POLN_HEVPA
ID POLN_HEVPA Reviewed; 1693 AA.
AC P33424; Q8UYD6;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 15-DEC-1998, sequence version 2.
DT 03-AUG-2022, entry version 107.
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/Pakistan/Sar-55) (HEV-1).
OC Viruses; Riboviria; Orthornavirae; Kitrinoviricota; Alsuviricetes;
OC Hepelivirales; Hepeviridae; Orthohepevirus; Hepatitis E virus.
OX NCBI_TaxID=33774;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=1731327; DOI=10.1073/pnas.89.2.559;
RA Tsarev S.A., Emerson S.U., Reyes G.R., Tsareva T.S., Legters L.J.,
RA Malik I.A., Iqbal M., Purcell R.H.;
RT "Characterization of a prototype strain of hepatitis E virus.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:559-563(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC STRAIN=Isolate pSK-HEV-2, and Isolate pSK-HEV-3;
RX PubMed=11742081; DOI=10.1073/pnas.251555098;
RA Emerson S.U., Zhang M., Meng X.J., Nguyen H., St Claire M.,
RA Govindarajan S., Huang Y.K., Purcell R.H.;
RT "Recombinant hepatitis E virus genomes infectious for primates: importance
RT of capping and discovery of a cis-reactive element.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:15270-15275(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 -!- 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; M80581; AAA45725.1; -; Genomic_RNA.
DR EMBL; AF444002; AAL50055.1; -; Genomic_RNA.
DR EMBL; AF444003; AAL50058.1; -; Genomic_RNA.
DR PIR; A38196; A38196.
DR SMR; P33424; -.
DR Proteomes; UP000001322; Genome.
DR Proteomes; UP000008498; Genome.
DR Proteomes; UP000180763; 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; 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 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..1693
FT /note="Non-structural polyprotein pORF1"
FT /id="PRO_0000100135"
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 712..771
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 732..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 VARIANT 766
FT /note="R -> G (in strain: Isolate pSK-HEV-2 and Isolate
FT pSK-HEV-3)"
SQ SEQUENCE 1693 AA; 185150 MW; 5A0F03FB1F1B99E8 CRC64;
MEAHQFIKAP GITTAIEQAA LAAANSALAN AVVVRPFLSH QQIEILINLM QPRQLVFRPE
VFWNHPIQRV IHNELELYCR ARSGRCLEIG AHPRSINDNP NVVHRCFLRP AGRDVQRWYT
APTRGPAANC RRSALRGLPA ADRTYCFDGF SGCNFPAETG IALYSLHDMS PSDVAEAMFR
HGMTRLYAAL HLPPEVLLPP GTYRTASYLL IHDGRRVVVT YEGDTSAGYN HDVSNLRSWI
RTTKVTGDHP LVIERVRAIG CHFVLLLTAA PEPSPMPYVP YPRSTEVYVR SIFGPGGTPS
LFPTSCSTKS TFHAVPAHIW DRLMLFGATL DDQAFCCSRL MTYLRGISYK VTVGTLVANE
GWNASEDALT AVITAAYLTI CHQRYLRTQA ISKGMRRLER EHAQKFITRL YSWLFEKSGR
DYIPGRQLEF YAQCRRWLSA GFHLDPRVLV FDESAPCHCR TAIRKAVSKF CCFMKWLGQE
CTCFLQPAEG VVGDQGHDNE AYEGSDVDPA ESAISDISGS YVVPGTALQP LYQALDLPAE
IVARAGRLTA TVKVSQVDGR IDCETLLGNK TFRTSFVDGA VLETNGPERH NLSFDASQST
MAAGPFSLTY AASAAGLEVR YVAAGLDHRA VFAPGVSPRS APGEVTAFCS ALYRFNREAQ
RLSLTGNFWF HPEGLLGPFA PFSPGHVWES ANPFCGESTL YTRTWSEVDA VPSPAQPDLG
FTSEPSIPSR AATPTPAAPL PPPAPDPSPT LSAPARGEPA PGATARAPAI THQTARHRRL
LFTYPDGSKV FAGSLFESTC TWLVNASNVD HRPGGGLCHA FYQRYPASFD AASFVMRDGA
AAYTLTPRPI IHAVAPDYRL EHNPKRLEAA YRETCSRLGT AAYPLLGTGI YQVPIGPSFD
AWERNHRPGD ELYLPELAAR WFEANRPTCP TLTITEDVAR TANLAIELDS ATDVGRACAG
CRVTPGVVQY QFTAGVPGSG KSRSITQADV DVVVVPTREL RNAWRRRGFA AFTPHTAARV
TQGRRVVIDE APSLPPHLLL LHMQRAATVH LLGDPNQIPA IDFEHAGLVP AIRPDLAPTS
WWHVTHRCPA DVCELIRGAY PMIQTTSRVL RSLFWGEPAV GQKLVFTQAA KAANPGSVTV
HEAQGATYTE TTIIATADAR GLIQSSRAHA IVALTRHTEK CVIIDAPGLL REVGISDAIV
NNFFLAGGEI GHQRPSVIPR GNPDANVDTL AAFPPSCQIS AFHQLAEELG HRPAPVAAVL
PPCPELEQGL LYLPQELTTC DSVVTFELTD IVHCRMAAPS QRKAVLSTLV GRYGRRTKLY
NASHSDVRDS LARFIPAIGP VQVTTCELYE LVEAMVEKGQ DGSAVLELDL CSRDVSRITF
FQKDCNKFTT GETIAHGKVG QGISAWSKTF CALFGPWFRA IEKAILALLP QGVFYGDAFD
DTVFSAAVAA AKASMVFEND FSEFDSTQNN FSLGLECAIM EECGMPQWLI RLYHLIRSAW
ILQAPKESLR GFWKKHSGEP GTLLWNTVWN MAVITHCYDF RDLQVAAFKG DDSIVLCSEY
RQSPGAAVLI AGCGLKLKVD FRPIGLYAGV VVAPGLGALP DVVRFAGRLT EKNWGPGPER
AEQLRLAVSD FLRKLTNVAQ MCVDVVSRVY GVSPGLVHNL IGMLQAVADG KAHFTESVKP
VLDLTNSILC RVE
