L_ANDV
ID L_ANDV Reviewed; 2153 AA.
AC Q9E005;
DT 25-MAY-2022, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2002, sequence version 4.
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:0000269|PubMed:27300328};
OS Andes orthohantavirus (ANDV) (Andes virus).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC Ellioviricetes; Bunyavirales; Hantaviridae; Mammantavirinae;
OC Orthohantavirus.
OX NCBI_TaxID=1980456;
OH NCBI_TaxID=29094; Abrothrix longipilis (Long-haired grass mouse) (Akodon longipilis).
OH NCBI_TaxID=9606; Homo sapiens (Human).
OH NCBI_TaxID=89122; Loxodontomys micropus (Southern big-eared mouse) (Auliscomys micropus).
OH NCBI_TaxID=37015; Oligoryzomys chacoensis (Chacoan pygmy rice rat).
OH NCBI_TaxID=218824; Oligoryzomys flavescens (yellow pygmy rice rat).
OH NCBI_TaxID=137207; Oligoryzomys longicaudatus (Long-tailed pygmy rice rat).
OH NCBI_TaxID=37019; Oligoryzomys sp..
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC STRAIN=Chile-9717869;
RX PubMed=11907216; DOI=10.1128/jvi.76.8.3765-3773.2002;
RA Bohlman M.C., Morzunov S.P., Meissner J., Taylor M.B., Ishibashi K.,
RA Rowe J., Levis S., Enria D., St Jeor S.C.;
RT "Analysis of hantavirus genetic diversity in Argentina: S segment-derived
RT phylogeny.";
RL J. Virol. 76:3765-3773(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Chile-9717869;
RX PubMed=12367756; DOI=10.1016/s0168-1702(02)00129-6;
RA Meissner J.D., Rowe J.E., Borucki M.K., St Jeor S.C.;
RT "Complete nucleotide sequence of a Chilean hantavirus.";
RL Virus Res. 89:131-143(2002).
RN [3]
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 [4]
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 [5]
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 [6] {ECO:0007744|PDB:6Q99}
RP X-RAY CRYSTALLOGRAPHY (2.95 ANGSTROMS) OF 1-200 IN COMPLEX WITH MANGANESE,
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND MUTAGENESIS OF ARG-35; HIS-36;
RP ASP-40; ILE-43; LYS-44; ASN-50; PRO-96; ASP-97; ASN-98; GLU-110; LYS-124;
RP LYS-127 AND ASN-167.
RC STRAIN=Chile-9717869;
RX PubMed=27300328; DOI=10.1371/journal.ppat.1005635;
RA Fernandez-Garcia Y., Reguera J., Busch C., Witte G., Sanchez-Ramos O.,
RA Betzel C., Cusack S., Guenther S., Reindl S.;
RT "Atomic Structure and Biochemical Characterization of an RNA Endonuclease
RT in the N Terminus of Andes Virus L Protein.";
RL PLoS Pathog. 12:e1005635-e1005635(2016).
RN [7]
RP FUNCTION.
RC STRAIN=Chile-9717869;
RX PubMed=23576516; DOI=10.1128/jvi.00043-13;
RA Heinemann P., Schmidt-Chanasit J., Guenther S.;
RT "The N terminus of Andes virus L protein suppresses mRNA and protein
RT expression in mammalian cells.";
RL J. Virol. 87:6975-6985(2013).
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. During transcription, synthesizes subgenomic
CC RNAs and assures their capping by a cap-snatching mechanism, which
CC involves the endonuclease activity cleaving the host capped pre-mRNAs
CC (Probable). These short capped RNAs are then used as primers for viral
CC transcription. Cleaves ssRNA substrates but not DNA (PubMed:27300328).
CC Seems to downregulate the expression of its own and heterologous mRNAs
CC through its endonuclease activity (PubMed:23576516).
CC {ECO:0000269|PubMed:23576516, ECO:0000269|PubMed:27300328,
CC ECO:0000305|PubMed:27300328}.
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:27300328};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:27300328};
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)
CC (PubMed:27300328). 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:0000269|PubMed:27300328}.
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; AF291704; AAG22533.4; -; Genomic_RNA.
DR PDB; 6Q99; X-ray; 2.95 A; A=1-200.
DR PDBsum; 6Q99; -.
DR SMR; Q9E005; -.
DR Proteomes; UP000204348; 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 3D-structure; Cap snatching; Endonuclease; Host cytoplasm; Hydrolase;
KW Magnesium; 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_0000455190"
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:0000305|PubMed:27300328"
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:0000305|PubMed:27300328"
FT BINDING 97
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000305|PubMed:27300328"
FT BINDING 110
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000305|PubMed:27300328"
FT BINDING 111
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000305|PubMed:27300328"
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 MUTAGEN 35
FT /note="R->H: Almost complete loss of cap-snatching
FT endonuclease activity."
FT /evidence="ECO:0000269|PubMed:15503219"
FT MUTAGEN 36
FT /note="H->R: Complete loss of cap-snatching endonuclease
FT activity."
FT /evidence="ECO:0000269|PubMed:15503219"
FT MUTAGEN 40
FT /note="D->E: 80% loss of cap-snatching endonuclease
FT activity."
FT /evidence="ECO:0000269|PubMed:15503219"
FT MUTAGEN 43
FT /note="I->A: 70% loss of cap-snatching endonuclease
FT activity."
FT /evidence="ECO:0000269|PubMed:15503219"
FT MUTAGEN 44
FT /note="K->A: 60% loss of cap-snatching endonuclease
FT activity."
FT /evidence="ECO:0000269|PubMed:15503219"
FT MUTAGEN 50
FT /note="N->A: Strongly reduced cap-snatching endonuclease
FT activity."
FT /evidence="ECO:0000269|PubMed:15503219"
FT MUTAGEN 96
FT /note="P->A: Strongly reduced cap-snatching endonuclease
FT activity."
FT /evidence="ECO:0000269|PubMed:15503219"
FT MUTAGEN 97
FT /note="D->E: Complete loss of cap-snatching endonuclease
FT activity."
FT /evidence="ECO:0000269|PubMed:15503219"
FT MUTAGEN 98
FT /note="N->A: 60% loss of cap-snatching endonuclease
FT activity."
FT /evidence="ECO:0000269|PubMed:15503219"
FT MUTAGEN 110
FT /note="E->A: Complete loss of cap-snatching endonuclease
FT activity."
FT /evidence="ECO:0000269|PubMed:15503219"
FT MUTAGEN 124
FT /note="K->A: Almost complete loss of cap-snatching
FT endonuclease activity."
FT /evidence="ECO:0000269|PubMed:15503219"
FT MUTAGEN 127
FT /note="K->A: Almost complete loss of cap-snatching
FT endonuclease activity."
FT /evidence="ECO:0000269|PubMed:15503219"
FT MUTAGEN 167
FT /note="N->A: No effect on cap-snatching endonuclease
FT activity."
FT /evidence="ECO:0000269|PubMed:15503219"
SQ SEQUENCE 2153 AA; 246857 MW; 84445F7EE20436EB CRC64;
MEKYREIHQR VRDLAPGTVS ALECIDLLDR LYAVRHDLVD QMIKHDWSDN KDVERPIGQV
LLMAGIPNDI IQGMEKKIIP NSPSGQVLKS FFRMTPDNYK ITGNLIEFIE VTVTADVSRG
IREKKIKYEG GLQFVEHLLE TESRKGNIPQ PYKITFSVVA VKTDGSNIST QWPSRRNDGV
VQHMRLVQAD INYVREHLIK LDERASLEAM FNLKFHVSGP KLRYFNIPDY RPQQLCEPRI
DNLIQYCKNW LTKEHKFVFK EVSGANVIQA FESHEQLHLQ KYNESRKPRN FLLLQLTVQG
AYLPSTISSD QCNTRIGCLE ISKNQPETPV QMLALDISYK YLSLTRDELI NYYSPRVHFQ
SSPNVKEPGT LKLGLSQLNP LSKSILDNVG KHKKDKGLFG EIIDSINVAS QIQINACAKI
IEQILSNLEI NIGEINASMP SPNKTTGVDD LLNKFYDNEL GKYMLSILRK TAAWHIGHLV
RDITESLIAH AGLRRSKYWS VHAYDHGNVI LFILPSKSLE VVGSYIRYFT VFKDGIGLID
ADNIDSKAEI DGVTWCYSKV MSIDLNRLLA LNIAFEKSLL ATATWFQYYT EDQGHFPLQH
ALRSIFSFHF LLCVSQKMKL CAIFDNLRYL IPSVTSLYSG YELLIEKFFE RPFKSSLDVY
LYSIIKSLLI SLAQNNKVRF YSRVRLLGLT VDHSTVGASG VYPSLMSRVV YKHYRSLISE
ATTCFFLFEK GLHGNLPEEA KIHLETIEWA RKFQEKEKQY GDILLKEGYT IESVINGEVD
VEQQLFCQEV SELSAQELNK YLQAKSQVLC ANIMNKHWDK PYFSQTRNIS LKGMSGALQE
DGHLAASVTL IEAIRFLNRS QTNPNVIDMY EQTKQSKAQA RIVRKYQRTE ADRGFFITTL
PTRVRLEIIE DYFDAIAKVV PEEYISYGGD KKVLNIQNAL EKALRWASGV SEITTSTGKS
IKFKRKLMYV SADATKWSPG DNSAKFRRFT QAIYDGLSDN KLKCCVVDAL RNIYETEFFM
SRKLHRYIDS MENHSDAVED FLAFFSNGVS ANVKGNWLQG NLNKCSSLFG AAVSLLFREV
WKQLFPELEC FFEFAHHSDD ALFIYGYLEP EDDGTDWFLY VSQQIQAGNF HWHAINQEMW
KSMFNLHEHL LLMGSIKVSP KKTTVSPTNA EFLSTFFEGC AVSIPFVKIL LGSLSDLPGL
GFFDDLAAAQ SRCVKSLDLG ACPQLAQLAI VLCTSKVERL YGTADGMVNS PTAFLKVNKA
HVPVPLGGDG SMSIMELATA GFGMADKNIL KNAFISYKHT RRDGDRYVLG LFKFLMSLSE
DVFQHDRLGE FSFVGKVQWK VFTPKAEFEF HDQFSHNYLL EWTRQHPVYD YIIPRNRDNL
LVYLVRKLND PSIITAMTMQ SPLQLRFRMQ AKQHMKVCRY EGEWVTFREV LAAADSFATS
YQPTERDMDL FNTLVSCTFS KEYAWKDFLN EVRCEVLTTR HVHRPKIART FTVREKDQAI
QNPINSVIGY KYALTVDEVS DVLDSAFFPE SLSADLQVMK DGVYRELGLD ISSPEVLKRI
APLLYKAGRS RVVIVEGNVE GTAESICSYW LKTMSLIKTI RVRPKKEVLK AMSLYSVKEN
IGLQDDIAAT RLCIEIWRWC KANEQDVKEW LTSLYFEKQT LMDWVERFRR KGVVPIDPEI
QCIGLLLYDV LGYKSVLQMQ ANRRAYSGKQ YDAYCVQTYN EETKLYEGDL RVTFNFGLDC
ARLEVFWDKK EYILETSITQ RHVLRLLMEE VSQELIRCGM RFKTEQVNQT RSLVLFKTEA
GFEWGKPNVP CIVYKHCVLR TGLRTKQPIN KEFMINVQSD GFRAIAQMDI ESPRFLLAHA
YHTLRDIRYQ AVQAVGNVWF KTEQHKLFIN PIISSGLLEN FMKGLPAAIP PAAYSLIMNK
AKISVDLFMF NELLALINRN NILNLDGIEE TSEGYSTVTS MSSKQWSEEM SLMSDDDIDD
MEDFTIALDD IDFEQINLEE DIQHFLQDES AYVGDLLIQT EDIEVKKIRG VTRVLEPVKL
LKSWVSKGLA IDKVYNPIGI ILMARYMSKT YNFSSTPLAL LNPYDLTELE SVVKGWGETV
NDRFKDLDIE AQTVVKEKGV QPEDVLPDSL FSFRHVDVLL RRLFPRDPVS TFY
