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214  structures 5324  species 0  interactions 10611  sequences 15  architectures

Family: P-II (PF00543)

Summary: Nitrogen regulatory protein P-II

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This is the Wikipedia entry entitled "Pii nitrogen regulatory proteins". More...

Pii nitrogen regulatory proteins Edit Wikipedia article

Nitrogen regulatory protein P-II
GlnB protein from E.coli. PDB 2pii[1] The GlnB protein in E. coli is 68% identical to GlnK.
Pfam clanCL0089

The PII family comprises a group of widely distributed signal transduction proteins found in nearly all Bacteria and also present in Archaea and in the chloroplasts of Algae and plants.[2] PII form barrel-like homotrimers with a flexible loop, namely T-loop, emerging from each subunit.[2]  PII proteins have extraordinary sensory properties; they can exist in a vast range of structural status accordingly to the levels of ATP, ADP and 2-oxogluratate.  These metabolites interact allosterically with PII in three conserved binding sites located in the lateral cavity between each PII subunit. ATP and ADP bind competitively to the nucleotide binding whereas the 2-oxoglutarate only interacts with PII in the presence of MgATP.[3]

In Proteobacteria, PII proteins are also subject to a cycle of reversible posttranslational modification (Huergo et al., 2013). Under a low nitrogen regime, the low intracellular glutamine level triggers the uridylyl-transferase activity of the bi-functional GlnD enzyme promoting the uridylylation of a conserved Tyr-51 located at the top the PII T-loop. Conversely, under a high nitrogen regime, accumulation of intracellular glutamine triggers the uridylyl-removing activity of GlnD and PII accumulate in its non-modified form (Huergo et al., 2013).

The ability of PII to sense important metabolites and integrate signals deriving from energy status (ATP and ADP ratio), carbon (2-oxogluratate) and nitrogen (glutamine and 2-oxoglutarate) levels were capitalized during evolution such that PII can act as a dissociable regulatory subunit of a range of transporters, transcriptional regulators and enzymes.[4]


PII proteins exist in trimers in vivo and bind ATP in a cleft between the subunits. There are two flexible loops call the B-loop and T-loop which are involved in regulation of the protein. The T-loop contains a conserved tyrosine which is the site of uridyl attachment.

Regulation of bacterial glutamine synthase (GlnA) by uridylylation of Pii proteins. Uridylyltransferase (GlnD) uridylylates the regulatory PII protein (GlnB) which determines whether adenylyltransferase (GlnE) adenylylates or deadenylylates glutamine synthase. The protein names are those in E. coli. Homologs in other bacteria may have different names.

Role in nitrogen metabolism

Following nitrogen starvation, increased intra-cellular concentrations of ammonia cause the de-uridylylation of GlnK. This then binds directly to the ammonia channel AmtB to block ammonia conduction.[5][6] PII proteins such as SbtB are also implicated in carbon metabolism regulation, these proteins are able to control the activity of Acetyl-CoA carboxylase in plants, algae and Bacteria [7]


  1. ^ Carr PD, Cheah E, Suffolk PM, Vasudevan SG, Dixon NE, Ollis DL (January 1996). "X-ray structure of the signal transduction protein from Escherichia coli at 1.9 A". Acta Crystallographica Section D. 52 (Pt 1): 93–104. doi:10.1107/S0907444995007293. PMID 15299730.
  2. ^ a b Huergo LF, Chandra G, Merrick M (March 2013). "P(II) signal transduction proteins: nitrogen regulation and beyond". FEMS Microbiology Reviews. 37 (2): 251–83. doi:10.1111/j.1574-6976.2012.00351.x. PMID 22861350.
  3. ^ Huergo LF, Pedrosa FO, Muller-Santos M, Chubatsu LS, Monteiro RA, Merrick M, Souza EM (January 2012). "PII signal transduction proteins: pivotal players in post-translational control of nitrogenase activity". Microbiology. 158 (Pt 1): 176–90. doi:10.1099/mic.0.049783-0. PMID 22210804.
  4. ^ Huergo LF, Dixon R (December 2015). "The Emergence of 2-Oxoglutarate as a Master Regulator Metabolite". Microbiology and Molecular Biology Reviews. 79 (4): 419–35. doi:10.1128/MMBR.00038-15. PMC 4651028. PMID 26424716.
  5. ^ Durand A, Merrick M (October 2006). "In vitro analysis of the Escherichia coli AmtB-GlnK complex reveals a stoichiometric interaction and sensitivity to ATP and 2-oxoglutarate". The Journal of Biological Chemistry. 281 (40): 29558–67. doi:10.1074/jbc.M602477200. PMID 16864585.
  6. ^ Conroy MJ, Durand A, Lupo D, Li XD, Bullough PA, Winkler FK, Merrick M (January 2007). "The crystal structure of the Escherichia coli AmtB-GlnK complex reveals how GlnK regulates the ammonia channel". Proceedings of the National Academy of Sciences of the United States of America. 104 (4): 1213–8. doi:10.1073/pnas.0610348104. PMC 1783118. PMID 17220269.
  7. ^ Gerhardt EC, Rodrigues TE, Müller-Santos M, Pedrosa FO, Souza EM, Forchhammer K, Huergo LF (March 2015). "The bacterial signal transduction protein GlnB regulates the committed step in fatty acid biosynthesis by acting as a dissociable regulatory subunit of acetyl-CoA carboxylase". Molecular Microbiology. 95 (6): 1025–35. doi:10.1111/mmi.12912. PMID 25557370.

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Nitrogen regulatory protein P-II Provide feedback

P-II modulates the activity of glutamine synthetase.

Literature references

  1. Cheah E, Carr PD, Suffolk PM, Vasudevan SG, Dixon NE, Ollis DL; , Structure 1994;2:981-990.: Structure of the Escherichia coli signal transducing protein P-II. PUBMED:7866749 EPMC:7866749

Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR002187

In Gram-negative bacteria, the activity and concentration of glutamine synthetase (GS) is regulated in response to nitrogen source availability. PII, a tetrameric protein encoded by the glnB gene, is a component of the adenylation cascade involved in the regulation of GS activity [ PUBMED:1702507 ]. 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 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.

P-II is a protein of about 110 amino acid residues extremely well conserved. The tyrosine which is uridylated is located in the central part of the protein. In cyanobacteria, P-II seems to be phosphorylated on a serine residue rather than being uridylated. In methanogenic archaebacteria, the nitrogenase iron protein gene (nifH) is followed by two open reading frames highly similar to the eubacterial P-II protein [ PUBMED:2068380 ]. These proteins could be involved in the regulation of nitrogen fixation. In the red alga, Porphyra purpurea, there is a glnB homologue encoded in the chloroplast genome.

Other proteins highly similar to glnB are:

Gene Ontology

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Domain organisation

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Pfam Clan

This family is a member of clan GlnB-like (CL0089), which has the following description:

The members of this clan are characterised by the fact the domains, each comprised of four beta-strand and two alpha helices, tend to form tetrameric structures [1].

The clan contains the following 12 members:

CBD_PlyG CdAMP_rec CutA1 DUF190 DUF2007 DUF2179 DUF3240 HisG_C Nit_Regul_Hom NRho P-II Rhomboid_N


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Seed source: SCOP
Previous IDs: none
Type: Domain
Sequence Ontology: SO:0000417
Author: Bateman A
Number in seed: 73
Number in full: 10611
Average length of the domain: 101.60 aa
Average identity of full alignment: 48 %
Average coverage of the sequence by the domain: 76.68 %

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HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 57096847 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 21.4 21.4
Trusted cut-off 21.4 21.4
Noise cut-off 21.3 21.3
Model length: 102
Family (HMM) version: 24
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Species distribution

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Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence


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For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the P-II domain has been found. There are 214 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.

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