identifier: METPO:1000332
label: pH range
definition: A pH phenotype with numerical limits that bounds the minimum and maximum
  external pH supporting growth of an organism.
definition_source: DOI:10.1038/nrmicro2549
trait_category: ENVIRONMENT
term_kind: CLASS
mapping_status: REVIEWED
parent_traits:
- METPO:1000531
- METPO:1000535
created_by: Luke Wang
evidence:
- reference: DOI:10.1038/nrmicro2549
  snippet: pH homeostasis
  notes: pH-homeostasis review supports the bounded external-pH span over which cytoplasmic
    pH homeostasis sustains growth as the basis of the pH-range phenotype.
- reference: DOI:10.1016/j.tim.2007.02.005
  snippet: highly impermeable cell membranes
  notes: pH-homeostasis review supports envelope-based proton barriers as the mechanism
    extending growth into acidic and alkaline extremes.
causal_graphs:
- graph_id: ph_range_bounded_homeostasis
  title: pH-range bounded cytoplasmic homeostasis
  description: DOI-backed graph linking acid- and alkaline-tolerance to the bounded
    span of growth-supporting external pH.
  nodes:
  - node_id: ph_range_trait
    label: pH range
    node_type: TRAIT
    grounding: METPO:1000332
    description: Span of external pH values supporting growth.
  - node_id: external_ph
    label: external pH
    node_type: ENVIRONMENTAL_FACTOR
    description: Ambient proton activity (pH) imposed on the cell.
  - node_id: acid_tolerance
    label: acid tolerance
    node_type: BIOLOGICAL_PROCESS
    description: Capacity to maintain cytoplasmic pH against an inward H+ gradient
      at low external pH.
  - node_id: alkaline_tolerance
    label: alkaline tolerance
    node_type: BIOLOGICAL_PROCESS
    description: Capacity to maintain cytoplasmic pH against an outward H+ gradient
      at high external pH.
  - node_id: bounded_growth_window
    label: bounded pH growth window
    node_type: BIOLOGICAL_PROCESS
    description: Span of external pH between the minimum and maximum that supports
      growth.
  - node_id: ph_gradient
    label: transmembrane pH gradient (ΔpH)
    node_type: CHEMICAL
    description: Difference between external and cytoplasmic pH, a component of the
      proton motive force.
  - node_id: membrane_potential
    label: membrane potential (Δψ)
    node_type: CHEMICAL
    description: Electrical component of the proton motive force across the cell membrane.
  - node_id: cytoplasmic_ph_homeostasis
    label: cytoplasmic pH homeostasis
    node_type: BIOLOGICAL_PROCESS
    description: Maintenance of a near-constant cytoplasmic pH compatible with macromolecular
      function.
    grounding: GO:0051453
  - node_id: membrane_proton_impermeability
    label: membrane proton impermeability
    node_type: QUALITY
    description: Reduced proton leak across the cell membrane that limits passive
      H+ influx.
  - node_id: mrp_antiporter_activity
    label: Mrp Na+/H+ antiporter activity
    node_type: MOLECULAR_FUNCTION
    description: Cation/proton antiport that imports protons while exporting Na+ to
      support pH homeostasis.
  - node_id: amino_acid_decarboxylation
    label: amino-acid decarboxylation
    node_type: BIOLOGICAL_PROCESS
    description: Glutamate or arginine decarboxylation that consumes intracellular
      protons and alkalinizes the cytoplasm.
  edges:
  - subject: external_ph
    predicate: defines
    object: bounded_growth_window
    description: External pH defines the axis over which the growth window is bounded.
    evidence:
    - reference: DOI:10.1038/nrmicro2549
      snippet: external pH
      notes: Supports external pH as the axis bounding the growth window.
    predicate_id: METPO:2007500
  - subject: acid_tolerance
    predicate: defines
    object: bounded_growth_window
    description: Acid tolerance sets the lower bound of the pH growth window.
    evidence:
    - reference: DOI:10.1016/j.tim.2007.02.005
      snippet: highly impermeable cell membranes
      notes: Supports envelope proton barriers as the lower-bound mechanism for low-pH
        growth.
    predicate_id: METPO:2007500
  - subject: alkaline_tolerance
    predicate: defines
    object: bounded_growth_window
    description: Alkaline tolerance sets the upper bound of the pH growth window.
    evidence:
    - reference: DOI:10.1038/nrmicro2549
      snippet: alkaliphiles
      notes: Supports alkaline-tolerance physiology as the upper-bound mechanism for
        high-pH growth.
    predicate_id: METPO:2007500
  - subject: bounded_growth_window
    predicate: manifests as
    object: ph_range_trait
    description: The bounded pH growth window manifests the pH-range phenotype.
    evidence:
    - reference: DOI:10.1038/nrmicro2549
      snippet: pH homeostasis
      notes: Supports the trait endpoint.
    predicate_id: METPO:2007400
  - subject: ph_gradient
    predicate: contributes to
    object: bounded_growth_window
    description: The transmembrane pH gradient sets whether cytoplasmic pH can be
      maintained across the external pH range.
    evidence:
    - reference: DOI:10.1038/nrmicro2549
      notes: PMF architecture (Δψ − 59 ΔpH) determines the range of pHout over which
        bacteria can tolerate or grow.
    predicate_id: RO:0002326
  - subject: membrane_potential
    predicate: compensates for
    object: external_ph
    description: Adjustment or reversal of the membrane-potential PMF component offsets
      extreme external pH stress.
    evidence:
    - reference: DOI:10.1038/nrmicro2549
      notes: Under strong pH stress the orientation of a PMF component can reverse
        to maintain homeostasis.
  - subject: cytoplasmic_ph_homeostasis
    predicate: enables
    object: bounded_growth_window
    description: Keeping cytoplasmic pH compatible with protein function enables growth
      across the external pH range.
    evidence:
    - reference: DOI:10.1038/nrmicro2549
      notes: Bacteria maintain a distinct cytoplasmic pH required for protein function,
        bounding the phenotype.
    predicate_id: RO:0002327
  - subject: membrane_proton_impermeability
    predicate: extends
    object: acid_tolerance
    description: Reduced proton leak helps maintain cytoplasmic pH and extends growth
      to lower external pH.
    evidence:
    - reference: DOI:10.3389/fmicb.2020.556140
      notes: Modification of membrane lipid composition to reduce proton permeability
        is a general acid-stress mechanism.
  - subject: mrp_antiporter_activity
    predicate: supports
    object: alkaline_tolerance
    description: Na+/H+ exchange imports protons and is a principal strategy for alkaline
      pH homeostasis.
    evidence:
    - reference: DOI:10.1038/nrmicro2549
      notes: Na+/H+ antiport is the principal strategy for cytoplasmic pH homeostasis
        at high external pH.
  - subject: amino_acid_decarboxylation
    predicate: alkalinizes
    object: cytoplasmic_ph_homeostasis
    description: Glutamate or arginine decarboxylation consumes intracellular protons,
      supporting cytoplasmic pH at acidic external pH.
    evidence:
    - reference: DOI:10.3389/fmicb.2020.556140
      notes: Decarboxylation of glutamate or arginine is a recurring proton-consuming
        acid-response module.
curation_history:
- timestamp: '2026-05-05T01:35:46.815188+00:00'
  curator: seed_from_metpo
  action: SEEDED_FROM_METPO
  changes: imported from data/raw/metpo.owl (CLASS)
  llm_assisted: false
- timestamp: '2026-05-13T10:00:00-07:00'
  curator: claude
  action: CURATED_CAUSAL_GRAPH
  changes: Added DOI-backed causal graph linking acid- and alkaline-tolerance to the
    bounded pH-range phenotype.
  llm_assisted: true
- timestamp: '2026-05-23T21:30:06Z'
  curator: claude
  action: GROUND_CAUSAL_PREDICATES
  changes: Grounded 1 causal-edge predicate_id field(s) via mappings/predicate_grounding.tsv
    (METPO:2007400×1).
  llm_assisted: true
- timestamp: '2026-05-24T07:37:39Z'
  curator: claude
  action: GROUND_CAUSAL_PREDICATES
  changes: Grounded 1 causal-edge predicate_id field(s) via mappings/predicate_grounding.tsv
    (METPO:2007500×1).
  llm_assisted: true
- timestamp: '2026-05-26T05:00:47Z'
  curator: claude
  action: RENAME_PREDICATE_LABELS
  changes: 'Renamed 2 causal-edge predicate label(s) to align with existing groundings:
    sets → defines ×2.'
  llm_assisted: true
- timestamp: '2026-05-26T05:00:50Z'
  curator: claude
  action: GROUND_CAUSAL_PREDICATES
  changes: Grounded 2 causal-edge predicate_id field(s) via mappings/predicate_grounding.tsv
    (METPO:2007500×2).
  llm_assisted: true
- timestamp: '2026-06-23T00:00:00Z'
  curator: claude
  action: ENRICH_CAUSAL_GRAPH
  changes: Added 6 evidence-backed generic edges (6 new nodes) from the deep-research
    report.
  llm_assisted: true
- timestamp: '2026-06-24T17:21:10Z'
  curator: claude
  action: GROUND_CAUSAL_PREDICATES
  changes: Grounded 2 causal-edge predicate_id field(s) via mappings/predicate_grounding.tsv
    (RO:0002326×1, RO:0002327×1).
  llm_assisted: true
- timestamp: '2026-06-24T17:21:17Z'
  curator: claude
  action: GROUND_CAUSAL_NODES
  changes: Grounded 1 causal-node grounding field(s) via mappings/node_grounding.tsv
    (GO:0051453×1).
  llm_assisted: true