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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: 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)DescriptionActionsGraphical viewLength
Active sitei1130For 3CLpro activityPROSITE-ProRule annotation1
Active sitei1154For 3CLpro activityPROSITE-ProRule annotation1
Active sitei1239For 3CLpro activityPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi560 – 567ATPPROSITE-ProRule annotation8

GO - Molecular functioni

GO - Biological processi

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

Enzyme and pathway databases

BRENDAi3.4.22.66. 8731.

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 virusesssRNA positive-strand viruses, no DNA stageCaliciviridaeNorovirus
Virus hostiHomo sapiens (Human) [TaxID: 9606]
Proteomesi
  • UP000000826 Componenti: Genome

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transmembranei359 – 379HelicalSequence analysisAdd BLAST21
Transmembranei402 – 422HelicalSequence analysisAdd BLAST21
Transmembranei870 – 890HelicalSequence analysisAdd BLAST21

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Host membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi394D → A, E or N: No effect on p48-p41 cleavage. 1 Publication1
Mutagenesisi395F → G: Complete loss of p48-p41 cleavage. 1 Publication1
Mutagenesisi395F → I or Y: No effect on p48-p41 cleavage. 1 Publication1
Mutagenesisi398Q → E or N: No effect on p48-p41 cleavage. 1 Publication1
Mutagenesisi398Q → G: Complete loss of p48-p41 cleavage. 1 Publication1
Mutagenesisi399G → A: No effect on p48-p41 cleavage. 1 Publication1
Mutagenesisi1154E → G: Complete loss of 3CLpro activity. 1 Publication1
Mutagenesisi1167D → G: No effect on 3CLpro activity. 1 Publication1
Mutagenesisi1281E → Q: No effect on 3CLpro activity. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003416171 – 1789Genome polyproteinAdd BLAST1789
ChainiPRO_00003416181 – 398Protein p48Add BLAST398
ChainiPRO_0000341619399 – 761NTPaseAdd BLAST363
ChainiPRO_0000341620762 – 962Protein p22Add BLAST201
ChainiPRO_0000341621963 – 1100Viral genome-linked proteinAdd BLAST138
ChainiPRO_00003416221101 – 12813C-like proteaseAdd BLAST181
ChainiPRO_00003416231282 – 1789RNA-directed RNA polymeraseAdd BLAST508

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei992O-(5'-phospho-RNA)-tyrosineBy similarity1

Post-translational modificationi

Specific enzymatic cleavages in vivo yield mature proteins. 3CLpro is first autocatalytically cleaved, then processes the whole polyprotein.PROSITE-ProRule annotation1 Publication
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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei398 – 399Cleavage; by 3CLpro2
Sitei761 – 762Cleavage; by 3CLpro2
Sitei962 – 963Cleavage; by 3CLpro2
Sitei1100 – 1101Cleavage; by 3CLpro2
Sitei1281 – 1282Cleavage; by 3CLpro2

Keywords - PTMi

Covalent protein-RNA linkage, Phosphoprotein

Proteomic databases

PRIDEiQ83883.

Interactioni

Subunit structurei

Protein p48 interacts with human VAPA.1 Publication

Structurei

Secondary structure

11789
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi1103 – 1106Combined sources4
Beta strandi1109 – 1112Combined sources4
Beta strandi1115 – 1128Combined sources14
Helixi1129 – 1131Combined sources3
Beta strandi1137 – 1139Combined sources3
Helixi1144 – 1146Combined sources3
Beta strandi1147 – 1152Combined sources6
Beta strandi1155 – 1162Combined sources8
Beta strandi1182 – 1188Combined sources7
Beta strandi1190 – 1192Combined sources3
Beta strandi1194 – 1209Combined sources16
Beta strandi1212 – 1221Combined sources10
Helixi1223 – 1225Combined sources3
Turni1227 – 1231Combined sources5
Turni1232 – 1234Combined sources3
Helixi1236 – 1238Combined sources3
Beta strandi1242 – 1247Combined sources6
Beta strandi1250 – 1260Combined sources11
Turni1262 – 1265Combined sources4
Beta strandi1266 – 1270Combined sources5
Beta strandi1275 – 1278Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
4XBBX-ray1.85A1101-1281[»]
4XBCX-ray1.60A1101-1281[»]
4XBDX-ray1.45A/B1101-1281[»]
5DG6X-ray2.35A/B1101-1281[»]
5DGJX-ray1.00A1101-1281[»]
5E0GX-ray1.20A1101-1281[»]
5E0HX-ray1.95A/B1101-1281[»]
5E0JX-ray1.20A1101-1281[»]
ProteinModelPortaliQ83883.
SMRiQ83883.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ83883.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini532 – 697SF3 helicasePROSITE-ProRule annotationAdd BLAST166
Domaini1101 – 1281Peptidase C37PROSITE-ProRule annotationAdd BLAST181
Domaini1516 – 1637RdRp catalyticPROSITE-ProRule annotationAdd BLAST122

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.
3.90.1720.10. 1 hit.
InterProiIPR000605. Helicase_SF3_ssDNA/RNA_vir.
IPR014759. Helicase_SF3_ssRNA_vir.
IPR000064. NLP_P60_dom.
IPR001665. Norovirus_pept_C37.
IPR027417. P-loop_NTPase.
IPR009003. Peptidase_S1_PA.
IPR001205. RNA-dir_pol_C.
IPR007094. RNA-dir_pol_PSvirus.
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:
EMBLi
GenBanki
DDBJi
Links Updated
M87661 Genomic RNA. Translation: AAB50465.1.
PIRiA53260.
C37471.
C53260.
D37471.
E37471.
RefSeqiNP_056820.1. NC_001959.2.

Genome annotation databases

GeneIDi1491970.
KEGGivg:1491970.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M87661 Genomic RNA. Translation: AAB50465.1.
PIRiA53260.
C37471.
C53260.
D37471.
E37471.
RefSeqiNP_056820.1. NC_001959.2.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
4XBBX-ray1.85A1101-1281[»]
4XBCX-ray1.60A1101-1281[»]
4XBDX-ray1.45A/B1101-1281[»]
5DG6X-ray2.35A/B1101-1281[»]
5DGJX-ray1.00A1101-1281[»]
5E0GX-ray1.20A1101-1281[»]
5E0HX-ray1.95A/B1101-1281[»]
5E0JX-ray1.20A1101-1281[»]
ProteinModelPortaliQ83883.
SMRiQ83883.
ModBaseiSearch...
MobiDBiSearch...

Protein family/group databases

MEROPSiC37.001.

Proteomic databases

PRIDEiQ83883.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi1491970.
KEGGivg:1491970.

Enzyme and pathway databases

BRENDAi3.4.22.66. 8731.

Miscellaneous databases

EvolutionaryTraceiQ83883.

Family and domain databases

Gene3Di3.40.50.300. 2 hits.
3.90.1720.10. 1 hit.
InterProiIPR000605. Helicase_SF3_ssDNA/RNA_vir.
IPR014759. Helicase_SF3_ssRNA_vir.
IPR000064. NLP_P60_dom.
IPR001665. Norovirus_pept_C37.
IPR027417. P-loop_NTPase.
IPR009003. Peptidase_S1_PA.
IPR001205. RNA-dir_pol_C.
IPR007094. RNA-dir_pol_PSvirus.
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]
ProtoNetiSearch...

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: November 30, 2016
This is version 107 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

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.