cheA

UniProt ID: Q88EW4
Organism: Pseudomonas putida (strain ATCC 47054 / DSM 6125 / CFBP 8728 / NCIMB 11950 / KT2440)
Review Status: DRAFT
Aliases:
PP_4338 cheA2
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Gene Description

cheA encodes the chemotaxis histidine kinase CheA of Pseudomonas putida KT2440. The protein is a 747 aa phosphorelay kinase with an N-terminal HPt domain, a central histidine kinase ATPase/dimerization region, and a C-terminal CheW-like domain. In KT2440 literature this locus corresponds to PP_4338/cheA2, the CheA paralog assigned to the canonical chemotaxis pathway rather than the Wsp-like c-di-GMP signaling branch. Its core role is to relay chemoreceptor input by autophosphorylating on histidine and transferring phosphate to response regulators such as CheY and CheB, thereby controlling chemotaxis.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0000155 phosphorelay sensor kinase activity
IEA
GO_REF:0000120
MARK AS OVER ANNOTATED
Summary: This annotation captures the general CheA-like phosphorelay kinase role, but it is broader than the more specific child term GO:0004673 protein histidine kinase activity, which is also already present for this gene.
Reason: Retaining the broader phosphorelay sensor kinase term adds little beyond the specific protein histidine kinase annotation and obscures the more informative catalytic term.
Supporting Evidence:
file:PSEPK/cheA/cheA-deep-research-falcon.md
GO:0000155 is broader than GO:0004673 and becomes redundant when the child protein histidine kinase term is already present.
GO:0004673 protein histidine kinase activity
IEA
GO_REF:0000120
ACCEPT
Summary: This is the best existing molecular-function term for cheA. UniProt assigns the canonical CheA chemistry: ATP-dependent autophosphorylation on histidine followed by phosphotransfer to downstream response regulators.
Reason: Protein histidine kinase activity precisely captures the catalytic role of CheA in the chemotaxis phosphorelay and is supported by conserved domain architecture, phosphohistidine annotation, and the established CheA reaction.
Supporting Evidence:
UniProt:Q88EW4
CheA is autophosphorylated; it can transfer its phosphate group to either CheB or CheY.
UniProt:Q88EW4
-!- CATALYTIC ACTIVITY: Reaction=ATP + protein L-histidine = ADP + protein N-phospho-L- histidine.; EC=2.7.13.3;
file:PSEPK/cheA/cheA-deep-research-falcon.md
CheA is the central histidine kinase of the canonical chemotaxis phosphorelay in KT2440.
GO:0016772 transferase activity, transferring phosphorus-containing groups
IEA
GO_REF:0000002
MARK AS OVER ANNOTATED
Summary: This annotation is technically true for a histidine kinase, but it is a very broad parent term that adds no information beyond GO:0004673.
Reason: The broader transferase term is redundant once the specific protein histidine kinase activity is retained.
Supporting Evidence:
file:PSEPK/cheA/cheA-deep-research-falcon.md
GO:0016772 is a very broad parent term and does not add useful specificity beyond protein histidine kinase activity.
GO:0000160 phosphorelay signal transduction system
IEA
GO_REF:0000002
ACCEPT
Summary: This is an appropriate core biological-process term for cheA because the protein is the autophosphorylating histidine kinase that relays sensory input to CheY/CheB response regulators.
Reason: The phosphorelay system is the direct mechanistic context of CheA function, and this term is specific enough to retain as a core process annotation.
Supporting Evidence:
UniProt:Q88EW4
CheA is autophosphorylated; it can transfer its phosphate group to either CheB or CheY.
file:PSEPK/cheA/cheA-deep-research-falcon.md
CheA is the central histidine kinase of the canonical chemotaxis phosphorelay in KT2440.
GO:0006935 chemotaxis
IEA
GO_REF:0000002
ACCEPT
Summary: Chemotaxis is a core process annotation for this locus. The strongest species-specific evidence in KT2440 shows that PP_4338/cheA2 is required for chemotaxis toward maize root exudates.
Reason: The KT2440 cheA2 mutant phenotype directly connects this paralog to the canonical chemotaxis pathway rather than only to generic signaling.
Supporting Evidence:
DOI:10.3389/fmicb.2019.00078
a cheA2 mutant was entirely deficient in MRE chemotaxis
file:PSEPK/cheA/cheA-deep-research-falcon.md
PP_4338/Q88EW4 is the CheA paralog for the flagellar chemotaxis pathway rather than the Wsp-like surface signaling pathway.
GO:0007165 signal transduction
IEA
GO_REF:0000002
MARK AS OVER ANNOTATED
Summary: This term is true but too broad. CheA participates specifically in phosphorelay signaling for chemotaxis, which is already captured by more informative child terms.
Reason: GO:0007165 is a very high-level parent of the more informative phosphorelay and chemotaxis terms already present for this gene.
Supporting Evidence:
file:PSEPK/cheA/cheA-deep-research-falcon.md
GO:0007165 is a broad parent term and does not add useful specificity once phosphorelay signal transduction system and chemotaxis are retained.
GO:0005737 cytoplasm
IEA
GO_REF:0000002
KEEP AS NON CORE
Summary: Cytoplasm is acceptable as a broad localization because CheA is a soluble signaling kinase rather than a transmembrane receptor. However, this term does not capture the membrane-proximal chemosensory array context in which the protein actually operates.
Reason: The annotation is not wrong, but it is too generic to represent the most informative localization context for the chemotaxis machinery.
Supporting Evidence:
UniProt:Q88EW4
GO; GO:0005737; C:cytoplasm; IEA:InterPro
file:PSEPK/cheA/cheA-deep-research-falcon.md
The safest curation decision is to keep cytoplasm as a non-core location rather than assert a more specific cell-pole or membrane-complex term.

Core Functions

CheA is the chemotaxis histidine kinase of the KT2440 chemosensory phosphorelay. It autophosphorylates on histidine and transfers phosphate to downstream response regulators such as CheY and CheB to couple chemoreceptor input to chemotactic behavior.

Supporting Evidence:
  • UniProt:Q88EW4
    Involved in the transmission of sensory signals from the chemoreceptors to the flagellar motors.
  • UniProt:Q88EW4
    CheA is autophosphorylated; it can transfer its phosphate group to either CheB or CheY.
  • DOI:10.3389/fmicb.2019.00078
    a cheA2 mutant was entirely deficient in MRE chemotaxis

References

Gene Ontology annotation through association of InterPro records with GO terms
  • InterPro mappings recover the broad conserved chemotaxis and phosphorelay context for CheA-family histidine kinases, but they also seed very broad parent terms that should be reviewed for redundancy.
Combined Automated Annotation using Multiple IEA Methods
  • Combined automated methods recover the kinase activity of CheA, but the broader phosphorelay sensor kinase term is less specific than protein histidine kinase activity for this gene.
UniProt:Q88EW4
UniProt entry Q88EW4 for Pseudomonas putida KT2440 chemotaxis protein CheA
  • UniProt identifies Q88EW4 as chemotaxis protein CheA and states that it is autophosphorylated and can transfer phosphate to CheB or CheY.
    "RecName: Full=Chemotaxis protein CheA...CheA is autophosphorylated; it can transfer its phosphate group to either CheB or CheY."
  • The sequence carries an HPt domain, a histidine kinase region, and a CheW-like domain, with a phosphohistidine annotated at residue 49.
DOI:10.3389/fmicb.2019.00078
Concentration Dependent Effect of Plant Root Exudates on the Chemosensory Systems of Pseudomonas putida KT2440
  • The KT2440 study identifies PP_4338 as cheA2 and reports that a cheA2 mutant is entirely deficient in maize root exudate chemotaxis.
  • The same study separates cheA paralog roles, with cheA1 affecting c-di-GMP and biofilm formation while cheA2 maps to the canonical chemotaxis pathway.
file:PSEPK/cheA/cheA-deep-research-falcon.md
Falcon deep research report for cheA in Pseudomonas putida KT2440
  • Synthesizes KT2440 cheA2 literature, conserved CheA domain architecture, and recent chemosensory-system reviews into a curation-focused assessment of core versus over-broad GO terms.

Suggested Questions for Experts

Q: Which KT2440 response regulators are the dominant in vivo phospho-acceptors for PP_4338/CheA during chemotaxis under rhizosphere conditions?

Suggested experts: Tino Krell, Miguel A Matilla, Jose A Reyes-Darias

Q: How are signaling duties partitioned among the three KT2440 CheA paralogs across defined attractants and surface-associated states?

Suggested experts: Tino Krell, Miguel A Matilla

Q: Does PP_4338 form stable polar chemosensory arrays with specific MCP and CheW partners in KT2440, and how condition-dependent is that assembly?

Suggested experts: Tino Krell

Suggested Experiments

Experiment: Purify PP_4338/CheA and test ATP-dependent autophosphorylation plus phosphotransfer to candidate KT2440 CheY and CheB proteins.

Hypothesis: PP_4338 is the cognate chemotaxis histidine kinase that directly transfers phosphate to the canonical chemotaxis response regulators.

Type: biochemical phosphotransfer assay

Experiment: Compare cheA1, cheA2, and cheA3 single and combinatorial mutants across defined attractants, root-exudate mixtures, motility, and root-colonization assays.

Hypothesis: cheA2 carries the core flagellar chemotaxis pathway, while the other paralogs control distinct surface-sensing or c-di-GMP-linked signaling branches.

Type: comparative mutant phenotyping

Experiment: Tag PP_4338 with a minimally perturbing fluorescent marker and image its localization relative to chemoreceptor arrays during planktonic and rhizosphere-like growth.

Hypothesis: The core chemotaxis CheA paralog forms membrane-proximal polar signaling arrays whose abundance changes with environmental context.

Type: live-cell localization microscopy

📚 Additional Documentation

Deep Research Falcon

(cheA-deep-research-falcon.md)

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gene_id: cheA
gene_symbol: cheA
uniprot_accession: Q88EW4
protein_description: 'RecName: Full=Chemotaxis protein CheA {ECO:0000256|ARBA:ARBA00021495};
EC=2.7.13.3 {ECO:0000256|ARBA:ARBA00012438};'
gene_info: Name=cheA {ECO:0000313|EMBL:AAN69917.1}; OrderedLocusNames=PP_4338 {ECO:0000313|EMBL:AAN69917.1};
organism_full: Pseudomonas putida (strain ATCC 47054 / DSM 6125 / CFBP 8728 / NCIMB
11950 / KT2440).
protein_family: Not specified in UniProt
protein_domains: Bact_Chemotaxis_CheA. (IPR051315); CheA-like_dim. (IPR004105);
CheA-like_homodim_sf. (IPR037006); CheW-like_dom_sf. (IPR036061); CheW-lke_dom.
(IPR002545)
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citation_count: 31


Question

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

BEFORE YOU BEGIN RESEARCH: You MUST verify you are researching the CORRECT gene/protein. Gene symbols can be ambiguous, especially for less well-characterized genes from non-model organisms.

Target Gene/Protein Identity (from UniProt):

  • UniProt Accession: Q88EW4
  • Protein Description: RecName: Full=Chemotaxis protein CheA {ECO:0000256|ARBA:ARBA00021495}; EC=2.7.13.3 {ECO:0000256|ARBA:ARBA00012438};
  • Gene Information: Name=cheA {ECO:0000313|EMBL:AAN69917.1}; OrderedLocusNames=PP_4338 {ECO:0000313|EMBL:AAN69917.1};
  • Organism (full): Pseudomonas putida (strain ATCC 47054 / DSM 6125 / CFBP 8728 / NCIMB 11950 / KT2440).
  • Protein Family: Not specified in UniProt
  • Key Domains: Bact_Chemotaxis_CheA. (IPR051315); CheA-like_dim. (IPR004105); CheA-like_homodim_sf. (IPR037006); CheW-like_dom_sf. (IPR036061); CheW-lke_dom. (IPR002545)

MANDATORY VERIFICATION STEPS:

  1. Check if the gene symbol "cheA" matches the protein description above
  2. Verify the organism is correct: Pseudomonas putida (strain ATCC 47054 / DSM 6125 / CFBP 8728 / NCIMB 11950 / KT2440).
  3. Check if protein family/domains align with what you find in literature
  4. If you find literature for a DIFFERENT gene with the same or similar symbol, STOP

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

DO NOT PROCEED WITH RESEARCH ON A DIFFERENT GENE. Instead:
- State clearly: "The gene symbol 'cheA' is ambiguous or literature is limited for this specific protein"
- Explain what you found (e.g., "Found extensive literature on a different gene with the same symbol in a different organism")
- Describe the protein based ONLY on the UniProt information provided above
- Suggest that the protein function can be inferred from domain/family information

Research Target:

Please provide a comprehensive research report on the gene cheA (gene ID: cheA, UniProt: Q88EW4) in PSEPK.

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Output

Question: You are an expert researcher providing comprehensive, well-cited information.

Provide detailed information focusing on:
1. Key concepts and definitions with current understanding
2. Recent developments and latest research (prioritize 2023-2024 sources)
3. Current applications and real-world implementations
4. Expert opinions and analysis from authoritative sources
5. Relevant statistics and data from recent studies

Format as a comprehensive research report with proper citations. Include URLs and publication dates where available.
Always prioritize recent, authoritative sources and provide specific citations for all major claims.

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

BEFORE YOU BEGIN RESEARCH: You MUST verify you are researching the CORRECT gene/protein. Gene symbols can be ambiguous, especially for less well-characterized genes from non-model organisms.

Target Gene/Protein Identity (from UniProt):

  • UniProt Accession: Q88EW4
  • Protein Description: RecName: Full=Chemotaxis protein CheA {ECO:0000256|ARBA:ARBA00021495}; EC=2.7.13.3 {ECO:0000256|ARBA:ARBA00012438};
  • Gene Information: Name=cheA {ECO:0000313|EMBL:AAN69917.1}; OrderedLocusNames=PP_4338 {ECO:0000313|EMBL:AAN69917.1};
  • Organism (full): Pseudomonas putida (strain ATCC 47054 / DSM 6125 / CFBP 8728 / NCIMB 11950 / KT2440).
  • Protein Family: Not specified in UniProt
  • Key Domains: Bact_Chemotaxis_CheA. (IPR051315); CheA-like_dim. (IPR004105); CheA-like_homodim_sf. (IPR037006); CheW-like_dom_sf. (IPR036061); CheW-lke_dom. (IPR002545)

MANDATORY VERIFICATION STEPS:

  1. Check if the gene symbol "cheA" matches the protein description above
  2. Verify the organism is correct: Pseudomonas putida (strain ATCC 47054 / DSM 6125 / CFBP 8728 / NCIMB 11950 / KT2440).
  3. Check if protein family/domains align with what you find in literature
  4. If you find literature for a DIFFERENT gene with the same or similar symbol, STOP

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

DO NOT PROCEED WITH RESEARCH ON A DIFFERENT GENE. Instead:
- State clearly: "The gene symbol 'cheA' is ambiguous or literature is limited for this specific protein"
- Explain what you found (e.g., "Found extensive literature on a different gene with the same symbol in a different organism")
- Describe the protein based ONLY on the UniProt information provided above
- Suggest that the protein function can be inferred from domain/family information

Research Target:

Please provide a comprehensive research report on the gene cheA (gene ID: cheA, UniProt: Q88EW4) in PSEPK.

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Research report: cheA2 (PP_4338; UniProt Q88EW4) in Pseudomonas putida KT2440

Executive summary (identity verified)

The UniProt accession Q88EW4 corresponds to Chemotaxis protein CheA (EC 2.7.13.3) encoded by cheA with ordered locus name PP_4338 in Pseudomonas putida KT2440; this locus is explicitly identified as cheA2 in KT2440 genetic work, which also distinguishes cheA1 (pp1492) and cheA3 (pp4988) paralogs. (lopezfarfan2019concentrationdependenteffect pages 5-6, lopezfarfan2019concentrationdependenteffect pages 3-5)

In KT2440, CheA2 (PP_4338) functions as the central histidine kinase of the canonical chemotaxis signaling pathway, required for chemotaxis to maize root exudates in quantitative capillary assays. (lopezfarfan2019concentrationdependenteffect pages 1-2, lopezfarfan2019concentrationdependenteffect pages 10-11)

1) Key concepts, definitions, and current understanding

1.1 What CheA is (definition)

CheA is the dimeric histidine kinase at the core of bacterial chemotaxis pathways. It is activated/inhibited by chemoreceptor signaling complexes and initiates a phosphorylation cascade by autophosphorylation and phosphotransfer to response regulators (CheY, CheB). (muok2024unpackingalternativefeatures pages 2-4, vass2023analysisofchew‐like pages 1-3)

1.2 Catalytic reaction and substrate specificity (for Q88EW4)

CheA catalyzes an ATP-dependent autophosphorylation on a conserved histidine in the P1 (Hpt/HPT) domain, driven by the P4 (ATP-binding catalytic) domain, and subsequently transfers the phosphoryl group to response regulators such as CheY (and typically CheB) as part of the chemotaxis two-component-like system. (muok2024unpackingalternativefeatures pages 2-4, vass2023analysisofchew‐like pages 1-3)

Direct biochemical evidence in P. putida shows purified CheA has strong [32P]ATPγP-dependent autophosphorylation and that addition of CheY yields CheY labeling with a reduction in CheA label, consistent with phosphate transfer from CheA to CheY. (he2025coordinatedregulationof pages 3-5)

1.3 Domain architecture (and mapping to UniProt domains)

A canonical CheA comprises five domains (P1–P5):
- P1 (Hpt/HPT): phosphoacceptor histidine-bearing domain
- P2: docking/binding of response regulators (CheY/CheB)
- P3: dimerization domain
- P4 (HATPase_c): ATP-binding/catalytic domain that phosphorylates P1
- P5 (CheW-like): coupling to receptors and CheW for array assembly

These functions and the five-domain model are summarized in authoritative recent reviews and are consistent with UniProt’s CheA-like/CheW-like domain annotations provided in the prompt. (muok2024unpackingalternativefeatures pages 2-4, he2025coordinatedregulationof pages 1-2)

1.4 Pathway role and cellular localization (current understanding)

CheA functions within chemosensory arrays (also called receptor arrays) made of chemoreceptors plus coupling proteins (CheW) and CheA. The core signaling unit (CSU) is commonly defined as one CheA dimer + two CheW + two receptor trimers-of-dimers, which then assemble into larger hexagonal lattices. (muok2024unpackingalternativefeatures pages 2-4)

Although the retrieved KT2440-specific texts did not directly image CheA2 localization, the conserved mechanism implies that KT2440 CheA2 operates at these membrane-proximal/polar chemosensory arrays to integrate receptor inputs and control downstream phosphorylation. (muok2024unpackingalternativefeatures pages 2-4)

2) KT2440-specific functional evidence for cheA2 (PP_4338; Q88EW4)

2.1 KT2440 has three cheA paralogs with distinct roles

In P. putida KT2440, three cheA paralogs are present (cheA1, cheA2, cheA3). Functional analyses support division of labor:
- cheA2 (PP_4338) is required for chemotaxis to maize root exudates (MRE)
- cheA1 aligns with a wsp-like pathway that modulates c-di-GMP/biofilm traits
- cheA3 showed no defect in the specific MRE chemotaxis assay and was described as similar to wild type under those conditions, with broader role unresolved
(lopezfarfan2019concentrationdependenteffect pages 1-2, lopezfarfan2019concentrationdependenteffect pages 10-11)

The key identity mapping—PP_4338 = cheA2—is explicitly stated in the KT2440 mutant construction methods and strain descriptions (including pp4338::km). (lopezfarfan2019concentrationdependenteffect pages 5-6, lopezfarfan2019concentrationdependenteffect pages 3-5)

2.2 Mutant phenotypes directly implicate CheA2 in chemotaxis

In KT2440, a cheA2 mutant was reported to be entirely deficient in MRE chemotaxis, supporting CheA2 as the primary kinase in the chemotaxis (che) pathway for this cue. (lopezfarfan2019concentrationdependenteffect pages 1-2, lopezfarfan2019concentrationdependenteffect pages 10-11)

In the same study, quantitative capillary assays provided CFU counts in the chemotaxis readout (means ± SD; replicated), demonstrating a measurable chemotactic response to MRE, though many effect sizes for genotype comparisons were presented in figures rather than fully tabulated in text. (lopezfarfan2019concentrationdependenteffect pages 11-12)

2.3 Genomic/operon context in KT2440

Transcriptional mapping in a KT2440 motility/chemotaxis region placed cheA in a cheYZA operon, i.e., transcriptional linkage with cheY and cheZ in at least one chemotaxis-associated operon context. This supports a functional module organization typical of chemotaxis systems. (navarro‐aviles2010physiologicalandtranscriptomic pages 1-2)

3) Regulation and cross-talk: recent mechanistic insights from P. putida

A 2025 study identified multiple CheA-interacting proteins and showed that at least two regulators, CsoR (a copper-binding repressor) and PhaD, can inhibit CheA autophosphorylation in vitro in a dose-dependent manner, without acting as ATPases, indicating direct modulation of CheA catalytic activity rather than ATP depletion. (he2025coordinatedregulationof pages 3-5, he2025coordinatedregulationof pages 5-8)

The study also reports a CheA-dependent chemorepellent response to copper and quantifies this behavior using response indices and tracking-based metrics; for example, perturbation of CsoR expression altered a response index (RI) from 0.373 ± 0.021 (vector control) to 0.428 ± 0.015 (pcsoR) and changed center-of-mass displacement (e.g., 21.77 ± 3.60 μm vs 13.85 ± 1.92 μm), illustrating how CheA activity integrates environmental stress sensing into motility behavior. (he2025coordinatedregulationof pages 11-13)

4) Recent developments (2023–2024) relevant to CheA2 annotation

4.1 Structural biology of arrays and CSUs (2023–2024)

Recent authoritative work emphasizes that mechanistic understanding of CheA regulation requires treating CheA as part of a supramolecular array, not an isolated kinase.
- A 2024 Annual Review synthesizes evidence that the CSU architecture (CheA dimer, CheW, and receptor trimers-of-dimers) is the fundamental signaling unit and highlights alternative/expanded architectures across bacteria. (muok2024unpackingalternativefeatures pages 2-4)
- 2023 studies further advanced CSU structural models of native arrays and interactions among CheA domains within these assemblies, helping explain long-range coupling between ligand binding and CheA kinase activity. (tran2023bacterialchemoreceptorsignaling pages 12-15)

These developments support annotation of KT2440 CheA2 as a multi-domain kinase whose activity is controlled by array assembly and receptor state, and whose localization is expected to be array-associated. (muok2024unpackingalternativefeatures pages 2-4, tran2023bacterialchemoreceptorsignaling pages 12-15)

4.2 Diversity of CheA architectures (2023–2024)

Comparative analyses show that although CheA is often described as five-domain, noncanonical architectures (e.g., loss of P2, acquisition of receiver domains, split proteins) are widespread across bacteria, which is important when interpreting paralogs (like cheA1–3) and predicting functional specialization. (berry2023diversityandevolution pages 34-41)

5) Current applications and real-world implementations

5.1 Plant-root colonization (KT2440)

Chemotaxis toward root exudates is a key determinant of rhizosphere performance. In KT2440, signaling through both a chemotaxis-associated pathway (involving cheA2) and a wsp-like pathway (involving cheA1) was reported as important for efficient maize root colonization, indicating that CheA paralogs contribute to ecologically relevant host-association outcomes. (lopezfarfan2019concentrationdependenteffect pages 1-2, lopezfarfan2019concentrationdependenteffect pages 10-11)

5.2 Bioremediation and pollutant degradation (P. putida strain example)

A soil microcosm study on a different P. putida strain (DLL-1) compared mutants and found that a cheA non-chemotaxis mutant (DAK) lost directed chemotaxis and showed reduced in-situ degradation performance for the hydrophobic pesticide methyl parathion (MP) relative to wild type, despite similar degradation in well-mixed liquid. For example, the cheA mutant degraded ~64.3–85.7% of MP in soil microcosms (reported 5-day endpoints), while both wild type and cheA mutant could degrade MP to nondetectable levels in ~18 h in shaken liquid medium, supporting the practical principle that chemotaxis enhances contact with poorly soluble substrates in heterogeneous environments. (guo2009comparisonofinsitu pages 1-2, guo2009comparisonofinsitu pages 4-5)

6) Statistics and data highlights (from available text)

  • KT2440 cheA2 identity: PP_4338 is explicitly designated cheA2 in mutant construction and strain definitions. (lopezfarfan2019concentrationdependenteffect pages 5-6, lopezfarfan2019concentrationdependenteffect pages 3-5)
  • Chemotaxis assay counts (KT2440): capillary assay CFU counts reported around 1960 ± 339 to 2133 ± 280 (means ± SD; biological replicates; triplicate technical replicates), illustrating quantitative chemotaxis readouts used in the KT2440 root-exudate study. (lopezfarfan2019concentrationdependenteffect pages 11-12)
  • Copper chemorepellent response metrics (P. putida): RI values such as 0.428 ± 0.015, 0.373 ± 0.021, and 0.324 ± 0.013, and center-of-mass changes (e.g., 13.85 ± 1.92 μm vs 21.77 ± 3.60 μm) under CsoR perturbation, linking CheA regulation to motility outputs. (he2025coordinatedregulationof pages 11-13)
  • Soil biodegradation endpoints: cheA mutant soil MP degradation ~64.3–85.7% (study endpoints) vs rapid removal in mixed liquid (~18 h). (guo2009comparisonofinsitu pages 1-2, guo2009comparisonofinsitu pages 4-5)

7) Expert synthesis for functional annotation of Q88EW4

CheA2 (PP_4338; Q88EW4) is an ATP-dependent protein histidine kinase that autophosphorylates and transfers phosphoryl groups to chemotaxis response regulators (e.g., CheY), thereby controlling chemotactic motility in P. putida KT2440; genetically, CheA2 is essential for chemotaxis toward maize root exudates. (he2025coordinatedregulationof pages 3-5, lopezfarfan2019concentrationdependenteffect pages 1-2)

Biological process/pathway

Chemotaxis signaling pathway (chemosensory array → CheA2 → CheY/CheB → flagellar motor/adaptation), contributing to environmental navigation and plant-root colonization. (muok2024unpackingalternativefeatures pages 2-4, lopezfarfan2019concentrationdependenteffect pages 1-2)

Cellular component/localization

CheA2 is expected to localize to chemosensory receptor arrays/core signaling units (often polar, membrane-associated supramolecular assemblies) through interactions mediated by its P5/CheW-like region and CheW; this is strongly supported for bacterial chemotaxis systems generally, but direct imaging for KT2440 CheA2 was not captured in the retrieved KT2440-specific sources. (muok2024unpackingalternativefeatures pages 2-4, muok2024unpackingalternativefeatures media cd438e27)

Notes on paralogy (to avoid annotation confusion)

KT2440 encodes three CheA paralogs. Functional attribution for PP_4338/Q88EW4 should be limited to cheA2 (chemotaxis-associated), not cheA1 (wsp-like, c-di-GMP/biofilm) or cheA3 (unclear/condition-dependent). (lopezfarfan2019concentrationdependenteffect pages 1-2, lopezfarfan2019concentrationdependenteffect pages 3-5)

Evidence summary table

Topic Key finding Evidence/assay type Organism/strain Publication (authors/year) URL/DOI Citation context ID
Identity UniProt Q88EW4 matches cheA2 / PP_4338 in Pseudomonas putida KT2440; the 2019 mutant construction paper explicitly states that PP_4338 is cheA2, distinguishing it from cheA1/PP_1492 and cheA3/PP_4988. Targeted mutant construction by homologous recombination; strain table/genetic mapping P. putida KT2440 López-Farfán et al. 2019 https://doi.org/10.3389/fmicb.2019.00078 (lopezfarfan2019concentrationdependenteffect pages 5-6, lopezfarfan2019concentrationdependenteffect pages 3-5)
Reaction CheA is the central chemotaxis histidine kinase that autophosphorylates using ATP and transfers phosphate to CheY; in vitro radiolabel assays showed strong CheA autophosphorylation and CheY labeling with reduced CheA label after CheY addition. Purified-protein phosphotransfer assay with [32P]ATPγP, SDS-PAGE/autoradiography P. putida KT2440 He et al. 2025 https://doi.org/10.7554/elife.100914.2 (he2025coordinatedregulationof pages 3-5, he2025coordinatedregulationof pages 5-8)
Domains CheA has the canonical five-domain architecture (P1–P5): P1/HPT phosphoacceptor, P2 CheY/CheB docking, P3 dimerization, P4 HATPase catalytic ATP-binding domain, P5 CheW-like receptor/CheW interaction domain; this matches UniProt and InterPro annotations for Q88EW4. Domain mapping from reviews and truncation/interactor mapping in P. putida P. putida KT2440; comparative bacterial systems Berry et al. 2024; Muok et al. 2024; He et al. 2025 https://doi.org/10.1128/spectrum.03464-23 ; https://doi.org/10.1146/annurev-micro-032421-110850 ; https://doi.org/10.7554/elife.100914.2 (he2025coordinatedregulationof pages 1-2, he2025coordinatedregulationof pages 5-8, muok2024unpackingalternativefeatures pages 2-4, berry2024diversedomainarchitectures pages 12-13)
Localization By current understanding, CheA localizes to chemosensory receptor arrays/core signaling units at the cell pole or membrane-proximal chemosensory arrays, where one CheA dimer associates with CheW and receptor trimers-of-dimers. Direct localization was not shown specifically for KT2440 PP_4338 in the retrieved KT2440 papers, so localization is inferred from conserved chemosensory architecture. Structural reviews; cryo-ET/core signaling unit model Comparative bacterial systems; inference for KT2440 CheA2 Muok et al. 2024; Cassidy et al. 2023 https://doi.org/10.1146/annurev-micro-032421-110850 ; https://doi.org/10.1128/mbio.00793-23 (muok2024unpackingalternativefeatures media cd438e27, muok2024unpackingalternativefeatures pages 2-4, tran2023bacterialchemoreceptorsignaling pages 12-15)
Pathway context KT2440 encodes three CheA paralogs with distinct pathway roles: cheA1 belongs to a wsp-like signaling cluster affecting c-di-GMP/biofilm, whereas cheA2 (PP_4338) belongs to the che/chemotaxis pathway and is required for maize root exudate chemotaxis; cheA3 remains less clearly assigned. Mutant phenotyping; pathway inference from paralog-specific phenotypes P. putida KT2440 López-Farfán et al. 2019 https://doi.org/10.3389/fmicb.2019.00078 (lopezfarfan2019concentrationdependenteffect pages 1-2, lopezfarfan2019concentrationdependenteffect pages 10-11)
Genomic context A KT2440 motility/chemotaxis region places cheA in a cheYZA operon, indicating transcriptional linkage with cheY and cheZ in at least one chemotaxis-associated cluster. RT-PCR transcriptional organization; transcriptomics P. putida KT2440 Navarro-Avilés & van Dillewijn 2010 https://doi.org/10.1111/j.1758-2229.2009.00084 (navarro‐aviles2010physiologicalandtranscriptomic pages 1-2)
Mutant phenotypes cheA2/PP_4338 mutants abolish chemotaxis to maize root exudates, whereas cheA1 mutants show reduced c-di-GMP, increased swimming, and early biofilm defects; cheA3 is similar to wild type in the tested chemotaxis assay. Quantitative capillary chemotaxis assays, c-di-GMP biosensor, swimming plates, biofilm assays P. putida KT2440 López-Farfán et al. 2019 https://doi.org/10.3389/fmicb.2019.00078 (lopezfarfan2019concentrationdependenteffect pages 1-2, lopezfarfan2019concentrationdependenteffect pages 10-11)
Regulation CsoR and PhaD interact with CheA and inhibit CheA autophosphorylation; interaction mapping implicated the P1, P3, and P4 regions, with P3 contributing strongly. Copper weakens the CsoR–CheA interaction, relieving inhibition and altering chemotaxis behavior. Pull-down/MS, bacterial two-hybrid, BiFC, MST, truncation analysis, autoradiography, semisolid chemotaxis assays P. putida KT2440 He et al. 2025 https://doi.org/10.7554/elife.100914.2 (he2025coordinatedregulationof pages 5-8, he2025coordinatedregulationof pages 3-5, he2025coordinatedregulationof pages 11-13, he2025coordinatedregulationof pages 1-2)
Applications Chemotaxis signaling through CheA-like proteins contributes to root colonization in KT2440 and, in another P. putida strain, cheA-dependent chemotaxis improves in-situ pollutant biodegradation in soil even when degradation kinetics in well-mixed liquid are unchanged. Competitive maize root colonization assays; soil microcosm biodegradation comparisons P. putida KT2440; P. putida DLL-1/DAK López-Farfán et al. 2019; Guo et al. 2009 https://doi.org/10.3389/fmicb.2019.00078 ; https://doi.org/10.1016/j.ibiod.2009.01.008 (lopezfarfan2019concentrationdependenteffect pages 10-11, lopezfarfan2019concentrationdependenteffect pages 11-12, guo2009comparisonofinsitu pages 1-2, guo2009comparisonofinsitu pages 4-5)
Quantitative notes Reported quantitative values include root colonization inoculum starting at 50 ± 3% WT vs mutant, chemotaxis assay counts around 1960 ± 339 to 2133 ± 280 in the cited panel, and copper-repellent response indices such as 0.428 ± 0.015 vs 0.373 ± 0.021 under CsoR perturbation; many KT2440 effect sizes were figure-based rather than fully tabulated in text. Replicated chemotaxis, colonization, and Cu-response measurements with statistics P. putida KT2440 López-Farfán et al. 2019; He et al. 2025 https://doi.org/10.3389/fmicb.2019.00078 ; https://doi.org/10.7554/elife.100914.2 (lopezfarfan2019concentrationdependenteffect pages 11-12, he2025coordinatedregulationof pages 11-13)

Table: This table summarizes organism-specific and comparative evidence supporting the functional annotation of Pseudomonas putida KT2440 CheA2 (PP_4338; UniProt Q88EW4). It highlights identity verification, catalytic activity, domains, pathway assignment, mutant phenotypes, regulatory interactions, and application-relevant phenotypes with traceable context IDs.

Visual evidence: core signaling unit and CheA domains

The following retrieved figure crops illustrate (i) the chemotaxis core signaling unit and (ii) the CheA P1–P5 domain architecture used throughout this report. (muok2024unpackingalternativefeatures media cd438e27, muok2024unpackingalternativefeatures media 770fbb22)

Limitations of this synthesis

Some KT2440 phenotype effect sizes (e.g., exact fold-changes in c-di-GMP fluorescence, swim halo diameters, biofilm biomass, and competitive colonization ratios) were reported primarily in figures/supplements and were not fully extractable from the provided text excerpts; the qualitative genotype-to-function mapping remains strongly supported. (lopezfarfan2019concentrationdependenteffect pages 10-11, lopezfarfan2019concentrationdependenteffect pages 11-12)

References

  1. (lopezfarfan2019concentrationdependenteffect pages 5-6): Diana López-Farfán, José A. Reyes-Darias, Miguel A. Matilla, and Tino Krell. Concentration dependent effect of plant root exudates on the chemosensory systems of pseudomonas putida kt2440. Frontiers in Microbiology, Jan 2019. URL: https://doi.org/10.3389/fmicb.2019.00078, doi:10.3389/fmicb.2019.00078. This article has 76 citations and is from a peer-reviewed journal.

  2. (lopezfarfan2019concentrationdependenteffect pages 3-5): Diana López-Farfán, José A. Reyes-Darias, Miguel A. Matilla, and Tino Krell. Concentration dependent effect of plant root exudates on the chemosensory systems of pseudomonas putida kt2440. Frontiers in Microbiology, Jan 2019. URL: https://doi.org/10.3389/fmicb.2019.00078, doi:10.3389/fmicb.2019.00078. This article has 76 citations and is from a peer-reviewed journal.

  3. (lopezfarfan2019concentrationdependenteffect pages 1-2): Diana López-Farfán, José A. Reyes-Darias, Miguel A. Matilla, and Tino Krell. Concentration dependent effect of plant root exudates on the chemosensory systems of pseudomonas putida kt2440. Frontiers in Microbiology, Jan 2019. URL: https://doi.org/10.3389/fmicb.2019.00078, doi:10.3389/fmicb.2019.00078. This article has 76 citations and is from a peer-reviewed journal.

  4. (lopezfarfan2019concentrationdependenteffect pages 10-11): Diana López-Farfán, José A. Reyes-Darias, Miguel A. Matilla, and Tino Krell. Concentration dependent effect of plant root exudates on the chemosensory systems of pseudomonas putida kt2440. Frontiers in Microbiology, Jan 2019. URL: https://doi.org/10.3389/fmicb.2019.00078, doi:10.3389/fmicb.2019.00078. This article has 76 citations and is from a peer-reviewed journal.

  5. (muok2024unpackingalternativefeatures pages 2-4): A.R. Muok, F.A. Olsthoorn, and A. Briegel. Unpacking alternative features of the bacterial chemotaxis system. Nov 2024. URL: https://doi.org/10.1146/annurev-micro-032421-110850, doi:10.1146/annurev-micro-032421-110850. This article has 6 citations and is from a peer-reviewed journal.

  6. (vass2023analysisofchew‐like pages 1-3): Luke R. Vass, Robert B. Bourret, and Clay A. Foster. Analysis of chew‐like domains provides insights into organization of prokaryotic chemotaxis systems. Oct 2023. URL: https://doi.org/10.1002/prot.26430, doi:10.1002/prot.26430. This article has 11 citations.

  7. (he2025coordinatedregulationof pages 3-5): Meina He, Yongxin Tao, Kexin Mu, Haoqi Feng, Ying Fan, Tong Liu, Qiaoyun Huang, Yujie Xiao, and Wenli Chen. Coordinated regulation of chemotaxis and resistance to copper by csor in pseudomonas putida. Jan 2025. URL: https://doi.org/10.7554/elife.100914.2, doi:10.7554/elife.100914.2. This article has 4 citations.

  8. (he2025coordinatedregulationof pages 1-2): Meina He, Yongxin Tao, Kexin Mu, Haoqi Feng, Ying Fan, Tong Liu, Qiaoyun Huang, Yujie Xiao, and Wenli Chen. Coordinated regulation of chemotaxis and resistance to copper by csor in pseudomonas putida. Jan 2025. URL: https://doi.org/10.7554/elife.100914.2, doi:10.7554/elife.100914.2. This article has 4 citations.

  9. (lopezfarfan2019concentrationdependenteffect pages 11-12): Diana López-Farfán, José A. Reyes-Darias, Miguel A. Matilla, and Tino Krell. Concentration dependent effect of plant root exudates on the chemosensory systems of pseudomonas putida kt2440. Frontiers in Microbiology, Jan 2019. URL: https://doi.org/10.3389/fmicb.2019.00078, doi:10.3389/fmicb.2019.00078. This article has 76 citations and is from a peer-reviewed journal.

  10. (navarro‐aviles2010physiologicalandtranscriptomic pages 1-2): G Navarro‐Avilés and P Van Dillewijn. Physiological and transcriptomic characterization of a flia mutant of pseudomonas putida kt2440. Unknown journal, 2010. URL: https://doi.org/10.1111/j.1758-2229.2009.00084, doi:10.1111/j.1758-2229.2009.00084.

  11. (he2025coordinatedregulationof pages 5-8): Meina He, Yongxin Tao, Kexin Mu, Haoqi Feng, Ying Fan, Tong Liu, Qiaoyun Huang, Yujie Xiao, and Wenli Chen. Coordinated regulation of chemotaxis and resistance to copper by csor in pseudomonas putida. Jan 2025. URL: https://doi.org/10.7554/elife.100914.2, doi:10.7554/elife.100914.2. This article has 4 citations.

  12. (he2025coordinatedregulationof pages 11-13): Meina He, Yongxin Tao, Kexin Mu, Haoqi Feng, Ying Fan, Tong Liu, Qiaoyun Huang, Yujie Xiao, and Wenli Chen. Coordinated regulation of chemotaxis and resistance to copper by csor in pseudomonas putida. Jan 2025. URL: https://doi.org/10.7554/elife.100914.2, doi:10.7554/elife.100914.2. This article has 4 citations.

  13. (tran2023bacterialchemoreceptorsignaling pages 12-15): Thomas Tran, Aruni P. K. K. Karunanayake Mudiyanselage, Stephen J. Eyles, and Lynmarie K. Thompson. Bacterial chemoreceptor signaling complexes control kinase activity by stabilizing the catalytic domain of chea. Proceedings of the National Academy of Sciences of the United States of America, Apr 2023. URL: https://doi.org/10.1101/2022.10.28.514197, doi:10.1101/2022.10.28.514197. This article has 0 citations and is from a highest quality peer-reviewed journal.

  14. (berry2023diversityandevolution pages 34-41): MA Berry. Diversity and evolution of chemosensory systems. Unknown journal, 2023.

  15. (guo2009comparisonofinsitu pages 1-2): Xinqiang Guo, Kai Chen, Yang Wen, Rong Li, Shunpeng Li, and Jiandong Jiang. Comparison of in-situ biodegrading abilities of pseudomonas putida mutants: leub― auxotroph, flic― non-motility, and chea― non-chemotaxis. International Biodeterioration & Biodegradation, 63:576-581, Jul 2009. URL: https://doi.org/10.1016/j.ibiod.2009.01.008, doi:10.1016/j.ibiod.2009.01.008. This article has 8 citations and is from a peer-reviewed journal.

  16. (guo2009comparisonofinsitu pages 4-5): Xinqiang Guo, Kai Chen, Yang Wen, Rong Li, Shunpeng Li, and Jiandong Jiang. Comparison of in-situ biodegrading abilities of pseudomonas putida mutants: leub― auxotroph, flic― non-motility, and chea― non-chemotaxis. International Biodeterioration & Biodegradation, 63:576-581, Jul 2009. URL: https://doi.org/10.1016/j.ibiod.2009.01.008, doi:10.1016/j.ibiod.2009.01.008. This article has 8 citations and is from a peer-reviewed journal.

  17. (muok2024unpackingalternativefeatures media cd438e27): A.R. Muok, F.A. Olsthoorn, and A. Briegel. Unpacking alternative features of the bacterial chemotaxis system. Nov 2024. URL: https://doi.org/10.1146/annurev-micro-032421-110850, doi:10.1146/annurev-micro-032421-110850. This article has 6 citations and is from a peer-reviewed journal.

  18. (berry2024diversedomainarchitectures pages 12-13): Marissa A. Berry, Ekaterina P. Andrianova, and Igor B. Zhulin. Diverse domain architectures of chea histidine kinase, a central component of bacterial and archaeal chemosensory systems. Jan 2024. URL: https://doi.org/10.1128/spectrum.03464-23, doi:10.1128/spectrum.03464-23. This article has 8 citations and is from a domain leading peer-reviewed journal.

  19. (muok2024unpackingalternativefeatures media 770fbb22): A.R. Muok, F.A. Olsthoorn, and A. Briegel. Unpacking alternative features of the bacterial chemotaxis system. Nov 2024. URL: https://doi.org/10.1146/annurev-micro-032421-110850, doi:10.1146/annurev-micro-032421-110850. This article has 6 citations and is from a peer-reviewed journal.

Citations

  1. he2025coordinatedregulationof pages 3-5
  2. muok2024unpackingalternativefeatures pages 2-4
  3. lopezfarfan2019concentrationdependenteffect pages 11-12
  4. he2025coordinatedregulationof pages 11-13
  5. tran2023bacterialchemoreceptorsignaling pages 12-15
  6. berry2023diversityandevolution pages 34-41
  7. lopezfarfan2019concentrationdependenteffect pages 5-6
  8. lopezfarfan2019concentrationdependenteffect pages 3-5
  9. lopezfarfan2019concentrationdependenteffect pages 1-2
  10. lopezfarfan2019concentrationdependenteffect pages 10-11
  11. he2025coordinatedregulationof pages 1-2
  12. he2025coordinatedregulationof pages 5-8
  13. guo2009comparisonofinsitu pages 1-2
  14. guo2009comparisonofinsitu pages 4-5
  15. berry2024diversedomainarchitectures pages 12-13
  16. 32P
  17. https://doi.org/10.3389/fmicb.2019.00078
  18. https://doi.org/10.7554/elife.100914.2
  19. https://doi.org/10.1128/spectrum.03464-23
  20. https://doi.org/10.1146/annurev-micro-032421-110850
  21. https://doi.org/10.1128/mbio.00793-23
  22. https://doi.org/10.1111/j.1758-2229.2009.00084
  23. https://doi.org/10.1016/j.ibiod.2009.01.008
  24. https://doi.org/10.3389/fmicb.2019.00078,
  25. https://doi.org/10.1146/annurev-micro-032421-110850,
  26. https://doi.org/10.1002/prot.26430,
  27. https://doi.org/10.7554/elife.100914.2,
  28. https://doi.org/10.1111/j.1758-2229.2009.00084,
  29. https://doi.org/10.1101/2022.10.28.514197,
  30. https://doi.org/10.1016/j.ibiod.2009.01.008,
  31. https://doi.org/10.1128/spectrum.03464-23,

Notes

(cheA-notes.md)

cheA Notes

  • Q88EW4 is the KT2440 chemotaxis histidine kinase locus PP_4338; the KT2440
    literature calls this paralog cheA2 [UniProt:Q88EW4 "OrderedLocusNames=PP_4338"]
    [DOI:10.3389/fmicb.2019.00078 "PP_4338 (cheA2)"].
  • UniProt gives the canonical CheA mechanism: transmission of receptor input to
    the flagellar pathway through autophosphorylation and phosphotransfer to CheB
    or CheY [UniProt:Q88EW4 "CheA is autophosphorylated; it can transfer its phosphate group to either CheB or CheY."].
  • The conserved phosphohistidine is His49 in the HPt domain, consistent with a
    phosphorelay histidine kinase [UniProt:Q88EW4 "MOD_RES 49 /note=\"Phosphohistidine\""]
    [UniProt:Q88EW4 "DOMAIN 2..106 /note=\"HPt\""].
  • The strongest KT2440 phenotype is in chemotaxis rather than generic signaling:
    Lopez-Farfan et al. report that a cheA2 mutant was entirely deficient in MRE chemotaxis [DOI:10.3389/fmicb.2019.00078 "a cheA2 mutant was entirely deficient in MRE chemotaxis"].
  • The same paper separates paralog function: cheA1 affected c-di-GMP and
    biofilm formation, whereas cheA2 mapped to the classical chemotaxis pathway
    [DOI:10.3389/fmicb.2019.00078 "a mutant in cheA1 showed reduced c-di-GMP levels and impaired biofilm formation"]
    [DOI:10.3389/fmicb.2019.00078 "indicating the existence of homologs of the P. aeruginosa wsp and che (chemotaxis) pathways"].
  • Annotation consequences:
    keep protein histidine kinase activity, phosphorelay signal transduction system, and chemotaxis; demote or remove broader parent terms like
    phosphorelay sensor kinase activity, transferase activity, transferring phosphorus-containing groups, and signal transduction.

📄 View Raw YAML

id: Q88EW4
gene_symbol: cheA
product_type: PROTEIN
aliases:
- PP_4338
- cheA2
status: DRAFT
taxon:
  id: NCBITaxon:160488
  label: Pseudomonas putida (strain ATCC 47054 / DSM 6125 / CFBP 8728 / NCIMB 11950
    / KT2440)
description: cheA encodes the chemotaxis histidine kinase CheA of Pseudomonas putida
  KT2440. The protein is a 747 aa phosphorelay kinase with an N-terminal HPt domain,
  a central histidine kinase ATPase/dimerization region, and a C-terminal CheW-like
  domain. In KT2440 literature this locus corresponds to PP_4338/cheA2, the CheA paralog
  assigned to the canonical chemotaxis pathway rather than the Wsp-like c-di-GMP signaling
  branch. Its core role is to relay chemoreceptor input by autophosphorylating on
  histidine and transferring phosphate to response regulators such as CheY and CheB,
  thereby controlling chemotaxis.
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
  findings:
  - statement: InterPro mappings recover the broad conserved chemotaxis and phosphorelay
      context for CheA-family histidine kinases, but they also seed very broad parent
      terms that should be reviewed for redundancy.
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings:
  - statement: Combined automated methods recover the kinase activity of CheA, but
      the broader phosphorelay sensor kinase term is less specific than protein histidine
      kinase activity for this gene.
- id: UniProt:Q88EW4
  title: UniProt entry Q88EW4 for Pseudomonas putida KT2440 chemotaxis protein CheA
  findings:
  - statement: UniProt identifies Q88EW4 as chemotaxis protein CheA and states that
      it is autophosphorylated and can transfer phosphate to CheB or CheY.
    supporting_text: >-
      RecName: Full=Chemotaxis protein CheA...CheA is autophosphorylated; it can
      transfer its phosphate group to either CheB or CheY.
  - statement: The sequence carries an HPt domain, a histidine kinase region, and
      a CheW-like domain, with a phosphohistidine annotated at residue 49.
- id: DOI:10.3389/fmicb.2019.00078
  title: Concentration Dependent Effect of Plant Root Exudates on the Chemosensory
    Systems of Pseudomonas putida KT2440
  findings:
  - statement: The KT2440 study identifies PP_4338 as cheA2 and reports that a cheA2
      mutant is entirely deficient in maize root exudate chemotaxis.
  - statement: The same study separates cheA paralog roles, with cheA1 affecting c-di-GMP
      and biofilm formation while cheA2 maps to the canonical chemotaxis pathway.
- id: file:PSEPK/cheA/cheA-deep-research-falcon.md
  title: Falcon deep research report for cheA in Pseudomonas putida KT2440
  findings:
  - statement: Synthesizes KT2440 cheA2 literature, conserved CheA domain architecture,
      and recent chemosensory-system reviews into a curation-focused assessment of
      core versus over-broad GO terms.
existing_annotations:
- term:
    id: GO:0000155
    label: phosphorelay sensor kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: This annotation captures the general CheA-like phosphorelay kinase role,
      but it is broader than the more specific child term GO:0004673 protein histidine
      kinase activity, which is also already present for this gene.
    action: MARK_AS_OVER_ANNOTATED
    reason: Retaining the broader phosphorelay sensor kinase term adds little beyond
      the specific protein histidine kinase annotation and obscures the more informative
      catalytic term.
    supported_by:
    - reference_id: file:PSEPK/cheA/cheA-deep-research-falcon.md
      supporting_text: GO:0000155 is broader than GO:0004673 and becomes redundant
        when the child protein histidine kinase term is already present.
- term:
    id: GO:0004673
    label: protein histidine kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: 'This is the best existing molecular-function term for cheA. UniProt
      assigns the canonical CheA chemistry: ATP-dependent autophosphorylation on histidine
      followed by phosphotransfer to downstream response regulators.'
    action: ACCEPT
    reason: Protein histidine kinase activity precisely captures the catalytic role
      of CheA in the chemotaxis phosphorelay and is supported by conserved domain
      architecture, phosphohistidine annotation, and the established CheA reaction.
    supported_by:
    - reference_id: UniProt:Q88EW4
      supporting_text: CheA is autophosphorylated; it can transfer its phosphate group
        to either CheB or CheY.
    - reference_id: UniProt:Q88EW4
      supporting_text: >-
        -!- CATALYTIC ACTIVITY: Reaction=ATP + protein L-histidine = ADP +
        protein N-phospho-L- histidine.; EC=2.7.13.3;
    - reference_id: file:PSEPK/cheA/cheA-deep-research-falcon.md
      supporting_text: CheA is the central histidine kinase of the canonical chemotaxis
        phosphorelay in KT2440.
- term:
    id: GO:0016772
    label: transferase activity, transferring phosphorus-containing groups
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: This annotation is technically true for a histidine kinase, but it is
      a very broad parent term that adds no information beyond GO:0004673.
    action: MARK_AS_OVER_ANNOTATED
    reason: The broader transferase term is redundant once the specific protein histidine
      kinase activity is retained.
    supported_by:
    - reference_id: file:PSEPK/cheA/cheA-deep-research-falcon.md
      supporting_text: GO:0016772 is a very broad parent term and does not add useful
        specificity beyond protein histidine kinase activity.
- term:
    id: GO:0000160
    label: phosphorelay signal transduction system
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: This is an appropriate core biological-process term for cheA because
      the protein is the autophosphorylating histidine kinase that relays sensory
      input to CheY/CheB response regulators.
    action: ACCEPT
    reason: The phosphorelay system is the direct mechanistic context of CheA function,
      and this term is specific enough to retain as a core process annotation.
    supported_by:
    - reference_id: UniProt:Q88EW4
      supporting_text: CheA is autophosphorylated; it can transfer its phosphate group
        to either CheB or CheY.
    - reference_id: file:PSEPK/cheA/cheA-deep-research-falcon.md
      supporting_text: CheA is the central histidine kinase of the canonical chemotaxis
        phosphorelay in KT2440.
- term:
    id: GO:0006935
    label: chemotaxis
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: Chemotaxis is a core process annotation for this locus. The strongest
      species-specific evidence in KT2440 shows that PP_4338/cheA2 is required for
      chemotaxis toward maize root exudates.
    action: ACCEPT
    reason: The KT2440 cheA2 mutant phenotype directly connects this paralog to the
      canonical chemotaxis pathway rather than only to generic signaling.
    supported_by:
    - reference_id: DOI:10.3389/fmicb.2019.00078
      supporting_text: a cheA2 mutant was entirely deficient in MRE chemotaxis
    - reference_id: file:PSEPK/cheA/cheA-deep-research-falcon.md
      supporting_text: PP_4338/Q88EW4 is the CheA paralog for the flagellar chemotaxis
        pathway rather than the Wsp-like surface signaling pathway.
- term:
    id: GO:0007165
    label: signal transduction
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: This term is true but too broad. CheA participates specifically in phosphorelay
      signaling for chemotaxis, which is already captured by more informative child
      terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: GO:0007165 is a very high-level parent of the more informative phosphorelay
      and chemotaxis terms already present for this gene.
    supported_by:
    - reference_id: file:PSEPK/cheA/cheA-deep-research-falcon.md
      supporting_text: GO:0007165 is a broad parent term and does not add useful specificity
        once phosphorelay signal transduction system and chemotaxis are retained.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: Cytoplasm is acceptable as a broad localization because CheA is a soluble
      signaling kinase rather than a transmembrane receptor. However, this term does
      not capture the membrane-proximal chemosensory array context in which the protein
      actually operates.
    action: KEEP_AS_NON_CORE
    reason: The annotation is not wrong, but it is too generic to represent the most
      informative localization context for the chemotaxis machinery.
    supported_by:
    - reference_id: UniProt:Q88EW4
      supporting_text: GO; GO:0005737; C:cytoplasm; IEA:InterPro
    - reference_id: file:PSEPK/cheA/cheA-deep-research-falcon.md
      supporting_text: The safest curation decision is to keep cytoplasm as a non-core
        location rather than assert a more specific cell-pole or membrane-complex
        term.
core_functions:
- description: CheA is the chemotaxis histidine kinase of the KT2440 chemosensory
    phosphorelay. It autophosphorylates on histidine and transfers phosphate to downstream
    response regulators such as CheY and CheB to couple chemoreceptor input to chemotactic
    behavior.
  molecular_function:
    id: GO:0004673
    label: protein histidine kinase activity
  directly_involved_in:
  - id: GO:0000160
    label: phosphorelay signal transduction system
  - id: GO:0006935
    label: chemotaxis
  supported_by:
  - reference_id: UniProt:Q88EW4
    supporting_text: Involved in the transmission of sensory signals from the chemoreceptors
      to the flagellar motors.
  - reference_id: UniProt:Q88EW4
    supporting_text: CheA is autophosphorylated; it can transfer its phosphate group
      to either CheB or CheY.
  - reference_id: DOI:10.3389/fmicb.2019.00078
    supporting_text: a cheA2 mutant was entirely deficient in MRE chemotaxis
proposed_new_terms: []
suggested_questions:
- question: Which KT2440 response regulators are the dominant in vivo phospho-acceptors
    for PP_4338/CheA during chemotaxis under rhizosphere conditions?
  experts:
  - Tino Krell
  - Miguel A Matilla
  - Jose A Reyes-Darias
- question: How are signaling duties partitioned among the three KT2440 CheA paralogs
    across defined attractants and surface-associated states?
  experts:
  - Tino Krell
  - Miguel A Matilla
- question: Does PP_4338 form stable polar chemosensory arrays with specific MCP and
    CheW partners in KT2440, and how condition-dependent is that assembly?
  experts:
  - Tino Krell
suggested_experiments:
- description: Purify PP_4338/CheA and test ATP-dependent autophosphorylation plus
    phosphotransfer to candidate KT2440 CheY and CheB proteins.
  hypothesis: PP_4338 is the cognate chemotaxis histidine kinase that directly transfers
    phosphate to the canonical chemotaxis response regulators.
  experiment_type: biochemical phosphotransfer assay
- description: Compare cheA1, cheA2, and cheA3 single and combinatorial mutants across
    defined attractants, root-exudate mixtures, motility, and root-colonization assays.
  hypothesis: cheA2 carries the core flagellar chemotaxis pathway, while the other
    paralogs control distinct surface-sensing or c-di-GMP-linked signaling branches.
  experiment_type: comparative mutant phenotyping
- description: Tag PP_4338 with a minimally perturbing fluorescent marker and image
    its localization relative to chemoreceptor arrays during planktonic and rhizosphere-like
    growth.
  hypothesis: The core chemotaxis CheA paralog forms membrane-proximal polar signaling
    arrays whose abundance changes with environmental context.
  experiment_type: live-cell localization microscopy