PA_I33A0
ID PA_I33A0 Reviewed; 716 AA.
AC P15659;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1990, sequence version 1.
DT 03-AUG-2022, entry version 111.
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/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=2308849; DOI=10.1093/nar/18.3.654;
RA Odagiri T., Tobita K.;
RT "Nucleotide sequence of the PA gene of influenza A/WSN/33(H1N1).";
RL Nucleic Acids Res. 18:654-654(1990).
RN [2]
RP MUTAGENESIS OF LEU-226.
RX PubMed=15613301; DOI=10.1128/jvi.79.2.732-744.2005;
RA Kawaguchi A., Naito T., Nagata K.;
RT "Involvement of influenza virus PA subunit in assembly of functional RNA
RT polymerase complexes.";
RL J. Virol. 79:732-744(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 -!- INTERACTION:
CC P15659; P03427: PB2; NbExp=3; IntAct=EBI-8431752, EBI-8430745;
CC P15659; P51784: USP11; Xeno; NbExp=2; IntAct=EBI-8431752, EBI-306876;
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=P15659-1; Sequence=Displayed;
CC Name=PA-X;
CC IsoId=P0DJW8-1; 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; X17336; CAA35212.1; -; Genomic_RNA.
DR PDB; 4IUJ; X-ray; 1.90 A; A=254-716.
DR PDB; 5IEQ; X-ray; 2.20 A; A=254-716.
DR PDB; 5IF2; X-ray; 2.35 A; A=254-716.
DR PDB; 5IF5; X-ray; 2.25 A; A=254-716.
DR PDB; 5IF7; X-ray; 2.65 A; A=254-716.
DR PDB; 5IF8; X-ray; 2.30 A; A=254-716.
DR PDB; 5IFB; X-ray; 2.45 A; A=254-716.
DR PDB; 5IFC; X-ray; 2.65 A; A=254-716.
DR PDB; 5IFD; X-ray; 2.65 A; A=254-716.
DR PDB; 5V0U; X-ray; 2.45 A; A=254-716.
DR PDB; 6CFP; X-ray; 2.45 A; A=254-716.
DR PDBsum; 4IUJ; -.
DR PDBsum; 5IEQ; -.
DR PDBsum; 5IF2; -.
DR PDBsum; 5IF5; -.
DR PDBsum; 5IF7; -.
DR PDBsum; 5IF8; -.
DR PDBsum; 5IFB; -.
DR PDBsum; 5IFC; -.
DR PDBsum; 5IFD; -.
DR PDBsum; 5V0U; -.
DR PDBsum; 6CFP; -.
DR SMR; P15659; -.
DR IntAct; P15659; 32.
DR MINT; P15659; -.
DR MEROPS; S62.001; -.
DR PRIDE; P15659; -.
DR Proteomes; UP000000834; 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: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:0006351; P:transcription, DNA-templated; IEA:UniProtKB-UniRule.
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 1: Evidence at protein level;
KW 3D-structure; 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; Reference proteome; Ribosomal frameshifting.
FT CHAIN 1..716
FT /note="Polymerase acidic protein"
FT /id="PRO_0000078801"
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 MUTAGEN 226
FT /note="L->P: Confers temperature sensitivity."
FT /evidence="ECO:0000269|PubMed:15613301"
FT STRAND 273..275
FT /evidence="ECO:0007829|PDB:4IUJ"
FT STRAND 280..282
FT /evidence="ECO:0007829|PDB:5IF8"
FT STRAND 290..294
FT /evidence="ECO:0007829|PDB:4IUJ"
FT TURN 298..301
FT /evidence="ECO:0007829|PDB:4IUJ"
FT HELIX 303..312
FT /evidence="ECO:0007829|PDB:4IUJ"
FT STRAND 317..324
FT /evidence="ECO:0007829|PDB:4IUJ"
FT STRAND 327..329
FT /evidence="ECO:0007829|PDB:5IF5"
FT HELIX 331..350
FT /evidence="ECO:0007829|PDB:4IUJ"
FT STRAND 351..353
FT /evidence="ECO:0007829|PDB:4IUJ"
FT STRAND 356..360
FT /evidence="ECO:0007829|PDB:4IUJ"
FT HELIX 364..369
FT /evidence="ECO:0007829|PDB:4IUJ"
FT HELIX 406..415
FT /evidence="ECO:0007829|PDB:4IUJ"
FT STRAND 419..421
FT /evidence="ECO:0007829|PDB:4IUJ"
FT HELIX 437..450
FT /evidence="ECO:0007829|PDB:4IUJ"
FT HELIX 454..475
FT /evidence="ECO:0007829|PDB:4IUJ"
FT TURN 476..478
FT /evidence="ECO:0007829|PDB:4IUJ"
FT STRAND 479..490
FT /evidence="ECO:0007829|PDB:4IUJ"
FT STRAND 496..506
FT /evidence="ECO:0007829|PDB:4IUJ"
FT STRAND 513..515
FT /evidence="ECO:0007829|PDB:5IFB"
FT STRAND 517..526
FT /evidence="ECO:0007829|PDB:4IUJ"
FT HELIX 530..532
FT /evidence="ECO:0007829|PDB:5IF5"
FT HELIX 534..537
FT /evidence="ECO:0007829|PDB:4IUJ"
FT STRAND 541..550
FT /evidence="ECO:0007829|PDB:4IUJ"
FT STRAND 555..571
FT /evidence="ECO:0007829|PDB:4IUJ"
FT HELIX 572..579
FT /evidence="ECO:0007829|PDB:4IUJ"
FT HELIX 580..582
FT /evidence="ECO:0007829|PDB:4IUJ"
FT HELIX 583..603
FT /evidence="ECO:0007829|PDB:4IUJ"
FT HELIX 608..612
FT /evidence="ECO:0007829|PDB:4IUJ"
FT HELIX 633..649
FT /evidence="ECO:0007829|PDB:4IUJ"
FT HELIX 653..675
FT /evidence="ECO:0007829|PDB:4IUJ"
FT HELIX 686..691
FT /evidence="ECO:0007829|PDB:4IUJ"
FT HELIX 698..712
FT /evidence="ECO:0007829|PDB:4IUJ"
SQ SEQUENCE 716 AA; 82531 MW; 2854E89F8949AE5E CRC64;
MEDFVRQCFN PMIVELAEKA MKEYGEDLKI ETNKFAAICT HLEVCFMYSD FHFIDEQGES
IVVELGDPNA LLKHRFEIIE GRDRTIAWTV INSICNTTGA EKPKFLPDLY DYKKNRFIEI
GVTRREVHIY YLEKANKIKS EKTHIHIFSF TGEEMATKAD YTLDEESRAR IKTRLFTIRQ
EMASRGLWDS FRQSERGEET IEERFEITGT MRKLADQSLP PNFSSLENFR AYVDGFEPNG
YIEGKLSQMS KEVNARIEPF LKSTPRPLRL PDGPPCSQRS KFLLMDALKL SIEDPSHEGE
GIPLYDAIKC MRTFFGWKEP NVVKPHEKGI NPNYLLSWKQ VLAELQDIEN EEKIPRTKNM
KKTSQLKWAL GENMAPEKVD FDDCKDVGDL KQYDSDEPEL RSLASWIQNE FNKACELTDS
SWIELDEIGE DAAPIEHIAS MRRNYFTAEV SHCRATEYIM KGVYINTALL NASCAAMDDF
QLIPMISKCR TKEGRRKTNL YGFIIKGRSH LRNDTDVVNF VSMEFSLTDP RLEPHKWEKY
CVLEVGDMLL RSAIGHVSRP MFLYVRTNGT SKIKMKWGME MRRCLLQSLQ QIESMIEAES
SVKEKDMTKE FFENKSETWP VGESPKGVEE GSIGKVCRTL LAKSVFNSLY ASPQLEGFSA
ESRKLLLIVQ ALRDNLEPGT FDLGGLYEAI EECLINDPWV LLNASWFNSF LTHALR
