POLN_HEVHY
ID POLN_HEVHY Reviewed; 1693 AA.
AC Q9WC28; O39221;
DT 20-MAY-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 96.
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 1 (isolate Human/India/Hyderabad) (HEV-1).
OC Viruses; Riboviria; Orthornavirae; Kitrinoviricota; Alsuviricetes;
OC Hepelivirales; Hepeviridae; Orthohepevirus; Hepatitis E virus.
OX NCBI_TaxID=512346;
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 RNA].
RX PubMed=10630959;
RX DOI=10.1002/(sici)1096-9071(200003)60:3<275::aid-jmv5>3.0.co;2-9;
RA Ansari I.H., Nanda S.K., Durgapal H., Agrawal S., Mohanty S.K., Gupta D.,
RA Jameel S., Panda S.K.;
RT "Cloning, sequencing, and expression of the hepatitis E virus (HEV)
RT nonstructural open reading frame 1 (ORF1).";
RL J. Med. Virol. 60:275-283(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC STRAIN=Infectious clone pSGI-HEV;
RX PubMed=10666275; DOI=10.1128/jvi.74.5.2430-2437.2000;
RA Panda S.K., Ansari I.H., Durgapal H., Agrawal S., Jameel S.;
RT "The in vitro-synthesized RNA from a cDNA clone of hepatitis E virus is
RT infectious.";
RL J. Virol. 74:2430-2437(2000).
RN [3]
RP FUNCTION (RNA-DIRECTED RNA POLYMERASE), AND RNA-BINDING.
RC STRAIN=Infectious clone pSGI-HEV;
RX PubMed=11259193; DOI=10.1006/viro.2000.0819;
RA Agrawal S., Gupta D., Panda S.K.;
RT "The 3' end of hepatitis E virus (HEV) genome binds specifically to the
RT viral RNA-dependent RNA polymerase (RdRp).";
RL Virology 282:87-101(2001).
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 ECO:0000269|PubMed:11259193}.
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 -!- INTERACTION:
CC Q9WC28; Q9WC28: ORF1; NbExp=81; IntAct=EBI-11179420, EBI-11179420;
CC Q9WC28; Q68985: ORF2; NbExp=2; IntAct=EBI-11179420, EBI-11180197;
CC Q9WC28; O90299: ORF3; NbExp=41; IntAct=EBI-11179420, EBI-11179411;
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; AF028091; AAB82002.2; -; Genomic_RNA.
DR EMBL; AF076239; AAC27934.2; -; Genomic_RNA.
DR SMR; Q9WC28; -.
DR IntAct; Q9WC28; 2.
DR PRIDE; Q9WC28; -.
DR Proteomes; UP000007244; 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:0042802; F:identical protein binding; IPI:IntAct.
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; 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; 1.
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 1: Evidence at protein level;
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..1693
FT /note="Non-structural polyprotein pORF1"
FT /id="PRO_0000334530"
FT DOMAIN 56..240
FT /note="Alphavirus-like MT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01079"
FT DOMAIN 775..921
FT /note="Macro"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00490"
FT DOMAIN 934..1082
FT /note="(+)RNA virus helicase ATP-binding"
FT DOMAIN 1083..1216
FT /note="(+)RNA virus helicase C-terminal"
FT DOMAIN 1454..1565
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..778
FT /note="Hinge"
FT /evidence="ECO:0000250"
FT REGION 716..769
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 785..942
FT /note="X-domain"
FT /evidence="ECO:0000250"
FT REGION 960..1204
FT /note="NTPase/helicase"
FT /evidence="ECO:0000250"
FT REGION 1207..1693
FT /note="RNA-directed RNA polymerase"
FT /evidence="ECO:0000250"
FT COMPBIAS 738..754
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 975..982
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255"
FT CONFLICT 1100
FT /note="Y -> F (in Ref. 2; AAC27934)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1693 AA; 185580 MW; FB37B87BF6BBB501 CRC64;
MEAHQFLKAP GITTAVEQAA LATANSALAN AVVVRPFLSH QQIEILINLM QPRQLVFRPE
VFWNQPIQRV IHNELELYCR ARSGRCLEIG AHPRSINDNP NVVHRCFLRP VGRDVQRWYT
APTRGPAANC RRSALRGLPA ADRTYCFDGF SGCSCPAETG IALYSLHDMS PSDVAEAMFR
HGMTRLYAAL HLPPEVLLPP GTYRTASYLL IHDGRRVVVT YEGDTSAGYN HDVSNLRSWI
RTTKVTGDHP LVIERVRAIG CHFVLLLTAA PEPSPMPYVP YPRSTEVYVR SIFGPGGTPS
LFPTSCSTKS TFHAVPAHIW DRLMLFGATL DDQAFCCSRL MTYLRGISYK VTVGTLVANE
GRNASEDALT AVITAAYLTI CHQRYLRTQA ISKGIRRLER EHDQKFITRL YSWLFEKSGR
DYIPGRQLEF YAQCRRWLSA GFHLDPRVLV FDESAPCHCR TVIRKALSKF CCFMKWLGQE
CTCFLQPAEG VVGDQGHDNE SYEGSDVDPA ESAISDISGS YVVPGTALQP LYQALDLPDE
IVARACRLTA TVKVSQVDGR IDCETLLGNK TFRTSFVDGA VLETNGPERH NLSFDASQST
MAAGPFSLTY AASAAGLEVR YVGAGLDHRA IFAPGVSPRS NPGEVTAFCS ALYRFNREAQ
RHSLTGNLWF HPEGLIGLFA PFSPGHVWES AKPFCGESTL YTRTWSEVDA VSSPTRPDLG
FMSEPPIPSR AATPTLAAPL PPLAPDPSPP SSAPALDEPA SAATSGVPAI THQTARHRRL
LFTYPDGSKV FAGSLFESTC TWLVNASNVD HCPGGGLCHA FYQRYPASFD AACFVMRDGA
AAYTLTPRPI IHRVAPDYRL EHNPKRLEAA YRETCSRLGT AAYPLLGTGI YQVPIGPSFD
AWERNHRPGD ELYLPELAAR WFEANRPTRP TLTITEDAAR TANLAIELDS ATDVGRACAG
CRVTPGVVQY QFTAGVPGSG KSRSITRADV DVVVVPTREL RNAWRRRGFA AFTPHTAARV
TDGRRVVIDE APSLPPHLLL LHMQRAATVH LLGDPNQIPA IDFEHPGLVP AIRPDLAPTS
WWHVTHRCPA DVCELIRGAY PMIQTTSRVL RSLFWGEPAV GQKLVFTQAA KPANPGSVTV
HDSQGATYTY TTIIATADAR GLIQSSRAHA IVALTRHTEK WVIIDAPGLL REVGISDAIV
NNFFLAGGEI GHQRPSVIPR GNPDANVDTL AAFPPSCQIS AFHQLAEELG HRPAPVAAVL
PPCPELEQGL LYLPQELTTC DSVVTFELTD IVHCRMAAPS QRKAVVSTLV GRYGRRTKLY
NASHSDVRDS LARFIPAIGP VQVTTCELYE LVEAMVEKGQ DGSAVLELDL CNRDVSRITF
FQKDCNKFTT GETIAHGKVG QGISAWSKTF CALFGPWFRA IEKAILALLP QGVFYGDAFD
DTVFSAAVAA AKASMVFEND FSEFDSTQNN FSLGLECAIM EECGMPQGLI RLYHLIRSAW
ILQAPKESLL GFWKKHSGEP GTLLWNTVWN MAVITHCYDF RDLQVAAFKG DDSIVLCSEY
RQSPGAAVLI AGCGLKLKVD FRPMRLYAGV VVAPGLGALP DVVRFAGRLT EKNWGPGPER
ADELRIAVSD FLRKLTNVAQ MCVDVVSRVY GVSPGLVHNL IGMLQAVADG KAHFTESVKP
VLDLTNSILC RVE
