PA_I75A3
ID PA_I75A3 Reviewed; 716 AA.
AC P31343;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1993, sequence version 1.
DT 03-AUG-2022, entry version 99.
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/Victoria/3/1975 H3N2).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC Insthoviricetes; Articulavirales; Orthomyxoviridae; Alphainfluenzavirus.
OX NCBI_TaxID=392809;
OH NCBI_TaxID=8782; Aves.
OH NCBI_TaxID=9721; Cetacea (whales).
OH NCBI_TaxID=9606; Homo sapiens (Human).
OH NCBI_TaxID=9709; Phocidae (true seals).
OH NCBI_TaxID=9823; Sus scrofa (Pig).
RN [1]
RP NUCLEOTIDE SEQUENCE.
RX PubMed=2773594; DOI=10.1016/0168-1702(89)90012-9;
RA de la Luna S., Martinez C., Ortin J.;
RT "Molecular cloning and sequencing of influenza virus A/Victoria/3/75
RT polymerase genes: sequence evolution and prediction of possible functional
RT domains.";
RL Virus Res. 13:143-156(1989).
RN [2]
RP PHOSPHORYLATION.
RX PubMed=9519825; DOI=10.1099/0022-1317-79-3-471;
RA Sanz-Ezquerro J.J., Fernandez-Santaren J., Sierra T., Aragon T., Ortega J.,
RA Ortin J., Smith G.L., Nieto A.;
RT "The PA influenza virus polymerase subunit is a phosphorylated protein.";
RL J. Gen. Virol. 79:471-478(1998).
RN [3]
RP FUNCTION.
RX PubMed=23847103; DOI=10.1093/nar/gkt603;
RA Datta K., Wolkerstorfer A., Szolar O.H., Cusack S., Klumpp K.;
RT "Characterization of PA-N terminal domain of Influenza A polymerase reveals
RT sequence specific RNA cleavage.";
RL Nucleic Acids Res. 41:8289-8299(2013).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS) OF 1-209, AND FUNCTION.
RX PubMed=19194459; DOI=10.1038/nature07745;
RA Dias A., Bouvier D., Crepin T., McCarthy A.A., Hart D.J., Baudin F.,
RA Cusack S., Ruigrok R.W.;
RT "The cap-snatching endonuclease of influenza virus polymerase resides in
RT the PA subunit.";
RL Nature 458:914-918(2009).
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 ECO:0000269|PubMed:19194459, ECO:0000269|PubMed:23847103}.
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 P31343; Q9Y224: RTRAF; Xeno; NbExp=4; IntAct=EBI-5800362, EBI-1104547;
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=P31343-1; Sequence=Displayed;
CC Name=PA-X;
CC IsoId=P31343-2; Sequence=Not described;
CC -!- PTM: Phosphorylated on serines and threonines by host kinases,
CC including human casein kinase II. {ECO:0000255|HAMAP-Rule:MF_04063,
CC ECO:0000269|PubMed:9519825}.
CC -!- SIMILARITY: Belongs to the influenza viruses PA family.
CC {ECO:0000255|HAMAP-Rule:MF_04063}.
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DR PDB; 2W69; X-ray; 2.05 A; A/B/D=1-209.
DR PDBsum; 2W69; -.
DR SMR; P31343; -.
DR DIP; DIP-61895N; -.
DR IntAct; P31343; 4.
DR BRENDA; 2.7.7.48; 7479.
DR EvolutionaryTrace; P31343; -.
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 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; Ribosomal frameshifting.
FT CHAIN 1..716
FT /note="Polymerase acidic protein"
FT /id="PRO_0000078800"
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 HELIX 1..8
FT /evidence="ECO:0007829|PDB:2W69"
FT HELIX 11..23
FT /evidence="ECO:0007829|PDB:2W69"
FT TURN 28..30
FT /evidence="ECO:0007829|PDB:2W69"
FT HELIX 32..49
FT /evidence="ECO:0007829|PDB:2W69"
FT HELIX 62..64
FT /evidence="ECO:0007829|PDB:2W69"
FT STRAND 75..78
FT /evidence="ECO:0007829|PDB:2W69"
FT HELIX 84..98
FT /evidence="ECO:0007829|PDB:2W69"
FT STRAND 108..111
FT /evidence="ECO:0007829|PDB:2W69"
FT TURN 112..115
FT /evidence="ECO:0007829|PDB:2W69"
FT STRAND 116..125
FT /evidence="ECO:0007829|PDB:2W69"
FT HELIX 127..135
FT /evidence="ECO:0007829|PDB:2W69"
FT STRAND 144..149
FT /evidence="ECO:0007829|PDB:2W69"
FT STRAND 154..156
FT /evidence="ECO:0007829|PDB:2W69"
FT HELIX 157..159
FT /evidence="ECO:0007829|PDB:2W69"
FT HELIX 165..184
FT /evidence="ECO:0007829|PDB:2W69"
FT HELIX 188..193
FT /evidence="ECO:0007829|PDB:2W69"
SQ SEQUENCE 716 AA; 82822 MW; B1FC817C171BB50F CRC64;
MEDFVRQCFN PMIVELAEKA MKEYGEDLKI ETNKFAAICT HLEVCFMYSD FHFINEQGES
IVVELDDPNA LLKHRFEIIE GRDRTMAWTV VNSICNTTGA EKPKFLPDLY DYKENRFIEI
GVTRREVHIY YLEKANKIKS ENTHIHIFSF TGEGMATKAD YTLDEESRAR IKTRLFTIRQ
EMANRGLWDS FRQSERGEET IEERFEITGT MRRLADQSLP PNFSCLENFR AYVDGFEPNG
CIEGKLSQMS KEVNAKIEPF LKTTPRPIKL PDGPPCFQRS KFLLMDALKL SIEDPSHEGE
GIPLYDAIKC MRTFFGWKEP YIVKPHERGI NSNYLLSWKQ VLAELQDIEN EEKIPRTKNM
KKTSQLKWAL GENMAPEKVD FDNCRDISDL KQYDSDEPEL RSLSSWIQNE FNKACELTDS
IWIELDEIGE DVAPIEYIAS MRRNYFTAEV SHCRATEYIM KGVYINTALL NASCAAMDDF
QLIPMISKCR TKEGRRKTNL YGFIIKGRSH LRNDTDVVNF VSMEFSLTDP RLEPHKWEKY
CVLEIGDMLL RSAIGQMSRP MFLYVRTNGT SKIKMKWGME MRRCLLQSLQ QIESMIEAES
SVKEKDMTKE FFENKSETWP IGESPKGVEE GSIGKVCRTL LAKSVFNSLY ASPQLEGFSA
ESRKLLLVVQ ALRDNLEPGT FDLGGLYEAI EECLINDPWV LLNASWFNSF LTHALR
