PB2_I34A1
ID PB2_I34A1 Reviewed; 759 AA.
AC P03428; A4GXH0; Q20N28; Q8JUU8;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 06-MAR-2007, sequence version 2.
DT 03-AUG-2022, entry version 138.
DE RecName: Full=Polymerase basic protein 2 {ECO:0000255|HAMAP-Rule:MF_04062};
DE AltName: Full=RNA-directed RNA polymerase subunit P3 {ECO:0000255|HAMAP-Rule:MF_04062};
GN Name=PB2 {ECO:0000255|HAMAP-Rule:MF_04062};
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=7060132; DOI=10.1016/0092-8674(82)90348-8;
RA Fields S., Winter G.;
RT "Nucleotide sequences of influenza virus segments 1 and 3 reveal mosaic
RT structure of a small viral RNA segment.";
RL Cell 28:303-313(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 SUBCELLULAR LOCATION.
RC STRAIN=A/WSN/33;
RX PubMed=15308710; DOI=10.1128/jvi.78.17.9144-9153.2004;
RA Fodor E., Smith M.;
RT "The PA subunit is required for efficient nuclear accumulation of the PB1
RT subunit of the influenza A virus RNA polymerase complex.";
RL J. Virol. 78:9144-9153(2004).
RN [6]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RC STRAIN=A/WSN/33;
RX PubMed=16242167; DOI=10.1016/j.virol.2005.08.041;
RA Carr S.M., Carnero E., Garcia-Sastre A., Brownlee G.G., Fodor E.;
RT "Characterization of a mitochondrial-targeting signal in the PB2 protein of
RT influenza viruses.";
RL Virology 344:492-508(2006).
RN [7]
RP FUNCTION.
RX PubMed=17030872; DOI=10.1099/vir.0.82199-0;
RA Deng T., Sharps J.L., Brownlee G.G.;
RT "Role of the influenza virus heterotrimeric RNA polymerase complex in the
RT initiation of replication.";
RL J. Gen. Virol. 87:3373-3377(2006).
RN [8]
RP FUNCTION, INTERACTION WITH HOST MAVS, AND SUBCELLULAR LOCATION.
RX PubMed=20538852; DOI=10.1128/jvi.00879-10;
RA Graef K.M., Vreede F.T., Lau Y.F., McCall A.W., Carr S.M., Subbarao K.,
RA Fodor E.;
RT "The PB2 subunit of the influenza virus RNA polymerase affects virulence by
RT interacting with the mitochondrial antiviral signaling protein and
RT inhibiting expression of beta interferon.";
RL J. Virol. 84:8433-8445(2010).
RN [9]
RP FUNCTION, AND INTERACTION WITH NUCLEOPROTEIN NP.
RX PubMed=22570712; DOI=10.1371/journal.pone.0036415;
RA Ng A.K., Chan W.H., Choi S.T., Lam M.K., Lau K.F., Chan P.K., Au S.W.,
RA Fodor E., Shaw P.C.;
RT "Influenza polymerase activity correlates with the strength of interaction
RT between nucleoprotein and PB2 through the host-specific residue K/E627.";
RL PLoS ONE 7:E36415-E36415(2012).
RN [10]
RP FUNCTION, AND INTERACTION WITH HOST MAVS.
RC STRAIN=A/WSN/33;
RX PubMed=23246644; DOI=10.1016/j.virusres.2012.12.003;
RA Patel D., Schultz L.W., Umland T.C.;
RT "Influenza A polymerase subunit PB2 possesses overlapping binding sites for
RT polymerase subunit PB1 and human MAVS proteins.";
RL Virus Res. 172:75-80(2013).
RN [11]
RP FUNCTION, AND INTERACTION WITH NUCLEOPROTEIN NP.
RC STRAIN=A/WSN/193;
RX PubMed=25043584; DOI=10.1016/j.virol.2014.06.033;
RA Gui X., Li R., Zhang X., Shen C., Yu H., Guo X., Kang Y., Chen J., Chen H.,
RA Chen Y., Xia N.;
RT "An important amino acid in nucleoprotein contributes to influenza A virus
RT replication by interacting with polymerase PB2.";
RL Virology 464:11-20(2014).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 535-759.
RX PubMed=19144639; DOI=10.1074/jbc.c800224200;
RA Kuzuhara T., Kise D., Yoshida H., Horita T., Murazaki Y., Nishimura A.,
RA Echigo N., Utsunomiya H., Tsuge H.;
RT "Structural basis of the influenza A virus RNA polymerase PB2 RNA-binding
RT domain containing the pathogenicity-determinant lysine 627 residue.";
RL J. Biol. Chem. 284:6855-6860(2009).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (1.32 ANGSTROMS) OF 318-483.
RX PubMed=23436652; DOI=10.1074/jbc.m112.392878;
RA Liu Y., Qin K., Meng G., Zhang J., Zhou J., Zhao G., Luo M., Zheng X.;
RT "Structural and functional characterization of K339T substitution
RT identified in the PB2 subunit cap-binding pocket of influenza A virus.";
RL J. Biol. Chem. 288:11013-11023(2013).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (1.93 ANGSTROMS) OF 318-484.
RX PubMed=24312396; DOI=10.1371/journal.pone.0082020;
RA Tsurumura T., Qiu H., Yoshida T., Tsumori Y., Hatakeyama D., Kuzuhara T.,
RA Tsuge H.;
RT "Conformational polymorphism of m7GTP in crystal structure of the PB2
RT middle domain from human influenza A virus.";
RL PLoS ONE 8:E82020-E82020(2013).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (2.42 ANGSTROMS) OF 318-484.
RX PubMed=24419622; DOI=10.1107/s2053230x13032603;
RA Tsurumura T., Qiu H., Yoshida T., Tsumori Y., Tsuge H.;
RT "Crystallization and preliminary X-ray diffraction studies of a surface
RT mutant of the middle domain of PB2 from human influenza A (H1N1) virus.";
RL Acta Crystallogr. F 70:72-75(2014).
CC -!- FUNCTION: Plays an essential role in transcription initiation and cap-
CC stealing mechanism, in which cellular capped pre-mRNAs are used to
CC generate primers for viral transcription. Recognizes and binds the 7-
CC methylguanosine-containing cap of the target pre-RNA which is
CC subsequently cleaved after 10-13 nucleotides by the viral protein PA.
CC Plays a role in the initiation of the viral genome replication and
CC modulates the activity of the ribonucleoprotein (RNP) complex. In
CC addition, participates in the inhibition of type I interferon induction
CC through interaction with and inhibition of the host mitochondrial
CC antiviral signaling protein MAVS. {ECO:0000255|HAMAP-Rule:MF_04062,
CC ECO:0000269|PubMed:16242167, ECO:0000269|PubMed:17030872,
CC ECO:0000269|PubMed:20538852, ECO:0000269|PubMed:22570712,
CC ECO:0000269|PubMed:23246644, ECO:0000269|PubMed:25043584}.
CC -!- SUBUNIT: Influenza RNA polymerase is composed of three subunits: PB1,
CC PB2 and PA. Interacts (via N-terminus) with PB1 (via C-terminus).
CC Interacts with nucleoprotein NP (via N-terminus). Interacts (via N-
CC terminus) with host MAVS (via N-terminus); this interaction inhibits
CC host innate immune response. {ECO:0000255|HAMAP-Rule:MF_04062,
CC ECO:0000269|PubMed:20538852, ECO:0000269|PubMed:22570712,
CC ECO:0000269|PubMed:23246644, ECO:0000269|PubMed:25043584}.
CC -!- INTERACTION:
CC P03428; P03466: NP; NbExp=3; IntAct=EBI-2547475, EBI-2547640;
CC P03428; P03431: PB1; NbExp=3; IntAct=EBI-2547475, EBI-2547514;
CC -!- SUBCELLULAR LOCATION: Virion {ECO:0000255|HAMAP-Rule:MF_04062}. Host
CC nucleus {ECO:0000255|HAMAP-Rule:MF_04062, ECO:0000269|PubMed:15308710,
CC ECO:0000269|PubMed:20538852}. Host mitochondrion {ECO:0000255|HAMAP-
CC Rule:MF_04062, ECO:0000269|PubMed:15308710,
CC ECO:0000269|PubMed:16242167, ECO:0000269|PubMed:20538852}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Polymerase basic protein 2;
CC IsoId=P03428-1; Sequence=Displayed;
CC Name=PB2-S1 {ECO:0000250|UniProtKB:P03427};
CC IsoId=P0DOG6-1; Sequence=External;
CC -!- SIMILARITY: Belongs to the influenza viruses PB2 family.
CC {ECO:0000255|HAMAP-Rule:MF_04062, ECO:0000305}.
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DR EMBL; V00603; CAA23855.1; -; Unassigned_RNA.
DR EMBL; AF389115; AAM75155.1; -; Genomic_RNA.
DR EMBL; EF467818; ABO21705.1; -; Genomic_RNA.
DR EMBL; CY009451; ABD77685.1; -; Genomic_RNA.
DR RefSeq; NP_040987.1; NC_002023.1.
DR PDB; 2ZTT; X-ray; 2.10 A; B/D=1-37.
DR PDB; 3A1G; X-ray; 1.70 A; B/D=1-37.
DR PDB; 3CW4; X-ray; 2.70 A; A=535-759.
DR PDB; 3WI0; X-ray; 2.00 A; A=318-484.
DR PDB; 3WI1; X-ray; 1.93 A; A=318-484.
DR PDB; 4ENF; X-ray; 1.32 A; A=318-483.
DR PDB; 4J2R; X-ray; 2.42 A; A/B=318-484.
DR PDB; 4U6O; X-ray; 1.30 A; A/B=318-483.
DR PDB; 7JYW; X-ray; 2.90 A; C=549-557.
DR PDB; 7JYX; X-ray; 2.95 A; C/F=549-559.
DR PDBsum; 2ZTT; -.
DR PDBsum; 3A1G; -.
DR PDBsum; 3CW4; -.
DR PDBsum; 3WI0; -.
DR PDBsum; 3WI1; -.
DR PDBsum; 4ENF; -.
DR PDBsum; 4J2R; -.
DR PDBsum; 4U6O; -.
DR PDBsum; 7JYW; -.
DR PDBsum; 7JYX; -.
DR SMR; P03428; -.
DR DIP; DIP-43997N; -.
DR IntAct; P03428; 172.
DR MINT; P03428; -.
DR BindingDB; P03428; -.
DR ChEMBL; CHEMBL3317339; -.
DR GeneID; 956536; -.
DR KEGG; vg:956536; -.
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; P03428; -.
DR PRO; PR:P03428; -.
DR Proteomes; UP000009255; Genome.
DR Proteomes; UP000116373; Genome.
DR Proteomes; UP000170967; Genome.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0033650; C:host cell mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0044423; C:virion component; IEA:UniProtKB-UniRule.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-UniRule.
DR GO; GO:0003968; F:RNA-directed 5'-3' RNA polymerase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0006370; P:7-methylguanosine mRNA capping; IEA:UniProtKB-UniRule.
DR GO; GO:0075526; P:cap snatching; 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:0039545; P:suppression by virus of host viral-induced cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS 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:InterPro.
DR Gene3D; 3.30.30.90; -; 1.
DR HAMAP; MF_04062; INV_PB2; 1.
DR InterPro; IPR001591; INV_PB2.
DR InterPro; IPR037258; PDB2_C.
DR Pfam; PF00604; Flu_PB2; 1.
DR SUPFAM; SSF160453; SSF160453; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cap snatching;
KW Eukaryotic host gene expression shutoff by virus;
KW Eukaryotic host transcription shutoff by virus;
KW Host gene expression shutoff by virus; Host mitochondrion; Host nucleus;
KW Host-virus interaction; Inhibition of host innate immune response by virus;
KW Inhibition of host MAVS by virus; Inhibition of host RLR pathway by virus;
KW Inhibition of host RNA polymerase II by virus; mRNA capping;
KW mRNA processing; Reference proteome; Viral immunoevasion;
KW Viral transcription; Virion.
FT CHAIN 1..759
FT /note="Polymerase basic protein 2"
FT /id="PRO_0000078834"
FT MOTIF 736..739
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04062"
FT SITE 627
FT /note="Mammalian adaptation"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04062"
FT CONFLICT 105
FT /note="I -> M (in Ref. 1; ABD77685)"
FT /evidence="ECO:0000305"
FT CONFLICT 251
FT /note="R -> K (in Ref. 1; ABD77685)"
FT /evidence="ECO:0000305"
FT CONFLICT 299
FT /note="R -> K (in Ref. 1; ABD77685)"
FT /evidence="ECO:0000305"
FT CONFLICT 309
FT /note="D -> G (in Ref. 1; ABD77685)"
FT /evidence="ECO:0000305"
FT CONFLICT 504
FT /note="I -> V (in Ref. 1; ABD77685)"
FT /evidence="ECO:0000305"
FT CONFLICT 701
FT /note="D -> N (in Ref. 2; ABO21705)"
FT /evidence="ECO:0000305"
FT CONFLICT 702
FT /note="K -> R (in Ref. 1; ABD77685)"
FT /evidence="ECO:0000305"
FT HELIX 1..10
FT /evidence="ECO:0007829|PDB:3A1G"
FT HELIX 14..22
FT /evidence="ECO:0007829|PDB:3A1G"
FT HELIX 27..33
FT /evidence="ECO:0007829|PDB:3A1G"
FT STRAND 323..325
FT /evidence="ECO:0007829|PDB:4U6O"
FT STRAND 328..335
FT /evidence="ECO:0007829|PDB:4U6O"
FT STRAND 338..345
FT /evidence="ECO:0007829|PDB:4U6O"
FT STRAND 351..359
FT /evidence="ECO:0007829|PDB:4U6O"
FT STRAND 361..366
FT /evidence="ECO:0007829|PDB:4U6O"
FT STRAND 368..377
FT /evidence="ECO:0007829|PDB:4U6O"
FT STRAND 380..390
FT /evidence="ECO:0007829|PDB:4U6O"
FT HELIX 391..405
FT /evidence="ECO:0007829|PDB:4U6O"
FT HELIX 408..411
FT /evidence="ECO:0007829|PDB:4U6O"
FT TURN 418..420
FT /evidence="ECO:0007829|PDB:4U6O"
FT HELIX 430..440
FT /evidence="ECO:0007829|PDB:4U6O"
FT HELIX 443..449
FT /evidence="ECO:0007829|PDB:4U6O"
FT STRAND 451..453
FT /evidence="ECO:0007829|PDB:4U6O"
FT HELIX 456..458
FT /evidence="ECO:0007829|PDB:4J2R"
FT STRAND 461..463
FT /evidence="ECO:0007829|PDB:4U6O"
FT STRAND 469..475
FT /evidence="ECO:0007829|PDB:4U6O"
FT STRAND 478..480
FT /evidence="ECO:0007829|PDB:4U6O"
FT HELIX 536..540
FT /evidence="ECO:0007829|PDB:3CW4"
FT HELIX 541..555
FT /evidence="ECO:0007829|PDB:3CW4"
FT HELIX 557..566
FT /evidence="ECO:0007829|PDB:3CW4"
FT HELIX 568..572
FT /evidence="ECO:0007829|PDB:3CW4"
FT HELIX 575..577
FT /evidence="ECO:0007829|PDB:3CW4"
FT HELIX 578..582
FT /evidence="ECO:0007829|PDB:3CW4"
FT TURN 586..588
FT /evidence="ECO:0007829|PDB:3CW4"
FT HELIX 589..605
FT /evidence="ECO:0007829|PDB:3CW4"
FT HELIX 612..618
FT /evidence="ECO:0007829|PDB:3CW4"
FT HELIX 619..622
FT /evidence="ECO:0007829|PDB:3CW4"
FT STRAND 634..638
FT /evidence="ECO:0007829|PDB:3CW4"
FT STRAND 641..643
FT /evidence="ECO:0007829|PDB:3CW4"
FT STRAND 645..651
FT /evidence="ECO:0007829|PDB:3CW4"
FT STRAND 656..658
FT /evidence="ECO:0007829|PDB:3CW4"
FT STRAND 660..662
FT /evidence="ECO:0007829|PDB:3CW4"
FT STRAND 664..674
FT /evidence="ECO:0007829|PDB:3CW4"
FT STRAND 687..691
FT /evidence="ECO:0007829|PDB:3CW4"
FT STRAND 694..699
FT /evidence="ECO:0007829|PDB:3CW4"
FT HELIX 702..704
FT /evidence="ECO:0007829|PDB:3CW4"
FT HELIX 710..714
FT /evidence="ECO:0007829|PDB:3CW4"
FT STRAND 721..727
FT /evidence="ECO:0007829|PDB:3CW4"
FT STRAND 730..736
FT /evidence="ECO:0007829|PDB:3CW4"
SQ SEQUENCE 759 AA; 86095 MW; 10D2D1608AE536D2 CRC64;
MERIKELRNL MSQSRTREIL TKTTVDHMAI IKKYTSGRQE KNPALRMKWM MAMKYPITAD
KRITEMIPER NEQGQTLWSK MNDAGSDRVM VSPLAVTWWN RNGPITNTVH YPKIYKTYFE
RVERLKHGTF GPVHFRNQVK IRRRVDINPG HADLSAKEAQ DVIMEVVFPN EVGARILTSE
SQLTITKEKK EELQDCKISP LMVAYMLERE LVRKTRFLPV AGGTSSVYIE VLHLTQGTCW
EQMYTPGGEV RNDDVDQSLI IAARNIVRRA AVSADPLASL LEMCHSTQIG GIRMVDILRQ
NPTEEQAVDI CKAAMGLRIS SSFSFGGFTF KRTSGSSVKR EEEVLTGNLQ TLKIRVHEGY
EEFTMVGRRA TAILRKATRR LIQLIVSGRD EQSIAEAIIV AMVFSQEDCM IKAVRGDLNF
VNRANQRLNP MHQLLRHFQK DAKVLFQNWG VEPIDNVMGM IGILPDMTPS IEMSMRGVRI
SKMGVDEYSS TERVVVSIDR FLRIRDQRGN VLLSPEEVSE TQGTEKLTIT YSSSMMWEIN
GPESVLVNTY QWIIRNWETV KIQWSQNPTM LYNKMEFEPF QSLVPKAIRG QYSGFVRTLF
QQMRDVLGTF DTAQIIKLLP FAAAPPKQSR MQFSSFTVNV RGSGMRILVR GNSPVFNYNK
ATKRLTVLGK DAGTLTEDPD EGTAGVESAV LRGFLILGKE DKRYGPALSI NELSNLAKGE
KANVLIGQGD VVLVMKRKRD SSILTDSQTA TKRIRMAIN
