PROSITE documentation PDOC00439

P-II protein family signatures and profile

P-II family proteins are regulators of nitrogen metabolism, with a length of ~110 amino acid residues, found throughout the bacteria and most archaea. P-II proteins sense cellular 2-oxoglutarate as an indicator for nitrogen limitation and bind and respond to ATP. The family is named after the P-II protein (gene glnB), a bacterial protein important for the control of glutamine synthetase [1,2,3]. In nitrogen-limiting conditions, when the ratio of glutamine to 2-ketoglutarate decreases, P-II is uridylylated on a tyrosine residue to form P-II-UMP. P-II-UMP allows the deadenylation of glutamine synthetase (GS), thus activating the enzyme. Conversely, in nitrogen excess, P-II-UMP is deuridylated and then promotes the adenylation of GS. P-II also indirectly controls the transcription of the GS gene (glnA) by preventing NR-II (ntrB) to phosphorylate NR-I (ntrC) which is the transcriptional activator of glnA. Once P-II is uridylylated, these events are reversed. The tyrosine which is uridylated is located in the T-loop in the central part of the protein.

Not all P-II family proteins have this site for sensing cellular glutamine [4]. In cyanobacteria, P-II seems to be phosphorylated on a serine residue rather than being uridylated. It has a different set of interacting proteins.

In methanogenic archaebacteria, the nitrogenase iron protein gene (nifH) is followed by two open reading frames highly similar to the eubacterial P-II protein [5]. These proteins could be involved in the regulation of nitrogen fixation.

In the red alga, Porphyra purpurea, there is a glnB homolog encoded in the chloroplast genome.

Other proteins highly similar to glnB are:

• Bacillus subtilis protein nrgB [6].
• Escherichia coli glnK [7].
• Plant P-II protein, which is localized to the chloroplast [8].

We developed two signature patterns for P-II protein. The first one is a conserved stretch (in eubacteria) of six residues which contains the uridylated tyrosine, the other is derived from a conserved region in the C-terminal part of the P-II protein. We also developed a profile that covers the whole P-II protein.