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UniProt release 2012_09

Published October 3, 2012

Headline

New discovery for an old virus: PA-X, influenza’s twelfth protein

Influenza A virus (IAV) remains a major cause of human mortality and morbidity due to its remarkable genetic variability which limits vaccine effectiveness. Understanding the determinants of influenza virus molecular biology is a fundamental step for effective control of viral epidemics, and this virus has been the subject of intensive research efforts for more than 60 years. The viral RNA genome was first sequenced in the early 80’s. It comprises eight segments totaling 13.5 kb, that was thought to encode eleven proteins. The eleventh protein PB1-F2 was characterized in 2001. Coinciding with the 30th anniversary of the first segment 3 sequence, Jagger et al. have published in Science the identification of the twelfth protein of influenza A virus. This protein is expressed by an unusual ribosomal frameshifting in the polymerase acidic (PA) protein open reading frame encoded on segment 3. The frameshift product, called PA-X, comprises the endonuclease domain of the viral PA protein with a C-terminal domain encoded by the X-ORF. Its function is to repress cellular gene expression and modulate IAV virulence in a mouse infection model, acting to decrease pathogenicity. It is not surprising to discover a new open reading frame in a small RNA virus 30 years after it was first sequenced, because non-structural viral proteins are often difficult to identify in the midst of host proteins. Moreover, PA-X expression relies on an unusual ribosomal frameshift which could not be predicted. This new finding will allow a better understanding of host-virus interactions and improve the surveillance of new outbreaks.

As of this release, 87 new PA-X entries have been manually annotated in UniProtKB/Swiss-Prot.

UniProtKB news

Changes to keywords

New keywords: Modified keyword:

Changes to the controlled vocabulary for PTMs

New term for the feature key ‘Modified residue’ (‘MOD_RES’ in the flat file):
  • N6-(3,6-diaminohexanoyl)-5-hydroxylysine