POLN_HEVMY
ID POLN_HEVMY Reviewed; 1693 AA.
AC Q04610;
DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1993, sequence version 1.
DT 03-AUG-2022, entry version 104.
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/Myanmar/HEVNE8L) (HEV-1).
OC Viruses; Riboviria; Orthornavirae; Kitrinoviricota; Alsuviricetes;
OC Hepelivirales; Hepeviridae; Orthohepevirus; Hepatitis E virus.
OX NCBI_TaxID=31769;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=8470371; DOI=10.1007/bf01702352;
RA Aye T.T., Uchida T., Ma M.Z., Iida F., Shikata T., Ichikawa M.,
RA Rikihisa T., Winn K.;
RT "Sequence and gene structure of the hepatitis E virus isolated from
RT Myanmar.";
RL Virus Genes 7:95-109(1993).
RN [2]
RP CHARACTERIZATION OF METHYLTRANSFERASE.
RX PubMed=11413290; DOI=10.1128/jvi.75.14.6249-6255.2001;
RA Magden J., Takeda N., Li T., Auvinen P., Ahola T., Miyamura T., Merits A.,
RA Kaeaeriaeinen L.;
RT "Virus-specific mRNA capping enzyme encoded by hepatitis E virus.";
RL J. Virol. 75:6249-6255(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; D10330; BAA01172.1; -; Genomic_RNA.
DR SMR; Q04610; -.
DR Proteomes; UP000007246; 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; 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_0000100134"
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 737..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..756
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"
SQ SEQUENCE 1693 AA; 185216 MW; AAB4C9140A7E21EA CRC64;
MEAHQFIKAH GITTAIEQAA LAAANSALAN AVVVRPFLSH QQIEILINLM QPRQLVFRPE
VFWNHPIQRV IHNELELYCR ARSGRCLEIG AHPRSINDNP NVVHRCFLLP VGRDVQRWYT
APTRGPAANC RRSALRGLPA VDRTYCLDGF 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 EHAQKFITPL YSWLFEKSGR
DYIPGRQLEF YAQCRRWLSA GFHLDPRVLV FDESAPCRCR TAIRKALSKF CCFMKWLGQE
CTCFLQPAEG VVGDQGHDNE AYEGSDVDPA ESAISDISGS YVVPGTALQP LYQALDLPAE
IVARAGRLTA TVKVSQVDGR IDCETLLGNK TFRTSFVDGA VLEANGPERY NLSFDASQST
MAAGPFSLTY AASAAGLEVR YVAAGLDHRA VFAPGVSPRS APGEVTAFCS ALYRFNREAQ
RHSLTGNLWF HPEGLIGLFA PFSPGHVWES ANPFCGESTL YTRTWSEVDA VSSPARPDLG
LMSEPSIPSR AATPTLAVLL PPPAPDPPPP PSAPALDEPA SGATAGAPAI THQTARHRRL
LFTYPDGSKV FAGSLFESTC TWLVNASNVD HRPGGGLCHA FYQRYPASFD AASFVMRDGA
AAYTLTPRPI IHAVAPDYRL EHNPKRLEAA YRETCSRLGT AAYSLLGTGI YQVPIGPSFD
AWERNHRPGD ELYLPELAAR WFEANRPTRP TLTITEDVAR TANLAIELDS ATDVGRACAG
CRVTPGVVQY QFTAGVPGSG KSRSITQADV DVVVVPTREL RNAWRRRGFA AFNPHTAARV
TQGRRVVIDE APSLPPHLLL LHMQRAATVH LLGDPNQIPA IDFEHAGLVP AIRPDLGPTS
WWHVTHRCPA DVCELIRGAY PMIQTTSRVL RSLFWGEPAV GQKLVFTQAA KAANPGSVTV
HEAQGATYTE TTIIATADAR GLIQSSRAHA IVALTRHTEK FVIIDAPGLL REVGISDAIV
NNFFLAGGEI GHQRPSVIPR GNPDANVDTL AAFPPSCQIS AFHQLAEELG HRPVPVAAVL
PPCPELEQGL LYLPQGLTAC DSVVTFELTD IVHCRMAAPN QRKAVLSTLV GRYGRRTKLY
NASHSDVRDS LARFIPAIGP VQVTTCELYE LVEAMVEKGQ DGSAVLELDL CNRDVSRITF
FQKDCNKFTT GETIAHGKVG QGISAWSKTF CALFGPWFRA IEKAILALLP QGVFYGDAFD
DTVFSAAVAA AKASMVFEND FSEFDSTQNN FSLGLECAIM EECGMPQWLI RLYHLIRSAW
ILQAPKESLR GFWKKHSGEP GTLLWNTVWN MAVITHCYDF RDFQVAAFKG DDSIVLCSEY
RQSPGAAVLI AGCGLKLKVD FRPIGLYAGV VVAPGLGALP DVVRFAGRLT EKNWGPGPER
AEQLRLAVSD FLRKLTNVAQ MCVDVVSRVY GVSPGLVHNL IGMLQAVADG KAHFTESVKP
VLDLTNSILC RVE
