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P08617 (POLG_HAVHM) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 135. 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 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 IB (isolate HM175) (HHAV) (Human hepatitis A virus (isolate Human/Australia/HM175/1976)) [Reference proteome]
Taxonomic identifier12098 [NCBI]
Taxonomic lineageVirusesssRNA positive-strand viruses, no DNA stagePicornaviralesPicornaviridaeHepatovirus
Virus hostCercopithecus hamlyni (Owl-faced monkey) (Hamlyn's monkey) [TaxID: 9536]
Homo sapiens (Human) [TaxID: 9606]
Macaca (macaques) [TaxID: 9539]
Pan troglodytes (Chimpanzee) [TaxID: 9598]

Protein attributes

Sequence length2227 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

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. Ref.13 Ref.17 Ref.19 Ref.20 Ref.21 Ref.24

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. Ref.13 Ref.17 Ref.19 Ref.20 Ref.21 Ref.24

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 pentamerization of P1-2A, which is the precursor of the structural proteins. 2A is proteolytically removed from particulate VP1-2A by a host protease and does not seem to be found in mature particles. Ref.13 Ref.17 Ref.19 Ref.20 Ref.21 Ref.24

Protein 2B and 2BC precursor affect membrane integrity and cause an increase in membrane permeability. Ref.13 Ref.17 Ref.19 Ref.20 Ref.21 Ref.24

Protein 2C: Associates with and induces structural rearrangements of intracellular membranes. It displays RNA-binding, nucleotide binding and NTPase activities By similarity. Ref.13 Ref.17 Ref.19 Ref.20 Ref.21 Ref.24

Protein 3A, via its hydrophobic domain, serves as membrane anchor to the 3AB and 3ABC precursors. Ref.13 Ref.17 Ref.19 Ref.20 Ref.21 Ref.24

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. Ref.13 Ref.17 Ref.19 Ref.20 Ref.21 Ref.24

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. Ref.13 Ref.17 Ref.19 Ref.20 Ref.21 Ref.24

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. Ref.13 Ref.17 Ref.19 Ref.20 Ref.21 Ref.24

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. Ref.13 Ref.17 Ref.19 Ref.20 Ref.21 Ref.24

RNA-directed RNA polymerase 3D-POL replicates genomic and antigenomic RNA by recognizing replications specific signals. Ref.13 Ref.17 Ref.19 Ref.20 Ref.21 Ref.24

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. Ref.16 Ref.17 Ref.22 Ref.24

Subcellular location

Protein VP2: Virion. Host cytoplasm Potential Ref.14 Ref.24.

Protein VP3: Virion. Host cytoplasm Potential Ref.14 Ref.24.

Protein VP1: Virion. Host cytoplasm Potential Ref.14 Ref.24.

Protein VP1-2A: Virion. Host cytoplasm Potential Ref.14 Ref.24.

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. Ref.14 Ref.24

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. Ref.14 Ref.24

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. Ref.14 Ref.24

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. Ref.14 Ref.24

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. Ref.14 Ref.24

Protein 3B: Virion Potential Ref.14 Ref.24.

Protease 3C: Host cytoplasm Potential Ref.14 Ref.24.

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. Ref.14 Ref.24

Post-translational modification

Specific enzymatic cleavages by 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.

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.

Wild-type HM175 (HM175/wt) comes from a sample isolated from a patient in Australia in 1976 and subsequently passaged three times in marmosets. HM175/7 is an attenuated strain derived from HM175 by 32 passages in African green monkey kidney cells. HM175/18f, HM175/24a, and HM175/43c are cytopathic isolates derived from HM175 by serial passages in FRhK-4 cells.

Mutations in proteins 2B and 2C seem to be essential for strain HM175 adaptation to growth in cell culture.

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. In vitro, both are used, with a preference for Met-3.

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 AAA45466.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
   Biological processEukaryotic host gene expression shutoff by virus
Eukaryotic host translation shutoff by virus
Host gene expression 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 term3D-structure
Complete proteome
Direct protein sequencing
Reference 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

suppression by virus of host MAVS activity

Inferred from electronic annotation. Source: UniProtKB-KW

suppression by virus of host MAVS activity by MAVS proteolysis

Inferred from direct assay Ref.24. Source: UniProtKB

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 – 22272227Genome polyprotein
PRO_0000308969
Chain1 – 245245Protein VP0 Potential
PRO_0000308970
Chain1 – 2323Protein VP4 Potential
PRO_0000039946
Chain24 – 245222Protein VP2 Potential
PRO_0000039947
Chain246 – 491246Protein VP3 Potential
PRO_0000039948
Chain492 – 836345Protein VP1-2A Potential
PRO_0000308971
Chain492 – 769278Protein VP1 Potential
PRO_0000039949
Chain770 – 83667Protein 2A Potential
PRO_0000039950
Chain837 – 1422586Protein 2BC Potential
PRO_0000308972
Chain837 – 1087251Protein 2B Potential
PRO_0000039951
Chain1088 – 1422335Protein 2C Potential
PRO_0000039952
Chain1423 – 2227805Protein 3ABCD Potential
PRO_0000308973
Chain1423 – 1738316Protein 3ABC Potential
PRO_0000308974
Chain1423 – 151997Protein 3AB Potential
PRO_0000308975
Chain1423 – 149674Protein 3A Potential
PRO_0000039953
Chain1497 – 151923Protein 3B Potential
PRO_0000039954
Chain1520 – 2227708Protein 3CD Potential
PRO_0000308976
Chain1520 – 1738219Protease 3C Potential
PRO_0000039955
Chain1739 – 2227489RNA-directed RNA polymerase 3D-POL Potential
PRO_0000039956

Regions

Topological domain1 – 14671467Cytoplasmic Potential
Intramembrane1468 – 148215 Potential
Topological domain1483 – 2227745Cytoplasmic Potential
Domain1204 – 1366163SF3 helicase
Domain1520 – 1716197Peptidase C3
Domain1976 – 2097122RdRp catalytic
Nucleotide binding1230 – 12378ATP Potential
Coiled coil1127 – 115226 Potential

Sites

Active site15631For protease 3C activity
Active site16031For protease 3C activity
Active site16911For protease 3C activity
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
Site836 – 8372Cleavage; by protease 3C
Site1087 – 10882Cleavage; by protease 3C Potential
Site1422 – 14232Cleavage; by protease 3C Potential
Site1496 – 14972Cleavage; by protease 3C Potential
Site1519 – 15202Cleavage; by protease 3C Potential
Site1738 – 17392Cleavage; by protease 3C

Amino acid modifications

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

Natural variations

Natural variant771K → R in strain: HM175/7, HM175/18f, HM175/24a and HM175/43c.
Natural variant3151D → A in strain: HM175/24a and HM175/43c.
Natural variant3361T → K in strain: HM175/18f.
Natural variant6381I → V in strain: HM175/24a.
Natural variant6881N → S in strain: HM175/24a and HM175/43c.
Natural variant7621S → P in strain: HM175/18f.
Natural variant7641E → V in strain: HM175/7.
Natural variant7671M → V in strain: HM175/24a and HM175/43c.
Natural variant8211N → S in strain: HM175/7.
Natural variant8381K → N in strain: HM175/18f, HM175/24a and HM175/43c.
Natural variant8491I → M in strain: HM175/18f, HM175/24a and HM175/43c.
Natural variant9411D → E in 24.
Natural variant9931D → H in strain: HM175/18f, HM175/24a and HM175/43c.
Natural variant10521A → V in strain: HM175/7, HM175/18f, HM175/24a and HM175/43c.
Natural variant10621G → A in strain: HM175/7.
Natural variant1109 – 11113AIY → GIC in strain: HM175/18f, HM175/24a and HM175/43c.
Natural variant11181K → M in strain: HM175/7.
Natural variant11511E → K in strain: HM175/7, HM175/18f, HM175/24a and HM175/43c.
Natural variant11631F → S in strain: HM175/7, HM175/18f, HM175/24a and HM175/43c.
Natural variant11801H → Y in strain: HM175/18f, HM175/24a and HM175/43c.
Natural variant12121S → F in strain: HM175/18f, HM175/24a and HM175/43c.
Natural variant12291Y → H in strain: HM175/18f, HM175/24a and HM175/43c.
Natural variant12771V → I in strain: HM175/7.
Natural variant14071E → D in strain: HM175/18f, HM175/24a and HM175/43c.
Natural variant14281Missing in strain: HM175/18f, HM175/24a and HM175/43c.
Natural variant14801F → V in strain: HM175/18f, HM175/24a and HM175/43c.
Natural variant14871R → H in strain: HM175/18f, HM175/24a and HM175/43c.
Natural variant15001H → Y in strain: HM175/7.
Natural variant15071Q → H in strain: HM175/18f, HM175/24a and HM175/43c.
Natural variant15241I → V in strain: HM175/43c.
Natural variant16201Q → E in strain: HM175/18f and HM175/24a.
Natural variant16751T → A in strain: HM175/43c.
Natural variant18051D → G in strain: HM175/7, HM175/18f, HM175/24a and HM175/43c.
Natural variant19301S → T in strain: HM175/7, HM175/18f, HM175/24a and HM175/43c.
Natural variant19621R → K in strain: HM175/18f, HM175/24a and HM175/43c.

Experimental info

Mutagenesis7691R → M: Complete loss of viral particles assembly. Ref.22
Mutagenesis8361Q → N: Partial loss of 2A-2B cleavage. Ref.5
Mutagenesis8361Q → R: Complete loss of 2A-2B cleavage. Ref.5
Mutagenesis16711T → A: Complete loss of enzymatic activity.
Mutagenesis16911C → A: Complete loss of proteolytic activity. Ref.23
Sequence conflict18251D → V in AAA45476. Ref.4
Sequence conflict18501G → R in AAA45476. Ref.4
Sequence conflict18561E → G in AAA45476. Ref.4

Secondary structure

.............................................. 2227
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P08617 [UniParc].

Last modified August 1, 1988. Version 1.
Checksum: 01E225E7AEB740A6

FASTA2,227251,508
        10         20         30         40         50         60 
MNMSRQGIFQ TVGSGLDHIL SLADIEEEQM IQSVDRTAVT GASYFTSVDQ SSVHTAEVGS 

        70         80         90        100        110        120 
HQVEPLRTSV DKPGSKKTQG 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 WKSDPSQGGG IKITHFTTWT 

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

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

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

       490        500        510        520        530        540 
PLYHAMDVTT QVGDDSGGFS TTVSTEQNVP DPQVGITTMK DLKGKANRGK MDVSGVQAPV 

       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 PRAPLNSNAM LSTESMMSRI AAGDLESSVD 

       790        800        810        820        830        840 
DPRSEEDKRF ESHIECRKPY KELRLEVGKQ RLKYAQEELS NEVLPPPRKM KGLFSQAKIS 

       850        860        870        880        890        900 
LFYTEEHEIM KFSWRGVTAD TRALRRFGFS LAAGRSVWTL EMDAGVLTGR LIRLNDEKWT 

       910        920        930        940        950        960 
EMKDDKIVSL IEKFTSNKYW SKVNFPHGML DLEEIAANSK DFPNMSETDL CFLLHWLNPK 

       970        980        990       1000       1010       1020 
KINLADRMLG LSGVQEIKEQ GVGLIAECRT FLDSIAGTLK SMMFGFHHSV TVEIINTVLC 

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

      1090       1100       1110       1120       1130       1140 
MMELRTQSFS NWLRDICSGI TIFKNFKDAI YWLYTKLKDF YEVNYGKKKD ILNILKDNQQ 

      1150       1160       1170       1180       1190       1200 
KIEKAIEEAD EFCILQIQDV EKFEQYQKGV DLIQKLRTVH SMAQVDPNLM VHLSPLRDCI 

      1210       1220       1230       1240       1250       1260 
ARVHQKLKNL GSINQAMVTR 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 
MSCVDLIMDG HNVSLMDLLS SLVMTVEIRK QNMTEFMELW SQGISDDDND SAVAEFFQSF 

      1450       1460       1470       1480       1490       1500 
PSGEPSNSKL SGFFQSVTNH KWVAVGAAVG ILGVLVGGWF VYKHFSRKEE EPIPAEGVYH 

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

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

      1630       1640       1650       1660       1670       1680 
HFIKKGDVPR ALNRLATLVT TVNGTPMLIS EGPLKMEEKA TYVHKKNDGT TVDLTVDQAW 

      1690       1700       1710       1720       1730       1740 
RGKGEGLPGM CGGALVSSNQ SIQNAILGIH VAGGNSILVA KLVTQEMFQN IDKKIESQRI 

      1750       1760       1770       1780       1790       1800 
MKVEFTQCSM NVVSKTLFRK SPIYHHIDKT MINFPAAMPF SKAEIDPMAV MLSKYSLPIV 

      1810       1820       1830       1840       1850       1860 
EEPEDYKEAS IFYQNKIVGK TQLVDDFLDL DMAITGAPGI DAINMDSSPG FPYVQEKLTK 

      1870       1880       1890       1900       1910       1920 
RDLIWLDENG LLLGVHPRLA QRILFNTVMM ENCSDLDVVF TTCPKDELRP LEKVLESKTR 

      1930       1940       1950       1960       1970       1980 
AIDACPLDYS ILCRMYWGPA ISYFHLNPGF HTGVAIGIDP DRQWDELFKT MIRFGDVGLD 

      1990       2000       2010       2020       2030       2040 
LDFSAFDASL SPFMIREAGR IMSELSGTPS HFGTALINTI IYSKHLLYNC CYHVCGSMPS 

      2050       2060       2070       2080       2090       2100 
GSPCTALLNS IINNVNLYYV FSKIFGKSPV FFCQALKILC YGDDVLIVFS RDVQIDNLDL 

      2110       2120       2130       2140       2150       2160 
IGQKIVDEFK KLGMTATSAD KNVPQLKPVS ELTFLKRSFN LVEDRIRPAI SEKTIWSLIA 

      2170       2180       2190       2200       2210       2220 
WQRSNAEFEQ NLENAQWFAF MHGYEFYQKF YYFVQSCLEK EMIEYRLKSY DWWRMRFYDQ 


CFICDLS 

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References

[1]"Complete nucleotide sequence of wild-type hepatitis A virus: comparison with different strains of hepatitis A virus and other picornaviruses."
Cohen J.I., Ticehurst J.R., Purcell R.H., Buckler-White A., Baroudy B.M.
J. Virol. 61:50-59(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
Strain: HM175/wt.
[2]"Complete nucleotide sequence of an attenuated hepatitis A virus: comparison with wild-type virus."
Cohen J.I., Rosenblum B., Ticehurst J.R., Daemer R.J., Feinstone S.M., Purcell R.H.
Proc. Natl. Acad. Sci. U.S.A. 84:2497-2501(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
Strain: HM175/7 MK-5.
[3]"Antigenic and genetic variation in cytopathic hepatitis A virus variants arising during persistent infection: evidence for genetic recombination."
Lemon S.M., Murphy P.C., Shields P.A., Ping L.H., Feinstone S.M., Cromeans T., Jansen R.W.
J. Virol. 65:2056-2065(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
Strain: HM175/18f, HM175/24a and HM175/43c.
[4]"Sequence analysis of hepatitis A virus cDNA coding for capsid proteins and RNA polymerase."
Baroudy B.M., Ticehurst J.R., Miele T.A., Maizel J.V. Jr., Purcell R.H., Feinstone S.M.
Proc. Natl. Acad. Sci. U.S.A. 82:2143-2147(1985) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1-854 AND 1724-2227.
[5]"Identification and site-directed mutagenesis of the primary (2A/2B) cleavage site of the hepatitis A virus polyprotein: functional impact on the infectivity of HAV RNA transcripts."
Martin A., Escriou N., Chao S.-F., Girard M., Lemon S.M., Wychowski C.
Virology 213:213-222(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 837-856, PROTEOLYTIC PROCESSING OF POLYPROTEIN, MUTAGENESIS OF GLN-836.
Strain: HM175p35.
[6]"Molecular cloning and characterization of hepatitis A virus cDNA."
Ticehurst J.R., Racaniello V.R., Baroudy B.M., Baltimore D., Purcell R.H., Feinstone S.M.
Proc. Natl. Acad. Sci. U.S.A. 80:5885-5889(1983) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 2090-2227.
[7]"Proteolytic activity of hepatitis A virus 3C protein."
Jia X.-Y., Ehrenfeld E., Summers D.F.
J. Virol. 65:2595-2600(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEOLYTIC PROCESSING OF POLYPROTEIN.
[8]"Hepatitis A virus polyprotein synthesis initiates from two alternative AUG codons."
Tesar M., Harmon S.A., Summers D.F., Ehrenfeld E.
Virology 186:609-618(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION OF N-TERMINUS.
Strain: HM175/7.
[9]"Analysis of a potential myristoylation site in hepatitis A virus capsid protein VP4."
Tesar M., Jia X.-Y., Summers D.F., Ehrenfeld E.
Virology 194:616-626(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF PROTEIN VP4.
Strain: HM175/7.
[10]"Primary cleavage of the HAV capsid protein precursor in the middle of the proposed 2A coding region."
Jia X.-Y., Summers D.F., Ehrenfeld E.
Virology 193:515-519(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEOLYTIC PROCESSING OF POLYPROTEIN.
[11]"Expression of hepatitis A virus precursor protein P3 in vivo and in vitro: polyprotein processing of the 3CD cleavage site."
Tesar M., Pak I., Jia X.-Y., Richards O.C., Summers D.F., Ehrenfeld E.
Virology 198:524-533(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEOLYTIC PROCESSING OF POLYPROTEIN.
[12]"Proteinase 3C-mediated processing of VP1-2A of two hepatitis A virus strains: in vivo evidence for cleavage at amino acid position 273/274 of VP1."
Probst C., Jecht M., Gauss-Mueller V.
J. Virol. 71:3288-3292(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEOLYTIC PROCESSING OF POLYPROTEIN.
[13]"Induction of intracellular membrane rearrangements by HAV proteins 2C and 2BC."
Teterina N.L., Bienz K., Egger D., Gorbalenya A.E., Ehrenfeld E.
Virology 237:66-77(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION OF PROTEIN 2C, FUNCTION OF PROTEIN 2BC.
Strain: HM175/24a, HM175/wt and HM175p35.
[14]"Membrane association and RNA binding of recombinant hepatitis A virus protein 2C."
Kusov Y.Y., Probst C., Jecht M., Jost P.D., Gauss-Mueller V.
Arch. Virol. 143:931-944(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION OF PROTEIN 2C, RNA-BINDING.
[15]"Processing of proteinase precursors and their effect on hepatitis A virus particle formation."
Probst C., Jecht M., Gauss-Mueller V.
J. Virol. 72:8013-8020(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEOLYTIC PROCESSING OF POLYPROTEIN.
[16]"The human homolog of HAVcr-1 codes for a hepatitis A virus cellular receptor."
Feigelstock D., Thompson P., Mattoo P., Zhang Y., Kaplan G.G.
J. Virol. 72:6621-6628(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION OF CAPSID WITH HUMAN HAVCR1.
[17]"Mapping of protein domains of hepatitis A virus 3AB essential for interaction with 3CD and viral RNA."
Beneduce F., Ciervo A., Kusov Y.Y., Gauss-Mueller V., Morace G.
Virology 264:410-421(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION OF PROTEIN 3AB, SUBUNIT, INTERACTION OF PROTEIN 3AB WITH PROTEIN 3CD.
Strain: HM175/7.
[18]"Hepatitis A virus capsid protein VP1 has a heterogeneous C terminus."
Graff J., Richards O.C., Swiderek K.M., Davis M.T., Rusnak F., Harmon S.A., Jia X.-Y., Summers D.F., Ehrenfeld E.
J. Virol. 73:6015-6023(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEOLYTIC PROCESSING OF POLYPROTEIN.
Strain: HM175p35 and HM175pE.
[19]"Membrane permeability induced by hepatitis A virus proteins 2B and 2BC and proteolytic processing of HAV 2BC."
Jecht M., Probst C., Gauss-Mueller V.
Virology 252:218-227(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION OF PROTEIN 2B, FUNCTION OF PROTEIN 2BC.
[20]"Intrinsic signals for the assembly of hepatitis A virus particles. Role of structural proteins VP4 and 2A."
Probst C., Jecht M., Gauss-Mueller V.
J. Biol. Chem. 274:4527-4531(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION OF PROTEIN VP1-2A, FUNCTION OF PROTEIN VP4.
[21]"Analysis of deletion mutants indicates that the 2A polypeptide of hepatitis A virus participates in virion morphogenesis."
Cohen L., Benichou D., Martin A.
J. Virol. 76:7495-7505(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION OF PROTEIN 2A.
Strain: HM175/18f.
[22]"Homogenous hepatitis A virus particles. Proteolytic release of the assembly signal 2A from procapsids by factor Xa."
Rachow A., Gauss-Mueller V., Probst C.
J. Biol. Chem. 278:29744-29751(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: CLEAVAGE OF PROTEIN VP1-2A, SUBUNIT, MUTAGENESIS OF ARG-769.
[23]"Hepatitis A virus proteinase 3C binding to viral RNA: correlation with substrate binding and enzyme dimerization."
Peters H., Kusov Y.Y., Meyer S., Benie A.J., Baeuml E., Wolff M., Rademacher C., Peters T., Gauss-Mueller V.
Biochem. J. 385:363-370(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF CYS-1691.
[24]"Disruption of innate immunity due to mitochondrial targeting of a picornaviral protease precursor."
Yang Y., Liang Y., Qu L., Chen Z., Yi M., Li K., Lemon S.M.
Proc. Natl. Acad. Sci. U.S.A. 104:7253-7258(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION OF PROTEIN 3ABC, SUBCELLULAR LOCATION OF PROTEIN 3ABC, INTERACTION OF PROTEIN 3ABC WITH HUMAN MAVS.
Strain: HM175/18f.
[25]"RNA interaction and cleavage of poly(C)-binding protein 2 by hepatitis A virus protease."
Zhang B., Seitz S., Kusov Y., Zell R., Gauss-Mueller V.
Biochem. Biophys. Res. Commun. 364:725-730(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: CLEAVAGE OF HOST PCBP2 BY PROTEASE 3C.
[26]"Picornaviral 3C cysteine proteinases have a fold similar to chymotrypsin-like serine proteinases."
Allaire M., Chernaia M.M., Malcolm B.A., James M.N.
Nature 369:72-76(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 1520-1736.
[27]"The refined crystal structure of the 3C gene product from hepatitis A virus: specific proteinase activity and RNA recognition."
Bergmann E.M., Mosimann S.C., Chernaia M.M., Malcolm B.A., James M.N.G.
J. Virol. 71:2436-2448(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 1520-1736.
[28]"Crystal structure of an inhibitor complex of the 3C proteinase from hepatitis A virus (HAV) and implications for the polyprotein processing in HAV."
Bergmann E.M., Cherney M.M., Mckendrick J., Frormann S., Luo C., Malcolm B.A., Vederas J.C., James M.N.G.
Virology 265:153-163(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 1520-1736 IN COMPLEX WITH THE INHIBITOR IODOACETYL-VALYL-PHENYLALANYL-AMIDE.
[29]"An episulfide cation (thiiranium ring) trapped in the active site of HAV 3C proteinase inactivated by peptide-based ketone inhibitors."
Yin J., Cherney M.M., Bergmann E.M., Zhang J., Huitema C., Pettersson H., Eltis L.D., Vederas J.C., James M.N.G.
J. Mol. Biol. 361:673-686(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.35 ANGSTROMS) OF 1520-1731 IN COMPLEX WITH PEPTIDE-BASED KETONE INHIBITORS.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M14707 Genomic RNA. Translation: AAA45465.1.
M14707 Genomic RNA. Translation: AAA45466.1. Different initiation.
M16632 Genomic RNA. Translation: AAA45471.1.
M59808 Genomic RNA. Translation: AAA45467.1.
M59809 Genomic RNA. Translation: AAA45469.1.
M59810 Genomic RNA. Translation: AAA45468.1.
M14114 Genomic RNA. Translation: AAA45475.1.
M14115 Genomic RNA. Translation: AAA45476.1.
K00386 Genomic RNA. No translation available.
PIRA03905.
GNNYHM. A25981.
GNNYMK. A94149.
RefSeqNP_041007.1. NC_001489.1.
NP_041008.1. NC_001489.1.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1HAVX-ray2.00A/B1520-1736[»]
1QA7X-ray1.90A/B/C/D1520-1736[»]
2H6MX-ray1.40A1520-1731[»]
2H9HX-ray1.39A1520-1731[»]
2HALX-ray1.35A1520-1731[»]
ProteinModelPortalP08617.
SMRP08617. Positions 1520-1735.
ModBaseSearch...
MobiDBSearch...

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID1493918.
1493919.

Family and domain databases

Gene3D2.60.120.20. 3 hits.
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.
IPR029053. Viral_coat.
[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...

Other

EvolutionaryTraceP08617.

Entry information

Entry namePOLG_HAVHM
AccessionPrimary (citable) accession number: P08617
Secondary accession number(s): P06443 expand/collapse secondary AC list , P26580, P26581, P26582, Q81082, Q81094
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1988
Last sequence update: August 1, 1988
Last modified: July 9, 2014
This is version 135 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