acgA

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005886 plasma membrane	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic inference of plasma membrane localization is consistent with the experimentally determined localization of ACG at the cell periphery of spores and its status as a single-pass type II membrane protein. Reason: ACG is a transmembrane receptor-type cyclase and is directly observed at the cell periphery in spores, so plasma membrane localization is correct and the IBA inference is supported by direct evidence for this gene. Supporting Evidence: PMID:17267449 In spores, ACG was localized at the cell periphery as would be expected for a transmembrane osmosensor
GO:0004016 adenylate cyclase activity	IBA GO_REF:0000033	ACCEPT	Summary: Adenylate cyclase activity is the core catalytic function of ACG and is directly demonstrated experimentally, so the phylogenetic inference is well supported. Reason: ACG catalyzes ATP to cAMP conversion (EC 4.6.1.1) and this activity is directly measured; the IBA inference is corroborated by direct evidence. Supporting Evidence: PMID:8798577 ACG activity, measured in aca-/ACG cells, was strongly stimulated by high osmolarity with optimal stimulation occurring at 200 milliosmolar.
GO:0001653 peptide receptor activity	IBA GO_REF:0000033	MARK AS OVER ANNOTATED	Summary: This IBA term is propagated from receptor-type cyclase family members based on the large extracellular (CHASE) domain. For ACG, however, the activating stimulus is high osmolality acting on an intramolecular osmosensor, and no peptide ligand has been shown to be required for activation (ACG is fully osmoactivatable in yeast without auxiliary sensors). A downstream link to the SDF-1 phosphopeptide has been proposed but not established as direct ligand binding. Reason: There is no experimental demonstration that ACG functions as a peptide receptor. Its extracellular domain acts as an intramolecular osmosensor, and activation does not require an external peptide ligand, so transferring peptide receptor activity from family members over-annotates ACG. Propagation Review Root cause: PROPAGATION BAD Failure modes: FUNCTIONAL DIVERGENCE Sources checked: PANTHER:PTN000229249 · PANTHER node for the receptor guanylyl-cyclase / natriuretic-peptide-receptor family SUPPORTS SOURCE BUT NOT TARGET Family node groups peptide-binding receptor guanylyl cyclases; ACG retained the cyclase fold but its extracellular CHASE domain acts as an intramolecular osmosensor rather than a peptide receptor UniProtKB:P16066 · human natriuretic peptide receptor 1 (guanylyl cyclase A) SUPPORTS SOURCE BUT NOT TARGET Bona fide peptide receptor in mammals, but ACG activation requires high osmolality and no peptide ligand, so the receptor role does not transfer Supporting Evidence: PMID:14718564 This strongly suggests that the ACG osmosensor is intramolecular, which would define ACG as the first characterized primary osmosensor in eukaryotes.
GO:0004016 adenylate cyclase activity	IEA GO_REF:0000120	ACCEPT	Summary: Electronic assignment of adenylate cyclase activity via EC 4.6.1.1 mapping is correct and matches the experimentally established catalytic function of ACG. Reason: ACG is a bona fide adenylate cyclase (ATP = cAMP + diphosphate); the IEA/EC-based inference agrees with direct evidence. Supporting Evidence: PMID:8798577 an atypical adenylyl cyclase, ACG, in mature spores
GO:0005886 plasma membrane	IEA GO_REF:0000117	ACCEPT	Summary: ARBA electronic inference of plasma membrane localization is consistent with the direct observation of ACG at the spore cell periphery. Reason: Plasma membrane localization is supported by direct evidence for ACG in spores; the electronic annotation is correct. Supporting Evidence: PMID:17267449 In spores, ACG was localized at the cell periphery as would be expected for a transmembrane osmosensor
GO:0007165 signal transduction	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: ACG participates in cAMP-mediated signaling, so signal transduction is correct but very general; more specific terms (osmosensory signaling pathway, cAMP biosynthetic process) better capture its role. Reason: Signal transduction is a broad parent process that is accurate for a cAMP-producing osmosensor but is not informative as a core function. Supporting Evidence: PMID:8798577 These data indicate that ACG is an osmosensor controlling spore germination through activation of protein kinase A.
GO:0009190 cyclic nucleotide biosynthetic process	IEA GO_REF:0000002	MODIFY	Summary: ACG synthesizes the cyclic nucleotide cAMP. The specific child term cAMP biosynthetic process more precisely captures this function than the general cyclic nucleotide biosynthetic process. Reason: ACG produces cAMP specifically (not cGMP), so the more specific cAMP biosynthetic process is the appropriate term. Proposed replacements: cAMP biosynthetic process Supporting Evidence: PMID:18640994 The osmolyte-activated adenylate cyclase, ACG, produces cAMP for prespore differentiation and inhibition of spore germination.
GO:0016020 membrane	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: Membrane localization is correct but redundant with the more specific plasma membrane annotation. Reason: ACG is an integral membrane protein; the general term membrane is subsumed by the more informative plasma membrane annotation. Supporting Evidence: PMID:17267449 ACG was localized at the cell periphery as would be expected for a transmembrane osmosensor
GO:0016849 phosphorus-oxygen lyase activity	IEA GO_REF:0000002	MODIFY	Summary: Phosphorus-oxygen lyase activity is the general parent of adenylate cyclase activity. It is technically correct but the specific child term is more informative. Reason: ACG's phosphorus-oxygen lyase activity is specifically adenylate cyclase activity; the more specific term should be used. Proposed replacements: adenylate cyclase activity Supporting Evidence: PMID:8798577 ACG activity, measured in aca-/ACG cells, was strongly stimulated by high osmolarity with optimal stimulation occurring at 200 milliosmolar.
GO:0035556 intracellular signal transduction	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: ACG produces intracellular cAMP that activates PKA, so intracellular signal transduction is accurate but general. Reason: This is a broad parent process; the intracellular messenger role of ACG-derived cAMP is better captured by cAMP biosynthetic process and the specific developmental/germination processes. Supporting Evidence: PMID:8798577 These data indicate that ACG is an osmosensor controlling spore germination through activation of protein kinase A.
GO:0019887 protein kinase regulator activity	IMP PMID:8798577 Adenylyl cyclase G, an osmosensor controlling germination of...	MARK AS OVER ANNOTATED	Summary: ACG activates PKA, but it does so indirectly by synthesizing the second messenger cAMP that binds the PKA regulatory subunit. ACG is not itself a direct protein kinase regulator; its molecular function is adenylate cyclase activity, and PKA activation is a downstream consequence. Reason: The IMP phenotype (loss of osmotic control of germination via PKA) reflects ACG acting upstream of PKA through cAMP, not a direct kinase-regulator molecular function. Assigning protein kinase regulator activity conflates the downstream signaling effect with ACG's true catalytic activity. Supporting Evidence: PMID:8798577 These data indicate that ACG is an osmosensor controlling spore germination through activation of protein kinase A.
GO:0007165 signal transduction	IMP PMID:21602484 The polyketide MPBD initiates the SDF-1 signaling cascade th...	KEEP AS NON CORE	Summary: In the SDF-1 signaling cascade, SDF-1 acts through ACG to activate PKA and amplify SDF-1 production. This supports a signal transduction role, though the term is general. Reason: ACG's involvement in the SDF-1 relay is a genuine but pleiotropic signaling role; signal transduction is too general to be a core function. Supporting Evidence: PMID:21602484 SDF-1 apparently acts through the adenylyl cyclase ACG to activate the cyclic AMP (cAMP)-dependent protein kinase A (PKA) and trigger the production of more SDF-1.
GO:0030435 sporulation resulting in formation of a cellular spore	IDA PMID:17267449 cAMP production by adenylyl cyclase G induces prespore diffe...	KEEP AS NON CORE	Summary: ACG protein is upregulated in prespore tissue and acg null mutants show reduced prespore differentiation, establishing a role in the sporulation program. This role is partly redundant with ACB. Reason: ACG contributes to prespore differentiation and hence sporulation, but this is a developmental/process role downstream of its catalytic and osmosensing molecular functions and is partially redundant with ACB. Supporting Evidence: PMID:17267449 acg null mutants show reduced prespore differentiation, which becomes very severe when ACB is also deleted. PMID:17267449 These data show that ACG induces prespore differentiation in wild-type cells, with ACB capable of partially taking over this function in its absence.
GO:0009992 intracellular water homeostasis	IDA PMID:14718564 Adenylyl cyclase G is activated by an intramolecular osmosen...	MARK AS OVER ANNOTATED	Summary: ACG is an osmosensor that detects high osmolality and triggers a cAMP signaling response; it is not itself an effector that maintains intracellular water balance. This term overstates the function. Reason: ACG senses osmotic conditions and signals through cAMP/PKA to control germination; it does not directly regulate cellular water content. Cellular response to osmotic stress and osmosensory signaling pathway better capture the evidence. Supporting Evidence: PMID:14718564 Adenylyl cyclase G (ACG) is activated by high osmolality and mediates inhibition of spore germination by this stress factor.
GO:1904360 negative regulation of spore germination	IMP PMID:14718564 Adenylyl cyclase G is activated by an intramolecular osmosen...	ACCEPT	Summary: ACG activation by high osmolality inhibits spore germination, keeping spores dormant in the fruiting body. This is a core biological role of ACG. Reason: Loss of ACG abolishes osmotic inhibition of germination, and ACG activation by osmolality mediates this inhibition, directly supporting negative regulation of spore germination. Supporting Evidence: PMID:14718564 Adenylyl cyclase G (ACG) is activated by high osmolality and mediates inhibition of spore germination by this stress factor.
GO:0071470 cellular response to osmotic stress	IMP PMID:8798577 Adenylyl cyclase G, an osmosensor controlling germination of...	ACCEPT	Summary: ACG activity is strongly stimulated by high osmolarity and mediates the cellular response that keeps spores dormant, directly supporting a role in the cellular response to osmotic stress. Reason: ACG is directly activated by high osmolarity and its disruption removes the osmotic inhibition of germination, supporting this term. Supporting Evidence: PMID:8798577 ACG activity, measured in aca-/ACG cells, was strongly stimulated by high osmolarity with optimal stimulation occurring at 200 milliosmolar.
GO:1904360 negative regulation of spore germination	IMP PMID:8798577 Adenylyl cyclase G, an osmosensor controlling germination of...	ACCEPT	Summary: acg null spores are no longer prevented from germinating by high osmolarity, demonstrating that ACG negatively regulates spore germination. Reason: The acg- germination phenotype directly establishes ACG as a negative regulator of spore germination under high osmolarity. Supporting Evidence: PMID:8798577 acg- cells developed into normal fruiting bodies with viable spores, but spore germination was no longer inhibited by high osmolarity
GO:0004016 adenylate cyclase activity	IDA PMID:8798577 Adenylyl cyclase G, an osmosensor controlling germination of...	ACCEPT	Summary: Direct measurement of osmolarity-stimulated ACG enzyme activity establishes adenylate cyclase activity as the core catalytic function. Reason: ACG adenylate cyclase activity was directly assayed and shown to convert ATP to cAMP in an osmolality-dependent manner; this is the core molecular function. Supporting Evidence: PMID:8798577 ACG activity, measured in aca-/ACG cells, was strongly stimulated by high osmolarity with optimal stimulation occurring at 200 milliosmolar.
GO:0007231 osmosensory signaling pathway	IMP PMID:14718564 Adenylyl cyclase G is activated by an intramolecular osmosen...	ACCEPT	Summary: ACG couples direct osmosensing to cAMP production, initiating an osmosensory signaling pathway that controls spore germination. Expression in yeast shows the osmosensor is intrinsic to ACG. Reason: ACG functions as a primary osmosensor that transduces high osmolality into cAMP signaling, directly supporting participation in an osmosensory signaling pathway. Supporting Evidence: PMID:14718564 This strongly suggests that the ACG osmosensor is intramolecular, which would define ACG as the first characterized primary osmosensor in eukaryotes.
GO:0005886 plasma membrane	IDA PMID:14718564 Adenylyl cyclase G is activated by an intramolecular osmosen...	ACCEPT	Summary: ACG is a transmembrane cyclase active at the plasma membrane, where its extracellular domain and osmosensor face the exterior. Direct localization places ACG at the spore cell periphery. Reason: As a single-pass type II membrane protein observed at the cell periphery of spores, ACG is active in the plasma membrane. Supporting Evidence: PMID:17267449 In spores, ACG was localized at the cell periphery as would be expected for a transmembrane osmosensor
GO:0004016 adenylate cyclase activity	IMP PMID:14718564 Adenylyl cyclase G is activated by an intramolecular osmosen...	ACCEPT	Summary: Dominant-negative and dimerization experiments confirm ACG cAMP production depends on its catalytic domain and dimerization, consistent with adenylate cyclase activity being the core function. Reason: ACG cAMP synthesis was measured and shown to require dimerization via a region outside the catalytic domain, supporting its adenylate cyclase activity. Supporting Evidence: PMID:14718564 This indicates that ACG activity requires dimerization via a region outside the catalytic domain
GO:0005034 osmosensor activity	IDA PMID:14718564 Adenylyl cyclase G is activated by an intramolecular osmosen...	ACCEPT	Summary: ACG harbors an intramolecular osmosensor; high osmolality directly activates cAMP synthesis, and this osmosensing is retained when ACG is expressed in a yeast adenylyl cyclase null mutant, showing no auxiliary sensor is required. This is a defining core molecular function. Reason: Direct evidence establishes ACG as a primary, intramolecular osmosensor, making osmosensor activity a core molecular function. Supporting Evidence: PMID:14718564 In yeast, cAMP production by ACG was similarly activated by high osmolality as in Dictyostelium. PMID:14718564 This strongly suggests that the ACG osmosensor is intramolecular, which would define ACG as the first characterized primary osmosensor in eukaryotes.
GO:0006970 response to osmotic stress	IMP PMID:14718564 Adenylyl cyclase G is activated by an intramolecular osmosen...	ACCEPT	Summary: ACG mediates the cellular response to high osmolality that inhibits spore germination, supporting a role in response to osmotic stress. Reason: ACG is directly activated by osmotic up-shift and its loss removes the osmotic block on germination, supporting response to osmotic stress. Supporting Evidence: PMID:14718564 Adenylyl cyclase G (ACG) is activated by high osmolality and mediates inhibition of spore germination by this stress factor.
GO:0042802 identical protein binding	IPI PMID:14718564 Adenylyl cyclase G is activated by an intramolecular osmosen...	KEEP AS NON CORE	Summary: ACG forms homodimers, which is required for its catalytic activity; size fractionation showed dimers between ACG molecules. This self-association is real but is better understood as a structural requirement for the cyclase rather than a standalone function. Reason: ACG homodimerization is experimentally demonstrated and functionally important for catalysis, but identical protein binding is not itself a core informative molecular function; it underpins the adenylate cyclase activity. Supporting Evidence: PMID:14718564 Size fractionation of native ACG showed that dimers were formed between ACG molecules
GO:0010447 response to acidic pH	IDA PMID:7883072 Regulation of Dictyostelium adenylylcyclases by morphogen-in...	KEEP AS NON CORE	Summary: ACG activity is strongly pH dependent, optimal at pH 8 and virtually absent below pH 7, and is inhibited by weak acids that lower cytosolic pH. This supports a response to acidic pH at the level of enzyme regulation. Reason: The pH sensitivity of ACG is an experimentally documented regulatory property but is a modulatory response rather than a core evolved function. Supporting Evidence: PMID:7883072 basal and GTP gamma S-stimulated ACA activity as well as ACG activity are optimal at pH 8 and are virtually absent below pH 7
GO:0031000 response to caffeine	IDA PMID:16952277 Pharmacological profiling of the Dictyostelium adenylate cyc...	KEEP AS NON CORE	Summary: Caffeine inhibits cAMP accumulation by ACG (as well as ACA and ACB), documenting a pharmacological response to caffeine. Reason: Caffeine sensitivity is an experimentally observed pharmacological response, not a physiological core function of ACG. Supporting Evidence: PMID:16952277 Caffeine, which was previously used to specifically block ACA function, also inhibited cAMP accumulation by ACB and ACG.
GO:0006970 response to osmotic stress	IEP PMID:18640994 From drought sensing to developmental control: evolution of ...	ACCEPT	Summary: Across the Dictyostelia, osmolyte-activated ACG activity and osmoregulation of spore germination are conserved, consistent with ACG acting in the response to osmotic stress. Reason: Comparative and expression evidence supports a conserved role for ACG in osmolality-activated cAMP signaling within the response to osmotic stress. Supporting Evidence: PMID:18640994 The osmolyte-activated adenylate cyclase, ACG, produces cAMP for prespore differentiation and inhibition of spore germination.

📄 View Raw YAML

id: Q03101
gene_symbol: acgA
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:44689
  label: Dictyostelium discoideum
description: acgA encodes adenylyl cyclase G (ACG), an atypical, receptor-type
  adenylyl cyclase of the class-4 adenylyl/guanylyl cyclase family. It is a
  single-pass type II membrane protein comprising a large extracellular domain
  (including a CHASE domain), a single transmembrane anchor, and a single
  intracellular catalytic cyclase domain that converts ATP to 3',5'-cyclic AMP.
  ACG is catalytically active as a dimer and, unlike the aggregation-stage
  cyclase ACA, is insensitive to G proteins. Its defining feature is an
  intramolecular osmosensor that directly couples high osmolality to cAMP
  synthesis, a property retained even when ACG is expressed heterologously in
  yeast. ACG is expressed predominantly in prespore and spore cells. In the
  fruiting body, the ambient high osmolality of the spore head activates ACG,
  and the resulting intracellular cAMP maintains high protein kinase A (PKA)
  activity that keeps spores dormant and prevents premature germination. Earlier
  in development ACG protein accumulates in the prespore region, where the cAMP
  it produces promotes prespore differentiation, a role partially redundant with
  the cyclase ACB (AcrA). ACG function in spore dormancy and germination is
  deeply conserved across the Dictyostelia and is thought to derive from an
  ancestral drought/osmolarity-sensing role in the encystation and excystation
  of solitary amoebae.
existing_annotations:
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: Phylogenetic inference of plasma membrane localization is consistent
      with the experimentally determined localization of ACG at the cell periphery
      of spores and its status as a single-pass type II membrane protein.
    action: ACCEPT
    reason: ACG is a transmembrane receptor-type cyclase and is directly observed
      at the cell periphery in spores, so plasma membrane localization is correct
      and the IBA inference is supported by direct evidence for this gene.
    supported_by:
    - reference_id: PMID:17267449
      supporting_text: In spores, ACG was localized at the cell periphery as would
        be expected for a transmembrane osmosensor
- term:
    id: GO:0004016
    label: adenylate cyclase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: Adenylate cyclase activity is the core catalytic function of ACG and
      is directly demonstrated experimentally, so the phylogenetic inference is
      well supported.
    action: ACCEPT
    reason: ACG catalyzes ATP to cAMP conversion (EC 4.6.1.1) and this activity is
      directly measured; the IBA inference is corroborated by direct evidence.
    supported_by:
    - reference_id: PMID:8798577
      supporting_text: ACG activity, measured in aca-/ACG cells, was strongly
        stimulated by high osmolarity with optimal stimulation occurring at 200
        milliosmolar.
- term:
    id: GO:0001653
    label: peptide receptor activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: This IBA term is propagated from receptor-type cyclase family members
      based on the large extracellular (CHASE) domain. For ACG, however, the
      activating stimulus is high osmolality acting on an intramolecular
      osmosensor, and no peptide ligand has been shown to be required for
      activation (ACG is fully osmoactivatable in yeast without auxiliary
      sensors). A downstream link to the SDF-1 phosphopeptide has been proposed
      but not established as direct ligand binding.
    action: MARK_AS_OVER_ANNOTATED
    propagation_review:
      root_cause: PROPAGATION_BAD
      failure_modes:
      - FUNCTIONAL_DIVERGENCE
      source_entities:
      - source_id: PANTHER:PTN000229249
        source_label: "PANTHER node for the receptor guanylyl-cyclase / natriuretic-peptide-receptor family"
        source_status: SUPPORTS_SOURCE_BUT_NOT_TARGET
        comment: "Family node groups peptide-binding receptor guanylyl cyclases; ACG retained the cyclase fold but its extracellular CHASE domain acts as an intramolecular osmosensor rather than a peptide receptor"
      - source_id: UniProtKB:P16066
        source_label: "human natriuretic peptide receptor 1 (guanylyl cyclase A)"
        source_status: SUPPORTS_SOURCE_BUT_NOT_TARGET
        comment: "Bona fide peptide receptor in mammals, but ACG activation requires high osmolality and no peptide ligand, so the receptor role does not transfer"
    reason: There is no experimental demonstration that ACG functions as a peptide
      receptor. Its extracellular domain acts as an intramolecular osmosensor, and
      activation does not require an external peptide ligand, so transferring
      peptide receptor activity from family members over-annotates ACG.
    supported_by:
    - reference_id: PMID:14718564
      supporting_text: This strongly suggests that the ACG osmosensor is
        intramolecular, which would define ACG as the first characterized primary
        osmosensor in eukaryotes.
- term:
    id: GO:0004016
    label: adenylate cyclase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: Electronic assignment of adenylate cyclase activity via EC 4.6.1.1
      mapping is correct and matches the experimentally established catalytic
      function of ACG.
    action: ACCEPT
    reason: ACG is a bona fide adenylate cyclase (ATP = cAMP + diphosphate); the
      IEA/EC-based inference agrees with direct evidence.
    supported_by:
    - reference_id: PMID:8798577
      supporting_text: an atypical adenylyl cyclase, ACG, in mature spores
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: located_in
  review:
    summary: ARBA electronic inference of plasma membrane localization is
      consistent with the direct observation of ACG at the spore cell periphery.
    action: ACCEPT
    reason: Plasma membrane localization is supported by direct evidence for ACG
      in spores; the electronic annotation is correct.
    supported_by:
    - reference_id: PMID:17267449
      supporting_text: In spores, ACG was localized at the cell periphery as would
        be expected for a transmembrane osmosensor
- term:
    id: GO:0007165
    label: signal transduction
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: ACG participates in cAMP-mediated signaling, so signal transduction
      is correct but very general; more specific terms (osmosensory signaling
      pathway, cAMP biosynthetic process) better capture its role.
    action: KEEP_AS_NON_CORE
    reason: Signal transduction is a broad parent process that is accurate for a
      cAMP-producing osmosensor but is not informative as a core function.
    supported_by:
    - reference_id: PMID:8798577
      supporting_text: These data indicate that ACG is an osmosensor controlling
        spore germination through activation of protein kinase A.
- term:
    id: GO:0009190
    label: cyclic nucleotide biosynthetic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: ACG synthesizes the cyclic nucleotide cAMP. The specific child term
      cAMP biosynthetic process more precisely captures this function than the
      general cyclic nucleotide biosynthetic process.
    action: MODIFY
    reason: ACG produces cAMP specifically (not cGMP), so the more specific
      cAMP biosynthetic process is the appropriate term.
    proposed_replacement_terms:
    - id: GO:0006171
      label: cAMP biosynthetic process
    supported_by:
    - reference_id: PMID:18640994
      supporting_text: The osmolyte-activated adenylate cyclase, ACG, produces cAMP
        for prespore differentiation and inhibition of spore germination.
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Membrane localization is correct but redundant with the more specific
      plasma membrane annotation.
    action: KEEP_AS_NON_CORE
    reason: ACG is an integral membrane protein; the general term membrane is
      subsumed by the more informative plasma membrane annotation.
    supported_by:
    - reference_id: PMID:17267449
      supporting_text: ACG was localized at the cell periphery as would be
        expected for a transmembrane osmosensor
- term:
    id: GO:0016849
    label: phosphorus-oxygen lyase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: Phosphorus-oxygen lyase activity is the general parent of adenylate
      cyclase activity. It is technically correct but the specific child term is
      more informative.
    action: MODIFY
    reason: ACG's phosphorus-oxygen lyase activity is specifically adenylate
      cyclase activity; the more specific term should be used.
    proposed_replacement_terms:
    - id: GO:0004016
      label: adenylate cyclase activity
    supported_by:
    - reference_id: PMID:8798577
      supporting_text: ACG activity, measured in aca-/ACG cells, was strongly
        stimulated by high osmolarity with optimal stimulation occurring at 200
        milliosmolar.
- term:
    id: GO:0035556
    label: intracellular signal transduction
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: ACG produces intracellular cAMP that activates PKA, so intracellular
      signal transduction is accurate but general.
    action: KEEP_AS_NON_CORE
    reason: This is a broad parent process; the intracellular messenger role of
      ACG-derived cAMP is better captured by cAMP biosynthetic process and the
      specific developmental/germination processes.
    supported_by:
    - reference_id: PMID:8798577
      supporting_text: These data indicate that ACG is an osmosensor controlling
        spore germination through activation of protein kinase A.
- term:
    id: GO:0019887
    label: protein kinase regulator activity
  evidence_type: IMP
  original_reference_id: PMID:8798577
  qualifier: enables
  review:
    summary: ACG activates PKA, but it does so indirectly by synthesizing the
      second messenger cAMP that binds the PKA regulatory subunit. ACG is not
      itself a direct protein kinase regulator; its molecular function is
      adenylate cyclase activity, and PKA activation is a downstream consequence.
    action: MARK_AS_OVER_ANNOTATED
    reason: The IMP phenotype (loss of osmotic control of germination via PKA)
      reflects ACG acting upstream of PKA through cAMP, not a direct
      kinase-regulator molecular function. Assigning protein kinase regulator
      activity conflates the downstream signaling effect with ACG's true
      catalytic activity.
    supported_by:
    - reference_id: PMID:8798577
      supporting_text: These data indicate that ACG is an osmosensor controlling
        spore germination through activation of protein kinase A.
- term:
    id: GO:0007165
    label: signal transduction
  evidence_type: IMP
  original_reference_id: PMID:21602484
  qualifier: involved_in
  review:
    summary: In the SDF-1 signaling cascade, SDF-1 acts through ACG to activate
      PKA and amplify SDF-1 production. This supports a signal transduction role,
      though the term is general.
    action: KEEP_AS_NON_CORE
    reason: ACG's involvement in the SDF-1 relay is a genuine but pleiotropic
      signaling role; signal transduction is too general to be a core function.
    supported_by:
    - reference_id: PMID:21602484
      supporting_text: SDF-1 apparently acts through the adenylyl cyclase ACG to
        activate the cyclic AMP (cAMP)-dependent protein kinase A (PKA) and
        trigger the production of more SDF-1.
- term:
    id: GO:0030435
    label: sporulation resulting in formation of a cellular spore
  evidence_type: IDA
  original_reference_id: PMID:17267449
  qualifier: involved_in
  review:
    summary: ACG protein is upregulated in prespore tissue and acg null mutants
      show reduced prespore differentiation, establishing a role in the
      sporulation program. This role is partly redundant with ACB.
    action: KEEP_AS_NON_CORE
    reason: ACG contributes to prespore differentiation and hence sporulation, but
      this is a developmental/process role downstream of its catalytic and
      osmosensing molecular functions and is partially redundant with ACB.
    supported_by:
    - reference_id: PMID:17267449
      supporting_text: acg null mutants show reduced prespore differentiation,
        which becomes very severe when ACB is also deleted.
    - reference_id: PMID:17267449
      supporting_text: These data show that ACG induces prespore differentiation
        in wild-type cells, with ACB capable of partially taking over this
        function in its absence.
- term:
    id: GO:0009992
    label: intracellular water homeostasis
  evidence_type: IDA
  original_reference_id: PMID:14718564
  qualifier: involved_in
  review:
    summary: ACG is an osmosensor that detects high osmolality and triggers a cAMP
      signaling response; it is not itself an effector that maintains intracellular
      water balance. This term overstates the function.
    action: MARK_AS_OVER_ANNOTATED
    reason: ACG senses osmotic conditions and signals through cAMP/PKA to control
      germination; it does not directly regulate cellular water content. Cellular
      response to osmotic stress and osmosensory signaling pathway better capture
      the evidence.
    supported_by:
    - reference_id: PMID:14718564
      supporting_text: Adenylyl cyclase G (ACG) is activated by high osmolality
        and mediates inhibition of spore germination by this stress factor.
- term:
    id: GO:1904360
    label: negative regulation of spore germination
  evidence_type: IMP
  original_reference_id: PMID:14718564
  qualifier: involved_in
  review:
    summary: ACG activation by high osmolality inhibits spore germination, keeping
      spores dormant in the fruiting body. This is a core biological role of ACG.
    action: ACCEPT
    reason: Loss of ACG abolishes osmotic inhibition of germination, and ACG
      activation by osmolality mediates this inhibition, directly supporting
      negative regulation of spore germination.
    supported_by:
    - reference_id: PMID:14718564
      supporting_text: Adenylyl cyclase G (ACG) is activated by high osmolality
        and mediates inhibition of spore germination by this stress factor.
- term:
    id: GO:0071470
    label: cellular response to osmotic stress
  evidence_type: IMP
  original_reference_id: PMID:8798577
  qualifier: involved_in
  review:
    summary: ACG activity is strongly stimulated by high osmolarity and mediates
      the cellular response that keeps spores dormant, directly supporting a role
      in the cellular response to osmotic stress.
    action: ACCEPT
    reason: ACG is directly activated by high osmolarity and its disruption
      removes the osmotic inhibition of germination, supporting this term.
    supported_by:
    - reference_id: PMID:8798577
      supporting_text: ACG activity, measured in aca-/ACG cells, was strongly
        stimulated by high osmolarity with optimal stimulation occurring at 200
        milliosmolar.
- term:
    id: GO:1904360
    label: negative regulation of spore germination
  evidence_type: IMP
  original_reference_id: PMID:8798577
  qualifier: involved_in
  review:
    summary: acg null spores are no longer prevented from germinating by high
      osmolarity, demonstrating that ACG negatively regulates spore germination.
    action: ACCEPT
    reason: The acg- germination phenotype directly establishes ACG as a negative
      regulator of spore germination under high osmolarity.
    supported_by:
    - reference_id: PMID:8798577
      supporting_text: acg- cells developed into normal fruiting bodies with viable
        spores, but spore germination was no longer inhibited by high osmolarity
- term:
    id: GO:0004016
    label: adenylate cyclase activity
  evidence_type: IDA
  original_reference_id: PMID:8798577
  qualifier: enables
  review:
    summary: Direct measurement of osmolarity-stimulated ACG enzyme activity
      establishes adenylate cyclase activity as the core catalytic function.
    action: ACCEPT
    reason: ACG adenylate cyclase activity was directly assayed and shown to
      convert ATP to cAMP in an osmolality-dependent manner; this is the core
      molecular function.
    supported_by:
    - reference_id: PMID:8798577
      supporting_text: ACG activity, measured in aca-/ACG cells, was strongly
        stimulated by high osmolarity with optimal stimulation occurring at 200
        milliosmolar.
- term:
    id: GO:0007231
    label: osmosensory signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:14718564
  qualifier: involved_in
  review:
    summary: ACG couples direct osmosensing to cAMP production, initiating an
      osmosensory signaling pathway that controls spore germination. Expression in
      yeast shows the osmosensor is intrinsic to ACG.
    action: ACCEPT
    reason: ACG functions as a primary osmosensor that transduces high osmolality
      into cAMP signaling, directly supporting participation in an osmosensory
      signaling pathway.
    supported_by:
    - reference_id: PMID:14718564
      supporting_text: This strongly suggests that the ACG osmosensor is
        intramolecular, which would define ACG as the first characterized primary
        osmosensor in eukaryotes.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:14718564
  qualifier: is_active_in
  review:
    summary: ACG is a transmembrane cyclase active at the plasma membrane, where
      its extracellular domain and osmosensor face the exterior. Direct
      localization places ACG at the spore cell periphery.
    action: ACCEPT
    reason: As a single-pass type II membrane protein observed at the cell
      periphery of spores, ACG is active in the plasma membrane.
    supported_by:
    - reference_id: PMID:17267449
      supporting_text: In spores, ACG was localized at the cell periphery as would
        be expected for a transmembrane osmosensor
- term:
    id: GO:0004016
    label: adenylate cyclase activity
  evidence_type: IMP
  original_reference_id: PMID:14718564
  qualifier: enables
  review:
    summary: Dominant-negative and dimerization experiments confirm ACG cAMP
      production depends on its catalytic domain and dimerization, consistent with
      adenylate cyclase activity being the core function.
    action: ACCEPT
    reason: ACG cAMP synthesis was measured and shown to require dimerization via a
      region outside the catalytic domain, supporting its adenylate cyclase
      activity.
    supported_by:
    - reference_id: PMID:14718564
      supporting_text: This indicates that ACG activity requires dimerization via a
        region outside the catalytic domain
- term:
    id: GO:0005034
    label: osmosensor activity
  evidence_type: IDA
  original_reference_id: PMID:14718564
  qualifier: enables
  review:
    summary: ACG harbors an intramolecular osmosensor; high osmolality directly
      activates cAMP synthesis, and this osmosensing is retained when ACG is
      expressed in a yeast adenylyl cyclase null mutant, showing no auxiliary
      sensor is required. This is a defining core molecular function.
    action: ACCEPT
    reason: Direct evidence establishes ACG as a primary, intramolecular
      osmosensor, making osmosensor activity a core molecular function.
    supported_by:
    - reference_id: PMID:14718564
      supporting_text: In yeast, cAMP production by ACG was similarly activated by
        high osmolality as in Dictyostelium.
    - reference_id: PMID:14718564
      supporting_text: This strongly suggests that the ACG osmosensor is
        intramolecular, which would define ACG as the first characterized primary
        osmosensor in eukaryotes.
- term:
    id: GO:0006970
    label: response to osmotic stress
  evidence_type: IMP
  original_reference_id: PMID:14718564
  qualifier: involved_in
  review:
    summary: ACG mediates the cellular response to high osmolality that inhibits
      spore germination, supporting a role in response to osmotic stress.
    action: ACCEPT
    reason: ACG is directly activated by osmotic up-shift and its loss removes the
      osmotic block on germination, supporting response to osmotic stress.
    supported_by:
    - reference_id: PMID:14718564
      supporting_text: Adenylyl cyclase G (ACG) is activated by high osmolality
        and mediates inhibition of spore germination by this stress factor.
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:14718564
  qualifier: enables
  review:
    summary: ACG forms homodimers, which is required for its catalytic activity;
      size fractionation showed dimers between ACG molecules. This
      self-association is real but is better understood as a structural
      requirement for the cyclase rather than a standalone function.
    action: KEEP_AS_NON_CORE
    reason: ACG homodimerization is experimentally demonstrated and functionally
      important for catalysis, but identical protein binding is not itself a core
      informative molecular function; it underpins the adenylate cyclase activity.
    supported_by:
    - reference_id: PMID:14718564
      supporting_text: Size fractionation of native ACG showed that dimers were
        formed between ACG molecules
- term:
    id: GO:0010447
    label: response to acidic pH
  evidence_type: IDA
  original_reference_id: PMID:7883072
  qualifier: involved_in
  review:
    summary: ACG activity is strongly pH dependent, optimal at pH 8 and virtually
      absent below pH 7, and is inhibited by weak acids that lower cytosolic pH.
      This supports a response to acidic pH at the level of enzyme regulation.
    action: KEEP_AS_NON_CORE
    reason: The pH sensitivity of ACG is an experimentally documented regulatory
      property but is a modulatory response rather than a core evolved function.
    supported_by:
    - reference_id: PMID:7883072
      supporting_text: basal and GTP gamma S-stimulated ACA activity as well as ACG
        activity are optimal at pH 8 and are virtually absent below pH 7
- term:
    id: GO:0031000
    label: response to caffeine
  evidence_type: IDA
  original_reference_id: PMID:16952277
  qualifier: involved_in
  review:
    summary: Caffeine inhibits cAMP accumulation by ACG (as well as ACA and ACB),
      documenting a pharmacological response to caffeine.
    action: KEEP_AS_NON_CORE
    reason: Caffeine sensitivity is an experimentally observed pharmacological
      response, not a physiological core function of ACG.
    supported_by:
    - reference_id: PMID:16952277
      supporting_text: Caffeine, which was previously used to specifically block
        ACA function, also inhibited cAMP accumulation by ACB and ACG.
- term:
    id: GO:0006970
    label: response to osmotic stress
  evidence_type: IEP
  original_reference_id: PMID:18640994
  qualifier: acts_upstream_of_or_within
  review:
    summary: Across the Dictyostelia, osmolyte-activated ACG activity and
      osmoregulation of spore germination are conserved, consistent with ACG
      acting in the response to osmotic stress.
    action: ACCEPT
    reason: Comparative and expression evidence supports a conserved role for ACG
      in osmolality-activated cAMP signaling within the response to osmotic stress.
    supported_by:
    - reference_id: PMID:18640994
      supporting_text: The osmolyte-activated adenylate cyclase, ACG, produces cAMP
        for prespore differentiation and inhibition of spore germination.
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
    vocabulary mapping, accompanied by conservative changes to GO terms applied by
    UniProt
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:14718564
  title: Adenylyl cyclase G is activated by an intramolecular osmosensor.
  findings:
  - statement: ACG is activated by high osmolality and mediates inhibition of spore
      germination by this stress factor.
    supporting_text: Adenylyl cyclase G (ACG) is activated by high osmolality and
      mediates inhibition of spore germination by this stress factor.
  - statement: The ACG osmosensor is intramolecular, defining ACG as the first
      characterized primary osmosensor in eukaryotes.
    supporting_text: This strongly suggests that the ACG osmosensor is
      intramolecular, which would define ACG as the first characterized primary
      osmosensor in eukaryotes.
  - statement: ACG activity requires dimerization via a region outside the catalytic
      domain, but dimerization does not mediate osmotic activation.
    supporting_text: This indicates that ACG activity requires dimerization via a
      region outside the catalytic domain
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PMC full text confirms ACG is an intramolecular osmosensor whose
      osmoactivation is retained in yeast; directly supports the osmosensor
      activity, osmosensory signaling, and germination-control annotations.
- id: PMID:16952277
  title: Pharmacological profiling of the Dictyostelium adenylate cyclases ACA, ACB
    and ACG.
  findings:
  - statement: Caffeine inhibits cAMP accumulation by ACG as well as by ACA and ACB.
    supporting_text: Caffeine, which was previously used to specifically block ACA
      function, also inhibited cAMP accumulation by ACB and ACG.
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Supports the response-to-caffeine annotation and confirms ACG is
      an osmosensor controlling spore germination that is not activated by G
      proteins.
- id: PMID:17267449
  title: cAMP production by adenylyl cyclase G induces prespore differentiation in
    Dictyostelium slugs.
  findings:
  - statement: ACG protein is upregulated in prespore tissue and acg null mutants
      show reduced prespore differentiation, severe when ACB is also deleted.
    supporting_text: acg null mutants show reduced prespore differentiation, which
      becomes very severe when ACB is also deleted.
  - statement: In spores, ACG localizes at the cell periphery as expected for a
      transmembrane osmosensor.
    supporting_text: In spores, ACG was localized at the cell periphery as would be
      expected for a transmembrane osmosensor
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Establishes the prespore-differentiation role of ACG-derived cAMP
      and the plasma-membrane localization of ACG in spores.
- id: PMID:18640994
  title: 'From drought sensing to developmental control: evolution of cyclic AMP signaling
    in social amoebas.'
  findings:
  - statement: The osmolyte-activated adenylate cyclase ACG produces cAMP for
      prespore differentiation and inhibition of spore germination, and this role
      is conserved across the Dictyostelia.
    supporting_text: The osmolyte-activated adenylate cyclase, ACG, produces cAMP
      for prespore differentiation and inhibition of spore germination.
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Provides the evolutionary/conservation context for ACG's
      osmosensing and germination-control functions across dictyostelid species.
- id: PMID:21602484
  title: The polyketide MPBD initiates the SDF-1 signaling cascade that coordinates
    terminal differentiation in Dictyostelium.
  findings:
  - statement: SDF-1 acts through ACG to activate PKA and trigger production of more
      SDF-1.
    supporting_text: SDF-1 apparently acts through the adenylyl cyclase ACG to
      activate the cyclic AMP (cAMP)-dependent protein kinase A (PKA) and trigger
      the production of more SDF-1.
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Supports a signal transduction role for ACG in the SDF-1 relay;
      the ACG-SDF-1 link is described as apparent, not a demonstrated direct
      peptide-receptor interaction.
- id: PMID:7883072
  title: Regulation of Dictyostelium adenylylcyclases by morphogen-induced modulation
    of cytosolic pH or Ca2+ levels.
  findings:
  - statement: ACG activity is optimal at pH 8 and virtually absent below pH 7, and
      is insensitive to Ca2+.
    supporting_text: basal and GTP gamma S-stimulated ACA activity as well as ACG
      activity are optimal at pH 8 and are virtually absent below pH 7
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Supports the pH-dependence (response to acidic pH) annotation and
      documents ACG's Ca2+ insensitivity.
- id: PMID:8798577
  title: Adenylyl cyclase G, an osmosensor controlling germination of Dictyostelium
    spores.
  findings:
  - statement: acg null cells form normal fruiting bodies with viable spores, but
      spore germination is no longer inhibited by high osmolarity.
    supporting_text: acg- cells developed into normal fruiting bodies with viable
      spores, but spore germination was no longer inhibited by high osmolarity
  - statement: ACG activity is strongly stimulated by high osmolarity, with optimal
      stimulation at 200 milliosmolar.
    supporting_text: ACG activity, measured in aca-/ACG cells, was strongly
      stimulated by high osmolarity with optimal stimulation occurring at 200
      milliosmolar.
  - statement: ACG is an osmosensor controlling spore germination through activation
      of protein kinase A.
    supporting_text: These data indicate that ACG is an osmosensor controlling spore
      germination through activation of protein kinase A.
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Original characterization of ACG as an osmosensor that controls
      spore germination via PKA; abstract-only cache but the key findings are
      explicit.
core_functions:
- description: ACG is an osmolality-activated adenylate cyclase that converts ATP to
    cAMP at the plasma membrane. High osmolality directly stimulates catalysis, and
    the resulting intracellular cAMP activates PKA to keep spores dormant and inhibit
    premature germination.
  molecular_function:
    id: GO:0004016
    label: adenylate cyclase activity
  locations:
  - id: GO:0005886
    label: plasma membrane
  directly_involved_in:
  - id: GO:0006171
    label: cAMP biosynthetic process
  - id: GO:1904360
    label: negative regulation of spore germination
  supported_by:
  - reference_id: PMID:8798577
    supporting_text: ACG activity, measured in aca-/ACG cells, was strongly
      stimulated by high osmolarity with optimal stimulation occurring at 200
      milliosmolar.
  - reference_id: PMID:8798577
    supporting_text: These data indicate that ACG is an osmosensor controlling spore
      germination through activation of protein kinase A.
- description: ACG functions as a primary, intramolecular osmosensor. Its
    extracellular/transmembrane region detects high osmolality and directly couples
    this stimulus to activation of the cytoplasmic cyclase domain, initiating an
    osmosensory cAMP signaling pathway. This osmosensing is intrinsic to ACG, as it
    is retained when ACG is expressed in a yeast adenylyl cyclase null mutant.
  molecular_function:
    id: GO:0005034
    label: osmosensor activity
  locations:
  - id: GO:0005886
    label: plasma membrane
  directly_involved_in:
  - id: GO:0007231
    label: osmosensory signaling pathway
  supported_by:
  - reference_id: PMID:14718564
    supporting_text: This strongly suggests that the ACG osmosensor is
      intramolecular, which would define ACG as the first characterized primary
      osmosensor in eukaryotes.
  - reference_id: PMID:14718564
    supporting_text: In yeast, cAMP production by ACG was similarly activated by
      high osmolality as in Dictyostelium.

Gene Description

Existing Annotations Review

Core Functions

ACG is an osmolality-activated adenylate cyclase that converts ATP to cAMP at the plasma membrane. High osmolality directly stimulates catalysis, and the resulting intracellular cAMP activates PKA to keep spores dormant and inhibit premature germination.

References

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