PA_I18A0
ID PA_I18A0 Reviewed; 716 AA.
AC Q3HM39;
DT 13-NOV-2007, integrated into UniProtKB/Swiss-Prot.
DT 08-NOV-2005, sequence version 1.
DT 03-AUG-2022, entry version 60.
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/Brevig Mission/1/1918 H1N1) (Influenza A virus
OS (strain A/South Carolina/1/1918 H1N1)).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC Insthoviricetes; Articulavirales; Orthomyxoviridae; Alphainfluenzavirus.
OX NCBI_TaxID=88776;
OH NCBI_TaxID=8782; Aves.
OH NCBI_TaxID=9606; Homo sapiens (Human).
OH NCBI_TaxID=9823; Sus scrofa (Pig).
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=16208372; DOI=10.1038/nature04230;
RA Taubenberger J.K., Reid A.H., Lourens R.M., Wang R., Jin G., Fanning T.G.;
RT "Characterization of the 1918 influenza virus polymerase genes.";
RL Nature 437:889-893(2005).
RN [2]
RP ALTERNATIVE SPLICING (ISOFORM PA-X).
RX PubMed=22745253; DOI=10.1126/science.1222213;
RA Jagger B.W., Wise H.M., Kash J.C., Walters K.A., Wills N.M., Xiao Y.L.,
RA Dunfee R.L., Schwartzman L.M., Ozinsky A., Bell G.L., Dalton R.M., Lo A.,
RA Efstathiou S., Atkins J.F., Firth A.E., Taubenberger J.K., Digard P.;
RT "An overlapping protein-coding region in influenza A virus segment 3
RT modulates the host response.";
RL Science 337:199-204(2012).
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=Q3HM39-1; Sequence=Displayed;
CC Name=PA-X;
CC IsoId=P0CK68-1; 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: South Carolina isolate has been sequenced from formalid
CC fixed-lung tissues of a 21-year-old male which died in 1918 at Ft.
CC Jackson, SC. Brevig Mission isolate has been sequenced from lung
CC tissues of an Inuit woman buried in the permafrost in a gravesite near
CC Brevig Mission, Alaska. This sample was recovered by John Hultin,
CC retired pathologist.
CC -!- SIMILARITY: Belongs to the influenza viruses PA family.
CC {ECO:0000255|HAMAP-Rule:MF_04063}.
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DR EMBL; DQ208311; ABA55040.1; -; mRNA.
DR PDB; 7NHA; EM; 2.91 A; A=1-716.
DR PDB; 7NHC; EM; 2.87 A; A=1-716.
DR PDB; 7NHX; EM; 3.23 A; A=1-716.
DR PDB; 7NI0; EM; 3.32 A; A=1-716.
DR PDB; 7NIK; EM; 6.20 A; A=1-716.
DR PDB; 7NIL; EM; 5.01 A; A=1-716.
DR PDB; 7NIR; EM; 6.70 A; A=1-716.
DR PDB; 7NIS; EM; 5.96 A; A=1-716.
DR PDB; 7NJ3; EM; 4.48 A; A=1-716.
DR PDB; 7NJ4; EM; 5.84 A; A=1-716.
DR PDB; 7NJ5; EM; 4.63 A; A=1-716.
DR PDB; 7NJ7; EM; 4.82 A; A=1-716.
DR PDB; 7NK1; EM; 4.22 A; A=1-716.
DR PDB; 7NK2; EM; 4.84 A; A=1-716.
DR PDB; 7NK4; EM; 5.32 A; A=1-716.
DR PDB; 7NK6; EM; 6.72 A; A=1-716.
DR PDB; 7NK8; EM; 5.34 A; A=1-716.
DR PDB; 7NKA; EM; 4.07 A; A=1-716.
DR PDB; 7NKC; EM; 4.46 A; A=1-716.
DR PDB; 7NKI; EM; 4.67 A; A=1-716.
DR PDB; 7NKR; EM; 5.60 A; A=1-716.
DR PDBsum; 7NHA; -.
DR PDBsum; 7NHC; -.
DR PDBsum; 7NHX; -.
DR PDBsum; 7NI0; -.
DR PDBsum; 7NIK; -.
DR PDBsum; 7NIL; -.
DR PDBsum; 7NIR; -.
DR PDBsum; 7NIS; -.
DR PDBsum; 7NJ3; -.
DR PDBsum; 7NJ4; -.
DR PDBsum; 7NJ5; -.
DR PDBsum; 7NJ7; -.
DR PDBsum; 7NK1; -.
DR PDBsum; 7NK2; -.
DR PDBsum; 7NK4; -.
DR PDBsum; 7NK6; -.
DR PDBsum; 7NK8; -.
DR PDBsum; 7NKA; -.
DR PDBsum; 7NKC; -.
DR PDBsum; 7NKI; -.
DR PDBsum; 7NKR; -.
DR SMR; Q3HM39; -.
DR MEROPS; S62.001; -.
DR Proteomes; UP000008430; 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 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_0000310571"
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 2..8
FT /evidence="ECO:0007829|PDB:7NHC"
FT HELIX 11..24
FT /evidence="ECO:0007829|PDB:7NHC"
FT TURN 28..30
FT /evidence="ECO:0007829|PDB:7NHC"
FT HELIX 32..49
FT /evidence="ECO:0007829|PDB:7NHC"
FT STRAND 56..58
FT /evidence="ECO:0007829|PDB:7NHC"
FT STRAND 68..70
FT /evidence="ECO:0007829|PDB:7NHA"
FT STRAND 75..78
FT /evidence="ECO:0007829|PDB:7NHC"
FT STRAND 80..82
FT /evidence="ECO:0007829|PDB:7NHA"
FT HELIX 84..98
FT /evidence="ECO:0007829|PDB:7NHC"
FT STRAND 108..111
FT /evidence="ECO:0007829|PDB:7NHC"
FT TURN 112..115
FT /evidence="ECO:0007829|PDB:7NHC"
FT STRAND 116..125
FT /evidence="ECO:0007829|PDB:7NHC"
FT HELIX 127..137
FT /evidence="ECO:0007829|PDB:7NHC"
FT STRAND 138..140
FT /evidence="ECO:0007829|PDB:7NHA"
FT STRAND 143..151
FT /evidence="ECO:0007829|PDB:7NHC"
FT STRAND 154..156
FT /evidence="ECO:0007829|PDB:7NHC"
FT HELIX 157..159
FT /evidence="ECO:0007829|PDB:7NHC"
FT HELIX 165..185
FT /evidence="ECO:0007829|PDB:7NHC"
FT HELIX 188..199
FT /evidence="ECO:0007829|PDB:7NHC"
FT HELIX 210..215
FT /evidence="ECO:0007829|PDB:7NHC"
FT HELIX 226..234
FT /evidence="ECO:0007829|PDB:7NHC"
FT HELIX 241..248
FT /evidence="ECO:0007829|PDB:7NHC"
FT STRAND 273..275
FT /evidence="ECO:0007829|PDB:7NHC"
FT STRAND 280..282
FT /evidence="ECO:0007829|PDB:7NHC"
FT STRAND 284..286
FT /evidence="ECO:0007829|PDB:7NHC"
FT STRAND 298..301
FT /evidence="ECO:0007829|PDB:7NHC"
FT HELIX 303..312
FT /evidence="ECO:0007829|PDB:7NHC"
FT STRAND 317..324
FT /evidence="ECO:0007829|PDB:7NHC"
FT STRAND 327..329
FT /evidence="ECO:0007829|PDB:7NHC"
FT HELIX 331..350
FT /evidence="ECO:0007829|PDB:7NHC"
FT STRAND 351..353
FT /evidence="ECO:0007829|PDB:7NHC"
FT STRAND 356..360
FT /evidence="ECO:0007829|PDB:7NHC"
FT HELIX 364..369
FT /evidence="ECO:0007829|PDB:7NHC"
FT STRAND 377..380
FT /evidence="ECO:0007829|PDB:7NHC"
FT TURN 381..383
FT /evidence="ECO:0007829|PDB:7NHC"
FT STRAND 384..386
FT /evidence="ECO:0007829|PDB:7NHC"
FT STRAND 390..392
FT /evidence="ECO:0007829|PDB:7NHX"
FT HELIX 405..414
FT /evidence="ECO:0007829|PDB:7NHC"
FT STRAND 419..421
FT /evidence="ECO:0007829|PDB:7NHC"
FT HELIX 434..451
FT /evidence="ECO:0007829|PDB:7NHC"
FT HELIX 454..475
FT /evidence="ECO:0007829|PDB:7NHC"
FT STRAND 477..491
FT /evidence="ECO:0007829|PDB:7NHC"
FT STRAND 496..506
FT /evidence="ECO:0007829|PDB:7NHC"
FT STRAND 517..526
FT /evidence="ECO:0007829|PDB:7NHC"
FT HELIX 534..537
FT /evidence="ECO:0007829|PDB:7NHC"
FT STRAND 540..548
FT /evidence="ECO:0007829|PDB:7NHC"
FT STRAND 553..556
FT /evidence="ECO:0007829|PDB:7NHC"
FT STRAND 559..571
FT /evidence="ECO:0007829|PDB:7NHC"
FT HELIX 572..578
FT /evidence="ECO:0007829|PDB:7NHC"
FT HELIX 579..582
FT /evidence="ECO:0007829|PDB:7NHC"
FT HELIX 583..602
FT /evidence="ECO:0007829|PDB:7NHC"
FT HELIX 608..613
FT /evidence="ECO:0007829|PDB:7NHC"
FT STRAND 619..624
FT /evidence="ECO:0007829|PDB:7NHC"
FT STRAND 627..631
FT /evidence="ECO:0007829|PDB:7NHC"
FT HELIX 633..649
FT /evidence="ECO:0007829|PDB:7NHC"
FT HELIX 653..673
FT /evidence="ECO:0007829|PDB:7NHC"
FT STRAND 679..681
FT /evidence="ECO:0007829|PDB:7NHC"
FT HELIX 683..691
FT /evidence="ECO:0007829|PDB:7NHC"
FT HELIX 698..713
FT /evidence="ECO:0007829|PDB:7NHC"
SQ SEQUENCE 716 AA; 82599 MW; 21ACA43508075CFE CRC64;
MEDFVRQCFN PMIVELAEKA MKEYGEDLKI ETNKFAAICT HLEVCFMYSD FHFINERGES
IIVESGDPNA LLKHRFEIIE GRDRTMAWTV VNSICNTTGA EKPKFLPDLY DYKENRFIEI
GVTRREVHIY YLEKANKIKS EKTHIHIFSF TGEEMATKAD YTLDEESRAR IKTRLFTIRQ
EMASRGLWDS FRQSERGEET IEERFEITGT MRRLADQSLP PNFSSLENFR AYVDGFEPNG
YIEGKLSQMS KEVNARIEPF LKTTPRPLRL PDGPPCSQRS KFLLMDALKL SIEDPSHEGE
GIPLYDAIKC MRTFFGWKEP NVVKPHEKGI NPNYLLAWKQ VLAELQDIEN EEKIPKTKNM
KKTSQLKWAL GENMAPEKVD FDDCKDVSDL KQYDSDEPEL RSLASWIQSE FNKACELTDS
SWIELDEIGE DVAPIEHIAS MRRNYFTAEV SHCRATEYIM KGVYINTALL NASCAAMDDF
QLIPMISKCR TKEGRRKTNL YGFIIKGRSH LRNDTDVVNF VSMEFSLTDP RLEPHKWEKY
CVLEIGDMLL RSAIGQVSRP MFLYVRTNGT SKIKMKWGME MRRCLLQSLQ QIESMIEAES
SVKEKDMTKE FFENKSETWP IGESPKGVEE GSIGKVCRTL LAKSVFNSLY ASPQLEGFSA
ESRKLLLIVQ ALRDNLEPGT FDLGGLYEAI EECLINDPWV LLNASWFNSF LTHALR
