RDRP_I34A1
ID RDRP_I34A1 Reviewed; 757 AA.
AC P03431; A4GXH1; Q20N30; Q8JUU7;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 02-OCT-2007, sequence version 2.
DT 03-AUG-2022, entry version 128.
DE RecName: Full=RNA-directed RNA polymerase catalytic subunit {ECO:0000255|HAMAP-Rule:MF_04065};
DE EC=2.7.7.48 {ECO:0000255|HAMAP-Rule:MF_04065};
DE AltName: Full=Polymerase basic protein 1 {ECO:0000255|HAMAP-Rule:MF_04065};
DE Short=PB1 {ECO:0000255|HAMAP-Rule:MF_04065};
DE AltName: Full=RNA-directed RNA polymerase subunit P1 {ECO:0000255|HAMAP-Rule:MF_04065};
GN Name=PB1 {ECO:0000255|HAMAP-Rule:MF_04065};
OS Influenza A virus (strain A/Puerto Rico/8/1934 H1N1).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC Insthoviricetes; Articulavirales; Orthomyxoviridae; Alphainfluenzavirus.
OX NCBI_TaxID=211044;
OH NCBI_TaxID=8782; Aves.
OH NCBI_TaxID=9606; Homo sapiens (Human).
OH NCBI_TaxID=9823; Sus scrofa (Pig).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=6281731; DOI=10.1093/nar/10.6.2135;
RA Winter G., Fields S.;
RT "Nucleotide sequence of human influenza A/PR/8/34 segment 2.";
RL Nucleic Acids Res. 10:2135-2143(1982).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=11779399; DOI=10.1098/rstb.2001.0979;
RA Schickli J.H., Flandorfer A., Nakaya T., Martinez-Sobrido L.,
RA Garcia-Sastre A., Palese P.;
RT "Plasmid-only rescue of influenza A virus vaccine candidates.";
RL Philos. Trans. R. Soc. Lond., B, Biol. Sci. 356:1965-1973(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA], AND REVERSE GENETICS.
RX PubMed=15163504; DOI=10.1016/j.virusres.2004.02.028;
RA de Wit E., Spronken M.I.J., Bestebroer T.M., Rimmelzwaan G.F.,
RA Osterhaus A.D.M.E., Fouchier R.A.M.;
RT "Efficient generation and growth of influenza virus A/PR/8/34 from eight
RT cDNA fragments.";
RL Virus Res. 103:155-161(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RA Ghedin E., Spiro D., Miller N., Zaborsky J., Feldblyum T., Subbu V.,
RA Shumway M., Sparenborg J., Groveman L., Halpin R., Sitz J., Koo H.,
RA Salzberg S.L., Webster R.G., Hoffmann E., Krauss S., Naeve C., Bao Y.,
RA Bolotov P., Dernovoy D., Kiryutin B., Lipman D.J., Tatusova T.;
RT "The NIAID influenza genome sequencing project.";
RL Submitted (MAR-2006) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP FUNCTION.
RX PubMed=8645093; DOI=10.1007/bf01718315;
RA Kobayashi M., Toyoda T., Ishihama A.;
RT "Influenza virus PB1 protein is the minimal and essential subunit of RNA
RT polymerase.";
RL Arch. Virol. 141:525-539(1996).
RN [6]
RP PHOSPHORYLATION BY HOST PRKCA.
RC STRAIN=A/WSN/33;
RX PubMed=19264651; DOI=10.1099/vir.0.009050-0;
RA Mahmoudian S., Auerochs S., Grone M., Marschall M.;
RT "Influenza A virus proteins PB1 and NS1 are subject to functionally
RT important phosphorylation by protein kinase C.";
RL J. Gen. Virol. 90:1392-1397(2009).
RN [7]
RP SUBCELLULAR LOCATION.
RC STRAIN=A/Victoria/3/75;
RX PubMed=19906916; DOI=10.1128/jvi.01533-09;
RA Huet S., Avilov S.V., Ferbitz L., Daigle N., Cusack S., Ellenberg J.;
RT "Nuclear import and assembly of influenza A virus RNA polymerase studied in
RT live cells by fluorescence cross-correlation spectroscopy.";
RL J. Virol. 84:1254-1264(2010).
RN [8]
RP REVIEW ON FUNCTION.
RX PubMed=23600869; DOI=10.4149/av_2013_02_113;
RA Fodor E.;
RT "The RNA polymerase of influenza a virus: mechanisms of viral transcription
RT and replication.";
RL Acta Virol. 57:113-122(2013).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 1-81, AND INTERACTION WITH PA.
RX PubMed=18660801; DOI=10.1038/nature07225;
RA Obayashi E., Yoshida H., Kawai F., Shibayama N., Kawaguchi A., Nagata K.,
RA Tame J.R., Park S.Y.;
RT "The structural basis for an essential subunit interaction in influenza
RT virus RNA polymerase.";
RL Nature 454:1127-1131(2008).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 678-757, AND INTERACTION WITH
RP PB2.
RX PubMed=19461581; DOI=10.1038/emboj.2009.138;
RA Sugiyama K., Obayashi E., Kawaguchi A., Suzuki Y., Tame J.R., Nagata K.,
RA Park S.Y.;
RT "Structural insight into the essential PB1-PB2 subunit contact of the
RT influenza virus RNA polymerase.";
RL EMBO J. 28:1803-1811(2009).
CC -!- FUNCTION: RNA-dependent RNA polymerase which is responsible for
CC replication and transcription of virus RNA segments. The transcription
CC of viral mRNAs occurs by a unique mechanism called cap-snatching. 5'
CC methylated caps of cellular mRNAs are cleaved after 10-13 nucleotides
CC by PA. In turn, these short capped RNAs are used as primers by PB1 for
CC transcription of viral mRNAs. During virus replication, PB1 initiates
CC RNA synthesis and copy vRNA into complementary RNA (cRNA) which in turn
CC serves as a template for the production of more vRNAs.
CC {ECO:0000255|HAMAP-Rule:MF_04065, ECO:0000269|PubMed:8645093,
CC ECO:0000305|PubMed:23600869}.
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|HAMAP-Rule:MF_04065};
CC -!- SUBUNIT: Influenza RNA polymerase is composed of three subunits: PB1,
CC PB2 and PA. Interacts (via N-terminus) with PA (via C-terminus).
CC Interacts (via C-terminus) with PB2 (via N-terminus); this interaction
CC is essential for transcription initiation. {ECO:0000255|HAMAP-
CC Rule:MF_04065, ECO:0000269|PubMed:18660801,
CC ECO:0000269|PubMed:19461581}.
CC -!- INTERACTION:
CC P03431; P03466: NP; NbExp=5; IntAct=EBI-2547514, EBI-2547640;
CC P03431; P03433: PA; NbExp=6; IntAct=EBI-2547514, EBI-2547616;
CC P03431; P03428: PB2; NbExp=3; IntAct=EBI-2547514, EBI-2547475;
CC P03431; Q14318: FKBP8; Xeno; NbExp=5; IntAct=EBI-2547514, EBI-724839;
CC P03431; Q99959: PKP2; Xeno; NbExp=8; IntAct=EBI-2547514, EBI-702235;
CC -!- SUBCELLULAR LOCATION: Host nucleus {ECO:0000255|HAMAP-Rule:MF_04065,
CC ECO:0000269|PubMed:19906916}. Host cytoplasm {ECO:0000255|HAMAP-
CC Rule:MF_04065, ECO:0000269|PubMed:19906916}.
CC -!- PTM: Phosphorylated by host PRKCA. {ECO:0000255|HAMAP-Rule:MF_04065,
CC ECO:0000269|PubMed:19264651}.
CC -!- SIMILARITY: Belongs to the influenza viruses polymerase PB1 family.
CC {ECO:0000255|HAMAP-Rule:MF_04065}.
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DR EMBL; J02151; AAA43581.1; -; Genomic_RNA.
DR EMBL; AF389116; AAM75156.1; -; Genomic_RNA.
DR EMBL; CY009450; ABD77683.1; -; Genomic_RNA.
DR EMBL; EF467819; ABO21706.1; -; Genomic_RNA.
DR PIR; A93418; P1IV34.
DR RefSeq; NP_040985.1; NC_002021.1.
DR PDB; 2ZNL; X-ray; 2.30 A; B=1-81.
DR PDB; 2ZTT; X-ray; 2.10 A; A/C=679-757.
DR PDB; 3A1G; X-ray; 1.70 A; A/C=678-757.
DR PDBsum; 2ZNL; -.
DR PDBsum; 2ZTT; -.
DR PDBsum; 3A1G; -.
DR SMR; P03431; -.
DR DIP; DIP-56974N; -.
DR IntAct; P03431; 141.
DR MINT; P03431; -.
DR BindingDB; P03431; -.
DR ChEMBL; CHEMBL4523676; -.
DR GeneID; 956534; -.
DR KEGG; vg:956534; -.
DR Reactome; R-HSA-168255; Influenza Infection.
DR Reactome; R-HSA-168271; Transport of Ribonucleoproteins into the Host Nucleus.
DR Reactome; R-HSA-168275; Entry of Influenza Virion into Host Cell via Endocytosis.
DR Reactome; R-HSA-168288; Fusion of the Influenza Virion to the Host Cell Endosome.
DR Reactome; R-HSA-168298; Release.
DR Reactome; R-HSA-168302; Budding.
DR Reactome; R-HSA-168303; Packaging of Eight RNA Segments.
DR Reactome; R-HSA-168325; Viral Messenger RNA Synthesis.
DR Reactome; R-HSA-168330; Viral RNP Complexes in the Host Cell Nucleus.
DR Reactome; R-HSA-168333; NEP/NS2 Interacts with the Cellular Export Machinery.
DR Reactome; R-HSA-168336; Uncoating of the Influenza Virion.
DR Reactome; R-HSA-192814; vRNA Synthesis.
DR Reactome; R-HSA-192823; Viral mRNA Translation.
DR Reactome; R-HSA-192869; cRNA Synthesis.
DR Reactome; R-HSA-192905; vRNP Assembly.
DR EvolutionaryTrace; P03431; -.
DR PRO; PR:P03431; -.
DR Proteomes; UP000009255; Genome.
DR Proteomes; UP000116373; Genome.
DR Proteomes; UP000170967; Genome.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0030430; C:host cell cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-UniRule.
DR GO; GO:0003723; F:RNA binding; IEA:InterPro.
DR GO; GO:0003968; F:RNA-directed 5'-3' RNA polymerase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0039523; P:suppression by virus of host mRNA transcription via inhibition of RNA polymerase II activity; IEA:UniProtKB-UniRule.
DR GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-UniRule.
DR GO; GO:0039694; P:viral RNA genome replication; IEA:UniProtKB-UniRule.
DR GO; GO:0019083; P:viral transcription; IEA:UniProtKB-KW.
DR HAMAP; MF_04065; INFV_RDRP; 1.
DR InterPro; IPR007099; RNA-dir_pol_NSvirus.
DR InterPro; IPR001407; RNA_pol_PB1_influenza.
DR Pfam; PF00602; Flu_PB1; 1.
DR PIRSF; PIRSF000827; RdRPol_OMV; 1.
DR PROSITE; PS50525; RDRP_SSRNA_NEG_SEG; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Eukaryotic host gene expression shutoff by virus;
KW Eukaryotic host transcription shutoff by virus; Host cytoplasm;
KW Host gene expression shutoff by virus; Host nucleus;
KW Host-virus interaction; Inhibition of host RNA polymerase II by virus;
KW Nucleotide-binding; Nucleotidyltransferase; Phosphoprotein;
KW Reference proteome; RNA-directed RNA polymerase; Transferase;
KW Viral RNA replication; Viral transcription.
FT CHAIN 1..757
FT /note="RNA-directed RNA polymerase catalytic subunit"
FT /id="PRO_0000078763"
FT DOMAIN 286..483
FT /note="RdRp catalytic"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04065"
FT REGION 53..82
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 249..256
FT /note="Promoter-binding site"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04065"
FT MOTIF 187..195
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04065"
FT MOTIF 203..216
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04065"
FT CONFLICT 53
FT /note="G -> A (in Ref. 1; AAA43581)"
FT /evidence="ECO:0000305"
FT CONFLICT 175
FT /note="K -> N (in Ref. 4; ABO21706 and 3; ABD77683)"
FT /evidence="ECO:0000305"
FT CONFLICT 205
FT /note="I -> M (in Ref. 4; ABO21706 and 3; ABD77683)"
FT /evidence="ECO:0000305"
FT CONFLICT 208
FT /note="K -> R (in Ref. 1; AAA43581)"
FT /evidence="ECO:0000305"
FT CONFLICT 300
FT /note="F -> L (in Ref. 1; AAA43581)"
FT /evidence="ECO:0000305"
FT CONFLICT 394
FT /note="P -> S (in Ref. 4; ABO21706 and 3; ABD77683)"
FT /evidence="ECO:0000305"
FT CONFLICT 473
FT /note="L -> H (in Ref. 1; AAA43581)"
FT /evidence="ECO:0000305"
FT CONFLICT 517
FT /note="I -> S (in Ref. 1; AAA43581)"
FT /evidence="ECO:0000305"
FT HELIX 5..10
FT /evidence="ECO:0007829|PDB:2ZNL"
FT HELIX 687..699
FT /evidence="ECO:0007829|PDB:3A1G"
FT HELIX 714..731
FT /evidence="ECO:0007829|PDB:3A1G"
FT HELIX 737..755
FT /evidence="ECO:0007829|PDB:3A1G"
SQ SEQUENCE 757 AA; 86576 MW; FB23E4976E06C18F CRC64;
MDVNPTLLFL KVPAQNAIST TFPYTGDPPY SHGTGTGYTM DTVNRTHQYS EKGRWTTNTE
TGAPQLNPID GPLPEDNEPS GYAQTDCVLE AMAFLEESHP GIFENSCIET MEVVQQTRVD
KLTQGRQTYD WTLNRNQPAA TALANTIEVF RSNGLTANES GRLIDFLKDV MESMKKEEMG
ITTHFQRKRR VRDNMTKKMI TQRTIGKKKQ RLNKRSYLIR ALTLNTMTKD AERGKLKRRA
IATPGMQIRG FVYFVETLAR SICEKLEQSG LPVGGNEKKA KLANVVRKMM TNSQDTELSF
TITGDNTKWN ENQNPRMFLA MITYMTRNQP EWFRNVLSIA PIMFSNKMAR LGKGYMFESK
SMKLRTQIPA EMLASIDLKY FNDSTRKKIE KIRPLLIEGT ASLSPGMMMG MFNMLSTVLG
VSILNLGQKR YTKTTYWWDG LQSSDDFALI VNAPNHEGIQ AGVDRFYRTC KLLGINMSKK
KSYINRTGTF EFTSFFYRYG FVANFSMELP SFGVSGINES ADMSIGVTVI KNNMINNDLG
PATAQMALQL FIKDYRYTYR CHRGDTQIQT RRSFEIKKLW EQTRSKAGLL VSDGGPNLYN
IRNLHIPEVC LKWELMDEDY QGRLCNPLNP FVSHKEIESM NNAVMMPAHG PAKNMEYDAV
ATTHSWIPKR NRSILNTSQR GVLEDEQMYQ RCCNLFEKFF PSSSYRRPVG ISSMVEAMVS
RARIDARIDF ESGRIKKEEF TEIMKICSTI EELRRQK
