I0DF35 · L_SFTS
- ProteinRNA-directed RNA polymerase L
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids2084 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
RNA-dependent RNA polymerase, which is responsible for the replication and transcription of the viral RNA genome using antigenomic RNA as an intermediate (By similarity).
During transcription, synthesizes subgenomic RNAs and assures their capping by a cap-snatching mechanism, which involves the endonuclease activity cleaving the host capped pre-mRNAs (PubMed:31914382).
These short capped RNAs are then used as primers for viral transcription. The 3'-end of subgenomic mRNAs molecules are not polyadenylated. During replication, the polymerase binds the 5' and 3' vRNA extremities at distinct sites (PubMed:32313945).
In turn, significant conformational changes occur in the polymerase and in vRNA to initiate active RNA synthesis (By similarity).
As a consequence of the use of the same enzyme for both transcription and replication, these mechanisms need to be well coordinated (By similarity).
During transcription, synthesizes subgenomic RNAs and assures their capping by a cap-snatching mechanism, which involves the endonuclease activity cleaving the host capped pre-mRNAs (PubMed:31914382).
These short capped RNAs are then used as primers for viral transcription. The 3'-end of subgenomic mRNAs molecules are not polyadenylated. During replication, the polymerase binds the 5' and 3' vRNA extremities at distinct sites (PubMed:32313945).
In turn, significant conformational changes occur in the polymerase and in vRNA to initiate active RNA synthesis (By similarity).
As a consequence of the use of the same enzyme for both transcription and replication, these mechanisms need to be well coordinated (By similarity).
Miscellaneous
Classified as His+ endonuclease since it has a histidine upstream of the active site that coordinates the first cation.
Catalytic activity
- a ribonucleoside 5'-triphosphate + RNA(n) = diphosphate + RNA(n+1)
Cofactor
Protein has several cofactor binding sites:
Mn2+ (UniProtKB | Rhea| CHEBI:29035 )
Note: For polymerase activity. Initiation activity is stronger in the presence of Mn2+ than in the presence of Mg2+.
Activity regulation
Inhibited by Baloxavir acid (BXA).
Features
Showing features for binding site, active site, site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 80 | Mn2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 112 | Mn2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 112 | Mn2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 126 | Mn2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Active site | 145 | For endonuclease activity | ||||
Sequence: K | ||||||
Binding site | 1127 | Mg2+ (UniProtKB | ChEBI); catalytic; for RdRp activity | ||||
Sequence: D | ||||||
Site | 1703 | Interaction with the cap substrate | ||||
Sequence: F | ||||||
Site | 1707 | Interaction with the cap substrate | ||||
Sequence: Q | ||||||
Site | 1719 | Interaction with the cap substrate | ||||
Sequence: Y | ||||||
Site | 1772 | Interaction with the cap substrate | ||||
Sequence: L |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | host cell endoplasmic reticulum | |
Cellular Component | host cell endoplasmic reticulum-Golgi intermediate compartment | |
Cellular Component | host cell Golgi apparatus | |
Cellular Component | virion component | |
Molecular Function | hydrolase activity | |
Molecular Function | metal ion binding | |
Molecular Function | RNA-dependent RNA polymerase activity | |
Biological Process | DNA-templated transcription | |
Biological Process | viral RNA genome replication |
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameRNA-directed RNA polymerase L
- EC number
- Short namesProtein L
- Alternative names
Including 1 domain:
- Recommended namecap-snatching endonuclease
- EC number
Organism names
- Strains
- Taxonomic lineageViruses > Riboviria > Orthornavirae > Negarnaviricota > Polyploviricotina > Ellioviricetes > Bunyavirales > Phenuiviridae > Bandavirus > Bandavirus dabieense
Accessions
- Primary accessionI0DF35
- Secondary accessions
Proteomes
Subcellular Location
UniProt Annotation
GO Annotation
Keywords
- Cellular component
Phenotypes & Variants
Features
Showing features for mutagenesis, natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 80 | Drastically decreased endonuclease activity. | ||||
Sequence: H → A | ||||||
Mutagenesis | 92 | Drastically decreased endonuclease activity. | ||||
Sequence: D → A | ||||||
Mutagenesis | 112 | Complete loss of endonclease activity. | ||||
Sequence: D → A | ||||||
Mutagenesis | 126 | Drastically decreased endonuclease activity. | ||||
Sequence: E → A | ||||||
Natural variant | 128 | in strain: SPL057A and Isolate AH12/China/2010 | ||||
Sequence: T → S | ||||||
Natural variant | 251 | in strain: SPL057A and Isolate AH12/China/2010 | ||||
Sequence: E → K | ||||||
Natural variant | 284 | in strain: SPL057A | ||||
Sequence: S → N | ||||||
Natural variant | 317 | in strain: SPL057A | ||||
Sequence: A → S | ||||||
Natural variant | 343 | in strain: SPL057A | ||||
Sequence: S → T | ||||||
Natural variant | 444-449 | in strain: SPL057A | ||||
Sequence: KESHDA → RESHET | ||||||
Natural variant | 448-449 | in strain: Isolate AH12/China/2010 | ||||
Sequence: DA → ET | ||||||
Natural variant | 470 | in strain: Isolate AH12/China/2010 | ||||
Sequence: A → T | ||||||
Natural variant | 479 | in strain: Isolate AH12/China/2010 | ||||
Sequence: V → I | ||||||
Natural variant | 570 | in strain: SPL057A | ||||
Sequence: I → V | ||||||
Natural variant | 586 | in strain: SPL057A and Isolate AH12/China/2010 | ||||
Sequence: E → D | ||||||
Natural variant | 1061 | in strain: Isolate AH12/China/2010 | ||||
Sequence: E → D | ||||||
Mutagenesis | 1126 | Complete loss of polymerase activity. | ||||
Sequence: D → A | ||||||
Natural variant | 1157 | in strain: SPL057A | ||||
Sequence: K → R | ||||||
Natural variant | 1208 | in strain: SPL057A | ||||
Sequence: T → S | ||||||
Natural variant | 1433 | in strain: SPL057A | ||||
Sequence: T → A | ||||||
Natural variant | 1711 | in strain: Isolate AH12/China/2010 | ||||
Sequence: I → V |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 16 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000456059 | 1-2084 | RNA-directed RNA polymerase L | |||
Sequence: MNLEVLCGRINVENGLSLGEPGLYDQIYDRPGLPDLDVTVDATGVTVDIGAVPDSASQLGSSINAGLITIQLSEAYKINHDFTFSGLSKTTDRRLSEVFPITHDGSDGMTPDVIHTRLDGTIVVVEFTTTRSHNIGGLEAAYRTKIEKYRDPISRRVDIMENPRVFFGVIVVSSGGVLSNMPLTQDEAEELMYRFCIANEIYTKARSMDADIELQKSEEELEAISRALSFFSLFEPNIERVEGTFPNSEIEMLEQFLSTPADVDFITKTLKAKEVEAYADLCDSHYLKPEKTIQERLEINRCEAIDKTQDLLAGLHARSNKQTSLNRGTVKLPPWLPKPSSESIDIKTDSGFGSLMDHGAYGELWAKCLLDVSLGNVEGVVSDPAKELDIAISDDPEKDTPKEAKITYRRFKPALSSSARQEFSLQGVEGKKWKRMAANQKKEKESHDALSPFLDVEDIGDFLTFNNLLADSRYGDESVQRAVSILLEKASAMQDTELTHALNDSFKRNLSSNVVQWSLWVSCLAQELASALKQHCRAGEFIIKKLKFWPIYVIIKPTKSSSHIFYSLGIRKADVTRRLTGRVFSETIDAGEWELTEFKSLKTCKLTNLVNLPCTMLNSIAFWREKLGVAPWLVRKPCSELREQVGLTFLISLEDKSKTEEIITLTRYTQMEGFVSPPMLPKPQKMLGKLDGPLRTKLQVYLLRKHLDCMVRIASQPFSLIPREGRVEWGGTFHAISGRSTNLENMVNSWYIGYYKNKEESTELNALGEMYKKIVEMEEDKPSSPEFLGWGDTDSPKKHEFSRSFLRAACSSLEREIAQRHGRQWKQNLEERVLREIGTKNILDLASMKATSNFSKDWELYSEVQTKEYHRSKLLEKMATLIEKGVMWYIDAVGQAWKAVLDDGCMRICLFKKNQHGGLREIYVMDANARLVQFGVETMARCVCELSPHETVANPRLKNSIIENHGLKSARSLGPGSININSSNDAKKWNQGHYTTKLALVLCWFMPAKFHRFIWAAISMFRRKKMMVDLRFLAHLSSKSESRSSDPFREAMTDAFHGNREVSWMDKGRTYIKTETGMMQGILHFTSSLLHSCVQSFYKSYFVSKLKEGYMGESISGVVDVIEGSDDSAIMISIRPKSDMDEVRSRFFVANLLHSVKFLNPLFGIYSSEKSTVNTVYCVEYNSEFHFHRHLVRPTLRWIAASHQISETEALASRQEDYSNLLTQCLEGGASFSLTYLIQCAQLLHHYMLLGLCLHPLFGTFMGMLISDPDPALGFFLMDNPAFAGGAGFRFNLWRACKTTDLGRKYAYYFNEIQGKTKGDEDYRALDATSGGTLSHSVMVYWGDRKKYQALLNRMGLPEDWVEQIDENPGVLYRRAANKKELLLKLAEKVHSPGVTSSLSKGHVVPRVVAAGVYLLSRHCFRFSSSIHGRGSTQKASLIKLLMMSSISAMKHGGSLNPNQERMLFPQAQEYDRVCTLLEEVEHLTGKFVVRERNIVRSRIDLFQEPVDLRCKAEDLVSEVWFGLKRTKLGPRLLKEEWDKLRASFAWLSTDPSETLRDGPFLSHVQFRNFIAHVDAKSRSVRLLGAPVKKSGGVTTISQVVRMNFFPGFSLEAEKSLDNQERLESISILKHVLFMVLNGPYTEEYKLEMIIEAFSTLVIPQPSEVIRKSRTMTLCLLSNYLSSRGGSILDQIERAQSGTLGGFSKPQKTFIRPGGGVGYKGKGVWTGVMEDTHVQILIDGDGTSNWLEEIRLSSDARLYDVIESIRRLCDDLGINNRVASAYRGHCMVRLSGFKIKPASRTDGCPVRIMERGFRIRELQNPDEVKMRVRGDILNLSVTIQEGRVMNILSYRPRDTDISESAAAYLWSNRDLFSFGKKEPSCSWICLKTLDNWAWSHASVLLANDRKTQGIDNRAMGNIFRDCLEGSLRKQGLMRSKLTEMVEKNVVPLTTQELVDILEEDIDFSDVIAVELSEGSLDIESIFDGAPILWSAEVEEFGEGVVAVSYSSKYYHLTLMDQAAITMCAIMGKEGCRGLLTEKRCMAAIREQVRPFLIFLQIPEDSISWVSDQFCDSRGLDEESTIMWG |
Interaction
Subunit
Homomultimer (By similarity).
Interacts with the glycoprotein N; this interaction allows efficient polymerase packaging into virus particles (By similarity).
Interacts with nucleoprotein N (By similarity).
Interacts with the glycoprotein N; this interaction allows efficient polymerase packaging into virus particles (By similarity).
Interacts with nucleoprotein N (By similarity).
Family & Domains
Features
Showing features for region, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 20-221 | Endonuclease | ||||
Sequence: EPGLYDQIYDRPGLPDLDVTVDATGVTVDIGAVPDSASQLGSSINAGLITIQLSEAYKINHDFTFSGLSKTTDRRLSEVFPITHDGSDGMTPDVIHTRLDGTIVVVEFTTTRSHNIGGLEAAYRTKIEKYRDPISRRVDIMENPRVFFGVIVVSSGGVLSNMPLTQDEAEELMYRFCIANEIYTKARSMDADIELQKSEEEL | ||||||
Domain | 969-1172 | RdRp catalytic | ||||
Sequence: SARSLGPGSININSSNDAKKWNQGHYTTKLALVLCWFMPAKFHRFIWAAISMFRRKKMMVDLRFLAHLSSKSESRSSDPFREAMTDAFHGNREVSWMDKGRTYIKTETGMMQGILHFTSSLLHSCVQSFYKSYFVSKLKEGYMGESISGVVDVIEGSDDSAIMISIRPKSDMDEVRSRFFVANLLHSVKFLNPLFGIYSSEKST | ||||||
Region | 1695-1810 | Cap-binding | ||||
Sequence: AQSGTLGGFSKPQKTFIRPGGGVGYKGKGVWTGVMEDTHVQILIDGDGTSNWLEEIRLSSDARLYDVIESIRRLCDDLGINNRVASAYRGHCMVRLSGFKIKPASRTDGCPVRIME |
Domain
The N-terminus contains the endonuclease activity (endoN) (PubMed:32313945, PubMed:32341479).
The central region contains the RdRp activity (PubMed:32313945, PubMed:32341479).
The C-terminus contains the cap-binding region (PubMed:32313945, PubMed:32341479).
The central region contains the RdRp activity (PubMed:32313945, PubMed:32341479).
The C-terminus contains the cap-binding region (PubMed:32313945, PubMed:32341479).
Sequence similarities
Belongs to the Bunyavirales RNA polymerase family.
Family and domain databases
Sequence
- Sequence statusComplete
- Length2,084
- Mass (Da)235,406
- Last updated2012-06-13 v1
- Checksum5605E4EFFED76AFA
Keywords
- Technical term