. [Graphical view]
Pfam	PF00548. Peptidase_C3. 1 hit. PF00680. RdRP_1. 1 hit. PF00073. Rhv. 2 hits. PF00910. RNA_helicase. 1 hit. PF08935. VP4_2. 1 hit. PF11475. VP_N-CPKC. 1 hit. [Graphical view]
PRINTS	PR00918. CALICVIRUSNS.
SUPFAM	SSF50494. Pept_Ser_Cys. 1 hit.
PROSITE	PS50507. RDRP_SSRNA_POS. 1 hit. PS51218. SF3_HELICASE_2. 1 hit. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

POLG_EMCV

Accession

Primary (citable) accession number: P03304
Secondary accession number(s): Q66764

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	July 21, 1986
Last modified:	May 1, 2013
This is version 117 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program