{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"P33453","uniProtkbId":"L_UUKS","entryAudit":{"firstPublicDate":"1994-02-01","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"1994-02-01","entryVersion":89,"sequenceVersion":1},"annotationScore":5.0,"organism":{"scientificName":"Uukuniemi virus (strain S23)","commonName":"UUKV","taxonId":487099,"lineage":["Viruses","Riboviria","Orthornavirae","Negarnaviricota","Polyploviricotina","Bunyaviricetes","Hareavirales","Phenuiviridae","Uukuvirus","Uukuvirus uukuniemiense","Uukuniemi phlebovirus"]},"organismHosts":[{"scientificName":"Homo sapiens","commonName":"Human","taxonId":9606},{"scientificName":"Ixodes ricinus","commonName":"Common tick","synonyms":["Acarus ricinus"],"taxonId":34613}],"proteinExistence":"3: Inferred from homology","proteinDescription":{"recommendedName":{"fullName":{"value":"RNA-directed RNA polymerase L"},"shortNames":[{"value":"Protein L"}],"ecNumbers":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"I0DF35"}],"value":"2.7.7.48"}]},"alternativeNames":[{"fullName":{"value":"Large structural protein"}},{"fullName":{"value":"Replicase"}},{"fullName":{"value":"Transcriptase"}}],"includes":[{"recommendedName":{"fullName":{"value":"cap-snatching endonuclease"},"ecNumbers":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"I0DF35"}],"value":"3.1.-.-"}]}}]},"genes":[{"geneName":{"value":"L"}}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"A5HC98"},{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"I0DF35"},{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P27316"}],"value":"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 (By similarity). 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 (By similarity). 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)"}],"commentType":"FUNCTION"},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"RNA(n) + a ribonucleoside 5'-triphosphate = RNA(n+1) + diphosphate","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:21248"},{"database":"Rhea","id":"RHEA-COMP:14527"},{"database":"Rhea","id":"RHEA-COMP:17342"},{"database":"ChEBI","id":"CHEBI:33019"},{"database":"ChEBI","id":"CHEBI:61557"},{"database":"ChEBI","id":"CHEBI:140395"}],"ecNumber":"2.7.7.48","evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU00539"}]}},{"commentType":"COFACTOR","cofactors":[{"name":"Mn(2+)","evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P27316"}],"cofactorCrossReference":{"database":"ChEBI","id":"CHEBI:29035"}}],"note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P27316"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31948728"}],"value":"For endonuclease activity. Binds 2 Mn(2+) ions in the active site (By similarity). The divalent metal ions are crucial for catalytic activity (PubMed:31948728)."}]}},{"commentType":"COFACTOR","cofactors":[{"name":"Mg(2+)","evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P27316"}],"cofactorCrossReference":{"database":"ChEBI","id":"CHEBI:18420"}},{"name":"Mn(2+)","evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P27316"}],"cofactorCrossReference":{"database":"ChEBI","id":"CHEBI:29035"}}],"note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P27316"}],"value":"For polymerase activity. Initiation activity is stronger in the presence of Mn(2+) than in the presence of Mg(2+)."}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P27316"}],"value":"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)"}],"commentType":"SUBUNIT"},{"commentType":"SUBCELLULAR LOCATION","subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"I0DF35"}],"value":"Host Golgi apparatus","id":"SL-0395"}},{"location":{"value":"Host endoplasmic reticulum","id":"SL-0388"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"I0DF35"}],"value":"Host endoplasmic reticulum-Golgi intermediate compartment","id":"SL-0391"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P20470"}],"value":"Virion","id":"SL-0274"}}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"I0DF35"}],"value":"The N-terminus contains the endonuclease activity (endoN) (By similarity). The central region contains the RdRp activity (By similarity). The C-terminus contains the cap-binding region (By similarity)"}],"commentType":"DOMAIN"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"31948728"}],"value":"Classified as His(+) endonuclease since it has a histidine upstream of the active site that coordinates the first cation"}],"commentType":"MISCELLANEOUS"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Belongs to the Bunyavirales RNA polymerase family"}],"commentType":"SIMILARITY"}],"features":[{"type":"Chain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":2103,"modifier":"EXACT"}},"description":"RNA-directed RNA polymerase L","featureId":"PRO_0000222028"},{"type":"Domain","location":{"start":{"value":978,"modifier":"EXACT"},"end":{"value":1175,"modifier":"EXACT"}},"description":"RdRp catalytic","evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU00539"}]},{"type":"Region","location":{"start":{"value":18,"modifier":"EXACT"},"end":{"value":216,"modifier":"EXACT"}},"description":"Endonuclease","evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"A5HC98"}]},{"type":"Region","location":{"start":{"value":1707,"modifier":"EXACT"},"end":{"value":1825,"modifier":"EXACT"}},"description":"Cap-binding","evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"A5HC98"}]},{"type":"Active site","location":{"start":{"value":144,"modifier":"EXACT"},"end":{"value":144,"modifier":"EXACT"}},"description":"For endonuclease activity","evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"I0DF35"}]},{"type":"Binding site","location":{"start":{"value":79,"modifier":"EXACT"},"end":{"value":79,"modifier":"EXACT"}},"description":"","featureCrossReferences":[{"database":"ChEBI","id":"CHEBI:29035"}],"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"A5HC98"}],"ligand":{"name":"Mn(2+)","id":"ChEBI:CHEBI:29035","label":"1"}},{"type":"Binding site","location":{"start":{"value":111,"modifier":"EXACT"},"end":{"value":111,"modifier":"EXACT"}},"description":"","featureCrossReferences":[{"database":"ChEBI","id":"CHEBI:29035"}],"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"A5HC98"}],"ligand":{"name":"Mn(2+)","id":"ChEBI:CHEBI:29035","label":"1"}},{"type":"Binding site","location":{"start":{"value":111,"modifier":"EXACT"},"end":{"value":111,"modifier":"EXACT"}},"description":"","featureCrossReferences":[{"database":"ChEBI","id":"CHEBI:29035"}],"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"A5HC98"}],"ligand":{"name":"Mn(2+)","id":"ChEBI:CHEBI:29035","label":"2"}},{"type":"Binding site","location":{"start":{"value":125,"modifier":"EXACT"},"end":{"value":125,"modifier":"EXACT"}},"description":"","featureCrossReferences":[{"database":"ChEBI","id":"CHEBI:29035"}],"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"A5HC98"}],"ligand":{"name":"Mn(2+)","id":"ChEBI:CHEBI:29035","label":"1"}},{"type":"Binding site","location":{"start":{"value":1139,"modifier":"EXACT"},"end":{"value":1139,"modifier":"EXACT"}},"description":"","featureCrossReferences":[{"database":"ChEBI","id":"CHEBI:18420"}],"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"I0DF35"}],"ligand":{"name":"Mg(2+)","id":"ChEBI:CHEBI:18420","note":"catalytic; 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