L_SINV
ID L_SINV Reviewed; 2153 AA.
AC Q89709; A0A059WB91;
DT 25-MAY-2022, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, 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: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 Sin Nombre orthohantavirus (SNV) (Sin Nombre virus).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC Ellioviricetes; Bunyavirales; Hantaviridae; Mammantavirinae;
OC Orthohantavirus.
OX NCBI_TaxID=1980491;
OH NCBI_TaxID=9606; Homo sapiens (Human).
OH NCBI_TaxID=10042; Peromyscus maniculatus (North American deer mouse).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=8178455; DOI=10.1006/viro.1994.1235;
RA Spiropoulou C.F., Morzunov S., Feldmann H., Sanchez A., Peters C.J.,
RA Nichol S.T.;
RT "Genome structure and variability of a virus causing hantavirus pulmonary
RT syndrome.";
RL Virology 200:715-723(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=7494336; DOI=10.1128/jvi.69.12.8132-8136.1995;
RA Chizhikov V.E., Spiropoulou C.F., Morzunov S.P., Monroe M.C., Peters C.J.,
RA Nichol S.T.;
RT "Complete genetic characterization and analysis of isolation of Sin Nombre
RT virus.";
RL J. Virol. 69:8132-8136(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC STRAIN=77734 {ECO:0000312|EMBL:AIA08875.1};
RX PubMed=24778254; DOI=10.1073/pnas.1401998111;
RA Safronetz D., Prescott J., Feldmann F., Haddock E., Rosenke R., Okumura A.,
RA Brining D., Dahlstrom E., Porcella S.F., Ebihara H., Scott D.P., Hjelle B.,
RA Feldmann H.;
RT "Pathophysiology of hantavirus pulmonary syndrome in rhesus macaques.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:7114-7119(2014).
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 INTERACTION WITH VIRAL NUCLEOPROTEIN.
RX PubMed=24850733; DOI=10.1128/jvi.00405-14;
RA Cheng E., Wang Z., Mir M.A.;
RT "Interaction between hantavirus nucleocapsid protein (N) and RNA-dependent
RT RNA polymerase (RdRp) mutants reveals the requirement of an N-RdRp
RT interaction for viral RNA synthesis.";
RL J. Virol. 88:8706-8712(2014).
RN [6]
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 [7]
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; this interaction is
CC required for RdRp function. {ECO:0000269|PubMed:24850733}.
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; L37901; AAC42204.1; -; Genomic_RNA.
DR EMBL; L37902; AAC42205.1; -; Genomic_RNA.
DR EMBL; KF537001; AIA08875.1; -; Viral_cRNA.
DR RefSeq; NP_941976.1; NC_005217.1.
DR GeneID; 2943143; -.
DR KEGG; vg:2943143; -.
DR Proteomes; UP000113911; Genome.
DR Proteomes; UP000167429; Genome.
DR Proteomes; UP000204632; 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 1: Evidence at protein level;
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_0000455193"
FT DOMAIN 957..1143
FT /note="RdRp catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00539"
FT REGION 1291..2153
FT /note="Interaction with the viral nucleoprotein"
FT /evidence="ECO:0000269|PubMed:24850733"
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 1100
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic; for RdRp activity"
FT /evidence="ECO:0000250|UniProtKB:I0DF35"
FT VARIANT 11
FT /note="V -> I (in strain:77734)"
FT /evidence="ECO:0000269|PubMed:24778254"
FT VARIANT 276
FT /note="S -> D (in strain:77734)"
FT /evidence="ECO:0000269|PubMed:24778254"
FT VARIANT 1791
FT /note="R -> K (in strain:77734)"
FT /evidence="ECO:0000269|PubMed:24778254"
FT VARIANT 1883
FT /note="A -> T (in strain:77734)"
FT /evidence="ECO:0000269|PubMed:24778254"
FT VARIANT 1940
FT /note="R -> K (in strain:77734)"
FT /evidence="ECO:0000269|PubMed:24778254"
FT VARIANT 2146
FT /note="H -> R (in strain:77734)"
FT /evidence="ECO:0000269|PubMed:24778254"
SQ SEQUENCE 2153 AA; 246568 MW; 8B7AD80D9B7B3009 CRC64;
MEKYREIHQR VKEIPPGGAS ALECLDLLDR LYAVRHDVVD QMIKHDWSDN KDMERPIGQV
LLMAGVPNDV IQGMEKKVIP TSPSGQILKS FFRMTPDNYK ITGALIEFIE VTVTADVAKG
IREKKLKYES GLQFVESLLS QEHKKGNINQ AYKITFDVVA VKTDGSNIST QWPSRRNDGV
VQHMRLVQAD INYVREHLIK PDERASLEAM FNLKFHVGGP KLRYFNIPDY KPQSLCQPEI
TNLIQYCKHW LTEDHDFVFK EVTGNNVMNS FENNESVYMS RYRESRKPRN FLLIQGSIQG
PYLPSTISSD QCDTRIGCLE VLKVHPETPV QAIAVDMAYK YMELNRDEII NYYNPRVHFQ
ATQSVKEPGT FKLGLSQLNP MSKSILDQVG KHKSEKGLFG EPLESINISS QIQQNECSRI
IESILSNLEI NVGEVTMSLA NPRKTTGVDE LLGKFYENEL SKYLISILRK TAAWHIGHLI
RDITESLIAH AGLKRSKYWS IHAYDHGGVI LFILPSKSLE VVGSYIRYFT VFKDGIGLID
EENLDSKVDI DGVQWCFSKV MSIDLNRLLA LNIAFEKALL ATATWFQYYT EDQGHFPLQH
ALRSVFSFHF LLCVSQKMKI CAIFDNLRYL IPAVTSLYSG YELLIEKFFE RPFKSALEVY
LYNIIKALLI SLAQNNKVRF YSKVRLLGLT VDHSTVGASG VYPSLMSRVV YKHYRSLISE
ATTCFFLFEK GLHGNLNEEA KIHLETVEWA RKFEAKERKY GDILMREGYT IDAIRVGDVQ
VEQQLFCQEV VELSAEELNK YLQAKSQVLS SNIMNKHWDK PYFSQTRNIS LKGMSGALQE
DGHLAASVTL IEAIRFLNRS QTNPNVIDMY EQTKQHKAQA RIVRKYQRTE ADRGFFITTL
PTRVRLEIIE DYYDAIARVV PEEYISYGGD KKILNIQTAL EKALRWASGS SEVITSTGNV
IKFKRRLMYV SADATKWSPG DNSAKFKRFT QALYDGLSDE KLKCCVVDAL RHVYETEFFM
SRKLHRYIDS MDEHSEAVQD FLDFFKGGVS ATVKGNWLQG NLNKCSSLFG AAVSLLFRRI
WAELFPELEC FFEFAHHSDD ALFIYGYLEP EDDGTDWFLY VSQQIQAGNY HWHAVNQEMW
KSMFNLHEHL LLMGSIKVSP KKTTVSPTNA EFLSTFFEGC AVSIPFIKIL LGSLSDLPGL
GFFDDLAAAQ SRCVKAMDLG ASPQLAQLAV VICTSKVERL YGTADGMVNS PVAFLKVTKA
HVPIPLGGDG SMSIMELATA GIGMADKNIL KQAFYSYKHT RRDGDRYVLG LFKFLMSLSE
DVFQHDRLGE FSFVGKVQWK VFTPKNEFEF FDQFSQSYLK SWTNQHPVYD YIIPRGRDNL
LVYLVRKLND PSIVTAMTMQ SPLQLRFRMQ AKQHMKVCKL EGEWVTFREV LAAADSFATK
YNPTEKDLDL FNTLVSCTFS KEYAWKDFLN EVRCEVVPTK HVHRSKIART FTVREKDQAI
QNPITAVIGY KYASTVDEIS DVLDSSFFPD SLSADLQVMK EGVYRELGLD IGLPEVLKRI
APLLYKAGRS RVVIVEGNVE GTAESICSYW LRSMSLVKTI KVRPKKEVLR AVSLYSTKEN
IGLQDDVAAT RLCIEVWRWC KANDQNVNDW LNALYFEKQT LMDWVERFRR KGVVPIDPEI
QCIALLLYDV LGYKSVLQMQ ANRRAYSGKQ YDAYCVQTYN EETRLYEGDL RVTFNFGLDC
ARLEIFWDKK EYILETSITQ RHVLKLMMEE VTQELLRCGM RFKTEQVSHT RSLVLFKTES
GFEWGKPNVP CIVFKHCALR TGLRTKQAIN KEFMINVQAD GFRAIAQMDM ESPRFLLAHA
YHTLRDVRYQ AVQAVGNVWF QTAQHKLFIN PIISSGLLEN FMKGLPAAIP PAAYSLIMNK
AKISVDLFMF NELLALVNPR NVLNLDGIEE TSEGYSTVTS ISSRQWSEEV SLMADDDIDD
EEEFTIALDD IDFEQINLDE DIQHFLQDES AYTGDLTIQT EEVEVKRIRG VTRVLEPVKL
IKSWVSKGLA IDKVYNPIGI VLMARYMSKN YDFSKIPLAL LNPYDLTEFE SVVKGWGETV
NDRFLEVDND AQRLVREKNI LPEDILPDSL FSFRHVDVLL KRLFPHDPVS SFY
