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Protein

Genome polyprotein

Gene
N/A
Organism
Theiler's murine encephalomyelitis virus (strain GDVII) (TMEV)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Protein inferred from homologyi

Functioni

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).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).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).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).By similarity
RNA-directed RNA polymerase 3D-POL replicates genomic and antigenomic RNA by recognizing replications specific signals.PROSITE-ProRule annotation
Protein 2A: is involved in host translation shutoff. Nuclear localization is required for this function (By similarity).By similarity

Catalytic activityi

Nucleoside triphosphate + RNA(n) = diphosphate + RNA(n+1).PROSITE-ProRule annotation
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.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei1680For protease 3C activitySequence analysis1
Active sitei1712For protease 3C activitySequence analysis1
Active sitei1793For protease 3C activitySequence analysis1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri3 – 14Sequence analysisAdd BLAST12
Nucleotide bindingi1312 – 1319ATPPROSITE-ProRule annotation8

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Helicase, Hydrolase, Ion channel, Nucleotidyltransferase, Protease, RNA-directed RNA polymerase, Thiol protease, Transferase, Viral ion channel

Keywords - Biological processi

Eukaryotic host gene expression shutoff by virus, Eukaryotic host translation shutoff by virus, Host gene expression shutoff by virus, Host mRNA suppression by virus, Host-virus interaction, Inhibition of host innate immune response by virus, Inhibition of host mRNA nuclear export by virus, Inhibition of host RIG-I 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

Keywords - Ligandi

ATP-binding, Metal-binding, Nucleotide-binding, RNA-binding, Zinc

Protein family/group databases

MEROPSiC03.010.

Names & Taxonomyi

Protein namesi
Recommended name:
Genome polyprotein
Cleaved into the following 13 chains:
Alternative name(s):
VP4-VP2
Alternative name(s):
P1A
Virion protein 4
Alternative name(s):
P1B
Virion protein 2
Alternative name(s):
P1C
Virion protein 3
Alternative name(s):
P1D
Virion protein 1
Protein 2A
Short name:
P2A
Protein 2B
Short name:
P2B
Protein 2C (EC:3.6.1.15)
Short name:
P2C
Protein 3A
Short name:
P3A
Protein 3B
Short name:
P3B
Alternative name(s):
VPg
Protease 3C (EC:3.4.22.28)
Short name:
P3C
Alternative name(s):
Picornain 3C
OrganismiTheiler's murine encephalomyelitis virus (strain GDVII) (TMEV)
Taxonomic identifieri12127 [NCBI]
Taxonomic lineageiVirusesssRNA virusesssRNA positive-strand viruses, no DNA stagePicornaviralesPicornaviridaeCardiovirus
Virus hostiMus musculus (Mouse) [TaxID: 10090]
Proteomesi
  • UP000008247 Componenti: Chromosome

Subcellular locationi

Protein 2A :
Protein 2B :
Protein 2C :
Protein 3A :
Protein 3B :
RNA-directed RNA polymerase 3D-POL :

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 1562CytoplasmicSequence analysisAdd BLAST1562
Intramembranei1563 – 1581Sequence analysisAdd BLAST19
Topological domaini1582 – 2303CytoplasmicSequence analysisAdd BLAST722

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Capsid protein, Host cytoplasm, Host cytoplasmic vesicle, Host membrane, Host nucleus, Membrane, Virion

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000401921 – 76Leader proteinAdd BLAST76
ChainiPRO_000031097277 – 414Protein VP0Sequence analysisAdd BLAST338
ChainiPRO_000004019377 – 147Protein VP4Sequence analysisAdd BLAST71
ChainiPRO_0000040194148 – 414Protein VP2Sequence analysisAdd BLAST267
ChainiPRO_0000040195415 – 646Protein VP3Sequence analysisAdd BLAST232
ChainiPRO_0000040196647 – 922Protein VP1Sequence analysisAdd BLAST276
ChainiPRO_0000040197923 – 1055Protein 2ASequence analysisAdd BLAST133
ChainiPRO_00000401981056 – 1191Protein 2BSequence analysisAdd BLAST136
ChainiPRO_00000401991192 – 1517Protein 2CSequence analysisAdd BLAST326
ChainiPRO_00000402001518 – 1605Protein 3ASequence analysisAdd BLAST88
ChainiPRO_00000402011606 – 1625Protein 3BSequence analysisAdd BLAST20
ChainiPRO_00000402021626 – 1842Protease 3CSequence analysisAdd BLAST217
ChainiPRO_00000402031843 – 2303RNA-directed RNA polymerase 3D-POLSequence analysisAdd BLAST461

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi77N-myristoyl glycine; by hostBy similarity1
Modified residuei1608O-(5'-phospho-RNA)-tyrosineBy similarity1

Post-translational modificationi

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).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).By similarity
Myristoylation of VP4 is required during RNA encapsidation and formation of the mature virus particle.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei147 – 148CleavageSequence analysis2
Sitei414 – 415Cleavage; by protease 3CSequence analysis2
Sitei646 – 647Cleavage; by protease 3CSequence analysis2
Sitei922 – 923Cleavage; by protease 3CSequence analysis2
Sitei1055 – 1056Cleavage; by ribosomal skipSequence analysis2
Sitei1191 – 1192Cleavage; by protease 3CSequence analysis2
Sitei1517 – 1518Cleavage; by protease 3CSequence analysis2
Sitei1605 – 1606Cleavage; by protease 3CSequence analysis2
Sitei1625 – 1626Cleavage; by protease 3CSequence analysis2
Sitei1842 – 1843Cleavage; by protease 3CSequence analysis2

Keywords - PTMi

Covalent protein-RNA linkage, Lipoprotein, Myristate, Phosphoprotein

Structurei

3D structure databases

ProteinModelPortaliP08545.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1283 – 1448SF3 helicasePROSITE-ProRule annotationAdd BLAST166
Domaini2071 – 2189RdRp catalyticPROSITE-ProRule annotationAdd BLAST119

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni30 – 46AcidicAdd BLAST17
Regioni60 – 73TheiloBy similarityAdd BLAST14

Domaini

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

Sequence similaritiesi

Belongs to the picornaviruses polyprotein family.Curated
Contains 2 peptidase C3 domains.Curated
Contains 1 RdRp catalytic domain.PROSITE-ProRule annotation
Contains 1 SF3 helicase domain.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri3 – 14Sequence analysisAdd BLAST12

Keywords - Domaini

Zinc-finger

Family and domain databases

CDDicd00205. rhv_like. 3 hits.
Gene3Di2.60.120.20. 3 hits.
4.10.90.10. 1 hit.
InterProiIPR015031. 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.
IPR009003. Peptidase_S1_PA.
IPR002527. Pico_P2B.
IPR001676. Picornavirus_capsid.
IPR033703. Rhv-like.
IPR001205. RNA-dir_pol_C.
IPR007094. RNA-dir_pol_PSvirus.
IPR029053. Viral_coat.
[Graphical view]
PfamiPF00548. 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]
PRINTSiPR00918. CALICVIRUSNS.
ProDomiPD649346. Pico_P2B. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SUPFAMiSSF50494. SSF50494. 1 hit.
PROSITEiPS50507. RDRP_SSRNA_POS. 1 hit.
PS51218. SF3_HELICASE_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P08545-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MACKHGYPDV CPICTAVDAT PDFEYLLMAD GEWFPTDLLC VDLDDDVFWP
60 70 80 90 100
SDTSTQPQTM EWTDVPLVCD TVMEPQGNAS SSDKSNSQSS GNEGVIINNF
110 120 130 140 150
YSNQYQNSID LSASGGNAGD APQNNGQLSS ILGGAANAFA TMAPLLMDQN
160 170 180 190 200
TEEMENLSDR VASDKAGNSA TNTQSTVGRL CGYGKSHHGE HPTSCADAAT
210 220 230 240 250
DKVLAAERYY TIDLASWTTS QEAFSHIRIP LPHVLAGEDG GVFGATLRRH
260 270 280 290 300
YLCKTGWRVQ VQCNASQFHA GSLLVFMAPE FYTGKGTKSG TMEPSDPFTM
310 320 330 340 350
DTTWRSPQSA PTGYRYDRQA GFFAMNHQNQ WQWTVYPHQI LNLRTNTTVD
360 370 380 390 400
LEVPYVNVAP SSSWTQHANW TLVVAVLSPL QYATGSSPDV QITASLQPVN
410 420 430 440 450
PVFNGLRHET VLAQSPIPVT VREHQGCFYS TNPDTTVPIY GKTISTPSDY
460 470 480 490 500
MCGEFSDLLE LCKLPTFLGN PSTDNKRYPY FSATNSVPAT SLVDYQVALS
510 520 530 540 550
CSCTANSMLA AVARNFNQYR GSLNFLFVFT GAAMVKGKFR IAYTPPGAGK
560 570 580 590 600
PTTRDQAMQA TYAIWDLGLN SSFNFTAPFI SPTHYRQTSY TSPTITSVDG
610 620 630 640 650
WVTVWQLTPL TYPSGTPTHS DILTLVSAGD DFTLRMPISP TKWVPQGIDN
660 670 680 690 700
AEKGKVSNDD ASVDFVAEPV KLPENQTRVA FFYDRAVPIG MLRPGQNMET
710 720 730 740 750
TFSYQENDFR LNCLLLTPLP SYCPDSSSGP VRTKAPVQWR WVRSGGANGA
760 770 780 790 800
NFPLMTKQDY AFLCFSPFTY YKCDLEVTVS AMGAGTVSSV LRWAPTGAPA
810 820 830 840 850
DVTDQLIGYT PSLGETRNPH MWIVGSGNSQ ISFVVPYNSP LSVLPAAWFN
860 870 880 890 900
GWSDFGNTKD FGVAPTSDFG RIWIQGNSSA SVRIRYKKMK VFCPRPTLFF
910 920 930 940 950
PWPTPTTTKI NADNPVPILE LENPASLYRI DLFITFTDEL ITFDYKVHGR
960 970 980 990 1000
PVLTFRIPGF GLTPAGRMLV CMGAKPAHSP FTSSKSLYHV IFTSTCNSFS
1010 1020 1030 1040 1050
FTIYKGRYRS WKKPIHDELV DRGYTTFREF FKAVRGYHAD YYKQRLIHDV
1060 1070 1080 1090 1100
EMNPGPVQSV FQPQGAVLTK SLAPQAGIQN ILLRLLGIEG DCSEVSKAIT
1110 1120 1130 1140 1150
VVTDLVAAWE KAKTTLVSPE FWSELILKTT KFIAASVLYL HNPDFTTTVC
1160 1170 1180 1190 1200
LSLMTGVDLL TNDSVFDWLK SKLSSFFRTP PPACPNVMQP QGPLREANEG
1210 1220 1230 1240 1250
FTFAKNIEWA TKTIQSIVNW LTSWFKQEED HPQSKLDKLL MEFPDHCRNI
1260 1270 1280 1290 1300
MDMRNGRKAY CECTASFKYF DDLYNLAVTC KRIPLASLCE KFKNRHDHSV
1310 1320 1330 1340 1350
TRPEPVVAVL RGAAGQGKSV TSQIIAQSVS KMAFGRQSVY SMPPDSEYFD
1360 1370 1380 1390 1400
GYENQFSVIM DDLGQNPDGE DFTVFCQMVS STNFLPNMAH LERKGTPFTS
1410 1420 1430 1440 1450
SFIVATTNLP KFRPVTVAHY PAVDRRITFD FTVTAGPHCK TPAGMLDIEK
1460 1470 1480 1490 1500
AFDEIPGSKP QLACFSADCP LLHKRGVMFT CNRTKTVYNL QQVVKMVNDT
1510 1520 1530 1540 1550
ITRKTENVKK MNSLVAQSPP DWQHFENILT CLRQNNAALQ DQVDELQEAF
1560 1570 1580 1590 1600
TQARERSDFL SDWLKVSAII FAGIVSLSAV IKLASKFKES IWPTPVRVEL
1610 1620 1630 1640 1650
SEGEQAAYAG RARAQKQALQ VLDIQGGGKV LAQAGNPVMD FELFCAKNMV
1660 1670 1680 1690 1700
SPITFYYPDK AEVTQSCLLL RAHLFVVNRH VAETEWTAFK LRDVRHERDT
1710 1720 1730 1740 1750
VVMRSVNRSG AETDLTFVKV TKGPLFKDNV NKFCSNKDDF PARNDTVTGI
1760 1770 1780 1790 1800
MNTGLAFVYS GNFLIGNQPV NTTTGACFNH CLHYRAQTRR GWCGSAIICN
1810 1820 1830 1840 1850
VNGKKAVYGM HSAGGGGLAA ATIITRELIE AAEKSMLALE PQGAIVDIST
1860 1870 1880 1890 1900
GSVVHVPRKT KLRRTVAHDV FQPKFEPAVL SRYDPRTDKD VDVVAFSKHT
1910 1920 1930 1940 1950
TNMESLPPIF DIVCGEYANR VFTILGKDNG LLTVEQAVLG LSGMDPMEKD
1960 1970 1980 1990 2000
TSPGLPYTQQ GLRRTDLLDF NTAKMTPQLD YAHSKLVLGV YDDVVYQSFL
2010 2020 2030 2040 2050
KDEIRPLEKI HEAKTRIVDV PPFAHCIWGR QLLGRFASKF QTKPGFELGS
2060 2070 2080 2090 2100
AIGTDPDVDW TRYAAELSGF NYVYDVDYSN FDASHSTAMF ECLINNFFTE
2110 2120 2130 2140 2150
QNGFDRRIAE YLRSLAVSRH AYEDRRVLIR GGLPSGCAAT SMLNTIMNNV
2160 2170 2180 2190 2200
IIRAALYLTY SNFEFDDIKV LSYGDDLLIG TNYQIDFNLV KERLAPFGYK
2210 2220 2230 2240 2250
ITPANKTTTF PLTSHLQDVT FLKRRFVRFN SYLFRPQMDA VNLKAMVSYC
2260 2270 2280 2290 2300
KPGTLKEKLM SIALLAVHSG PDIYDEIFLP FRNVGIVVPT YDSMLYRWLS

LFR
Length:2,303
Mass (Da):256,344
Last modified:January 1, 1990 - v2
Checksum:i5D0FBE6E47F72A04
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti1747 – 1750VTGI → CYRD in AAA47933 (PubMed:3023668).Curated4
Sequence conflicti1992 – 2000DDVVYQSFL → GRRCLPIIF in AAA47933 (PubMed:3023668).Curated9
Sequence conflicti2003E → Q (PubMed:3023668).Curated1
Sequence conflicti2008E → H in AAA47933 (PubMed:3023668).Curated1
Sequence conflicti2046F → L in AAA47933 (PubMed:3023668).Curated1
Sequence conflicti2128 – 2134LIRGGLP → YSWGPA in AAA47933 (PubMed:3023668).Curated7

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M20562 Genomic RNA. Translation: AAA47929.1.
M14703 Genomic RNA. Translation: AAA47933.1.
PIRiA26100.
A29193. GNNYTP.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M20562 Genomic RNA. Translation: AAA47929.1.
M14703 Genomic RNA. Translation: AAA47933.1.
PIRiA26100.
A29193. GNNYTP.

3D structure databases

ProteinModelPortaliP08545.
ModBaseiSearch...
MobiDBiSearch...

Protein family/group databases

MEROPSiC03.010.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Family and domain databases

CDDicd00205. rhv_like. 3 hits.
Gene3Di2.60.120.20. 3 hits.
4.10.90.10. 1 hit.
InterProiIPR015031. 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.
IPR009003. Peptidase_S1_PA.
IPR002527. Pico_P2B.
IPR001676. Picornavirus_capsid.
IPR033703. Rhv-like.
IPR001205. RNA-dir_pol_C.
IPR007094. RNA-dir_pol_PSvirus.
IPR029053. Viral_coat.
[Graphical view]
PfamiPF00548. 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]
PRINTSiPR00918. CALICVIRUSNS.
ProDomiPD649346. Pico_P2B. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SUPFAMiSSF50494. SSF50494. 1 hit.
PROSITEiPS50507. RDRP_SSRNA_POS. 1 hit.
PS51218. SF3_HELICASE_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPOLG_TMEVG
AccessioniPrimary (citable) accession number: P08545
Secondary accession number(s): Q88593, Q88594
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1988
Last sequence update: January 1, 1990
Last modified: November 30, 2016
This is version 137 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

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.

Keywords - Technical termi

Complete proteome

Documents

  1. Peptidase families
    Classification of peptidase families and list of entries
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.