Polymerase acidic protein

Details

Name
Polymerase acidic protein
Synonyms
  • 3.1.-.-
  • RNA-directed RNA polymerase subunit P2
Gene Name
PA
Organism
Influenza A virus (strain A/Puerto Rico/8/1934 H1N1)
Amino acid sequence
>lcl|BSEQ0052098|Polymerase acidic protein
MEDFVRQCFNPMIVELAEKTMKEYGEDLKIETNKFAAICTHLEVCFMYSDFHFINEQGES
IIVELGDPNALLKHRFEIIEGRDRTMAWTVVNSICNTTGAEKPKFLPDLYDYKENRFIEI
GVTRREVHIYYLEKANKIKSEKTHIHIFSFTGEEMATKADYTLDEESRARIKTRLFTIRQ
EMASRGLWDSFRQSERGEETIEERFEITGTMRKLADQSLPPNFSSLENFRAYVDGFEPNG
YIEGKLSQMSKEVNARIEPFLKTTPRPLRLPNGPPCSQRSKFLLMDALKLSIEDPSHEGE
GIPLYDAIKCMRTFFGWKEPNVVKPHEKGINPNYLLSWKQVLAELQDIENEEKIPKTKNM
KKTSQLKWALGENMAPEKVDFDDCKDVGDLKQYDSDEPELRSLASWIQNEFNKACELTDS
SWIELDEIGEDVAPIEHIASMRRNYFTSEVSHCRATEYIMKGVYINTALLNASCAAMDDF
QLIPMISKCRTKEGRRKTNLYGFIIKGRSHLRNDTDVVNFVSMEFSLTDPRLEPHKWEKY
CVLEIGDMLIRSAIGQVSRPMFLYVRTNGTSKIKMKWGMEMRRCLLQSLQQIESMIEAES
SVKEKDMTKEFFENKSETWPIGESPKGVEESSIGKVCRTLLAKSVFNSLYASPQLEGFSA
ESRKLLLIVQALRDNLEPGTFDLGGLYEAIEECLINDPWVLLNASWFNSFLTHALS
Number of residues
716
Molecular Weight
82587.575
Theoretical pI
Not Available
GO Classification
Functions
endonuclease activity / metal ion binding / RNA binding
Processes
cap snatching / fusion of virus membrane with host plasma membrane / intracellular transport of virus / receptor-mediated endocytosis of virus by host cell / suppression by virus of host RNA polymerase II activity / transcription, DNA-templated / uncoating of virus / viral budding from plasma membrane / viral genome maturation / viral genome packaging / viral RNA genome replication / viral transcription / virion attachment to host cell
Components
cytosol / endosome lumen / extracellular region / host cell cytoplasm / host cell nucleus / nucleoplasm
General Function
Plays an essential role in viral RNA transcription and replication by forming the heterotrimeric polymerase complex together with PB1 and PB2 subunits. The complex transcribes viral mRNAs by using a unique mechanism called cap-snatching. It consists in the hijacking and cleavage of host capped pre-mRNAs. These short capped RNAs are then used as primers for viral mRNAs. The PB2 subunit is responsible for the binding of the 5' cap of cellular pre-mRNAs which are subsequently cleaved after 10-13 nucleotides by the PA subunit that carries the endonuclease activity.
Specific Function
Endonuclease activity
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Host cytoplasm
Gene sequence
>lcl|BSEQ0052099|Polymerase acidic protein (PA)
ATGGAAGATTTTGTGCGACAATGCTTCAATCCGATGATTGTCGAGCTTGCGGAAAAAACA
ATGAAAGAGTATGGGGAGGACCTGAAAATCGAAACAAACAAATTTGCAGCAATATGCACT
CACTTGGAAGTATGCTTCATGTATTCAGATTTCCACTTCATCAATGAGCAAGGCGAGTCA
ATAATCGTAGAACTTGGTGATCCTAATGCACTTTTGAAGCACAGATTTGAAATAATCGAG
GGAAGAGATCGCACAATGGCCTGGACAGTAGTAAACAGTATTTGCAACACTACAGGGGCT
GAGAAACCAAAGTTTCTACCAGATTTGTATGATTACAAGGAAAATAGATTCATCGAAATT
GGAGTAACAAGGAGAGAAGTTCACATATACTATCTGGAAAAGGCCAATAAAATTAAATCT
GAGAAAACACACATCCACATTTTCTCGTTCACTGGGGAAGAAATGGCCACAAAGGCCGAC
TACACTCTCGATGAAGAAAGCAGGGCTAGGATCAAAACCAGGCTATTCACCATAAGACAA
GAAATGGCCAGCAGAGGCCTCTGGGATTCCTTTCGTCAGTCCGAGAGAGGAGAAGAGACA
ATTGAAGAAAGGTTTGAAATCACAGGAACAATGCGCAAGCTTGCCGACCAAAGTCTCCCG
CCGAACTTCTCCAGCCTTGAAAATTTTAGAGCCTATGTGGATGGATTCGAACCGAACGGC
TACATTGAGGGCAAGCTGTCTCAAATGTCCAAAGAAGTAAATGCTAGAATTGAACCTTTT
TTGAAAACAACACCACGACCACTTAGACTTCCGAATGGGCCTCCCTGTTCTCAGCGGTCC
AAATTCCTGCTGATGGATGCCTTAAAATTAAGCATTGAGGACCCAAGTCATGAAGGAGAG
GGAATACCGCTATATGATGCAATCAAATGCATGAGAACATTCTTTGGATGGAAGGAACCC
AATGTTGTTAAACCACACGAAAAGGGAATAAATCCAAATTATCTTCTGTCATGGAAGCAA
GTACTGGCAGAACTGCAGGACATTGAGAATGAGGAGAAAATTCCAAAGACTAAAAATATG
AAAAAAACAAGTCAGCTAAAGTGGGCACTTGGTGAGAACATGGCACCAGAAAAGGTAGAC
TTTGACGACTGTAAAGATGTAGGTGATTTGAAGCAATATGATAGTGATGAACCAGAATTG
AGGTCGCTTGCAAGTTGGATTCAGAATGAGTTCAACAAGGCATGCGAACTGACAGATTCA
AGCTGGATAGAGCTTGATGAGATTGGAGAAGATGTGGCTCCAATTGAACACATTGCAAGC
ATGAGAAGGAATTATTTCACATCAGAGGTGTCTCACTGCAGAGCCACAGAATACATAATG
AAGGGGGTGTACATCAATACTGCCTTACTTAATGCATCTTGTGCAGCAATGGATGATTTC
CAATTAATTCCAATGATAAGCAAGTGTAGAACTAAGGAGGGAAGGCGAAAGACCAACTTG
TATGGTTTCATCATAAAAGGAAGATCCCACTTAAGGAATGACACCGACGTGGTAAACTTT
GTGAGCATGGAGTTTTCTCTCACTGACCCAAGACTTGAACCACACAAATGGGAGAAGTAC
TGTGTTCTTGAGATAGGAGATATGCTTCTAAGAAGTGCCATAGGCCAGGTTTCAAGGCCC
ATGTTCTTGTATGTGAGGACAAATGGAACCTCAAAAATTAAAATGAAATGGGGAATGGAG
ATGAGGCGTTGTCTCCTCCAGTCACTTCAACAAATTGAGAGTATGATTGAAGCTGAGTCC
TCTGTCAAAGAGAAAGACATGACCAAAGAGTTCTTTGAGAACAAATCAGAAACATGGCCC
ATTGGAGAGTCTCCCAAAGGAGTGGAGGAAAGTTCCATTGGGAAGGTCTGCAGGACTTTA
TTAGCAAAGTCGGTATTTAACAGCTTGTATGCATCTCCACAACTAGAAGGATTTTCAGCT
GAATCAAGAAAACTGCTTCTTATCGTTCAGGCTCTTAGGGACAATCTGGAACCTGGGACC
TTTGATCTTGGGGGGCTATATGAAGCAATTGAGGAGTGCCTAATTAATGATCCCTGGGTT
TTGCTTAATGCTTCTTGGTTCAACTCCTTCCTTACACATGCATTGAGTTAG
Chromosome Location
Not Available
Locus
Not Available
External Identifiers
ResourceLink
UniProtKB IDP03433
UniProtKB Entry NamePA_I34A1
General References
  1. Fields S, Winter G: Nucleotide sequences of influenza virus segments 1 and 3 reveal mosaic structure of a small viral RNA segment. Cell. 1982 Feb;28(2):303-13. doi: 10.1016/0092-8674(82)90348-8. [PubMed:7060132]
  2. Schickli JH, Flandorfer A, Nakaya T, Martinez-Sobrido L, Garcia-Sastre A, Palese P: Plasmid-only rescue of influenza A virus vaccine candidates. Philos Trans R Soc Lond B Biol Sci. 2001 Dec 29;356(1416):1965-73. doi: 10.1098/rstb.2001.0979. [PubMed:11779399]
  3. de Wit E, Spronken MI, Bestebroer TM, Rimmelzwaan GF, Osterhaus AD, Fouchier RA: Efficient generation and growth of influenza virus A/PR/8/34 from eight cDNA fragments. Virus Res. 2004 Jul;103(1-2):155-61. doi: 10.1016/j.virusres.2004.02.028. [PubMed:15163504]
  4. Nieto A, de la Luna S, Barcena J, Portela A, Ortin J: Complex structure of the nuclear translocation signal of influenza virus polymerase PA subunit. J Gen Virol. 1994 Jan;75 ( Pt 1):29-36. doi: 10.1099/0022-1317-75-1-29. [PubMed:8113737]
  5. Sanz-Ezquerro JJ, Fernandez Santaren J, Sierra T, Aragon T, Ortega J, Ortin J, Smith GL, Nieto A: The PA influenza virus polymerase subunit is a phosphorylated protein. J Gen Virol. 1998 Mar;79 ( Pt 3):471-8. doi: 10.1099/0022-1317-79-3-471. [PubMed:9519825]
  6. Fodor E, Smith M: The PA subunit is required for efficient nuclear accumulation of the PB1 subunit of the influenza A virus RNA polymerase complex. J Virol. 2004 Sep;78(17):9144-53. doi: 10.1128/JVI.78.17.9144-9153.2004. [PubMed:15308710]
  7. Dias A, Bouvier D, Crepin T, McCarthy AA, Hart DJ, Baudin F, Cusack S, Ruigrok RW: The cap-snatching endonuclease of influenza virus polymerase resides in the PA subunit. Nature. 2009 Apr 16;458(7240):914-8. doi: 10.1038/nature07745. Epub 2009 Feb 4. [PubMed:19194459]
  8. Suzuki T, Ainai A, Nagata N, Sata T, Sawa H, Hasegawa H: A novel function of the N-terminal domain of PA in assembly of influenza A virus RNA polymerase. Biochem Biophys Res Commun. 2011 Nov 4;414(4):719-26. doi: 10.1016/j.bbrc.2011.09.142. Epub 2011 Oct 6. [PubMed:22001919]
  9. Obayashi E, Yoshida H, Kawai F, Shibayama N, Kawaguchi A, Nagata K, Tame JR, Park SY: The structural basis for an essential subunit interaction in influenza virus RNA polymerase. Nature. 2008 Aug 28;454(7208):1127-31. doi: 10.1038/nature07225. Epub 2008 Jul 27. [PubMed:18660801]
  10. Fudo S, Yamamoto N, Nukaga M, Odagiri T, Tashiro M, Neya S, Hoshino T: Structural and computational study on inhibitory compounds for endonuclease activity of influenza virus polymerase. Bioorg Med Chem. 2015 Sep 1;23(17):5466-75. doi: 10.1016/j.bmc.2015.07.046. Epub 2015 Jul 29. [PubMed:26252962]
  11. Fudo S, Yamamoto N, Nukaga M, Odagiri T, Tashiro M, Hoshino T: Two Distinctive Binding Modes of Endonuclease Inhibitors to the N-Terminal Region of Influenza Virus Polymerase Acidic Subunit. Biochemistry. 2016 May 10;55(18):2646-60. doi: 10.1021/acs.biochem.5b01087. Epub 2016 Apr 26. [PubMed:27088785]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB13997Baloxavir marboxilapproved, investigationalunknowninhibitorDetails