POLG_HAVGA
ID POLG_HAVGA Reviewed; 808 AA.
AC Q02381;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1993, sequence version 1.
DT 03-AUG-2022, entry version 91.
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 Flags: Fragment;
OS Human hepatitis A virus genotype IIIA (isolate GA76) (HHAV) (Human
OS hepatitis A virus (isolate Human/Georgia/GA76/1976)).
OC Viruses; Riboviria; Orthornavirae; Pisuviricota; Pisoniviricetes;
OC Picornavirales; Picornaviridae; Hepatovirus.
OX NCBI_TaxID=31706;
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=1316423; DOI=10.1002/jmv.1890360208;
RA Khanna B., Spelbring J.E., Innis B.L., Robertson B.H.;
RT "Characterization of a genetic variant of human hepatitis A virus.";
RL J. Med. Virol. 36:118-124(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 743-798.
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 -!- 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 -!- 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 -!- 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: [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}.
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DR EMBL; M66695; AAA45477.1; -; Genomic_RNA.
DR EMBL; L07668; -; NOT_ANNOTATED_CDS; Genomic_RNA.
DR SMR; Q02381; -.
DR GO; GO:0072494; C:host multivesicular body; IEA:UniProtKB-SubCell.
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:0005216; F:ion channel 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:0046718; P:viral entry into host cell; IEA:UniProtKB-KW.
DR GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-KW.
DR CDD; cd00205; rhv_like; 2.
DR Gene3D; 2.60.120.20; -; 3.
DR InterPro; IPR024354; Hepatitis_A_VP1-2A.
DR InterPro; IPR001676; Picornavirus_capsid.
DR InterPro; IPR033703; Rhv-like.
DR InterPro; IPR029053; Viral_coat.
DR Pfam; PF12944; HAV_VP; 1.
DR Pfam; PF00073; Rhv; 2.
PE 3: Inferred from homology;
KW Capsid protein; Host endosome; Host-virus interaction; Ion channel;
KW Ion transport; T=pseudo3 icosahedral capsid protein; Transport;
KW Viral attachment to host cell; Viral ion channel; Virion;
KW Virus entry into host cell.
FT CHAIN <1..>808
FT /note="Genome polyprotein"
FT /id="PRO_0000311004"
FT CHAIN <1..224
FT /note="Capsid protein VP0"
FT /id="PRO_0000311005"
FT CHAIN <1..2
FT /note="Capsid protein VP4"
FT /id="PRO_0000039941"
FT CHAIN 3..224
FT /note="Capsid protein VP2"
FT /id="PRO_0000039942"
FT CHAIN 225..470
FT /note="Capsid protein VP3"
FT /id="PRO_0000039943"
FT CHAIN 471..>808
FT /note="Protein VP1-2A"
FT /id="PRO_0000311006"
FT CHAIN 471..744
FT /note="Capsid protein VP1"
FT /id="PRO_0000039944"
FT CHAIN 745..>808
FT /note="Assembly signal 2A"
FT /id="PRO_0000039945"
FT REGION 34..55
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 146..150
FT /note="(L)YPX(n)L motif"
FT /evidence="ECO:0000250|UniProtKB:P08617"
FT MOTIF 179..184
FT /note="(L)YPX(n)L motif"
FT /evidence="ECO:0000250|UniProtKB:P08617"
FT SITE 2..3
FT /note="Cleavage"
FT /evidence="ECO:0000255"
FT SITE 224..225
FT /note="Cleavage; by protease 3C"
FT /evidence="ECO:0000250|UniProtKB:P08617"
FT SITE 470..471
FT /note="Cleavage; by protease 3C"
FT /evidence="ECO:0000250|UniProtKB:P08617"
FT SITE 744..745
FT /note="Cleavage; partial; by host"
FT /evidence="ECO:0000250|UniProtKB:P08617"
FT SITE 748
FT /note="Important for VP1 folding and capsid assembly"
FT /evidence="ECO:0000250|UniProtKB:P08617"
FT CONFLICT 763
FT /note="T -> S (in Ref. 2)"
FT /evidence="ECO:0000305"
FT NON_TER 1
FT NON_TER 808
SQ SEQUENCE 808 AA; 90633 MW; D80CE7E57A479C12 CRC64;
LADVEEEQMI QSVDRTAVTG ASYFTSVDQS SVHTAEVGSH QPEPLKTSVD KPGSKRTQGE
KFFLIHSADW LTTHALFHEV AKLDVVKLLY NEQFAVQGLL RYHTYARFGI EIQVQINPTP
FQQGGLICAM VPGDQSYGSI ASLTVYPHGL LNCNINNVVR IKVPFIYTRG AYHFKDPQYP
VWELTIRVWS ELNIGTGTSA YTSLNVLARF TDLELHGLTP LSTQMMRNEF RVSTTENVVN
LSNYEDARAK MSFALDQEDW KSDASQGGGI KITHFTTWTS IPTLAAQFPF NASDSVGQQI
KVIPVDPYFF QMTNTNPEQK CITALASICQ MFCFWRGDLV FDFQVFPTKY HSGRLLFCFV
PGNELIDVSH ITLKQATTAP CAVMDITGVQ STLRFRVPWI SDTPYRVNRY TKSSHQKGEY
TAIGKLIVYC YNRLTSPSNV ASHVRVNVYL SAINLECFAP LYHAMDVTTQ VGDDSGGFST
TVSTKQNVPD PQVGITTVKD LKGRANQGKM DISGVQAPVG AITTIEDPVL AKKVPETFPE
LKPGESRHTS DHMSIYKFMG RSHFLCTFTF NSNNKEYTFP ITLSSTSNPP HGLPATLRWF
FNLFQLYRGP LDLTIIITGA TDVDGMAWFT PVGLAVDTPW VEKESALSID YKTALGAVRF
NTRRTGNDQI RLPWYSYLYA VSGALDGLGD KTDSTFGLVS IQIANYNHSD EYLSFSCYLS
VTEQSEFYFP RAPLNTNAMM SSETVMDRIA LGDLESSVDD PRTEEDRKFE SHIEKRKPYK
ELRLEVGKQR LKYAQEELSN EVLPPPRK
