L_UUKS
ID L_UUKS Reviewed; 2103 AA.
AC P33453;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1994, sequence version 1.
DT 03-AUG-2022, entry version 80.
DE RecName: Full=RNA-directed RNA polymerase L;
DE Short=Protein L;
DE EC=2.7.7.48 {ECO:0000250|UniProtKB:I0DF35};
DE AltName: Full=Large structural protein;
DE AltName: Full=Replicase;
DE AltName: Full=Transcriptase;
DE Includes:
DE RecName: Full=cap-snatching endonuclease;
DE EC=3.1.-.- {ECO:0000250|UniProtKB:I0DF35};
GN Name=L;
OS Uukuniemi virus (strain S23) (UUKV).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC Ellioviricetes; Bunyavirales; Phenuiviridae; Phlebovirus.
OX NCBI_TaxID=487099;
OH NCBI_TaxID=9606; Homo sapiens (Human).
OH NCBI_TaxID=34613; Ixodes ricinus (Common tick) (Acarus ricinus).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=1629699; DOI=10.1099/0022-1317-73-7-1745;
RA Elliott R.M., Dunn E., Simons J.F., Pettersson R.F.;
RT "Nucleotide sequence and coding strategy of the Uukuniemi virus L RNA
RT segment.";
RL J. Gen. Virol. 73:1745-1752(1992).
RN [2]
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 [3]
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 (By similarity). These short capped RNAs are
CC then used as primers for viral transcription. The 3'-end of subgenomic
CC mRNAs molecules are not polyadenylated. During replication, the
CC polymerase binds the 5' and 3' vRNA extremities at distinct sites (By
CC similarity). In turn, significant conformational changes occur in the
CC polymerase and in vRNA to initiate active RNA synthesis (By
CC similarity). As a consequence of the use of the same enzyme for both
CC transcription and replication, these mechanisms need to be well
CC coordinated (By similarity). {ECO:0000250|UniProtKB:A5HC98,
CC ECO:0000250|UniProtKB:I0DF35, ECO:0000250|UniProtKB:P27316}.
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:P27316};
CC Note=For endonuclease activity. Binds 2 Mn(2+) ions in the active site
CC (By similarity). The divalent metal ions are crucial for catalytic
CC activity (PubMed:31948728). {ECO:0000250|UniProtKB:P27316,
CC ECO:0000269|PubMed:31948728};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P27316};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:P27316};
CC Note=For polymerase activity. Initiation activity is stronger in the
CC presence of Mn(2+) than in the presence of Mg(2+).
CC {ECO:0000250|UniProtKB:P27316};
CC -!- SUBUNIT: Homomultimer (By similarity). Interacts with the glycoprotein
CC N; this interaction allows efficient polymerase packaging into virus
CC particles (By similarity). Interacts with nucleoprotein N (By
CC similarity). {ECO:0000250|UniProtKB:P27316}.
CC -!- SUBCELLULAR LOCATION: Host Golgi apparatus
CC {ECO:0000250|UniProtKB:I0DF35}. Host endoplasmic reticulum. Host
CC endoplasmic reticulum-Golgi intermediate compartment
CC {ECO:0000250|UniProtKB:I0DF35}. Virion {ECO:0000250|UniProtKB:P20470}.
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:I0DF35}.
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; D10759; BAA01590.1; -; Genomic_RNA.
DR PIR; JQ1621; JQ1621.
DR SMR; P33453; -.
DR IntAct; P33453; 1.
DR PRIDE; P33453; -.
DR Proteomes; UP000008595; Genome.
DR GO; GO:0001882; F:nucleoside binding; IEA:InterPro.
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: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; IPR022531; DUF3770.
DR InterPro; IPR029124; L_protein_N.
DR InterPro; IPR007099; RNA-dir_pol_NSvirus.
DR InterPro; IPR014385; RNA-dir_pol_phlebovirus.
DR InterPro; IPR007322; RNA_pol_bunyavir.
DR Pfam; PF04196; Bunya_RdRp; 1.
DR Pfam; PF12603; DUF3770; 1.
DR Pfam; PF15518; L_protein_N; 1.
DR PIRSF; PIRSF000826; L_PhleboV; 1.
DR PROSITE; PS50525; RDRP_SSRNA_NEG_SEG; 1.
PE 3: Inferred from homology;
KW Host endoplasmic reticulum; Host Golgi apparatus; Hydrolase; Magnesium;
KW Manganese; Metal-binding; Nucleotide-binding; Nucleotidyltransferase;
KW Reference proteome; RNA-directed RNA polymerase; Transferase;
KW Viral RNA replication; Virion.
FT CHAIN 1..2103
FT /note="RNA-directed RNA polymerase L"
FT /id="PRO_0000222028"
FT DOMAIN 978..1175
FT /note="RdRp catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00539"
FT REGION 18..216
FT /note="Endonuclease"
FT /evidence="ECO:0000250|UniProtKB:A5HC98"
FT REGION 1707..1825
FT /note="Cap-binding"
FT /evidence="ECO:0000250|UniProtKB:A5HC98"
FT ACT_SITE 144
FT /note="For endonuclease activity"
FT /evidence="ECO:0000250|UniProtKB:I0DF35"
FT BINDING 79
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:A5HC98"
FT BINDING 111
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:A5HC98"
FT BINDING 111
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:A5HC98"
FT BINDING 125
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:A5HC98"
FT BINDING 1139
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic; for RdRp activity"
FT /evidence="ECO:0000250|UniProtKB:I0DF35"
FT SITE 1714
FT /note="Interaction with the cap substrate"
FT /evidence="ECO:0000250|UniProtKB:A2SZS3"
FT SITE 1718
FT /note="Interaction with the cap substrate"
FT /evidence="ECO:0000250|UniProtKB:A2SZS3"
FT SITE 1729
FT /note="Interaction with the cap substrate"
FT /evidence="ECO:0000250|UniProtKB:A2SZS3"
FT SITE 1784
FT /note="Interaction with the cap substrate"
FT /evidence="ECO:0000250|UniProtKB:A2SZS3"
SQ SEQUENCE 2103 AA; 241041 MW; B0EA708451B0B6BD CRC64;
MLLAICSRTI RQQGLNCPPA VTFTSSHMRP PIPSFLLWTE GSDVLMDFDL DTIPAGSVTG
SSIGPKFKIK TQAASSFVHD FTFAHWCDAS DMPLRDHFPL VNDTFDHWTP DFISQRLDGS
KVVVEFTTNR SDQEQSLISA FNTKVGKYEV ALHNRSTTSS ILFGVVVVSE TTVVTNLNLN
QQEVDELCFR FLVARAVHLE MTTKMIIPEY DDEDEDKRSR EVKAAFHSVQ PDWNVTEANF
APFSRRMFSN FAQMEPDKEY LAHIILDSLK QAQADLDGNH YLNESLTEQA RLDRNREESL
NMVKDFERDF NNAAQRSAWS HKSTVPFPGV IPKVSGDTTS LSRLVELPVI TGGSDATIRA
WRSAYGSVSN GTVERCDEDV ERERRAALCS LTVEELEESK ALRMKYHRCK IDNGMMDKLD
LAMQGVEAKE FKNHPSIIKK RSKSKKTFPL TADTRDIDLF LHHDDLMFNN EHSQTPPAAM
IEAVKAGADA QSLHGLDKSA NPWYASALWF LGLPIGLWLF MCTCIGVELS ISLKQHCGRQ
KFIIKKLRFF DIFLLIKPTN SGSHVFYSIA FPESAILGKL HRSQCFKGLQ FEDGWFWTEF
SSFKMSKLTN VVKCLSTGFN LFWFWRDYYE VPFWAGNEKD FQTGKQRANK MFKFCLLMLL
EDKARTEEIA TLSRYVMMEG FVSPPCIPKP QKMIEKLPNL ARTKFQVWLI SRMLQTIIRV
SDYPFKITAG HKSANWTGMF NWVTGEPIES TQKLISLFYL GYLKNKEESP ERNASIGMYK
KILEYEDKHP GRYTYLGLGD PPSDDTRFHE YSISLLKHLC IHAEHDLRRN WGESFKAMIS
RDIVDAIASL DLERLATLKA SSNFNEEWYQ KRGDGKTYHR SKVLEKVSKY VKKSSSHVHH
IMEECLRKVE SQGCMHVCLF KKPQHGGLRE IYVLGFEERV VQLVIETIAR QICKRFKSET
LTNPKQKLAI PETHGLRAVK TCGIHHETVA TSDDAAKWNQ CHHVTKFALM LCHFTDPLFH
GFIIRGCSMF MKKRIMIDQS LIDIIDSHTT LETSDAYLQK IHRGYHGSLD DQPRWISRGG
AFVQTETGMM QGILHYTSSL LHTLLQEWLR TFSQRFIRTR VSVDQRPDVL VDVLQSSDDS
GMMISFPSTD KGATGKYRYL SALIFKYKKV IGKYLGIYSS VKSTNNTLHL LEFNSEFFFH
INHNRPLLRW ITACDTISEQ ESLASRQEEM YNNLTSVLEG GGSFSLVSFC QFGQLLLHYT
LLGMTVSPLF LEYIKLVSEI KDPSLGYFLM DHPFGSGLSG FKYNVWVAVQ NSILGSRYRS
LLEAIQNSDS AAPKKTLDTT TSGTFVQSTI IRFGDRKKWQ RLVDRLNLPE DWLDVIDKNP
EIVYRRPRDG FEVSLRIAEK VHSPGVSNSL SKGNCIIRVI SSSVYILSRS ILSDGLAWLY
DEEEEVKRPL LYKVMNQPEL DLHSRLTPAQ LSTLFPMMAE FEKLQTHLRS YMKIEGEFIS
KKKVITQTRV NILETERFLR ARPEDLIADK WFGFTRTRMT PRTFKEEWEN LTSVFPWLTG
NPSETLELSP FQHHVQLRNF FSRLDLKGRD IRIIGAPIKK SSGVSNVSTA IRDNFFPRFV
LTHIPDEAAM ERIEAAGILK HALFLTVTGP YTDQSKLDMC RDFITSSEPI TLKPNHGKTR
TNVLSLFQDY FSKRGPDIIF NRIQMANCGV IGGFTSPQKP KEVDGKIVYT GDGVWRGIVD
GFQIQLVITY MPKQKSNELK SITVNSDRCI SALSSFCQSW CKEMGVFNTE DFSKTQRFSK
ASFFMHKFKI SGSKQTLGAP IFIVSEKIFR PICWDPSKLE FRVRGNTLNL TYKEVNPGAG
QRMFNILSYT VKDTDVSDEN AFKLMSLSPR HKFHGREPST SWICMRALPI STIDKLLERI
LNRERISGSI DNERLAECFK NVMESTLRRK GVFLSEFSRA TQKMLDGLSR DMLDFFAEAG
LNDDLLLEEE PWLSGLDTFM LDDEAYLEEY NLGPFGVFSV EQEMNTKYYH HLLLDSLVED
VIQKLSLDGL RKLFQEEEAP LEYKKEVIRL LNILQRDASQ IKWKSRDLLS ENMGLDVDDD
MFG
