ID   L_AMPV1                 Reviewed;        2005 AA.
AC   Q2Y2L8;
DT   15-DEC-2009, integrated into UniProtKB/Swiss-Prot.
DT   10-FEB-2021, sequence version 2.
DT   03-AUG-2022, entry version 82.
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:0000250|UniProtKB:P28887};
DE              EC=3.6.1.- {ECO:0000250|UniProtKB:P28887};
DE   Includes:
DE     RecName: Full=GDP polyribonucleotidyltransferase {ECO:0000305};
DE              EC=2.7.7.88 {ECO:0000250|UniProtKB:P28887};
DE     AltName: Full=PRNTase {ECO:0000305};
DE   Includes:
DE     RecName: Full=mRNA cap methyltransferase {ECO:0000305};
DE              EC=2.1.1.375 {ECO:0000250|UniProtKB:P03523};
DE     AltName: Full=mRNA (guanine-N(7)-)-methyltransferase {ECO:0000250|UniProtKB:P03523};
DE              Short=G-N7-MTase {ECO:0000250|UniProtKB:P03523};
DE     AltName: Full=mRNA (nucleoside-2'-O-)-methyltransferase {ECO:0000250|UniProtKB:P03523};
DE              Short=N1-2'-O-MTase {ECO:0000250|UniProtKB:P03523};
GN   Name=L;
OS   Avian metapneumovirus (isolate Canada goose/Minnesota/15a/2001) (AMPV).
OC   Viruses; Riboviria; Orthornavirae; Negarnaviricota; Haploviricotina;
OC   Monjiviricetes; Mononegavirales; Pneumoviridae; Metapneumovirus.
OX   NCBI_TaxID=652954;
OH   NCBI_TaxID=8847; Anser sp. (goose).
OH   NCBI_TaxID=9103; Meleagris gallopavo (Wild turkey).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=15666873; DOI=10.1637/7208-051804r;
RA   Bennett R.S., Nezworski J., Velayudhan B.T., Nagaraja K.V., Zeman D.H.,
RA   Dyer N., Graham T., Lauer D.C., Njenga M.K., Halvorson D.A.;
RT   "Evidence of avian pneumovirus spread beyond Minnesota among wild and
RT   domestic birds in central North America.";
RL   Avian Dis. 48:902-908(2004).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=16282483; DOI=10.1128/jvi.79.23.14834-14842.2005;
RA   Bennett R.S., LaRue R., Shaw D., Yu Q., Nagaraja K.V., Halvorson D.A.,
RA   Njenga M.K.;
RT   "A wild goose metapneumovirus containing a large attachment glycoprotein is
RT   avirulent but immunoprotective in domestic turkeys.";
RL   J. Virol. 79:14834-14842(2005).
CC   -!- FUNCTION: Responsible for RNA synthesis (replicase and transcriptase),
CC       cap addition, and cap methylation. Performs also the polyadenylation of
CC       subgenomic mRNAs by a stuttering mechanism at a slipery stop site
CC       present at the end of viral genes. The template is composed of the
CC       viral RNA tightly encapsidated by the nucleoprotein (N). The viral
CC       polymerase binds to the genomic RNA at two differents sites in the 3'
CC       leader promoter thereby initiating either genome replication or mRNA
CC       transcription. In the transcription mode, the polymerase performs the
CC       sequential transcription of all mRNAs using a termination-reinitiation
CC       mechanism responding to gene start and gene end signals. Some
CC       polymerase disengage from the template at each gene junction, resulting
CC       in a decreasing abundance of transcripts from the 3' to the 5' end of
CC       the genome. The first gene is the most transcribed, and the last the
CC       least transcribed. Needs as cofactors the phosphoprotein for
CC       processivity and the M2-1 anti-termination protein. Polyribonucleotidyl
CC       transferase (PRNTase) adds the cap structure when the nascent RNA chain
CC       length has reached few nucleotides (By similarity). Ribose 2'-O
CC       methylation of viral mRNA cap precedes and facilitates subsequent
CC       guanine-N-7 methylation (By similarity). In the replication mode, the
CC       polymerase replicates the whole viral genome without recognizing the
CC       gene end transcriptional signals. The ability of the polymerase to
CC       override the gene end signals as it is producing the antigenome is
CC       probably due to replicative RNA becoming encapsidated with
CC       nucleoprotein as it is synthesized (By similarity).
CC       {ECO:0000250|UniProtKB:P03523, ECO:0000250|UniProtKB:P28887}.
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   -!- CATALYTIC ACTIVITY:
CC       Reaction=GTP + H2O = GDP + H(+) + phosphate; Xref=Rhea:RHEA:19669,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:37565,
CC         ChEBI:CHEBI:43474, ChEBI:CHEBI:58189;
CC         Evidence={ECO:0000250|UniProtKB:P28887};
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:0000250|UniProtKB:P28887};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a 5'-end (5'-triphosphoguanosine)-adenylyl-adenylyl-cytidylyl-
CC         adenosine in mRNA + 2 S-adenosyl-L-methionine = a 5'-end (N(7)-methyl
CC         5'-triphosphoguanosine)-(2'-O-methyladenylyl)-adenylyl-cytidylyl-
CC         adenosine in mRNA + H(+) + 2 S-adenosyl-L-homocysteine;
CC         Xref=Rhea:RHEA:65376, Rhea:RHEA-COMP:16797, Rhea:RHEA-COMP:16798,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789,
CC         ChEBI:CHEBI:156483, ChEBI:CHEBI:156484; EC=2.1.1.375;
CC         Evidence={ECO:0000250|UniProtKB:P03523};
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 + H(+) + S-adenosyl-L-homocysteine;
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:0000250|UniProtKB:P03523};
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:0000250|UniProtKB:P03523};
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000250|UniProtKB:P28887};
CC       Note=For RNA-directed RNA polymerase activity. Mn(2+) can stimulate de
CC       novo initiation but it is inefficient at supporting elongation of de
CC       novo initiated RNA. {ECO:0000250|UniProtKB:P28887};
CC   -!- SUBUNIT: Interacts with the phosphoprotein (via C-terminus); the
CC       association of P and L forms the polymerase complex.
CC       {ECO:0000250|UniProtKB:P28887}.
CC   -!- SUBCELLULAR LOCATION: Virion {ECO:0000250|UniProtKB:P28887}. Host
CC       cytoplasm {ECO:0000250|UniProtKB:P28887}. Note=Localizes in cytoplasmic
CC       inclusion bodies. {ECO:0000250|UniProtKB:P28887}.
CC   -!- DOMAIN: Contains an RNA-dependent RNA polymerase (RdRp) domain, a
CC       polyribonucleotidyl transferase (PRNTase or capping) domain and a
CC       methyltransferase (MTase) domain. {ECO:0000250|UniProtKB:P28887}.
CC   -!- SIMILARITY: Belongs to the paramyxovirus L protein family.
CC       {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAY82583.1; Type=Frameshift; Evidence={ECO:0000305};
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DR   EMBL; DQ009484; AAY82583.1; ALT_FRAME; Viral_cRNA.
DR   RefSeq; YP_443845.1; NC_007652.1.
DR   SMR; Q2Y2L8; -.
DR   Proteomes; UP000002471; Genome.
DR   GO; GO:0030430; C:host cell cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0003924; F:GTPase activity; IEA:RHEA.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0004482; F:mRNA (guanine-N7-)-methyltransferase activity; IEA:InterPro.
DR   GO; GO:0003968; F:RNA-directed 5'-3' RNA polymerase activity; IEA:UniProtKB-KW.
DR   InterPro; IPR039736; L_poly_C.
DR   InterPro; IPR026890; Mononeg_mRNAcap.
DR   InterPro; IPR014023; Mononeg_RNA_pol_cat.
DR   InterPro; IPR025786; Mononega_L_MeTrfase.
DR   Pfam; PF14318; Mononeg_mRNAcap; 1.
DR   Pfam; PF00946; Mononeg_RNA_pol; 1.
DR   TIGRFAMs; TIGR04198; paramyx_RNAcap; 1.
DR   PROSITE; PS50526; RDRP_SSRNA_NEG_NONSEG; 1.
DR   PROSITE; PS51590; SAM_MT_MNV_L; 1.
PE   3: Inferred from homology;
KW   ATP-binding; Host cytoplasm; Hydrolase; Magnesium; Metal-binding;
KW   Methyltransferase; mRNA capping; mRNA processing; Multifunctional enzyme;
KW   Nucleotide-binding; Nucleotidyltransferase; Reference proteome;
KW   RNA-directed RNA polymerase; S-adenosyl-L-methionine; Transferase;
KW   Viral RNA replication; Virion.
FT   CHAIN           1..2005
FT                   /note="RNA-directed RNA polymerase L"
FT                   /id="PRO_0000390364"
FT   DOMAIN          628..811
FT                   /note="RdRp catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00539"
FT   DOMAIN          1662..1857
FT                   /note="Mononegavirus-type SAM-dependent 2'-O-MTase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00923"
FT   REGION          902..1379
FT                   /note="GDP polyribonucleotidyltransferase"
FT                   /evidence="ECO:0000250|UniProtKB:P28887"
FT   ACT_SITE        1263
FT                   /note="Nucleophile; for GDP polyribonucleotidyltransferase
FT                   activity"
FT                   /evidence="ECO:0000250|UniProtKB:P03523"
FT   ACT_SITE        1673
FT                   /note="For mRNA (nucleoside-2'-O-)-methyltransferase
FT                   activity"
FT                   /evidence="ECO:0000250|UniProtKB:Q6WB93"
FT   ACT_SITE        1779
FT                   /note="For mRNA (nucleoside-2'-O-)-methyltransferase
FT                   activity"
FT                   /evidence="ECO:0000250|UniProtKB:Q6WB93"
FT   ACT_SITE        1817
FT                   /note="For mRNA (nucleoside-2'-O-)-methyltransferase
FT                   activity"
FT                   /evidence="ECO:0000250|UniProtKB:Q6WB93"
FT   ACT_SITE        1848
FT                   /note="For mRNA (nucleoside-2'-O-)-methyltransferase
FT                   activity"
FT                   /evidence="ECO:0000250|UniProtKB:Q6WB93"
FT   BINDING         635
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         745
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         1696..1700
FT                   /ligand="substrate"
FT                   /ligand_note="for mRNA (nucleoside-2'-O-)-methyltransferase
FT                   activity"
FT                   /evidence="ECO:0000250|UniProtKB:Q6WB93"
SQ   SEQUENCE   2005 AA;  228894 MW;  D6C87E72A95BF80B CRC64;
     MDPLNEGVVN VYLTDSYLKG VISFSETNAI GSCLLGKHYL KKDNTSKVAI ESPVVEHIRL
     RNAFQTRIKE KNLRVVEPVN MQSEVMRNSY TCELNLLKQL ITRSKDISSL KLDMICDWLQ
     LKSTSENPSV LKFVDVRCIP DWVSTWFSSW YNLNKLILEF RREEVACTGS IICKTIGSIM
     FIISSFGCVI KSNKSKRISF MTYNQVLTWK DVMLSRFNAN LCVWISNSLN KNQEGLGLRS
     NLQGALVNKL YEIVDSMLSV CSNEGFTLVK EFEGFIMSEI LKITEHAQFS TRFRNTLLNG
     LVDQLAKMRG LNRKRVSGTV LEGNQYPMYE TTLATLGGAL KTIRLLVNKN LDNAAELYYI
     FRIFGHPMVE EREAMDAVRL NNEITKILKL ESLTELRGAF ILRIIKGFVD TNKRWPKIKN
     LKVLSRRWIM YFKAKSYPSQ LELSSQDFLE LAGVQFEQEF AIPERTNLEM VLNDKAISPP
     KNLIWSVFPK NYLPTNIRER FTEEMFNSSE KLKTRRVLEY YLKDNKFDQN DLKKYVVRQE
     YLGDKEHVVS LTGKERELSV GRMFAMQPGK QRQVQILAEK LLADNIVPFF PETLTKYGDL
     ELQRIMEIKS ELSSVKSRRN DSYNNYIARA SIVTDLSKFN QAFRYETSSV CADVVDELHG
     TQSLFCWLHL TVPLTTMICT YRHAPPETEG VYDIDKIKEQ SGLYRFHMGG IEGWCQKLWT
     MEAVSLLDVV SVKNRVQLTS LLNGDNQSID VSKPVRLSQG VDEVKADYSL AVKMLKEIRN
     AYKDIGHKLK EGETYISRDL QFMSKVIQSE GVMHPSPIKK ILRVGPWINT ILDDIKTSAE
     SIGSLCQELE FRGESLLVSL ILRNFWLYEL WMHESKSHPL AGKQLYRQLS KTLAITQKFF
     GITKETDVVN LWMNVPMQFG GGDPVVLYRS FYRRTPDFLT EAVSHMSVLL KVYGKAKEGS
     KKDFFKALLS VDKNKRATLT TLMRDPQAVG SERQARVTSE INRAAVTSVL SLSPNQLFCD
     SAIHYSRNEE EVGLIAQNIT PVYPHGLRVL YESLPFHKAE KVVNMISGTK SITNLLQRTS
     AINGEDIDRA VSMMLENLGL LSRILSVCQD DITLPTKANG DLICCQVSRT LRERSWDNME
     IVGVTSPSIV TCMNIVYSSS SQLKGITIEK FSTDKTTRGQ RGPKSPWVGS STQEKKLVPV
     YNRQILSKQQ KEQLEAIGKL RWVYKGTQGL RRLLDKICIG SLGISYKNVK PLLPRFMSVN
     FLHRLSVSSR PMEFPASVPA YRTTNYHFDT SPVNQTLSER FGNEDINLVF QNAISCGISV
     MSVVEQLTGR SPKQLVMIPQ LEEIDIMPPP VFLGKFDYKL VEKISSDQHI FSPDKLDLVT
     LGKMLMPSTS GAKSDQFWNR KENFFHGNNL VESLSAALAC HWCGILTEQC NENNIFRREW
     GDGFVTDHAF IDFKTFVGVF KTKLLCGWGS RGGDIKDRDM IDESIDKLIR VDNSFWRMFS
     KVILEPKVRK RVMLFDVKIL SLVGYAGFKN WFIDHLRSSD LCEVPWVVNA DSEIVEVSAV
     KIYLQLLRVS SPLRITVLNY SDMAHAITRL IRRKSMHDNV PSISRTLSPA ELAPVVEPTV
     QMNLFPKITF ERLKNYETVS GSTRGKLTRN YMVMLPWQHI NRFNFVFSST GCKISVKACI
     GRLIQDLNPT VFYFVGEGAG NWMARTACEY PNAKFVYRSL KDDLDHHFPL EFQRVLGNMN
     RVIDGGEGLS MDTTDATQKT HWDLIHRICK DALLITLCDA EFKDRDDFFK MVTLWRKHVL
     SCRICTTYGT DLYLFAKYHA KEQSIKLPYF VRSIATYVMQ GSKLSGSECY VLLTLGHHNN
     LPCHGEVQSS KLKLAVCNDF SIPRKVEVKA VEANCKSLLS GLRTPINRAE LDRQKKMLTL
     RSYHSSVATV GGSRVIESKW LSKKATTIIE WLEHILNSPK GELNYDFFEA LENTYPNMVK
     LLDNLGSAEL KKLIKVTGYM LMSKK