L_TULV
ID L_TULV Reviewed; 2153 AA.
AC Q9YQR5;
DT 25-MAY-2022, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 87.
DE RecName: Full=RNA-directed RNA polymerase L;
DE Short=Protein L;
DE EC=2.7.7.48 {ECO:0000255|PROSITE-ProRule:PRU00539};
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:0000250|UniProtKB:P23456};
OS Tula orthohantavirus (TULV) (Tula virus).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC Ellioviricetes; Bunyavirales; Hantaviridae; Mammantavirinae;
OC Orthohantavirus.
OX NCBI_TaxID=1980494;
OH NCBI_TaxID=9606; Homo sapiens (Human).
OH NCBI_TaxID=47230; Microtus arvalis (Common vole) (Field vole).
OH NCBI_TaxID=523745; Microtus obscurus.
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC STRAIN=Isolate Tula/Moravia/5302Ma/94 {ECO:0000305};
RX PubMed=8837887; DOI=10.1016/0168-1702(95)00086-0;
RA Plyusnin A., Cheng Y., Vapalahti O., Pejcoch M., Unar J., Jelinkova Z.,
RA Lehvaeslaiho H., Lundkvist A., Vaheri A.;
RT "Genetic variation in Tula hantaviruses: sequence analysis of the S and M
RT segments of strains from Central Europe.";
RL Virus Res. 39:237-250(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1-1063.
RC STRAIN=Isolate Tula/Moravia/5302v/95 {ECO:0000305};
RX PubMed=9000098; DOI=10.1099/0022-1317-77-12-3063;
RA Vapalahti O., Lundkvist A., Kukkonen S.K., Cheng Y., Gilljam M.,
RA Kanerva M., Manni T., Pejcoch M., Niemimaa J., Kaikusalo A., Henttonen H.,
RA Vaheri A., Plyusnin A.;
RT "Isolation and characterization of Tula virus, a distinct serotype in the
RT genus Hantavirus, family Bunyaviridae.";
RL J. Gen. Virol. 77:3063-3067(1996).
RN [3]
RP SUBCELLULAR LOCATION.
RC STRAIN=Tula/Moravia/ Ma5302V;
RX PubMed=15105534; DOI=10.1099/vir.0.19748-0;
RA Kukkonen S.K.J., Vaheri A., Plyusnin A.;
RT "Tula hantavirus L protein is a 250 kDa perinuclear membrane-associated
RT protein.";
RL J. Gen. Virol. 85:1181-1189(2004).
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).
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. These short capped RNAs are then used as
CC primers for viral transcription. Cleaves ssRNA substrates but not DNA
CC (By similarity). Seems to downregulate the expression of its own and
CC heterologous mRNAs through its endonuclease activity (By similarity).
CC {ECO:0000250|UniProtKB:Q9E005}.
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 -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:P23456};
CC Note=For endonuclease activity. Binds 2 Mn2+ ions in the active site.
CC The divalent metal ions are crucial for catalytic activity
CC (PubMed:31948728). {ECO:0000250|UniProtKB:P23456,
CC ECO:0000269|PubMed:31948728};
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 -!- SUBUNIT: Interacts with the viral nucleoprotein.
CC {ECO:0000250|UniProtKB:Q89709}.
CC -!- SUBCELLULAR LOCATION: Host cytoplasm, host perinuclear region
CC {ECO:0000269|PubMed:15105534}.
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; AJ005637; CAA06640.1; -; Genomic_RNA.
DR EMBL; Z69992; -; NOT_ANNOTATED_CDS; Genomic_RNA.
DR Proteomes; UP000243699; Genome.
DR GO; GO:0044220; C:host cell perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0004519; F:endonuclease activity; IEA:UniProtKB-KW.
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; IEA:UniProtKB-KW.
DR GO; GO:0006351; P:transcription, DNA-templated; IEA:InterPro.
DR GO; GO:0039694; P:viral RNA genome replication; 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 3: Inferred from homology;
KW Cap snatching; Endonuclease; Host cytoplasm; Hydrolase; Magnesium;
KW Manganese; Metal-binding; Nuclease; Nucleotide-binding;
KW Nucleotidyltransferase; RNA-directed RNA polymerase; Transferase;
KW Viral RNA replication.
FT CHAIN 1..2153
FT /note="RNA-directed RNA polymerase L"
FT /id="PRO_0000455192"
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:0000250|UniProtKB:P23456"
FT BINDING 36
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9E005"
FT BINDING 54
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P23456"
FT BINDING 97
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9E005"
FT BINDING 97
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9E005"
FT BINDING 110
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9E005"
FT BINDING 111
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9E005"
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"
SQ SEQUENCE 2153 AA; 246818 MW; 2C8B162EB610E9A5 CRC64;
MEKYTEIHNR MRECVPGEVS AVECLDLLDR FYAVRHDVVD QMIKHDWSDN KDKEQPIGHV
LLMAGVPNEV IQGMEKKIIP GSPSGQILRS FFKMTPDNYK ITGSLIEFIE VTVTADVARG
TREKILKYQA GLEYIEQLLH QESERGNLPG GYRIKFDVVA VRTDGSNIST QWPSQRNEGV
VQTMRLIQAD INYVREHLIK NDERSALEAM FNLKFHVSGP KARTFDIPDY RPQQLCNPNI
DNLLNYCKNW LTREHEFAFD EVKGQRVFNI FEAEEIKHKE RYNPSRKPRN FLLIQGTVQG
PYLPSTIASD QYDTKVGCLE ILKNHPETPI QILARDMALK YIMLDKDDLI NYYNPRAYFK
QTANIKEPGT FKLNLSSMDP KAKALLDVIS KNSKKGVFGE VIDSIEISSL IQQNECSKVI
EKILSDLEIN VGETSQGLDN PKRTTGVDDI LKKFYDNELV KYMLHIVRKT TAWHMGHLLR
DITECLIAHA GLKRSKYWSI HGFSHGGILL MILPSKSLEV AGSYIRFFTV FKDGLGLIDY
ENLDSTVVID GVSWCFSKVM SLDLNRLLAL NISFEKTLLA TATWFQYYTE DQGHFPLQHA
LRSVFAFHFL LTVTQKMKLC AIFDNLRYLI PAVTSLYSGY KPLIVKFFER PFKSALDVYL
YTIIKTLLVS LAQNNKIRFY SKVRLLGLTV DQSTIGASGV YPSLMSRVVY KHYKSLISEA
TTCFFLFEKG LHGNLTEEAK IHLETVEWAR KFSDKEKAYG AYIMEEGYTI KDVVDGNIPV
EQQLFCQEVV ELSAMELNTY LEAKSQVMAA NIMNKHWDRP YFSQTRNISL KGMSGALQED
GHLSASVTLI EAIRFLNQSQ QNPSVLEMYE QTKRQKAMAR IVRKYQRTEA DRGFFITTLP
TRVRLEIIED YFDAIAKVVP EEYISYGGER KILNIQQALE KALRWASGES EIQISMGQVI
KLKRKLMYVS ADATKWSPGD NSAKFRRFTQ ALHDGLRDDK LKRCVVDALR NIYETDFFMS
RKLHRYIDGM DDLSEFVEDF LSFFPNKVSA AIKGNWLQGN LNKCSSLFGA AVSLLFRKIW
SLLYPELDCF FEFAHHSDDA LFIYGYLEPT DDGTEWFRFV TQQIQAGNLH WYAVNQEMWK
SMFNLHEHIL LMGSIKISPK KTTVSPTNAE FLSTFFEGCA VSIPFIKILL GSLSDLPGLG
YFDDLAAAQS RCVKALDMGA CPQLAQLGIV LCTSKVERLY GTATGMVNNP TSFLKVERSS
IPIPLGGDGS MSIMELATAG IGMADKNVLK NAYISFKHTK RDSDRYILGL FKFLMSLSDD
VFQHDRLGEF SFVGKVQWKV FTPKSEFEFF DQYSSKYLQL WTEQHPVYDY IIPRGRDNLL
VYLVRKLNDP SIVTAMTMQS PLQLRFRMQA KQHMKVCRLN GEWVTFREVL AAADSFAQSF
KPSQSDMELF QTLVNCTFSK EYAWRDFLNE VKCEVLTTRQ VHRPKVARTF TVKERDQAIQ
NSITAVIGYK YANKADEISD VLDSAVHPDS LSTDLQVMRE GVYRELGLDI NYPNVLKRVA
PLLYKSGKSR VVIVQGNIEG TAESICSYWL KTMSLVKTIK VRPKKEVLKA VSLFSKKEKI
GDLTHLAATR LCIDVWRWCK ANEQDPKAWL SALYFEGRTL MQWVDVFLDK GVVPVDPEIQ
CMGLMIYDLT GQKNLLQMQA NRRAYSGKQY DAYCVQTYNE ETKLYEGDLR VTFNFGIDCA
RLEIFWDKQD YLLETSITQR HVLKILMEEV TKELLRCGMR FKTEQVNSSR SVVLFKTDAG
FEWGKPNIPC IVFRNCALRT GLRVRHPINK SFTITIQAGG FRAMAQLDEE NPRFLLAHAY
HNLKDIRYQA LQAIGNIWFK TQQHKLFINP IISAGLLENF MKGLPAAIPP AAYSLIMNKA
KISVDLFMFN ELLALINPKN VLNLDGIEET SEGYSTVSTI SSTQWSEEVS LVMDDSDDED
QPDYTIDLDD IDFETIDLKE DIEHFLQDES AYTGDLLIQT DDTEIKKLRG MTRILEPIKL
IKSWVSKGLS IEKVYSPVGI ILMARYMSKH YDFNKAPLSL LNPYDLTEFE SIVKGWGECV
NDRFIEYDHE AERKVKEEKI QPEDVLPDSL FSFRHADILL RRLFPKDSAA SFY
