PA_I97A1
ID PA_I97A1 Reviewed; 716 AA.
AC O89752; O56265; Q779I2; Q77VG0;
DT 06-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 81.
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/Hong Kong/156/1997 H5N1 genotype Gs/Gd).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC Insthoviricetes; Articulavirales; Orthomyxoviridae; Alphainfluenzavirus.
OX NCBI_TaxID=130763;
OH NCBI_TaxID=8782; Aves.
OH NCBI_TaxID=9685; Felis catus (Cat) (Felis silvestris catus).
OH NCBI_TaxID=9606; Homo sapiens (Human).
OH NCBI_TaxID=9691; Panthera pardus (Leopard) (Felis pardus).
OH NCBI_TaxID=9694; Panthera tigris (Tiger).
OH NCBI_TaxID=9823; Sus scrofa (Pig).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=9658115; DOI=10.1128/jvi.72.8.6678-6688.1998;
RA Suarez D.L., Perdue M.L., Cox N., Rowe T., Bender C., Huang J.,
RA Swayne D.E.;
RT "Comparisons of highly virulent H5N1 influenza A viruses isolated from
RT humans and chickens from Hong Kong.";
RL J. Virol. 72:6678-6688(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=10920197; DOI=10.1073/pnas.160270697;
RA Lin Y.P., Shaw M., Gregory V., Cameron K., Lim W., Klimov A., Subbarao K.,
RA Guan Y., Krauss S., Shortridge K., Webster R., Cox N., Hay A.;
RT "Avian-to-human transmission of H9N2 subtype influenza A viruses:
RT relationship between H9N2 and H5N1 human isolates.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:9654-9658(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=10769072; DOI=10.1099/0022-1317-81-5-1293;
RA Hiromoto Y., Yamazaki Y., Fukushima T., Saito T., Lindstrom S.E., Omoe K.,
RA Nerome R., Lim W., Sugita S., Nerome K.;
RT "Evolutionary characterization of the six internal genes of H5N1 human
RT influenza A virus.";
RL J. Gen. Virol. 81:1293-1303(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1-577.
RX PubMed=9430591; DOI=10.1126/science.279.5349.393;
RA Subbarao K., Klimov A., Katz J., Regnery H., Lim W., Hall H., Perdue M.,
RA Swayne D., Bender C., Huang J., Hemphill M., Rowe T., Shaw M., Xu X.,
RA Fukuda K., Cox N.;
RT "Characterization of an avian influenza A (H5N1) virus isolated from a
RT child with a fatal respiratory illness.";
RL Science 279:393-396(1998).
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=O89752-1; Sequence=Displayed;
CC Name=PA-X;
CC IsoId=P0DJR8-1; 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; AF046095; AAC32097.1; -; Genomic_RNA.
DR EMBL; AJ289874; CAB95840.1; -; Genomic_RNA.
DR EMBL; AF084267; AAF74317.1; -; Genomic_RNA.
DR EMBL; AF036361; AAC34270.1; -; Genomic_RNA.
DR SMR; O89752; -.
DR MEROPS; S62.001; -.
DR Proteomes; UP000008587; 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_0000078786"
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 142
FT /note="E -> K (in Ref. 4; AAF74317)"
FT CONFLICT 448
FT /note="A -> G (in Ref. 2; AAC34270)"
SQ SEQUENCE 716 AA; 82749 MW; 1F90020B425BF585 CRC64;
MEDFVRQCFN PMIVELAEKT MKEYGEDPKI ETNKFAAICT HLEVCFMYSD FHFIDERGES
IIVESGDPNA LLKHRFEIIE GRDRAMAWTV VNSICNTTGV DKPKFLPDLY DYKENRFTEI
GVTRREVHIY YLEKANKIKS EETHIHIFSF TGEEMATKAD YTLDEESRAR IKTRLFTIRQ
EMASRGLWDS FRQSERGEET IEERFEITGT MRRLADQSLP PNFSSLENFR AYVDGFKPNG
CIEGKLSQMS KEVNARIEPF LKTTPRPLRL PDGPPCSQRS KFLLMDALKL SIEDPSHEGE
GIPLYDAIKC MKTFFGWREP NIIKPHEKGI NPNYLLAWKQ VLAELQDIEN EDKIPKTKNM
KKTSQLMWAL GENMAPEKVD FEDCKDIDDL KQYHSDEPEL RSLASWIQNE FNKACELTDS
SWIELDEIGE DVAPIEHIAS MRRNYFTAEV SHCRATEYIM KGVYINTALL NASCAAMDDF
QLIPMISKCR TKEGRRRTNL YGFIVKGRSH LRNDTDVVNF VSMEFSLTDP RLEPHKWEKY
CVLEIGEMLL RTAIGQVSRP MFLYVRTNGT SKIKMKWGME MRRCLLQSLQ QIESMIEAES
SIKEKDMTKE FFENRSETWP IGESPKGVEE GSIGKVCRTL LAKSVFNSLY SSPQLEGFSA
ESRKLLLIVQ ALRDNLEPGT FDLEGLYGAI EECLINDPWV LLNASWFNSF LTHALR
