UniProtKB - P28887 (L_HRSVA)
RNA-directed RNA polymerase L
L
Functioni
Responsible for RNA synthesis (replicase and transcriptase), cap addition, and cap methylation (PubMed:25010481, PubMed:31495574).
Performs also the polyadenylation of subgenomic mRNAs by a stuttering mechanism at a slipery stop site present at the end of viral genes (PubMed:8794332).
The template is composed of the viral RNA tightly encapsidated by the nucleoprotein (N) (Probable). 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 (PubMed:29873775).
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 (PubMed:8794332).
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 (Probable). The first gene is the most transcribed, and the last the least transcribed (Probable). Needs as cofactors the phosphoprotein for processivity and the M2-1 anti-termination protein (PubMed:8552680, PubMed:31495574).
Polyribonucleotidyl transferase (PRNTase) adds the cap structure when the nascent RNA chain length has reached few nucleotides (PubMed:16189012, PubMed:8445369).
Ribose 2'-O methylation of viral mRNA cap precedes and facilitates subsequent guanine-N-7 methylation (PubMed:33956914).
In the replication mode, the polymerase replicates the whole viral genome without recognizing the gene end transcriptional signals (PubMed:15681446).
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 (PubMed:15681446).
By similarityCurated8 PublicationsCatalytic activityi
- a ribonucleoside 5'-triphosphate + RNA(n) = diphosphate + RNA(n+1)PROSITE-ProRule annotation1 PublicationEC:2.7.7.48PROSITE-ProRule annotation1 Publication
- a 5'-end triphospho-adenylyl-adenylyl-cytidylyl-adenosine in mRNA + GDP + H+ = a 5'-end (5'-triphosphoguanosine)-adenylyl-adenylyl-cytidylyl-adenosine in mRNA + diphosphate1 PublicationEC:2.7.7.881 Publication
- 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-homocysteine2 PublicationsEC:2.1.1.3752 Publications
Cofactori
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 700 | Magnesium; catalytic; for RNA-directed RNA polymerase1 Publication | 1 | |
Metal bindingi | 811 | Magnesium; catalytic; for RNA-directed RNA polymerase1 Publication | 1 | |
Active sitei | 1338 | Nucleophile; for GDP polyribonucleotidyltransferaseBy similarity | 1 | |
Active sitei | 1831 | For mRNA (nucleoside-2'-O-)-methyltransferase 2By similarity | 1 | |
Active sitei | 1936 | For mRNA (nucleoside-2'-O-)-methyltransferase 2By similarity | 1 | |
Active sitei | 1973 | For mRNA (nucleoside-2'-O-)-methyltransferase 2By similarity | 1 | |
Active sitei | 2004 | For mRNA (nucleoside-2'-O-)-methyltransferase 2By similarity | 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
GO - Biological processi
- negative stranded viral RNA replication Source: UniProtKB
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 |
Enzyme and pathway databases
BRENDAi | 2.7.7.48, 17394 |
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:2.7.7.482 Publications) 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 respiratory syncytial virus A (strain A2) |
Taxonomic identifieri | 11259 [NCBI] |
Taxonomic lineagei | Viruses › Riboviria › Orthornavirae › Negarnaviricota › Haploviricotina › Monjiviricetes › Mononegavirales › Pneumoviridae › Orthopneumovirus › |
Virus hosti | Homo sapiens (Human) [TaxID: 9606] |
Proteomesi |
|
Subcellular locationi
- Virion Curated
- Host cytoplasm 1 Publication Note: Localizes in cytoplasmic inclusion bodies.1 Publication
Keywords - Cellular componenti
Host cytoplasm, VirionPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 811 | D → A: Complete loss of RNA synthesis. 1 Publication | 1 | |
Mutagenesisi | 812 | N → A: Complete loss of RNA synthesis. 1 Publication | 1 | |
Mutagenesisi | 1261 | P → A: Inhibition of RNA synthesis. 1 Publication | 1 | |
Mutagenesisi | 1262 | W → A: Inhibition of RNA synthesis. 1 Publication | 1 | |
Mutagenesisi | 1274 | P → A: No effect on RNA synthesis. | 1 | |
Mutagenesisi | 1276 | Y → A: No effect on RNA synthesis. | 1 | |
Mutagenesisi | 1820 | R → A: Complete loss of methyltransferase activity. 1 Publication | 1 | |
Mutagenesisi | 1855 | G → S: Complete loss of methyltransferase activity. 1 Publication | 1 | |
Mutagenesisi | 1936 | D → A: About 90% loss of methyltransferase activity. 1 Publication | 1 | |
Mutagenesisi | 1938 | E → A: Complete loss of methyltransferase activity. 1 Publication | 1 | |
Mutagenesisi | 1998 | S → A: Complete loss of methyltransferase activity. 1 Publication | 1 | |
Mutagenesisi | 2004 | E → A: Complete loss of methyltransferase activity. 1 Publication | 1 |
Chemistry databases
ChEMBLi | CHEMBL4630897 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000142727 | 1 – 2165 | RNA-directed RNA polymerase LAdd BLAST | 2165 |
Interactioni
Subunit structurei
Interacts with the phosphoprotein (via C-terminus); the association of P and L forms the polymerase complex.
3 PublicationsProtein-protein interaction databases
IntActi | P28887, 15 interactors |
Structurei
Secondary structure
3D structure databases
SMRi | P28887 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 693 – 877 | RdRp catalyticPROSITE-ProRule annotationAdd BLAST | 185 | |
Domaini | 1820 – 2008 | Mononegavirus-type SAM-dependent 2'-O-MTasePROSITE-ProRule annotationAdd BLAST | 189 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 968 – 1460 | GDP polyribonucleotidyltransferase1 PublicationAdd BLAST | 493 | |
Regioni | 1853 – 1857 | Substrate binding for mRNA (nucleoside-2'-O-)-methyltransferase 2By similarity | 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 IPR016269, RNA-dir_pol_paramyxovirus |
Pfami | View protein in Pfam PF14318, Mononeg_mRNAcap, 1 hit PF00946, Mononeg_RNA_pol, 1 hit |
PIRSFi | PIRSF000830, RNA_pol_ParamyxoV, 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
MDPIINGNSA NVYLTDSYLK GVISFSECNA LGSYIFNGPY LKNDYTNLIS
60 70 80 90 100
RQNPLIEHMN LKKLNITQSL ISKYHKGEIK LEEPTYFQSL LMTYKSMTSS
110 120 130 140 150
EQIATTNLLK KIIRRAIEIS DVKVYAILNK LGLKEKDKIK SNNGQDEDNS
160 170 180 190 200
VITTIIKDDI LSAVKDNQSH LKADKNHSTK QKDTIKTTLL KKLMCSMQHP
210 220 230 240 250
PSWLIHWFNL YTKLNNILTQ YRSNEVKNHG FTLIDNQTLS GFQFILNQYG
260 270 280 290 300
CIVYHKELKR ITVTTYNQFL TWKDISLSRL NVCLITWISN CLNTLNKSLG
310 320 330 340 350
LRCGFNNVIL TQLFLYGDCI LKLFHNEGFY IIKEVEGFIM SLILNITEED
360 370 380 390 400
QFRKRFYNSM LNNITDAANK AQKNLLSRVC HTLLDKTVSD NIINGRWIIL
410 420 430 440 450
LSKFLKLIKL AGDNNLNNLS ELYFLFRIFG HPMVDERQAM DAVKINCNET
460 470 480 490 500
KFYLLSSLSM LRGAFIYRII KGFVNNYNRW PTLRNAIVLP LRWLTYYKLN
510 520 530 540 550
TYPSLLELTE RDLIVLSGLR FYREFRLPKK VDLEMIINDK AISPPKNLIW
560 570 580 590 600
TSFPRNYMPS HIQNYIEHEK LKFSESDKSR RVLEYYLRDN KFNECDLYNC
610 620 630 640 650
VVNQSYLNNP NHVVSLTGKE RELSVGRMFA MQPGMFRQVQ ILAEKMIAEN
660 670 680 690 700
ILQFFPESLT RYGDLELQKI LELKAGISNK SNRYNDNYNN YISKCSIITD
710 720 730 740 750
LSKFNQAFRY ETSCICSDVL DELHGVQSLF SWLHLTIPHV TIICTYRHAP
760 770 780 790 800
PYIGDHIVDL NNVDEQSGLY RYHMGGIEGW CQKLWTIEAI SLLDLISLKG
810 820 830 840 850
KFSITALING DNQSIDISKP IRLMEGQTHA QADYLLALNS LKLLYKEYAG
860 870 880 890 900
IGHKLKGTET YISRDMQFMS KTIQHNGVYY PASIKKVLRV GPWINTILDD
910 920 930 940 950
FKVSLESIGS LTQELEYRGE SLLCSLIFRN VWLYNQIALQ LKNHALCNNK
960 970 980 990 1000
LYLDILKVLK HLKTFFNLDN IDTALTLYMN LPMLFGGGDP NLLYRSFYRR
1010 1020 1030 1040 1050
TPDFLTEAIV HSVFILSYYT NHDLKDKLQD LSDDRLNKFL TCIITFDKNP
1060 1070 1080 1090 1100
NAEFVTLMRD PQALGSERQA KITSEINRLA VTEVLSTAPN KIFSKSAQHY
1110 1120 1130 1140 1150
TTTEIDLNDI MQNIEPTYPH GLRVVYESLP FYKAEKIVNL ISGTKSITNI
1160 1170 1180 1190 1200
LEKTSAIDLT DIDRATEMMR KNITLLIRIL PLDCNRDKRE ILSMENLSIT
1210 1220 1230 1240 1250
ELSKYVRERS WSLSNIVGVT SPSIMYTMDI KYTTSTISSG IIIEKYNVNS
1260 1270 1280 1290 1300
LTRGERGPTK PWVGSSTQEK KTMPVYNRQV LTKKQRDQID LLAKLDWVYA
1310 1320 1330 1340 1350
SIDNKDEFME ELSIGTLGLT YEKAKKLFPQ YLSVNYLHRL TVSSRPCEFP
1360 1370 1380 1390 1400
ASIPAYRTTN YHFDTSPINR ILTEKYGDED IDIVFQNCIS FGLSLMSVVE
1410 1420 1430 1440 1450
QFTNVCPNRI ILIPKLNEIH LMKPPIFTGD VDIHKLKQVI QKQHMFLPDK
1460 1470 1480 1490 1500
ISLTQYVELF LSNKTLKSGS HVNSNLILAH KISDYFHNTY ILSTNLAGHW
1510 1520 1530 1540 1550
ILIIQLMKDS KGIFEKDWGE GYITDHMFIN LKVFFNAYKT YLLCFHKGYG
1560 1570 1580 1590 1600
KAKLECDMNT SDLLCVLELI DSSYWKSMSK VFLEQKVIKY ILSQDASLHR
1610 1620 1630 1640 1650
VKGCHSFKLW FLKRLNVAEF TVCPWVVNID YHPTHMKAIL TYIDLVRMGL
1660 1670 1680 1690 1700
INIDRIHIKN KHKFNDEFYT SNLFYINYNF SDNTHLLTKH IRIANSELEN
1710 1720 1730 1740 1750
NYNKLYHPTP ETLENILANP IKSNDKKTLN DYCIGKNVDS IMLPLLSNKK
1760 1770 1780 1790 1800
LIKSSAMIRT NYSKQDLYNL FPMVVIDRII DHSGNTAKSN QLYTTTSHQI
1810 1820 1830 1840 1850
SLVHNSTSLY CMLPWHHINR FNFVFSSTGC KISIEYILKD LKIKDPNCIA
1860 1870 1880 1890 1900
FIGEGAGNLL LRTVVELHPD IRYIYRSLKD CNDHSLPIEF LRLYNGHINI
1910 1920 1930 1940 1950
DYGENLTIPA TDATNNIHWS YLHIKFAEPI SLFVCDAELS VTVNWSKIII
1960 1970 1980 1990 2000
EWSKHVRKCK YCSSVNKCML IVKYHAQDDI DFKLDNITIL KTYVCLGSKL
2010 2020 2030 2040 2050
KGSEVYLVLT IGPANIFPVF NVVQNAKLIL SRTKNFIMPK KADKESIDAN
2060 2070 2080 2090 2100
IKSLIPFLCY PITKKGINTA LSKLKSVVSG DILSYSIAGR NEVFSNKLIN
2110 2120 2130 2140 2150
HKHMNILKWF NHVLNFRSTE LNYNHLYMVE STYPYLSELL NSLTTNELKK
2160
LIKITGSLLY NFHNE
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural varianti | 17 | S → G. | 1 | |
Natural varianti | 319 | C → Y in strain: Cold-passage attenuated. | 1 | |
Natural varianti | 831 | Q → L. | 1 | |
Natural varianti | 1049 | N → D. | 1 | |
Natural varianti | 1183 | D → E. | 1 | |
Natural varianti | 1690 | H → Y in strain: Cold-passage attenuated. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M75730 Genomic RNA Translation: AAA47418.1 U27298 Genomic RNA Translation: AAA84898.1 U50362 Genomic RNA Translation: AAB86667.1 U50363 Genomic RNA Translation: AAB86679.1 U63644 Genomic RNA Translation: AAC55973.1 AF035006 Genomic RNA Translation: AAC14905.1 |
PIRi | A40317, RRNZA2 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M75730 Genomic RNA Translation: AAA47418.1 U27298 Genomic RNA Translation: AAA84898.1 U50362 Genomic RNA Translation: AAB86667.1 U50363 Genomic RNA Translation: AAB86679.1 U63644 Genomic RNA Translation: AAC55973.1 AF035006 Genomic RNA Translation: AAC14905.1 |
PIRi | A40317, RRNZA2 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
6PZK | electron microscopy | 3.20 | A | 1-2165 | [»] | |
6UEN | electron microscopy | 3.67 | A | 1-1500 | [»] | |
SMRi | P28887 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
IntActi | P28887, 15 interactors |
Chemistry databases
ChEMBLi | CHEMBL4630897 |
Enzyme and pathway databases
BRENDAi | 2.7.7.48, 17394 |
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 IPR016269, RNA-dir_pol_paramyxovirus |
Pfami | View protein in Pfam PF14318, Mononeg_mRNAcap, 1 hit PF00946, Mononeg_RNA_pol, 1 hit |
PIRSFi | PIRSF000830, RNA_pol_ParamyxoV, 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_HRSVA | |
Accessioni | P28887Primary (citable) accession number: P28887 Secondary accession number(s): O41355 Q82021 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | December 1, 1992 |
Last sequence update: | December 1, 1992 | |
Last modified: | February 23, 2022 | |
This is version 119 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