PB1F2_I18A0
ID PB1F2_I18A0 Reviewed; 90 AA.
AC P0C574;
DT 13-NOV-2007, integrated into UniProtKB/Swiss-Prot.
DT 13-NOV-2007, sequence version 1.
DT 23-FEB-2022, entry version 53.
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/Brevig Mission/1/1918 H1N1) (Influenza A virus
OS (strain A/South Carolina/1/1918 H1N1)).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC Insthoviricetes; Articulavirales; Orthomyxoviridae; Alphainfluenzavirus.
OX NCBI_TaxID=88776;
OH NCBI_TaxID=8782; Aves.
OH NCBI_TaxID=9606; Homo sapiens (Human).
OH NCBI_TaxID=9823; Sus scrofa (Pig).
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=16208372; DOI=10.1038/nature04230;
RA Taubenberger J.K., Reid A.H., Lourens R.M., Wang R., Jin G., Fanning T.G.;
RT "Characterization of the 1918 influenza virus polymerase genes.";
RL Nature 437:889-893(2005).
RN [2]
RP MUTAGENESIS OF SER-66.
RX PubMed=17922571; DOI=10.1371/journal.ppat.0030141;
RA Conenello G.M., Zamarin D., Perrone L.A., Tumpey T., Palese P.;
RT "A single mutation in the PB1-F2 of H5N1 (HK/97) and 1918 Influenza A
RT viruses contributes to increased virulence.";
RL PLoS Pathog. 3:1414-1421(2007).
RN [3]
RP ROLE IN PATHOGENICITY.
RA McAuley J.L., Hornung F., Boyd K.L., Smith A.M., McKeon R., Bennick J.,
RA Yewdell J.W., McCullers J.A.;
RT "Expression of the 1918 Influenza A virus PB1-F2 enhances the pathogenesis
RT of viral and secondary bacterial pneumonia.";
RL Cell Host Microbe 2:240-249(2007).
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}.
CC -!- SUBUNIT: Oligomer. Interacts with human SLC25A6/ANT3 and VDAC1.
CC Interacts with host MAVS. {ECO:0000255|HAMAP-Rule:MF_04064}.
CC -!- SUBCELLULAR LOCATION: Host mitochondrion inner membrane
CC {ECO:0000255|HAMAP-Rule:MF_04064}. Host nucleus {ECO:0000255|HAMAP-
CC Rule:MF_04064}. Host cytoplasm, host cytosol {ECO:0000255|HAMAP-
CC Rule:MF_04064}. Note=Inner mitochondrial membrane in most cells types.
CC Otherwise is detected in the nucleus and cytosol. {ECO:0000255|HAMAP-
CC Rule:MF_04064}.
CC -!- MISCELLANEOUS: Is not encoded in all strains, and seems to be
CC dispensable for replication.
CC -!- MISCELLANEOUS: South Carolina isolate has been sequenced from formalid
CC fixed-lung tissues of a 21-year-old male which died in 1918 at Ft.
CC Jackson, SC. Brevig Mission isolate has been sequenced from lung
CC tissues of an Inuit woman buried in the permafrost in a gravesite near
CC Brevig Mission, Alaska. This sample was recovered by John Hultin,
CC retired pathologist.
CC -!- SIMILARITY: Belongs to the influenza viruses PB1-F2 family.
CC {ECO:0000255|HAMAP-Rule:MF_04064}.
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DR EMBL; DQ208310; -; NOT_ANNOTATED_CDS; mRNA.
DR SMR; P0C574; -.
DR Proteomes; UP000008430; 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; ISS: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 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; Viral immunoevasion.
FT CHAIN 1..90
FT /note="Protein PB1-F2"
FT /id="PRO_0000310572"
FT REGION 1..34
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..21
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 66
FT /note="High pathogenicity"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04064"
FT SITE 66
FT /note="Important for pathogenicity, S is highly pathogenic
FT whereas N is low pathogenic"
FT MUTAGEN 66
FT /note="S->N: Reduces 50% lethal dose by 3-log in mice."
FT /evidence="ECO:0000269|PubMed:17922571"
SQ SEQUENCE 90 AA; 10810 MW; 81FAE70341B06964 CRC64;
MGQEQDTPWI LSTGHISTQK REDGQQTPRL EHHNSTRLMD HCQKTMNQVV MPKQIVYWKQ
WLSLRSPTPV SLKTRVLKRW RLFSKHEWTS
