L_BCCV
ID L_BCCV Reviewed; 2153 AA.
AC V5IVB1;
DT 25-MAY-2022, integrated into UniProtKB/Swiss-Prot.
DT 19-FEB-2014, sequence version 1.
DT 03-AUG-2022, entry version 26.
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:P23456};
GN Name=RdRp {ECO:0000312|EMBL:ADZ76455.1};
OS Black Creek Canal orthohantavirus (BCCV) (Black Creek Canal virus).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC Ellioviricetes; Bunyavirales; Hantaviridae; Mammantavirinae;
OC Orthohantavirus.
OX NCBI_TaxID=1980460;
OH NCBI_TaxID=9606; Homo sapiens (Human).
OH NCBI_TaxID=42415; Sigmodon hispidus (Hispid cotton rat).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC STRAIN=SPB 9408076 {ECO:0000312|EMBL:ADZ76455.1};
RA Cajimat M.N.B., Richter M.H., Milazzo M.L., Fulhorst C.F.;
RT "volutionary history of the large (L) genomic segments of hantaviruses
RT native to the New World.";
RL Submitted (MAR-2010) to the EMBL/GenBank/DDBJ databases.
RN [2]
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 [3]
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 [4]
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: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}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; GU997097; ADZ76455.1; -; Viral_cRNA.
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_0000455189"
FT DOMAIN 957..1143
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 1100
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; 247171 MW; DFAA343AB13623BA CRC64;
MEKYREIHQR VREIAPGTGS ALDCMDLLDR LYAVRHDLVD QMIKHDWSDN KDVETPIGQV
LLMAGVPNDI IQGMEKKIIP NSPTGQILKS FFKMTPDNFK ITGNQIEFIE VTVTADVARG
IREKRLKYES GLRFTEELLE LEVKKGNLQQ VYRISFNVVA VKTDGSNIST QWPSRRNEGV
VQQMRLVQAD INYVREHLIM QDERASLEAM FNLKFHVTGP RLRYFSIPDY RPQPLCNPTI
DGLLQYCKQW LTEEHKFIFK EVSGTNVMGS FEVNEKKHKE RYLESRKPRN FLLLQTTIQG
SYLPSTISSD QCNTRIGCLE ICKNIPETPV QALASDIAFK YISLDKDEVI NYYNPRIHFK
PGQNVKEPGT LKIGLSQMNP LSKAILDNIG KHKSDKGLFG QAIESINIAS QIQLNECSKV
IEQILSNLEI NISDVSENIP LPKKTTCVDE LLGKFYENEI TKYMLGILRK TVAWHIGHLI
RDITESLIAH SGLRRSKYWS VHAYDHGNVI LFILPSKSLE VAGSYIRFFT VFKDGIGLVD
NDNTDSKTEI DGITWIYSKV MSIDLNRLLA LNIAFEKALL ATATWFQYYT EDQGHFPLQH
ALRSVFSFHL LLCVSQKMKI CAIFDNLRYL IPSVTSLYSG YELLIEKFFE RPFKSALDVY
LYSIIKSLLV SLAQNNKVRF YSKVRLLGLT VDQSTVGASG VYPSLMSRVV YKHYRSLISE
ATTCFFLFEK GLHGNLTEEA KIHLETVEWA RKFNEKENRY GDILMKEGYT IELVENQNVT
VEQQLFCQEV VELSAMELNK YLHAKSQVLC ANIMNKHWDK PYFSQVRNIS LKGMSGSLQE
DGHLASSVTL IEAIRFLNSS QINPNVIDMY ERTKHCKAQA RIVRKYQRTE ADRGFFITTL
PTRVRLEIIE DYYDAIAKVV PEEYISYGGE RKILNIQSAL EKALRWASGI SEIITSTGKK
IRFKRKLMYV SADATKWSPG DNSAKFRRFT QAIYDGLNDD KLKCCVVDSL KNIYETEFFM
SRKLHRYIDS MESKSEAVED FLSFFSGGVS ATVKGNWLQG NLNKCSSLFG VAVSLLFKRV
WVELFPELEC FFEFAHHSDD ALFIYGYLEP EDDGTDWFMY VSQQIQAGHY HWHAVNQEMW
KSMFNLHEQL LLMGSIRVSP KKTTVSPTNA EFLSTFFEGC AVSIPFIKIL LGSLSDLPGL
GFFDDLAASQ SRCVKALDLG ACPQLAQLAI VLCTSKVERL YGTADGMINS PISFLKVNKA
HIPIALGGDG SMSIMELATA GIGMADKNIL KKAFYSYKHT KRDGDRYILG LFKFLMSLSD
DVFQHDRLGE FSFVGKVQWK VFTPKSEFEF YDQYSMTYLQ AWSKQHPVYD YIIPRGRDNL
LVYLVRKLND PSIITAMTMQ SPLQLRFRMQ AKQHMKVCKL EGEWVTFREI LAAADSFAST
YQPNEKDLDL FNTLVSCTFS KEYAWKDFLN EVRCEVTTAR HVHRPKVART FTVREKDQVI
QNPITSVIGY KYASTVDEIS DVLDSAFFPD SLSADLQVMK EGVYRELGLD IGLPEVLKRI
APLLYKAGKS RIVIVEGNIE GTAESICSYW LKNMSLIKTI KVKPRKEVLK AVSLYGTKDN
LSLQDDLAAT RICIEVWRWC KANNQNVQEW FTALYFENQT LYDWIERFRR KGVVPVDPEI
QCMALLLYDV LGFKNVLQMQ ANRRAYSGKQ YDAYCVQTYN EETKLYEGDL RVTFNFGLDC
ARLEVFWDKK EYVLETSITQ KHVLRLMMEE VSKELVRCGM RFKTEQVSHT RSLVLFKTES
GFEWGKPNIP CIVYKHCALR TGLRTKHPIN KEFMINIQSD GFRAIAQMDI ESPRFLLAHA
YHTLRDVRYQ AVQAVGNVWF RTEQHKLFIN PIISSGLLEN FMKGLPAAIP PAAYSLIMNK
AKISVDLFMF NELLALINKN NILDLSGIEE TSEGYSTVTS MSSKQWSEEM SLMSDDDIDD
DEEFTIALDD IDFEQVDLEE DIQHFLQDES AYVGDLLIQT EEVEVKRIRG VTRILEPVKL
IKSWVSKGLA IDKVYNPVGI LLMARYMSKN YDFHSVPLAL MNPYDLTEFE SVVKGWGETI
NDRFQEIDLE AQRLVREQNI QPEDILPDSL FSFRHVDVLL KRLFPRDPIS SFY
