P17593 (POLG_EMCVB) 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 (strain emc-b nondiabetogenic) [Complete proteome]
Taxonomic identifier	12105 [NCBI]
Taxonomic lineage	Viruses › ssRNA viruses › ssRNA positive-strand viruses, no DNA stage › Picornavirales › Picornaviridae › Cardiovirus › Encephalomyocarditis virus
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	2292 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Inferred from homology

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 By similarity.
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_0000039792
	Chain	68 – 393	326	Protein VP0 Potential		PRO_0000310968
	Chain	68 – 137	70	Protein VP4 Potential		PRO_0000039793
	Chain	138 – 393	256	Protein VP2 Potential		PRO_0000039794
	Chain	394 – 624	231	Protein VP3 Potential		PRO_0000039795
	Chain	625 – 901	277	Protein VP1 Potential		PRO_0000039796
	Chain	902 – 1044	143	Protein 2A Potential		PRO_0000039797
	Chain	1045 – 1194	150	Protein 2B Potential		PRO_0000039798
	Chain	1195 – 1519	325	Protein 2C Potential		PRO_0000039799
	Chain	1520 – 1607	88	Protein 3A Potential		PRO_0000039800
	Chain	1608 – 1627	20	Protein 3B Potential		PRO_0000039801
	Chain	1628 – 1832	205	Picornain 3C Potential		PRO_0000039802
	Chain	1833 – 2292	460	RNA-directed RNA polymerase 3D-POL Potential		PRO_0000039803
Regions
	Topological domain	1 – 1564	1564	Cytoplasmic Potential
	Intramembrane	1565 – 1583	19	Potential
	Topological domain	1584 – 2292	709	Cytoplasmic Potential
	Domain	1281 – 1447	167	SF3 helicase
	Domain	2061 – 2179	119	RdRp catalytic
	Nucleotide binding	1313 – 1320	8	ATP Potential
Sites
	Active site	1673	1	For picornain 3C activity Potential
	Active site	1705	1	For picornain 3C activity Potential
	Active site	1786	1	For picornain 3C activity Potential
	Site	137 – 138	2	Cleavage Potential
	Site	393 – 394	2	Cleavage; by picornain 3C Potential
	Site	624 – 625	2	Cleavage; by picornain 3C Potential
	Site	901 – 902	2	Cleavage; by picornain 3C Potential
	Site	1044 – 1045	2	Cleavage; by ribosomal skip Potential
	Site	1194 – 1195	2	Cleavage; by picornain 3C Potential
	Site	1519 – 1520	2	Cleavage; by picornain 3C Potential
	Site	1607 – 1608	2	Cleavage; by picornain 3C Potential
	Site	1627 – 1628	2	Cleavage; by picornain 3C Potential
	Site	1832 – 1833	2	Cleavage; by picornain 3C Potential
Amino acid modifications
	Modified residue	1610	1	O-(5'-phospho-RNA)-tyrosine By similarity
	Lipidation	68	1	N-myristoyl glycine; by host By similarity

Sequences

	Sequence		Length	Mass (Da)
	P17593 [UniParc]. Last modified August 1, 1990. Version 1. Checksum: 8540D0EB1437E8D4	FASTA	2,292	255,497
	10 20 30 40 50 60 MATTMEQEIC AHSLTLKGCP KCSALQYRNG FYLLKYDEEW YPEELLTDGE DDVFDPELDM 70 80 90 100 110 120 EVVFELQGNS TSSDKNNSSS DGNEGVIINN FYSNQYQNSI DLSANATGSD PPRTYGQFSN 130 140 150 160 170 180 LLSGAVNAFS NMIPLLADQN TEEMENLSDR VLQDTAGNTV TNTQSTVGRL VGYGAVHDGE 190 200 210 220 230 240 HPASCADTAS EKILAVERYY TFKVNDWTST QKPFEYIRIP LPHVLSGEDG GVFGAALRRH 250 260 270 280 290 300 YLVKTGWRVQ VQCNASQFHA GSLLVFMAPE YPTLDAFAMD NRWSKDNLPN GTKTQTNRKG 310 320 330 340 350 360 PFAMDHQNFW QWTLYPHQFL NLRTNTTVDL EVPYVNIAPT SSWTQHASWT LVIAVVAPLT 370 380 390 400 410 420 YSTGASTSLD ITASIQPVRP VFNGLRHETL SRQSPIPVTI REHAGTWYST LPDSTVPIYG 430 440 450 460 470 480 KTPVAPANYM VGEYKDFLEI AQIPTFIGNK IPNAVPYIEA SNTAVKTQPL ATYQVTLSCS 490 500 510 520 530 540 CLANTFLAAL SRNFAQYRGS LVYTFVFTGT AMMKGKFLIA YTPPGAGKPT SRDQAMQATY 550 560 570 580 590 600 AIWDLGLNSS YSFTVPFISP THFRMVGTDQ VNITNVDGWV TVWQLTPLTY PPGCPTSAKI 610 620 630 640 650 660 LTMVSAGKDF SLKMPISPAP WSPQGVENAE RGVTEDTDAT ADFVAQPVYL PENQTKVAFF 670 680 690 700 710 720 YDRSSPIGAF TVKSGSLESG FTPFSNQTCP NSVILTPGPQ FDPAYDQLRP QRLTEIWGNG 730 740 750 760 770 780 NEETSKVFPL KSKQDYSFCL FSPFVYYKCD LEVTLSPHTS GNHGLLVRWC PTGTPTKPTT 790 800 810 820 830 840 QVLHEVSSLS EGRTPQVYSA GPGITNQISF VVPYNSPLSV LPAVWYNGHK RFDNTGSLGI 850 860 870 880 890 900 APNSDFGTLF FAGTKPDIKF TVYLRYKNMR VFCPRPTVFF PWPSSGDKID MTPRAGVLML 910 920 930 940 950 960 ESPNALDISR TYPTLHILIQ FNHGGLEIRL FRHGMFWAEA HADVILRSRT KQISFLNNGS 970 980 990 1000 1010 1020 FPSMDARAPW NPWKNTYHAV LRAEPYRVTM DVYHKRIRPF RLPLVQKEWN VREENVFGLY 1030 1040 1050 1060 1070 1080 GIFNAHYAGY FADLLIHDIE TNPGPFMAKP KKQVFQTQGA AVSSMAQTLL PNDLASKVMG 1090 1100 1110 1120 1130 1140 SAFTALLDAN EDAQKAMRII KTLSSLSDAW ENVKETLNNP EFWKQLLSRC VQLIAGMTIA 1150 1160 1170 1180 1190 1200 VMHPDPLTLL CLGTLTAAEI TSQTSLCEEI VAKFKKIFTT PPPRFPTISL FQQQSPLKQV 1210 1220 1230 1240 1250 1260 NDVFSLAKNL DWAVKTVEKV VDWFGTWVVQ EEKEQTLDQL LQRFPEHAKR ISDLRNGMSA 1270 1280 1290 1300 1310 1320 YVECKESFDF FEKLYNQAVK EKRTGIAAVC EKFRQKHDHA TARCEPVVIV LRGDAGQGKS 1330 1340 1350 1360 1370 1380 LSSQVIAQAV SKTIFGRQSV YSLPPDSDFF DGYENQFAAI MDDLGQNPDG SDFTTFCQMV 1390 1400 1410 1420 1430 1440 STTNFLPNMA SLERNGTPFT SQIVVATTNL PEFRPVTIAH YPAVERRITF DYSVSAGPVC 1450 1460 1470 1480 1490 1500 SKTEAGYKVL DVERAFRPTG DAPLPCFQNN CLFLEKAGLQ FRDNRTKEIL SLVDVIERAV 1510 1520 1530 1540 1550 1560 ARIERKKKVL TTVQTLVAQA PVDEVSFHSV VQQLKARQEA TDEQLEELQE AFAKTQERSS 1570 1580 1590 1600 1610 1620 VFSDWMKISA MLCAATLALS QVVKMAKTVK QMVRPDLVRV QLDEQEQGPY NEAVRAKPKT 1630 1640 1650 1660 1670 1680 LQLLDIQGPN PVMDFEKYVA KFVTAPIDFV YPTGVSTQTC LLVKGRTLAV NRHMAESDWS 1690 1700 1710 1720 1730 1740 SIVVRGVTHA RSTVRILAIA KAGKETDVSF IRLSSGPLFR DNTSKFVKAD DVLPATSAPV 1750 1760 1770 1780 1790 1800 IGIMNTDIPM MFTGTFLKAG VSVPVETGQT FNHCIHYKAN TRKGWCGSAL LADLGGKKKI 1810 1820 1830 1840 1850 1860 LGMHSAGSMG RTAASIVSQE MICAVVSAFE PQGALERLPD GPRIHVPRKT ALRPTVARRV 1870 1880 1890 1900 1910 1920 FQPAYAPAVL SKFDPRTEAD VDEVAFSKHT SNQESLPPVF RMVAKEYANR VFTLLGRDNG 1930 1940 1950 1960 1970 1980 RLTVKQALEG LEGMDPMDKN TSPGLPYTAL GMRRTDVVDW ESATLIPYAA DRLKKMNEGD 1990 2000 2010 2020 2030 2040 FSDIVYQTFL KDELRPVEKV QAAKTRIVDV PPFEHCILGR QLLGRFASKF QTQPGLELGS 2050 2060 2070 2080 2090 2100 AIGCDPDVHW TAFGVAMQGF ERVYDVDYSN FDSTHSVAMF RLLAEEFFTP ENGFDPLVKE 2110 2120 2130 2140 2150 2160 YLESLAISTH AFEEKRYLIT GGLPSGCAAT SMLNTIMNNI IIRAGLYLTY KNFEFDDVKV 2170 2180 2190 2200 2210 2220 LSYGDDLLVA TNYQLNFDKV RASLAKTGYK ITPANKTSTF PLDSTLEDVV FLKRKFKKEG 2230 2240 2250 2260 2270 2280 PLYRPVMNRE ALEAMLSYYR PGTLSEKLTS ITMLAVHSGK PEYDRLFAPF REVGVVVPSF 2290 ESVEYRWRSL FW

References

[1]	"Genomic differences between the diabetogenic and nondiabetogenic variants of encephalomyocarditis virus." Bae Y.S., Eun H.M., Yoon J.W. Virology 170:282-287(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[2]	"Molecular identification of diabetogenic viral gene." Bae Y.S., Eun H.M., Yoon J.W. Diabetes 38:316-320(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].

Cross-references

Sequence databases
EMBL GenBank DDBJ	M22457 Genomic RNA. Translation: AAA43033.1. Sequence problems.
PIR	GNNYEB. B31473.
3D structure databases
ProteinModelPortal	P17593.
SMR	P17593. Positions 1-32, 76-898.
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_EMCVB

Accession

Primary (citable) accession number: P17593

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1990
Last sequence update:	August 1, 1990
Last modified:	May 1, 2013
This is version 114 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program