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Q83883 (POLG_NVN68) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 91. 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·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Genome polyprotein

Cleaved into the following 6 chains:

  1. Protein p48
  2. NTPase
    EC=3.6.1.15
    Alternative name(s):
    p41
  3. Protein p22
  4. Viral genome-linked protein
    Alternative name(s):
    VPG
  5. 3C-like protease
    Short name=3CLpro
    EC=3.4.22.66
    Alternative name(s):
    Calicivirin
  6. RNA-directed RNA polymerase
    Short name=RdRp
    EC=2.7.7.48
Gene names
ORF Names:ORF1
OrganismNorwalk virus (strain GI/Human/United States/Norwalk/1968) (Hu/NV/NV/1968/US) [Reference proteome]
Taxonomic identifier524364 [NCBI]
Taxonomic lineageVirusesssRNA positive-strand viruses, no DNA stageCaliciviridaeNorovirus
Virus hostHomo sapiens (Human) [TaxID: 9606]

Protein attributes

Sequence length1789 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Protein p48 may play a role in viral replication by interacting with host VAPA, a vesicle-associated membrane protein that plays a role in SNARE-mediated vesicle fusion. This interaction may target replication complex to intracellular membranes. Ref.3 Ref.4

NTPase presumably plays a role in replication. Despite having similarities with helicases, does not seem to display any helicase activity. Ref.3 Ref.4

Protein P22 may play a role in targeting replication complex to intracellular membranes. Ref.3 Ref.4

Viral genome-linked protein is covalently linked to the 5'-end of the positive-strand, negative-strand genomic RNAs and subgenomic RNA. Acts as a genome-linked replication primer. May recruit ribosome to viral RNA thereby promoting viral proteins translation. Ref.3 Ref.4

3C-like protease processes the polyprotein: 3CLpro-RdRp is first released by autocleavage, then all other proteins are cleaved. May cleave host polyadenylate-binding protein thereby inhibiting cellular translation By similarity. Ref.3 Ref.4

RNA-directed RNA polymerase replicates genomic and antigenomic RNA by recognizing replications specific signals. Transcribes also a subgenomic mRNA by initiating RNA synthesis internally on antigenomic RNA. This sgRNA codes for structural proteins. Catalyzes the covalent attachment VPg with viral RNAs By similarity. Ref.3 Ref.4

Catalytic activity

NTP + H2O = NDP + phosphate.

Endopeptidase with a preference for cleavage when the P1 position is occupied by Glu-|-Xaa and the P1' position is occupied by Gly-|-Yaa.

Nucleoside triphosphate + RNA(n) = diphosphate + RNA(n+1).

Subunit structure

Protein p48 interacts with human VAPA. Ref.6

Subcellular location

Protein p48: Host membrane; Single-pass membrane protein Potential.

NTPase: Host membrane; Single-pass membrane protein Potential.

Protein p22: Host membrane; Single-pass membrane protein Potential.

Post-translational modification

Specific enzymatic cleavages in vivo yield mature proteins. 3CLpro is first autocatalytically cleaved, then processes the whole polyprotein. Ref.7

VPg is uridylylated by the polymerase and is covalently attached to the 5'-end of the polyadenylated genomic and subgenomic RNAs. This uridylylated form acts as a nucleotide-peptide primer for the polymerase By similarity.

Sequence similarities

Contains 1 peptidase C37 domain.

Contains 1 RdRp catalytic domain.

Contains 1 SF3 helicase domain.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 17891789Genome polyprotein
PRO_0000341617
Chain1 – 398398Protein p48
PRO_0000341618
Chain399 – 761363NTPase
PRO_0000341619
Chain762 – 962201Protein p22
PRO_0000341620
Chain963 – 1100138Viral genome-linked protein
PRO_0000341621
Chain1101 – 12811813C-like protease
PRO_0000341622
Chain1282 – 1789508RNA-directed RNA polymerase
PRO_0000341623

Regions

Transmembrane359 – 37921Helical; Potential
Transmembrane402 – 42221Helical; Potential
Transmembrane870 – 89021Helical; Potential
Domain532 – 697166SF3 helicase
Domain1101 – 1281181Peptidase C37
Domain1516 – 1637122RdRp catalytic
Nucleotide binding560 – 5678ATP Potential

Sites

Active site11301For 3CLpro activity By similarity
Active site11541For 3CLpro activity By similarity
Active site12391For 3CLpro activity By similarity
Site398 – 3992Cleavage; by 3CLpro
Site761 – 7622Cleavage; by 3CLpro
Site962 – 9632Cleavage; by 3CLpro
Site1100 – 11012Cleavage; by 3CLpro
Site1281 – 12822Cleavage; by 3CLpro

Amino acid modifications

Modified residue9921O-(5'-phospho-RNA)-tyrosine By similarity

Experimental info

Mutagenesis3941D → A, E or N: No effect on p48-p41 cleavage. Ref.5
Mutagenesis3951F → G: Complete loss of p48-p41 cleavage. Ref.5
Mutagenesis3951F → I or Y: No effect on p48-p41 cleavage. Ref.5
Mutagenesis3981Q → E or N: No effect on p48-p41 cleavage. Ref.5
Mutagenesis3981Q → G: Complete loss of p48-p41 cleavage. Ref.5
Mutagenesis3991G → A: No effect on p48-p41 cleavage. Ref.5
Mutagenesis11541E → G: Complete loss of 3CLpro activity. Ref.5
Mutagenesis11671D → G: No effect on 3CLpro activity. Ref.5
Mutagenesis12811E → Q: No effect on 3CLpro activity. Ref.5

Secondary structure

..................................... 1789
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q83883 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: 6C84EF9EE62809B9

FASTA1,789198,694
        10         20         30         40         50         60 
MMMASKDVVP TAASSENANN NSSIKSRLLA RLKGSGGATS PPNSIKITNQ DMALGLIGQV 

        70         80         90        100        110        120 
PAPKATSVDV PKQQRDRPPR TVAEVQQNLR WTERPQDQNV KTWDELDHTT KQQILDEHAE 

       130        140        150        160        170        180 
WFDAGGLGPS TLPTSHERYT HENDEGHQVK WSAREGVDLG ISGLTTVSGP EWNMCPLPPV 

       190        200        210        220        230        240 
DQRSTTPATE PTIGDMIEFY EGHIYHYAIY IGQGKTVGVH SPQAAFSITR ITIQPISAWW 

       250        260        270        280        290        300 
RVCYVPQPKQ RLTYDQLKEL ENEPWPYAAV TNNCFEFCCQ VMCLEDTWLQ RKLISSGRFY 

       310        320        330        340        350        360 
HPTQDWSRDT PEFQQDSKLE MVRDAVLAAI NGLVSRPFKD LLGKLKPLNV LNLLSNCDWT 

       370        380        390        400        410        420 
FMGVVEMVVL LLELFGIFWN PPDVSNFIAS LLPDFHLQGP EDLARDLVPI VLGGIGLAIG 

       430        440        450        460        470        480 
FTRDKVSKMM KNAVDGLRAA TQLGQYGLEI FSLLKKYFFG GDQTEKTLKD IESAVIDMEV 

       490        500        510        520        530        540 
LSSTSVTQLV RDKQSARAYM AILDNEEEKA RKLSVRNADP HVVSSTNALI SRISMARAAL 

       550        560        570        580        590        600 
AKAQAEMTSR MRPVVIMMCG PPGIGKTKAA EHLAKRLANE IRPGGKVGLV PREAVDHWDG 

       610        620        630        640        650        660 
YHGEEVMLWD DYGMTKIQED CNKLQAIADS APLTLNCDRI ENKGMQFVSD AIVITTNAPG 

       670        680        690        700        710        720 
PAPVDFVNLG PVCRRVDFLV YCTAPEVEHT RKVSPGDTTA LKDCFKPDFS HLKMELAPQG 

       730        740        750        760        770        780 
GFDNQGNTPF GKGVMKPTTI NRLLIQAVAL TMERQDEFQL QGPTYDFDTD RVAAFTRMAR 

       790        800        810        820        830        840 
ANGLGLISMA SLGKKLRSVT TIEGLKNALS GYKISKCSIQ WQSRVYIIES DGASVQIKED 

       850        860        870        880        890        900 
KQALTPLQQT INTASLAITR LKAARAVAYA SCFQSAITTI LQMAGSALVI NRAVKRMFGT 

       910        920        930        940        950        960 
RTAAMALEGP GKEHNCRVHK AKEAGKGPIG HDDMVERFGL CETEEEESED QIQMVPSDAV 

       970        980        990       1000       1010       1020 
PEGKNKGKTK KGRGRKNNYN AFSRRGLSDE EYEEYKKIRE EKNGNYSIQE YLEDRQRYEE 

      1030       1040       1050       1060       1070       1080 
ELAEVQAGGD GGIGETEMEI RHRVFYKSKS KKHQQEQRRQ LGLVTGSDIR KRKPIDWTPP 

      1090       1100       1110       1120       1130       1140 
KNEWADDDRE VDYNEKINFE APPTLWSRVT KFGSGWGFWV SPTVFITTTH VVPTGVKEFF 

      1150       1160       1170       1180       1190       1200 
GEPLSSIAIH QAGEFTQFRF SKKMRPDLTG MVLEEGCPEG TVCSVLIKRD SGELLPLAVR 

      1210       1220       1230       1240       1250       1260 
MGAIASMRIQ GRLVHGQSGM LLTGANAKGM DLGTIPGDCG APYVHKRGND WVVCGVHAAA 

      1270       1280       1290       1300       1310       1320 
TKSGNTVVCA VQAGEGETAL EGGDKGHYAG HEIVRYGSGP ALSTKTKFWR SSPEPLPPGV 

      1330       1340       1350       1360       1370       1380 
YEPAYLGGKD PRVQNGPSLQ QVLRDQLKPF ADPRGRMPEP GLLEAAVETV TSMLEQTMDT 

      1390       1400       1410       1420       1430       1440 
PSPWSYADAC QSLDKTTSSG YPHHKRKNDD WNGTTFVGEL GEQAAHANNM YENAKHMKPI 

      1450       1460       1470       1480       1490       1500 
YTAALKDELV KPEKIYQKVK KRLLWGADLG TVVRAARAFG PFCDAIKSHV IKLPIKVGMN 

      1510       1520       1530       1540       1550       1560 
TIEDGPLIYA EHAKYKNHFD ADYTAWDSTQ NRQIMTESFS IMSRLTASPE LAEVVAQDLL 

      1570       1580       1590       1600       1610       1620 
APSEMDVGDY VIRVKEGLPS GFPCTSQVNS INHWIITLCA LSEATGLSPD VVQSMSYFSF 

      1630       1640       1650       1660       1670       1680 
YGDDEIVSTD IDFDPARLTQ ILKEYGLKPT RPDKTEGPIQ VRKNVDGLVF LRRTISRDAA 

      1690       1700       1710       1720       1730       1740 
GFQGRLDRAS IERQIFWTRG PNHSDPSETL VPHTQRKIQL ISLLGEASLH GEKFYRKISS 

      1750       1760       1770       1780 
KVIHEIKTGG LEMYVPGWQA MFRWMRFHDL GLWTGDRDLL PEFVNDDGV 

« Hide

References

[1]"Sequence and genomic organization of Norwalk virus."
Jiang X., Wang M., Wang K., Estes M.K.
Virology 195:51-61(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 3-1789.
[2]"Completion of the Norwalk virus genome sequence."
Hardy M.E., Estes M.K.
Virus Genes 12:287-290(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1-3.
[3]"Presence of a covalently linked protein on calicivirus RNA."
Burroughs J.N., Brown F.
J. Gen. Virol. 41:443-446(1978) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION OF VPG.
[4]"Polypeptide p41 of a Norwalk-like virus is a nucleic acid-independent nucleoside triphosphatase."
Pfister T., Wimmer E.
J. Virol. 75:1611-1619(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION OF NTPASE.
[5]"Substrate specificity of the Norwalk virus 3C-like proteinase."
Hardy M.E., Crone T.J., Brower J.E., Ettayebi K.
Virus Res. 89:29-39(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF ASP-394; PHE-395; GLN-398; GLY-399; GLU-1154; ASP-1167 AND GLU-1281.
[6]"Norwalk virus nonstructural protein p48 forms a complex with the SNARE regulator VAP-A and prevents cell surface expression of vesicular stomatitis virus G protein."
Ettayebi K., Hardy M.E.
J. Virol. 77:11790-11797(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HUMAN VAPA.
[7]"Differential cleavage of the norovirus polyprotein precursor by two active forms of the viral protease."
Scheffler U., Rudolph W., Gebhardt J., Rohayem J.
J. Gen. Virol. 88:2013-2018(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEOLYTIC PROCESSING OF POLYPROTEIN.
[8]"Norovirus protein structure and function."
Hardy M.E.
FEMS Microbiol. Lett. 253:1-8(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[9]"X-ray crystallographic structure of the Norwalk virus protease at 1.5-A resolution."
Zeitler C.E., Estes M.K., Venkataram Prasad B.V.
J. Virol. 80:5050-5058(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 1100-1281.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M87661 Genomic RNA. Translation: AAB50465.1.
PIRA53260.
C37471.
C53260.
D37471.
E37471.
RefSeqNP_056820.1. NC_001959.2.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2FYQX-ray1.50A1101-1281[»]
2FYRX-ray2.20A1101-1281[»]
2LNCNMR-A1101-1281[»]
3UR6X-ray1.50A/B1101-1281[»]
3UR9X-ray1.65A/B1101-1281[»]
4IMQX-ray1.50A1101-1281[»]
4IMZX-ray1.70A1101-1281[»]
4IN1X-ray2.05A1101-1281[»]
4IN2X-ray2.40A/B1100-1281[»]
4INHX-ray1.70A/B/C/D/E/F/G/H1101-1281[»]
ProteinModelPortalQ83883.
SMRQ83883. Positions 1101-1280, 1285-1787.
ModBaseSearch...
MobiDBSearch...

Protein family/group databases

MEROPSC37.001.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID1491970.

Family and domain databases

Gene3D3.40.50.300. 2 hits.
InterProIPR000605. Helicase_SF3_ssDNA/RNA_vir.
IPR014759. Helicase_SF3_ssRNA_vir.
IPR001665. Norovirus_pept_C37.
IPR027417. P-loop_NTPase.
IPR001205. RNA-dir_pol_C.
IPR007094. RNA-dir_pol_PSvirus.
IPR009003. Trypsin-like_Pept_dom.
IPR013614. Viral_PP_Calicivir_N.
[Graphical view]
PfamPF08405. Calici_PP_N. 1 hit.
PF05416. Peptidase_C37. 1 hit.
PF00680. RdRP_1. 1 hit.
PF00910. RNA_helicase. 1 hit.
[Graphical view]
PRINTSPR00917. SRSVCYSPTASE.
SUPFAMSSF50494. SSF50494. 1 hit.
SSF52540. SSF52540. 1 hit.
PROSITEPS51537. NV_3CL_PRO. 1 hit.
PS50507. RDRP_SSRNA_POS. 1 hit.
PS51218. SF3_HELICASE_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ83883.

Entry information

Entry namePOLG_NVN68
AccessionPrimary (citable) accession number: Q83883
Entry history
Integrated into UniProtKB/Swiss-Prot: July 1, 2008
Last sequence update: November 1, 1996
Last modified: July 9, 2014
This is version 91 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