ID   POLG_HAVMB              Reviewed;        2227 AA.
AC   P13901; Q81083; Q81084; Q81085; Q81086; Q81087; Q81088; Q81089; Q81090;
AC   Q81091; Q81092; Q81093;
DT   01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT   01-JAN-1990, sequence version 1.
DT   24-JAN-2024, entry version 169.
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};
OS   Human hepatitis A virus genotype IB (isolate MBB) (HHAV) (Human hepatitis A
OS   virus (isolate Human/Northern Africa/MBB/1978)).
OC   Viruses; Riboviria; Orthornavirae; Pisuviricota; Pisoniviricetes;
OC   Picornavirales; Picornaviridae; Heptrevirinae; Hepatovirus; Hepatovirus A.
OX   NCBI_TaxID=12100;
OH   NCBI_TaxID=9536; Cercopithecus hamlyni (Owl-faced monkey) (Hamlyn's monkey).
OH   NCBI_TaxID=9606; Homo sapiens (Human).
OH   NCBI_TaxID=9539; Macaca (macaques).
OH   NCBI_TaxID=9598; Pan troglodytes (Chimpanzee).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=2823500; DOI=10.1016/0168-1702(87)90026-8;
RA   Paul A.V., Tada H., der Helm K., Wissel T., Kiehn R., Wimmer E.,
RA   Deinhardt F.;
RT   "The entire nucleotide sequence of the genome of human hepatitis A virus
RT   (isolate MBB).";
RL   Virus Res. 8:153-171(1987).
RN   [2]
RP   X-RAY CRYSTALLOGRAPHY (1.4 ANGSTROMS) OF 1520-1738 IN COMPLEX WITH THE
RP   INHIBITOR N-CBZ-L-SERINE B-LACTONE, AND ACTIVE SITE (PROTEASE 3C).
RX   PubMed=16288920; DOI=10.1016/j.jmb.2005.09.074;
RA   Yin J., Bergmann E.M., Cherney M.M., Lall M.S., Jain R.P., Vederas J.C.,
RA   James M.N.G.;
RT   "Dual modes of modification of hepatitis A virus 3C protease by a serine-
RT   derived beta-lactone: selective crystallization and formation of a
RT   functional catalytic triad in the active site.";
RL   J. Mol. Biol. 354:854-871(2005).
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 RIG-I/IFIH1 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; M20273; AAA45474.1; -; Genomic_RNA.
DR   PDB; 2A4O; X-ray; 1.55 A; A=1520-1738.
DR   PDB; 2CXV; X-ray; 1.40 A; A=1520-1738.
DR   PDBsum; 2A4O; -.
DR   PDBsum; 2CXV; -.
DR   BMRB; P13901; -.
DR   SMR; P13901; -.
DR   DrugBank; DB04634; N-BENZYLOXYCARBONYL-L-SERINE-BETALACTONE.
DR   DrugBank; DB04029; Phenylalanylamide.
DR   MEROPS; C03.005; -.
DR   EvolutionaryTrace; P13901; -.
DR   Proteomes; UP000007904; Genome.
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:0016020; C:membrane; 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:0005216; F:monoatomic ion channel activity; IEA:UniProtKB-KW.
DR   GO; GO:0017111; F:ribonucleoside triphosphate phosphatase activity; IEA:UniProtKB-EC.
DR   GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR   GO; GO:0003724; F:RNA helicase activity; IEA:InterPro.
DR   GO; GO:0003968; F:RNA-dependent RNA polymerase activity; IEA:UniProtKB-KW.
DR   GO; GO:0005198; F:structural molecule activity; IEA:InterPro.
DR   GO; GO:0006351; P:DNA-templated transcription; IEA:InterPro.
DR   GO; GO:0051259; P:protein complex oligomerization; IEA:UniProtKB-KW.
DR   GO; GO:0006508; P:proteolysis; 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: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   GO; GO:0039707; P:virus-mediated pore formation in host cell membrane; IEA:UniProtKB-KW.
DR   CDD; cd23215; Hepatovirus_RdRp; 1.
DR   CDD; cd00205; rhv_like; 2.
DR   Gene3D; 1.20.960.20; -; 1.
DR   Gene3D; 2.60.120.20; -; 3.
DR   Gene3D; 3.30.70.270; -; 1.
DR   Gene3D; 2.40.10.10; Trypsin-like serine proteases; 2.
DR   InterPro; IPR049133; 2B_soluble.
DR   InterPro; IPR043502; DNA/RNA_pol_sf.
DR   InterPro; IPR004004; Helic/Pol/Pept_Calicivir-typ.
DR   InterPro; IPR000605; Helicase_SF3_ssDNA/RNA_vir.
DR   InterPro; IPR014759; Helicase_SF3_ssRNA_vir.
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; PF20758; 2B_soluble; 1.
DR   Pfam; PF12944; HAV_VP; 1.
DR   Pfam; PF00548; Peptidase_C3; 1.
DR   Pfam; PF00680; RdRP_1; 1.
DR   Pfam; PF00073; Rhv; 2.
DR   Pfam; PF00910; RNA_helicase; 1.
DR   PRINTS; PR00918; CALICVIRUSNS.
DR   SUPFAM; SSF56672; DNA/RNA polymerases; 1.
DR   SUPFAM; SSF88633; Positive stranded ssRNA viruses; 3.
DR   SUPFAM; SSF50494; Trypsin-like serine proteases; 1.
DR   PROSITE; PS51874; PCV_3C_PRO; 1.
DR   PROSITE; PS50507; RDRP_SSRNA_POS; 1.
DR   PROSITE; PS51218; SF3_HELICASE_2; 1.
PE   1: Evidence at protein level;
KW   3D-structure; ATP-binding; Capsid protein; Coiled coil;
KW   Covalent protein-RNA linkage; Disulfide bond; Helicase; Host cytoplasm;
KW   Host cytoplasmic vesicle; 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..2227
FT                   /note="Genome polyprotein"
FT                   /id="PRO_0000311015"
FT   CHAIN           1..245
FT                   /note="Capsid protein VP0"
FT                   /id="PRO_0000311016"
FT   CHAIN           1..23
FT                   /note="Capsid protein VP4"
FT                   /id="PRO_0000039968"
FT   CHAIN           24..245
FT                   /note="Capsid protein VP2"
FT                   /id="PRO_0000039969"
FT   CHAIN           246..491
FT                   /note="Capsid protein VP3"
FT                   /id="PRO_0000039970"
FT   CHAIN           492..836
FT                   /note="Protein VP1-2A"
FT                   /id="PRO_0000039971"
FT   CHAIN           492..765
FT                   /note="Capsid protein VP1"
FT                   /id="PRO_0000311017"
FT   CHAIN           766..836
FT                   /note="Assembly signal 2A"
FT                   /id="PRO_0000039972"
FT   CHAIN           837..1422
FT                   /note="Protein 2BC"
FT                   /id="PRO_0000311018"
FT   CHAIN           837..1087
FT                   /note="Protein 2B"
FT                   /id="PRO_0000039973"
FT   CHAIN           1088..1422
FT                   /note="Protein 2C"
FT                   /id="PRO_0000039974"
FT   CHAIN           1423..2227
FT                   /note="Protein 3ABCD"
FT                   /id="PRO_0000311019"
FT   CHAIN           1423..1738
FT                   /note="Protein 3ABC"
FT                   /id="PRO_0000311020"
FT   CHAIN           1423..1519
FT                   /note="Protein 3AB"
FT                   /id="PRO_0000311021"
FT   CHAIN           1423..1496
FT                   /note="Protein 3A"
FT                   /id="PRO_0000039975"
FT   CHAIN           1497..1519
FT                   /note="Viral protein genome-linked"
FT                   /id="PRO_0000039976"
FT   CHAIN           1520..2227
FT                   /note="Protein 3CD"
FT                   /id="PRO_0000311022"
FT   CHAIN           1520..1738
FT                   /note="Protease 3C"
FT                   /id="PRO_0000039977"
FT   CHAIN           1739..2227
FT                   /note="RNA-directed RNA polymerase 3D-POL"
FT                   /id="PRO_0000039978"
FT   TRANSMEM        1010..1030
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1462..1482
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          1204..1366
FT                   /note="SF3 helicase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00551"
FT   DOMAIN          1514..1728
FT                   /note="Peptidase C3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01222"
FT   DOMAIN          1976..2097
FT                   /note="RdRp catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00539"
FT   REGION          766..836
FT                   /note="Involved in P1-2A pentamerization"
FT                   /evidence="ECO:0000250|UniProtKB:P08617"
FT   REGION          1043..1070
FT                   /note="Membrane-penetrating ability"
FT                   /evidence="ECO:0000250|UniProtKB:P08617"
FT   COILED          1127..1152
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        1563
FT                   /note="For protease 3C activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01222,
FT                   ECO:0000269|PubMed:16288920"
FT   ACT_SITE        1603
FT                   /note="For protease 3C activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01222,
FT                   ECO:0000269|PubMed:16288920"
FT   ACT_SITE        1691
FT                   /note="For protease 3C activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01222,
FT                   ECO:0000269|PubMed:16288920"
FT   BINDING         1230..1237
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00551"
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            765..766
FT                   /note="Cleavage; partial; by host"
FT                   /evidence="ECO:0000250|UniProtKB:P08617"
FT   SITE            769
FT                   /note="Important for VP1 folding and capsid assembly"
FT                   /evidence="ECO:0000250|UniProtKB:P08617"
FT   SITE            836..837
FT                   /note="Cleavage; by protease 3C"
FT                   /evidence="ECO:0000250|UniProtKB:P08617"
FT   SITE            1087..1088
FT                   /note="Cleavage; by protease 3C"
FT                   /evidence="ECO:0000250|UniProtKB:P08617"
FT   SITE            1422..1423
FT                   /note="Cleavage; by protease 3C"
FT                   /evidence="ECO:0000250|UniProtKB:P08617"
FT   SITE            1496..1497
FT                   /note="Cleavage; by protease 3C"
FT                   /evidence="ECO:0000250|UniProtKB:P08617"
FT   SITE            1519..1520
FT                   /note="Cleavage; by protease 3C"
FT                   /evidence="ECO:0000250|UniProtKB:P08617"
FT   SITE            1738..1739
FT                   /note="Cleavage; by protease 3C"
FT                   /evidence="ECO:0000250|UniProtKB:P08617"
FT   MOD_RES         1499
FT                   /note="O-(5'-phospho-RNA)-tyrosine"
FT                   /evidence="ECO:0000250"
FT   DISULFID        1543
FT                   /note="Interchain"
FT                   /evidence="ECO:0000250|UniProtKB:P08617"
FT   HELIX           1521..1531
FT                   /evidence="ECO:0007829|PDB:2CXV"
FT   STRAND          1532..1538
FT                   /evidence="ECO:0007829|PDB:2CXV"
FT   STRAND          1545..1555
FT                   /evidence="ECO:0007829|PDB:2CXV"
FT   STRAND          1557..1561
FT                   /evidence="ECO:0007829|PDB:2CXV"
FT   HELIX           1562..1564
FT                   /evidence="ECO:0007829|PDB:2CXV"
FT   TURN            1565..1567
FT                   /evidence="ECO:0007829|PDB:2CXV"
FT   HELIX           1571..1573
FT                   /evidence="ECO:0007829|PDB:2CXV"
FT   STRAND          1574..1580
FT                   /evidence="ECO:0007829|PDB:2CXV"
FT   STRAND          1583..1588
FT                   /evidence="ECO:0007829|PDB:2CXV"
FT   HELIX           1589..1591
FT                   /evidence="ECO:0007829|PDB:2CXV"
FT   STRAND          1592..1600
FT                   /evidence="ECO:0007829|PDB:2CXV"
FT   STRAND          1603..1608
FT                   /evidence="ECO:0007829|PDB:2CXV"
FT   HELIX           1619..1621
FT                   /evidence="ECO:0007829|PDB:2CXV"
FT   HELIX           1625..1631
FT                   /evidence="ECO:0007829|PDB:2CXV"
FT   STRAND          1636..1642
FT                   /evidence="ECO:0007829|PDB:2CXV"
FT   STRAND          1645..1651
FT                   /evidence="ECO:0007829|PDB:2CXV"
FT   STRAND          1655..1665
FT                   /evidence="ECO:0007829|PDB:2CXV"
FT   STRAND          1671..1683
FT                   /evidence="ECO:0007829|PDB:2CXV"
FT   STRAND          1694..1698
FT                   /evidence="ECO:0007829|PDB:2CXV"
FT   HELIX           1700..1702
FT                   /evidence="ECO:0007829|PDB:2CXV"
FT   STRAND          1706..1714
FT                   /evidence="ECO:0007829|PDB:2CXV"
FT   STRAND          1717..1722
FT                   /evidence="ECO:0007829|PDB:2CXV"
FT   HELIX           1725..1730
FT                   /evidence="ECO:0007829|PDB:2CXV"
SQ   SEQUENCE   2227 AA;  251427 MW;  EC983ED2A7C86349 CRC64;
     MNMSRQGIFQ TVGSGLDHIL SLADIEEEQM IQSVDRTAVT GASYFTSVDQ SSVHTAEVGS
     HQVEPLRTSV 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 VPGNELIDVS GITLKQATTA PCAVMDITGV QSTLRFRVPW
     ISDTPYRVNR YTKSAHQKGE YTAIGKLIVY CYNRLTSPSN VASHVRVNVY LSAINLECFA
     PLYHAMDVTT QVGDDSGGFS TTVSTEQNVP DPQVGITTMK DLKGKANRGK MDVSGVQAPV
     GAITTIEDPV LAKKVPETFP ELKPGESRHT SDHMSIYKFM GRSHFLCTFT FNSNNKEYTF
     PITLSSTSNP PHGLPSTLRW FFNLFQLYRG PLDLTIIIIG ATDVDGMAWF TPVGLAVDTP
     WVEKESALSI DYKTALGAVR FNTRRTGNIQ IRLPWYSYLY AVSGALDGLG DKTDSTFGLV
     SIQIANYNHS DEYLSFSCYL SVTEQSEFYF PRAPLNSNAM LSTESMMSRI AAGDLESSVD
     DPRSEEDKRF ESHIECRKPY KELRLEVGKQ RLKYAQEELS NEVLPPPRKK KGLFSQAKIS
     LFYTEEHEIM KFSWRGVTAD TRALRRFGFS LAAGRSVWTL EMDAGVLTGR LIRLNDEKWT
     EMKDDKIVSL IEKFTSNKYW SKVNFPHGML DLEEIAANSK DFPNMSETDL CFLLHWLNPK
     KINLADRMLG LSGVQEIKEQ GVGLIAECRT FLDSIAGTLK SMMFGFHHSV TVEIINTVLC
     FVKSGILLYV MQQLNQDEHS HIIGLLRVMN YVDIGCSVIS CGKVFSKMLE TVFNWQMDSR
     MMELRTQSFS NWLRDICSGI TIFKNFKDAI YWLYTKLNDF YEVNYGKKKD ILNILKDNQQ
     KIEKAIEEAD KFSILQIQDV EKFEQYQKGV DLIQKLRTVH SMAQVDPNLM VHLSPLRDCI
     ARVHQKLKNL GSINQAMVTR CEPVVCYLYG KRGGGKSLTS IALATKICKH YGVEPEKNIY
     TKPVASDYWD GYSGQLVCII DDIGQNTTDE DWSDFCQLVS GCPLRLNMAS LEEKGRHFSS
     PFIIATSNWS NPSPKTVYVK EAIDRRLHFK VEVNPASFSK NPHNDMLNVN LAKTNDAIKD
     MSCVDLIMDG HNVSLMDLLS SLVMTVEIRK QNMTAFMELW SQGISDDDND SAMAEFFQSF
     PSGEPSNSKL SGFFQSVTNH KWVAVGAAVG ILGVLVGGWF VYKHFSRKEE EPIPAEGVYH
     GVTKPKQVIK LDADPVESQS TLEIAGLVRK NLVQFGVGEK NGCVRWVMNA LGVKDDWLLV
     PSHAYKFEKD YEMMEFYFNR GGTYYSISAG NVVIQSLDVG FQDVVLMKVP TIPKFRDITQ
     HFIKKGDVPR ALNRLATLVT TVNGTPMLIS EGPLKMEEKA TYVHKKNDGT TVDLTVDQAW
     RGKGEGLPGM CGGALVSSNQ SIQNAILGIH VAGGNSILVA KLVTQEMFQN IDKKIESQRI
     MKVEFTQCSM NVVSKTLFRK SPIHHHIDKT MINFPAAMPF SKAEIDPMAM MLSKYSLPIV
     EEPEDYKEAS IFYQNKIVGK TQLVDDFLDL DMAITGAPGI DAINMDSSPG FPYVQERLTK
     RDLIWLDENG LLLGVHPRLA QRILFNTVMM ENCSDLDVVF TTCPKDELRP LEKVLESKTR
     AIDACPLDYT ILCRMYWGPA ISYFHLNPGF HTGVAIGIDP DCQWDELFKT MIRFGDVGLD
     LDFSAFDASL SPFMIREAGR IMSELSGTPS HFGTALMNTI IYSKHLLYNC CYHVCGSMPS
     GSPCTALLNS IINNVNLYYV FSKIFGKSPV FFCQALKILC YGDDVLIVFS RDVQIDNLDL
     IGQKIVDEFK KLGMTATSAD KNVPQLKPVS ELTFLKRSFN LVEDRIRPAI SEKTIWSLIA
     WQRSNAEFEQ NLENAQWFAF MHGYEFYQKF YYFVQSCLEK EMIEYRLKSY DWWRMRFYDQ
     CFICDLS
//