ID   POLG_HPE2W              Reviewed;        2179 AA.
AC   O73556;
DT   15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT   01-AUG-1998, sequence version 1.
DT   03-AUG-2022, entry version 148.
DE   RecName: Full=Genome polyprotein;
DE   Contains:
DE     RecName: Full=Capsid protein VP0;
DE     AltName: Full=P1AB;
DE     AltName: Full=Virion protein 0;
DE   Contains:
DE     RecName: Full=Capsid protein VP3;
DE     AltName: Full=P1C;
DE     AltName: Full=Virion protein 3;
DE   Contains:
DE     RecName: Full=Capsid protein VP1;
DE     AltName: Full=P1D;
DE     AltName: Full=Virion protein 1;
DE   Contains:
DE     RecName: Full=Protein 2A;
DE              Short=P2A;
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 3A;
DE              Short=P3A;
DE   Contains:
DE     RecName: Full=Protein 3B;
DE              Short=P3B;
DE     AltName: Full=VPg;
DE   Contains:
DE     RecName: Full=Protease 3C;
DE              Short=P3C;
DE              EC=3.4.22.28;
DE              EC=3.4.22.29;
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;
OS   Human parechovirus 2 (strain Williamson) (HPeV-2) (Echovirus 23).
OC   Viruses; Riboviria; Orthornavirae; Pisuviricota; Pisoniviricetes;
OC   Picornavirales; Picornaviridae; Parechovirus.
OX   NCBI_TaxID=122962;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=9820139; DOI=10.1099/0022-1317-79-11-2641;
RA   Ghazi F., Hughes P.J., Hyypiae T., Stanway G.;
RT   "Molecular analysis of human parechovirus type 2 (formerly echovirus 23).";
RL   J. Gen. Virol. 79:2641-2650(1998).
CC   -!- FUNCTION: [Protein 2A]: Is not a protease. {ECO:0000250}.
CC   -!- FUNCTION: [Protein 2B]: Affects membrane integrity and cause an
CC       increase in membrane permeability. {ECO:0000250}.
CC   -!- FUNCTION: [Protein 2C]: Associates with and induces structural
CC       rearrangements of intracellular membranes. It displays RNA-binding,
CC       nucleotide binding and NTPase activities (By similarity).
CC       {ECO:0000250}.
CC   -!- FUNCTION: Protein 3A, via its hydrophobic domain, serves as membrane
CC       anchor. {ECO:0000250}.
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 (By
CC       similarity). {ECO:0000250}.
CC   -!- FUNCTION: RNA-directed RNA polymerase 3D-POL replicates genomic and
CC       antigenomic RNA by recognizing replications specific signals.
CC       {ECO:0000255|PROSITE-ProRule:PRU00539}.
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:0000255|PROSITE-ProRule:PRU00539};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Selective cleavage of Tyr-|-Gly bond in the picornavirus
CC         polyprotein.; EC=3.4.22.29;
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   -!- 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   -!- SUBCELLULAR LOCATION: [Capsid protein VP3]: Virion {ECO:0000250}. Host
CC       cytoplasm {ECO:0000305}.
CC   -!- SUBCELLULAR LOCATION: [Capsid protein VP1]: Virion {ECO:0000250}. Host
CC       cytoplasm {ECO:0000305}.
CC   -!- SUBCELLULAR LOCATION: [Protein 2B]: Host cytoplasmic vesicle membrane
CC       {ECO:0000305}; Peripheral membrane protein {ECO:0000305}; Cytoplasmic
CC       side {ECO:0000305}. Note=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 (By similarity). {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: [Protein 2C]: Host cytoplasmic vesicle membrane
CC       {ECO:0000305}; Peripheral membrane protein {ECO:0000305}; Cytoplasmic
CC       side {ECO:0000305}. Note=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 (By similarity). {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: [Protein 3A]: Host cytoplasmic vesicle membrane
CC       {ECO:0000305}; Peripheral membrane protein {ECO:0000305}; Cytoplasmic
CC       side {ECO:0000305}. Note=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 (By similarity). {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: [Protein 3B]: Virion {ECO:0000305}.
CC   -!- SUBCELLULAR LOCATION: [Protease 3C]: Host cytoplasm {ECO:0000305}.
CC   -!- SUBCELLULAR LOCATION: [RNA-directed RNA polymerase 3D-POL]: Host
CC       cytoplasmic vesicle membrane {ECO:0000305}; Peripheral membrane protein
CC       {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Note=Probably localizes
CC       to the surface of intracellular membrane vesicles that are induced
CC       after virus infection as the site for viral RNA replication. These
CC       vesicles are derived from the endoplasmic reticulum (By similarity).
CC       {ECO:0000250}.
CC   -!- PTM: VPg is uridylylated by the polymerase and is covalently linked to
CC       the 5'-end of genomic RNA. This uridylylated form acts as a nucleotide-
CC       peptide primer for the polymerase (By similarity). {ECO:0000250}.
CC   -!- PTM: Specific enzymatic cleavages yield mature proteins. All cleavages
CC       are catalyzed by P3C.
CC   -!- SIMILARITY: Belongs to the picornaviruses polyprotein family.
CC       {ECO:0000305}.
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DR   EMBL; AJ005695; CAA06679.1; -; Genomic_RNA.
DR   SMR; O73556; -.
DR   PRIDE; O73556; -.
DR   Proteomes; UP000000670; Genome.
DR   GO; GO:0044162; C:host cell cytoplasmic vesicle membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0044385; C:integral to membrane of host cell; IEA:UniProtKB-KW.
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: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:0003724; F:RNA helicase activity; IEA:InterPro.
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:0039520; P:induction by virus of host autophagy; ISS:UniProtKB.
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:0039611; P:suppression by virus of host translation initiation factor activity; ISS:UniProtKB.
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; -; 1.
DR   Gene3D; 2.60.120.20; -; 3.
DR   Gene3D; 3.30.70.270; -; 1.
DR   Gene3D; 3.40.50.300; -; 1.
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; IPR007053; LRAT_dom.
DR   InterPro; IPR027417; P-loop_NTPase.
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   InterPro; IPR009419; VPP_parechovir_P3A.
DR   InterPro; IPR009407; VPP_parechovir_P3B.
DR   Pfam; PF06344; Parecho_VpG; 1.
DR   Pfam; PF00548; Peptidase_C3; 1.
DR   Pfam; PF06363; Picorna_P3A; 1.
DR   Pfam; PF00680; RdRP_1; 1.
DR   Pfam; PF00073; Rhv; 1.
DR   Pfam; PF00910; RNA_helicase; 1.
DR   PRINTS; PR00918; CALICVIRUSNS.
DR   SUPFAM; SSF50494; SSF50494; 1.
DR   SUPFAM; SSF52540; SSF52540; 1.
DR   SUPFAM; SSF56672; SSF56672; 1.
DR   PROSITE; PS51934; LRAT; 1.
DR   PROSITE; PS51874; PCV_3C_PRO; 1.
DR   PROSITE; PS50507; RDRP_SSRNA_POS; 1.
DR   PROSITE; PS51218; SF3_HELICASE_2; 1.
PE   3: Inferred from homology;
KW   ATP-binding; Capsid protein; Covalent protein-RNA linkage; Helicase;
KW   Host cytoplasm; Host cytoplasmic vesicle; Host membrane;
KW   Host-virus interaction; Hydrolase; Ion channel; Ion transport; Lipoprotein;
KW   Membrane; Myristate; Nucleotide-binding; Nucleotidyltransferase;
KW   Phosphoprotein; Protease; Reference proteome; RNA-binding;
KW   RNA-directed RNA polymerase; T=pseudo3 icosahedral capsid protein;
KW   Thiol protease; Transferase; Transport; Viral attachment to host cell;
KW   Viral ion channel; Viral RNA replication; Virion;
KW   Virus entry into host cell.
FT   CHAIN           1..289
FT                   /note="Capsid protein VP0"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000039750"
FT   CHAIN           290..542
FT                   /note="Capsid protein VP3"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000039751"
FT   CHAIN           543..775
FT                   /note="Capsid protein VP1"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000039752"
FT   CHAIN           776..922
FT                   /note="Protein 2A"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000039753"
FT   CHAIN           923..1044
FT                   /note="Protein 2B"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000039754"
FT   CHAIN           1045..1373
FT                   /note="Protein 2C"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000039755"
FT   CHAIN           1374..1490
FT                   /note="Protein 3A"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000039756"
FT   CHAIN           1491..1510
FT                   /note="Protein 3B"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000039757"
FT   CHAIN           1511..1710
FT                   /note="Protease 3C"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000039758"
FT   CHAIN           1711..2179
FT                   /note="RNA-directed RNA polymerase 3D-POL"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000039759"
FT   DOMAIN          786..881
FT                   /note="LRAT"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01283"
FT   DOMAIN          1156..1317
FT                   /note="SF3 helicase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00551"
FT   DOMAIN          1517..1707
FT                   /note="Peptidase C3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01222"
FT   DOMAIN          1944..2058
FT                   /note="RdRp catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00539"
FT   MOTIF           763..765
FT                   /note="Cell attachment site"
FT                   /evidence="ECO:0000255"
FT   ACT_SITE        1557
FT                   /note="For protease 3C activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01222"
FT   ACT_SITE        1595
FT                   /note="For protease 3C activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01222"
FT   ACT_SITE        1669
FT                   /note="For protease 3C activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01222"
FT   ACT_SITE        2044
FT                   /note="For RdRp activity"
FT                   /evidence="ECO:0000250|UniProtKB:P12296"
FT   BINDING         1184..1191
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00551"
FT   SITE            775..776
FT                   /note="Cleavage; by protease 2A"
FT                   /evidence="ECO:0000255"
FT   MOD_RES         1493
FT                   /note="O-(5'-phospho-RNA)-tyrosine"
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   2179 AA;  245874 MW;  96803C0BB8856664 CRC64;
     METIKSIADM ATGVTKTIDA TINSVNEIIT NTDNASGGDI LTKVADDASN ILGPNCYATT
     SEPENKDVVQ ATTTVNTTNL TQHPSAPTLP FTPDFSNVDT FHSMAYDTTT GSKNPNKLVR
     LTTHAWASTL QRGHQIDHVN LPVDFWDEQR KPAYGHAKYF AAVRCGFHFQ VQVNVNQGTA
     GSALVVYEPK PVVDYDKDLE FGAFTNLPHV LMNLAETTQA DLCIPYVADT NYVKTDSSDL
     GQLKVYVWTP LSIPSGSSNQ VDVTILGSLL QLDFQNPRVY GQNVDIYDTA PSKPIPLRKT
     KYLTMSTKYK WTRNKVDIAE GPGSMNMANV LSTTAAQSVA LVGERAFYDP RTAGSKSRFD
     DLVKISQLFS VMADSTTPSA NHGIDQKGYF KWSANSDPQA IVHRNLVHLN LFPNLKVFEN
     SYSYFRGSLI IRLSVYASTF NRGRLNGFFP NSSTDETSEI DNAIYTICDI GSDNSFEITI
     PYSFSTWMRK THGKPIGLFQ IEVLNRLTYN YSSPNEVYCI VQGKMGQDAK FFCPTGSLVT
     FQNSWGSQMD LTDPLCIEDS VEDCKQTITP TELGLTSAQD DGPLGNDKPN YFLNFKSMNV
     DIFTVSHTKV DNIFGRAWFA HVHDFTNDGL WRQGLEFPKE GHGALSLLFA YFTGELNIHV
     LFLSDRGFLR VGHTYDTETN RTNFLSSSGI ITVPAGEQMT LSVPSYSNKP LRTVRSSNAL
     GYLLCKPLLT GTSSGRIEIF LSLRCPNFFF PLPAPKPATR KYRGDLATWS DQSPYGRQGK
     KQLMKLAYLD RGFYKHYGIV VGDDVYQLDS DDIFKTALTG KAKFTKTRLT PDWVVEEECE
     LDYFRIKYLE SSVNSEHIFS VDNNCETIAK DIFGSHSLSQ HQQIGLIGTI LLTAGLMSTI
     KTPVNPTTIK EFFNHAIEGD EQGLSLLVQK CTTFFSSAAT ELLDNDLVKF IIKILVRILC
     YMVLYCHKPN ILTTACLSTL LVMDVTSSSV LSPSCKALMQ CLMDGDVKKL AEVVAESMSN
     TDDDEIKEQI CDTVKYTKQI LSNQGPFKGF NEISTAFRHI DWWIQTLLKI KDMVLSVFKP
     SVEKRAVEWL ERNKEHVCSI LDYASDIIVK SKDQTKMKTQ EFYQRYNDCL SKFKPIMAMC
     FRSCHNSISN TVYRLFQELA RIPNRMATQN DLIRVEPIGI WIQGEPGQGK SFLTHTLSKQ
     LQKTCGLQGI YTNPTASEFM DGYDNQDIHL IDDLGQTRKE RDIEMLCNCI SSDPDIVPMA
     HLEEKGKFYT SKLVIATTNK PDFSSTVLLD SGALRRRFPY IMHIRAAKHY SKSGKLNVSQ
     AMPHMSTGEC WEVSKNGRDW ETLKLKELID KITVDYKERI ANYNTWKKQL EDQTLDDLDD
     AVSYIKHNYP DAIPYIDEYL NIEMSTLIEQ MEAFIEPKPS VFKCFASRVG DKIKEASREV
     VKWFSDKLKS MLNFVERNKA WLTVVSAVTS AIGILLLVTK IFKKEESKDE RAYNPTLPVA
     KPKGTFPVSQ REFKNEAPYD GQLEHIISQM AYITGSTTGH ITHCAGYQHD EIILHGHSIK
     YLEQEEELTL HYKNKVFPIE QPSVTQVTLG GKPMDLAIVK CKLPFRFKKN SKYYTNKIGT
     ESMLIWMTEQ GIITKEVQRV HHSGGIKTRE GTESTKTISY TVKSCKGMCG GLLISKVEGN
     FKILGMHIAG NGEMGVAIPF NFLKNDMSDQ GIVTEVTPIQ PMYINTKSQI HKSPVYGAVE
     VKMGPAVLSK SDTRLEEPVD CLVKKSASKY RVNKFQVNNE LWQGVKACVK SKFREIFGVN
     GIVDMKTAIL GTSHVNSMDL STSAGYSFVK SGYKKKDLIC LEPFSVSPML EKLVQEKFHN
     LLKGNQITTI FNTCLKDELR KLDKIATGKT RCIEACEIDY CIVYRMIMME IYDKIYQTPC
     YYSGLAVGIN PYRDWHFMIN ALNDYNYEMD YSQYDGSLSS MLLWEAVQVL AYCHDSPDLV
     MQLHKPVIDS DHVVFNERWL IHGGMPSGSP CTTVLNSLCN LMMCIYTTNL ISPGIDCLPI
     VYGDDVILSL DKEIEPERLQ SIMAESFGAE VTGSRKDEPP SLKPRMEVEF LKRKPGYFPE
     STFIVGKLDT ENMIQHLMWM KNFSTFKQQL QSYLMELCLH GKDTYQHYVK ILNPYLKEWN
     IPVDDYEVVI GKLVPMVFD