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P08544 (POLG_TMEVB) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 137. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Genome polyprotein

Cleaved into the following 13 chains:

  1. Leader protein
  2. Protein VP0
    Alternative name(s):
    VP4-VP2
  3. Protein VP4
    Alternative name(s):
    P1A
    Virion protein 4
  4. Protein VP2
    Alternative name(s):
    P1B
    Virion protein 2
  5. Protein VP3
    Alternative name(s):
    P1C
    Virion protein 3
  6. Protein VP1
    Alternative name(s):
    P1D
    Virion protein 1
  7. Protein 2A
    Short name=P2A
  8. Protein 2B
    Short name=P2B
  9. Protein 2C
    Short name=P2C
    EC=3.6.1.15
  10. Protein 3A
    Short name=P3A
  11. Protein 3B
    Short name=P3B
    Alternative name(s):
    VPg
  12. Protease 3C
    Short name=P3C
    EC=3.4.22.28
    Alternative name(s):
    Picornain 3C
  13. RNA-directed RNA polymerase 3D-POL
    Short name=P3D-POL
    EC=2.7.7.48
OrganismTheiler's murine encephalomyelitis virus (strain BeAn 8386) (TMEV) [Complete proteome]
Taxonomic identifier12125 [NCBI]
Taxonomic lineageVirusesssRNA positive-strand viruses, no DNA stagePicornaviralesPicornaviridaeCardiovirus
Virus hostMus musculus (Mouse) [TaxID: 10090]

Protein attributes

Sequence length2303 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Leader protein: promotes host NUP98 phosphorylation and blocks the export of host mRNA from the nucleus. The resulting inhibition of cellular protein synthesis serves to ensure maximal viral gene expression and to evade host immune response. The leader protein also inhibit host interferon regulatory factor 3 (IRF3) dimerization, thereby blocking the transcriptional activation of IFN genes By similarity.

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.

Protein VP0: 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.

Protease 3C: 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 cooperatively to the protease By similarity.

RNA-directed RNA polymerase 3D-POL replicates genomic and antigenomic RNA by recognizing replications specific signals By similarity.

Protein 2A: is involved in host translation shutoff. Nuclear localization is required for this function 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 2A: Host nucleus By similarity.

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.

Protease 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.

Domain

The Theilo and zinc-finger regions may both play a role in the inhibition of host mRNA export and IRF-3 dimerization antagonism by the L protein 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.

Miscellaneous

Persistent strains of Theiler's virus (e.g. DA, TO, BeAn) cause persistent demyelinating disease whereas neurovirulent strains (such as GDVII) cause acute encephalitis.

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 processHost gene expression shutoff by virus
Host translation shutoff by virus
Host-virus interaction
Inhibition of host innate immune response by virus
Inhibition of host IRF3 by virus
Inhibition of host RLR pathway by virus
Ion transport
Transport
Viral attachment to host cell
Viral immunoevasion
Viral RNA replication
Virus entry into host cell
   Cellular componentCapsid protein
Host cytoplasm
Host cytoplasmic vesicle
Host membrane
Host nucleus
Membrane
Virion
   DomainZinc-finger
   LigandATP-binding
Metal-binding
Nucleotide-binding
RNA-binding
Zinc
   Molecular functionHelicase
Hydrolase
Ion channel
Nucleotidyltransferase
Protease
RNA-directed RNA polymerase
Thiol protease
Transferase
Viral ion channel
   PTMCovalent protein-RNA linkage
Disulfide bond
Lipoprotein
Myristate
Phosphoprotein
   Technical term3D-structure
Complete proteome
Gene Ontology (GO)
   Biological_processRNA-protein covalent cross-linking

Inferred from electronic annotation. Source: UniProtKB-KW

pore formation by virus in membrane of host cell

Inferred from electronic annotation. Source: UniProtKB-KW

protein oligomerization

Inferred from electronic annotation. Source: UniProtKB-KW

proteolysis

Inferred from electronic annotation. Source: UniProtKB-KW

suppression by virus of host IRF3 activity

Inferred from electronic annotation. Source: UniProtKB-KW

suppression by virus of host translation

Inferred from electronic annotation. Source: UniProtKB-KW

transcription, DNA-templated

Inferred from electronic annotation. Source: InterPro

viral RNA genome replication

Inferred from electronic annotation. Source: InterPro

viral entry into host cell

Inferred from electronic annotation. Source: UniProtKB-KW

virion attachment to host cell

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componenthost cell cytoplasmic vesicle membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

host cell nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

icosahedral viral capsid

Inferred from electronic annotation. Source: InterPro

integral to membrane of host cell

Inferred from electronic annotation. Source: UniProtKB-KW

membrane

Inferred from electronic annotation. Source: UniProtKB-KW

   Molecular_functionATP 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

ion channel activity

Inferred from electronic annotation. Source: UniProtKB-KW

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

structural molecule activity

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 7676Leader protein
PRO_0000040168
Chain77 – 414338Protein VP0 Potential
PRO_0000310970
Chain77 – 14771Protein VP4 Potential
PRO_0000040169
Chain148 – 414267Protein VP2 Potential
PRO_0000040170
Chain415 – 646232Protein VP3 Potential
PRO_0000040171
Chain647 – 922276Protein VP1 Potential
PRO_0000040172
Chain923 – 1055133Protein 2A Potential
PRO_0000040173
Chain1056 – 1191136Protein 2B Potential
PRO_0000040174
Chain1192 – 1517326Protein 2C Potential
PRO_0000040175
Chain1518 – 160588Protein 3A Potential
PRO_0000040176
Chain1606 – 162520Protein 3B Potential
PRO_0000040177
Chain1626 – 1842217Protease 3C Potential
PRO_0000040178
Chain1843 – 2303461RNA-directed RNA polymerase 3D-POL Potential
PRO_0000040179

Regions

Topological domain1 – 15621562Cytoplasmic Potential
Intramembrane1563 – 158119 Potential
Topological domain1582 – 2303722Cytoplasmic Potential
Domain1283 – 1448166SF3 helicase
Domain2071 – 2189119RdRp catalytic
Zinc finger3 – 1412 Potential
Nucleotide binding1312 – 13198ATP Potential
Region30 – 4617Acidic
Region60 – 7314Theilo By similarity
Compositional bias79 – 824Poly-Ser
Compositional bias1306 – 13094Poly-Val
Compositional bias1814 – 18174Poly-Gly

Sites

Active site16801For protease 3C activity Potential
Active site17931For protease 3C activity Potential
Site147 – 1482Cleavage Potential
Site414 – 4152Cleavage; by protease 3C Potential
Site646 – 6472Cleavage; by protease 3C Potential
Site922 – 9232Cleavage; by protease 3C Potential
Site1055 – 10562Cleavage; by ribosomal skip Potential
Site1191 – 11922Cleavage; by protease 3C Potential
Site1517 – 15182Cleavage; by protease 3C Potential
Site1605 – 16062Cleavage; by protease 3C Potential
Site1625 – 16262Cleavage; by protease 3C Potential
Site1842 – 18432Cleavage; by protease 3C Potential

Amino acid modifications

Modified residue16081O-(5'-phospho-RNA)-tyrosine By similarity
Lipidation771N-myristoyl glycine; by host By similarity
Disulfide bond501 ↔ 503

Secondary structure

.................................................................................................................... 2303
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P08544 [UniParc].

Last modified August 1, 1988. Version 1.
Checksum: E2C7737DFDBEB786

FASTA2,303256,282
        10         20         30         40         50         60 
MACKHGYPDV CPICTAVDAT PGFEYLLMAD GEWYPTDLLC VDLDDDVFWP SDTSNQSQTM 

        70         80         90        100        110        120 
DWTDVPLIRD IVMEPQGNSS SSDKSNSQSS GNEGVIINNF YSNQYQNSID LSASGGNAGD 

       130        140        150        160        170        180 
APQTNGQLSN ILGGAANAFA TMAPLLLDQN TEEMENLSDR VASDKAGNSA TNTQSTVGRL 

       190        200        210        220        230        240 
CGYGKSHHGE HPASCADTAT DKVLAAERYY TIDLASWTTS QEAFSHIRIP LPHVLAGEDG 

       250        260        270        280        290        300 
GVFGATLRRH YLCKTGWRVQ VQCNASQFHA GSLLVFMAPE FYTGKGTKTG TMEPSDPFTM 

       310        320        330        340        350        360 
DTEWRSPQGA PTGYRYDSRT GFFATNHQNQ WQWTVYPHQI LNLRTNTTVD LEVPYVNVAP 

       370        380        390        400        410        420 
SSSWTQHANW TLVVAVLSPL QYATGSSPDV QITASLQPVN PVFNGLRHET VIAQSPIPVT 

       430        440        450        460        470        480 
VREHKGCFYS TNPDTTVPIY GKTISTPSDY MCGEFSDLLE LCKLPTFLGN PNTNNKRYPY 

       490        500        510        520        530        540 
FSATNSVPAT SMVDYQVALS CSCMANSMLA AVARNFNQYR GSLNFLFVFT GAAMVKGKFL 

       550        560        570        580        590        600 
IAYTPPGAGK PTTRDQAMQS TYAIWDLGLN SSFNFTAPFI SPTHYRQTSY TSPTITSVDG 

       610        620        630        640        650        660 
WVTVWKLTPL TYPSGTPTNS DILTLVSAGD DFTLRMPISP TKWVPQGVDN AEKGKVSNDD 

       670        680        690        700        710        720 
ASVDFVAEPV KLPENQTRVA FFYDRAVPIG MLRPGQNMET TFNYQENDYR LNCLLLTPLP 

       730        740        750        760        770        780 
SFCPDSSSGP QKTKAPVQWR WVRSGGVNGA NFPLMTKQDY AFLCFSPFTF YKCDLEVTVS 

       790        800        810        820        830        840 
ALGMTRVASV LRWAPTGAPA DVTDQLIGYT PSLGETRNPH MWLVGAGNSQ VSFVVPYNSP 

       850        860        870        880        890        900 
LSVLPAAWFN GWSDFGNTKD FGVAPNADFG RLWIQGNTSA SVRIRYKKMK VFCPRPTLFF 

       910        920        930        940        950        960 
PWPTPTTTKI NADNPVPILE LENPAALYRI DLFITFTDEF ITFDYKVHGR PVLTFRIPGF 

       970        980        990       1000       1010       1020 
GLTPAGRMLV CMGEQPAHGP FTSSRSLYHV IFTATCSSFS FSIYKGRYRS WKKPIHDELV 

      1030       1040       1050       1060       1070       1080 
DRGYTTFGEF FKAVRGYHAD YYRQRLIHDV ETNPGPVQSV FQPQGAVLTK SLAPQAGIQN 

      1090       1100       1110       1120       1130       1140 
LLLRLLGIDG DCSEVSKAIT VVTDLVAAWE KAKTTLVSPE FWSKLILKTT KFIAASVLYL 

      1150       1160       1170       1180       1190       1200 
HNPDFTTTVC LSLMTGVDLL TNDSVFDWLK QKLSSFFRTP PPACPNVMQP QGPLREANEG 

      1210       1220       1230       1240       1250       1260 
FTFAKNIEWA MKTIQSVVNW LTSWFKQEED HPQSKLDKLL MEFPDHCRNI MDMRNGRKAY 

      1270       1280       1290       1300       1310       1320 
CECTASFKYF DELYNLAVTC KRIPLASLCE KFKNRHDHSV TRPEPVVVVL RGAAGQGKSV 

      1330       1340       1350       1360       1370       1380 
TSQIIAQSVS KMAFGRQSVY SMPPDSEYFD GYENQFSVIM DDLGQNPDGE DFTVFCQMVS 

      1390       1400       1410       1420       1430       1440 
STNFLPNMAH LERKGTPFTS SFIVATTNLP KFRPVTVAHY PAVDRRITFD FTVTAGPHCK 

      1450       1460       1470       1480       1490       1500 
TPAGMLDVEK AFDEIPGSKP QLACFSADCP LLHKRGVMFT CNRTQTVYNL QQVVKMVNDT 

      1510       1520       1530       1540       1550       1560 
ITRKTENVKK MNSLVAQSPP DWEHFENILT CLRQNNAALQ DQLDELQEAF AQARERSDFL 

      1570       1580       1590       1600       1610       1620 
SDWLKVSAII FAGIASLSAV IKLASKFKES IWPTPVRVEL SEGEQAAYAG RARAQKQALQ 

      1630       1640       1650       1660       1670       1680 
VLDIQGGGKV LAQAGNPVMD FELFCAKNIV APITFYYPDK AEVTQSCLLL RAHLFVVNRH 

      1690       1700       1710       1720       1730       1740 
VAETDWTAFK LKDVRHERHT VALRSVNRSG AKTDLTFIKV TKGPLFKDNV NKFCSNKDDF 

      1750       1760       1770       1780       1790       1800 
PARNDTVTGI MNTGLAFVYS GNFLIGNQPV NTTTGACFNH CLHYRAQTRR GWCGSAIICN 

      1810       1820       1830       1840       1850       1860 
VNGKKAVYGM HSAGGGGLAA ATIITKELIE AAEKSMLALE PQGAIVDIAT GSVVHVPRKT 

      1870       1880       1890       1900       1910       1920 
KLRRTVAHDV FQPKFEPAVL SRYDPRTDKD VDVVAFSKHT TNMESLPPIF DVVCGEYANR 

      1930       1940       1950       1960       1970       1980 
VFTILGKENG LLTVEQAVLG LPGMDPMEKD TSPGLPYTQQ GLRRTDLLNF ITAKMTPQLD 

      1990       2000       2010       2020       2030       2040 
YAHSKLVIGV YDDVVYQSFL KDEIRPIEKI HEAKTRIVDV PPFAHCIWGR QLLGRFASKF 

      2050       2060       2070       2080       2090       2100 
QTKPGLELGS AIGTDPDVDW TRYAVELSGF NYVYDVDYSN FDASHSTAMF ECLINNFFTE 

      2110       2120       2130       2140       2150       2160 
QNGFDRRIAE YLRSLAVSRH AYEDRRVLIR GGLPSGCAAT SMLNTIMNNV IIRAALYLTY 

      2170       2180       2190       2200       2210       2220 
SNFDFDDIKV LSYGDDLLIG TNYQIDFNLV KERLAPFGYK ITPANKTTTF PLTSHLQDVT 

      2230       2240       2250       2260       2270       2280 
FLKRRFVRFN SYLFRPQMDA VNLKAMVSYC KPGTLKEKLM SIALLAVHSG PDIYDEIFLP 

      2290       2300 
FRNVGIVVPT YSSMLYRWLS LFR 

« Hide

References

[1]"Analysis of the complete nucleotide sequence of the picornavirus Theiler's murine encephalomyelitis virus indicates that it is closely related to cardioviruses."
Pevear D.C., Calenoff M., Rozhon E., Lipton H.L.
J. Virol. 61:1507-1516(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[2]"Three-dimensional structure of Theiler murine encephalomyelitis virus (BeAn strain)."
Luo M., He C., Toth K.S., Zhang C.X., Lipton H.L.
Proc. Natl. Acad. Sci. U.S.A. 89:2409-2413(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.5 ANGSTROMS) OF 148-922.

Web resources

Virus Particle ExploreR db

Icosahedral capsid structure

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M16020 Genomic RNA. Translation: AAA47930.1.
PIRGNNYTM. A29535.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1TMFX-ray3.501647-922[»]
2148-414[»]
3415-646[»]
ProteinModelPortalP08544.
SMRP08544. Positions 85-146, 148-922.
ModBaseSearch...
MobiDBSearch...

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Family and domain databases

Gene3D4.10.90.10. 1 hit.
InterProIPR015031. 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]
PfamPF00548. 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]
PRINTSPR00918. CALICVIRUSNS.
ProDomPD649346. Pico_P2B. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SUPFAMSSF50494. SSF50494. 1 hit.
PROSITEPS50507. RDRP_SSRNA_POS. 1 hit.
PS51218. SF3_HELICASE_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP08544.

Entry information

Entry namePOLG_TMEVB
AccessionPrimary (citable) accession number: P08544
Secondary accession number(s): Q88583 expand/collapse secondary AC list , Q88584, Q88585, Q88586, Q88587, Q88588, Q88589, Q88590, Q88591, Q88592
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1988
Last sequence update: August 1, 1988
Last modified: April 16, 2014
This is version 137 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references