Polymerase acidic protein

UniProt P03433 Organism Influenza A virus (strain A/Puerto Rico/8/1934 H1N1) Gene PA EC 3.1.-.-

Also known as: PA

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.

Classification

Family (Pfam): PF00603 Flu_PA
InterPro: INFV_PA, PA/PA-X, PA/PA-X_sf
Functional cluster: Viral Structural & Replication Proteins

Experimental structures · PDB · 11

2ZNL X-ray 2.30A
4YYL X-ray 1.91A
4ZHZ X-ray 2.50A
4ZI0 X-ray 1.80A
4ZQQ X-ray 1.80A
5FDD X-ray 2.51A
5FDG X-ray 2.10A
5I13 X-ray 2.15A
5JHT X-ray 1.75A
5JHV X-ray 2.75A
7XGC X-ray 1.60A

A predicted model is available from AlphaFold.

Gene Ontology · 13

Drugs targeting this protein · 3

FAVIPIRAVIR inhibitor
BALOXAVIR inhibitor
BALOXAVIR MARBOXIL inhibitor

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Polymerase acidic protein 2 shared papers
RNA-directed RNA polymerase catalytic subunit 4 shared papers
PB2-S1 3 shared papers
Protein PA-X 3 shared papers
Polymerase basic protein 2 4 shared papers
Hemagglutinin 2 shared papers
Nucleoprotein 2 shared papers
Neuraminidase 2 shared papers
Nuclear export protein 2 shared papers
Matrix protein 2 2 shared papers
Non-structural protein 1 2 shared papers
Matrix protein 1 2 shared papers

Literature · 11 cited papers

Comparative influenza protein interactomes identify the role of plakophilin 2 in virus restriction. Nat. Commun. · 2017
Two distinctive binding modes of endonuclease inhibitors to the N-terminal region of Influenza virus polymerase acidic subunit. Biochemistry · 2016
Structural and computational study on inhibitory compounds for endonuclease activity of influenza virus polymerase. Bioorg. Med. Chem. · 2015
A novel function of the N-terminal domain of PA in assembly of influenza A virus RNA polymerase. Biochem. Biophys. Res. Commun. · 2011
The cap-snatching endonuclease of influenza virus polymerase resides in the PA subunit. Nature · 2009
The structural basis for an essential subunit interaction in influenza virus RNA polymerase. Nature · 2008
Efficient generation and growth of influenza virus A/PR/8/34 from eight cDNA fragments. Virus Res. · 2004
Plasmid-only rescue of influenza A virus vaccine candidates. Philos. Trans. R. Soc. Lond., B, Biol. Sci. · 2001
The PA influenza virus polymerase subunit is a phosphorylated protein. J. Gen. Virol. · 1998
Complex structure of the nuclear translocation signal of influenza virus polymerase PA subunit. J. Gen. Virol. · 1994
Nucleotide sequences of influenza virus segments 1 and 3 reveal mosaic structure of a small viral RNA segment. Cell · 1982

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