PB1F2_I34A1
ID PB1F2_I34A1 Reviewed; 87 AA.
AC P0C0U1; A4GXH2; Q20N29;
DT 06-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 06-DEC-2005, sequence version 1.
DT 25-MAY-2022, entry version 91.
DE RecName: Full=Protein PB1-F2 {ECO:0000255|HAMAP-Rule:MF_04064};
GN Name=PB1 {ECO:0000255|HAMAP-Rule:MF_04064};
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], 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 [3]
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 [4]
RP CHARACTERIZATION.
RX PubMed=11726970; DOI=10.1038/nm1201-1306;
RA Chen W., Calvo P.A., Malide D., Gibbs J., Schubert U., Bacik I., Basta S.,
RA O'Neill R., Schickli J., Palese P., Henklein P., Bennink J.R.,
RA Yewdell J.W.;
RT "A novel influenza A virus mitochondrial protein that induces cell death.";
RL Nat. Med. 7:1306-1312(2001).
RN [5]
RP SUBCELLULAR LOCATION.
RX PubMed=12805420; DOI=10.1128/jvi.77.13.7214-7224.2003;
RA Gibbs J.S., Malide D., Hornung F., Bennink J.R., Yewdell J.W.;
RT "The influenza A virus PB1-F2 protein targets the inner mitochondrial
RT membrane via a predicted basic amphipathic helix that disrupts
RT mitochondrial function.";
RL J. Virol. 77:7214-7224(2003).
RN [6]
RP INTERACTION WITH HUMAN SLC25A6/ANT3 AND VDAC1.
RX PubMed=16201016; DOI=10.1371/journal.ppat.0010004;
RA Zamarin D., Garcia-Sastre A., Xiao X., Wang R., Palese P.;
RT "Influenza virus PB1-F2 protein induces cell death through mitochondrial
RT ANT3 and VDAC1.";
RL PLoS Pathog. 1:40-54(2005).
RN [7]
RP STRUCTURE BY NMR OF 50-87.
RX PubMed=17052982; DOI=10.1074/jbc.m606494200;
RA Bruns K., Studtrucker N., Sharma A., Fossen T., Mitzner D., Eissmann A.,
RA Tessmer U., Roder R., Henklein P., Wray V., Schubert U.;
RT "Structural characterization and oligomerization of PB1-F2, a proapoptotic
RT Influenza A Virus protein.";
RL J. Biol. Chem. 282:353-363(2007).
RN [8]
RP FUNCTION.
RX PubMed=21695240; DOI=10.1371/journal.ppat.1002067;
RA Varga Z.T., Ramos I., Hai R., Schmolke M., Garcia-Sastre A.,
RA Fernandez-Sesma A., Palese P.;
RT "The influenza virus protein PB1-F2 inhibits the induction of type I
RT interferon at the level of the MAVS adaptor protein.";
RL PLoS Pathog. 7:E1002067-E1002067(2011).
CC -!- FUNCTION: Plays an important role in promoting lung pathology in both
CC primary viral infection and secondary bacterial infection. Promotes
CC alteration of mitochondrial morphology, dissipation of mitochondrial
CC membrane potential, and cell death. Alternatively, inhibits the
CC production of interferon in the infected cell at the level of host
CC mitochondrial antiviral signaling MAVS. Its level of expression differs
CC greatly depending on which cell type is infected, in a manner that is
CC independent of the levels of expression of other viral proteins.
CC Monocytic cells are more affected than epithelial cells. Seems to
CC disable virus-infected monocytes or other host innate immune cells.
CC During early stage of infection, predisposes the mitochondria to
CC permeability transition through interaction with host SLC25A6/ANT3 and
CC VDAC1. These proteins participate in the formation of the permeability
CC transition pore complex (PTPC) responsible of the release of
CC mitochondrial products that triggers apoptosis. {ECO:0000255|HAMAP-
CC Rule:MF_04064, ECO:0000269|PubMed:21695240}.
CC -!- SUBUNIT: Oligomer. Interacts with human SLC25A6/ANT3 and VDAC1.
CC Interacts with host MAVS. {ECO:0000255|HAMAP-Rule:MF_04064,
CC ECO:0000269|PubMed:16201016}.
CC -!- INTERACTION:
CC P0C0U1; P12236: SLC25A6; Xeno; NbExp=5; IntAct=EBI-12579807, EBI-356254;
CC P0C0U1; P21796: VDAC1; Xeno; NbExp=4; IntAct=EBI-12579807, EBI-354158;
CC -!- SUBCELLULAR LOCATION: Host mitochondrion inner membrane
CC {ECO:0000255|HAMAP-Rule:MF_04064, ECO:0000269|PubMed:12805420}. Host
CC nucleus {ECO:0000255|HAMAP-Rule:MF_04064, ECO:0000269|PubMed:12805420}.
CC Host cytoplasm, host cytosol {ECO:0000255|HAMAP-Rule:MF_04064,
CC ECO:0000269|PubMed:12805420}. Note=Inner mitochondrial membrane in most
CC cells types. Otherwise is detected in the nucleus and cytosol.
CC {ECO:0000255|HAMAP-Rule:MF_04064}.
CC -!- MISCELLANEOUS: Is not encoded in all strains, and seems to be
CC dispensable for replication.
CC -!- SIMILARITY: Belongs to the influenza viruses PB1-F2 family.
CC {ECO:0000255|HAMAP-Rule:MF_04064}.
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DR EMBL; J02151; -; NOT_ANNOTATED_CDS; Genomic_RNA.
DR EMBL; EF467819; ABO21707.1; -; Genomic_RNA.
DR EMBL; CY009450; ABD77684.1; -; Genomic_RNA.
DR RefSeq; YP_418248.1; NC_002021.1.
DR PDB; 2HN8; NMR; -; A=50-87.
DR PDB; 3BUY; X-ray; 2.60 A; C=62-70.
DR PDBsum; 2HN8; -.
DR PDBsum; 3BUY; -.
DR BMRB; P0C0U1; -.
DR SMR; P0C0U1; -.
DR IntAct; P0C0U1; 17.
DR GeneID; 3802042; -.
DR KEGG; vg:3802042; -.
DR Reactome; R-HSA-168277; Influenza Virus Induced Apoptosis.
DR Reactome; R-HSA-192823; Viral mRNA Translation.
DR EvolutionaryTrace; P0C0U1; -.
DR Proteomes; UP000009255; Genome.
DR Proteomes; UP000170967; Genome.
DR GO; GO:0044164; C:host cell cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0044192; C:host cell mitochondrial inner membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-UniRule.
DR GO; GO:0039526; P:modulation by virus of host apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0039545; P:suppression by virus of host viral-induced cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS activity; IDA:UniProtKB.
DR HAMAP; MF_04064; INFV_PB1F2; 1.
DR InterPro; IPR021045; Flu_proapoptotic_PB1-F2.
DR Pfam; PF11986; PB1-F2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Apoptosis; Host cytoplasm; Host membrane; Host mitochondrion;
KW Host mitochondrion inner membrane; Host nucleus; Host-virus interaction;
KW Inhibition of host innate immune response by virus;
KW Inhibition of host MAVS by virus; Inhibition of host RLR pathway by virus;
KW Membrane; Modulation of host cell apoptosis by virus; Reference proteome;
KW Viral immunoevasion.
FT CHAIN 1..87
FT /note="Protein PB1-F2"
FT /id="PRO_0000078743"
FT REGION 1..38
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 65..87
FT /note="Mitochondrial targeting sequence"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04064"
FT COMPBIAS 1..24
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 66
FT /note="Low pathogenicity"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04064"
FT VARIANT 22
FT /note="Q -> E"
FT VARIANT 59..60
FT /note="KQ -> RR"
FT HELIX 52..62
FT /evidence="ECO:0007829|PDB:2HN8"
FT HELIX 65..86
FT /evidence="ECO:0007829|PDB:2HN8"
SQ SEQUENCE 87 AA; 10483 MW; 832A7E34E350B454 CRC64;
MGQEQDTPWI LSTGHISTQK RQDGQQTPKL EHRNSTRLMG HCQKTMNQVV MPKQIVYWKQ
WLSLRNPILV FLKTRVLKRW RLFSKHE
