POLN_HEVUS
ID POLN_HEVUS Reviewed; 1708 AA.
AC Q9YLR1;
DT 20-MAY-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 90.
DE RecName: Full=Non-structural polyprotein pORF1;
DE Includes:
DE RecName: Full=Methyltransferase;
DE EC=2.1.1.-;
DE EC=2.7.7.-;
DE Includes:
DE RecName: Full=Putative papain-like cysteine protease;
DE Short=PLP;
DE EC=3.4.22.-;
DE Includes:
DE RecName: Full=NTPase/helicase;
DE EC=3.6.4.-;
DE Includes:
DE RecName: Full=RNA-directed RNA polymerase;
DE Short=RdRp;
DE EC=2.7.7.48;
GN ORFNames=ORF1;
OS Hepatitis E virus genotype 3 (isolate Human/United States/US2) (HEV-3).
OC Viruses; Riboviria; Orthornavirae; Kitrinoviricota; Alsuviricetes;
OC Hepelivirales; Hepeviridae; Orthohepevirus; Hepatitis E virus.
OX NCBI_TaxID=509615;
OH NCBI_TaxID=69079; Bandicota bengalensis (lesser bandicoot rat).
OH NCBI_TaxID=9481; Callithrix.
OH NCBI_TaxID=9536; Cercopithecus hamlyni (Owl-faced monkey) (Hamlyn's monkey).
OH NCBI_TaxID=9534; Chlorocebus aethiops (Green monkey) (Cercopithecus aethiops).
OH NCBI_TaxID=9606; Homo sapiens (Human).
OH NCBI_TaxID=9539; Macaca (macaques).
OH NCBI_TaxID=10090; Mus musculus (Mouse).
OH NCBI_TaxID=9598; Pan troglodytes (Chimpanzee).
OH NCBI_TaxID=9520; Saimiri (squirrel monkeys).
OH NCBI_TaxID=9823; Sus scrofa (Pig).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=10092008; DOI=10.1099/0022-1317-80-3-681;
RA Erker J.C., Desai S.M., Schlauder G.G., Dawson G.J., Mushahwar I.K.;
RT "A hepatitis E virus variant from the United States: molecular
RT characterization and transmission in cynomolgus macaques.";
RL J. Gen. Virol. 80:681-690(1999).
CC -!- FUNCTION: Methyltransferase: Displays a capping enzyme activity. This
CC function is necessary since all viral RNAs are synthesized in the
CC cytoplasm, and host capping enzymes are restricted to the nucleus. The
CC enzymatic reaction involves a covalent link between 7-methyl-GMP and
CC the methyltransferase, whereas eukaryotic capping enzymes form a
CC covalent complex only with GMP. Methyltransferase catalyzes transfer of
CC a methyl group from S-adenosylmethionine to GTP and GDP to yield
CC m(7)GTP or m(7)GDP. This enzyme also displays guanylyltransferase
CC activity to form a covalent complex, methyltransferase-m(7)GMP, from
CC which 7-methyl-GMP is transferred to the mRNA to create the cap
CC structure. {ECO:0000250|UniProtKB:Q81862}.
CC -!- FUNCTION: Papain-like cysteine protease: May participate in the
CC processing of polyprotein pORF1 together with cellular proteases and
CC the cleavage of capsid protein ORF2. {ECO:0000250|UniProtKB:Q81862}.
CC -!- FUNCTION: NTPase/helicase: Multi-functional protein that exhibits
CC NTPase and RNA unwinding activities. Hydrolyzes all NTPs efficiently
CC and unwinds RNA duplexes containing 5' overhangs. Possesses a sequence
CC independent RNA-5'-triphosphatase (RTPase) activity suggestive of its
CC role in forming viral cap structure (By similarity). Participates also
CC in viral genome replication, RNA translocation and genome
CC packaging/unpackaging (By similarity). {ECO:0000250|UniProtKB:P29324,
CC ECO:0000250|UniProtKB:Q81862}.
CC -!- FUNCTION: RNA-directed RNA polymerase: Plays an essential role in the
CC virus replication. Binds to the 3'-end of the genomic RNA to initiate
CC viral replication. {ECO:0000250|UniProtKB:Q81862}.
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:Q81862};
CC -!- SUBCELLULAR LOCATION: Host cytoplasm {ECO:0000250|UniProtKB:Q81862}.
CC -!- PTM: It is not yet clear whether the ORF1-encoded polyprotein contains
CC multiple biochemical activities, or undergoes cis or trans- processing
CC to release biochemically distinct peptides. No processing has been
CC observed in mammalian expression systems. However, the baculovirus
CC expressed polyprotein is processed into smaller protein, probably by a
CC cysteine protease.
CC -!- SIMILARITY: Belongs to the hepevirus non-structural polyprotein family.
CC {ECO:0000305}.
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DR EMBL; AF060669; AAD15815.1; -; Genomic_DNA.
DR PRIDE; Q9YLR1; -.
DR Proteomes; UP000007247; Genome.
DR GO; GO:0030430; C:host cell cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0008234; F:cysteine-type peptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0004386; F:helicase activity; IEA:UniProtKB-KW.
DR GO; GO:0008174; F:mRNA methyltransferase activity; IEA:InterPro.
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:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR GO; GO:0006396; P:RNA processing; IEA:InterPro.
DR GO; GO:0006351; P:transcription, DNA-templated; IEA:InterPro.
DR GO; GO:0019082; P:viral protein processing; IEA:InterPro.
DR GO; GO:0039694; P:viral RNA genome replication; IEA:InterPro.
DR CDD; cd21557; Macro_X_Nsp3-like; 1.
DR Gene3D; 3.40.220.10; -; 1.
DR Gene3D; 3.40.50.300; -; 2.
DR InterPro; IPR027351; (+)RNA_virus_helicase_core_dom.
DR InterPro; IPR002588; Alphavirus-like_MT_dom.
DR InterPro; IPR043502; DNA/RNA_pol_sf.
DR InterPro; IPR008748; Hepatitis-E_Cys-pept.
DR InterPro; IPR022202; Hepatitis-E_hinge.
DR InterPro; IPR002589; Macro_dom.
DR InterPro; IPR043472; Macro_dom-like.
DR InterPro; IPR044371; Macro_X_NSP3-like.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR007094; RNA-dir_pol_PSvirus.
DR InterPro; IPR001788; Tymovirus_RNA-dep_RNA_pol.
DR Pfam; PF12526; DUF3729; 1.
DR Pfam; PF01661; Macro; 1.
DR Pfam; PF05417; Peptidase_C41; 1.
DR Pfam; PF00978; RdRP_2; 1.
DR Pfam; PF01443; Viral_helicase1; 1.
DR Pfam; PF01660; Vmethyltransf; 1.
DR SMART; SM00506; A1pp; 1.
DR SUPFAM; SSF52540; SSF52540; 2.
DR SUPFAM; SSF52949; SSF52949; 1.
DR SUPFAM; SSF56672; SSF56672; 1.
DR PROSITE; PS51743; ALPHAVIRUS_MT; 1.
DR PROSITE; PS51154; MACRO; 1.
DR PROSITE; PS51657; PSRV_HELICASE; 1.
DR PROSITE; PS50507; RDRP_SSRNA_POS; 1.
PE 3: Inferred from homology;
KW ATP-binding; Helicase; Host cytoplasm; Hydrolase; Methyltransferase;
KW Nucleotide-binding; Nucleotidyltransferase; Protease; RNA-binding;
KW RNA-directed RNA polymerase; Thiol protease; Transferase;
KW Viral RNA replication.
FT CHAIN 1..1708
FT /note="Non-structural polyprotein pORF1"
FT /id="PRO_0000334531"
FT DOMAIN 56..240
FT /note="Alphavirus-like MT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01079"
FT DOMAIN 790..936
FT /note="Macro"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00490"
FT DOMAIN 949..1097
FT /note="(+)RNA virus helicase ATP-binding"
FT DOMAIN 1098..1231
FT /note="(+)RNA virus helicase C-terminal"
FT DOMAIN 1469..1580
FT /note="RdRp catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00539"
FT REGION 60..240
FT /note="Methyltransferase"
FT /evidence="ECO:0000250"
FT REGION 239..439
FT /note="Y-domain"
FT /evidence="ECO:0000250"
FT REGION 440..610
FT /note="Putative papain-like cysteine protease"
FT /evidence="ECO:0000250"
FT REGION 712..731
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 714..793
FT /note="Hinge"
FT /evidence="ECO:0000250"
FT REGION 743..794
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 800..957
FT /note="X-domain"
FT /evidence="ECO:0000250"
FT REGION 975..1219
FT /note="NTPase/helicase"
FT /evidence="ECO:0000250"
FT REGION 1222..1708
FT /note="RNA-directed RNA polymerase"
FT /evidence="ECO:0000250"
FT COMPBIAS 768..787
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 990..997
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255"
SQ SEQUENCE 1708 AA; 187269 MW; BE0DF5EBEEDAB547 CRC64;
MEAHQFIKAP GITTAIEQAA LAAANSALAN AVVVRPFLSR VQTEILINLM QPRQLVFRPE
VLWNHPIQRV IHNELEQYCR ARAGRCLEVG AHPRSINDNP NVLHRCFLRP VGRDVQRWYS
APTRGPAANC RRSALRGLPP VDRTYCFDGF SRCAFAAETG VALYSLHDLW PADVAEAMAR
HGMTRLYAAL HLPPEVLLPP GTYHTTSYLL IHDGNRAVVT YEGDTSAGYN HDVSILRAWI
RTTKIVGDHP LVIERVRAIG CHFVLLLTAA PEPSPMPYVP YPRSTEVYVR SIFGPGGSPS
LFPSACSTKS TFHAVPVHIW DXLMLFGATL XDQAFCCSRL MTYLRGISYK VTVGALVANE
GWNASEDALT AVITAAYLTI CHQRYLRTQA ISKGMRRLEV EHAQKFITRL YSWLFEKSGR
DYIPGRQLQF YAQCRRWLSA GFHLXPRXLV FDESVPCRCR TFLKKVAGKF CCFMRWLGQE
CTCFLEPAEG LVGDQGHDNE AYEGSEVDPA EPAHLDVSGT YAVHGHQLEA LYRALNVPHD
IAARASRLTA TVELVASPDR LECRTVLGNK TFRTTVVDGA HLEANGPEEY VLSFDASRQS
MGAGSHSLTY ELTPAGLQVK ISSNGLDCTA TFPPGGAPSA APGEVAAFCS ALYRYNRFTQ
RHSLTGGLWL HPEGLLGIFP PFSPGHIWES ANPFCGEGTL YTRTWSTSGF SSDFSPPEAA
APASAAAPGL PYPTPPVSDI WVLPPPSEES HVDAASVPSV PEPAGLTSPI VLTPPPPPPP
VRKPATSPPP RTRRLLYTYP DGAKVYAGSL XESDCDWLVN ASNPGHRPGG GLCHAFYQRF
PEAFYSTEFI MREGLAAYTL TPRPIIHAVA PDYRVEQNPK RLEAAYRETC SRRGTAAYPL
LGSGIYQVPV SLSFDAWERN HRPGDELYLT EPAAAWFEAN KPAQPALTIT EDTARTANLA
LEIDAATEVG RACAGCTISP GIVHYQFTAG VPGSGKSRSI QQGDVDVVVV PTRELRNSWR
RRGFAAFTPH TAARVTIGRR VVIDEAPSLP PHLLLLHMQR ASSVHLLGDP NQIPAIDFEH
AGLVPAIRPE LAPTSWWHVT HRCPADVCEL IRGAYPKIQT TSRVLRSLFW NEPAIGQKLV
FTQAAKAANP GAITVHEAQG ATFTETTIIA TADARGLIQS SRAHAIVALT RHTEKCVILD
APGLLREVGI SDVIVNNFFL AGGEVGHHRP SVIPRGNPDQ NLGTLQAFPP SCQISAYHQL
AEELGHRPAP VAAVLPPCPE LEQGLLYMPQ ELTVSDSVLV FELTDIVHCR MAAPSQRKAV
LSTLVGRYGR RTKLYEAAHS DVRESLARFI PTIGPVRATT CELYELVEAM VEKGQDGSAV
LELDLCNRDV SRITFFQKDC NKFTTGETIA HGKVGQGISA WSKTFCALFG PWFRAIEKEI
LALLPPNIFY GDAYEESVFA AAVSGAGSCM VFENDFSEFD STQNNFSLGL ECVVMEECGM
PQWLIRLYHL VRSAWILQAP KESLKGFWKK HSGEPGTLLW NTVWNMAIIA HCYEFRDFRV
AAFKGDDSVV LCSDYRQXRN AAALIAGCGL KLKVDYRPIG LYAGVVVAPG LGTLPDVVRF
AGRLSEKNWG PGPERAEQLR LAVCDFLRGL TNVAQVCVDV VSRVYGVSPG LVHNLIGMLQ
TIADGKAHFT ENIKPVLDLT NSIIQRVE
