ID   PA_I80A8                Reviewed;         716 AA.
AC   P13178; Q20NN6;
DT   01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT   01-JAN-1990, sequence version 1.
DT   03-AUG-2022, entry version 106.
DE   RecName: Full=Polymerase acidic protein {ECO:0000255|HAMAP-Rule:MF_04063};
DE            EC=3.1.-.- {ECO:0000255|HAMAP-Rule:MF_04063};
DE   AltName: Full=RNA-directed RNA polymerase subunit P2 {ECO:0000255|HAMAP-Rule:MF_04063};
GN   Name=PA {ECO:0000255|HAMAP-Rule:MF_04063};
OS   Influenza A virus (strain A/Turkey/Minnesota/833/1980 H4N2).
OC   Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC   Insthoviricetes; Articulavirales; Orthomyxoviridae; Alphainfluenzavirus.
OX   NCBI_TaxID=383603;
OH   NCBI_TaxID=8782; Aves.
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=2800339; DOI=10.1016/0042-6822(89)90202-x;
RA   Okazaki K., Kawaoka Y., Webster R.G.;
RT   "Evolutionary pathways of the PA genes of influenza A viruses.";
RL   Virology 172:601-608(1989).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=16439620; DOI=10.1126/science.1121586;
RA   Obenauer J.C., Denson J., Mehta P.K., Su X., Mukatira S., Finkelstein D.B.,
RA   Xu X., Wang J., Ma J., Fan Y., Rakestraw K.M., Webster R.G., Hoffmann E.,
RA   Krauss S., Zheng J., Zhang Z., Naeve C.W.;
RT   "Large-scale sequence analysis of avian influenza isolates.";
RL   Science 311:1576-1580(2006).
CC   -!- FUNCTION: Plays an essential role in viral RNA transcription and
CC       replication by forming the heterotrimeric polymerase complex together
CC       with PB1 and PB2 subunits. The complex transcribes viral mRNAs by using
CC       a unique mechanism called cap-snatching. It consists in the hijacking
CC       and cleavage of host capped pre-mRNAs. These short capped RNAs are then
CC       used as primers for viral mRNAs. The PB2 subunit is responsible for the
CC       binding of the 5' cap of cellular pre-mRNAs which are subsequently
CC       cleaved after 10-13 nucleotides by the PA subunit that carries the
CC       endonuclease activity. {ECO:0000255|HAMAP-Rule:MF_04063}.
CC   -!- COFACTOR:
CC       Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC         Evidence={ECO:0000255|HAMAP-Rule:MF_04063};
CC       Note=Binds 2 manganese ions per subunit. {ECO:0000255|HAMAP-
CC       Rule:MF_04063};
CC   -!- SUBUNIT: Influenza RNA polymerase is composed of three subunits: PB1,
CC       PB2 and PA. Interacts (via C-terminus) with PB1 (via N-terminus).
CC       {ECO:0000250|UniProtKB:P03433, ECO:0000255|HAMAP-Rule:MF_04063}.
CC   -!- SUBCELLULAR LOCATION: Host cytoplasm {ECO:0000255|HAMAP-Rule:MF_04063}.
CC       Host nucleus {ECO:0000255|HAMAP-Rule:MF_04063}. Note=PB1 and PA are
CC       transported in the host nucleus as a complex.
CC       {ECO:0000250|UniProtKB:P03433, ECO:0000255|HAMAP-Rule:MF_04063}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Ribosomal frameshifting; Named isoforms=2;
CC       Name=PA;
CC         IsoId=P13178-1; Sequence=Displayed;
CC       Name=PA-X;
CC         IsoId=P0DJV7-1; Sequence=External;
CC   -!- PTM: Phosphorylated on serines and threonines by host kinases,
CC       including human casein kinase II. {ECO:0000250|UniProtKB:P03433,
CC       ECO:0000255|HAMAP-Rule:MF_04063}.
CC   -!- SIMILARITY: Belongs to the influenza viruses PA family.
CC       {ECO:0000255|HAMAP-Rule:MF_04063}.
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DR   EMBL; M26084; AAA43685.1; -; Genomic_RNA.
DR   EMBL; CY005911; ABB21826.1; -; Genomic_RNA.
DR   SMR; P13178; -.
DR   MEROPS; S62.001; -.
DR   Proteomes; UP000008579; Genome.
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:0004519; F:endonuclease activity; IEA:UniProtKB-KW.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0003723; F:RNA binding; 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:0006351; P:transcription, DNA-templated; IEA:UniProtKB-UniRule.
DR   GO; GO:0039694; P:viral RNA genome replication; IEA:InterPro.
DR   Gene3D; 3.40.91.90; -; 1.
DR   HAMAP; MF_04063; INFV_PA; 1.
DR   InterPro; IPR037534; INFV_PA.
DR   InterPro; IPR001009; PA/PA-X.
DR   InterPro; IPR038372; PA/PA-X_sf.
DR   Pfam; PF00603; Flu_PA; 1.
PE   3: Inferred from homology;
KW   Cap snatching; Endonuclease;
KW   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; Hydrolase;
KW   Inhibition of host RNA polymerase II by virus; Manganese; Metal-binding;
KW   Nuclease; Phosphoprotein; Ribosomal frameshifting.
FT   CHAIN           1..716
FT                   /note="Polymerase acidic protein"
FT                   /id="PRO_0000078799"
FT   MOTIF           124..139
FT                   /note="Nuclear localization signal 1 (NLS1)"
FT                   /evidence="ECO:0000250|UniProtKB:P03433, ECO:0000255|HAMAP-
FT                   Rule:MF_04063"
FT   MOTIF           184..247
FT                   /note="Nuclear localization signal 2 (NLS2)"
FT                   /evidence="ECO:0000250|UniProtKB:P03433, ECO:0000255|HAMAP-
FT                   Rule:MF_04063"
FT   BINDING         41
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04063"
FT   BINDING         80
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04063"
FT   BINDING         108
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04063"
FT   BINDING         108
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04063"
FT   BINDING         119
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04063"
FT   BINDING         120
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04063"
FT   CONFLICT        482
FT                   /note="V -> L (in Ref. 2; ABB21826)"
SQ   SEQUENCE   716 AA;  82550 MW;  92D7C689FB03583E CRC64;
     MEDFVRQCFN PMIVELAEKA MKEYGEDPKI ETNKFAAICT HLEVCFMYSD FHFIDERGES
     IIVESGDPNA LLKHRFEIIE GRDRTMAWTV VNSICNTTGV EKPKFLPDLY DYKENRFIEI
     GVTRREVHIY YLEKANKIKS EKTHIHIFSF TGEEMATKAD YTLDEESRAR IKTRLFTIRQ
     EMASRGLWDS FRQSERGEET IEERFEITGT MRRLADQSLP PNFSSLENFR AYVDGFEPNG
     CIEGKLSQMS KEVNARIEPF LKTTPRPLRL PDGPPCSQRS KFLLMDALKL SIEDPSHEGE
     GIPLYDAIKC MKTFFGWKEP NIIKPHEKGI NPNYLLAWKQ VLAELQDIEN EEKIPKTKNM
     KKTSQLKWAL GENMAPEKVD FEDCKDISDL KQYDSDEPEP RSLASWIQSE FNKACELTDS
     SWIELDEIGE DIAPIEHIAS MRRNYFTAEV SHCRATEYIM KGVYINTALL NASCAAMDDF
     QVIPMISKCR TKEGRRKTNL YGFIIKGRSH LRNDTDVVNF VSMEFSLTDP RLEPHKWEKY
     CVLEIGDMLL RTAIGQVSRP MFLYVRTNGT SKIKMKWGME MRRCLLQSLQ QIESMIEAES
     SVKEKDMTKE FFENKSETWP IGESPKGVEE GSIGKVCRTL LAKSVFNSLY ASPQLEGFSA
     ESRKLLLIVQ ALRDNLEPGT FDLGGLYEAI EECLINDPWV LLNASWFNSF LTHALK