gpaB

id: P16051
gene_symbol: gpaB
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:44689
  label: Dictyostelium discoideum
description: >-
  gpaB encodes Gα2 (G alpha-2), the heterotrimeric G-protein alpha subunit of
  Dictyostelium discoideum that couples the cyclic AMP chemoattractant receptor
  cAR1 to intracellular signaling during the aggregation stage of development.
  Like other Gα subunits it binds guanine nucleotides and cycles between an
  inactive GDP-bound heterotrimeric state (associated with Gβγ) and an active
  GTP-bound state, functioning as a molecular switch with intrinsic GTPase
  activity. Gα2 is N-myristoylated on Gly-2 and S-palmitoylated on Cys-4,
  lipid modifications required for its plasma membrane localization; it also
  maintains a cytosolic pool that is shuttled to the membrane upon receptor
  activation. Upon cAMP stimulation, activated Gα2 engages downstream effectors
  including the Rap1-specific guanine nucleotide exchange factor GflB, thereby
  linking the GPCR to Ras/Rap signaling at the leading edge, as well as the
  RasGAP C2GAP1, and it is required for chemoattractant-stimulated phospholipase
  C activity. Gα2 is essential for cAMP relay, chemotaxis, cell aggregation and
  the transition to multicellular development, and cells lacking Gα2 fail to
  enter the developmental phase. Its amino-terminal MAPK docking (D-) motif is
  required for cAMP-stimulated nucleocytoplasmic shuttling of the GtaC
  transcription factor during aggregation.
existing_annotations:
- term:
    id: GO:0003925
    label: G protein activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: >-
      Phylogenetic (IBA) inference that Gα2 has G protein activity. This is the
      canonical molecular function of a heterotrimeric Gα subunit and is
      independently supported by direct experimental evidence in Dictyostelium.
    action: ACCEPT
    reason: >-
      Gα2 is a bona fide heterotrimeric G-protein alpha subunit that acts as a
      molecular switch (GTPase-driven GDP/GTP cycling). The IBA inference is
      correct and represents a core function of the gene.
    supported_by:
    - reference_id: PMID:8280098
      supporting_text: mutant fgd A, lacking the G-protein alpha-subunit G alpha 2, showed no stimulation by either cAMP...indicating that G alpha 2 is the stimulatory G-protein
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: >-
      IBA inference that Gα2 is active in the cytoplasm. Gα2 does maintain a
      cytosolic pool (sequestered by Gip1) in addition to its membrane pool,
      so cytoplasmic activity is reasonable, though the primary site of action
      is the plasma membrane.
    action: ACCEPT
    reason: >-
      A cytosolic pool of the G protein exists and is shuttled to the membrane
      upon receptor activation, consistent with cytoplasmic localization/activity.
    supported_by:
    - reference_id: PMID:27044073
      supporting_text: Gip1 was found to bind and sequester G proteins in cytosolic pools
- term:
    id: GO:0007188
    label: adenylate cyclase-modulating G protein-coupled receptor signaling pathway
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: >-
      IBA inference placing Gα2 in cAMP-receptor (adenylate cyclase-modulating)
      GPCR signaling. This matches the established role of Gα2 as the transducer
      coupling the cAR1 cAMP receptor during aggregation.
    action: ACCEPT
    reason: >-
      Gα2 is the alpha subunit coupling the cAMP chemoattractant GPCR to
      downstream effectors during aggregation, a core process. Also supported by
      a direct-evidence annotation to the same term (PMID:15563608).
    supported_by:
    - reference_id: PMID:34418534
      supporting_text: required for chemotaxis to cAMP during the onset of multicellular development
- term:
    id: GO:0005834
    label: heterotrimeric G-protein complex
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: part_of
  review:
    summary: >-
      IBA inference of heterotrimeric G-protein complex membership. Directly
      confirmed in Dictyostelium by FRET between Gα2 and Gβγ subunits.
    action: ACCEPT
    reason: >-
      Gα2 assembles with Gβ and Gγ into a heterotrimer that dissociates on
      receptor activation; this is a core cellular-component assignment.
    supported_by:
    - reference_id: PMID:11264536
      supporting_text: The G-protein heterotrimer rapidly dissociated and reassociated upon addition and removal of chemoattractant
- term:
    id: GO:0001664
    label: G protein-coupled receptor binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: >-
      InterPro2GO (IEA) inference that Gα2 binds a GPCR. Gα subunits are
      activated by, and physically couple to, agonist-occupied receptors; this
      is also supported by a direct-evidence annotation (PMID:11264536).
    action: ACCEPT
    reason: >-
      Receptor-catalyzed nucleotide exchange requires Gα2 engagement with the
      occupied cAMP receptor, a core aspect of its signaling function.
    supported_by:
    - reference_id: PMID:11264536
      supporting_text: occupied receptors, whether or not they are phosphorylated, catalyze the G-protein cycle
- term:
    id: GO:0003924
    label: GTPase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: >-
      IEA inference of GTPase activity. The intrinsic GTPase of the Gα subunit
      is the timer that returns the protein to its inactive GDP-bound state and
      is intrinsic to G protein switch function.
    action: ACCEPT
    reason: >-
      Gα2 contains the canonical G-alpha GTP-binding/hydrolysis motifs (G1-G5)
      and functions as a GTPase-driven molecular switch. This is a core
      molecular function, closely related to the more specific term
      GO:0003925 (G protein activity).
    supported_by:
    - reference_id: PMID:15715993
      supporting_text: The switch mechanism is a function of the inherent GTPase activity of the alpha-subunit
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:42121920
  qualifier: enables
  review:
    summary: >-
      IPI protein-binding annotation from the C2GAP1 interaction study. Gα2
      directly associates with the RasGAP C2GAP1, preferentially in its activated
      state, to attenuate Ras signaling during gradient sensing. The bare
      "protein binding" term is uninformative; the interaction itself is real
      but not a core molecular function descriptor.
    action: KEEP_AS_NON_CORE
    reason: >-
      The physical interaction with C2GAP1 is experimentally supported, but
      GO:0005515 is too generic to represent a core function. Retained as
      non-core evidence of an effector interaction.
    supported_by:
    - reference_id: PMID:42121920
      supporting_text: C2GAP1 directly associates with Gα2 in both GDP- and GTP-bound states, with preferential binding to activated Gα2
- term:
    id: GO:0005525
    label: GTP binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: >-
      IEA inference of GTP binding, consistent with the guanine-nucleotide
      binding site in the G-alpha fold. Also supported by an IC annotation
      (PMID:8280098) and by numerous conserved GTP-binding residues in UniProt.
    action: ACCEPT
    reason: >-
      GTP binding is intrinsic to Gα2 function as a nucleotide-dependent
      molecular switch; a core molecular function.
    supported_by:
    - reference_id: PMID:8280098
      supporting_text: mutant fgd A, lacking the G-protein alpha-subunit G alpha 2, showed no stimulation by either cAMP
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: located_in
  review:
    summary: >-
      ARBA machine-learning (IEA) localization to cytoplasm. Broad and partially
      redundant with the more specific plasma membrane and cytosol annotations;
      Gα2 does have a cytosolic pool in addition to its membrane pool.
    action: ACCEPT
    reason: >-
      Correct localization (a cytosolic pool of Gα2 exists), consistent with the
      IBA cytoplasm annotation, though the functionally important sites are the
      plasma membrane and the cytosolic reserve pool.
    supported_by:
    - reference_id: PMID:27044073
      supporting_text: Gip1 was found to bind and sequester G proteins in cytosolic pools
- term:
    id: GO:0005834
    label: heterotrimeric G-protein complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: part_of
  review:
    summary: >-
      InterPro2GO (IEA) heterotrimeric complex membership, redundant with and
      corroborated by direct-evidence annotations (PMID:11264536, PMID:12217653).
    action: ACCEPT
    reason: >-
      Gα2 is a subunit of the heterotrimeric G protein; a core cellular
      component assignment.
    supported_by:
    - reference_id: PMID:11264536
      supporting_text: The G-protein heterotrimer rapidly dissociated and reassociated upon addition and removal of chemoattractant
- term:
    id: GO:0007010
    label: cytoskeleton organization
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: >-
      ARBA (IEA) inference of a broad cytoskeleton-organization role. Gα2
      signaling does drive actin cytoskeletal reorganization during
      chemoattractant-directed migration, but this is an indirect, downstream
      consequence and the term is very general.
    action: KEEP_AS_NON_CORE
    reason: >-
      The link to the cytoskeleton is real but indirect (via Ras/Rap and actin
      dynamics downstream of Gα2) and the generic ARBA term does not represent a
      core molecular function.
    supported_by:
    - reference_id: PMID:27237792
      supporting_text: resulting in defective chemotaxis
- term:
    id: GO:0007165
    label: signal transduction
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: >-
      IEA inference of the generic parent term "signal transduction". Correct
      but subsumed by the more specific GPCR-signaling annotations.
    action: KEEP_AS_NON_CORE
    reason: >-
      Accurate but too high-level to be informative; the specific role is in
      cAMP GPCR signaling captured by GO:0007186/GO:0007188.
    supported_by:
    - reference_id: PMID:15715993
      supporting_text: act as molecular switches to relay information from transmembrane receptors to intracellular effectors
- term:
    id: GO:0007186
    label: G protein-coupled receptor signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: >-
      IEA inference placing Gα2 in GPCR signaling. This is the defining process
      for a heterotrimeric Gα subunit coupling the cAMP receptor cAR1.
    action: ACCEPT
    reason: >-
      GPCR signaling is a core biological process for Gα2; well supported by the
      experimental literature on cAMP receptor coupling.
    supported_by:
    - reference_id: PMID:34418534
      supporting_text: required for chemotaxis to cAMP during the onset of multicellular development
- term:
    id: GO:0019001
    label: guanyl nucleotide binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: >-
      IEA inference of guanyl nucleotide binding, the parent of GTP binding.
      Correct but redundant with the more specific GO:0005525 (GTP binding).
    action: KEEP_AS_NON_CORE
    reason: >-
      Accurate but non-specific; the informative term is GTP binding.
    supported_by:
    - reference_id: PMID:8280098
      supporting_text: mutant fgd A, lacking the G-protein alpha-subunit G alpha 2, showed no stimulation by either cAMP
- term:
    id: GO:0031683
    label: G-protein beta/gamma-subunit complex binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: >-
      IEA inference that Gα2 binds the Gβγ dimer. This is intrinsic to
      heterotrimer assembly and is directly demonstrated by Gα2/Gβγ FRET and by
      the beta-subunit binding annotation (PMID:15563608).
    action: ACCEPT
    reason: >-
      Association with Gβγ is a defining property of the Gα subunit; core
      molecular function related to complex assembly.
    supported_by:
    - reference_id: PMID:15563608
      supporting_text: triggers dissociation of Galpha and Gbetagamma subunits
- term:
    id: GO:1904776
    label: regulation of protein localization to cell cortex
  evidence_type: IMP
  original_reference_id: PMID:40934557
  qualifier: acts_upstream_of_or_within
  review:
    summary: >-
      IMP annotation from the DydA RasG-reporter study, where cortical/leading-edge
      localization of the activated-RasG biosensor required GPCR (Car1/3) and
      G-protein signaling. This places Gα2 upstream of the cortical recruitment
      of a downstream Ras effector.
    action: KEEP_AS_NON_CORE
    reason: >-
      The effect on cortical protein localization is an indirect, downstream
      consequence of Gα2-initiated chemoattractant signaling rather than a core
      molecular function.
    supported_by:
    - reference_id: PMID:40934557
      supporting_text: This localization required GPCR Car1/3 and G-protein signaling
- term:
    id: GO:0007264
    label: small GTPase-mediated signal transduction
  evidence_type: IMP
  original_reference_id: PMID:8280098
  qualifier: involved_in
  review:
    summary: >-
      IMP annotation to small GTPase-mediated signal transduction citing the
      phospholipase C study. Gα2 is a heterotrimeric (not small) GTPase, and the
      cited paper concerns cAMP/GTP-analog regulation of phospholipase C rather
      than small GTPase signaling per se. The cached content does not establish
      this specific term, and I cannot verify the curator's full-text basis.
    action: UNDECIDED
    reason: >-
      The cited reference (abstract available) addresses G alpha 2 as the
      stimulatory G protein for phospholipase C, not small GTPase-mediated signal
      transduction. Although Gα2 does act upstream of Ras/Rap small GTPases in
      other studies, the term-to-reference support here cannot be confirmed, so
      per policy this is left UNDECIDED rather than removed.
- term:
    id: GO:0005091
    label: guanyl-nucleotide exchange factor adaptor activity
  evidence_type: IDA
  original_reference_id: PMID:27237792
  qualifier: enables
  review:
    summary: >-
      Direct-evidence annotation: activated Gα2 binds and stimulates the
      Rap1-specific GEF GflB, directly coupling the cAMP GPCR to Rap1. Gα2 thus
      acts as a Gα-stimulated GEF adaptor for monomeric G-protein signaling.
    action: ACCEPT
    reason: >-
      This captures a well-supported, receptor-proximal core molecular function
      of Gα2 as an effector-activating adaptor at the leading edge.
    supported_by:
    - reference_id: PMID:27237792
      supporting_text: we identify GflB, a Gα2 binding partner that directly couples the Dictyostelium cyclic AMP GPCR to Rap1
    - reference_id: PMID:27237792
      supporting_text: functions as a Gα-stimulated, Rap1-specific guanine nucleotide exchange factor
- term:
    id: GO:0030695
    label: GTPase regulator activity
  evidence_type: IDA
  original_reference_id: PMID:21103944
  qualifier: enables
  review:
    summary: >-
      IDA annotation reflecting that chemoattractant-stimulated activation of the
      small GTPase Rap1 requires Gα2. Gα2 regulates Rap1 activation state
      (via GflB), consistent with GTPase regulator activity.
    action: KEEP_AS_NON_CORE
    reason: >-
      Correct but generic; the more precise mechanistic function is the
      GflB-stimulating GEF-adaptor activity (GO:0005091). Retained as non-core.
    supported_by:
    - reference_id: PMID:21103944
      supporting_text: was absent in cells lacking chemoattractant cAMP receptors cAR1/cAR3 or a subunit of the heterotrimeric G-protein complex Gα2
- term:
    id: GO:0009617
    label: response to bacterium
  evidence_type: IDA
  original_reference_id: PMID:35544746
  qualifier: acts_upstream_of_or_within
  review:
    summary: >-
      IDA annotation citing an environmental-microbiology study of Dictyostelium
      predation on metal-reducing bacteria. The cached abstract does not mention
      Gα2/gpaB, and I cannot verify a specific role for Gα2 in this response
      from the available text.
    action: UNDECIDED
    reason: >-
      Per policy, an experimental annotation whose supporting publication I
      cannot verify (abstract-only, no mention of the gene) is left UNDECIDED
      rather than removed.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:27044073
  qualifier: is_active_in
  review:
    summary: >-
      Direct-evidence plasma membrane localization/activity. Receptor activation
      recruits the G protein to the plasma membrane from the cytosol (Gip1
      shuttling), the site where Gα2 signaling occurs.
    action: ACCEPT
    reason: >-
      The plasma membrane is the principal site of Gα2 action; well supported by
      the shuttling data and by palmitoylation-dependent membrane targeting.
    supported_by:
    - reference_id: PMID:27044073
      supporting_text: Receptor activation induced G-protein translocation to the plasma membrane from the cytosol in a Gip1-dependent manner
- term:
    id: GO:0006355
    label: regulation of DNA-templated transcription
  evidence_type: IMP
  original_reference_id: PMID:34418534
  qualifier: involved_in
  review:
    summary: >-
      IMP annotation from the MAPK docking-motif study. The Gα2 D-motif is
      required for cAMP-stimulated nucleocytoplasmic shuttling of the GtaC
      transcription factor, a process linked to gene regulation during
      aggregation. Gα2 thus influences transcription indirectly via control of
      GtaC.
    action: KEEP_AS_NON_CORE
    reason: >-
      The transcriptional effect is indirect (mediated through GtaC
      localization) rather than a direct/core molecular function of Gα2.
    supported_by:
    - reference_id: PMID:34418534
      supporting_text: shuttling of GtaC is thought to be an important process for gene regulation during the aggregation phase of development
    - reference_id: PMID:34418534
      supporting_text: Expression of the Gα2 subunit but not the Gα2D− subunit fully restored the ability of cAMP to stimulate the translocation of the GtaC transcription factor
- term:
    id: GO:0046825
    label: regulation of protein export from nucleus
  evidence_type: IMP
  original_reference_id: PMID:34418534
  qualifier: involved_in
  review:
    summary: >-
      IMP annotation reflecting the requirement of the Gα2 D-motif for
      cAMP-stimulated movement of the GtaC transcription factor from the nucleus
      to the cytoplasm.
    action: KEEP_AS_NON_CORE
    reason: >-
      Gα2 regulates GtaC nuclear export indirectly through its signaling and
      docking-motif function; a downstream, non-core role.
    supported_by:
    - reference_id: PMID:34418534
      supporting_text: movement of GtaC from the nucleus to the cytoplasm
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: PMID:27044073
  qualifier: located_in
  review:
    summary: >-
      Direct-evidence cytosolic localization: a pool of the heterotrimeric G
      protein is sequestered in the cytosol by Gip1 and shuttled to the membrane
      upon receptor activation.
    action: ACCEPT
    reason: >-
      A defined cytosolic reserve pool of Gα2 exists and is functionally
      important for extending the dynamic range of chemotaxis.
    supported_by:
    - reference_id: PMID:27044073
      supporting_text: Gip1 was found to bind and sequester G proteins in cytosolic pools
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:11264536
  qualifier: is_active_in
  review:
    summary: >-
      Direct-evidence plasma membrane localization/activity consistent with the
      FRET studies of receptor-mediated G-protein activation at the cell surface
      and with palmitoylation-dependent membrane targeting.
    action: ACCEPT
    reason: >-
      The plasma membrane is the principal site of Gα2 signaling; corroborated
      across multiple studies.
    supported_by:
    - reference_id: PMID:29352733
      supporting_text: plasma membrane localization
- term:
    id: GO:0031681
    label: G-protein beta-subunit binding
  evidence_type: IDA
  original_reference_id: PMID:15563608
  qualifier: enables
  review:
    summary: >-
      Direct-evidence binding to the G-protein beta subunit, demonstrated by
      Gα/Gβγ FRET showing receptor-triggered dissociation and reassociation of
      the subunits.
    action: ACCEPT
    reason: >-
      Association with the Gβ(γ) subunit is a defining, core property of Gα2
      within the heterotrimer.
    supported_by:
    - reference_id: PMID:15563608
      supporting_text: triggers dissociation of Galpha and Gbetagamma subunits
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: PMID:11264536
  qualifier: located_in
  review:
    summary: >-
      Direct-evidence cytosolic localization, consistent with the cytosolic pool
      of heterotrimeric G protein described in Dictyostelium.
    action: ACCEPT
    reason: >-
      Gα2 has a documented cytosolic pool in addition to its membrane pool.
    supported_by:
    - reference_id: PMID:27044073
      supporting_text: Gip1 was found to bind and sequester G proteins in cytosolic pools
- term:
    id: GO:0005525
    label: GTP binding
  evidence_type: IC
  original_reference_id: PMID:8280098
  qualifier: enables
  review:
    summary: >-
      Curator-inferred (IC) GTP binding, consistent with the GTP-analog-dependent
      stimulation of phospholipase C through Gα2 and the conserved
      guanine-nucleotide-binding fold.
    action: ACCEPT
    reason: >-
      GTP binding is an intrinsic, core molecular function of the Gα2 subunit.
    supported_by:
    - reference_id: PMID:8280098
      supporting_text: mutant fgd A, lacking the G-protein alpha-subunit G alpha 2, showed no stimulation by either cAMP...indicating that G alpha 2 is the stimulatory G-protein
- term:
    id: GO:0003925
    label: G protein activity
  evidence_type: IMP
  original_reference_id: PMID:8280098
  qualifier: enables
  review:
    summary: >-
      IMP annotation: loss of Gα2 (mutant fgd A) abolishes cAMP- and
      GTP-analog-stimulated phospholipase C activity, identifying Gα2 as the
      functional stimulatory G protein. Direct genetic support for G protein
      activity.
    action: ACCEPT
    reason: >-
      This is core molecular-function evidence: the Gα2-null phenotype
      demonstrates that Gα2 provides the stimulatory G protein activity coupling
      the cAMP receptor to phospholipase C.
    supported_by:
    - reference_id: PMID:8280098
      supporting_text: mutant fgd A, lacking the G-protein alpha-subunit G alpha 2, showed no stimulation by either cAMP...indicating that G alpha 2 is the stimulatory G-protein
- term:
    id: GO:0001664
    label: G protein-coupled receptor binding
  evidence_type: IDA
  original_reference_id: PMID:11264536
  qualifier: enables
  review:
    summary: >-
      Direct-evidence GPCR binding: in living cells, occupied cAMP receptors
      catalyze the Gα2 G-protein cycle, demonstrating functional coupling of Gα2
      to the receptor.
    action: ACCEPT
    reason: >-
      Physical/functional coupling to the occupied cAMP receptor is a core
      aspect of Gα2 activation.
    supported_by:
    - reference_id: PMID:11264536
      supporting_text: occupied receptors, whether or not they are phosphorylated, catalyze the G-protein cycle
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15563608
  qualifier: enables
  review:
    summary: >-
      Generic IPI protein-binding annotation from the FRET study; the meaningful
      interaction (with the Gβγ subunit) is better captured by GO:0031681
      (G-protein beta-subunit binding) annotated from the same paper.
    action: KEEP_AS_NON_CORE
    reason: >-
      GO:0005515 is uninformative; the specific interaction is already recorded
      as beta-subunit binding. Retained as non-core.
    supported_by:
    - reference_id: PMID:15563608
      supporting_text: triggers dissociation of Galpha and Gbetagamma subunits
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23576747
  qualifier: enables
  review:
    summary: >-
      IPI protein-binding annotation from the Ric8 study. Gα proteins were used
      as bait to identify Ric8 as a nonreceptor GEF for Gα, evidencing a
      physical Gα2-Ric8 interaction. The bare term is uninformative.
    action: KEEP_AS_NON_CORE
    reason: >-
      The Ric8 interaction is experimentally supported but GO:0005515 is too
      generic to be a core function descriptor; retained as non-core.
    supported_by:
    - reference_id: PMID:23576747
      supporting_text: nonreceptor guanine nucleotide exchange factor for Gα-protein
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24349132
  qualifier: enables
  review:
    summary: >-
      IPI protein-binding annotation reflecting the interaction between the
      RabGAP Dd Rbg-3 and Gα subunits (including Gα2) in an activity-dependent
      manner. Bare "protein binding" is uninformative.
    action: KEEP_AS_NON_CORE
    reason: >-
      The Dd Rbg-3 interaction is supported but the generic term is not a core
      function; retained as non-core.
    supported_by:
    - reference_id: PMID:24349132
      supporting_text: Dd Rbg-3 interacts with 2 Gα subunits in an activity-dependent manner in vitro
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24930026
  qualifier: enables
  review:
    summary: >-
      IPI protein-binding annotation from the DdRACK1 (gpbB) study, which shows
      DdRACK1 interacts with G-protein alpha, beta and gamma subunits by yeast
      two-hybrid, pulldown and immunoprecipitation. Bare term is uninformative.
    action: KEEP_AS_NON_CORE
    reason: >-
      The DdRACK1 interaction is supported but GO:0005515 is too generic for a
      core function; retained as non-core.
    supported_by:
    - reference_id: PMID:24930026
      supporting_text: DdRACK1 interacts with G protein subunits alpha, beta and gamma as shown by yeast two-hybrid, pulldown, and immunoprecipitation assays
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:27044073
  qualifier: enables
  review:
    summary: >-
      IPI protein-binding annotation reflecting the Gip1-G protein interaction,
      by which Gip1 binds and sequesters the heterotrimeric G protein in the
      cytosol. Bare term is uninformative.
    action: KEEP_AS_NON_CORE
    reason: >-
      The Gip1 interaction is supported but the generic term does not represent
      a core function; retained as non-core.
    supported_by:
    - reference_id: PMID:27044073
      supporting_text: Gip1 was found to bind and sequester G proteins in cytosolic pools
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:27237792
  qualifier: enables
  review:
    summary: >-
      IPI protein-binding annotation for the Gα2-GflB interaction. This
      interaction is functionally captured by the GEF-adaptor activity
      annotation (GO:0005091) from the same study; the bare term is
      uninformative on its own.
    action: KEEP_AS_NON_CORE
    reason: >-
      The GflB interaction is core to Gα2 signaling but is better represented by
      GO:0005091; GO:0005515 itself is retained as non-core.
    supported_by:
    - reference_id: PMID:27237792
      supporting_text: we identify GflB, a Gα2 binding partner that directly couples the Dictyostelium cyclic AMP GPCR to Rap1
- term:
    id: GO:0005834
    label: heterotrimeric G-protein complex
  evidence_type: IDA
  original_reference_id: PMID:11264536
  qualifier: part_of
  review:
    summary: >-
      Direct-evidence heterotrimeric complex membership: FRET between Gα2 and
      Gβγ demonstrates the assembled heterotrimer dissociating and reassociating
      with receptor activation.
    action: ACCEPT
    reason: >-
      Core cellular-component assignment, directly demonstrated in living cells.
    supported_by:
    - reference_id: PMID:11264536
      supporting_text: The G-protein heterotrimer rapidly dissociated and reassociated upon addition and removal of chemoattractant
- term:
    id: GO:0005834
    label: heterotrimeric G-protein complex
  evidence_type: IDA
  original_reference_id: PMID:12217653
  qualifier: part_of
  review:
    summary: >-
      Direct-evidence heterotrimeric complex membership from the FRET
      methodology paper, in which Galpha2 and Gbetagamma were tagged to monitor
      the state of the G-protein heterotrimer.
    action: ACCEPT
    reason: >-
      Corroborates the core heterotrimeric-complex assignment for Gα2.
    supported_by:
    - reference_id: PMID:12217653
      supporting_text: The Galpha(2)and Gbetagamma proteins were tagged with cyan and yellow fluorescent proteins and used to observe the state of the G-protein heterotrimer
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:29352733
  qualifier: is_active_in
  review:
    summary: >-
      Direct-evidence plasma membrane localization. Gα2 is palmitoylated on
      Cys-4, and loss of this palmitoylation site redistributes Gα2 within the
      cell, establishing palmitoylation-dependent plasma membrane targeting.
    action: ACCEPT
    reason: >-
      The plasma membrane is the principal functional site of Gα2, dependent on
      its lipid modifications; a core localization.
    supported_by:
    - reference_id: PMID:29352733
      supporting_text: Loss of this palmitoylation site results in redistribution of Gα2 within the cell
    - reference_id: PMID:29352733
      supporting_text: plasma membrane localization
- term:
    id: GO:0007189
    label: adenylate cyclase-activating G protein-coupled receptor signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:15715993
  qualifier: involved_in
  review:
    summary: >-
      IMP annotation from the loss-of-function mutant screen. Gα2 is essential
      for the cAMP-driven aggregation program; loss of Gα2 blocks entry into
      development. The specific "adenylate cyclase-activating" wording is a
      curator interpretation of the cAMP-relay role.
    action: KEEP_AS_NON_CORE
    reason: >-
      Gα2 is required for the aggregation-stage cAMP signaling program, but
      adenylate cyclase activation in Dictyostelium is classically driven by
      Gβγ; the core Gα2 processes are better captured by chemotaxis, aggregation,
      and adenylate cyclase-modulating GPCR signaling. Retained as non-core.
    supported_by:
    - reference_id: PMID:15715993
      supporting_text: G alpha2 is essential for the developmental life cycle of Dictyostelium
- term:
    id: GO:0006909
    label: phagocytosis
  evidence_type: IMP
  original_reference_id: PMID:9647646
  qualifier: acts_upstream_of_or_within
  review:
    summary: >-
      IMP annotation citing the Gβ-null study. That paper explicitly reports
      that single Gα-subunit nulls, specifically Gα2 (and Gα4), do NOT show
      reduced phagocytosis; the phagocytosis defect is a property of the shared
      Gβ subunit, not Gα2. The annotation is therefore contradicted by its own
      cited reference.
    action: REMOVE
    reason: >-
      The cited reference directly states that Gα2-null mutants are not impaired
      in phagocytosis, so attributing phagocytosis to Gα2 is not supported and is
      contradicted by the evidence. Phagocytosis in this context depends on Gβ,
      not the aggregation-stage Gα2.
    supported_by:
    - reference_id: PMID:9647646
      supporting_text: nor did we find reduced phagocytosis rates in Gα2 and Gα4 null mutants
- term:
    id: GO:0030041
    label: actin filament polymerization
  evidence_type: IMP
  original_reference_id: PMID:9647646
  qualifier: acts_upstream_of_or_within
  review:
    summary: >-
      IMP annotation citing the Gβ-null study, whose actin-polymerization
      phenotypes were characterized in Gβ-null cells. Chemoattractant
      (cAMP)-induced actin responses do require Gα2 upstream, so Gα2 can be
      considered upstream of actin polymerization during chemotaxis, but this is
      an indirect, downstream role.
    action: KEEP_AS_NON_CORE
    reason: >-
      Gα2 signaling drives actin remodeling during chemoattractant-directed
      migration, but actin filament polymerization is a downstream cytoskeletal
      output rather than a core molecular function of Gα2.
    supported_by:
    - reference_id: PMID:9647646
      supporting_text: signaling through heterotrimeric G proteins is required for regulating the actin cytoskeleton during phagocytic uptake, as previously shown for chemotaxis
- term:
    id: GO:0006935
    label: chemotaxis
  evidence_type: IMP
  original_reference_id: PMID:15715993
  qualifier: acts_upstream_of_or_within
  review:
    summary: >-
      IMP annotation: Gα2 is required for chemotaxis to cAMP at the onset of
      multicellular development, and loss-of-function Gα2 mutations block the
      developmental/aggregation program.
    action: ACCEPT
    reason: >-
      Chemotaxis toward cAMP is a core biological process mediated by Gα2 and is
      strongly supported by the genetics.
    supported_by:
    - reference_id: PMID:34418534
      supporting_text: required for chemotaxis to cAMP during the onset of multicellular development
    - reference_id: PMID:15715993
      supporting_text: the loss of G alpha2 function results in a
- term:
    id: GO:0031152
    label: aggregation involved in sorocarp development
  evidence_type: IMP
  original_reference_id: PMID:15715993
  qualifier: acts_upstream_of_or_within
  review:
    summary: >-
      IMP annotation: Gα2 is essential for aggregation and the developmental life
      cycle; loss of Gα2 causes failure of cells to enter the developmental
      phase. This is the defining Gα2-null phenotype.
    action: ACCEPT
    reason: >-
      Aggregation during sorocarp (fruiting body) development is a core
      biological process for Gα2, essential and well established.
    supported_by:
    - reference_id: PMID:15715993
      supporting_text: G alpha2 is essential for the developmental life cycle of Dictyostelium
    - reference_id: PMID:34418534
      supporting_text: The Dictyostelium Gα2 G protein subunit is required for chemotaxis to cAMP during the onset of multicellular development
- term:
    id: GO:0007188
    label: adenylate cyclase-modulating G protein-coupled receptor signaling pathway
  evidence_type: IDA
  original_reference_id: PMID:15563608
  qualifier: involved_in
  review:
    summary: >-
      Direct-evidence involvement in cAMP GPCR (adenylate cyclase-modulating)
      signaling, from the quantitative single-cell imaging of chemoattractant
      receptor activation and G-protein dynamics.
    action: ACCEPT
    reason: >-
      Gα2 transduces cAMP GPCR signaling during gradient sensing, a core process.
    supported_by:
    - reference_id: PMID:15563608
      supporting_text: triggers dissociation of Galpha and Gbetagamma subunits
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: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:11264536
  title: Receptor-mediated activation of heterotrimeric G-proteins in living cells.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      FRET between Gα2 and Gβγ in living Dictyostelium cells directly demonstrates
      receptor-triggered heterotrimer dissociation; supports G-protein activity,
      heterotrimeric complex membership and receptor coupling.
- id: PMID:12217653
  title: Monitoring receptor-mediated activation of heterotrimeric G-proteins by fluorescence
    resonance energy transfer.
  findings: []
- id: PMID:15563608
  title: Quantitative imaging of single live cells reveals spatiotemporal dynamics
    of multistep signaling events of chemoattractant gradient sensing in Dictyostelium.
  findings: []
- id: PMID:15715993
  title: Loss-of-function mutations identified in the Helical domain of the G protein
    alpha-subunit, G alpha2, of Dictyostelium discoideum.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Loss-of-function screen establishing that Gα2 is essential for the
      developmental life cycle; supports the aggregation and chemotaxis core
      processes.
- id: PMID:21103944
  title: Chemoattractant-mediated Rap1 activation requires GPCR/G proteins.
  findings: []
- id: PMID:23576747
  title: Dictyostelium Ric8 is a nonreceptor guanine exchange factor for heterotrimeric
    G proteins and is important for development and chemotaxis.
  findings: []
- id: PMID:24349132
  title: A RabGAP regulates life-cycle duration via trimeric G-protein cascades in
    Dictyostelium discoideum.
  findings: []
- id: PMID:24930026
  title: The Dictyostelium discoideum RACK1 orthologue has roles in growth and development.
  findings: []
- id: PMID:27044073
  title: Heterotrimeric G-protein shuttling via Gip1 extends the dynamic range of
    eukaryotic chemotaxis.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Establishes the cytosolic reserve pool of the heterotrimeric G protein and
      Gip1-dependent shuttling to the plasma membrane; supports plasma membrane
      and cytosol localization annotations.
- id: PMID:27237792
  title: A Gα-Stimulated RapGEF Is a Receptor-Proximal Regulator of Dictyostelium
    Chemotaxis.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Identifies GflB as a Gα2 binding partner and Gα-stimulated Rap1 GEF that
      couples the cAMP GPCR to Rap1; primary support for the GEF-adaptor core
      function.
- id: PMID:29352733
  title: Localization of palmitoylated and activated G protein α-subunit in Dictyostelium
    discoideum.
  findings: []
- id: PMID:34418534
  title: MAPK docking motif in the Dictyostelium Gα2 subunit is required for aggregation
    and transcription factor translocation.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Full text available; the Gα2 amino-terminal D-motif is required for
      cAMP-stimulated GtaC transcription-factor nucleocytoplasmic shuttling and
      for aggregation; supports the transcription/nuclear-export non-core roles.
- id: PMID:35544746
  title: Soil Amoebae Affect Iron and Chromium Reduction through Preferential Predation
    between Two Metal-Reducing Bacteria.
  findings: []
  reference_review:
    relevance: LOW
    correctness: UNVERIFIED
    review_notes: >-
      Environmental-microbiology predation study; cached abstract does not
      mention Gα2/gpaB, so its support for a Gα2 response-to-bacterium annotation
      could not be verified.
- id: PMID:40934557
  title: The Ras association domain of DydA as a specific reporter of activated RasG
    in Dictyostelium.
  findings: []
- id: PMID:42121920
  title: Heterotrimeric G Protein-RasGAP Coupling Drives Adaptation During Chemotaxis.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      Shows the RasGAP C2GAP1 directly associates with Gα2 (preferentially the
      activated state) as a G-protein effector; supports the C2GAP1 interaction.
- id: PMID:8280098
  title: Phospholipase C in Dictyostelium discoideum. Identification of stimulatory
    and inhibitory surface receptors and G-proteins.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Gα2-null (fgd A) abolishes cAMP/GTP-analog-stimulated phospholipase C,
      identifying Gα2 as the stimulatory G protein; supports G protein activity
      and GTP binding.
- id: PMID:9647646
  title: G protein beta subunit-null mutants are impaired in phagocytosis and chemotaxis
    due to inappropriate regulation of the actin cytoskeleton.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: MISCITED
    review_notes: >-
      This is a Gβ-null study; it explicitly reports that Gα2-null mutants are
      NOT impaired in phagocytosis, so it does not support a Gα2 phagocytosis
      annotation (the phagocytosis phenotype is Gβ-specific).
core_functions:
- description: >-
    Gα2 is the heterotrimeric G-protein alpha subunit that transduces cAMP
    chemoattractant signals from the cAR1 GPCR during aggregation. As the
    guanine-nucleotide-binding subunit it cycles between an inactive GDP-bound
    heterotrimeric state (with Gβγ) and an active GTP-bound state via its
    intrinsic GTPase activity, acting as the molecular switch for aggregation-stage
    cAMP signaling.
  molecular_function:
    id: GO:0003925
    label: G protein activity
  directly_involved_in:
  - id: GO:0007188
    label: adenylate cyclase-modulating G protein-coupled receptor signaling pathway
  - id: GO:0031152
    label: aggregation involved in sorocarp development
  locations:
  - id: GO:0005886
    label: plasma membrane
  - id: GO:0005829
    label: cytosol
  in_complex:
    id: GO:0005834
    label: heterotrimeric G-protein complex
  supported_by:
  - reference_id: PMID:8280098
    supporting_text: mutant fgd A, lacking the G-protein alpha-subunit G alpha 2, showed no stimulation by either cAMP...indicating that G alpha 2 is the stimulatory G-protein
  - reference_id: PMID:11264536
    supporting_text: The G-protein heterotrimer rapidly dissociated and reassociated upon addition and removal of chemoattractant
  - reference_id: PMID:15715993
    supporting_text: G alpha2 is essential for the developmental life cycle of Dictyostelium
- description: >-
    Activated Gα2 directly couples the cAMP receptor to monomeric G-protein
    signaling by binding and stimulating the Rap1-specific guanine nucleotide
    exchange factor GflB, functioning as a Gα-stimulated GEF adaptor that balances
    Ras and Rap signaling at the leading edge during chemotaxis.
  molecular_function:
    id: GO:0005091
    label: guanyl-nucleotide exchange factor adaptor activity
  directly_involved_in:
  - id: GO:0006935
    label: chemotaxis
  locations:
  - id: GO:0005886
    label: plasma membrane
  supported_by:
  - reference_id: PMID:27237792
    supporting_text: we identify GflB, a Gα2 binding partner that directly couples the Dictyostelium cyclic AMP GPCR to Rap1
  - reference_id: PMID:27237792
    supporting_text: functions as a Gα-stimulated, Rap1-specific guanine nucleotide exchange factor