POLG_HAVHA
ID POLG_HAVHA Reviewed; 2052 AA.
AC Q05794; Q67800; Q67801; Q67802; Q67803; Q67804; Q67805; Q67806; Q67807;
DT 13-NOV-2007, integrated into UniProtKB/Swiss-Prot.
DT 13-NOV-2007, sequence version 2.
DT 03-AUG-2022, entry version 111.
DE RecName: Full=Genome polyprotein;
DE Contains:
DE RecName: Full=Capsid protein VP0;
DE AltName: Full=VP4-VP2;
DE Contains:
DE RecName: Full=Capsid protein VP4;
DE AltName: Full=P1A;
DE AltName: Full=Virion protein 4;
DE Contains:
DE RecName: Full=Capsid protein VP2;
DE AltName: Full=P1B;
DE AltName: Full=Virion protein 2;
DE Contains:
DE RecName: Full=Capsid protein VP3;
DE AltName: Full=P1C;
DE AltName: Full=Virion protein 3;
DE Contains:
DE RecName: Full=Protein VP1-2A;
DE AltName: Full=VPX;
DE Contains:
DE RecName: Full=Capsid protein VP1;
DE AltName: Full=P1D;
DE AltName: Full=Virion protein 1;
DE Contains:
DE RecName: Full=Assembly signal 2A;
DE AltName: Full=pX {ECO:0000250|UniProtKB:P08617};
DE Contains:
DE RecName: Full=Protein 2BC;
DE Contains:
DE RecName: Full=Protein 2B;
DE Short=P2B;
DE Contains:
DE RecName: Full=Protein 2C;
DE Short=P2C;
DE EC=3.6.1.15;
DE Contains:
DE RecName: Full=Protein 3ABCD;
DE Short=P3;
DE Contains:
DE RecName: Full=Protein 3ABC;
DE Contains:
DE RecName: Full=Protein 3AB;
DE Contains:
DE RecName: Full=Protein 3A;
DE Short=P3A;
DE Contains:
DE RecName: Full=Viral protein genome-linked;
DE Short=VPg;
DE AltName: Full=Protein 3B;
DE Short=P3B;
DE Contains:
DE RecName: Full=Protein 3CD;
DE Contains:
DE RecName: Full=Protease 3C;
DE Short=P3C;
DE EC=3.4.22.28 {ECO:0000250|UniProtKB:P08617};
DE AltName: Full=Picornain 3C;
DE Contains:
DE RecName: Full=RNA-directed RNA polymerase 3D-POL;
DE Short=P3D-POL;
DE EC=2.7.7.48 {ECO:0000250|UniProtKB:P08617};
DE Flags: Fragments;
OS Human hepatitis A virus genotype IA (isolate HAS-15) (HHAV) (Human
OS hepatitis A virus (isolate Human/Arizona/HAS-15/1979)).
OC Viruses; Riboviria; Orthornavirae; Pisuviricota; Pisoniviricetes;
OC Picornavirales; Picornaviridae; Hepatovirus.
OX NCBI_TaxID=470424;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RA Sverdlov S.D., Tsarev S.A., Markova S.V., Vasilenko S.K., Chizhikov V.E.,
RA Petrov N.A., Kusov Y.Y., Nastashenko T.A., Balayan M.S.;
RT "Cloning and expression of hepatitis A virus genome in E. coli cells.";
RL Mol. Genet. Microbiol. Virol. 6:129-133(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1-906.
RX PubMed=3000718;
RA Ovchinnikov Y.A., Sverdlov E.D., Tsarev S.A., Arsenian S.G., Rokhlina T.O.;
RT "Sequence of 3372 RNA nucleotide links in the hepatitis A virus coding for
RT capsid VP4-VP1 and nonstructural proteins.";
RL Dokl. Akad. Nauk SSSR 285:1014-1018(1985).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 758-813.
RX PubMed=1318940; DOI=10.1099/0022-1317-73-6-1365;
RA Robertson B.H., Jansen R.W., Khanna B., Totsuka A., Nainan O.V., Siegl G.,
RA Widell A., Margolis H.S., Isomura S., Ito K., Ishizu T., Moritsugu Y.,
RA Lemon S.M.;
RT "Genetic relatedness of hepatitis A virus strains recovered from different
RT geographical regions.";
RL J. Gen. Virol. 73:1365-1377(1992).
CC -!- FUNCTION: [Capsid protein VP1]: Capsid proteins VP1, VP2, and VP3 form
CC a closed capsid enclosing the viral positive strand RNA genome. All
CC these proteins contain a beta-sheet structure called beta-barrel jelly
CC roll. Together they form an icosahedral capsid (T=3) composed of 60
CC copies of each VP1, VP2, and VP3, with a diameter of approximately 300
CC Angstroms. VP1 is situated at the 12 fivefold axes, whereas VP2 and VP3
CC are located at the quasi-sixfold axes. The naked capsid interacts with
CC the host receptor HAVCR1 to provide virion attachment to and probably
CC entry into the target cell. {ECO:0000250|UniProtKB:P08617}.
CC -!- FUNCTION: [Capsid protein VP2]: Capsid proteins VP1, VP2, and VP3 form
CC a closed capsid enclosing the viral positive strand RNA genome. All
CC these proteins contain a beta-sheet structure called beta-barrel jelly
CC roll. Together they form an icosahedral capsid (T=3) composed of 60
CC copies of each VP1, VP2, and VP3, with a diameter of approximately 300
CC Angstroms. VP1 is situated at the 12 fivefold axes, whereas VP2 and VP3
CC are located at the quasi-sixfold axes. The naked capsid interacts with
CC the host receptor HAVCR1 to provide virion attachment to and probably
CC entry into the target cell. {ECO:0000250|UniProtKB:P08617}.
CC -!- FUNCTION: [Capsid protein VP3]: Capsid proteins VP1, VP2, and VP3 form
CC a closed capsid enclosing the viral positive strand RNA genome. All
CC these proteins contain a beta-sheet structure called beta-barrel jelly
CC roll. Together they form an icosahedral capsid (T=3) composed of 60
CC copies of each VP1, VP2, and VP3, with a diameter of approximately 300
CC Angstroms. VP1 is situated at the 12 fivefold axes, whereas VP2 and VP3
CC are located at the quasi-sixfold axes. The naked capsid interacts with
CC the host receptor HAVCR1 to provide virion attachment to and probably
CC entry into the target cell. {ECO:0000250|UniProtKB:P08617}.
CC -!- FUNCTION: [Capsid protein VP0]: VP0 precursor is a component of the
CC immature procapsids. {ECO:0000250|UniProtKB:P08617}.
CC -!- FUNCTION: [Capsid protein VP4]: Plays a role in the assembly of the 12
CC pentamers into an icosahedral structure. Has not been detected in
CC mature virions, supposedly owing to its small size.
CC {ECO:0000250|UniProtKB:P08617}.
CC -!- FUNCTION: [Protein VP1-2A]: Precursor component of immature procapsids
CC that corresponds to an extended form of the structural protein VP1.
CC After maturation, possibly by the host Cathepsin L, the assembly signal
CC 2A is cleaved to give rise to the mature VP1 protein.
CC {ECO:0000250|UniProtKB:P08617}.
CC -!- FUNCTION: [Protein 2B]: Functions as a viroporin. Affects membrane
CC integrity and causes an increase in membrane permeability. Involved in
CC host intracellular membrane rearrangements probably to give rise to the
CC viral factories. Does not disrupt calcium homeostasis or glycoprotein
CC trafficking. Antagonizes the innate immune response of the host by
CC suppressing IFN-beta synthesis, which it achieves by interfering with
CC the DDX58/IFIH1 (RIG-I/MDA5) pathway. {ECO:0000250|UniProtKB:P08617}.
CC -!- FUNCTION: [Protein 2BC]: Affects membrane integrity and causes an
CC increase in membrane permeability. {ECO:0000250|UniProtKB:P08617}.
CC -!- FUNCTION: [Protein 2C]: Associates with and induces structural
CC rearrangements of intracellular membranes. Displays RNA-binding
CC activity. {ECO:0000250|UniProtKB:P08617}.
CC -!- FUNCTION: [Protein 3ABC]: The precursor 3ABC is targeted to the
CC mitochondrial membrane where protease 3C activity cleaves and inhibits
CC the host antiviral protein MAVS, thereby disrupting activation of IRF3
CC through the IFIH1/MDA5 pathway. In vivo, the protease activity of 3ABC
CC precursor is more efficient in cleaving the 2BC precursor than that of
CC protein 3C. The 3ABC precursor may therefore play a role in the
CC proteolytic processing of the polyprotein. Possible viroporin.
CC {ECO:0000250|UniProtKB:P08617}.
CC -!- FUNCTION: [Protein 3AB]: Interacts with the 3CD precursor and with RNA
CC structures found at both the 5'- and 3'-termini of the viral genome.
CC Since the 3AB precursor contains the hydrophobic domain 3A, it probably
CC anchors the whole viral replicase complex to intracellular membranes on
CC which viral RNA synthesis occurs. {ECO:0000250|UniProtKB:P08617}.
CC -!- FUNCTION: [Protein 3A]: May serve as membrane anchor to the 3AB and
CC 3ABC precursors via its hydrophobic domain. May interact with RNA.
CC {ECO:0000250|UniProtKB:P08617}.
CC -!- FUNCTION: [Viral protein genome-linked]: Acts as a primer for viral RNA
CC replication and remains covalently bound to viral genomic RNA. VPg is
CC uridylylated prior to priming replication into VPg-pUpU. The VPg-pUpU
CC is then used as primer on the genomic RNA poly(A) by the RNA-dependent
CC RNA polymerase to replicate the viral genome.
CC {ECO:0000250|UniProtKB:P03300, ECO:0000250|UniProtKB:P08617}.
CC -!- FUNCTION: [Protease 3C]: Cysteine protease that generates mature viral
CC proteins from the precursor polyprotein. In addition to its proteolytic
CC activity, it binds to viral RNA, and thus influences viral genome
CC replication. RNA and substrate bind cooperatively to the protease.
CC Cleaves IKBKG/NEMO to impair innate immune signaling. Cleaves host
CC PABPC1 which may participate in the switch of viral translation to RNA
CC synthesis. {ECO:0000250|UniProtKB:P08617}.
CC -!- FUNCTION: [Protein 3CD]: Interacts with the 3AB precursor and with RNA
CC structures found at both the 5'- and 3'-termini of the viral genome.
CC Disrupts TLR3 signaling by degrading the host adapter protein
CC TICAM1/TRIF. {ECO:0000250|UniProtKB:P08617}.
CC -!- FUNCTION: RNA-directed RNA polymerase 3D-POL replicates genomic and
CC antigenomic RNA by recognizing replications specific signals.
CC {ECO:0000250|UniProtKB:P08617}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a ribonucleoside 5'-triphosphate + RNA(n) = diphosphate +
CC RNA(n+1); Xref=Rhea:RHEA:21248, Rhea:RHEA-COMP:14527, Rhea:RHEA-
CC COMP:17342, ChEBI:CHEBI:33019, ChEBI:CHEBI:61557, ChEBI:CHEBI:140395;
CC EC=2.7.7.48; Evidence={ECO:0000250|UniProtKB:P08617,
CC ECO:0000255|PROSITE-ProRule:PRU00539};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a ribonucleoside 5'-triphosphate + H2O = a ribonucleoside 5'-
CC diphosphate + H(+) + phosphate; Xref=Rhea:RHEA:23680,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:57930, ChEBI:CHEBI:61557; EC=3.6.1.15;
CC Evidence={ECO:0000250|UniProtKB:P08617};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Selective cleavage of Gln-|-Gly bond in the poliovirus
CC polyprotein. In other picornavirus reactions Glu may be substituted
CC for Gln, and Ser or Thr for Gly.; EC=3.4.22.28;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU01222};
CC -!- SUBUNIT: [Protein 2B]: Homodimer. Homomultimer; probably interacts with
CC membranes in a multimeric form. Seems to assemble into amyloid-like
CC fibers. {ECO:0000250|UniProtKB:P08617}.
CC -!- SUBUNIT: [Protein 3AB]: Homodimer. Monomer. Interacts with protein 3CD.
CC {ECO:0000250|UniProtKB:P08617}.
CC -!- SUBUNIT: [Protein 3A]: Interacts with host ACBD3 (By similarity).
CC {ECO:0000250|UniProtKB:P08617}.
CC -!- SUBUNIT: [Protein 3CD]: Interacts with protein 3AB.
CC {ECO:0000250|UniProtKB:P08617}.
CC -!- SUBUNIT: [Protein 3ABC]: Interacts with human MAVS.
CC {ECO:0000250|UniProtKB:P08617}.
CC -!- SUBUNIT: [Protease 3C]: Homodimer; disulfide-linked.
CC {ECO:0000250|UniProtKB:P08617}.
CC -!- SUBUNIT: [Protein VP1-2A]: Homopentamer. Homooligomer.
CC {ECO:0000250|UniProtKB:P08617}.
CC -!- SUBUNIT: [Capsid protein VP1]: Interacts with capsid protein VP2.
CC Interacts with capsid protein VP3. {ECO:0000250|UniProtKB:P08617}.
CC -!- SUBUNIT: [Capsid protein VP2]: Interacts with capsid protein VP1.
CC Interacts with capsid protein VP3. {ECO:0000250|UniProtKB:P08617}.
CC -!- SUBUNIT: [Capsid protein VP3]: Interacts with capsid protein VP1.
CC Interacts with capsid protein VP2. {ECO:0000250|UniProtKB:P08617}.
CC -!- SUBCELLULAR LOCATION: [Capsid protein VP2]: Virion
CC {ECO:0000250|UniProtKB:P08617}. Host endosome, host multivesicular body
CC {ECO:0000250|UniProtKB:P08617}. Note=The egress of newly formed virions
CC occurs through an exosome-like mechanism involving endosomal budding of
CC viral capsids into multivesicular bodies.
CC {ECO:0000250|UniProtKB:P08617}.
CC -!- SUBCELLULAR LOCATION: [Capsid protein VP3]: Virion
CC {ECO:0000250|UniProtKB:P08617}. Host endosome, host multivesicular body
CC {ECO:0000250|UniProtKB:P08617}. Note=The egress of newly formed virions
CC occurs through an exosome-like mechanism involving endosomal budding of
CC viral capsids into multivesicular bodies.
CC {ECO:0000250|UniProtKB:P08617}.
CC -!- SUBCELLULAR LOCATION: [Capsid protein VP1]: Virion
CC {ECO:0000250|UniProtKB:P08617}. Host endosome, host multivesicular body
CC {ECO:0000250|UniProtKB:P08617}. Note=The egress of newly formed virions
CC occurs through an exosome-like mechanism involving endosomal budding of
CC viral capsids into multivesicular bodies.
CC {ECO:0000250|UniProtKB:P08617}.
CC -!- SUBCELLULAR LOCATION: [Capsid protein VP4]: Virion
CC {ECO:0000250|UniProtKB:P08617}. Note=Present in the full mature virion.
CC The egress of newly formed virions occurs through an exosome-like
CC mechanism involving endosomal budding of viral capsids into
CC multivesicular bodies. {ECO:0000250|UniProtKB:P08617}.
CC -!- SUBCELLULAR LOCATION: [Protein 2B]: Host membrane
CC {ECO:0000250|UniProtKB:P08617}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:P08617}. Note=Probably localizes to
CC intracellular membrane vesicles that are induced after virus infection
CC as the site for viral RNA replication. {ECO:0000250|UniProtKB:P08617}.
CC -!- SUBCELLULAR LOCATION: [Protein 2C]: Host membrane
CC {ECO:0000250|UniProtKB:P08617}; Single-pass membrane protein
CC {ECO:0000250|UniProtKB:P08617}. Note=Probably localizes to
CC intracellular membrane vesicles that are induced after virus infection
CC as the site for viral RNA replication. May associate with membranes
CC through a N-terminal amphipathic helix. {ECO:0000250|UniProtKB:P08617}.
CC -!- SUBCELLULAR LOCATION: [Protein 3ABC]: Host membrane
CC {ECO:0000250|UniProtKB:P08617}; Single-pass membrane protein
CC {ECO:0000255}. Host mitochondrion outer membrane
CC {ECO:0000250|UniProtKB:P08617}; Single-pass membrane protein
CC {ECO:0000250|UniProtKB:P08617}. Note=Probably localizes to
CC intracellular membrane vesicles that are induced after virus infection
CC as the site for viral RNA replication. {ECO:0000250|UniProtKB:P08617}.
CC -!- SUBCELLULAR LOCATION: [Protein 3AB]: Host membrane
CC {ECO:0000250|UniProtKB:P08617}; Single-pass membrane protein
CC {ECO:0000255}. Note=Probably localizes to intracellular membrane
CC vesicles that are induced after virus infection as the site for viral
CC RNA replication. {ECO:0000250|UniProtKB:P08617}.
CC -!- SUBCELLULAR LOCATION: [Protein 3A]: Host membrane
CC {ECO:0000250|UniProtKB:P08617}; Single-pass membrane protein
CC {ECO:0000255}. Note=Probably localizes to intracellular membrane
CC vesicles that are induced after virus infection as the site for viral
CC RNA replication. {ECO:0000250|UniProtKB:P08617}.
CC -!- SUBCELLULAR LOCATION: [Viral protein genome-linked]: Virion
CC {ECO:0000250|UniProtKB:P08617}.
CC -!- SUBCELLULAR LOCATION: [Protease 3C]: Host cytoplasm
CC {ECO:0000250|UniProtKB:P08617}.
CC -!- SUBCELLULAR LOCATION: [RNA-directed RNA polymerase 3D-POL]: Host
CC cytoplasmic vesicle membrane {ECO:0000250|UniProtKB:P08617}; Peripheral
CC membrane protein {ECO:0000250|UniProtKB:P08617}; Cytoplasmic side
CC {ECO:0000250|UniProtKB:P08617}. Note=Interacts with membranes in a
CC complex with viral protein 3AB. Probably localizes to the surface of
CC intracellular membrane vesicles that are induced after virus infection
CC as the site for viral RNA replication. These vesicles are derived from
CC the endoplasmic reticulum. {ECO:0000250|UniProtKB:P08617}.
CC -!- DOMAIN: [Protein VP1-2A]: The assembly signal 2A region mediates
CC pentamerization of P1-2A. {ECO:0000250|UniProtKB:P08617}.
CC -!- DOMAIN: [Genome polyprotein]: Late-budding domains (L domains) are
CC short sequence motifs essential for viral particle budding. They
CC recruit proteins of the host ESCRT machinery (Endosomal Sorting Complex
CC Required for Transport) or ESCRT-associated proteins. The genome
CC polyprotein contains two L domains: a tandem of (L)YPX(n)L domain which
CC is known to bind the PDCD6IP/ALIX adaptater protein.
CC {ECO:0000250|UniProtKB:P08617}.
CC -!- DOMAIN: [Capsid protein VP2]: Late-budding domains (L domains) are
CC short sequence motifs essential for viral particle budding. They
CC recruit proteins of the host ESCRT machinery (Endosomal Sorting Complex
CC Required for Transport) or ESCRT-associated proteins. Capsid protein
CC VP2 contains two L domains: a tandem of (L)YPX(n)L domain which is
CC known to bind the Alix adaptater protein.
CC {ECO:0000250|UniProtKB:P08617}.
CC -!- DOMAIN: [Protein 2B]: The C-terminus displays a membrane-penetrating
CC ability. {ECO:0000250|UniProtKB:P08617}.
CC -!- PTM: [Genome polyprotein]: Specific enzymatic cleavages by viral
CC protease in vivo yield a variety of precursors and mature proteins.
CC Polyprotein processing intermediates are produced, such as P1-2A which
CC is a functional precursor of the structural proteins, VP0 which is a
CC VP4-VP2 precursor, VP1-2A precursor, 3ABC precursor which is a stable
CC and catalytically active precursor of 3A, 3B and 3C proteins, 3AB and
CC 3CD precursors. The assembly signal 2A is removed from VP1-2A by a host
CC protease, possibly host Cathepsin L. This cleavage occurs over a region
CC of 3 amino-acids probably generating VP1 proteins with heterogeneous C-
CC termini. {ECO:0000250|UniProtKB:P08617}.
CC -!- PTM: [Capsid protein VP0]: During virion maturation, immature virions
CC are rendered infectious following cleavage of VP0 into VP4 and VP2.
CC This maturation seems to be an autocatalytic event triggered by the
CC presence of RNA in the capsid and is followed by a conformational
CC change of the particle. {ECO:0000250|UniProtKB:P03303}.
CC -!- PTM: [Protein VP1-2A]: The assembly signal 2A is removed from VP1-2A by
CC a host protease, possibly host Cathepsin L in naked virions. This
CC cleavage does not occur in enveloped virions. This cleavage occurs over
CC a region of 3 amino-acids probably generating VP1 proteins with
CC heterogeneous C-termini. {ECO:0000250|UniProtKB:P08617}.
CC -!- PTM: [Viral protein genome-linked]: VPg is uridylylated prior to
CC priming replication into VPg-pUpU. {ECO:0000250|UniProtKB:P03300}.
CC -!- PTM: [Capsid protein VP4]: Unlike other picornaviruses, does not seem
CC to be myristoylated. {ECO:0000250|UniProtKB:P08617}.
CC -!- MISCELLANEOUS: [Genome polyprotein]: The need for an intact eIF4G
CC factor for the initiation of translation of HAV results in an inability
CC to shut off host protein synthesis by a mechanism similar to that of
CC other picornaviruses. {ECO:0000250|UniProtKB:P08617}.
CC -!- MISCELLANEOUS: [Genome polyprotein]: During infection, enveloped
CC virions (eHAV) are released from cells. These eHAV are cloaked in host-
CC derived membranes and resemble exosomes. The membrane of eHAV is devoid
CC of viral proteins and thus prevents their neutralization by antibodies.
CC eHAV budding is dependent on ESCRT-associated proteins VPS4B and
CC PDCD6IP/ALIX. eHAV are produced and released in the serum and plasma,
CC but not in bile and feces which only contain the naked, nonenveloped
CC virions. It is likely that eHAV also use HAVCR1 as a functional
CC receptor to infect cells, an evolutionary trait that may enhance HAV
CC infectivity. {ECO:0000250|UniProtKB:P08617}.
CC -!- SIMILARITY: Belongs to the picornaviridae polyprotein family.
CC {ECO:0000305}.
CC -!- CAUTION: It is uncertain whether Met-1 or Met-3 is the initiator.
CC {ECO:0000250|UniProtKB:P08617}.
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DR EMBL; X15463; CAA33491.1; -; Genomic_RNA.
DR EMBL; X15464; CAA33492.1; -; Genomic_RNA.
DR EMBL; L07669; -; NOT_ANNOTATED_CDS; Genomic_RNA.
DR SMR; Q05794; -.
DR MEROPS; C03.005; -.
DR GO; GO:0044162; C:host cell cytoplasmic vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0044193; C:host cell mitochondrial outer membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0072494; C:host multivesicular body; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0044385; C:integral to membrane of host cell; IEA:UniProtKB-KW.
DR GO; GO:0039618; C:T=pseudo3 icosahedral viral capsid; IEA:UniProtKB-KW.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IEA:UniProtKB-EC.
DR GO; GO:0004386; F:helicase activity; IEA:UniProtKB-KW.
DR GO; GO:0005216; F:ion channel activity; IEA:UniProtKB-KW.
DR GO; GO:0017111; F:nucleoside-triphosphatase activity; IEA:RHEA.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0003968; F:RNA-directed 5'-3' RNA polymerase activity; IEA:UniProtKB-KW.
DR GO; GO:0005198; F:structural molecule activity; IEA:InterPro.
DR GO; GO:0039707; P:pore formation by virus in membrane of host cell; IEA:UniProtKB-KW.
DR GO; GO:0051259; P:protein complex oligomerization; IEA:UniProtKB-KW.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR GO; GO:0018144; P:RNA-protein covalent cross-linking; IEA:UniProtKB-KW.
DR GO; GO:0039545; P:suppression by virus of host viral-induced cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS activity; IEA:UniProtKB-KW.
DR GO; GO:0006351; P:transcription, DNA-templated; IEA:InterPro.
DR GO; GO:0046718; P:viral entry into host cell; IEA:UniProtKB-KW.
DR GO; GO:0039694; P:viral RNA genome replication; IEA:InterPro.
DR GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-KW.
DR CDD; cd00205; rhv_like; 2.
DR Gene3D; 2.40.10.10; -; 2.
DR Gene3D; 2.60.120.20; -; 3.
DR Gene3D; 3.30.70.270; -; 1.
DR InterPro; IPR043502; DNA/RNA_pol_sf.
DR InterPro; IPR024354; Hepatitis_A_VP1-2A.
DR InterPro; IPR044067; PCV_3C_PRO.
DR InterPro; IPR000199; Peptidase_C3A/C3B_picornavir.
DR InterPro; IPR009003; Peptidase_S1_PA.
DR InterPro; IPR043504; Peptidase_S1_PA_chymotrypsin.
DR InterPro; IPR001676; Picornavirus_capsid.
DR InterPro; IPR043128; Rev_trsase/Diguanyl_cyclase.
DR InterPro; IPR033703; Rhv-like.
DR InterPro; IPR001205; RNA-dir_pol_C.
DR InterPro; IPR007094; RNA-dir_pol_PSvirus.
DR InterPro; IPR029053; Viral_coat.
DR Pfam; PF12944; HAV_VP; 1.
DR Pfam; PF00548; Peptidase_C3; 1.
DR Pfam; PF00680; RdRP_1; 1.
DR Pfam; PF00073; Rhv; 2.
DR SUPFAM; SSF50494; SSF50494; 1.
DR SUPFAM; SSF56672; SSF56672; 1.
DR PROSITE; PS51874; PCV_3C_PRO; 1.
DR PROSITE; PS50507; RDRP_SSRNA_POS; 1.
PE 3: Inferred from homology;
KW ATP-binding; Capsid protein; Coiled coil; Covalent protein-RNA linkage;
KW Disulfide bond; Helicase; Host cytoplasm; Host cytoplasmic vesicle;
KW Host endosome; Host membrane; Host mitochondrion;
KW Host mitochondrion outer membrane; Host-virus interaction; Hydrolase;
KW Inhibition of host innate immune response by virus;
KW Inhibition of host MAVS by virus; Inhibition of host RLR pathway by virus;
KW Interferon antiviral system evasion; Ion channel; Ion transport; Membrane;
KW Nucleotide-binding; Nucleotidyltransferase; Phosphoprotein; Protease;
KW RNA-binding; RNA-directed RNA polymerase;
KW T=pseudo3 icosahedral capsid protein; Thiol protease; Transferase;
KW Transmembrane; Transmembrane helix; Transport;
KW Viral attachment to host cell; Viral immunoevasion; Viral ion channel;
KW Viral RNA replication; Virion; Virus entry into host cell.
FT CHAIN 1..2052
FT /note="Genome polyprotein"
FT /id="PRO_0000311062"
FT CHAIN 1..245
FT /note="Capsid protein VP0"
FT /id="PRO_0000311063"
FT CHAIN 1..23
FT /note="Capsid protein VP4"
FT /id="PRO_5000145525"
FT CHAIN 24..245
FT /note="Capsid protein VP2"
FT /id="PRO_5000145526"
FT CHAIN 246..491
FT /note="Capsid protein VP3"
FT /id="PRO_5000145527"
FT CHAIN 492..830
FT /note="Protein VP1-2A"
FT /id="PRO_0000311064"
FT CHAIN 492..759
FT /note="Capsid protein VP1"
FT /id="PRO_5000145528"
FT CHAIN 760..830
FT /note="Assembly signal 2A"
FT /id="PRO_5000145529"
FT CHAIN 831..1258
FT /note="Protein 2BC"
FT /id="PRO_0000311065"
FT CHAIN 831..1081
FT /note="Protein 2B"
FT /id="PRO_5000145530"
FT CHAIN 1082..1258
FT /note="Protein 2C"
FT /id="PRO_5000145531"
FT CHAIN 1259..2052
FT /note="Protein 3ABCD"
FT /id="PRO_0000311066"
FT CHAIN 1259..1572
FT /note="Protein 3ABC"
FT /id="PRO_0000311067"
FT CHAIN 1259..1353
FT /note="Protein 3AB"
FT /id="PRO_0000311068"
FT CHAIN 1259..1330
FT /note="Protein 3A"
FT /id="PRO_5000145521"
FT CHAIN 1331..1353
FT /note="Viral protein genome-linked"
FT /id="PRO_5000145522"
FT CHAIN 1354..2052
FT /note="Protein 3CD"
FT /id="PRO_0000311069"
FT CHAIN 1354..1572
FT /note="Protease 3C"
FT /id="PRO_5000145523"
FT CHAIN 1573..2052
FT /note="RNA-directed RNA polymerase 3D-POL"
FT /id="PRO_5000145524"
FT TRANSMEM 1005..1025
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1296..1316
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 1348..1562
FT /note="Peptidase C3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01222"
FT DOMAIN 1810..1931
FT /note="RdRp catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00539"
FT REGION 502..522
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 760..830
FT /note="Involved in P1-2A pentamerization"
FT /evidence="ECO:0000250|UniProtKB:P08617"
FT REGION 1037..1064
FT /note="Membrane-penetrating ability"
FT /evidence="ECO:0000250|UniProtKB:P08617"
FT COILED 1121..1146
FT /evidence="ECO:0000255"
FT MOTIF 167..171
FT /note="(L)YPX(n)L motif"
FT /evidence="ECO:0000250|UniProtKB:P08617"
FT MOTIF 200..205
FT /note="(L)YPX(n)L motif"
FT /evidence="ECO:0000250|UniProtKB:P08617"
FT ACT_SITE 1397
FT /note="For protease 3C activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01222"
FT ACT_SITE 1437
FT /note="For protease 3C activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01222"
FT ACT_SITE 1525
FT /note="For protease 3C activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01222"
FT SITE 23..24
FT /note="Cleavage"
FT /evidence="ECO:0000255"
FT SITE 245..246
FT /note="Cleavage; by protease 3C"
FT /evidence="ECO:0000250|UniProtKB:P08617"
FT SITE 491..492
FT /note="Cleavage; by protease 3C"
FT /evidence="ECO:0000250|UniProtKB:P08617"
FT SITE 759..760
FT /note="Cleavage; partial; by host"
FT /evidence="ECO:0000250|UniProtKB:P08617"
FT SITE 763
FT /note="Important for VP1 folding and capsid assembly"
FT /evidence="ECO:0000250|UniProtKB:P08617"
FT SITE 830..831
FT /note="Cleavage; by protease 3C"
FT /evidence="ECO:0000250|UniProtKB:P08617"
FT SITE 1081..1082
FT /note="Cleavage; by protease 3C"
FT /evidence="ECO:0000250|UniProtKB:P08617"
FT SITE 1258..1259
FT /note="Cleavage; by protease 3C"
FT /evidence="ECO:0000250|UniProtKB:P08617"
FT SITE 1330..1331
FT /note="Cleavage; by protease 3C"
FT /evidence="ECO:0000250|UniProtKB:P08617"
FT SITE 1353..1354
FT /note="Cleavage; by protease 3C"
FT /evidence="ECO:0000250|UniProtKB:P08617"
FT SITE 1572..1573
FT /note="Cleavage; by protease 3C"
FT /evidence="ECO:0000250|UniProtKB:P08617"
FT MOD_RES 1333
FT /note="O-(5'-phospho-RNA)-tyrosine"
FT /evidence="ECO:0000250"
FT DISULFID 1377
FT /note="Interchain"
FT /evidence="ECO:0000250|UniProtKB:P08617"
FT NON_CONS 1161..1162
FT /evidence="ECO:0000305"
SQ SEQUENCE 2052 AA; 231976 MW; 971E03905B81110A CRC64;
MNMSKQGIFQ TVGSGLDHIL SLADIEEEQM IQSVDRTAVT GASYFTSVDQ SSVHTAEVGS
HQIEPLKTSV DKPGSKKTQG EKFFLIHSAD WLTTHALFHE VAKLDVVKLL YNEQFAVQGL
LRYHTYARFG IEIQVQINPT PFQQGGLICA MVPGDQSYGS IASLTVYPHG LLNCNINNVV
RIKVPFIYTR GAYHFKDPQY PVWELTIRVW SELNIGTGTS AYTSLNVLAR FTDLELHGLT
PLSTQMMRNE FRVSTTENVV NLSNYEDARA KMSFALDQED WKSDPSQGGG IKITHFTTWT
SIPTLAAQFP FNASDSVGQQ IKVIPVDPYF FQMTNTNPDQ KCITALASIC QMFCFWRGDL
VFDFQVFPTK YHSGRLLFCF VPGNELIDVT GITLKQATTA PCAVMDITGV QSTLRFRVPW
ISDTPYRVNR YTKSAHQKGE YTAIGKLIVY CYNRLTSPSN VASHVRVNVY LSAINLECFA
PLYHAMDVTT QVGDDSGGFS TTVSTEQNVP DPQVGIKGKA NRGKMDVSGV QAPVGAITTI
EDPVLAKKVP ETFPELKPGE SRHTSDHMSI YKFMGRSHFL CTFTFNSNNK EYTFPITLSS
TSNPPHGLPS TLRWFFNLFQ LYRGPLDLTI IITGATDVDG MAWFTPVGLA VDTPWVEKKS
ALSIDYKTAL GAVRFNTRRT GNIQIRLPWY SYLYAVSGAL DGLGDKTDST FGLVSIQIAN
YNHSDEYLSF SCYLSVTEQS EFYFPRAPLN SNAMLSTESM MSRIAAGDLE SSVDDPRSEE
DRRFESHIEC RKPYKELRLE VGKQRLKYAQ EELSNEVLPP PRKMKGLFSQ AKISLFYTEE
HEIMKFSWRG VTADTRALRR FGFSLAAGRS VWTLEMDAGV LTGRLIRLND EKWTEMKDDK
IVSLIEKFTS NKYWSKVNFP HGMLDLEEIA ANSKDFPNMS ETDLCFLLHW LNPKKINLAD
RMLGLSGVQE IKEQGVGLIA ECRTFLDSIA GTLKSMIFGF HHSVTVEIIN IVLCFIKSGI
LLYVIQQLNQ DEHSHIIGLL RVMNYADIGC SVISCGKVFS KMLETVFNWQ MDSRMMELRT
QSFSNWLRDI CSGITIFKSF KDAIYWLCTK LKDFYEVNYG KKKDVLNILK DNQQKIEKAI
EEADNFCILQ IQDVEKFDQY QTSNWSNPSP KTVYVKEAID RRLHFKVEVK PASFFKNPHN
DMLNVNLAKT NDAIKDMSCV DLIMDGHNIS LMDLLSSLVM TVEIRKQNMS EFMELWSQGI
SDDDSAVAEF FQSFPSGEPS NSKLSSFFQS VTNHKWVAVG AAVGILGLLV GGWFVYKHFS
RKEEEPIPAE GVYHGVTKPK QVIKLDADPV ESQSTLEIAG LVRKNLVQFG VGEKNGCVRW
VMNALGVKDD WLLVPSHAYK FEKDYEMMEF YFNRGGTYYS ISAGNVVIQS LDVGFQDVVL
MKVPTIPKFR DITQHFIKKG DVPRALNRLA TLVTTVNGTP MLISEGPLKM EEKATYVHKK
NDGTTVDLTV DQAWRGKGEG LPGMCGGALV SSNQSIQNAI LGIHVAGGNS ILVAKLITQE
MFQNIDKKIE SQRIMKVEFT QCSMNVVSKT LFRKSPIHHH IDKTMINFPA AMPFSKAEID
PMAMMLSKYS LPIVEEPEDY KEASVFYQNK IVGKTQLVDD FLDLDMAITG APGIDAINMD
SSPGFPYVQE KLTKRDLIWL DENGLLLGVH PRLAQRILFN TVMMENCSDL DVVFTTCPKD
ELRPLEKVLE SKTRAIDACP LDYTILCRMY WGPAISYFHL NPGFHTGVAI GIDPDRQWDE
LFKTMIRFGD VGLDLDFSAF DASLSPFMIR EAGRIMSELS GTPSHFGTAL INTIIYSKHL
LYNCCYHVCG SMPSGSPCTA LLNSIINNIN LYYVFSKIFG KSPVFFCQAL RILCYGDDVL
IVFSRDVQID NLDLIGQKIV DEFKKLGMTA TSADKNVPQL KPVSELTFLK RSFNLVEDRI
RPAISEKTIW SLIAWQRSNA EFEQNLENAQ WFAFMHGYEF YQKFYYFVQS CLEKEMIEYR
LKSYDWWRMR FY
