ID A0A2P1JNT3_LASV Unreviewed; 2220 AA. AC A0A2P1JNT3; DT 23-MAY-2018, integrated into UniProtKB/TrEMBL. DT 23-MAY-2018, sequence version 1. DT 24-JAN-2024, entry version 22. DE RecName: Full=RNA-directed RNA polymerase L {ECO:0000256|HAMAP-Rule:MF_04086}; DE Short=Protein L {ECO:0000256|HAMAP-Rule:MF_04086}; DE EC=2.7.7.48 {ECO:0000256|HAMAP-Rule:MF_04086}; DE AltName: Full=Large structural protein {ECO:0000256|HAMAP-Rule:MF_04086}; DE AltName: Full=Replicase {ECO:0000256|HAMAP-Rule:MF_04086}; DE AltName: Full=Transcriptase {ECO:0000256|HAMAP-Rule:MF_04086}; DE Includes: DE RecName: Full=cap-snatching endonuclease {ECO:0000256|HAMAP-Rule:MF_04086}; DE EC=3.1.-.- {ECO:0000256|HAMAP-Rule:MF_04086}; GN Name=L {ECO:0000256|HAMAP-Rule:MF_04086, ECO:0000313|EMBL:AVO03702.1}; OS Mammarenavirus lassaense. OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina; OC Ellioviricetes; Bunyavirales; Arenaviridae; Mammarenavirus. OX NCBI_TaxID=3052310 {ECO:0000313|EMBL:AVO03702.1}; OH NCBI_TaxID=9606; Homo sapiens (Human). OH NCBI_TaxID=10112; Mastomys natalensis (African soft-furred rat) (Praomys natalensis). OH NCBI_TaxID=10114; Rattus. RN [1] {ECO:0000313|EMBL:AVO03702.1} RP NUCLEOTIDE SEQUENCE. RC STRAIN=Lassa virus/H.sapiens-wt/NGA/2016/ISTH_1123 RC {ECO:0000313|EMBL:AVO03702.1}, and Lassa RC virus/H.sapiens-wt/NGA/2016/ISTH_1250 {ECO:0000313|EMBL:AVO03770.1}; RA Odia I., Ehaine P., Oguzie J.U., Siddle K.J., Mehta S., Barnes K.M., RA Winnicki S.M., Brehio P., Shah R., Chak B., Yozwiak N., Amao A., RA Nosamiefan I., Birren B.W., Park D.J., Folarin O., Okokhere P., RA Sabeti P.C., Happi C.T.; RT "Lassa virus outbreak genomics and epidemiology from Nigeria."; RL Submitted (MAR-2018) to the EMBL/GenBank/DDBJ databases. 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 These short capped RNAs are then used as primers for viral CC transcription. The 3'-end of subgenomic mRNAs molecules are CC heterogeneous and not polyadenylated. The replicase function is to CC direct synthesis of antigenomic and genomic RNA which are encapsidated CC and non capped. As a consequence of the use of the same enzyme for both CC transcription and replication, these mechanisms need to be well CC coordinated. These processes may be regulated by proteins N and Z in a CC dose-dependent manner. {ECO:0000256|HAMAP-Rule:MF_04086, CC ECO:0000256|PIRNR:PIRNR000836}. 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:0000256|ARBA:ARBA00024517, CC ECO:0000256|HAMAP-Rule:MF_04086, ECO:0000256|PIRNR:PIRNR000836}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000256|HAMAP-Rule:MF_04086}; CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; CC Evidence={ECO:0000256|HAMAP-Rule:MF_04086}; CC Note=For polymerase activity. {ECO:0000256|HAMAP-Rule:MF_04086}; CC -!- COFACTOR: CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; CC Evidence={ECO:0000256|HAMAP-Rule:MF_04086}; CC Note=For endonuclease activity. Binds 2 Mn(2+) ions in the active site. CC The divalent metal ions are crucial for catalytic activity. CC {ECO:0000256|HAMAP-Rule:MF_04086}; CC -!- SUBUNIT: Homomultimer; the oligomeric structure is essential for the CC polymerase activity. Interacts with nucleoprotein N. Interacts with CC protein Z; this interaction inhibits viral transcription and CC replication. {ECO:0000256|HAMAP-Rule:MF_04086}. CC -!- SUBCELLULAR LOCATION: Virion {ECO:0000256|HAMAP-Rule:MF_04086, CC ECO:0000256|PIRNR:PIRNR000836}. Host cytoplasm {ECO:0000256|HAMAP- CC Rule:MF_04086, ECO:0000256|PIRNR:PIRNR000836}. CC -!- DOMAIN: The N-terminus contains the endonuclease activity (endoN). The CC central region contains the RdRp activity. {ECO:0000256|HAMAP- CC Rule:MF_04086}. CC -!- MISCELLANEOUS: Classified as His(-) endonuclease since it does not have CC a histidine upstream of the active site that coordinates the first CC cation. His(-) endonucleases display very low activity in vitro, CC although they are clearly active in vivo. {ECO:0000256|HAMAP- CC Rule:MF_04086}. CC -!- SIMILARITY: Belongs to the Bunyavirales RNA polymerase family. CC {ECO:0000256|HAMAP-Rule:MF_04086, ECO:0000256|PIRNR:PIRNR000836}. CC -!- CAUTION: Lacks conserved residue(s) required for the propagation of CC feature annotation. {ECO:0000256|HAMAP-Rule:MF_04086}. 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; MH053512; AVO03702.1; -; Genomic_RNA. DR EMBL; MH053587; AVO03770.1; -; Genomic_RNA. DR GO; GO:0030430; C:host cell cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0044423; C:virion component; IEA:UniProtKB-KW. DR GO; GO:0016787; F:hydrolase activity; IEA:UniProtKB-KW. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-UniRule. DR GO; GO:0003968; F:RNA-dependent RNA polymerase activity; IEA:UniProtKB-UniRule. DR GO; GO:0075526; P:cap snatching; IEA:UniProtKB-UniRule. DR GO; GO:0039689; P:negative stranded viral RNA replication; IEA:UniProtKB-UniRule. DR Gene3D; 3.30.70.2640; Arenavirus RNA polymerase; 1. DR Gene3D; 1.20.1440.300; RNA-directed RNA polymerase L, helical domain; 1. DR HAMAP; MF_04086; ARENA_L; 1. DR InterPro; IPR026382; CapSnatch_arenavir. DR InterPro; IPR048006; CapSnatch_bunyavir. DR InterPro; IPR007099; RNA-dir_pol_NSvirus. DR InterPro; IPR010453; RNA_pol_arenavir. DR NCBIfam; TIGR04202; capSnatchArena; 1. DR Pfam; PF06317; Arena_RNA_pol; 1. DR Pfam; PF17296; ArenaCapSnatch; 1. DR PIRSF; PIRSF000836; L_ArenaV; 1. DR PROSITE; PS50525; RDRP_SSRNA_NEG_SEG; 1. PE 3: Inferred from homology; KW Cap snatching {ECO:0000256|ARBA:ARBA00022715, ECO:0000256|HAMAP- KW Rule:MF_04086}; KW Host cytoplasm {ECO:0000256|HAMAP-Rule:MF_04086, KW ECO:0000256|PIRNR:PIRNR000836}; KW Hydrolase {ECO:0000256|ARBA:ARBA00022801, ECO:0000256|HAMAP-Rule:MF_04086}; KW Magnesium {ECO:0000256|ARBA:ARBA00022842, ECO:0000256|HAMAP-Rule:MF_04086}; KW Manganese {ECO:0000256|HAMAP-Rule:MF_04086}; KW Metal-binding {ECO:0000256|ARBA:ARBA00022723, ECO:0000256|HAMAP- KW Rule:MF_04086}; KW Nucleotide-binding {ECO:0000256|HAMAP-Rule:MF_04086, KW ECO:0000256|PIRNR:PIRNR000836}; KW Nucleotidyltransferase {ECO:0000256|HAMAP-Rule:MF_04086, KW ECO:0000256|PIRNR:PIRNR000836}; KW RNA-directed RNA polymerase {ECO:0000256|HAMAP-Rule:MF_04086, KW ECO:0000256|PIRNR:PIRNR000836}; KW Transferase {ECO:0000256|HAMAP-Rule:MF_04086, KW ECO:0000256|PIRNR:PIRNR000836}; KW Viral RNA replication {ECO:0000256|HAMAP-Rule:MF_04086, KW ECO:0000256|PIRNR:PIRNR000836}; KW Virion {ECO:0000256|ARBA:ARBA00022844, ECO:0000256|HAMAP-Rule:MF_04086}. FT DOMAIN 1177..1372 FT /note="RdRp catalytic" FT /evidence="ECO:0000259|PROSITE:PS50525" FT ACT_SITE 115 FT /evidence="ECO:0000256|HAMAP-Rule:MF_04086" FT BINDING 51 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="1" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04086" FT BINDING 89 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="2" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04086" FT BINDING 89 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="1" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04086" FT BINDING 102 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="1" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04086" FT BINDING 1334 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_note="catalytic; for RdRp activity" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04086" SQ SEQUENCE 2220 AA; 253956 MW; 1F9C8990C036F77D CRC64; MEEDIANAKD LISKYLADNE KLSRQKLAFL VQTEPRMLLM EGLKLLSLCI EIDSCKANGC EHNTEDKTVE SILSDHGILT PALCFVVPDG YKLTGNVLIL LECFVRSSPA NFEQKYLEDH KKLEQLKNDL ESVGINLIPL IDGRTTFYNE QIPDWVNDKL RDTLFTLLKY SQESNALFEE SEYSRLCESL ALTSGRLSGI ESINVLTDKR AKHFEEIISS CHQGINNKLT SHEVKSLIEE EYQIFRNKLR QGDIENQFVR TDKVRLLEDF KKLYSDKIDT CDDSIEQLTF QFRRASPVLK FLYADLDSGE ERAADSQSEQ MQCWRSFLNK IKSLRILNTR RKLLLIFDVL ILLASRLDRI KHGDGLLAGW LGSCFVSVND RLVSLESTKR DLKRWIDSRK RTRDRNVGVL SPKEERNCEL LAIINRVLTR ATNALREVGI ETNSYGIDFK ILDCDVYDAI MDIEITGITP TISYQKTQED MFPYTLGVID ILDATDLERL SSLSLALINS MKTSSTVKLR QNEFGPSRYQ VVRCKEAYCQ EFFINRMGFK LLYQKTGECS KCYAINNNIT GEVCSFYADP KRFFPSVFSS DVLQKVVDVM VSWIEECTEL SEQLITIKLL TKMILVLILT HPSKRCQKFL QNIRYFVMAF VSDFYHKDLI EKIREDLITE VEYLLYRLVR HLLKIILSEE VVSMMTNRFK FVLNVSYMCH FITKETPDRL TDQIKCFEKF LEPKLEFGHV SVNPKDDASE EELAEMVHNA RRFLSKECCA DAEKIRYKKP GVSKKFISLL VSSFNNGSLF KEKEVKRTLR DPLITSGCAT ALDLASNKSV VVNKYTDGSR ILDYDFNKLT ALAVTQLTEV FARKGKFLLN KQDYDYKIQQ AMSNLVLGSK GGSGDTNNAD LDEILLDGGA SEYFDQLRCT VDNIVSQYRE QPERQQQADC NAPSISDLDK VVEEKLLIRL IKSELSNHMI EDFDREILSE DQYIKICENI YNDADLRSKY FYVGPMNSCP ISELTKAVVT RTFLDQEYFQ CFKSILLVMN GNKLMGRYSH YKSKCLNFKF DTGRLAEDVR ISERESNSEA LSKALSLTNC TTAMLKNLCF YSQESPQSYN STGPDTGRLK FSLSYKEQVG GNRELYIGDL RTKMFTRLIE DYFEALTSQL AGSCLNNEKE FDNAILSMKL NVSSAHVSYS MDHSKWGPMM CPFLFLTIIQ NLILLSDDLQ ADLKGKDYLS TLLTWHMHKM VEIPFNVVSA MMKSYIKSQL GLKKKTTQSV TEDFFNSNFQ IGTVPSHISS ILDMGQGILH NTSDFYALIS ERFINFAVRC VSGGQIDAYT SSDDQISLFD QNLTELLSRD AEEFKTLLEF HYYMSDQLNK FVSPKSAIGR FVAEFKSRFY VWGDEVPLLT KFVAAALHNI KCKEPHQLAE TIDTIIDQSV ANGVPVDLCN QIQKRTLSLL CYAKYPIDPF LLNCETDVRD WVDGNRSYRI MRQIERLIPD ACKKMRSMLR ILFNKLKTGE LHEEFTTNYL SGEHTTSLQN LFKLLGIEPL SDSDLGYHWL NLATHHPLRM VLRQKIIYSG AVNLEDEKVP TIVKTLQNRL SSTFTRGAQK LLSEAINKSA FQSSIASGFV GLCRTLGSKC VRGPNKENLY IRSIQTQLLG TQGVEVVMGD NGIQIWKVSP EVKDGGDTVV TYLRPLLWDY MCITLSTAIE LGAWVLGEPK QAQILDFFKH NPCDYFPLRP TVSKLLEDRV GMSHIIHSLR RLYPSLFEKH ILPFMSDLAS TKMKWSPRIK FLDLCVALDV NCEALSLVSH IVKWKREEHY VVLASELRNS HSRTHEPMME ERVVSTTDAV DNFMRQIYFE SYVRSFVATT RTLGSFTWFP HKTSIPEGEG LQRLGPFSSF IEKAIYKGIE RPMFKFDLMM GYAWIDFDIE PAQINLNQLI ASGLTEELRL DSLEDFFDLL STMPMDSVQF YQTIRYKIKS QDASFKETFS IHLNMIGLVN QCGEFVVNDV QALYSGSVSP CVLSDCWRLA LSGPTFKGRS AWFVESDVVN EFLKDTQQLG DVIPMKLIIN PDKLQFSEFD FTKVGPDNEP VPLVVCRGAL WESDRRVATF SPSIQDQDLE MFVREIGDGS PHLLVGALKS MMSDRLKQRI QWTGVDIVSI LTKQRPLDYA DILSELLESL GEWIDFKGYA LCYSKSKQKV MIQSSGGSLR LKGRTCSELF GPERCVEDIE //