POLG_HAVLC
ID POLG_HAVLC Reviewed; 341 AA.
AC P13672;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1990, sequence version 1.
DT 03-AUG-2022, entry version 93.
DE RecName: Full=Genome polyprotein;
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 Flags: Fragment;
OS Human hepatitis A virus genotype IA (isolate LCDC-1) (HHAV) (Human
OS hepatitis A virus (isolate Human/China/LCDC-1/1984)).
OC Viruses; Riboviria; Orthornavirae; Pisuviricota; Pisoniviricetes;
OC Picornavirales; Picornaviridae; Hepatovirus.
OX NCBI_TaxID=12093;
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=2542903; DOI=10.1093/nar/17.9.3594;
RA Andonov A.P., Lau P., Chaudhary R.;
RT "Nucleotide sequence of the VP1 gene from a Chinese strain of hepatitis A
RT virus (HAV).";
RL Nucleic Acids Res. 17:3594-3594(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 268-323.
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 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: [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 -!- SUBUNIT: [Protein VP1-2A]: Homopentamer. Homooligomer.
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 -!- 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 -!- 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: [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 -!- 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}.
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DR EMBL; X14666; CAA32794.1; -; Genomic_RNA.
DR EMBL; L07714; -; NOT_ANNOTATED_CDS; Genomic_RNA.
DR PIR; S04137; S04137.
DR SMR; P13672; -.
DR PRIDE; P13672; -.
DR GO; GO:0072494; C:host multivesicular body; IEA:UniProtKB-SubCell.
DR GO; GO:0039618; C:T=pseudo3 icosahedral viral capsid; IEA:UniProtKB-KW.
DR GO; GO:0046718; P:viral entry into host cell; IEA:UniProtKB-KW.
DR GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-KW.
DR Gene3D; 2.60.120.20; -; 1.
DR InterPro; IPR024354; Hepatitis_A_VP1-2A.
DR InterPro; IPR029053; Viral_coat.
DR Pfam; PF12944; HAV_VP; 1.
PE 3: Inferred from homology;
KW Capsid protein; Host endosome; Host-virus interaction;
KW T=pseudo3 icosahedral capsid protein; Viral attachment to host cell;
KW Virion; Virus entry into host cell.
FT CHAIN <1..>341
FT /note="Genome polyprotein"
FT /id="PRO_0000310997"
FT CHAIN <1..1
FT /note="Capsid protein VP3"
FT /id="PRO_0000039900"
FT CHAIN 2..340
FT /note="Protein VP1-2A"
FT /id="PRO_0000039901"
FT CHAIN 2..269
FT /note="Capsid protein VP1"
FT /id="PRO_0000310998"
FT CHAIN 270..340
FT /note="Assembly signal 2A"
FT /id="PRO_0000039902"
FT REGION 1..32
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 270..340
FT /note="Involved in P1-2A pentamerization"
FT /evidence="ECO:0000250|UniProtKB:P08617"
FT REGION 321..341
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..21
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 1..2
FT /note="Cleavage; by protease 3C"
FT /evidence="ECO:0000250|UniProtKB:P08617"
FT SITE 269..270
FT /note="Cleavage; partial; by host"
FT /evidence="ECO:0000250|UniProtKB:P08617"
FT SITE 273
FT /note="Important for VP1 folding and capsid assembly"
FT /evidence="ECO:0000250|UniProtKB:P08617"
FT SITE 340..341
FT /note="Cleavage; by protease 3C"
FT /evidence="ECO:0000250|UniProtKB:P08617"
FT CONFLICT 306
FT /note="E -> D (in Ref. 2)"
FT /evidence="ECO:0000305"
FT NON_TER 1
FT NON_TER 341
SQ SEQUENCE 341 AA; 38004 MW; 066918289BF126D5 CRC64;
QVGDDSGGFS TTVSTEQNVP DPQVGIKGKA NRGKMDVSGV QAPVGAITTI EDPVLAKKVP
ETFPELKPGE SRHTSDHMSI YKFMGRSHFL CTFTFNSNNK EYTFPITLSS TSNPPHGLPS
TLRWFFNLFQ LYRGPLDLTI IITGATDVDG MAWFTPVGLA VDTPWVEKAS ALSIDYKTAL
GAVRFNTRRT GNIQIRLPWY SYLYAVSGAL DGLGDKTDST FGLVSIQIAN YNHSDEYLSF
SCYLSVTEQS EFYFPRAPLN SNAMLSTESM MSRIAAGDLE SSVDDPRSEE DRRFESHIEC
RKPYKELRLE VGKQRLKYAQ EELSNEVLPP PRKMKGLFSQ S
