Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q9DWR1 (POLG_HAVNO) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 83. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | 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 18 chains:

  1. Protein VP0
    Alternative name(s):
    VP4-VP2
  2. Protein VP4
    Alternative name(s):
    P1A
    Virion protein 4
  3. Protein VP2
    Alternative name(s):
    P1B
    Virion protein 2
  4. Protein VP3
    Alternative name(s):
    P1C
    Virion protein 3
  5. Protein VP1-2A
    Alternative name(s):
    PX
  6. Protein VP1
    Alternative name(s):
    P1D
    Virion protein 1
  7. Protein 2A
    Short name=P2A
  8. Protein 2BC
  9. Protein 2B
    Short name=P2B
  10. Protein 2C
    Short name=P2C
    EC=3.6.1.15
  11. Protein 3ABCD
    Short name=P3
  12. Protein 3ABC
  13. Protein 3AB
  14. Protein 3A
    Short name=P3A
  15. Protein 3B
    Short name=P3B
    Alternative name(s):
    VPg
  16. Protein 3CD
  17. Protease 3C
    Short name=P3C
    EC=3.4.22.28
    Alternative name(s):
    Picornain 3C
  18. RNA-directed RNA polymerase 3D-POL
    Short name=P3D-POL
    EC=2.7.7.48
OrganismHuman hepatitis A virus genotype IIIA (isolate NOR-21) (HHAV) (Human hepatitis A virus (isolate Human/Norway/NOR-21/1998)) [Complete proteome]
Taxonomic identifier470593 [NCBI]
Taxonomic lineageVirusesssRNA positive-strand viruses, no DNA stagePicornaviralesPicornaviridaeHepatovirus
Virus hostHomo sapiens (Human) [TaxID: 9606]

Protein attributes

Sequence length2228 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceInferred from homology

General annotation (Comments)

Function

Capsid proteins VP1, VP2, and VP3 form a closed capsid enclosing the viral positive strand RNA genome. All these 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. The capsid interacts with HAVCR1 to provide virion attachment to target cell By similarity.

Protein VP0: VP0 precursor is a component of immature procapsids. The N-terminal domain of VP0, protein VP4, is needed for the assembly of 12 pentamers into the icosahedral structure. Unlike other picornaviruses, HAV VP4 does not seem to be myristoylated and has not been detected in mature virions, supposedly owing to its small size By similarity.

VP1-2A precursor is a component of immature procapsids and corresponds to an extended form of the structural protein VP1. The C-terminal domain of VP1-2A, protein 2A, acts as an assembly signal that allows multimerization of VP1-2A and formation of pentamers of VP1-VP2-VP3 trimers. It is proteolytically removed from the precursor by a host protease and does not seem to be found in mature particles By similarity.

Protein 2B and 2BC precursor affect 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.

Protein 3A, via its hydrophobic domain, serves as membrane anchor to the 3AB and 3ABC precursors By similarity.

The 3AB precursor interacts with the 3CD precursor and with RNA structures found at both the 5'- and 3'-termini of the viral genome. Since the 3AB precursor contains the hydrophobic domain 3A, it probably anchors the whole viral replicase complex to intracellular membranes on which viral RNA synthesis occurs By similarity.

The 3ABC precursor is targeted to the mitochondrial membrane where protease 3C activity cleaves and inhibits the host antiviral protein MAVS, thereby disrupting activation of IRF3 through the IFIH1/MDA5 pathway. In vivo, the protease activity of 3ABC precursor is more efficient in cleaving the 2BC precursor than that of protein 3C. The 3ABC precursor may therefore play a role in the proteolytic processing of the polyprotein By similarity.

Protein 3B is covalently linked to the 5'-end of both the positive-strand and negative-strand genomic RNAs. It acts as a genome-linked replication primer 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. Also cleaves host proteins such as PCBP2 By similarity.

RNA-directed RNA polymerase 3D-POL replicates genomic and antigenomic RNA by recognizing replications specific signals By similarity.

Catalytic activity

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

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.

Subunit structure

3AB precursor is a homodimer. 3AB precursor interacts with 3CD precursor. Protein 3ABC interacts with human MAVS By similarity.

Subcellular location

Protein VP2: Virion By similarity. Host cytoplasm Potential.

Protein VP3: Virion By similarity. Host cytoplasm Potential.

Protein VP1: Virion By similarity. Host cytoplasm Potential.

Protein VP1-2A: Virion By similarity. Host cytoplasm Potential.

Protein 2B: Host cytoplasmic vesicle membrane; Peripheral membrane protein; Cytoplasmic side Potential. Note: Probably localizes to the surface of intracellular membrane vesicles that are induced after virus infection as the site for viral RNA replication. These vesicles are derived from the endoplasmic reticulum By similarity.

Protein 2C: Host cytoplasmic vesicle membrane; Peripheral membrane protein; Cytoplasmic side Potential. Note: Probably localizes to the surface of intracellular membrane vesicles that are induced after virus infection as the site for viral RNA replication. These vesicles are derived from the endoplasmic reticulum. May associate with membranes through a N-terminal amphipathic helix By similarity.

Protein 3ABC: Host cytoplasmic vesicle membrane; Peripheral membrane protein; Cytoplasmic side Potential. Host mitochondrion outer membrane; Peripheral membrane protein; Cytoplasmic side Potential. Note: Probably localizes to the surface of intracellular membrane vesicles that are induced after virus infection as the site for viral RNA replication. These vesicles are derived from the endoplasmic reticulum By similarity.

Protein 3AB: Host cytoplasmic vesicle membrane; Peripheral membrane protein; Cytoplasmic side Potential. Note: Probably localizes to the surface of intracellular membrane vesicles that are induced after virus infection as the site for viral RNA replication. These vesicles are derived from the endoplasmic reticulum By similarity.

Protein 3A: Host cytoplasmic vesicle membrane; Peripheral membrane protein; Cytoplasmic side Potential. Note: Probably localizes to the surface of intracellular membrane vesicles that are induced after virus infection as the site for viral RNA replication. These vesicles are derived from the endoplasmic reticulum By similarity.

Protein 3B: Virion Potential.

Protease 3C: Host cytoplasm Potential.

RNA-directed RNA polymerase 3D-POL: Host cytoplasmic vesicle membrane; Peripheral membrane protein; Cytoplasmic side Potential. Note: Interacts with membranes in a complex with viral protein 3AB. Probably localizes to the surface of intracellular membrane vesicles that are induced after virus infection as the site for viral RNA replication. These vesicles are derived from the endoplasmic reticulum By similarity.

Post-translational modification

Specific enzymatic cleavages by the viral protease in vivo yield a variety of precursors and mature proteins. Polyprotein processing intermediates are produced, such as P1-2A which is a functional precursor of the structural proteins, VP0 which is a VP4-VP2 precursor, VP1-2A precursor, 3ABC precursor which is a stable and catalytically active precursor of 3A, 3B and 3C proteins, 3AB and 3CD precursors. The assembly signal 2A is removed from VP1-2A by a host protease. 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 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.

Miscellaneous

The need for an intact eIF4G factor for the initiation of translation of HAV results in an inability to shut off host protein synthesis by a mechanism similar to that of other picornaviruses.

Sequence similarities

Belongs to the picornaviridae polyprotein family.

Contains 1 peptidase C3 domain.

Contains 1 RdRp catalytic domain.

Contains 1 SF3 helicase domain.

Caution

It is uncertain whether Met-1 or Met-3 is the initiator.

Protein VP1 seems to have a heterogeneous C-terminus in cell culture. It may be reduced by a few amino acids compared to the sequence shown.

Sequence caution

The sequence CAC14074.3 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
   Biological processHost gene expression shutoff by virus
Host translation shutoff by virus
Host-virus interaction
Inhibition of host innate immune response by virus
Inhibition of host MAVS by virus
Inhibition of host RLR pathway by virus
Interferon antiviral system evasion
Ion transport
Transport
Viral attachment to host cell
Viral immunoevasion
Viral RNA replication
Virus entry into host cell
   Cellular componentCapsid protein
Host cytoplasm
Host cytoplasmic vesicle
Host membrane
Host mitochondrion
Host mitochondrion outer membrane
Membrane
Virion
   DomainCoiled coil
   LigandATP-binding
Nucleotide-binding
RNA-binding
   Molecular functionHelicase
Hydrolase
Ion channel
Nucleotidyltransferase
Protease
RNA-directed RNA polymerase
Thiol protease
Transferase
Viral ion channel
   PTMCovalent protein-RNA linkage
Phosphoprotein
   Technical termComplete proteome
Gene Ontology (GO)
   Biological_processRNA-protein covalent cross-linking

Inferred from electronic annotation. Source: UniProtKB-KW

pore formation by virus in membrane of host cell

Inferred from electronic annotation. Source: UniProtKB-KW

protein oligomerization

Inferred from electronic annotation. Source: UniProtKB-KW

proteolysis

Inferred from electronic annotation. Source: UniProtKB-KW

suppression by virus of host MAVS activity

Inferred from electronic annotation. Source: UniProtKB-KW

suppression by virus of host translation

Inferred from electronic annotation. Source: UniProtKB-KW

transcription, DNA-templated

Inferred from electronic annotation. Source: InterPro

viral RNA genome replication

Inferred from electronic annotation. Source: InterPro

viral entry into host cell

Inferred from electronic annotation. Source: UniProtKB-KW

virion attachment to host cell

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componenthost cell cytoplasmic vesicle membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

host cell mitochondrial outer membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

integral to membrane of host cell

Inferred from electronic annotation. Source: UniProtKB-KW

membrane

Inferred from electronic annotation. Source: UniProtKB-KW

viral capsid

Inferred from electronic annotation. Source: UniProtKB-KW

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

RNA binding

Inferred from electronic annotation. Source: UniProtKB-KW

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

ion channel activity

Inferred from electronic annotation. Source: UniProtKB-KW

structural molecule activity

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 245245Protein VP0 Potential
PRO_0000310674
Chain1 – 2323Protein VP4 Potential
PRO_0000310675
Chain24 – 245222Protein VP2 Potential
PRO_0000310676
Chain246 – 491246Protein VP3 Potential
PRO_0000310677
Chain492 – 836345Protein VP1-2A Potential
PRO_0000310678
Chain492 – 769278Protein VP1 Potential
PRO_0000310679
Chain770 – 83667Protein 2A Potential
PRO_0000310680
Chain837 – 1422586Protein 2BC Potential
PRO_0000310681
Chain837 – 1087251Protein 2B Potential
PRO_0000310682
Chain1088 – 1422335Protein 2C Potential
PRO_0000310683
Chain1423 – 2228806Protein 3ABCD Potential
PRO_5000066775
Chain1423 – 1739317Protein 3ABC Potential
PRO_0000310684
Chain1423 – 151997Protein 3AB Potential
PRO_0000310685
Chain1423 – 149674Protein 3A Potential
PRO_0000310686
Chain1497 – 151923Protein 3B Potential
PRO_0000310687
Chain1520 – 2228709Protein 3CD Potential
PRO_0000310688
Chain1520 – 1739220Protease 3C Potential
PRO_0000310689
Chain1740 – 2228489RNA-directed RNA polymerase 3D-POL Potential
PRO_0000310690

Regions

Topological domain1 – 14671467Cytoplasmic Potential
Intramembrane1468 – 148215 Potential
Topological domain1483 – 2228746Cytoplasmic Potential
Domain1204 – 1366163SF3 helicase
Domain1520 – 1716197Peptidase C3
Domain1977 – 2098122RdRp catalytic
Nucleotide binding1230 – 12378ATP Potential
Coiled coil1127 – 115327 Potential

Sites

Active site15631For protease 3C activity By similarity
Active site16031For protease 3C activity By similarity
Active site16911For protease 3C activity By similarity
Site23 – 242Cleavage Potential
Site245 – 2462Cleavage; by protease 3C Potential
Site491 – 4922Cleavage; by protease 3C Potential
Site769 – 7702Cleavage; by host Potential
Site7691Important for VP1 folding and capsid assembly By similarity
Site836 – 8372Cleavage; by protease 3C By similarity
Site1087 – 10882Cleavage; by protease 3C Potential
Site1422 – 14232Cleavage; by protease 3C Potential
Site1496 – 14972Cleavage; by protease 3C Potential
Site1519 – 15202Cleavage; by protease 3C Potential
Site1739 – 17402Cleavage; by protease 3C By similarity

Amino acid modifications

Modified residue14991O-(5'-phospho-RNA)-tyrosine By similarity

Sequences

Sequence LengthMass (Da)Tools
Q9DWR1 [UniParc].

Last modified November 13, 2007. Version 4.
Checksum: A1C11AE46A6B96B0

FASTA2,228251,719
        10         20         30         40         50         60 
MNMSRQGIFQ TVGSGLDHIL SLADVEEEQM IQSVDRTAVT GASYFTSVDQ SSVHTAEVGS 

        70         80         90        100        110        120 
HQPEPLKTSV DKPGSKRTQG EKFFLIHSAD WLTTHALFHE VAKLDVVKLL YNEQFAVQGL 

       130        140        150        160        170        180 
LRYHTYARFG IEIQVQINPT PFQQGGLICA MVPGDQSYGS IASLTVYPHG LLNCNINNVV 

       190        200        210        220        230        240 
RIKVPFIYTR GAYHFKDPQY PVWELTIRVW SELNIGTGTS AYTSLNVLAR FTDLELHGLT 

       250        260        270        280        290        300 
PLSTQMMRNE FRVSTTENVV NLSNYEDARA KMSFALDQED WKSDASQGGG IKITHFTTWT 

       310        320        330        340        350        360 
SIPTLAAQFP FNASDSVGQQ IKVIPVDPYF FQMTNTNPEQ KCITALASIC QMFCFWRGDL 

       370        380        390        400        410        420 
VFDFQVFPTK YHSGRLLFCF VPGNELIDVS HITLKQATTA PCAVMDITGV QSTLRFRVPW 

       430        440        450        460        470        480 
ISDTPYRVNR YTKSSHQKGE YTAIGKLIVY CYNRLTSPSN VASHVRVNVY LSAINLECFA 

       490        500        510        520        530        540 
PLYHAMDVTT QVGDDSGGFS TTVSTKQNVP DPQVGITTVK DLKGRANQGK MDISGVQAPV 

       550        560        570        580        590        600 
GAITTIEDPV LAKKVPETFP ELKPGESRHT SDHMSIYKFM GRSHFLCTFT FNSNNKEYTF 

       610        620        630        640        650        660 
PITLSSTSNP PHGLPSTLRW FFNLFQLYRG PLDLTIIITG ATDVDGMAWF TPVGLAVDTP 

       670        680        690        700        710        720 
WVEKESALSI DYKTALGAVR FNTRRTGNIQ IRLPWYSYLY AVSGALDGLG DKTDSTFGLV 

       730        740        750        760        770        780 
SIQIANYNHS DEYLSFSCYL SVTEQSEFYF PRAPLNTNAM MSSETMMDRI ALGDLESSVD 

       790        800        810        820        830        840 
DPRSEEDRKF ESHIEKRKPY KELRLEVGKQ RLKYAQEELS NEVLPPPRKI KGVFSQAKIS 

       850        860        870        880        890        900 
LFYTEDHEIM KFSWKGITAD TRALRRFGFS LAAGRSVWTL EMDAGVLTGR LVRVNDEKWT 

       910        920        930        940        950        960 
EMKDDKIVSL VEKFTSNKHW SKVNFPHGML DLEEIAANAK EFPNMSETDL CFLLHWLNPK 

       970        980        990       1000       1010       1020 
KINLADRMLG LSGIQEIKEK GVGLIGECRA FLDSITSTLK SMMFGFHHSV TVEIINTVLC 

      1030       1040       1050       1060       1070       1080 
FVKSGILLYV IQQLNQEEHS HIIGLLRVMN YADIGCSVIS CGKVFSKMLE TVFNWQMDSR 

      1090       1100       1110       1120       1130       1140 
MMELRTQSIS NWLRDICSGI TIFKSFKDAI YWLYTKIREY YDLNYGNKKD VLNILKDHQQ 

      1150       1160       1170       1180       1190       1200 
KIERAIEEAD NFCVLQIQDV EKFEQYQKGV DLIQKLRTVH SMAQVDPGLT VHLAPLRDCI 

      1210       1220       1230       1240       1250       1260 
ARVHQKLKNL GSINQAMVPR CEPVVCYLYG KRGGGKSLTS IALATKICKH YGVEPEKNIY 

      1270       1280       1290       1300       1310       1320 
TKPVASDYWD GYSGQLVCII DDIGQNTTDE DWSDFCQLVS GCPMRLNMAS LEEKGRHFSS 

      1330       1340       1350       1360       1370       1380 
PFIIATSNWS NPSPKTVYVK EAIDRRLHFK VEVKPASFFK NPHNDMLNVN LAKTNDAIKD 

      1390       1400       1410       1420       1430       1440 
MSCVDLVMDN HNVSLSELLS SLVMTVEIRK QNMSEFMELW SQGLSDDDND SAVAEFFQSF 

      1450       1460       1470       1480       1490       1500 
PSGEPSGSRL SQFFQSVTNH KWVAVGAAVG VLGVLVGGWY VYKHFTKKQE ESIPSEGVYH 

      1510       1520       1530       1540       1550       1560 
GVTKPKQVIK LDADPVESQS TLEIAGLVRK NLVQFGVGEK NGCVRWVMNA LGIKDDWLLV 

      1570       1580       1590       1600       1610       1620 
PSHAYKFEKD YEMMEFYFNR GGTYYSISAG NVVIQSLDVG FQDVVLMKVP TIPKFRDITE 

      1630       1640       1650       1660       1670       1680 
HFIKKSDVPR ALNRLATLVT TVNGTPMLIS EGPLKMEEKA TYVHKKNDGT TIDLTVDQAW 

      1690       1700       1710       1720       1730       1740 
RGKGEGLPGM CGGALISSNQ SIQNAILGIH VAGGNSILVA KLVTQEMFQN IDKKIVESQR 

      1750       1760       1770       1780       1790       1800 
IMKVEFTQCS MNVVSKTLFR KSPIHHHIDK NMINFPAVMP FSRAEIDPMA VMLSKYSLPI 

      1810       1820       1830       1840       1850       1860 
VDEPDDYKDV SVFFQNKILG KSPLVDDFLD IEMAITGAPG IDAINMDSSP GYPYVQEKLT 

      1870       1880       1890       1900       1910       1920 
KRDLIWLDDN GMFLGLHPRL AQRILFNTTM MENCSDLDVV FTTCPKDELR PLDKVLESKT 

      1930       1940       1950       1960       1970       1980 
RAIDSCPLDY TILCRMYWGP AISYFHLNPG FHTGVAIGID PDRQWDQLFK TMIRFGDVGL 

      1990       2000       2010       2020       2030       2040 
DLDFSAFDAS LSPFMIREAG RILTEMSGAP VHFGEALINT IIYSKHLLYN CCYHVCGSMP 

      2050       2060       2070       2080       2090       2100 
SGSPCTALLN SIINNVNLYY VFSKIFKKSP VFFCDAVRIL CYGDDVLIVF SRQVQIDNLD 

      2110       2120       2130       2140       2150       2160 
SIGQRIVDEF KKLGMTATSA DKSVPQLKPV SELTFLKRSF NLVEDRIRPA IAEKTIWSLV 

      2170       2180       2190       2200       2210       2220 
AWQRNNAEFE QNLENAQWFA FMHGYEFYQQ FYHFVQSCLE KEMIEYRLKS YDWWRMKFND 


QCFVCDLS 

« Hide

References

[1]"Characterization and genetic variability of Hepatitis A virus genotype IIIA."
Stene-Johansen K., Jonassen T.O., Skaug K.
J. Gen. Virol. 86:2739-2745(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AJ299464 Genomic RNA. Translation: CAC14074.3. Different initiation.

3D structure databases

ProteinModelPortalQ9DWR1.
SMRQ9DWR1. Positions 1520-1735.
ModBaseSearch...
MobiDBSearch...

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Family and domain databases

InterProIPR004004. Helic/Pol/Pept_Calicivir-typ.
IPR000605. Helicase_SF3_ssDNA/RNA_vir.
IPR014759. Helicase_SF3_ssRNA_vir.
IPR024354. Hepatitis_A_VP1-2A.
IPR000199. Peptidase_C3A/C3B_picornavir.
IPR001676. Picornavirus_capsid.
IPR001205. RNA-dir_pol_C.
IPR007094. RNA-dir_pol_PSvirus.
IPR009003. Trypsin-like_Pept_dom.
[Graphical view]
PfamPF12944. DUF3840. 1 hit.
PF00548. Peptidase_C3. 1 hit.
PF00680. RdRP_1. 1 hit.
PF00073. Rhv. 2 hits.
PF00910. RNA_helicase. 1 hit.
[Graphical view]
PRINTSPR00918. CALICVIRUSNS.
SUPFAMSSF50494. SSF50494. 1 hit.
PROSITEPS50507. RDRP_SSRNA_POS. 1 hit.
PS51218. SF3_HELICASE_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Entry information

Entry namePOLG_HAVNO
AccessionPrimary (citable) accession number: Q9DWR1
Entry history
Integrated into UniProtKB/Swiss-Prot: November 13, 2007
Last sequence update: November 13, 2007
Last modified: April 16, 2014
This is version 83 of the entry and version 4 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