PB2_I33A0
ID PB2_I33A0 Reviewed; 759 AA.
AC P03427;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 21-JUL-1986, sequence version 1.
DT 03-AUG-2022, entry version 118.
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/Wilson-Smith/1933 H1N1) (Influenza A virus
OS (strain A/WS/1933 H1N1)).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC Insthoviricetes; Articulavirales; Orthomyxoviridae; Alphainfluenzavirus.
OX NCBI_TaxID=381518;
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=7045393; DOI=10.1128/jvi.42.1.55-63.1982;
RA Kaptein J.S., Nayak D.P.;
RT "Complete nucleotide sequence of the polymerase 3 gene of human influenza
RT virus A/WSN/33.";
RL J. Virol. 42:55-63(1982).
RN [2]
RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF LYS-736; ARG-737; LYS-738 AND
RP ARG-739.
RX PubMed=1985200; DOI=10.1128/jvi.65.1.245-253.1991;
RA Mukaigawa J., Nayak D.P.;
RT "Two signals mediate nuclear localization of influenza virus (A/WSN/33)
RT polymerase basic protein 2.";
RL J. Virol. 65:245-253(1991).
RN [3]
RP MUTAGENESIS OF TRP-49; TRP-78; PHE-130; ARG-142 AND LYS-190.
RX PubMed=12692212; DOI=10.1128/jvi.77.9.5098-5108.2003;
RA Gastaminza P., Perales B., Falcon A.M., Ortin J.;
RT "Mutations in the N-terminal region of influenza virus PB2 protein affect
RT virus RNA replication but not transcription.";
RL J. Virol. 77:5098-5108(2003).
RN [4]
RP FUNCTION, AND INTERACTION WITH PB1 AND NP.
RX PubMed=15033571; DOI=10.1016/j.virol.2003.12.022;
RA Poole E., Elton D., Medcalf L., Digard P.;
RT "Functional domains of the influenza A virus PB2 protein: identification of
RT NP- and PB1-binding sites.";
RL Virology 321:120-133(2004).
RN [5]
RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF LEU-7 AND LEU-10.
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 [6]
RP ALTERNATIVE SPLICING (PB2-S1).
RX PubMed=26491155; DOI=10.1128/jvi.02175-15;
RA Yamayoshi S., Watanabe M., Goto H., Kawaoka Y.;
RT "Identification of a novel viral protein expressed from the PB2 segment of
RT Influenza A virus.";
RL J. Virol. 90:444-456(2015).
RN [7]
RP FUNCTION, INTERACTION WITH HOST ANP32A, AND MUTAGENESIS OF GLN-447 AND
RP GLY-450.
RX PubMed=30666459; DOI=10.1007/s00705-018-04139-z;
RA Wei X., Liu Z., Wang J., Yang R., Yang J., Guo Y., Tan H., Chen H., Liu Q.,
RA Liu L.;
RT "The interaction of cellular protein ANP32A with influenza A virus
RT polymerase component PB2 promotes vRNA synthesis.";
RL Arch. Virol. 164:787-798(2019).
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:30666459}.
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. Interacts with host ANP32A (via C-
CC terminus); this interaction promotes viral RNA synthesis.
CC {ECO:0000255|HAMAP-Rule:MF_04062, ECO:0000269|PubMed:15033571,
CC ECO:0000269|PubMed:30666459}.
CC -!- INTERACTION:
CC P03427; P15659: PA; NbExp=3; IntAct=EBI-8430745, EBI-8431752;
CC P03427; P03430: PB1; NbExp=3; IntAct=EBI-8430745, EBI-8434155;
CC P03427; O00571: DDX3X; Xeno; NbExp=3; IntAct=EBI-8430745, EBI-353779;
CC P03427; O00505: KPNA3; Xeno; NbExp=3; IntAct=EBI-8430745, EBI-358297;
CC P03427; P06748: NPM1; Xeno; NbExp=3; IntAct=EBI-8430745, EBI-78579;
CC P03427; P49411: TUFM; Xeno; NbExp=9; IntAct=EBI-8430745, EBI-359097;
CC -!- SUBCELLULAR LOCATION: Virion {ECO:0000255|HAMAP-Rule:MF_04062}. Host
CC nucleus {ECO:0000255|HAMAP-Rule:MF_04062}. Host mitochondrion
CC {ECO:0000255|HAMAP-Rule:MF_04062, ECO:0000269|PubMed:16242167,
CC ECO:0000269|PubMed:1985200}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Polymerase basic protein 2;
CC IsoId=P03427-1; Sequence=Displayed;
CC Name=PB2-S1 {ECO:0000303|PubMed:26491155};
CC IsoId=P0DOG3-1; 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; J02179; AAA43611.1; -; Genomic_RNA.
DR SMR; P03427; -.
DR IntAct; P03427; 264.
DR MINT; P03427; -.
DR PRO; PR:P03427; -.
DR Proteomes; UP000000834; Genome.
DR GO; GO:0033650; C:host cell mitochondrion; IDA:CACAO.
DR GO; GO:0042025; C:host cell nucleus; IDA:UniProtKB.
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:0039689; P:negative stranded viral RNA replication; IDA:UniProtKB.
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 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 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_0000078841"
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 MUTAGEN 7
FT /note="L->A: Complete loss of mitochondrial localization."
FT /evidence="ECO:0000269|PubMed:16242167"
FT MUTAGEN 10
FT /note="L->A: Complete loss of mitochondrial localization."
FT /evidence="ECO:0000269|PubMed:16242167"
FT MUTAGEN 49
FT /note="W->A: Partial loss of replication. No effect on
FT transcription."
FT /evidence="ECO:0000269|PubMed:12692212"
FT MUTAGEN 78
FT /note="W->A: Complete loss of protein expression."
FT /evidence="ECO:0000269|PubMed:12692212"
FT MUTAGEN 130
FT /note="F->A: Complete loss of replication. No effect on
FT transcription."
FT /evidence="ECO:0000269|PubMed:12692212"
FT MUTAGEN 130
FT /note="F->Y: Enhances viral replication."
FT /evidence="ECO:0000269|PubMed:12692212"
FT MUTAGEN 142
FT /note="R->A: Partial loss of replication. No effect on
FT transcription."
FT /evidence="ECO:0000269|PubMed:12692212"
FT MUTAGEN 142
FT /note="R->K: Partial loss of replication. No effect on
FT transcription."
FT /evidence="ECO:0000269|PubMed:12692212"
FT MUTAGEN 190
FT /note="K->A: No effect on replication or transcription."
FT /evidence="ECO:0000269|PubMed:12692212"
FT MUTAGEN 447
FT /note="Q->A: Loss of interaction with ANP32A."
FT /evidence="ECO:0000269|PubMed:30666459"
FT MUTAGEN 450
FT /note="G->A: Loss of interaction with ANP32A."
FT /evidence="ECO:0000269|PubMed:30666459"
FT MUTAGEN 736
FT /note="K->Q: Partial loss of nuclear localization."
FT /evidence="ECO:0000269|PubMed:1985200"
FT MUTAGEN 737
FT /note="R->Q: Complete loss of nuclear localization."
FT /evidence="ECO:0000269|PubMed:1985200"
FT MUTAGEN 738
FT /note="K->Q: Complete loss of nuclear localization."
FT /evidence="ECO:0000269|PubMed:1985200"
FT MUTAGEN 739
FT /note="R->Q: Partial loss of nuclear localization."
FT /evidence="ECO:0000269|PubMed:1985200"
SQ SEQUENCE 759 AA; 85796 MW; E7FA3844C44EB62D CRC64;
MERIKELRNL MSQSRTREIL TKTTVDHMAI IKKYTSGRQE KNPALRMKWM MAMKYPITAD
KRITEMIPER NEQGQTLWSK MNDAGSDRVM VSPLAVTWWN RNGPVTSTVH YPKIYKTYFE
KVERLKHGTF GPVHFRNQVK IRRRVDINPG HADLSAKEAQ DVIMEVVFPN EVGARILTSE
SQLTTTKEKK EELQGCKISP LMVAYMLERE LVRKTRFLPV AGGTSSVYIE VLHLTQGTCW
EQMYTPGGEA RNDDVDQSLI IAARNIVRRA TVSADPLASL LEMCHSTQIG GIRMVNILRQ
NPTEEQAVDI CKAAMGLRIS SSFSFGGFTF KRTSGSSVKR EEEVLTGNLQ TLKIRVHEGY
EEFTMVGRRA TAILRKATRR LIQLIVSGRD EQSIAEAIIV AMVFSQEDCM IKAVRGDLNF
VNRANQRLNP MHQLLRHFQK DAKALFQNWG IESIDNVMGM IGILPDMTPS TEMSMRGVRI
SKMGVDEYSS AEKIVVSIDR FLRVRDQRGN VLLSPEEVSE TQGTEKLTIT YSSSMMWEIN
GPESVLVNTY QWIIRNWETV KIQWSQNPTM LYNKMEFEPF QSLVPKAVRG QYSGFVRTLF
QQMRDVLGTF DTAQIIKLLP FAAAPPKQSG MQFSSLTINV RGSGMRILVR GNSPIFNYNK
TTKRLTVLGK DAGPLTEDPD EGTAGVESAV LRGFLILGKE DRRYGPALSI NELSNLAKGE
KANVLIGQGD VVLVMKRKRN SSILTDSQTA TKRIRMAIN
