Bacterial nitrogen-regulatory PTS phosphorelay

A species-neutral proteobacterial signaling module in which enzyme I(Ntr) accepts phosphate from phosphoenolpyruvate, NPr relays it, and EIIA(Ntr) acts as the terminal phosphorylation-state-dependent regulator. Unlike carbohydrate PTS pathways, this module does not transport or phosphorylate a sugar.

MODULE:bacterial_nitrogen_regulatory_ptsCOMPLETECONCRETEBiological Processmodules/bacterial_nitrogen_regulatory_pts.yaml
protein phosphorylationGO:0006468
PMID:23517463
Reciprocal regulation of the autophosphorylation of enzyme INtr by glutamine and α-ketoglutarate in Escherichia coli.
Most proteobacteria carry the PTS(Ntr) paralogous to the sugar PTS; E. coli EI(Ntr) autophosphorylation is reciprocally regulated by glutamine and 2-oxoglutarate through its GAF domain, giving the relay a nitrogen-status input.
PMID:10473571
Enzyme I(Ntr) from Escherichia coli. A novel enzyme of the phosphoenolpyruvate-dependent phosphotransferase system exhibiting strict specificity for its phosphoryl acceptor, NPr.
Purified E. coli EI(Ntr) phosphorylates NPr but not HPr, defining an EI(Ntr)-NPr-IIA(Ntr) chain distinct from the EI-HPr-IIA(sugar) chain.
PMID:17416664
The phosphotransferase system formed by PtsP, PtsO, and PtsN proteins controls production of polyhydroxyalkanoates in Pseudomonas putida
Genetic analysis identifies PtsP, PtsO/NPr, and PtsN as a regulatory phosphotransfer system controlling PHA accumulation in KT2440.
PMID:18296519
Evidence of in vivo cross talk between the nitrogen-related and fructose-related branches of the carbohydrate phosphotransferase system of Pseudomonas putida
In vivo phosphorylation-state analysis establishes the primary flow as PEP to PtsP to PtsO/NPr to PtsN and separates this branch from sugar uptake, while documenting conditional FruB cross-talk.
PMID:26224366
Interplay of the PtsN (EIIA(Ntr)) protein of Pseudomonas putida with its target sensor kinase KdpD
KT2440 PtsN directly interacts with KdpD and controls kdpFABC expression in a phosphorylation-state- and potassium-dependent manner.
PMID:21236318
The interplay of the EIIA(Ntr) component of the nitrogen-related phosphotransferase system (PTS(Ntr)) of Pseudomonas putida with pyruvate dehydrogenase
Non-phosphorylated KT2440 PtsN directly interacts with AceE and inhibits pyruvate dehydrogenase activity.
PMID:19400808
Stimulation of the potassium sensor KdpD kinase activity by interaction with the phosphotransferase protein IIA(Ntr) in Escherichia coli
E. coli EI(Ntr), NPr, and IIA(Ntr) form a regulatory phosphotransfer chain parallel to the carbohydrate-transport PTS, supporting the cross-species module boundary.
PMID:17289841
Escherichia coli enzyme IIANtr regulates the K+ transporter TrkA.
Dephosphorylated E. coli IIA(Ntr) binds TrkA and limits K+ accumulation, a second potassium-homeostasis output of the terminal regulator.
file:PSEPK/ptsP/ptsP-uniprot.txt
PSEPK PtsP UniProt record
Q88CN5 contains GAF, EI(Ntr), and PEP-utilizer domains.
file:PSEPK/ptsH/ptsH-uniprot.txt
PSEPK NPr/PtsH UniProt record
Q88PA2 is the phosphocarrier experimentally assigned as NPr/PtsO between PtsP and PtsN in KT2440.
file:PSEPK/ptsN/ptsN-uniprot.txt
PSEPK PtsN UniProt record
Q88PA0 carries the nitrogen-regulatory EIIA domain.

Scope and generalization: the PTS(Ntr) is a proteobacterial paralogue of the sugar PTS, so the module is written species-neutrally with Pseudomonadota as context and two experimentally characterized exemplars per step, E. coli K-12 (enzymology, KdpD and TrkA outputs) and P. putida KT2440 (in vivo relay order, KdpD and AceE outputs). In the current UniProt record, KT2440 NPr is named ptsH (PP_0948, Q88PA2), whereas the primary literature calls the same functional role ptsO/NPr. FruB can feed phosphate into NPr/PtsN during fructose growth in P. putida, but this experimentally demonstrated cross-talk is an alternative input rather than a required part of the nitrogen-regulatory PTS. The conserved PtsN-KdpD regulatory interaction is represented on the terminal annoton with the sign-neutral protein kinase regulator activity, because E. coli IIA(Ntr) stimulates KdpD while P. putida PtsN represses kdpFABC through KdpD; the Kdp and Trk transport apparatus, PHA control, AceE and LpxD regulation, and other lineage-specific outputs are not required module parts. Family grounding: the entry and terminal steps use the PANTHER subfamilies that contain both exemplars (PTHR46244:SF1 EI(Ntr), PTHR47738:SF1 nitrogen regulatory protein). The NPr step uses PTHR33705:SF2, which contains both NPr exemplars but also canonical sugar-PTS HPr proteins of Firmicutes and other lineages and, within the declared Pseudomonadota context itself, HPr-named proteins of Neisseria, Xylella and Cupriavidus (see the PTHR33705 family review). The id over-selects inside the module's taxon as well as outside it; SF2 therefore records membership of an HPr-domain phosphocarrier, and the NPr role is assigned by pathway context (rpoN-operon ptsO, EI(Ntr) acceptor specificity). The PAINT node PTN002021052 attached to the PtsN family carries the activator term GO:0030295; the PTHR47738 review judges that placement too deep for the activator sign, and the module asserts only the parent regulator activity. Ontology gaps (curation, not biology): GO has no biological-process term for the nitrogen-regulatory PtsP-NPr-PtsN phosphorelay, and GO:0009401 is explicitly the sugar PTS and must not be propagated to this non-transport branch, so the relay is represented with protein phosphorylation and intracellular signal transduction. GO also lacks a specific molecular-function term for the PTS histidyl phosphocarrier step; GO:0016775 (phosphotransferase activity, nitrogenous group as acceptor) is used for NPr.

4Nodes
3Parts
0Variant Sets
0Variants
3Annotons
2Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✗ none found

No MODULE:bacterial_nitrogen_regulatory_pts deep-research report alongside the module YAML.

Leaf nodes lacking representative members

✓ every leaf node grounds to a representative protein.

Template conformance

✓ every declared conforms_to bundle matches its template motif.

Function consistency and core coverage

6 gene-function check(s) reflected in core functions · 0 conflict(s) · 0 evidence or coverage gap(s) (9 comparison(s))

Retained noncore functions are reported separately; they do not require promotion to core functions. Support from representative genes does not establish conservation across the whole family. Missing reviews or identifiers leave a claim unverified.

AnnotonParticipantFunctionAssessment
ptsp_enzyme_i_ntr ptsP (ECOLI)
UniProtKB:P37177
Family Representative 		phosphoenolpyruvate-protein phosphotransferase activity
GO:0008965 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ptsp_enzyme_i_ntr ptsP (PSEPK)
UniProtKB:Q88CN5
Family Representative 		phosphoenolpyruvate-protein phosphotransferase activity
GO:0008965 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
npr_phosphocarrier ptsO (ECOLI)
UniProtKB:P0A9N0
Family Representative 		phosphotransferase activity, nitrogenous group as acceptor
GO:0016775 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
npr_phosphocarrier ptsH (PSEPK)
UniProtKB:Q88PA2
Family Representative 		phosphotransferase activity, nitrogenous group as acceptor
GO:0016775 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ptsn_eiia_ntr ptsN (ECOLI)
UniProtKB:P69829
Family Representative 		protein kinase regulator activity
GO:0019887 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ptsn_eiia_ntr ptsN (PSEPK)
UniProtKB:Q88PA0
Family Representative 		protein kinase regulator activity
GO:0019887 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ptsp_enzyme_i_ntr PtsP enzyme I(Ntr) family
PANTHER:PTHR46244:SF1
Family 		phosphoenolpyruvate-protein phosphotransferase activity
GO:0008965 		Family Supported
Family review supports GO:0008965 FAMILY_WIDE. Enzyme I, EI(Ntr) and the multiphosphoryl transfer proteins all autophosphorylate from PEP on the central-domain histidine and transfer the phosphoryl group to an HPr-like carrier; the activity is shown directly for E. coli enzyme I and EI(Ntr) and in vivo for P. putida PtsP. This supersedes the earlier UNRESOLVED scope from the fused-fructose architecture audit, which found the activity independently supported for standalone PtsI, regulatory PtsP and the fused FruB exemplars but had not adjudicated the descendant set; the root PAINT node PTN000532509 is assessed SOUND here. The grant establishes only PEP-dependent entry chemistry, not fusion, fructose specificity or an internal EIIA relay.
npr_phosphocarrier nitrogen-regulatory NPr phosphocarrier family
PANTHER:PTHR33705:SF2
Family 		phosphotransferase activity, nitrogenous group as acceptor
GO:0016775 		Family Supported
Family review supports GO:0016775 for PANTHER:PTHR33705:SF2. HPr and NPr accept a phosphoryl group on their active-site histidine and donate it to the histidine of an EIIA domain (a nitrogenous acceptor). This is shown for E. coli NPr and P. putida NPr and is the textbook HPr reaction; it is granted to SF1 (HPr) and SF2 (HPr and NPr). The Crh subfamily SF5 was not assessed and is excluded.
ptsn_eiia_ntr nitrogen-regulatory EIIA family
PANTHER:PTHR47738:SF1
Family 		protein kinase regulator activity
GO:0019887 		Family Supported
Family review supports GO:0019887 for PANTHER:PTHR47738:SF1. Direct binding and regulation of the KdpD sensor kinase is shown for E. coli IIA(Ntr) (stimulation) and P. putida PtsN (repression of kdpFABC through KdpD), both SF1. The sugar EIIA subfamilies SF2 and SF4 have no such role.

Gene-review completeness (6/6 grounded genes reviewed)

6 complete review(s) · 1 with deep research · 0 missing review · 5 reviewed but lacking deep research

Gene Review Complete Deep research
ptsH Q88PA2 ✓ ✓ ✗
ptsN P69829 ✓ ✓ ✗
ptsN Q88PA0 ✓ ✓ ✓
ptsO P0A9N0 ✓ ✓ ✗
ptsP P37177 ✓ ✓ ✗
ptsP Q88CN5 ✓ ✓ ✗

Details

Context
PseudomonadotaNCBITaxon:1224
Bacterial nitrogen-regulatory PTS phosphorelayBiological Processbacterial_nitrogen_regulatory_pts
protein phosphorylationGO:0006468
Context
PseudomonadotaNCBITaxon:1224

Connections

Part 1: PEP-dependent phosphorylation entry
PtsP enzyme I(Ntr) phosphate entryReactionptsp_phosphate_entry

PtsP accepts phosphate from phosphoenolpyruvate on its EI histidine and transfers it to the NPr phosphocarrier.

Annotons

PtsP enzyme I(Ntr)
ptsp_enzyme_i_ntr
Participant: Family: PtsP enzyme I(Ntr) family
Family:
PtsP enzyme I(Ntr) familyPANTHER:PTHR46244:SF1
Representative Members: ptsP (ECOLI)UniProtKB:P37177 ptsP (PSEPK)UniProtKB:Q88CN5

Function

phosphoenolpyruvate-protein phosphotransferase activityGO:0008965

Entry enzyme that couples PEP dephosphorylation to phosphorylation of the soluble NPr carrier; its GAF domain receives nitrogen-status signals (glutamine and 2-oxoglutarate in E. coli).

Part 2: NPr phosphocarrier relay
NPr phosphocarrier relayReactionnpr_phosphocarrier_relay

NPr receives phosphate from PtsP and transfers it to EIIA(Ntr).

Annotons

NPr phosphocarrier
npr_phosphocarrier
Participant: Family: nitrogen-regulatory NPr phosphocarrier family
Family:
nitrogen-regulatory NPr phosphocarrier familyPANTHER:PTHR33705:SF2 NPr proteins assigned by pathway context to the carrier step between EI(Ntr) and EIIA(Ntr). Grounded to PTHR33705:SF2, the subfamily that contains both exemplars; SF2 also includes canonical carbohydrate-PTS HPr proteins, so the family id records HPr-domain membership, not the NPr role.
Representative Members: ptsO (ECOLI)UniProtKB:P0A9N0 ptsH (PSEPK)UniProtKB:Q88PA2

Function

phosphotransferase activity, nitrogenous group as acceptorGO:0016775

Soluble intermediate carrier between PtsP and PtsN, carrying the phosphoryl group on its active-site histidine and donating it to the EIIA(Ntr) histidine; GO:0016775 is used because GO lacks a specific PTS phosphocarrier molecular-function term.

Part 3: Terminal EIIA(Ntr) phosphorylation-state regulator
PtsN EIIA(Ntr) terminal regulatorReactionptsn_terminal_regulator

PtsN receives phosphate from NPr; its phosphorylation state controls interactions with downstream metabolic and transport targets.

Annotons

PtsN EIIA(Ntr)
ptsn_eiia_ntr
Participant: Family: nitrogen-regulatory EIIA family
Family:
nitrogen-regulatory EIIA familyPANTHER:PTHR47738:SF1
Representative Members: ptsN (ECOLI)UniProtKB:P69829 ptsN (PSEPK)UniProtKB:Q88PA0

Function

protein kinase regulator activityGO:0019887

Processes

intracellular signal transductionGO:0035556 regulation of potassium ion transmembrane transportGO:1901379

Terminal phosphorelay component and phosphorylation-state-dependent regulatory effector. KdpD regulation is supported in both P. putida and E. coli, although the direction differs; TrkA inhibition (E. coli), AceE inhibition and PHA outputs (P. putida) remain lineage-specific extensions of the conserved relay.