Q83883 (POLG_NVN68) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Norwalk virus (strain GI/Human/United States/Norwalk/1968) (Hu/NV/NV/1968/US) [Reference proteome]

Taxonomic identifier

524364 [NCBI]

Taxonomic lineage

Viruses › ssRNA viruses › ssRNA positive-strand viruses, no DNA stage › Caliciviridae › Norovirus › Norwalk virus › Norovirus isolates

Virus host

Homo sapiens (Human) [TaxID: 9606]

Protein attributes

Sequence length	1789 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 encodes 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.

Ontologies

Keywords
Biological process	Host-virus interaction Viral RNA replication
Cellular component	Host membrane Membrane
Domain	Transmembrane Transmembrane helix
Ligand	ATP-binding Nucleotide-binding
Molecular function	Hydrolase Nucleotidyltransferase Protease RNA-directed RNA polymerase Thiol protease Transferase
PTM	Covalent protein-RNA linkage Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	RNA-protein covalent cross-linking Inferred from electronic annotation. Source: UniProtKB-KW proteolysis Inferred from electronic annotation. Source: UniProtKB-KW transcription, DNA-dependent Inferred from electronic annotation. Source: InterPro viral genome replication Inferred from electronic annotation. Source: InterPro virus-host interaction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	host cell membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW RNA binding Inferred from electronic annotation. Source: InterPro 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
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1789

1789

Genome polyprotein

PRO_0000341617

Chain

1 – 398

398

Protein p48

PRO_0000341618

Chain

399 – 761

363

NTPase

PRO_0000341619

Chain

762 – 962

201

Protein p22

PRO_0000341620

Chain

963 – 1100

138

Viral genome-linked protein

PRO_0000341621

Chain

1101 – 1281

181

3C-like protease

PRO_0000341622

Chain

1282 – 1789

508

RNA-directed RNA polymerase

PRO_0000341623

Regions

Transmembrane

359 – 379

21

Helical; Potential

Transmembrane

402 – 422

21

Helical; Potential

Transmembrane

870 – 890

21

Helical; Potential

Domain

532 – 697

166

SF3 helicase

Domain

1101 – 1281

181

Peptidase C37

Domain

1516 – 1637

122

RdRp catalytic

Nucleotide binding

560 – 567

8

ATP Potential

Sites

Active site

1130

1

For 3CLpro activity By similarity

Active site

1154

1

For 3CLpro activity By similarity

Active site

1239

1

For 3CLpro activity By similarity

Site

398 – 399

2

Cleavage; by 3CLpro

Site

761 – 762

2

Cleavage; by 3CLpro

Site

962 – 963

2

Cleavage; by 3CLpro

Site

1100 – 1101

2

Cleavage; by 3CLpro

Site

1281 – 1282

2

Cleavage; by 3CLpro

Amino acid modifications

Modified residue

992

1

O-(5'-phospho-RNA)-tyrosine By similarity

Experimental info

Mutagenesis

394

1

D → A, E or N: No effect on p48-p41 cleavage. Ref.5

Mutagenesis

395

1

F → G: Complete loss of p48-p41 cleavage. Ref.5

Mutagenesis

395

1

F → I or Y: No effect on p48-p41 cleavage. Ref.5

Mutagenesis

398

1

Q → E or N: No effect on p48-p41 cleavage. Ref.5

Mutagenesis

398

1

Q → G: Complete loss of p48-p41 cleavage. Ref.5

Mutagenesis

399

1

G → A: No effect on p48-p41 cleavage. Ref.5

Mutagenesis

1154

1

E → G: Complete loss of 3CLpro activity. Ref.5

Mutagenesis

1167

1

D → G: No effect on 3CLpro activity. Ref.5

Mutagenesis

1281

1

E → Q: No effect on 3CLpro activity. Ref.5

Secondary structure

1

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1789

Helix Strand Turn

Details...

Helix

1103 – 1107

5

Beta strand

1109 – 1112

4

Beta strand

1115 – 1128

14

Helix

1129 – 1131

3

Beta strand

1137 – 1139

3

Helix

1144 – 1146

3

Beta strand

1147 – 1152

6

Beta strand

1155 – 1162

8

Beta strand

1182 – 1188

7

Beta strand

1190 – 1192

3

Beta strand

1194 – 1209

16

Beta strand

1212 – 1221

10

Beta strand

1223 – 1225

3

Beta strand

1229 – 1233

5

Helix

1236 – 1238

3

Beta strand

1242 – 1247

6

Beta strand

1250 – 1260

11

Beta strand

1262 – 1270

9

Sequences

	Sequence		Length	Mass (Da)
	Q83883 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 6C84EF9EE62809B9	FASTA	1,789	198,694
	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

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.

PIR

A53260.
C37471.
C53260.
D37471.
E37471.

RefSeq

NP_056820.1. NC_001959.2.

3D structure databases

PDBe
RCSB PDB
PDBj

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	1101-1277	[»]
4IN2	X-ray	2.40	A/B	1100-1281	[»]
4INH	X-ray	1.70	A/B/C/D/E/F/G/H	1101-1281	[»]

ProteinModelPortal

Q83883.

SMR

Q83883. Positions 1101-1280, 1285-1787.

ModBase

Search...

Protein family/group databases

MEROPS

C37.001.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Family and domain databases

InterPro

IPR000605. Helicase_SF3_ssDNA/RNA_vir.
IPR014759. Helicase_SF3_ssRNA_vir.
IPR001665. Norovirus_pept_C37.
IPR001205. RNA-dir_pol_C.
IPR007094. RNA-dir_pol_PSvirus.
IPR009003. Trypsin-like_Pept_dom.
IPR013614. Viral_PP_Calicivir_N.
[Graphical view]

Pfam

PF08405. Calici_PP_N. 1 hit.
PF05416. Peptidase_C37. 1 hit.
PF00680. RdRP_1. 1 hit.
PF00910. RNA_helicase. 1 hit.
[Graphical view]

PRINTS

PR00917. SRSVCYSPTASE.

SUPFAM

SSF50494. Pept_Ser_Cys. 1 hit.

PROSITE

PS51537. NV_3CL_PRO. 1 hit.
PS50507. RDRP_SSRNA_POS. 1 hit.
PS51218. SF3_HELICASE_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q83883.

Entry information

Entry name

POLG_NVN68

Accession

Primary (citable) accession number: Q83883

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 2008
Last sequence update:	November 1, 1996
Last modified:	May 1, 2013
This is version 84 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program