ID   PA_I80A2                Reviewed;         716 AA.
AC   Q2VC91;
DT   06-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT   10-JAN-2006, sequence version 1.
DT   03-AUG-2022, entry version 66.
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/Seal/Massachusetts/1/1980 H7N7).
OC   Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC   Insthoviricetes; Articulavirales; Orthomyxoviridae; Alphainfluenzavirus.
OX   NCBI_TaxID=384493;
OH   NCBI_TaxID=8782; Aves.
OH   NCBI_TaxID=9796; Equus caballus (Horse).
OH   NCBI_TaxID=9606; Homo sapiens (Human).
OH   NCBI_TaxID=9709; Phocidae (true seals).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC   STRAIN=SC35M mouse-adapted;
RX   PubMed=16339318; DOI=10.1073/pnas.0507415102;
RA   Gabriel G., Dauber B., Wolff T., Planz O., Klenk H.D., Stech J.;
RT   "The viral polymerase mediates adaptation of an avian influenza virus to a
RT   mammalian host.";
RL   Proc. Natl. Acad. Sci. U.S.A. 102:18590-18595(2005).
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=Q2VC91-1; Sequence=Displayed;
CC       Name=PA-X;
CC         IsoId=P0DJU3-1; 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   -!- MISCELLANEOUS: SC35 was derived from A/Seal/Massachussetts/1/80 (H7N7)
CC       by serial passages in chicken embryo cells, thereby acquiring a
CC       multibasic cleavage site in its hemagglutinin (HA) and becoming 100%
CC       lethal for chickens. SC35 was then passaged 11 times in mouse lung,
CC       yielding the mouse-adapted variant SC35M.
CC   -!- SIMILARITY: Belongs to the influenza viruses PA family.
CC       {ECO:0000255|HAMAP-Rule:MF_04063}.
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DR   EMBL; DQ266099; ABB90272.1; -; Genomic_RNA.
DR   SMR; Q2VC91; -.
DR   Proteomes; UP000008576; 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_0000279261"
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"
SQ   SEQUENCE   716 AA;  82555 MW;  34514C4AD34E65A6 CRC64;
     MEDFVRQCFN PMIVELAEKA MKEYGEDPKI ETNKFAAICT HLEVCFMYSD FHFVDERGES
     IIVESGDPNA LLKHRFEIIE GRDRTMAWTV VNSICNTTGI EKPKFLPDLY DYKENRFIEI
     GVTRREVHIY YLEKANKIKS EKTHIHIFSF TGEEMATKAD YTLDEESRAR IKTRLFTIRQ
     EMASRGLWDS FRQSERGEET IEERFEITGT MRRLANQSLP PNFSSLENFR AYVDGFEPNG
     CIEGKLSQMS KEVNARIEPF LKTTPRPLRL PEGPPCSQRS KFLLMDALKL SIEDPSHEGE
     GIPLYDAIKC MKTFFGWKEP NIVKPHEKGI NPNYLLAWKQ VLAELQDIEN EEKIPKTKNM
     KKTSQLKWAL GENMAPEKVD FEDCKDVSDL KQYDSDEPEQ RSLASWIQSE FNKACELTDS
     SWIELDEIGE DVAPIEHIAS MRRNYFTAEV SRCRATEYIM KGVYINTALL NASSAAMDDF
     QLIPMISKCR TKEGRRKTNL YGFIIKGRSH LRNDTDVVNF VSMEFSLTDP RLEPHKWEKY
     CVLEIGDMLL RTAIGQVSRP MFLYVRTNGT SKIKMKWGME MRRCLLQSLQ QIESMIEAES
     SVKEKDMTKE FFENNSETWP IGESPKGVEE GSIGKVCRTL LAKSVFNSLY ASPQLEGFSA
     ESRKLLLIVQ ALRDNLEPGT FDLGGLYEAI EECLINDPWV LLNASWFNSF LTHALK