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Q83883

- POLG_NVN68

UniProt

Q83883 - POLG_NVN68

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Protein

Genome polyprotein

Gene

ORF1

Organism
Norwalk virus (strain GI/Human/United States/Norwalk/1968) (Hu/NV/NV/1968/US)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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.
NTPase presumably plays a role in replication. Despite having similarities with helicases, does not seem to display any helicase activity.
Protein P22 may play a role in targeting replication complex to intracellular membranes.
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.
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).By similarity
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).PROSITE-ProRule annotation

Catalytic activityi

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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei398 – 3992Cleavage; by 3CLpro
Sitei761 – 7622Cleavage; by 3CLpro
Sitei962 – 9632Cleavage; by 3CLpro
Sitei1100 – 11012Cleavage; by 3CLpro
Active sitei1130 – 11301For 3CLpro activityPROSITE-ProRule annotation
Active sitei1154 – 11541For 3CLpro activityPROSITE-ProRule annotation
Active sitei1239 – 12391For 3CLpro activityPROSITE-ProRule annotation
Sitei1281 – 12822Cleavage; by 3CLpro

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi560 – 5678ATPPROSITE-ProRule annotation

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. cysteine-type endopeptidase activity Source: InterPro
  3. RNA binding Source: InterPro
  4. RNA-directed RNA polymerase activity Source: UniProtKB-KW
  5. RNA helicase activity Source: InterPro

GO - Biological processi

  1. RNA-protein covalent cross-linking Source: UniProtKB-KW
  2. transcription, DNA-templated Source: InterPro
  3. viral RNA genome replication Source: InterPro
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Nucleotidyltransferase, Protease, RNA-directed RNA polymerase, Thiol protease, Transferase

Keywords - Biological processi

Host-virus interaction, Viral RNA replication

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Protein family/group databases

MEROPSiC37.001.

Names & Taxonomyi

Protein namesi
Recommended name:
Genome polyprotein
Cleaved into the following 6 chains:
Alternative name(s):
p41
Alternative name(s):
VPG
3C-like protease (EC:3.4.22.66)
Short name:
3CLpro
Alternative name(s):
Calicivirin
Gene namesi
ORF Names:ORF1
OrganismiNorwalk virus (strain GI/Human/United States/Norwalk/1968) (Hu/NV/NV/1968/US)
Taxonomic identifieri524364 [NCBI]
Taxonomic lineageiVirusesssRNA positive-strand viruses, no DNA stageCaliciviridaeNorovirus
Virus hostiHomo sapiens (Human) [TaxID: 9606]
ProteomesiUP000000826: Genome

Subcellular locationi

GO - Cellular componenti

  1. host cell membrane Source: UniProtKB-KW
  2. integral component of membrane Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Host membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi394 – 3941D → A, E or N: No effect on p48-p41 cleavage. 1 Publication
Mutagenesisi395 – 3951F → G: Complete loss of p48-p41 cleavage. 1 Publication
Mutagenesisi395 – 3951F → I or Y: No effect on p48-p41 cleavage. 1 Publication
Mutagenesisi398 – 3981Q → E or N: No effect on p48-p41 cleavage. 1 Publication
Mutagenesisi398 – 3981Q → G: Complete loss of p48-p41 cleavage. 1 Publication
Mutagenesisi399 – 3991G → A: No effect on p48-p41 cleavage. 1 Publication
Mutagenesisi1154 – 11541E → G: Complete loss of 3CLpro activity. 1 Publication
Mutagenesisi1167 – 11671D → G: No effect on 3CLpro activity. 1 Publication
Mutagenesisi1281 – 12811E → Q: No effect on 3CLpro activity. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 17891789Genome polyproteinPRO_0000341617Add
BLAST
Chaini1 – 398398Protein p48PRO_0000341618Add
BLAST
Chaini399 – 761363NTPasePRO_0000341619Add
BLAST
Chaini762 – 962201Protein p22PRO_0000341620Add
BLAST
Chaini963 – 1100138Viral genome-linked proteinPRO_0000341621Add
BLAST
Chaini1101 – 12811813C-like proteasePRO_0000341622Add
BLAST
Chaini1282 – 1789508RNA-directed RNA polymerasePRO_0000341623Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei992 – 9921O-(5'-phospho-RNA)-tyrosineBy similarity

Post-translational modificationi

Specific enzymatic cleavages in vivo yield mature proteins. 3CLpro is first autocatalytically cleaved, then processes the whole polyprotein.1 PublicationPROSITE-ProRule annotation
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).By similarity

Keywords - PTMi

Covalent protein-RNA linkage, Phosphoprotein

Interactioni

Subunit structurei

Protein p48 interacts with human VAPA.1 Publication

Structurei

Secondary structure

1
1789
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi1103 – 11075
Beta strandi1109 – 11124
Beta strandi1115 – 112814
Helixi1129 – 11313
Beta strandi1137 – 11393
Helixi1144 – 11463
Beta strandi1147 – 11526
Beta strandi1155 – 11628
Beta strandi1182 – 11887
Beta strandi1190 – 11923
Beta strandi1194 – 120916
Beta strandi1212 – 122110
Beta strandi1223 – 12253
Beta strandi1229 – 12335
Helixi1236 – 12383
Beta strandi1242 – 12476
Beta strandi1250 – 126011
Beta strandi1262 – 12709
Beta strandi1275 – 12784

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
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[»]
ProteinModelPortaliQ83883.
SMRiQ83883. Positions 1101-1280, 1285-1787.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ83883.

Transmembrane

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei359 – 37921HelicalSequence AnalysisAdd
BLAST
Transmembranei402 – 42221HelicalSequence AnalysisAdd
BLAST
Transmembranei870 – 89021HelicalSequence AnalysisAdd
BLAST

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini532 – 697166SF3 helicasePROSITE-ProRule annotationAdd
BLAST
Domaini1101 – 1281181Peptidase C37PROSITE-ProRule annotationAdd
BLAST
Domaini1516 – 1637122RdRp catalyticPROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Contains 1 peptidase C37 domain.PROSITE-ProRule annotation
Contains 1 RdRp catalytic domain.PROSITE-ProRule annotation
Contains 1 SF3 helicase domain.PROSITE-ProRule annotation

Keywords - Domaini

Transmembrane, Transmembrane helix

Family and domain databases

Gene3Di3.40.50.300. 2 hits.
InterProiIPR000605. 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]
PfamiPF08405. Calici_PP_N. 1 hit.
PF05416. Peptidase_C37. 1 hit.
PF00680. RdRP_1. 1 hit.
PF00910. RNA_helicase. 1 hit.
[Graphical view]
PRINTSiPR00917. SRSVCYSPTASE.
SUPFAMiSSF50494. SSF50494. 1 hit.
SSF52540. SSF52540. 1 hit.
PROSITEiPS51537. NV_3CL_PRO. 1 hit.
PS50507. 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.

Q83883-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MMMASKDVVP TAASSENANN NSSIKSRLLA RLKGSGGATS PPNSIKITNQ
60 70 80 90 100
DMALGLIGQV PAPKATSVDV PKQQRDRPPR TVAEVQQNLR WTERPQDQNV
110 120 130 140 150
KTWDELDHTT KQQILDEHAE WFDAGGLGPS TLPTSHERYT HENDEGHQVK
160 170 180 190 200
WSAREGVDLG ISGLTTVSGP EWNMCPLPPV DQRSTTPATE PTIGDMIEFY
210 220 230 240 250
EGHIYHYAIY IGQGKTVGVH SPQAAFSITR ITIQPISAWW RVCYVPQPKQ
260 270 280 290 300
RLTYDQLKEL ENEPWPYAAV TNNCFEFCCQ VMCLEDTWLQ RKLISSGRFY
310 320 330 340 350
HPTQDWSRDT PEFQQDSKLE MVRDAVLAAI NGLVSRPFKD LLGKLKPLNV
360 370 380 390 400
LNLLSNCDWT FMGVVEMVVL LLELFGIFWN PPDVSNFIAS LLPDFHLQGP
410 420 430 440 450
EDLARDLVPI VLGGIGLAIG FTRDKVSKMM KNAVDGLRAA TQLGQYGLEI
460 470 480 490 500
FSLLKKYFFG GDQTEKTLKD IESAVIDMEV LSSTSVTQLV RDKQSARAYM
510 520 530 540 550
AILDNEEEKA RKLSVRNADP HVVSSTNALI SRISMARAAL AKAQAEMTSR
560 570 580 590 600
MRPVVIMMCG PPGIGKTKAA EHLAKRLANE IRPGGKVGLV PREAVDHWDG
610 620 630 640 650
YHGEEVMLWD DYGMTKIQED CNKLQAIADS APLTLNCDRI ENKGMQFVSD
660 670 680 690 700
AIVITTNAPG PAPVDFVNLG PVCRRVDFLV YCTAPEVEHT RKVSPGDTTA
710 720 730 740 750
LKDCFKPDFS HLKMELAPQG GFDNQGNTPF GKGVMKPTTI NRLLIQAVAL
760 770 780 790 800
TMERQDEFQL QGPTYDFDTD RVAAFTRMAR ANGLGLISMA SLGKKLRSVT
810 820 830 840 850
TIEGLKNALS GYKISKCSIQ WQSRVYIIES DGASVQIKED KQALTPLQQT
860 870 880 890 900
INTASLAITR LKAARAVAYA SCFQSAITTI LQMAGSALVI NRAVKRMFGT
910 920 930 940 950
RTAAMALEGP GKEHNCRVHK AKEAGKGPIG HDDMVERFGL CETEEEESED
960 970 980 990 1000
QIQMVPSDAV PEGKNKGKTK KGRGRKNNYN AFSRRGLSDE EYEEYKKIRE
1010 1020 1030 1040 1050
EKNGNYSIQE YLEDRQRYEE ELAEVQAGGD GGIGETEMEI RHRVFYKSKS
1060 1070 1080 1090 1100
KKHQQEQRRQ LGLVTGSDIR KRKPIDWTPP KNEWADDDRE VDYNEKINFE
1110 1120 1130 1140 1150
APPTLWSRVT KFGSGWGFWV SPTVFITTTH VVPTGVKEFF GEPLSSIAIH
1160 1170 1180 1190 1200
QAGEFTQFRF SKKMRPDLTG MVLEEGCPEG TVCSVLIKRD SGELLPLAVR
1210 1220 1230 1240 1250
MGAIASMRIQ GRLVHGQSGM LLTGANAKGM DLGTIPGDCG APYVHKRGND
1260 1270 1280 1290 1300
WVVCGVHAAA TKSGNTVVCA VQAGEGETAL EGGDKGHYAG HEIVRYGSGP
1310 1320 1330 1340 1350
ALSTKTKFWR SSPEPLPPGV YEPAYLGGKD PRVQNGPSLQ QVLRDQLKPF
1360 1370 1380 1390 1400
ADPRGRMPEP GLLEAAVETV TSMLEQTMDT PSPWSYADAC QSLDKTTSSG
1410 1420 1430 1440 1450
YPHHKRKNDD WNGTTFVGEL GEQAAHANNM YENAKHMKPI YTAALKDELV
1460 1470 1480 1490 1500
KPEKIYQKVK KRLLWGADLG TVVRAARAFG PFCDAIKSHV IKLPIKVGMN
1510 1520 1530 1540 1550
TIEDGPLIYA EHAKYKNHFD ADYTAWDSTQ NRQIMTESFS IMSRLTASPE
1560 1570 1580 1590 1600
LAEVVAQDLL APSEMDVGDY VIRVKEGLPS GFPCTSQVNS INHWIITLCA
1610 1620 1630 1640 1650
LSEATGLSPD VVQSMSYFSF YGDDEIVSTD IDFDPARLTQ ILKEYGLKPT
1660 1670 1680 1690 1700
RPDKTEGPIQ VRKNVDGLVF LRRTISRDAA GFQGRLDRAS IERQIFWTRG
1710 1720 1730 1740 1750
PNHSDPSETL VPHTQRKIQL ISLLGEASLH GEKFYRKISS KVIHEIKTGG
1760 1770 1780
LEMYVPGWQA MFRWMRFHDL GLWTGDRDLL PEFVNDDGV
Length:1,789
Mass (Da):198,694
Last modified:November 1, 1996 - v1
Checksum:i6C84EF9EE62809B9
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
M87661 Genomic RNA. Translation: AAB50465.1.
PIRiA53260.
C37471.
C53260.
D37471.
E37471.
RefSeqiNP_056820.1. NC_001959.2.

Genome annotation databases

GeneIDi1491970.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
M87661 Genomic RNA. Translation: AAB50465.1 .
PIRi A53260.
C37471.
C53260.
D37471.
E37471.
RefSeqi NP_056820.1. NC_001959.2.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
2FYQ X-ray 1.50 A 1101-1281 [» ]
2FYR X-ray 2.20 A 1101-1281 [» ]
2LNC NMR - A 1101-1281 [» ]
3UR6 X-ray 1.50 A/B 1101-1281 [» ]
3UR9 X-ray 1.65 A/B 1101-1281 [» ]
4IMQ X-ray 1.50 A 1101-1281 [» ]
4IMZ X-ray 1.70 A 1101-1281 [» ]
4IN1 X-ray 2.05 A 1101-1281 [» ]
4IN2 X-ray 2.40 A/B 1100-1281 [» ]
4INH X-ray 1.70 A/B/C/D/E/F/G/H 1101-1281 [» ]
ProteinModelPortali Q83883.
SMRi Q83883. Positions 1101-1280, 1285-1787.
ModBasei Search...
MobiDBi Search...

Protein family/group databases

MEROPSi C37.001.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

GeneIDi 1491970.

Miscellaneous databases

EvolutionaryTracei Q83883.

Family and domain databases

Gene3Di 3.40.50.300. 2 hits.
InterProi IPR000605. 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 ]
Pfami PF08405. Calici_PP_N. 1 hit.
PF05416. Peptidase_C37. 1 hit.
PF00680. RdRP_1. 1 hit.
PF00910. RNA_helicase. 1 hit.
[Graphical view ]
PRINTSi PR00917. SRSVCYSPTASE.
SUPFAMi SSF50494. SSF50494. 1 hit.
SSF52540. SSF52540. 1 hit.
PROSITEi PS51537. NV_3CL_PRO. 1 hit.
PS50507. RDRP_SSRNA_POS. 1 hit.
PS51218. SF3_HELICASE_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  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.

Entry informationi

Entry nameiPOLG_NVN68
AccessioniPrimary (citable) accession number: Q83883
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 2008
Last sequence update: November 1, 1996
Last modified: October 29, 2014
This is version 94 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. Peptidase families
    Classification of peptidase families and list of entries
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3