gpaB

UniProt ID: P16051
Organism: Dictyostelium discoideum
Review Status: COMPLETE
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Gene 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 Review

GO Term Evidence Action Reason
GO:0003925 G protein activity
IBA
GO_REF:0000033
ACCEPT
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.
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.
Supporting Evidence:
PMID:8280098
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
GO:0005737 cytoplasm
IBA
GO_REF:0000033
ACCEPT
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.
Reason: A cytosolic pool of the G protein exists and is shuttled to the membrane upon receptor activation, consistent with cytoplasmic localization/activity.
Supporting Evidence:
PMID:27044073
Gip1 was found to bind and sequester G proteins in cytosolic pools
GO:0007188 adenylate cyclase-modulating G protein-coupled receptor signaling pathway
IBA
GO_REF:0000033
ACCEPT
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.
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).
Supporting Evidence:
PMID:34418534
required for chemotaxis to cAMP during the onset of multicellular development
GO:0005834 heterotrimeric G-protein complex
IBA
GO_REF:0000033
ACCEPT
Summary: IBA inference of heterotrimeric G-protein complex membership. Directly confirmed in Dictyostelium by FRET between Gα2 and Gβγ subunits.
Reason: Gα2 assembles with Gβ and Gγ into a heterotrimer that dissociates on receptor activation; this is a core cellular-component assignment.
Supporting Evidence:
PMID:11264536
The G-protein heterotrimer rapidly dissociated and reassociated upon addition and removal of chemoattractant
GO:0001664 G protein-coupled receptor binding
IEA
GO_REF:0000002
ACCEPT
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).
Reason: Receptor-catalyzed nucleotide exchange requires Gα2 engagement with the occupied cAMP receptor, a core aspect of its signaling function.
Supporting Evidence:
PMID:11264536
occupied receptors, whether or not they are phosphorylated, catalyze the G-protein cycle
GO:0003924 GTPase activity
IEA
GO_REF:0000120
ACCEPT
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.
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).
Supporting Evidence:
PMID:15715993
The switch mechanism is a function of the inherent GTPase activity of the alpha-subunit
GO:0005515 protein binding
IPI
PMID:42121920
Heterotrimeric G Protein-RasGAP Coupling Drives Adaptation D...
KEEP AS NON CORE
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.
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.
Supporting Evidence:
PMID:42121920
C2GAP1 directly associates with Gα2 in both GDP- and GTP-bound states, with preferential binding to activated Gα2
GO:0005525 GTP binding
IEA
GO_REF:0000002
ACCEPT
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.
Reason: GTP binding is intrinsic to Gα2 function as a nucleotide-dependent molecular switch; a core molecular function.
Supporting Evidence:
PMID:8280098
mutant fgd A, lacking the G-protein alpha-subunit G alpha 2, showed no stimulation by either cAMP
GO:0005737 cytoplasm
IEA
GO_REF:0000117
ACCEPT
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.
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.
Supporting Evidence:
PMID:27044073
Gip1 was found to bind and sequester G proteins in cytosolic pools
GO:0005834 heterotrimeric G-protein complex
IEA
GO_REF:0000002
ACCEPT
Summary: InterPro2GO (IEA) heterotrimeric complex membership, redundant with and corroborated by direct-evidence annotations (PMID:11264536, PMID:12217653).
Reason: Gα2 is a subunit of the heterotrimeric G protein; a core cellular component assignment.
Supporting Evidence:
PMID:11264536
The G-protein heterotrimer rapidly dissociated and reassociated upon addition and removal of chemoattractant
GO:0007010 cytoskeleton organization
IEA
GO_REF:0000117
KEEP AS NON CORE
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.
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.
Supporting Evidence:
PMID:27237792
resulting in defective chemotaxis
GO:0007165 signal transduction
IEA
GO_REF:0000002
KEEP AS NON CORE
Summary: IEA inference of the generic parent term "signal transduction". Correct but subsumed by the more specific GPCR-signaling annotations.
Reason: Accurate but too high-level to be informative; the specific role is in cAMP GPCR signaling captured by GO:0007186/GO:0007188.
Supporting Evidence:
PMID:15715993
act as molecular switches to relay information from transmembrane receptors to intracellular effectors
GO:0007186 G protein-coupled receptor signaling pathway
IEA
GO_REF:0000002
ACCEPT
Summary: IEA inference placing Gα2 in GPCR signaling. This is the defining process for a heterotrimeric Gα subunit coupling the cAMP receptor cAR1.
Reason: GPCR signaling is a core biological process for Gα2; well supported by the experimental literature on cAMP receptor coupling.
Supporting Evidence:
PMID:34418534
required for chemotaxis to cAMP during the onset of multicellular development
GO:0019001 guanyl nucleotide binding
IEA
GO_REF:0000002
KEEP AS NON CORE
Summary: IEA inference of guanyl nucleotide binding, the parent of GTP binding. Correct but redundant with the more specific GO:0005525 (GTP binding).
Reason: Accurate but non-specific; the informative term is GTP binding.
Supporting Evidence:
PMID:8280098
mutant fgd A, lacking the G-protein alpha-subunit G alpha 2, showed no stimulation by either cAMP
GO:0031683 G-protein beta/gamma-subunit complex binding
IEA
GO_REF:0000002
ACCEPT
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).
Reason: Association with Gβγ is a defining property of the Gα subunit; core molecular function related to complex assembly.
Supporting Evidence:
PMID:15563608
triggers dissociation of Galpha and Gbetagamma subunits
GO:1904776 regulation of protein localization to cell cortex
IMP
PMID:40934557
The Ras association domain of DydA as a specific reporter of...
KEEP AS NON CORE
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.
Reason: The effect on cortical protein localization is an indirect, downstream consequence of Gα2-initiated chemoattractant signaling rather than a core molecular function.
Supporting Evidence:
PMID:40934557
This localization required GPCR Car1/3 and G-protein signaling
GO:0007264 small GTPase-mediated signal transduction
IMP
PMID:8280098
Phospholipase C in Dictyostelium discoideum. Identification ...
UNDECIDED
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.
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.
GO:0005091 guanyl-nucleotide exchange factor adaptor activity
IDA
PMID:27237792
A Gα-Stimulated RapGEF Is a Receptor-Proximal Regulator of D...
ACCEPT
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.
Reason: This captures a well-supported, receptor-proximal core molecular function of Gα2 as an effector-activating adaptor at the leading edge.
Supporting Evidence:
PMID:27237792
we identify GflB, a Gα2 binding partner that directly couples the Dictyostelium cyclic AMP GPCR to Rap1
PMID:27237792
functions as a Gα-stimulated, Rap1-specific guanine nucleotide exchange factor
GO:0030695 GTPase regulator activity
IDA
PMID:21103944
Chemoattractant-mediated Rap1 activation requires GPCR/G pro...
KEEP AS NON CORE
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.
Reason: Correct but generic; the more precise mechanistic function is the GflB-stimulating GEF-adaptor activity (GO:0005091). Retained as non-core.
Supporting Evidence:
PMID:21103944
was absent in cells lacking chemoattractant cAMP receptors cAR1/cAR3 or a subunit of the heterotrimeric G-protein complex Gα2
GO:0009617 response to bacterium
IDA
PMID:35544746
Soil Amoebae Affect Iron and Chromium Reduction through Pref...
UNDECIDED
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.
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.
GO:0005886 plasma membrane
IDA
PMID:27044073
Heterotrimeric G-protein shuttling via Gip1 extends the dyna...
ACCEPT
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.
Reason: The plasma membrane is the principal site of Gα2 action; well supported by the shuttling data and by palmitoylation-dependent membrane targeting.
Supporting Evidence:
PMID:27044073
Receptor activation induced G-protein translocation to the plasma membrane from the cytosol in a Gip1-dependent manner
GO:0006355 regulation of DNA-templated transcription
IMP
PMID:34418534
MAPK docking motif in the Dictyostelium Gα2 subunit is requi...
KEEP AS NON CORE
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.
Reason: The transcriptional effect is indirect (mediated through GtaC localization) rather than a direct/core molecular function of Gα2.
Supporting Evidence:
PMID:34418534
shuttling of GtaC is thought to be an important process for gene regulation during the aggregation phase of development
PMID:34418534
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
GO:0046825 regulation of protein export from nucleus
IMP
PMID:34418534
MAPK docking motif in the Dictyostelium Gα2 subunit is requi...
KEEP AS NON CORE
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.
Reason: Gα2 regulates GtaC nuclear export indirectly through its signaling and docking-motif function; a downstream, non-core role.
Supporting Evidence:
PMID:34418534
movement of GtaC from the nucleus to the cytoplasm
GO:0005829 cytosol
IDA
PMID:27044073
Heterotrimeric G-protein shuttling via Gip1 extends the dyna...
ACCEPT
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.
Reason: A defined cytosolic reserve pool of Gα2 exists and is functionally important for extending the dynamic range of chemotaxis.
Supporting Evidence:
PMID:27044073
Gip1 was found to bind and sequester G proteins in cytosolic pools
GO:0005886 plasma membrane
IDA
PMID:11264536
Receptor-mediated activation of heterotrimeric G-proteins in...
ACCEPT
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.
Reason: The plasma membrane is the principal site of Gα2 signaling; corroborated across multiple studies.
Supporting Evidence:
PMID:29352733
plasma membrane localization
GO:0031681 G-protein beta-subunit binding
IDA
PMID:15563608
Quantitative imaging of single live cells reveals spatiotemp...
ACCEPT
Summary: Direct-evidence binding to the G-protein beta subunit, demonstrated by Gα/Gβγ FRET showing receptor-triggered dissociation and reassociation of the subunits.
Reason: Association with the Gβ(γ) subunit is a defining, core property of Gα2 within the heterotrimer.
Supporting Evidence:
PMID:15563608
triggers dissociation of Galpha and Gbetagamma subunits
GO:0005829 cytosol
IDA
PMID:11264536
Receptor-mediated activation of heterotrimeric G-proteins in...
ACCEPT
Summary: Direct-evidence cytosolic localization, consistent with the cytosolic pool of heterotrimeric G protein described in Dictyostelium.
Reason: Gα2 has a documented cytosolic pool in addition to its membrane pool.
Supporting Evidence:
PMID:27044073
Gip1 was found to bind and sequester G proteins in cytosolic pools
GO:0005525 GTP binding
IC
PMID:8280098
Phospholipase C in Dictyostelium discoideum. Identification ...
ACCEPT
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.
Reason: GTP binding is an intrinsic, core molecular function of the Gα2 subunit.
Supporting Evidence:
PMID:8280098
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
GO:0003925 G protein activity
IMP
PMID:8280098
Phospholipase C in Dictyostelium discoideum. Identification ...
ACCEPT
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.
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.
Supporting Evidence:
PMID:8280098
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
GO:0001664 G protein-coupled receptor binding
IDA
PMID:11264536
Receptor-mediated activation of heterotrimeric G-proteins in...
ACCEPT
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.
Reason: Physical/functional coupling to the occupied cAMP receptor is a core aspect of Gα2 activation.
Supporting Evidence:
PMID:11264536
occupied receptors, whether or not they are phosphorylated, catalyze the G-protein cycle
GO:0005515 protein binding
IPI
PMID:15563608
Quantitative imaging of single live cells reveals spatiotemp...
KEEP AS NON CORE
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.
Reason: GO:0005515 is uninformative; the specific interaction is already recorded as beta-subunit binding. Retained as non-core.
Supporting Evidence:
PMID:15563608
triggers dissociation of Galpha and Gbetagamma subunits
GO:0005515 protein binding
IPI
PMID:23576747
Dictyostelium Ric8 is a nonreceptor guanine exchange factor ...
KEEP AS NON CORE
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.
Reason: The Ric8 interaction is experimentally supported but GO:0005515 is too generic to be a core function descriptor; retained as non-core.
Supporting Evidence:
PMID:23576747
nonreceptor guanine nucleotide exchange factor for Gα-protein
GO:0005515 protein binding
IPI
PMID:24349132
A RabGAP regulates life-cycle duration via trimeric G-protei...
KEEP AS NON CORE
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.
Reason: The Dd Rbg-3 interaction is supported but the generic term is not a core function; retained as non-core.
Supporting Evidence:
PMID:24349132
Dd Rbg-3 interacts with 2 Gα subunits in an activity-dependent manner in vitro
GO:0005515 protein binding
IPI
PMID:24930026
The Dictyostelium discoideum RACK1 orthologue has roles in g...
KEEP AS NON CORE
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.
Reason: The DdRACK1 interaction is supported but GO:0005515 is too generic for a core function; retained as non-core.
Supporting Evidence:
PMID:24930026
DdRACK1 interacts with G protein subunits alpha, beta and gamma as shown by yeast two-hybrid, pulldown, and immunoprecipitation assays
GO:0005515 protein binding
IPI
PMID:27044073
Heterotrimeric G-protein shuttling via Gip1 extends the dyna...
KEEP AS NON CORE
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.
Reason: The Gip1 interaction is supported but the generic term does not represent a core function; retained as non-core.
Supporting Evidence:
PMID:27044073
Gip1 was found to bind and sequester G proteins in cytosolic pools
GO:0005515 protein binding
IPI
PMID:27237792
A Gα-Stimulated RapGEF Is a Receptor-Proximal Regulator of D...
KEEP AS NON CORE
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.
Reason: The GflB interaction is core to Gα2 signaling but is better represented by GO:0005091; GO:0005515 itself is retained as non-core.
Supporting Evidence:
PMID:27237792
we identify GflB, a Gα2 binding partner that directly couples the Dictyostelium cyclic AMP GPCR to Rap1
GO:0005834 heterotrimeric G-protein complex
IDA
PMID:11264536
Receptor-mediated activation of heterotrimeric G-proteins in...
ACCEPT
Summary: Direct-evidence heterotrimeric complex membership: FRET between Gα2 and Gβγ demonstrates the assembled heterotrimer dissociating and reassociating with receptor activation.
Reason: Core cellular-component assignment, directly demonstrated in living cells.
Supporting Evidence:
PMID:11264536
The G-protein heterotrimer rapidly dissociated and reassociated upon addition and removal of chemoattractant
GO:0005834 heterotrimeric G-protein complex
IDA
PMID:12217653
Monitoring receptor-mediated activation of heterotrimeric G-...
ACCEPT
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.
Reason: Corroborates the core heterotrimeric-complex assignment for Gα2.
Supporting Evidence:
PMID:12217653
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
GO:0005886 plasma membrane
IDA
PMID:29352733
Localization of palmitoylated and activated G protein α-subu...
ACCEPT
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.
Reason: The plasma membrane is the principal functional site of Gα2, dependent on its lipid modifications; a core localization.
Supporting Evidence:
PMID:29352733
Loss of this palmitoylation site results in redistribution of Gα2 within the cell
PMID:29352733
plasma membrane localization
GO:0007189 adenylate cyclase-activating G protein-coupled receptor signaling pathway
IMP
PMID:15715993
Loss-of-function mutations identified in the Helical domain ...
KEEP AS NON CORE
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.
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.
Supporting Evidence:
PMID:15715993
G alpha2 is essential for the developmental life cycle of Dictyostelium
GO:0006909 phagocytosis
IMP
PMID:9647646
G protein beta subunit-null mutants are impaired in phagocyt...
REMOVE
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.
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.
Supporting Evidence:
PMID:9647646
nor did we find reduced phagocytosis rates in Gα2 and Gα4 null mutants
GO:0030041 actin filament polymerization
IMP
PMID:9647646
G protein beta subunit-null mutants are impaired in phagocyt...
KEEP AS NON CORE
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.
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.
Supporting Evidence:
PMID:9647646
signaling through heterotrimeric G proteins is required for regulating the actin cytoskeleton during phagocytic uptake, as previously shown for chemotaxis
GO:0006935 chemotaxis
IMP
PMID:15715993
Loss-of-function mutations identified in the Helical domain ...
ACCEPT
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.
Reason: Chemotaxis toward cAMP is a core biological process mediated by Gα2 and is strongly supported by the genetics.
Supporting Evidence:
PMID:34418534
required for chemotaxis to cAMP during the onset of multicellular development
PMID:15715993
the loss of G alpha2 function results in a
GO:0031152 aggregation involved in sorocarp development
IMP
PMID:15715993
Loss-of-function mutations identified in the Helical domain ...
ACCEPT
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.
Reason: Aggregation during sorocarp (fruiting body) development is a core biological process for Gα2, essential and well established.
Supporting Evidence:
PMID:15715993
G alpha2 is essential for the developmental life cycle of Dictyostelium
PMID:34418534
The Dictyostelium Gα2 G protein subunit is required for chemotaxis to cAMP during the onset of multicellular development
GO:0007188 adenylate cyclase-modulating G protein-coupled receptor signaling pathway
IDA
PMID:15563608
Quantitative imaging of single live cells reveals spatiotemp...
ACCEPT
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.
Reason: Gα2 transduces cAMP GPCR signaling during gradient sensing, a core process.
Supporting Evidence:
PMID:15563608
triggers dissociation of Galpha and Gbetagamma subunits

Core Functions

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.

Supporting Evidence:
  • PMID:8280098
    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
  • PMID:11264536
    The G-protein heterotrimer rapidly dissociated and reassociated upon addition and removal of chemoattractant
  • PMID:15715993
    G alpha2 is essential for the developmental life cycle of Dictyostelium

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.

Directly Involved In:
Cellular Locations:
Supporting Evidence:
  • PMID:27237792
    we identify GflB, a Gα2 binding partner that directly couples the Dictyostelium cyclic AMP GPCR to Rap1
  • PMID:27237792
    functions as a Gα-stimulated, Rap1-specific guanine nucleotide exchange factor

References

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