POLN_HEVCH
ID POLN_HEVCH Reviewed; 1693 AA.
AC Q81862; Q81344; Q81863; Q81864; Q81865; Q81866; Q81867; Q81868; Q81869;
DT 30-NOV-2010, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
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 Includes:
DE RecName: Full=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/China/HeBei/1987) (HEV).
OC Viruses; Riboviria; Orthornavirae; Kitrinoviricota; Alsuviricetes;
OC Hepelivirales; Hepeviridae; Orthohepevirus; Hepatitis E virus.
OX NCBI_TaxID=652674;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=8346669; DOI=10.1016/0168-1702(93)90024-h;
RA Bi S.L., Purdy M.A., McCaustland K.A., Margolis H.S., Bradley D.W.;
RT "The sequence of hepatitis E virus isolated directly from a single source
RT during an outbreak in China.";
RL Virus Res. 28:233-247(1993).
RN [2]
RP FUNCTION (NTPASE/HELICASE).
RX PubMed=20592074; DOI=10.1128/jvi.00492-10;
RA Karpe Y.A., Lole K.S.;
RT "RNA 5'-triphosphatase activity of the hepatitis E virus helicase domain.";
RL J. Virol. 84:9637-9641(2010).
RN [3]
RP FUNCTION (NTPASE/HELICASE), AND MUTAGENESIS OF LEU-1110 AND VAL-1120.
RX PubMed=24630891; DOI=10.1016/j.virusres.2014.02.018;
RA Devhare P., Sharma K., Mhaindarkar V., Arankalle V., Lole K.;
RT "Analysis of helicase domain mutations in the hepatitis E virus derived
RT from patients with fulminant hepatic failure: effects on enzymatic
RT activities and virus replication.";
RL Virus Res. 184:103-110(2014).
RN [4]
RP FUNCTION (PAPAIN-LIKE CYSTEINE PROTEASE), AND MUTAGENESIS OF HIS-443;
RP CYS-472; CYS-481 AND CYS-483.
RX PubMed=24795447; DOI=10.1099/vir.0.066142-0;
RA Paliwal D., Panda S.K., Kapur N., Varma S.P., Durgapal H.;
RT "Hepatitis E virus (HEV) protease: a chymotrypsin-like enzyme that
RT processes both non-structural (pORF1) and capsid (pORF2) protein.";
RL J. Gen. Virol. 95:1689-1700(2014).
RN [5]
RP FUNCTION (RNA-DIRECTED RNA POLYMERASE), AND MUTAGENESIS OF
RP 1551-ASN--ASN-1552.
RX PubMed=27324050; DOI=10.1099/jgv.0.000528;
RA Mahilkar S., Paingankar M.S., Lole K.S.;
RT "Hepatitis E virus RNA-dependent RNA polymerase: RNA template
RT specificities, recruitment and synthesis.";
RL J. Gen. Virol. 97:2231-2242(2016).
RN [6]
RP SUBCELLULAR LOCATION.
RX PubMed=29112323; DOI=10.1111/cmi.12804;
RA Farhat R., Ankavay M., Lebsir N., Gouttenoire J., Jackson C.L.,
RA Wychowski C., Moradpour D., Dubuisson J., Rouille Y., Cocquerel L.;
RT "Identification of GBF1 as a cellular factor required for hepatitis E virus
RT RNA replication.";
RL Cell. Microbiol. 20:0-0(2018).
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.
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:0000269|PubMed:24795447}.
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 (PubMed:20592074). Participates
CC also in viral genome replication, RNA translocation and genome
CC packaging/unpackaging (By similarity) (PubMed:24630891).
CC {ECO:0000250|UniProtKB:P29324, ECO:0000269|PubMed:20592074,
CC ECO:0000269|PubMed:24630891}.
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: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 -!- SUBCELLULAR LOCATION: Host cytoplasm {ECO:0000269|PubMed:29112323}.
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 (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the hepevirus non-structural polyprotein family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA96139.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; M94177; AAA96139.1; ALT_FRAME; Genomic_RNA.
DR EMBL; L08816; AAA03182.1; -; Genomic_RNA.
DR EMBL; L08816; AAA03183.1; -; Genomic_RNA.
DR EMBL; L08816; AAA03184.1; -; Genomic_RNA.
DR EMBL; L08816; AAA03185.1; -; Genomic_RNA.
DR EMBL; L08816; AAA03186.1; -; Genomic_RNA.
DR EMBL; L08816; AAA03187.1; -; Genomic_RNA.
DR EMBL; L08816; AAA03188.1; -; Genomic_RNA.
DR EMBL; L08816; AAA03189.1; -; Genomic_RNA.
DR RefSeq; NP_056779.1; NC_001434.1.
DR SMR; Q81862; -.
DR PRIDE; Q81862; -.
DR DNASU; 1494415; -.
DR GeneID; 1494415; -.
DR KEGG; vg:1494415; -.
DR SABIO-RK; Q81862; -.
DR Proteomes; UP000006705; Genome.
DR Proteomes; UP000102625; 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; Reference proteome;
KW RNA-binding; RNA-directed RNA polymerase; Thiol protease; Transferase;
KW Viral RNA replication.
FT CHAIN 1..1693
FT /note="Non-structural polyprotein pORF1"
FT /id="PRO_0000402397"
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 732..768
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 735..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"
FT MUTAGEN 443
FT /note="H->A: Complete loss of capsid protein ORF2
FT cleavage."
FT /evidence="ECO:0000269|PubMed:24795447"
FT MUTAGEN 472
FT /note="C->A: Complete loss of capsid protein ORF2
FT cleavage."
FT /evidence="ECO:0000269|PubMed:24795447"
FT MUTAGEN 481
FT /note="C->A: Complete loss of capsid protein ORF2
FT cleavage."
FT /evidence="ECO:0000269|PubMed:24795447"
FT MUTAGEN 483
FT /note="C->A: Complete loss of capsid protein ORF2
FT cleavage."
FT /evidence="ECO:0000269|PubMed:24795447"
FT MUTAGEN 1110
FT /note="L->F: About 20% loss of viral replication,."
FT /evidence="ECO:0000269|PubMed:24630891"
FT MUTAGEN 1120
FT /note="V->I: About 70% loss of viral replication."
FT /evidence="ECO:0000269|PubMed:24630891"
FT MUTAGEN 1551..1552
FT /note="DD->AA: More than 95% loss of viral replication."
FT /evidence="ECO:0000269|PubMed:27324050"
SQ SEQUENCE 1693 AA; 185054 MW; D3363602435B8FF5 CRC64;
MEAHQFIKAP GITTAIEQAA LAAANSALAN AVVVRPFLSH QQIEILINLM QPRQLVFRPE
VFWNHPIQRV IHNELELYCR ARSGRCLEIG AHPRSINDNP NVVHRCFLRP AGRDVQRWYT
APTRGPAANC RRSALRGLPA ADRTYCFDGF SGCNFPAETG VALYSLHDMS PSDVAEAMFR
HGMTRLYAAL HLPPEVLLPP GTYRTASYLL IHDGRRVVVT YEGDTSAGYN HDVSNLRSWI
RTTKVTGDHP LVIERVRAIG CHFVLLLTAA PEPSPTPYVP YPRSTEVYVR SIFGPGGTPS
LFPTSCSTKS TFHAVPAHIW DRLMLFGATL DDQAFCCSRL MTYLRGISYK VTVGTLVANE
GWNASEVALT AVITAAYLTI CHQRYLRTQA ISKGMRRLER EHAQKFITRL YSWLFEKSGR
DYIPGRQLEF YAQCRRWLSA GFHLDPRVLV FDESAPCHCR TAIRKAVSKF CCFMKWLGQE
CTCFLQPAEG AVGDQGHDNE AYEGSDVDPA ESAISDISGS YVVPGTALQP LYQALDLPAE
IVARAGRLTA TVKVSQVDGR IDCETLLGNK TFRTSFVDGA VLETNGPERH NLSFDASQST
MAAGPFSLTY AASAAGLEVR YVAAGLDHRA VFAPGVSPRS APGEVTAFCS ALYRFNREAQ
RLSLTGNFWF HPEGLLGPFA PFSPGHVWES ANPFCGESTL YTRTWSEVDA VSSPAQPDLG
FISEPSIPSR AATLTPAAPL PPPAPDPSPT PSAPARGEPA PGATARAPAI THQAARHRRL
LFTYPDGSKV FAGSLFESTC TWLVNASNVD HRPGGGLCHA FYQRYPASFD AASFVMRDGA
AAYTLTPRPI IHAVAPDYRL EHNPKMLEAA 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 GHYGRRTKLY
NASHSDVRDS LARFIPAIGH VQVTTCELYE LVEAMVEKGQ DGSAVLELDL CNRDVSRITF
FQKDCNKFTT GETIAHGKVG QGISAWSKTF CALFGPWFRA IEKAILALLP QGVFYGDAFD
DTVFSAAVAA ARASMVFEND FSEFDSTQNN FSLGLECAIM VECGMPQWLI RLYHLIRSAW
ILQAPKESLR GFWKKHSGEP GTLLWNTVWN MAVITHCYDF RDLQVAAFKG DDSIVLCSEY
RQSPGAAVLI AGCGLKLKVD FRPIGLYAGV VVAPGLGALP DVVRFAGRLT EKNWGPGPER
AKQLRLAVSD FLRKLTNVAQ MCVDVVSRVY GVSPGLVHNL IGMLQAVADG KAHFTESVKP
VLDLTNSILC RVE
