P13899 (POLG_TMEVD) 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 Protein 2A Short name=P2A 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	Theiler's murine encephalomyelitis virus (strain DA) (TMEV) [Complete proteome]
Taxonomic identifier	12126 [NCBI]
Taxonomic lineage	Viruses › ssRNA viruses › ssRNA positive-strand viruses, no DNA stage › Picornavirales › Picornaviridae › Cardiovirus › Theilovirus › Theiler's encephalomyelitis virus
Virus host	Mus musculus (Mouse) [TaxID: 10090]

Protein attributes

Sequence length	2301 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 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.
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	3D-structure 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 – 76

76

Leader peptide

PRO_0000040180

Chain

77 – 414

338

Protein VP0 Potential

PRO_0000310971

Chain

77 – 147

71

Protein VP4 Potential

PRO_0000040181

Chain

148 – 414

267

Protein VP2 Potential

PRO_0000040182

Chain

415 – 646

232

Protein VP3 Potential

PRO_0000040183

Chain

647 – 920

274

Protein VP1 Potential

PRO_0000040184

Chain

921 – 1053

133

Protein 2A Potential

PRO_0000040185

Chain

1054 – 1189

136

Protein 2B Potential

PRO_0000040186

Chain

1190 – 1515

326

Protein 2C Potential

PRO_0000040187

Chain

1516 – 1603

88

Protein 3A Potential

PRO_0000040188

Chain

1604 – 1623

20

Protein 3B Potential

PRO_0000040189

Chain

1624 – 1840

217

Picornain 3C Potential

PRO_0000040190

Chain

1841 – 2301

461

RNA-directed RNA polymerase 3D-POL Potential

PRO_0000040191

Regions

Topological domain

1 – 1560

1560

Cytoplasmic Potential

Intramembrane

1561 – 1579

19

Potential

Topological domain

1580 – 2301

722

Cytoplasmic Potential

Domain

1281 – 1446

166

SF3 helicase

Domain

2069 – 2187

119

RdRp catalytic

Nucleotide binding

1310 – 1317

8

ATP Potential

Sites

Active site

1678

1

For picornain 3C activity Potential

Active site

1710

1

For picornain 3C activity Potential

Active site

1791

1

For picornain 3C activity Potential

Site

147 – 148

2

Cleavage Potential

Site

414 – 415

2

Cleavage; by picornain 3C Potential

Site

646 – 647

2

Cleavage; by picornain 3C Potential

Site

920 – 921

2

Cleavage; by picornain 3C Potential

Site

1053 – 1054

2

Cleavage; by ribosomal skip Potential

Site

1189 – 1190

2

Cleavage; by picornain 3C Potential

Site

1515 – 1516

2

Cleavage; by picornain 3C Potential

Site

1603 – 1604

2

Cleavage; by picornain 3C Potential

Site

1623 – 1624

2

Cleavage; by picornain 3C Potential

Site

1840 – 1841

2

Cleavage; by picornain 3C Potential

Amino acid modifications

Modified residue

1606

1

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

Lipidation

77

1

N-myristoyl glycine; by host By similarity

Secondary structure

1

.

.

.

.

.

2301

Helix Strand Turn

Details...

Beta strand

90 – 92

3

Helix

103 – 106

4

Sequences

	Sequence		Length	Mass (Da)
	P13899 [UniParc]. Last modified January 1, 1990. Version 1. Checksum: 0B6095DF153DBFDF	FASTA	2,301	256,161
	10 20 30 40 50 60 MACKHGYPDV CPICTAVDVT PGFEYLLLAD GEWFPTDLLC VDLDDDVFWP SNSSNQSETM 70 80 90 100 110 120 EWTDLPLVRD IVMEPQGNAS SSDKSNSQSS GNEGVIINNF YSNQYQNSID LSASGGNAGD 130 140 150 160 170 180 APQNNGQLSN ILGGAANAFA TMAPLLLDQN TEEMENLSDR VASDKAGNSA TNTQSTVGRL 190 200 210 220 230 240 CGYGEAHHGE HPASCADTAT DKVLAAERYY TIDLASWTTT QEAFSHIRIP LPHVLAGEDG 250 260 270 280 290 300 GVFGATLRRH YLCKTGWRVQ VQCNASQFHA GSLLVFMAPE FYTGKGTKTG DMEPTDPFTM 310 320 330 340 350 360 DTTWRAPQGA PTGYRYDSRT GFFAMNHQNQ WQWTVYPHQI LNLRTNTTVD LEVPYVNIAP 370 380 390 400 410 420 TSSWTQHANW TLVVAVFSPL QYASGSSSDV QITASIQPVN PVFNGLRHET VIAQSPIAVT 430 440 450 460 470 480 VREHKGCFYS TNPDTTVPIY GKTISTPNDY MCGEFSDLLE LCKLPTFLGN PNSNNKRYPY 490 500 510 520 530 540 FSATNSVPTT SLVDYQVALS CSCMCNSMLA AVARNFNQYR GSLNFLFVFT GAAMVKGKFL 550 560 570 580 590 600 IAYTPPGAGK PTTRDQAMQA TYAIWDLGLN SSFVFTAPFI SPTHYRQTSY TSATIASVDG 610 620 630 640 650 660 WVTVWQLTPL TYPSGAPVNS DILTLVSAGD DFTLRMPISP TKWAPQGSDN AEKGKVSNDD 670 680 690 700 710 720 ASVDFVAEPV KLPENQTRVA FFYDRAVPIG MLRPGQNIES TFVYQENDLR LNCLLLTPLP 730 740 750 760 770 780 SFCPDSTSGP VKTKAPVQWR WVRSGGTTNF PLMTKQDYAF LCFSPFTYYK CDLEVTVSAL 790 800 810 820 830 840 GTDTVASVLR WAPTGAPADV TDQLIGYTPS LGETRNPHMW LVGAGNTQIS FVVPYNSPLS 850 860 870 880 890 900 VLPAAWFNGW SDFGNTKDFG VAPNADFGRL WIQGNTSASV RIRYKKMKVF CPRPTLFFPW 910 920 930 940 950 960 PVSTRSKINA DNPVPILELE NPAAFYRIDL FITFIDEFIT FDYKVHGRPV LTFRIPGFGL 970 980 990 1000 1010 1020 TPAGRMLVCM GEKPAHGPFT SSRSLYHVIF TATCSSFSFS IYKGRYRSWK KPIHDELVDR 1030 1040 1050 1060 1070 1080 GYTTFGEFFR AVRAYHADYY KQRLIHDVEM NPGPVQSVFQ PQGAVLTKSL APQAGIQNLL 1090 1100 1110 1120 1130 1140 LRLLGIDGDC SEVSKAITVV TDLFAAWERA KTTLVSPEFW SKLILKTTKF IAASVLYLHN 1150 1160 1170 1180 1190 1200 PDFTTTVCLS LMTGVDLLTN DSVFDWLKNK LSSFFRTPPP VCPNVLQPQG PLREANEGFT 1210 1220 1230 1240 1250 1260 FAKNIEWAMK TIQSIVNWLT SWFKQEEDHP QSKLDKFLME FPDHCRNIMD MRNGRKAYCE 1270 1280 1290 1300 1310 1320 CTASFKYFDE LYNLAVTCKR IPLASLCEKF KNRHDHSVTR PEPVVVVLRG AAGQGKSVTS 1330 1340 1350 1360 1370 1380 QIIAQSVSKM AFGRQSVYSM PPDSEYFDGY ENQFSVIMDD LGQNPDGEDF TVFCQMVSST 1390 1400 1410 1420 1430 1440 NFLPNMAHLE RKGTPFTSSF IVATTNLPKF RPVTVAHYPA VDRRITFDFT VTAGPHCTTS 1450 1460 1470 1480 1490 1500 NGMLDIEKAF DEIPGSKPQL ACFSADCPLL HKRGVMFTCN RTKAVYNLQQ VVKMVNDTIT 1510 1520 1530 1540 1550 1560 RKTENVKKMN SLVAQSPPDW EHFENILTCL RQNNAALQDQ LDELQEAFAQ ARERSDFLSD 1570 1580 1590 1600 1610 1620 WLKVSAIIFA GIASLSAVIK LASKFKESIW PSPVRVELSE GEQAAYAGRA RAQKQALQVL 1630 1640 1650 1660 1670 1680 DIQGGGKVLA QAGNPVMDFE LFCAKNMVAP ITFYYPDKAE VTQSCLLLRA HLFVVNRHVA 1690 1700 1710 1720 1730 1740 ETEWTAFKLK DVRHERDTVV TRSVNRSGAE TDLTFIKVTK GPLFKDNVNK FCSNKDDFPA 1750 1760 1770 1780 1790 1800 RNDAVTGIMN TGLAFVYSGN FLIGNQPVNT TTGACFNHCL HYRAQTRRGW CGSAVICNVN 1810 1820 1830 1840 1850 1860 GKKAVYGMHS AGGGGLAAAT IITRELIEAA EKSMLALEPQ GAIVDISTGS VVHVPRKTKL 1870 1880 1890 1900 1910 1920 RRTVAHDVFQ PKFEPAVLSR YDPRTDKDVD VVAFSKHTTN MESLPPVFDI VCDEYANRVF 1930 1940 1950 1960 1970 1980 TILGKDNGLL TVEQAVLGLP GMDPMEKDTS PGLPYTQQGL RRTDLLNFNT AKMTPQLDYA 1990 2000 2010 2020 2030 2040 HSKLVLGVYD DVVYQSFLKD EIRPLEKIHE AKTRIVDVPP FAHCIWGRQL LGRFASKFQT 2050 2060 2070 2080 2090 2100 KPGLELGSAI GTDPDVDWTP YAAELSGFNY VYDVDYSNFD ASHSTAMFEC LIKNFFTEQN 2110 2120 2130 2140 2150 2160 GFDRRIAEYL RSLAVSRHAY EDRRVLIRGG LLSGCAATSM LNTIMNNVII RAALYLTYSN 2170 2180 2190 2200 2210 2220 FEFDDIKVLS YGDDLLIGTN YQIDFNLVKE RLAPFGYKIT PANKTTTFPL TSHLQDVTFL 2230 2240 2250 2260 2270 2280 KRRFVRFNSY LFRPQMDAVN LKAMVSYCKP GTLKEKLMSI ALLAVHSGPD IYDEIFLPFR 2290 2300 NVGIVVPTYS SMLYRWLSLF R

References

[1]	"Molecular cloning and sequence determination of DA strain of Theiler's murine encephalomyelitis viruses." Ohara Y., Stein S., Fu J., Stillman L., Klaman L., Roos R.P. Virology 164:245-255(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[2]	"Three-dimensional structure of Theiler virus." Grant R.A., Filman D.J., Fujinami R.S., Icenogle J.P., Hogle J.M. Proc. Natl. Acad. Sci. U.S.A. 89:2061-2065(1992) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS).
+	Additional computationally mapped references.

Web resources

Virus Particle ExploreR db

Icosahedral capsid structure

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M20301 Genomic RNA. Translation: AAA47928.1.

PIR

GNNYTN. A31228.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1TME	X-ray	2.80	1	647-920	[»]
			2	148-414	[»]
			3	415-650	[»]
			4	77-147	[»]
1TMF	X-ray	3.50	4	90-130	[»]

ProteinModelPortal

P13899.

SMR

P13899. Positions 85-146, 159-413, 415-902.

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.
IPR000199. Peptidase_C3A/C3B_picornavir.
IPR002527. Pico_P2B.
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.
[Graphical view]

PRINTS

PR00918. CALICVIRUSNS.

ProDom

PD649346. Pico_P2B. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SUPFAM

SSF50494. Pept_Ser_Cys. 1 hit.

PROSITE

PS50507. RDRP_SSRNA_POS. 1 hit.
PS51218. SF3_HELICASE_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P13899.

Entry information

Entry name

POLG_TMEVD

Accession

Primary (citable) accession number: P13899
Secondary accession number(s): Q88564 , Q88565, Q88566, Q88567, Q88568, Q88569, Q88570, Q88571, Q88572, Q88573, Q88574, Q89580

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 1, 1990
Last sequence update:	January 1, 1990
Last modified:	May 1, 2013
This is version 134 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program