UniProtKB - Q6WB93 (L_HMPVC)
RNA-directed RNA polymerase L
L
Functioni
Responsible for RNA synthesis (replicase and transcriptase), cap addition, and cap methylation. Performs also the polyadenylation of subgenomic mRNAs by a stuttering mechanism at a slipery stop site present at the end of viral genes. The template is composed of the viral RNA tightly encapsidated by the nucleoprotein (N). The viral polymerase binds to the genomic RNA at two differents sites in the 3' leader promoter thereby initiating either genome replication or mRNA transcription. In the transcription mode, the polymerase performs the sequential transcription of all mRNAs using a termination-reinitiation mechanism responding to gene start and gene end signals. Some polymerase disengage from the template at each gene junction, resulting in a decreasing abundance of transcripts from the 3' to the 5' end of the genome. The first gene is the most transcribed, and the last the least transcribed. Needs as cofactors the phosphoprotein for processivity and the M2-1 anti-termination protein. Polyribonucleotidyl transferase (PRNTase) adds the cap structure when the nascent RNA chain length has reached few nucleotides (By similarity).
Ribose 2'-O methylation of viral mRNA cap precedes and facilitates subsequent guanine-N-7 methylation (By similarity).
In the replication mode, the polymerase replicates the whole viral genome without recognizing the gene end transcriptional signals. The ability of the polymerase to override the gene end signals as it is producing the antigenome is probably due to replicative RNA becoming encapsidated with nucleoprotein as it is synthesized (By similarity).
By similarityCatalytic activityi
- EC:2.7.7.48PROSITE-ProRule annotation
- a 5'-end triphospho-adenylyl-adenylyl-cytidylyl-adenosine in mRNA + GDP + H+ = a 5'-end (5'-triphosphoguanosine)-adenylyl-adenylyl-cytidylyl-adenosine in mRNA + diphosphateBy similarityEC:2.7.7.88By similarity
- a 5'-end (5'-triphosphoguanosine)-adenylyl-adenylyl-cytidylyl-adenosine in mRNA + 2 S-adenosyl-L-methionine = a 5'-end (N7-methyl 5'-triphosphoguanosine)-(2'-O-methyladenylyl)-adenylyl-cytidylyl-adenosine in mRNA + H+ + 2 S-adenosyl-L-homocysteine1 PublicationEC:2.1.1.3751 Publication
Cofactori
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 635 | Magnesium; catalytic; for RNA-directed RNA polymeraseBy similarity | 1 | |
Metal bindingi | 745 | Magnesium; catalytic; for RNA-directed RNA polymerase1 Publication | 1 | |
Active sitei | 1263 | Nucleophile; for GDP polyribonucleotidyltransferaseBy similarity | 1 | |
Active sitei | 1673 | For mRNA (nucleoside-2'-O-)-methyltransferase 21 Publication | 1 | |
Active sitei | 1779 | For mRNA (nucleoside-2'-O-)-methyltransferase 21 Publication | 1 | |
Active sitei | 1817 | For mRNA (nucleoside-2'-O-)-methyltransferase 21 Publication | 1 | |
Active sitei | 1848 | For mRNA (nucleoside-2'-O-)-methyltransferase 21 Publication | 1 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- GTPase activity Source: RHEA
- metal ion binding Source: UniProtKB-KW
- mRNA (guanine-N7-)-methyltransferase activity Source: InterPro
- RNA-directed 5'-3' RNA polymerase activity Source: UniProtKB-KW
Keywordsi
Molecular function | Hydrolase, Methyltransferase, Multifunctional enzyme, Nucleotidyltransferase, RNA-directed RNA polymerase, Transferase |
Biological process | mRNA capping, mRNA processing, Viral RNA replication |
Ligand | ATP-binding, Magnesium, Metal-binding, Nucleotide-binding, S-adenosyl-L-methionine |
Names & Taxonomyi
Protein namesi | Recommended name: RNA-directed RNA polymerase LShort name: Protein L Alternative name(s): Large structural protein Replicase Transcriptase Including the following 4 domains: RNA-directed RNA polymerase (EC:2.7.7.48By similarity) Alternative name(s): PRNTaseCurated Alternative name(s): mRNA (guanine-N(7)-)-methyltransferaseBy similarity Short name: G-N7-MTaseBy similarity mRNA (nucleoside-2'-O-)-methyltransferaseBy similarity Short name: N1-2'-O-MTaseBy similarity |
Gene namesi | Name:L |
Organismi | Human metapneumovirus (strain CAN97-83) (HMPV) |
Taxonomic identifieri | 694067 [NCBI] |
Taxonomic lineagei | Viruses › Riboviria › Orthornavirae › Negarnaviricota › Haploviricotina › Monjiviricetes › Mononegavirales › Pneumoviridae › Metapneumovirus › |
Virus hosti | Homo sapiens (Human) [TaxID: 9606] |
Proteomesi |
|
Subcellular locationi
- Virion By similarity
- Host cytoplasm By similarity Note: Localizes in cytoplasmic inclusion bodies.By similarity
Keywords - Cellular componenti
Host cytoplasm, VirionPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 745 | D → A: Complete loss of polymerase activity. 1 Publication | 1 | |
Mutagenesisi | 1696 | G → A: Impaired cell-cell spread and/or viral replication. Loss of 2'-O methylation activity but not G-N-7 methylation activity. 1 Publication | 1 | |
Mutagenesisi | 1700 | G → A: Impaired cell-cell spread and/or viral replication. 70-80% reduction in N-protein expression. Loss of 2'-O methylation activity but not G-N-7 methylation activity. 1 Publication | 1 | |
Mutagenesisi | 1755 | D → A: Impaired cell-cell spread and/or viral replication. 50-70% reduction in N-protein expression. Loss of 2'-O methylation activity but not G-N-7 methylation activity. 1 Publication | 1 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000394810 | 1 – 2005 | RNA-directed RNA polymerase LAdd BLAST | 2005 |
Proteomic databases
PRIDEi | Q6WB93 |
Interactioni
Subunit structurei
Interacts with the phosphoprotein (via C-terminus); the association of P and L forms the polymerase complex.
By similarityProtein-protein interaction databases
IntActi | Q6WB93, 1 interactor |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 628 – 811 | RdRp catalyticPROSITE-ProRule annotationAdd BLAST | 184 | |
Domaini | 1662 – 1852 | Mononegavirus-type SAM-dependent 2'-O-MTasePROSITE-ProRule annotationAdd BLAST | 191 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 902 – 1379 | GDP polyribonucleotidyltransferaseBy similarityAdd BLAST | 478 | |
Regioni | 1696 – 1700 | Substrate binding for mRNA (nucleoside-2'-O-)-methyltransferase 21 Publication | 5 |
Domaini
Sequence similaritiesi
Family and domain databases
InterProi | View protein in InterPro IPR039736, L_poly_C IPR026890, Mononeg_mRNAcap IPR014023, Mononeg_RNA_pol_cat IPR025786, Mononega_L_MeTrfase |
Pfami | View protein in Pfam PF14318, Mononeg_mRNAcap, 1 hit PF00946, Mononeg_RNA_pol, 1 hit |
TIGRFAMsi | TIGR04198, paramyx_RNAcap, 1 hit |
PROSITEi | View protein in PROSITE PS50526, RDRP_SSRNA_NEG_NONSEG, 1 hit PS51590, SAM_MT_MNV_L, 1 hit |
i Sequence
Sequence statusi: Complete.
10 20 30 40 50
MDPLNESTVN VYLPDSYLKG VISFSETNAI GSCLLKRPYL KNDNTAKVAI
60 70 80 90 100
ENPVIEHVRL KNAVNSKMKI SDYKVVEPVN MQHEIMKNVH SCELTLLKQF
110 120 130 140 150
LTRSKNISTL KLNMICDWLQ LKSTSDDTSI LSFIDVEFIP SWVSNWFSNW
160 170 180 190 200
YNLNKLILEF RREEVIRTGS ILCRSLGKLV FIVSSYGCIV KSNKSKRVSF
210 220 230 240 250
FTYNQLLTWK DVMLSRFNAN FCIWVSNSLN ENQEGLGLRS NLQGMLTNKL
260 270 280 290 300
YETVDYMLSL CCNEGFSLVK EFEGFIMSEI LRITEHAQFS TRFRNTLLNG
310 320 330 340 350
LTDQLTKLKN KNRLRVHSTV LENNDYPMYE VVLKLLGDTL RCIKLLINKN
360 370 380 390 400
LENAAELYYI FRIFGHPMVD ERDAMDAVKL NNEITKILRL ESLTELRGAF
410 420 430 440 450
ILRIIKGFVD NNKRWPKIKN LKVLSKRWTM YFKAKNYPSQ LELSEQDFLE
460 470 480 490 500
LAAIQFEQEF SVPEKTNLEM VLNDKAISPP KRLIWSVYPK NYLPETIKNR
510 520 530 540 550
YLEETFNASD SLKTRRVLEY YLKDNKFDQK ELKSYVVRQE YLNDKEHIVS
560 570 580 590 600
LTGKERELSV GRMFAMQPGK QRQIQILAEK LLADNIVPFF PETLTKYGDL
610 620 630 640 650
DLQRIMEIKS ELSSIKTRRN DSYNNYIARA SIVTDLSKFN QAFRYETTAI
660 670 680 690 700
CADVADELHG TQSLFCWLHL IVPMTTMICA YRHAPPETKG EYDIDKIEEQ
710 720 730 740 750
SGLYRYHMGG IEGWCQKLWT MEAISLLDVV SVKTRCQMTS LLNGDNQSID
760 770 780 790 800
VSKPVKLSEG LDEVKADYRL AVKMLKEIRD AYRNIGHKLK EGETYISRDL
810 820 830 840 850
QFISKVIQSE GVMHPTPIKK VLRVGPWINT ILDDIKTSAE SIGSLCQELE
860 870 880 890 900
FRGESIIVSL ILRNFWLYNL YMHESKQHPL AGKQLFKQLN KTLTSVQRFF
910 920 930 940 950
EIKRENEVVD LWMNIPMQFG GGDPVVFYRS FYRRTPDFLT EAISHVDILL
960 970 980 990 1000
KISANIKNET KVSFFKALLS IEKNERATLT TLMRDPQAVG SERQAKVTSD
1010 1020 1030 1040 1050
INRTAVTSIL SLSPNQLFSD SAIHYSRNEE EVGIIAENIT PVYPHGLRVL
1060 1070 1080 1090 1100
YESLPFHKAE KVVNMISGTK SITNLLQRTS AINGEDIDRA VSMMLENLGL
1110 1120 1130 1140 1150
LSRILSVVVD SIEIPIKSNG RLICCQISRT LRETSWNNME IVGVTSPSIT
1160 1170 1180 1190 1200
TCMDVIYATS SHLKGIIIEK FSTDRTTRGQ RGPKSPWVGS STQEKKLVPV
1210 1220 1230 1240 1250
YNRQILSKQQ REQLEAIGKM RWVYKGTPGL RRLLNKICLG SLGISYKCVK
1260 1270 1280 1290 1300
PLLPRFMSVN FLHRLSVSSR PMEFPASVPA YRTTNYHFDT SPINQALSER
1310 1320 1330 1340 1350
FGNEDINLVF QNAISCGISI MSVVEQLTGR SPKQLVLIPQ LEEIDIMPPP
1360 1370 1380 1390 1400
VFQGKFNYKL VDKITSDQHI FSPDKIDMLT LGKMLMPTIK GQKTDQFLNK
1410 1420 1430 1440 1450
RENYFHGNNL IESLSAALAC HWCGILTEQC IENNIFKKDW GDGFISDHAF
1460 1470 1480 1490 1500
MDFKIFLCVF KTKLLCSWGS QGKNIKDEDI VDESIDKLLR IDNTFWRMFS
1510 1520 1530 1540 1550
KVMFEPKVKK RIMLYDVKFL SLVGYIGFKN WFIEQLRSAE LHEIPWIVNA
1560 1570 1580 1590 1600
EGDLVEIKSI KIYLQLIEQS LFLRITVLNY TDMAHALTRL IRKKLMCDNA
1610 1620 1630 1640 1650
LLTPISSPMV NLTQVIDPTT QLDYFPKITF ERLKNYDTSS NYAKGKLTRN
1660 1670 1680 1690 1700
YMILLPWQHV NRYNFVFSST GCKVSLKTCI GKLMKDLNPK VLYFIGEGAG
1710 1720 1730 1740 1750
NWMARTACEY PDIKFVYRSL KDDLDHHYPL EYQRVIGELS RIIDSGEGLS
1760 1770 1780 1790 1800
METTDATQKT HWDLIHRVSK DALLITLCDA EFKDRDDFFK MVILWRKHVL
1810 1820 1830 1840 1850
SCRICTTYGT DLYLFAKYHA KDCNVKLPFF VRSVATFIMQ GSKLSGSECY
1860 1870 1880 1890 1900
ILLTLGHHNS LPCHGEIQNS KMKIAVCNDF YAAKKLDNKS IEANCKSLLS
1910 1920 1930 1940 1950
GLRIPINKKE LDRQRRLLTL QSNHSSVATV GGSKIIESKW LTNKASTIID
1960 1970 1980 1990 2000
WLEHILNSPK GELNYDFFEA LENTYPNMIK LIDNLGNAEI KKLIKVTGYM
LVSKK
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AY297749 Genomic RNA Translation: AAQ67700.1 |
RefSeqi | YP_012613.1, NC_004148.2 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AY297749 Genomic RNA Translation: AAQ67700.1 |
RefSeqi | YP_012613.1, NC_004148.2 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
4UCJ | X-ray | 3.26 | A/B | 1600-2005 | [»] | |
6U5O | electron microscopy | 3.70 | L | 1-2005 | [»] | |
SMRi | Q6WB93 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
IntActi | Q6WB93, 1 interactor |
Proteomic databases
PRIDEi | Q6WB93 |
Family and domain databases
InterProi | View protein in InterPro IPR039736, L_poly_C IPR026890, Mononeg_mRNAcap IPR014023, Mononeg_RNA_pol_cat IPR025786, Mononega_L_MeTrfase |
Pfami | View protein in Pfam PF14318, Mononeg_mRNAcap, 1 hit PF00946, Mononeg_RNA_pol, 1 hit |
TIGRFAMsi | TIGR04198, paramyx_RNAcap, 1 hit |
PROSITEi | View protein in PROSITE PS50526, RDRP_SSRNA_NEG_NONSEG, 1 hit PS51590, SAM_MT_MNV_L, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | L_HMPVC | |
Accessioni | Q6WB93Primary (citable) accession number: Q6WB93 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | June 15, 2010 |
Last sequence update: | July 5, 2004 | |
Last modified: | September 29, 2021 | |
This is version 83 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Viral Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families