ID L_VSIVA Reviewed; 2109 AA. AC P03523; Q86125; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1995, sequence version 2. DT 04-NOV-2026, entry version 164. DE RecName: Full=RNA-directed RNA polymerase L; DE Short=Protein L; DE AltName: Full=Large structural protein; DE AltName: Full=Replicase; DE AltName: Full=Transcriptase; DE Includes: DE RecName: Full=RNA-directed RNA polymerase; DE EC=2.7.7.48 {ECO:0000250|UniProtKB:P28887}; DE Includes: DE RecName: Full=GTP phosphohydrolase {ECO:0000305}; DE EC=3.6.1.- {ECO:0000269|PubMed:18003731}; DE Includes: DE RecName: Full=GDP polyribonucleotidyltransferase {ECO:0000305}; DE EC=2.7.7.88 {ECO:0000269|PubMed:26602696, ECO:0000269|PubMed:28053102}; DE AltName: Full=PRNTase {ECO:0000303|PubMed:28053102}; DE Includes: DE RecName: Full=mRNA cap methyltransferase {ECO:0000305}; DE AltName: Full=mRNA (guanine-N(7)-)-methyltransferase {ECO:0000303|PubMed:19710136}; DE Short=G-N7-MTase {ECO:0000303|PubMed:31354644}; DE AltName: Full=mRNA (nucleoside-2'-O-)-methyltransferase {ECO:0000303|PubMed:19710136}; DE Short=N1-2'-O-MTase {ECO:0000303|PubMed:31354644}; GN Name=L; OS Vesicular stomatitis Indiana virus (strain San Juan) (VSIV). OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Haploviricotina; OC Monjiviricetes; Mononegavirales; Rhabdoviridae; Alpharhabdovirinae; OC Vesiculovirus; Vesiculovirus indiana. OX NCBI_TaxID=11285; OH NCBI_TaxID=7158; Aedes. OH NCBI_TaxID=9913; Bos taurus (Bovine). OH NCBI_TaxID=58271; Culicoides. OH NCBI_TaxID=9793; Equus asinus (Donkey) (Equus africanus asinus). OH NCBI_TaxID=9796; Equus caballus (Horse). OH NCBI_TaxID=9606; Homo sapiens (Human). OH NCBI_TaxID=252607; Lutzomyia. OH NCBI_TaxID=7370; Musca domestica (House fly). OH NCBI_TaxID=7190; Simuliidae (black flies). OH NCBI_TaxID=9823; Sus scrofa (Pig). RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA]. RX PubMed=6086959; DOI=10.1128/jvi.51.2.505-514.1984; RA Schubert M., Harmison G.G., Meier E.; RT "Primary structure of the vesicular stomatitis virus polymerase (L) gene: RT evidence for a high frequency of mutations."; RL J. Virol. 51:505-514(1984). RN [2] RP CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=201777; DOI=10.1128/jvi.24.3.786-793.1977; RA Testa D., Banerjee A.K.; RT "Two methyltransferase activities in the purified virions of vesicular RT stomatitis virus."; RL J. Virol. 24:786-793(1977). RN [3] RP SUBCELLULAR LOCATION. RX PubMed=2999788; DOI=10.1073/pnas.82.23.7984; RA Schubert M., Harmison G.G., Richardson C.D., Meier E.; RT "Expression of a cDNA encoding a functional 241-kilodalton vesicular RT stomatitis virus RNA polymerase."; RL Proc. Natl. Acad. Sci. U.S.A. 82:7984-7988(1985). RN [4] RP FUNCTION. RX PubMed=2844966; DOI=10.1099/0022-1317-69-10-2555; RA Hunt D.M., Mehta R., Hutchinson K.L.; RT "The L protein of vesicular stomatitis virus modulates the response of the RT polyadenylic acid polymerase to S-adenosylhomocysteine."; RL J. Gen. Virol. 69:2555-2561(1988). RN [5] RP REVIEW. RX PubMed=12213662; DOI=10.1016/s0167-4781(02)00462-1; RA Barr J.N., Whelan S.P., Wertz G.W.; RT "Transcriptional control of the RNA-dependent RNA polymerase of vesicular RT stomatitis virus."; RL Biochim. Biophys. Acta 1577:337-353(2002). RN [6] RP FUNCTION, MUTAGENESIS OF LYS-1651; GLY-1674; PHE-1691; ASP-1762; LYS-1795 RP AND GLU-1833, CATALYTIC ACTIVITY, AND ACTIVE SITE. RX PubMed=16227259; DOI=10.1128/jvi.79.21.13373-13384.2005; RA Li J., Fontaine-Rodriguez E.C., Whelan S.P.; RT "Amino acid residues within conserved domain VI of the vesicular stomatitis RT virus large polymerase protein essential for mRNA cap methyltransferase RT activity."; RL J. Virol. 79:13373-13384(2005). RN [7] RP FUNCTION. RX PubMed=16709677; DOI=10.1073/pnas.0509821103; RA Li J., Wang J.T., Whelan S.P.; RT "A unique strategy for mRNA cap methylation used by vesicular stomatitis RT virus."; RL Proc. Natl. Acad. Sci. U.S.A. 103:8493-8498(2006). RN [8] RP CATALYTIC ACTIVITY. RX PubMed=18003731; DOI=10.1128/jvi.02107-07; RA Li J., Rahmeh A., Morelli M., Whelan S.P.; RT "A conserved motif in region v of the large polymerase proteins of RT nonsegmented negative-sense RNA viruses that is essential for mRNA RT capping."; RL J. Virol. 82:775-784(2008). RN [9] RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF LYS-1651; ASP-1762; RP LYS-1795 AND GLU-1833. RX PubMed=19710136; DOI=10.1128/jvi.01426-09; RA Rahmeh A.A., Li J., Kranzusch P.J., Whelan S.P.; RT "Ribose 2'-O methylation of the vesicular stomatitis virus mRNA cap RT precedes and facilitates subsequent guanine-N-7 methylation by the large RT polymerase protein."; RL J. Virol. 83:11043-11050(2009). RN [10] RP SUBUNIT. RX PubMed=21041632; DOI=10.1073/pnas.1013559107; RA Rahmeh A.A., Schenk A.D., Danek E.I., Kranzusch P.J., Liang B., Walz T., RA Whelan S.P.; RT "Molecular architecture of the vesicular stomatitis virus RNA polymerase."; RL Proc. Natl. Acad. Sci. U.S.A. 107:20075-20080(2010). RN [11] RP REVIEW. RX PubMed=21945214; DOI=10.1016/j.virusres.2011.09.012; RA Ogino T., Banerjee A.K.; RT "An unconventional pathway of mRNA cap formation by vesiculoviruses."; RL Virus Res. 162:100-109(2011). RN [12] RP FUNCTION. RX PubMed=22908284; DOI=10.1073/pnas.1209147109; RA Rahmeh A.A., Morin B., Schenk A.D., Liang B., Heinrich B.S., Brusic V., RA Walz T., Whelan S.P.; RT "Critical phosphoprotein elements that regulate polymerase architecture and RT function in vesicular stomatitis virus."; RL Proc. Natl. Acad. Sci. U.S.A. 109:14628-14633(2012). RN [13] RP FUNCTION. RX PubMed=22246179; DOI=10.1038/emboj.2011.483; RA Morin B., Rahmeh A.A., Whelan S.P.; RT "Mechanism of RNA synthesis initiation by the vesicular stomatitis virus RT polymerase."; RL EMBO J. 31:1320-1329(2012). RN [14] RP SUBCELLULAR LOCATION. RX PubMed=24055706; DOI=10.1016/j.bbrc.2013.09.064; RA Hodges J., Tang X., Landesman M.B., Ruedas J.B., Ghimire A., Gudheti M.V., RA Perrault J., Jorgensen E.M., Gerton J.M., Saffarian S.; RT "Asymmetric packaging of polymerases within vesicular stomatitis virus."; RL Biochem. Biophys. Res. Commun. 440:271-276(2013). RN [15] RP FUNCTION. RX PubMed=24526687; DOI=10.1074/jbc.m113.542761; RA Morin B., Whelan S.P.; RT "Sensitivity of the polymerase of vesicular stomatitis virus to 2' RT substitutions in the template and nucleotide triphosphate during initiation RT and elongation."; RL J. Biol. Chem. 289:9961-9969(2014). RN [16] RP REVIEW. RX PubMed=23602472; DOI=10.1016/j.coviro.2013.03.008; RA Morin B., Kranzusch P.J., Rahmeh A.A., Whelan S.P.; RT "The polymerase of negative-stranded RNA viruses."; RL Curr. Opin. Virol. 3:103-110(2013). RN [17] RP MUTAGENESIS OF LYS-1651; GLY-1670; GLY-1674 AND ASP-1735. RC STRAIN=NL; RX PubMed=25056882; DOI=10.1128/jvi.00876-14; RA Zhang Y., Wei Y., Zhang X., Cai H., Niewiesk S., Li J.; RT "Rational design of human metapneumovirus live attenuated vaccine RT candidates by inhibiting viral mRNA cap methyltransferase."; RL J. Virol. 88:11411-11429(2014). RN [18] RP CATALYTIC ACTIVITY. RX PubMed=26602696; DOI=10.1093/nar/gkv1286; RA Neubauer J., Ogino M., Green T.J., Ogino T.; RT "Signature motifs of GDP polyribonucleotidyltransferase, a non-segmented RT negative strand RNA viral mRNA capping enzyme, domain in the L protein are RT required for covalent enzyme-pRNA intermediate formation."; RL Nucleic Acids Res. 44:330-341(2016). RN [19] RP ACTIVE SITE, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND RP BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=28053102; DOI=10.1128/jvi.02322-16; RA Ogino M., Ogino T.; RT "5'-Phospho-RNA Acceptor Specificity of GDP Polyribonucleotidyltransferase RT of Vesicular Stomatitis Virus in mRNA Capping."; RL J. Virol. 91:0-0(2017). RN [20] RP REVIEW. RX PubMed=31354644; DOI=10.3389/fmicb.2019.01490; RA Ogino T., Green T.J.; RT "RNA Synthesis and Capping by Non-segmented Negative Strand RNA Viral RT Polymerases: Lessons From a Prototypic Virus."; RL Front. Microbiol. 10:1490-1490(2019). RN [21] RP CATALYTIC ACTIVITY, DOMAIN, AND MUTAGENESIS OF LYS-1177; ARG-1178; ARG-1181 RP AND ARG-1183. RX PubMed=35108335; DOI=10.1371/journal.ppat.1010287; RA Ogino M., Green T.J., Ogino T.; RT "GDP polyribonucleotidyltransferase domain of vesicular stomatitis virus RT polymerase regulates leader-promoter escape and polyadenylation-coupled RT termination during stop-start transcription."; RL PLoS Pathog. 18:e1010287-e1010287(2022). RN [22] {ECO:0007744|PDB:5A22} RP STRUCTURE BY ELECTRON MICROSCOPY, DOMAIN, AND ZINC-BINDING. RX PubMed=26144317; DOI=10.1016/j.cell.2015.06.018; RA Liang B., Li Z., Jenni S., Rahmeh A.A., Morin B.M., Grant T., RA Grigorieff N., Harrison S.C., Whelan S.P.; RT "Structure of the L protein of vesicular stomatitis virus from electron RT cryomicroscopy."; RL Cell 162:314-327(2015). RN [23] {ECO:0007744|PDB:6U1X} RP STRUCTURE BY ELECTRON MICROSCOPY, ZINC-BINDING, DOMAIN, INTERACTION WITH RP THE PHOSPHOPROTEIN, AND FUNCTION. RX PubMed=31914397; DOI=10.1016/j.celrep.2019.12.024; RA Jenni S., Bloyet L.M., Diaz-Avalos R., Liang B., Whelan S.P.J., RA Grigorieff N., Harrison S.C.; RT "Structure of the Vesicular Stomatitis Virus L Protein in Complex with Its RT Phosphoprotein Cofactor."; RL Cell Rep. 30:53-60.e5(2020). RN [24] RP STRUCTURE BY ELECTRON MICROSCOPY OF THE VIRION, SUBCELLULAR LOCATION, RP FUNCTION, INTERACTION WITH THE NUCLEOPROTEIN, AND INTERACTION WITH THE RP PHOSPHOPROTEIN. RX PubMed=35476516; DOI=10.1073/pnas.2111948119; RA Si Z., Zhou K., Tsao J., Luo M., Zhou Z.H.; RT "Locations and in situ structure of the polymerase complex inside the RT virion of vesicular stomatitis virus."; RL Proc. Natl. Acad. Sci. U.S.A. 119:e2111948119-e2111948119(2022). CC -!- FUNCTION: Multifunctional enzyme responsible for RNA synthesis CC (replicase and transcriptase), cap addition, and cap methylation CC (PubMed:24526687). Also performs the polyadenylation of subgenomic CC mRNAs by a stuttering mechanism at a slipery stop site present at the CC end of viral genes (PubMed:2844966). The template is composed of the CC viral RNA tightly encapsidated by the nucleoprotein (N) CC (PubMed:31914397). L is packaged into virions during assembly and CC translocates to the 3' leader promoter to initiate transcription after CC entering the host cells (PubMed:35476516). During transcription and CC replication of the genome, L does not bind the N-RNA complex directly, CC but is bridged by its non-catalytic cofactor P, which interacts with L CC and N oligomers simultaneously (PubMed:35476516). In the transcription CC mode, the polymerase performs the sequential transcription of all mRNAs CC using a termination-reinitiation mechanism responding to gene start and CC gene end signals. Some polymerase disengage from the template at each CC gene junction, resulting in a decreasing abundance of transcripts from CC the 3' to the 5' end of the genome (By similarity). The first gene is CC the most transcribed, and the last the least transcribed (Probable). CC The viral phosphoprotein helps the polymerase to engage the N-RNA CC template and acts as a processivity factor (PubMed:22246179, CC PubMed:22908284). Polyribonucleotidyl transferase (PRNTase) adds the CC cap structure when the nascent RNA chain length has reached few CC nucleotides (PubMed:19710136). Ribose 2'-O methylation of viral mRNA CC cap precedes and facilitates subsequent guanine-N-7 methylation, both CC activities being carried by the viral polymerase (PubMed:16227259, CC PubMed:16709677, PubMed:19710136). In the replication mode, the CC polymerase replicates the whole viral genome without recognizing the CC gene end transcriptional signals (By similarity). The ability of the CC polymerase to override the gene end signals as it is producing the CC antigenome is probably due to replicative RNA becoming encapsidated CC with nucleoprotein as it is synthesized (By similarity). CC {ECO:0000250|UniProtKB:P28887, ECO:0000269|PubMed:16227259, CC ECO:0000269|PubMed:16709677, ECO:0000269|PubMed:19710136, CC ECO:0000269|PubMed:22246179, ECO:0000269|PubMed:22908284, CC ECO:0000269|PubMed:24526687, ECO:0000269|PubMed:2844966, CC ECO:0000269|PubMed:31914397, ECO:0000269|PubMed:35476516, ECO:0000305}. CC -!- CATALYTIC ACTIVITY: CC Reaction=RNA(n) + a ribonucleoside 5'-triphosphate = RNA(n+1) + CC diphosphate; 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 -!- CATALYTIC ACTIVITY: CC Reaction=GTP + H2O = GDP + phosphate + H(+); Xref=Rhea:RHEA:19669, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:37565, CC ChEBI:CHEBI:43474, ChEBI:CHEBI:58189; CC Evidence={ECO:0000269|PubMed:19710136}; CC -!- CATALYTIC ACTIVITY: CC Reaction=a 5'-end triphospho-adenylyl-adenylyl-cytidylyl-adenosine in CC mRNA + GDP + H(+) = a 5'-end (5'-triphosphoguanosine)-adenylyl- CC adenylyl-cytidylyl-adenosine in mRNA + diphosphate; CC Xref=Rhea:RHEA:65436, Rhea:RHEA-COMP:16797, Rhea:RHEA-COMP:16799, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:33019, ChEBI:CHEBI:58189, CC ChEBI:CHEBI:156484, ChEBI:CHEBI:156503; EC=2.7.7.88; CC Evidence={ECO:0000269|PubMed:18003731, ECO:0000269|PubMed:26602696, CC ECO:0000269|PubMed:28053102}; CC -!- CATALYTIC ACTIVITY: CC Reaction=a 5'-end (5'-triphosphoguanosine)-adenylyl-adenylyl-cytidylyl- CC adenosine in mRNA + S-adenosyl-L-methionine = a 5'-end (5'- CC triphosphoguanosine)-(2'-O-methyladenylyl)-adenylyl-cytidylyl- CC adenosine in mRNA + S-adenosyl-L-homocysteine + H(+); CC Xref=Rhea:RHEA:65380, Rhea:RHEA-COMP:16797, Rhea:RHEA-COMP:16801, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, CC ChEBI:CHEBI:156482, ChEBI:CHEBI:156484; CC Evidence={ECO:0000269|PubMed:16227259, ECO:0000269|PubMed:19710136, CC ECO:0000269|PubMed:201777}; CC -!- CATALYTIC ACTIVITY: CC Reaction=a 5'-end (5'-triphosphoguanosine)-(2'-O-methyladenylyl)- CC adenylyl-cytidylyl-adenosine in mRNA + S-adenosyl-L-methionine = a CC 5'-end (N(7)-methyl 5'-triphosphoguanosine)-(2'-O-methyladenylyl)- CC adenylyl-cytidylyl-adenosine in mRNA + S-adenosyl-L-homocysteine; CC Xref=Rhea:RHEA:65440, Rhea:RHEA-COMP:16798, Rhea:RHEA-COMP:16801, CC ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:156482, CC ChEBI:CHEBI:156483; Evidence={ECO:0000269|PubMed:19710136, CC ECO:0000269|PubMed:201777}; CC -!- ACTIVITY REGULATION: The GDP polyribonucleotidyltransferase activity is CC inhibited by the GDP analog DAPDP. {ECO:0000269|PubMed:28053102}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=0.5 uM for mRNA (nucleoside-2'-O-)-methyltransferase CC {ECO:0000269|PubMed:201777}; CC KM=10 uM for mRNA (guanine-N(7)-)-methyltransferase CC {ECO:0000269|PubMed:201777}; CC KM=0.031 uM for GDP polyribonucleotidyltransferase CC {ECO:0000269|PubMed:28053102}; CC -!- SUBUNIT: May form homodimer (PubMed:21041632). Interacts with the P CC protein; the association of P and L forms the polymerase complex, CC positions it on the template and allows to package the L polymerase in CC the virion, since P acts as a bridge between N and L (PubMed:31914397, CC PubMed:35476516). L binds loosely to N and is further bridged by the P CC protein, which interacts with L and N oligomers simultaneously CC (PubMed:35476516). {ECO:0000269|PubMed:21041632, CC ECO:0000269|PubMed:31914397, ECO:0000269|PubMed:35476516}. CC -!- SUBCELLULAR LOCATION: Virion {ECO:0000269|PubMed:24055706, CC ECO:0000269|PubMed:35476516}. Host cytoplasm CC {ECO:0000269|PubMed:2999788}. Note=L and P are packaged asymmetrically CC towards the blunt end of the virus. About 55 copies of L are present in CC the virion (PubMed:28053102). {ECO:0000269|PubMed:28053102}. CC -!- DOMAIN: The RNA-dependent RNA polymerase (RdRp) domain is responsible CC for the RNA sythesis (Probable). The polyribonucleotidyl transferase CC (PRNTase) domain is responsible for the initiation of transcription at CC the 3'-end of the genome (priming) and pre-mRNA 5'-capping during CC start-stop transcription (PubMed:35108335). The methyltransferase CC (MTase) domain is responsible for the cap methylation CC (PubMed:26144317). {ECO:0000269|PubMed:26144317, CC ECO:0000269|PubMed:35108335, ECO:0000305|PubMed:26144317}. CC -!- SIMILARITY: Belongs to the rhabdoviridae protein L 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; X00939; CAA25453.1; -; Genomic_RNA. DR EMBL; J02428; AAA48371.1; -; Genomic_RNA. DR PIR; A04119; ZLVN. DR RefSeq; NP_041716.1; NC_001560.1. DR PDB; 5A22; EM; 3.80 A; A=1-2109. DR PDB; 6U1X; EM; 3.00 A; A=1-2109. DR EMDB; EMD-20614; -. DR EMDB; EMD-6337; -. DR SMR; P03523; -. DR GeneID; 1489835; -. DR KEGG; vg:1489835; -. DR BRENDA; 2.1.1.375; 14216. DR BRENDA; 2.7.7.88; 14216. DR CD-CODE; 01BEC43A; Synthetic Condensate 000315. DR CD-CODE; 0E37FC39; Cytoplasmic viral factory. DR EvolutionaryTrace; P03523; -. DR PRO; PR:P03523; -. DR Proteomes; UP000002327; Segment. DR GO; GO:0030430; C:host cell cytoplasm; EXP:UniProtKB. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0003924; F:GTPase activity; EXP:UniProtKB. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0004482; F:mRNA 5'-cap (guanine-N7-)-methyltransferase activity; IEA:InterPro. DR GO; GO:0062105; F:RNA 2'-O-methyltransferase activity; IEA:RHEA. DR GO; GO:0003968; F:RNA-directed RNA polymerase activity; IEA:UniProtKB-KW. DR GO; GO:0039689; P:negative stranded viral RNA replication; IDA:UniProtKB. DR GO; GO:0019083; P:viral transcription; IEA:UniProtKB-KW. DR FunFam; 3.40.50.150:FF:000473; RNA-directed RNA polymerase L; 1. DR Gene3D; 3.40.50.150; Vaccinia Virus protein VP39; 1. DR InterPro; IPR039530; L_methyltransferase_rhabdo. DR InterPro; IPR039736; L_poly_C. DR InterPro; IPR048398; Methyltrans_Mon_C. DR InterPro; IPR048397; Methyltrans_Mon_CD. DR InterPro; IPR026890; Mononeg_mRNAcap. DR InterPro; IPR014023; Mononeg_RNA_pol_cat. DR InterPro; IPR025786; Mononega_L_MeTrfase. DR InterPro; IPR017234; RNA-dir_pol_rhabdovirus. DR InterPro; IPR029063; SAM-dependent_MTases_sf. DR NCBIfam; TIGR04198; paramyx_RNAcap; 1. DR Pfam; PF21080; Methyltrans_Mon_1st; 1. DR Pfam; PF14314; Methyltrans_Mon_2nd; 1. DR Pfam; PF21081; Methyltrans_Mon_3rd; 1. DR Pfam; PF14318; Mononeg_mRNAcap; 1. DR Pfam; PF00946; Mononeg_RNA_pol; 1. DR PIRSF; PIRSF037546; RNA_pol_RhabdoV_sub; 1. DR PROSITE; PS52108; MNV_L_PRNTASE; 1. DR PROSITE; PS50526; RDRP_SSRNA_NEG_NONSEG; 1. DR PROSITE; PS51590; SAM_MT_MNV_L; 1. PE 1: Evidence at protein level; KW 3D-structure; ATP-binding; Host cytoplasm; Hydrolase; Magnesium; KW Metal-binding; Methyltransferase; mRNA capping; mRNA processing; KW Multifunctional enzyme; Nucleotide-binding; Nucleotidyltransferase; KW Reference proteome; RNA-directed RNA polymerase; S-adenosyl-L-methionine; KW Transferase; Viral RNA replication; Viral transcription; Virion; Zinc. FT CHAIN 1..2109 FT /note="RNA-directed RNA polymerase L" FT /id="PRO_0000222844" FT DOMAIN 598..784 FT /note="RdRp catalytic" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00539" FT DOMAIN 870..1327 FT /note="PRNTase (capping)" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01452, FT ECO:0000269|PubMed:35108335" FT DOMAIN 1640..1837 FT /note="Mononegavirus-type SAM-dependent 2'-O-MTase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00923" FT REGION 866..1334 FT /note="Capping domain" FT /evidence="ECO:0000269|PubMed:26144317, FT ECO:0000269|PubMed:31914397" FT REGION 1157..1173 FT /note="priming-capping loop" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01452, FT ECO:0000269|PubMed:35108335" FT REGION 1358..1557 FT /note="Connector domain" FT /evidence="ECO:0000269|PubMed:26144317, FT ECO:0000269|PubMed:31914397" FT MOTIF 1090..1104 FT /note="PRNTase motif A" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01452" FT MOTIF 1152..1157 FT /note="PRNTase motif B" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01452" FT MOTIF 1188 FT /note="PRNTase motif C" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01452" FT MOTIF 1227..1228 FT /note="PRNTase motif D" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01452" FT MOTIF 1264..1273 FT /note="PRNTase motif E" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01452" FT ACT_SITE 1227 FT /note="Nucleophile; for GDP polyribonucleotidyltransferase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01452, FT ECO:0000269|PubMed:28053102" FT ACT_SITE 1651 FT /note="For mRNA (guanine-N(7)-)-methyltransferase and mRNA FT (nucleoside-2'-O-)-methyltransferase" FT /evidence="ECO:0000305|PubMed:16227259" FT ACT_SITE 1762 FT /note="For mRNA (guanine-N(7)-)-methyltransferase and mRNA FT (nucleoside-2'-O-)-methyltransferase" FT /evidence="ECO:0000305|PubMed:16227259" FT ACT_SITE 1795 FT /note="For mRNA (guanine-N(7)-)-methyltransferase and mRNA FT (nucleoside-2'-O-)-methyltransferase" FT /evidence="ECO:0000305|PubMed:16227259" FT ACT_SITE 1833 FT /note="For mRNA (guanine-N(7)-)-methyltransferase and mRNA FT (nucleoside-2'-O-)-methyltransferase" FT /evidence="ECO:0000305|PubMed:16227259" FT BINDING 605 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_note="catalytic; for RNA-directed RNA polymerase FT activity" FT /evidence="ECO:0000250|UniProtKB:P28887" FT BINDING 714 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_note="catalytic; for RNA-directed RNA polymerase FT activity" FT /evidence="ECO:0000250|UniProtKB:P28887" FT BINDING 1081 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /ligand_note="structural" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01452, FT ECO:0000269|PubMed:26144317, ECO:0000269|PubMed:31914397" FT BINDING 1108 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /ligand_note="structural" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01452, FT ECO:0000269|PubMed:26144317, ECO:0000269|PubMed:31914397" FT BINDING 1120 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /ligand_note="structural" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01452, FT ECO:0000269|PubMed:26144317" FT BINDING 1123 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /ligand_note="structural" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01452, FT ECO:0000269|PubMed:26144317" FT BINDING 1294 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /ligand_note="structural" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01452, FT ECO:0000269|PubMed:26144317" FT BINDING 1296 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /ligand_note="structural" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01452, FT ECO:0000269|PubMed:26144317" FT BINDING 1299 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /ligand_note="structural" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01452, FT ECO:0000269|PubMed:26144317, ECO:0000269|PubMed:31914397" FT BINDING 1302 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /ligand_note="structural" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01452, FT ECO:0000269|PubMed:26144317, ECO:0000269|PubMed:31914397" FT BINDING 1667..1676 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255" FT SITE 704 FT /note="Interaction with the phosphoprotein" FT /evidence="ECO:0000269|PubMed:31914397" FT SITE 1183 FT /note="Important for escaping from the 3'-terminal leader FT promoter followed by the formation of a stable leader RNA FT elongation complex" FT /evidence="ECO:0000269|PubMed:35108335" FT SITE 1419 FT /note="Interaction with the phosphoprotein" FT /evidence="ECO:0000269|PubMed:31914397" FT SITE 1427 FT /note="Interaction with the phosphoprotein" FT /evidence="ECO:0000269|PubMed:31914397" FT SITE 1496 FT /note="Interaction with the phosphoprotein" FT /evidence="ECO:0000269|PubMed:31914397" FT SITE 1911 FT /note="Interaction with the phosphoprotein" FT /evidence="ECO:0000269|PubMed:31914397" FT SITE 1981 FT /note="Interaction with the phosphoprotein" FT /evidence="ECO:0000269|PubMed:31914397" FT SITE 2022 FT /note="Interaction with the phosphoprotein" FT /evidence="ECO:0000269|PubMed:31914397" FT SITE 2097 FT /note="Interaction with the phosphoprotein" FT /evidence="ECO:0000269|PubMed:31914397" FT SITE 2098 FT /note="Interaction with the phosphoprotein" FT /evidence="ECO:0000269|PubMed:31914397" FT VARIANT 228 FT /note="P -> R" FT VARIANT 467 FT /note="H -> D" FT VARIANT 548..549 FT /note="FP -> LR" FT VARIANT 670 FT /note="P -> R" FT VARIANT 910 FT /note="S -> F" FT VARIANT 1026 FT /note="P -> A" FT VARIANT 1348 FT /note="A -> G" FT VARIANT 1589 FT /note="P -> A" FT VARIANT 2026 FT /note="I -> T" FT MUTAGEN 1177 FT /note="K->A: Reduces the capping activity." FT /evidence="ECO:0000269|PubMed:35108335" FT MUTAGEN 1178 FT /note="R->A,K: Decreases the efficiency of poly(A)-coupled FT termination of mRNA synthesis. Diminution of de novo FT initiation of leader RNA. No effect on P-L interaction." FT /evidence="ECO:0000269|PubMed:35108335" FT MUTAGEN 1181 FT /note="R->A: Reduces the capping activity. No effect on P-L FT interaction." FT /evidence="ECO:0000269|PubMed:35108335" FT MUTAGEN 1183 FT /note="R->A,K: Drastic reduction of leader RNA synthesis. FT No effect on capping activity. No effect on P-L FT interaction." FT /evidence="ECO:0000269|PubMed:35108335" FT MUTAGEN 1651 FT /note="K->A: Complete loss of G-N-7 and 2'-O methylation FT activity." FT /evidence="ECO:0000269|PubMed:16227259, FT ECO:0000269|PubMed:19710136, ECO:0000269|PubMed:25056882" FT MUTAGEN 1670 FT /note="G->A: Complete loss of G-N-7 methylation activity FT but not 2'-O methylation activity." FT /evidence="ECO:0000269|PubMed:25056882" FT MUTAGEN 1674 FT /note="G->A: No effect on G-N-7 and 2'-O methylation FT activity, but sensitive to the substrate concentration." FT /evidence="ECO:0000269|PubMed:19710136, FT ECO:0000269|PubMed:25056882" FT MUTAGEN 1691 FT /note="F->A: About 95% loss of G-N-7 and 2'-O methylation FT activity." FT /evidence="ECO:0000269|PubMed:16227259" FT MUTAGEN 1735 FT /note="D->A: 70%loss of G-N-7 and methylation activity and FT 2'-O methylation activity." FT /evidence="ECO:0000269|PubMed:16227259, FT ECO:0000269|PubMed:19710136, ECO:0000269|PubMed:25056882" FT MUTAGEN 1762 FT /note="D->A: Almost complete loss of G-N-7 and 2'-O FT methylation activity." FT /evidence="ECO:0000269|PubMed:16227259, FT ECO:0000269|PubMed:19710136" FT MUTAGEN 1795 FT /note="K->A: Almost complete loss of G-N-7 and 2'-O FT methylation activity." FT /evidence="ECO:0000269|PubMed:16227259, FT ECO:0000269|PubMed:19710136" FT MUTAGEN 1833 FT /note="E->A,Q: Almost complete loss of G-N-7 and 2'-O FT methylation activity." FT /evidence="ECO:0000269|PubMed:16227259, FT ECO:0000269|PubMed:19710136" FT STRAND 47..49 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 50..57 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 64..67 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 72..79 FT /evidence="ECO:0007829|PDB:6U1X" FT TURN 80..82 FT /evidence="ECO:0007829|PDB:6U1X" FT TURN 87..89 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 91..98 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 107..134 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 144..146 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 148..171 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 176..185 FT /evidence="ECO:0007829|PDB:6U1X" FT STRAND 188..192 FT /evidence="ECO:0007829|PDB:6U1X" FT STRAND 194..196 FT /evidence="ECO:0007829|PDB:6U1X" FT STRAND 198..204 FT /evidence="ECO:0007829|PDB:6U1X" FT TURN 205..207 FT /evidence="ECO:0007829|PDB:6U1X" FT STRAND 208..213 FT /evidence="ECO:0007829|PDB:6U1X" FT STRAND 216..219 FT /evidence="ECO:0007829|PDB:6U1X" FT TURN 220..223 FT /evidence="ECO:0007829|PDB:6U1X" FT STRAND 224..226 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 228..246 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 258..277 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 280..282 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 283..286 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 289..301 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 312..326 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 331..339 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 345..352 FT /evidence="ECO:0007829|PDB:6U1X" FT TURN 353..358 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 365..376 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 384..406 FT /evidence="ECO:0007829|PDB:6U1X" FT TURN 413..415 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 424..427 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 434..437 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 438..440 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 444..446 FT /evidence="ECO:0007829|PDB:6U1X" FT STRAND 460..464 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 474..483 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 494..500 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 506..516 FT /evidence="ECO:0007829|PDB:6U1X" FT STRAND 520..522 FT /evidence="ECO:0007829|PDB:6U1X" FT STRAND 524..526 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 546..558 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 559..563 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 564..566 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 576..586 FT /evidence="ECO:0007829|PDB:6U1X" FT TURN 587..589 FT /evidence="ECO:0007829|PDB:6U1X" FT STRAND 595..604 FT /evidence="ECO:0007829|PDB:6U1X" FT TURN 607..611 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 615..628 FT /evidence="ECO:0007829|PDB:6U1X" FT STRAND 632..635 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 638..642 FT /evidence="ECO:0007829|PDB:6U1X" FT STRAND 645..648 FT /evidence="ECO:0007829|PDB:6U1X" FT STRAND 655..658 FT /evidence="ECO:0007829|PDB:6U1X" FT STRAND 660..669 FT /evidence="ECO:0007829|PDB:6U1X" FT STRAND 672..674 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 685..703 FT /evidence="ECO:0007829|PDB:6U1X" FT STRAND 707..714 FT /evidence="ECO:0007829|PDB:6U1X" FT STRAND 716..724 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 730..758 FT /evidence="ECO:0007829|PDB:6U1X" FT TURN 764..766 FT /evidence="ECO:0007829|PDB:6U1X" FT STRAND 768..778 FT /evidence="ECO:0007829|PDB:6U1X" FT STRAND 780..782 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 790..794 FT /evidence="ECO:0007829|PDB:6U1X" FT TURN 795..798 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 810..824 FT /evidence="ECO:0007829|PDB:6U1X" FT STRAND 826..828 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 831..849 FT /evidence="ECO:0007829|PDB:6U1X" FT TURN 852..855 FT /evidence="ECO:0007829|PDB:6U1X" FT STRAND 862..865 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 871..879 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 892..895 FT /evidence="ECO:0007829|PDB:6U1X" FT STRAND 897..899 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 903..917 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 921..930 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 940..942 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 943..948 FT /evidence="ECO:0007829|PDB:6U1X" FT STRAND 949..951 FT /evidence="ECO:0007829|PDB:6U1X" FT STRAND 955..957 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 961..975 FT /evidence="ECO:0007829|PDB:6U1X" FT STRAND 976..979 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 983..994 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 997..1005 FT /evidence="ECO:0007829|PDB:6U1X" FT STRAND 1007..1009 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 1011..1019 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 1024..1030 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 1037..1042 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 1046..1068 FT /evidence="ECO:0007829|PDB:6U1X" FT TURN 1069..1071 FT /evidence="ECO:0007829|PDB:6U1X" FT STRAND 1072..1075 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 1082..1094 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 1106..1109 FT /evidence="ECO:0007829|PDB:6U1X" FT STRAND 1114..1118 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 1122..1125 FT /evidence="ECO:0007829|PDB:6U1X" FT STRAND 1130..1135 FT /evidence="ECO:0007829|PDB:6U1X" FT TURN 1136..1139 FT /evidence="ECO:0007829|PDB:6U1X" FT STRAND 1166..1168 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 1175..1180 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 1181..1185 FT /evidence="ECO:0007829|PDB:6U1X" FT TURN 1186..1188 FT /evidence="ECO:0007829|PDB:6U1X" FT STRAND 1192..1194 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 1197..1207 FT /evidence="ECO:0007829|PDB:6U1X" FT STRAND 1226..1228 FT /evidence="ECO:0007829|PDB:6U1X" FT STRAND 1231..1233 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 1244..1247 FT /evidence="ECO:0007829|PDB:6U1X" FT STRAND 1251..1254 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 1259..1262 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 1269..1283 FT /evidence="ECO:0007829|PDB:6U1X" FT TURN 1284..1286 FT /evidence="ECO:0007829|PDB:6U1X" FT STRAND 1291..1296 FT /evidence="ECO:0007829|PDB:6U1X" FT TURN 1300..1303 FT /evidence="ECO:0007829|PDB:6U1X" FT TURN 1327..1329 FT /evidence="ECO:0007829|PDB:6U1X" FT STRAND 1351..1353 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 1355..1376 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 1380..1382 FT /evidence="ECO:0007829|PDB:6U1X" FT STRAND 1383..1387 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 1389..1391 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 1397..1416 FT /evidence="ECO:0007829|PDB:6U1X" FT TURN 1417..1419 FT /evidence="ECO:0007829|PDB:6U1X" FT TURN 1422..1424 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 1428..1443 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 1447..1450 FT /evidence="ECO:0007829|PDB:6U1X" FT TURN 1451..1453 FT /evidence="ECO:0007829|PDB:6U1X" FT STRAND 1454..1456 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 1457..1462 FT /evidence="ECO:0007829|PDB:6U1X" FT STRAND 1472..1474 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 1477..1492 FT /evidence="ECO:0007829|PDB:6U1X" FT TURN 1493..1498 FT /evidence="ECO:0007829|PDB:6U1X" FT STRAND 1505..1507 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 1511..1513 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 1516..1533 FT /evidence="ECO:0007829|PDB:6U1X" FT STRAND 1534..1536 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 1539..1556 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 1565..1567 FT /evidence="ECO:0007829|PDB:6U1X" FT STRAND 1571..1575 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 1580..1582 FT /evidence="ECO:0007829|PDB:6U1X" FT STRAND 1609..1613 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 1626..1629 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 1635..1639 FT /evidence="ECO:0007829|PDB:6U1X" FT STRAND 1644..1646 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 1649..1658 FT /evidence="ECO:0007829|PDB:6U1X" FT STRAND 1664..1670 FT /evidence="ECO:0007829|PDB:6U1X" FT STRAND 1672..1674 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 1675..1683 FT /evidence="ECO:0007829|PDB:6U1X" FT STRAND 1689..1692 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 1705..1710 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 1711..1715 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 1720..1722 FT /evidence="ECO:0007829|PDB:6U1X" FT TURN 1724..1730 FT /evidence="ECO:0007829|PDB:6U1X" FT STRAND 1736..1738 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 1739..1752 FT /evidence="ECO:0007829|PDB:6U1X" FT STRAND 1758..1761 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 1768..1779 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 1782..1785 FT /evidence="ECO:0007829|PDB:6U1X" FT STRAND 1791..1797 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 1798..1803 FT /evidence="ECO:0007829|PDB:6U1X" FT STRAND 1805..1807 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 1808..1815 FT /evidence="ECO:0007829|PDB:6U1X" FT STRAND 1816..1824 FT /evidence="ECO:0007829|PDB:6U1X" FT STRAND 1833..1841 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 1852..1854 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 1856..1859 FT /evidence="ECO:0007829|PDB:6U1X" FT TURN 1863..1865 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 1868..1879 FT /evidence="ECO:0007829|PDB:6U1X" FT TURN 1883..1886 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 1889..1891 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 1895..1905 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 1910..1922 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 1928..1942 FT /evidence="ECO:0007829|PDB:6U1X" FT STRAND 1949..1951 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 1952..1956 FT /evidence="ECO:0007829|PDB:6U1X" FT TURN 1958..1961 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 1962..1979 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 1982..1993 FT /evidence="ECO:0007829|PDB:6U1X" FT STRAND 1999..2003 FT /evidence="ECO:0007829|PDB:6U1X" FT STRAND 2008..2021 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 2030..2044 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 2054..2062 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 2072..2075 FT /evidence="ECO:0007829|PDB:6U1X" FT HELIX 2079..2083 FT /evidence="ECO:0007829|PDB:6U1X" SQ SEQUENCE 2109 AA; 240883 MW; 011EC2C0B5967C27 CRC64; MEVHDFETDE FNDFNEDDYA TREFLNPDER MTYLNHADYN LNSPLISDDI DNLIRKFNSL PIPSMWDSKN WDGVLEMLTS CQANPISTSQ MHKWMGSWLM SDNHDASQGY SFLHEVDKEA EITFDVVETF IRGWGNKPIE YIKKERWTDS FKILAYLCQK FLDLHKLTLI LNAVSEVELL NLARTFKGKV RRSSHGTNIC RIRVPSLGPT FISEGWAYFK KLDILMDPNF LLMVKDVIIG RMQTVLSMVC RIDNLFSEQD IFSLLNIYRI GDKIVERQGN FSYDLIKMVE PICNLKLMKL ARESRPLVPQ FPHFENHIKT SVDEGAKIDR GIRFLHDQIM SVKTVDLTLV IYGSFRHWGH PFIDYYTGLE KLHSQVTMKK DIDVSYAKAL ASDLARIVLF QQFNDHKKWF VNGDLLPHDH PFKSHVKENT WPTAAQVQDF GDKWHELPLI KCFEIPDLLD PSIIYSHKSH SMNRSEVLKH VRMNPNTPIP SKKVLQTMLD TKATNWKEFL KEIDEKGLDD DDLIIGLKGK ERELKLAGRF FSLMSWKFPE YFVITEYLIK THFVPMFKGL TMADDLTAVI KKMLDSSSGQ GLKSYEAICI ANHIDYEKWN NHQRKLSNGP VFRVMGQFLG YPSLIERTHE FFEKSLIYYN GRPDLMRVHN NTLINSTSQP VCWQGQEGGL EGLRQKGWTI LNLLVIQREA KIRNTAVKVL AQGDNQVICT QYKTKKSRNV VELQGALNQM VSNNEKIMTA IKIGTGKLGL LINDDETMQS ADYLNYGKIP IFRGVIRGLE TKRWSRVTCV TNDQIPTCAN IMSSVSTNAL TVAHFAENPI NAMIQYNYFG TFARLLLMMH DPALRQSLYE VQDKIPGLHS STFKYAMLYL DPSIGGVSGM SLSRFLIRAF PDPVTESLSS WRFIHVHARS EHLKEMSAVF GNPEIAKFRI THIDKLVEDP TSLNIAMGMS PANLLKTEVK KCLIESRQTI RNQVIKDATI YLYHEEDRLR SFLWSINPLF PRFLSEFKSG TFLGVPDGLI SLFQNSRTIR NSFKKKYHRE LDDLIVRSEV SSLTHLGKLH LRRGSCKMWT CSATHADTLR YKSWGRTVIG TTVPHPLEML GPQHRKETPC APCNTSGFNY VSVHCPDGIH DVFSSRGPLP AYLGSKTSES TSILQPWERE SKVPLIKRAT RLRDAISWFV EPDSKLAMTI LSNIHSLTGE EWTKRQHGFK RTGSALHRFS TSRMSHGGFA SQSTAALTRL MATTDTMRDL GDQNFDFLFQ ATLLYAQITT TVARDGWITS CTDHYHIACK SCLRPIEEIT LDSSMDYTPP DVSHVLKTWR NGEGSWGQEI KQIYPLEANW KNLAPAEQSY QVGRCIGFLY GDLAYRKSTH AEDSSLFPLS IQGRIRGRGF LKGLLDGLMR ASCCQVIHRR SLAHLKRPAN AVYGGLIYLI DKLSVSPPFL SLTRSGPIRD ELETIPHKIP TSYPTSNRDM GVIVRNYFKY QCRLIEKGKY RSHYSQLWLF SDVLSIDFIG PFSISTTLLQ ILYKPFLSGK DKNELRELAN LSSLLRSGEG WEDIHVKFFT KDILLCPEEI RHACKFGIPK DNNKDMSYPP WGRESRGTIT TIPVYYTTTP YPKMLEMPPR IQNPLLSGIR LGQLPTGAHY KIRSILHGMG IHYRDFLSCG DGSGGMTAAL LRENVHSRGI FNSLLELSGS VMRGASPEPP SALETLGGDK SRCVNGETCW EYPSDLCDPR TWDYFLRLKA GLGLQIDLIV MDMEVRDSST SLKIETNVRN YVHRILDEQG VLIYKTYGTY ICESEKNAVT ILGPMFKTVD LVQTEFSSSQ TSEVYMVCKG LKKLIDEPNP DWSSINESWK NLYAFQSSEQ EFARAKKVST YFTLTGIPSQ FIPDPFVNIE TMLQIFGVPT GVSHAAALKS SDRPADLLTI SLFYMAIISY YNINHIRVGP IPPNPPSDGI AQNVGIAITG ISFWLSLMEK DIPLYQQCLA VIQQSFPIRW EAVSVKGGYK QKWSTRGDGL PKDTRISDSL APIGNWIRSL ELVRNQVRLN PFNEILFNQL CRTVDNHLKW SNLRRNTGMI EWINRRISKE DRSILMLKSD LHEENSWRD //