L_HANTV
ID L_HANTV Reviewed; 2151 AA.
AC P23456;
DT 01-NOV-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 3.
DT 03-AUG-2022, entry version 88.
DE RecName: Full=RNA-directed RNA polymerase L;
DE Short=Protein L;
DE EC=2.7.7.48;
DE AltName: Full=Large structural protein;
DE AltName: Full=RdRp {ECO:0000305};
DE AltName: Full=Replicase;
DE AltName: Full=Transcriptase;
DE Includes:
DE RecName: Full=cap-snatching endonuclease;
DE EC=3.1.-.- {ECO:0000269|PubMed:27304209};
GN Name=L;
OS Hantaan virus (strain 76-118) (Korean hemorrhagic fever virus).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC Ellioviricetes; Bunyavirales; Hantaviridae; Mammantavirinae;
OC Orthohantavirus.
OX NCBI_TaxID=11602;
OH NCBI_TaxID=39030; Apodemus agrarius (Eurasian field mouse).
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=2123544; DOI=10.1093/nar/18.22.6728;
RA Schmaljohn C.S.;
RT "Nucleotide sequence of the L genome segment of Hantaan virus.";
RL Nucleic Acids Res. 18:6728-6728(1990).
RN [2]
RP SEQUENCE REVISION.
RX PubMed=1626424; DOI=10.1016/0168-1702(92)90029-9;
RA Antic D., Kang C.Y., Spik K., Schmaljohn C.S., Vapalahti O., Vaheri A.;
RT "Comparison of the deduced gene products of the L, M and S genome segments
RT of hantaviruses.";
RL Virus Res. 24:35-46(1992).
RN [3]
RP SEQUENCE REVISION TO 353-354; 916 AND 1953.
RA Schmaljohn C.S.;
RL Submitted (JUN-1994) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP REVIEW.
RX PubMed=15503219; DOI=10.1007/s00705-004-0414-8;
RA Kukkonen S.K., Vaheri A., Plyusnin A.;
RT "L protein, the RNA-dependent RNA polymerase of hantaviruses.";
RL Arch. Virol. 150:533-556(2005).
RN [5]
RP REVIEW.
RX PubMed=28418734; DOI=10.1080/1040841x.2017.1307805;
RA Amroun A., Priet S., de Lamballerie X., Querat G.;
RT "Bunyaviridae RdRps: structure, motifs, and RNA synthesis machinery.";
RL Crit. Rev. Microbiol. 43:753-778(2017).
RN [6]
RP REVIEW.
RX PubMed=31948728; DOI=10.1016/j.tim.2019.12.006;
RA Olschewski S., Cusack S., Rosenthal M.;
RT "The Cap-Snatching Mechanism of Bunyaviruses.";
RL Trends Microbiol. 28:293-303(2020).
RN [7] {ECO:0007744|PDB:5IZE}
RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 1-179 IN COMPLEX WITH MANGANESE,
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, MUTAGENESIS OF HIS-36; GLU-54;
RP ASP-97; LYS-124 AND LYS-127, AND ACTIVITY REGULATION.
RX PubMed=27304209; DOI=10.1371/journal.ppat.1005636;
RA Reguera J., Gerlach P., Rosenthal M., Gaudon S., Coscia F., Guenther S.,
RA Cusack S.;
RT "Comparative Structural and Functional Analysis of Bunyavirus and
RT Arenavirus Cap-Snatching Endonucleases.";
RL PLoS Pathog. 12:e1005636-e1005636(2016).
CC -!- FUNCTION: RNA-dependent RNA polymerase, which is responsible for the
CC replication and transcription of the viral RNA genome using antigenomic
CC RNA as an intermediate (By similarity). During transcription,
CC synthesizes subgenomic RNAs and assures their capping by a cap-
CC snatching mechanism, which involves the endonuclease activity cleaving
CC the host capped pre-mRNAs (PubMed:27304209). These short capped RNAs
CC are then used as primers for viral transcription. Cleaves ssRNA
CC substrates but not DNA (By similarity). Seems to downregulate the
CC expression of its own and heterologous mRNAs through its endonuclease
CC activity (By similarity). {ECO:0000250|UniProtKB:Q9E005,
CC ECO:0000269|PubMed:27304209}.
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 ECO:0000269|PubMed:27304209};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:27304209};
CC Note=For endonuclease activity. Binds 2 Mn(2+) ions in the active site
CC (PubMed:27304209). Displays nuclease activity with Mn(2+) and also some
CC with Co(2+), but not with Mg(2+), Ca(2+), Ni(2+), and Zn(2+)
CC (PubMed:27304209). {ECO:0000269|PubMed:27304209};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:A2SZS3};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:A2SZS3};
CC Note=For polymerase activity. {ECO:0000250|UniProtKB:A2SZS3};
CC -!- ACTIVITY REGULATION: Inhibited by 2,4-dioxo-4-phenylbutanoic acid
CC (DPBA). {ECO:0000269|PubMed:27304209}.
CC -!- SUBUNIT: Interacts with the viral nucleoprotein.
CC {ECO:0000250|UniProtKB:Q89709}.
CC -!- SUBCELLULAR LOCATION: Host cytoplasm, host perinuclear region
CC {ECO:0000250|UniProtKB:Q9YQR5}.
CC -!- DOMAIN: The N-terminus contains the endonuclease activity (endoN) (By
CC similarity). The central region contains the RdRp activity (By
CC similarity). The C-terminus contains the cap-binding region (By
CC similarity). {ECO:0000250|UniProtKB:A2SZS3,
CC ECO:0000250|UniProtKB:I0DF35, ECO:0000250|UniProtKB:Q9E005}.
CC -!- MISCELLANEOUS: Classified as His(+) endonuclease since it has a
CC histidine upstream of the active site that coordinates the first
CC cation. {ECO:0000303|PubMed:31948728}.
CC -!- SIMILARITY: Belongs to the Bunyavirales RNA polymerase family.
CC {ECO:0000305}.
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DR EMBL; X55901; CAA39394.1; -; Genomic_RNA.
DR PIR; S13553; S13553.
DR PDB; 5IZE; X-ray; 1.70 A; A/B=1-179.
DR PDBsum; 5IZE; -.
DR SMR; P23456; -.
DR PRIDE; P23456; -.
DR Proteomes; UP000008627; Genome.
DR GO; GO:0044220; C:host cell perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0004519; F:endonuclease activity; IMP:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-KW.
DR GO; GO:0003968; F:RNA-directed 5'-3' RNA polymerase activity; IEA:UniProtKB-KW.
DR GO; GO:0075526; P:cap snatching; IMP:UniProtKB.
DR GO; GO:0039689; P:negative stranded viral RNA replication; ISS:UniProtKB.
DR GO; GO:0039696; P:RNA-templated viral transcription; ISS:UniProtKB.
DR GO; GO:0006351; P:transcription, DNA-templated; IEA:InterPro.
DR InterPro; IPR016268; RNA-dir_pol_hantavirus.
DR InterPro; IPR024378; RNA-dir_pol_N_hantavirus.
DR InterPro; IPR007099; RNA-dir_pol_NSvirus.
DR InterPro; IPR007322; RNA_pol_bunyavir.
DR Pfam; PF04196; Bunya_RdRp; 1.
DR Pfam; PF12426; DUF3674; 1.
DR PIRSF; PIRSF000825; L_HantaV; 1.
DR PROSITE; PS50525; RDRP_SSRNA_NEG_SEG; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cap snatching; Endonuclease; Host cytoplasm; Hydrolase;
KW Magnesium; Manganese; Metal-binding; Nuclease; Nucleotide-binding;
KW Nucleotidyltransferase; Reference proteome; RNA-directed RNA polymerase;
KW Transferase; Viral RNA replication.
FT CHAIN 1..2151
FT /note="RNA-directed RNA polymerase L"
FT /id="PRO_0000222021"
FT DOMAIN 956..1142
FT /note="RdRp catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00539"
FT ACT_SITE 124
FT /note="For endonuclease activity"
FT /evidence="ECO:0000305|PubMed:27304209"
FT BINDING 36
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:27304209"
FT BINDING 54
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:27304209"
FT BINDING 97
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:27304209"
FT BINDING 97
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:27304209"
FT BINDING 110
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:27304209"
FT BINDING 111
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:27304209"
FT BINDING 1099
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic; for RdRp activity"
FT /evidence="ECO:0000250|UniProtKB:I0DF35"
FT MUTAGEN 36
FT /note="H->A: Complete loss of cap-snatching endonuclease
FT activity."
FT /evidence="ECO:0000269|PubMed:27304209"
FT MUTAGEN 54
FT /note="E->G: Loss of binding to 1 Mn(2+) ion. Complete loss
FT of cap-snatching endonuclease activity."
FT /evidence="ECO:0000269|PubMed:27304209"
FT MUTAGEN 97
FT /note="D->A: Loss of binding to 2 Mn(2+) ions. Complete
FT loss of cap-snatching endonuclease activity."
FT /evidence="ECO:0000269|PubMed:27304209"
FT MUTAGEN 124
FT /note="K->A: Complete loss of cap-snatching endonuclease
FT activity."
FT /evidence="ECO:0000269|PubMed:27304209"
FT MUTAGEN 127
FT /note="K->A: Severe loss of cap-snatching endonuclease
FT activity."
FT /evidence="ECO:0000269|PubMed:27304209"
FT HELIX 1..11
FT /evidence="ECO:0007829|PDB:5IZE"
FT HELIX 12..14
FT /evidence="ECO:0007829|PDB:5IZE"
FT HELIX 21..46
FT /evidence="ECO:0007829|PDB:5IZE"
FT STRAND 51..53
FT /evidence="ECO:0007829|PDB:5IZE"
FT HELIX 57..63
FT /evidence="ECO:0007829|PDB:5IZE"
FT HELIX 68..74
FT /evidence="ECO:0007829|PDB:5IZE"
FT HELIX 88..91
FT /evidence="ECO:0007829|PDB:5IZE"
FT STRAND 97..102
FT /evidence="ECO:0007829|PDB:5IZE"
FT STRAND 105..115
FT /evidence="ECO:0007829|PDB:5IZE"
FT HELIX 117..144
FT /evidence="ECO:0007829|PDB:5IZE"
FT STRAND 147..150
FT /evidence="ECO:0007829|PDB:5IZE"
FT STRAND 153..166
FT /evidence="ECO:0007829|PDB:5IZE"
FT STRAND 168..171
FT /evidence="ECO:0007829|PDB:5IZE"
SQ SEQUENCE 2151 AA; 246499 MW; DBD2A901351DFE0B CRC64;
MDKYREIHNK LKEFSPGTLT AVECIDYLDR LYAVRHDIVD QMIKHDWSDN KDSEEAIGKV
LLFAGVPSNI ITALEKKIIP NHPTGKSLKA FFKMTPDNYK ISGTTIEFVE VTVTADVDKG
IREKKLKYEA GLTYIEQELH KFFLKGEIPQ PYKITFNVVA VRTDGSNITT QWPSRRNDGV
VQYMRLVQAE ISYVREHLIK TEERAALEAM FNLKFNISTH KSQPYYIPDY KGMEPIGANI
EDLVDYSKDW LSRARNFSFF EVKGTAVFEC FNSNEANHCQ RYPMSRKPRN FLLIQCSLIT
SYKPATTLSD QIDSRRACSY ILNLIPDTPA SYLIHDMAYR YINLTREDMI NYYAPRIQFK
QTQNVREPGT FKLTSSMLRA ESKAMLDLLN NHKSGEKHGA QIESLNIASH IVQSESVSLI
TKILSDLELN ITEPSTQEYS TTKHTYVDTV LDKFFQNETQ KYLIDVLKKT TAWHIGHLIR
DITESLIAHS GLKRSKYWSL HSYNNGNVIL FILPSKSLEV AGSFIRFITV FRIGPGLVDK
DNLDTILIDG DSQWGVSKVM SIDLNRLLAL NIAFEKALIA TATWFQYYTE DQGQFPLQYA
IRSVFANHFL LAICQKMKLC AIFDNLRYLI PAVTSLYSGF PSLIEKLFER PFKSSLEVYI
YYNIKSLLVA LAQNNKARFY SKVKLLGLTV DQSTVGASGV YPSFMSRIVY KHYRSLISEV
TTCFFLFEKG LHGNMNEEAK IHLETVEWAL KFREKEEKYG ESLVENGYMM WELRANAELA
EQQLYCQDAI ELAAIELNKV LATKSSVVAN SILSKNWEEP YFSQTRNISL KGMSGQVQED
GHLSSSVTII EAIRYLSNSR HNPSLLKLYE ETREQKAMAR IVRKYQRTEA DRGFFITTLP
TRCRLEIIED YYDAIAKNIS EEYISYGGEK KILAIQGALE KALRWASGES FIELSNHKFI
RMKRKLMYVS ADATKWSPGD NSAKFRRFTS MLHNGLPNNK LKNCVIDALK QVYKTDFFMS
RKLRNYIDSM ESLDPHIKQF LDFFPDGHHG EVKGNWLQGN LNKCSSLFGV AMSLLFKQVW
TNLFPELDCF FEFAHHSDDA LFIYGYLEPV DDGTDWFLFV SQQIQAGHLH WFSVNTEMWK
SMFNLHEHIL LLGSIKISPK KTTVSPTNAE FLSTFFEGCA VSIPFVKILL GSLSDLPGLG
YFDDLAAAQS RCVKALDLGA SPQVAQLAVA LCTSKVERLY GTAPGMVNHP AAYLQVKHTD
TPIPLGGNGA MSIMELATAG IGMSDKNLLK RALLGYSHKR QKSMLYILGL FKFLMKLSDE
TFQHERLGQF SFIGKVQWKI FTPKSEFEFA DMYTSKFLEL WSSQHVTYDY IIPKGRDNLL
IYLVRKLNDP SIVTAMTMQS PLQLRFRMQA KQHMKVCRLD GEWVTFREVL AAANSFAENY
SATSQDMDLF QTLTSCTFSK EYAWKDFLNG IHCDVIPTKQ VQRAKVARTF TVREKDQIIQ
NSIPAVIGYK FAVTVEEMSD VLDTAKFPDS LSVDLKTMKD GVYRELGLDI SLPDVMKRIA
PMLYKSSKSR VVIVQGNVEG TAEAICRYWL KSMSLVKTIR VKPHKEVLQA VSIFNRKEDI
GQQKDLAALK LCIEVWRWCK ANSAPYRDWF QALWFEDKTF SEWLDRFCRV GVPPIDPEIQ
CAALMIADIK GDYSVLQLQA NRRAYSGKQY DAYCVQTYNE VTKLYEGDLR VTFNFGLDCA
RLEIFWDKKA YILETSITQK HVLKIMMDEV SKELIKCGMR FNTEQVQGVR HMVLFKTESG
FEWGKPNIPC IVYKNCVLRT SLRTTQAINH KFMITIKDDG LRAIAQHDED SPRFLLAHAF
HTIRDIRYQA VDAVSNVWFI HKGVKLYLNP IISSGLLENF MKNLPAAIPP AAYSLIMNRA
KISVDLFMFN DLLKLINPRN TLDLSGLETT GDEFSTVSSM SSRLWSEEMS LVDDDEELDD
EFTIDLQDVD FENIDIEADI EHFLQDESSY TGDLLISTEE TESKKMRGIV KILEPVRLIK
SWVSRGLSIE KVYSPVNIIL MSRYISKTFN LSTKQVSLLD PYDLTELESI VRGWGECVID
QFESLDREAQ NMVVNKGICP EDVIPDSLFS FRHTMVLLRR LFPQDSISSF Y
