Function
Processes
Locations
Controls PedR2 phosphorylation according to the lanthanide-responsive physiological input; the direct molecular ligand remains unresolved.
A reusable pseudomonad module coupling PedS2/PedR2 two-component signaling to metal-conditioned periplasmic alcohol oxidation. In the absence of usable lanthanides, phosphorylated PedR2 favors expression of the calcium-dependent PQQ alcohol dehydrogenase PedE. Lanthanide availability shifts the system toward the lanthanide-dependent paralog PedH. Both enzymes oxidize diverse alcohols in the periplasm and pass electrons to cytochrome c. PQQ biosynthesis, downstream aldehyde metabolism, and lanthanide uptake are adjacent systems and are outside this module. The enzymes carry the cytochrome-c alcohol dehydrogenase assignment, but their specific physiological cytochrome c partner in KT2440 remains inferred.
Scope is deliberately pseudomonad (CONCRETE, NCBITaxon:286) rather than generalized to all lanthanide switches. A calcium/lanthanide switch between PQQ dehydrogenases also operates in methylotrophs such as Methylorubrum extorquens (MxaFI versus XoxF methanol dehydrogenases), but that system is an analogous rather than homologous circuit: its enzymes are methanol dehydrogenases of a different PANTHER subfamily (PTHR32303:SF4, cytochrome cL-linked), and its control runs through other regulators (MxbD/MxbM, MxcQ/MxcE) with XoxF itself required for the switch. Merging the two would assert a shared PedS2/PedR2 regulatory architecture that has not been shown outside Pseudomonas. The methylotroph switch is better modeled as a sibling module, and the M. extorquens lanthanide-dependent ethanol dehydrogenase ExaF, although in the same SF20 subfamily as PedE and PedH, is not added as a member because its regulation is not PedS2/PedR2-mediated. P. putida KT2440 proteins are exemplars of the Ped system, not species-specific required members. PANTHER groundings were adopted from the maintainer grounding pass and checked against interpro/panther/panther.obo and the UniProt PANTHER cross-references: PedS2 is PTHR24421 (SF10), PedR2 is PTHR43214 (SF43), and PedE and PedH are both PTHR32303:SF20. Each family id grounds only the generic activity (sensor kinase, response regulator, cytochrome c-linked alcohol dehydrogenase), as recorded in the FamilyReviews; the lanthanide responsiveness of PedS2, the pedE/pedH targets of PedR2, and the metal dependence that separates the PedE and PedH variants are member-level properties supported by PMID:28655819 and PMID:30158283. Because SF20 does not separate the two metal variants, each variant keeps only its own paralog as representative member. The PedS2/PedR2 bundle is a simple two-component instance of MODULE:two_component_relay without the Hpt tier; it declares `conforms_to` that template WITH_DEVIATIONS for the collapsed Hpt step, as the template prescribes and as the Kdp and Ntr modules do. PedH-dependent feedback on pedE/pedH transcription is retained as a knowledge gap rather than assigning PedH a transcription-regulatory molecular function.
All recommended fields populated.
✓ present
✓ every leaf node grounds to a representative protein.
3 conformance issue(s):
4 gene-function check(s) reflected in core functions · 0 conflict(s) · 0 evidence or coverage gap(s) (8 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.
| Annoton | Participant | Function | Assessment |
|---|---|---|---|
| peds2_sensor_kinase | PedS2 (Pseudomonas putida KT2440) UniProtKB:Q88JH8 Family Representative |
phosphorelay sensor kinase activity GO:0000155 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| pedr2_response_regulator | PedR2/ExaE (Pseudomonas putida KT2440) UniProtKB:Q88JH7 Family Representative |
phosphorelay response regulator activity GO:0000156 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| pede_alcohol_dehydrogenase | PedE (Pseudomonas putida KT2440) UniProtKB:Q88JH5 Family Representative |
alcohol dehydrogenase (cytochrome c) activity GO:0052934 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| pedh_alcohol_dehydrogenase | PedH (Pseudomonas putida KT2440) UniProtKB:Q88JH0 Family Representative |
alcohol dehydrogenase (cytochrome c) activity GO:0052934 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| peds2_sensor_kinase | HisKA_3 sensor histidine kinase family (PedS2 member) PANTHER:PTHR24421 Family |
phosphorelay sensor kinase activity GO:0000155 |
Family Supported
Family review supports GO:0000155 FAMILY_WIDE. Every characterized member is a two-component sensor histidine kinase with the HisKA_3 phosphoacceptor and HATPase_c catalytic domains, and characterized members across subfamilies (NarX, NarQ, UhpB, DesK, PedS2) phosphorylate a cognate response regulator. Sensor input and partner regulator are member-specific and are not covered by this assessment. |
| pedr2_response_regulator | NarL/FixJ-type response regulator family (PedR2 member) PANTHER:PTHR43214 Family |
phosphorelay response regulator activity GO:0000156 |
Family Supported
Family review supports GO:0000156 FAMILY_WIDE. All members share the CheY-like receiver domain with the conserved phospho-accepting aspartate (Asp59 in NarL), and characterized members across subfamilies (NarL, NarP, UhpA, RcsB, DegU, PedR2) are regulated by phosphotransfer from a cognate kinase or Hpt. PAINT does not currently assert this term at any node in the family. |
| pede_alcohol_dehydrogenase | calcium-dependent PedE-type quinoprotein ethanol dehydrogenase PANTHER:PTHR32303:SF20 Family |
alcohol dehydrogenase (cytochrome c) activity GO:0052934 |
Family Supported
Family review supports GO:0052934 for PANTHER:PTHR32303:SF20. Cytochrome c-linked oxidation of primary and secondary alcohols is the function of the characterized SF20 type I alcohol dehydrogenases, whether calcium-dependent (PedE, ExaA) or lanthanide-dependent (PedH, ExaF). It is not safe for SF4, whose glucose, quinate and glycerol dehydrogenases reduce ubiquinone and whose methanol dehydrogenases are the distinct cytochrome cL-linked enzymes, nor for SF10 (BamB). The catalytic metal is not determined by subfamily, so this assessment does not license calcium- or lanthanide-specific claims. |
| pedh_alcohol_dehydrogenase | lanthanide-dependent PedH-type quinoprotein ethanol dehydrogenase PANTHER:PTHR32303:SF20 Family |
alcohol dehydrogenase (cytochrome c) activity GO:0052934 |
Family Supported
Family review supports GO:0052934 for PANTHER:PTHR32303:SF20. Cytochrome c-linked oxidation of primary and secondary alcohols is the function of the characterized SF20 type I alcohol dehydrogenases, whether calcium-dependent (PedE, ExaA) or lanthanide-dependent (PedH, ExaF). It is not safe for SF4, whose glucose, quinate and glycerol dehydrogenases reduce ubiquinone and whose methanol dehydrogenases are the distinct cytochrome cL-linked enzymes, nor for SF10 (BamB). The catalytic metal is not determined by subfamily, so this assessment does not license calcium- or lanthanide-specific claims. |
✓ every negative regulator described as feedback has an upstream edge closing the loop.
4 complete review(s) · 4 with deep research · 0 missing review · 0 reviewed but lacking deep research
| Gene | Review | Complete | Deep research |
|---|---|---|---|
| exaE Q88JH7 | ✓ | ✓ | ✓ |
| pedE Q88JH5 | ✓ | ✓ | ✓ |
| pedH Q88JH0 | ✓ | ✓ | ✓ |
| PP_2671 Q88JH8 | ✓ | ✓ | ✓ |
The sensor histidine kinase PedS2 autophosphorylates according to the lanthanide-responsive input and phosphorylates the conserved receiver aspartate of PedR2, which effects the transcriptional switch. This is a simple two-component instance of the MODULE:two_component_relay motif without its histidine-phosphotransfer (Hpt) tier: PedS2 has HAMP, histidine-kinase and HATPase domains but no Hpt or receiver domain, so it transfers phosphate directly to PedR2.
Controls PedR2 phosphorylation according to the lanthanide-responsive physiological input; the direct molecular ligand remains unresolved.
Phosphorylated PedR2 activates pedE expression and contributes to pedH repression when usable lanthanides are absent.
Performs PQQ-dependent alcohol oxidation when calcium is available and the lanthanide switch favors pedE expression.
Performs PQQ-dependent alcohol oxidation when usable lanthanides are available and the switch favors pedH.